i

MANAGEMENT OF ATRIAL FIBRILLATION AND HEART FAILURE IN
OUTPATIENT SETTINGS

By

Joselyn Law
BScN, McMaster University, 2012
MScN-FNP, University of Northern British Columbia, 2021

PROJECT SUBMITTED IN PARTIAL FULFILLMENT OF
THE REQUIREMENTS FOR THE DEGREE OF
MASTER OF SCIENCE
IN
NURSING-FAMILY NURSE PRACTITIONER

UNIVERSITY OF NORTHERN BRITISH COLUMBIA
July 2021
© Joselyn Law, 2021

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Abstract
Atrial fibrillation (AF) and heart failure (HF) have a highly interconnected relationship
with similar risk factors and shared pathophysiology. They often occur together and are
associated with increased morbidity and mortality. Unfortunately, the presence of one condition
has implications for the treatment of the other. Guidelines exist for each disease, however, do not
provide clarity when treating the conditions together. Due to the complex nature of the combined
diseases, management requires a systematic and collaborative approach in primary care settings.
The integrative review seeks to explore the following question, “How can the nurse
practitioner (NP) best manage HF patients with AF in outpatient settings to help reduce the
burden on the healthcare system?” A comprehensive search of the literature was undertaken and
20 articles were selected based on the inclusion criteria. The review findings provide insight into
the diverse treatment options available to persons living with concomitant AF and HF. From the
literature, catheter ablation, an invasive and specialized procedure, emerged as a superior
treatment strategy for patients with combined AF and HF, particularly when compared the
pharmacotherapy of rate and/or rhythm control. The management of AF in the setting of HF
requires a collaborative approach between primary care providers (PCP) as well as specialists
that are able to help manage the population of interest, such as cardiologist and
electrophysiologists. Recommendations for practice, education, research, and policy have been
made to support the role of PCPs, including NPs, in the management of AF in the HF population.

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Table of Contents
Abstract

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Table of Contents

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Lists of Tables

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Acknowledgements

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Chapter I: Introduction and Background
Background
Atrial Fibrillation
Pathophysiology
Epidemiology
Management
Heart Failure
Pathophysiology
Epidemiology
Management
Atrial Fibrillation and Heart Failure
Epidemiology
Pathophysiology
Management
Primary Care Setting
Nurse Practitioner Role

1
2
4
5
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11
16
17
21
23
29
30
31
32
34
36

Chapter II: Methodology
Integrative Review Methods
Development of the Research Question and Search Strategy
Search Strategy
Search Terms
Preliminary Review of the Literature and Focused Search
Eligibility Criteria
Analysis and Reporting

39
39
40
41
41
42
42
43

Chapter III: Findings
Catheter Ablation is Superior to Medical Therapy
Rehospitalizations
AF Recurrence
Mortality
QoL and Functional Capacity
LVEF
Safety Considerations
Low Complication Rates of Catheter Ablation
Safety of Catheter Ablation
Differing Treatment for HFrEF and HFpEF

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46
48
52
56
61
65
67
68
69
72

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Summary

76

Chapter IV: Discussion
Catheter Ablation as an Alternative to Medical Therapy
Improved QoL and Functional Capacity
Reduced Healthcare Burden
Safety Considerations
Discordant Evidence and Guidelines
AF and HF Guidelines
Recommendations
Education and Professional Development
Practice
Research
Policy
Limitations
Conclusion

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79
80
82
84
86
87
87
89
94
97
98
99

References

101

Appendix A: Database Searches

119

Appendix B: PRSIMA Flow Diagram

120

Appendix C: Literature Review Matrix
Single Studies
Systematic Reviews and Meta-Analyses

121
121
143

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Lists of Tables
Table 1: Search Terms and MeSH Terms for the Literature Review

42

Table 2: Catheter Ablation is Superior to Medical Therapy for AF in Presence of HF

47

Table 3: QoL and Functional Capacity

62

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Acknowledgements
I would like to pay my special regards to my project supervisor, Dr. Davina BannerLukaris (RN, PhD), and committee member, Liz Mulvaney NP(F), for their ongoing support and
contributions to this capstone project. Your encouragement, academically-informed guidance,
and passion for cardiac care has been inspirational throughout my journey.
Thank you to my friends and triathlon community in Kelowna for supporting my
dedication to the sport and encouragement to maintain a healthy and well balanced lifestyle
during my endeavors of completing my master’s degree and capstone project. Lastly, I would
like to express my gratitude to my mother, father, and sister in Ontario for their ongoing support
and encouragement as I pursue the nurse practitioner profession.

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CHAPTER I: INTRODUCTION AND BACKGROUND
Heart failure (HF) and atrial fibrillation (AF) are highly interrelated cardiovascular
disorders. AF often contributes to worsening HF symptoms, and the prevalence of AF parallels
the severity of HF (Verbrugge & Mullens, 2014). HF is a risk factor, as well as an adverse
clinical cardiovascular outcome associated with AF. HF and AF often co-exist, predispose each
other, and share common risk factors including hypertension, diabetes, coronary disease, and
valvular disease (Staerk et al., 2017). The prevalence of AF in patients with HF ranges from
13%–27% (Staerk et al., 2017). In a Framingham Heart Study cohort, HF was associated with
4.5-fold risk of AF in men and 5.9-fold risk in woman (Benjamin et al., 1994), while other
epidemiological studies demonstrate a 2.67- to 3.37-fold increased risk of AF associated with HF
(Staerk et al., 2017). Unfortunately, the occurrence of one condition has implications for the
treatment of the other, and the presence of one condition often hinders treatment for the other
(Verbrugge & Mullens, 2014). As such, the problem is that as the population ages, the
prevalence of AF and HF is expected to increase dramatically (Smigorowsky et al., 2017), and
together they cause greater healthcare burdens.
As AF is a “predictor of progression, hospitalization, and death” in HF patients (Andrade
et al., 2018, p. 1384), attention is needed to develop strategies to best manage individuals with
concomitant HF and AF in the outpatient setting. These combined conditions also give rise to
significant financial burdens. Specifically, patients frequently present with exacerbations of AF
at the emergency department, resulting in AF hospitalizations that cost the Canadian healthcare
system approximately $815 million annually, which is projected to increase (Smigorowsky et al.,
2017; Verbrugge & Mullens, 2014). Likewise, the individual may face impaired quality of life
(QoL) and significant personal impacts (Maisel & Stevenson, 2003). As such, the research

2
question to guide the literature review is as follows, “How can the nurse practitioner (NP) best
manage HF patients with AF in outpatient settings to help reduce the burden on the healthcare
system?” Due to the predicted inability to meet the future demands for healthcare traditionally
provided by a physician, NPs are able to focus on individualized patient education and follow up
based on their patients’ health care needs (Smigorowsky et al., 2017). To reduce the burden on
the healthcare system, defined therapeutic approaches with supporting evidence require further
exploration (Kotecha et al., 2014).
To contextualize the topic further, I will provide an overview of AF and HF with respect
to their pathophysiology, epidemiology, and management on their own, in addition to being
concomitant diseases. Following the background, I will present the methodology of the
integrative review stages that were undertaken as follows, 1) Development of the research
question, 2) Preliminary search, 3) Focused search, and 4) Analysis and reporting. After, the
findings of the integrative literature review will be explored with a focus on the following
themes, 1) Catheter ablation is superior to medical therapy, 2) Safety considerations, and 3)
Differing treatment for HF with reduced ejection fraction (HFrEF) and HF with preserved
ejection fraction (HFpEF). Finally, the findings of the review will be discussed, focusing on the
relevance towards to primary care providers (PCPs), including NPs.
Background
AF is the most common sustained cardiac arrhythmia and is associated with impaired
functional capacity and reduced QoL. AF is characterized by disorganised electrical impulses
that lead to a rapid cardiac rhythm and result in the desynchrony of the atrial and ventricular
chambers of the heart (Andrade et al., 2020; McCance & Huether, 2019). Changes in mechanical
functioning of the heart, as well as electrical remodeling within the atria, occur in AF. As AF

3
continues, structural changes give rise to electrical changes that generates and propagates ectopic
foci. These are additional sources of electrical impulses and mechanisms that cause inappropriate
conductions. As a result, AF begets AF and the longer a person remains in AF, the harder it is to
restore a normal heart rhythm (McCance & Huether, 2019).
The prevalence of AF is 1-2% in the general population, and increases significantly in the
aging population. Specifically, the prevalence is 1% in up to 50 years of age, 4% at 65 years, and
15% for individuals aged 80 or older (Andrade et al., 2020). The global AF burden is
underestimated, as about one-third of the total AF population is asymptomatic (Kornej et al.,
2020). AF is associated with increased mortality, and although the arrhythmia does not directly
cause individuals to be deceased, there are various accompanying comorbidities and
complications, including HF, myocardial infarction, chronic kidney disease, venous
thromboembolism, stroke, and dementia (Kornej et al., 2020). Aside from their shared risk
factors, there are multiple direct causal interactions between AF and its comorbidities, resulting
in an interdependence in disease development. Specifically, AF is associated with four- to fivefold increased risk of stroke, and thus the significantly increasing incidence and prevalence
makes AF a relevant disease in the population with high morbidity, mortality, and significant
health care costs (Kornej et al., 2020).
HF and AF are highly interrelated cardiovascular disorders that require multidisciplinary
collaboration, including utilizing NPs in the primary care and cardiac clinic setting for optimal
management (Verbrugge & Mullens, 2014). Both disorders occur commonly in developed
countries and frequently coexist in up to 30% of patients (Prabhu et al., 2017). As the population
ages, prevalence of AF and HF is expected to increase, contributing to healthcare crisis. The rise
in healthcare demands are influenced by an overwhelmed healthcare system and financial burden

4
(Smigorowsky et al., 2017). Optimal treatment includes antiarrhythmic drug (AAD) therapy,
however, the selection of therapies is challenging for the AF and HF population, as there are
limited medications that may be associated with considerable safety concerns (Piccini &
Fauchier, 2016). In addition to antiarrhythmic pharmacological management, other rhythm
control strategies, such as catheter ablation and cardioversion, have also becoming more
available and their perceived benefit are worth exploring (Verbrugge & Mullens, 2014).
This literature review will identify strategies to best manage and support patients with AF
in the presence of HF. There is an opportunity to further understand the synergistic relationship
of AF and HF, and to explore primary care practices that may improve patient outcomes and
decrease healthcare costs by reducing complications and rehospitalizations of the combined
disorders. The research question is as follows, “How can the NP best manage HF patients with
AF in outpatient settings to help reduce the burden on the healthcare system?” The following
sections will explore AF and HF through a succinct overview of their individual epidemiology,
pathophysiology, and management, as well as the combination of the concomitant disorders.
Atrial Fibrillation
AF is the most common arrhythmia with an estimated lifetime risk of 22% to 26% for
individuals between 40 and 55 years of age (Andrade et al., 2020). AF incidence and prevalence
is increasing globally, as the prevalence of AF has increased three-fold over the last 50 years
(Kornej et al., 2020). Dysrhythmias, or heart rhythm disorders, are classified according to the site
of origin of the abnormality, and whether the heart rate is increased or decreased (McCance &
Huether, 2019; Ritter et al., 2020). AF involves uncoordinated atrial activity, and an irregularly
irregular rhythm is the hallmark of AF. As such, AF is defined as an atrial arrhythmia. The onset
of AF requires an initiating trigger and an anatomical substrate, which will be further explored

5
(Zathar et al., 2019). The management is challenging, as the best approach is often not clear and
treatment must be highly individualized based on the cause (Buttaro et al., 2013). AF may occur
in the absence of known structural or electrophysiological abnormalities, such as ectopic firing or
substrate, that changes how the electricity is conducted in the heart. Structural, architectural, and
electrophysiological atrial abnormalities promote the perpetuation of AF by stabilizing re-entry.
Once AF is established, tachycardia further induces electrophysiological atrial remodeling
resulting in persistence of AF (Staerk et al., 2017).
Pathophysiology
Normal heart rhythms are generated by the sinoatrial node and move through the heart's
conduction system, causing the atrial and ventricular myocardium to contract and relax at a
regular rate required to maintain adequate circulation (McCance & Huether, 2019). Normal
automaticity is the cardiac cells’ ability to generate spontaneous activity, and the sinoatrial node
possess the highest intrinsic rate, thus making it the primary pacemaker of the heart
(Antzelevitch & Burashnikov, 2011). Cardiac dysrhythmias can be caused by either an abnormal
rate of impulse generated by the sinoatrial node or by the abnormal conduction of impulses, such
as a heart block, through the heart's conduction system (McCance & Huether, 2019).
AF is characterized by high-frequency excitation of the atrium, leading to
dyssynchronous atrial contraction and irregularity of ventricular excitation (Staerk et al.,
2017). AF involves disturbances that promote ectopic firing and re-entrant mechanisms,
including ion channel dysfunction, calcium abnormalities, structural remodeling, and autonomic
neural dysregulation (Andrade et al., 2014). Atrial substrates that promote re-entry are
characterized by abnormalities of the atrial cardiomyocyte and fibrotic changes (Staerk et al.,
2017). Thus, AF occurs due to diverse mechanisms that cause altered atrial tissue, and

6
consequently create abnormal impulses and propagation of electrical impulses (January et al.,
2014). AF is characterized by rapid excitation of the atrium that results in dyssynchronous atrial
contraction, as well as irregularity of ventricular excitation. AF may occur without known
structural or electrophysical abnormalities, however, comorbid conditions have been shown to
cause structural and histopathological changes (Staerk et al., 2017).
In AF, cardiac output may decrease significantly due to an impaired atrial systole caused
by the rapid ventricular rate (tachycardia), and irregular electrical activity in the atria (McCance
& Heuther, 2019; Stegmann & Hindricks, 2019). The rapid atrial activity, which is between 350
and 650 beats per minute, and irregularly irregular ventricular response occurs as action
potentials travel through the atrioventricular node, during which only a fraction of the atrial
impulses reach the ventricle (Buttaro et al., 2013). Thus, there is no coordinated atrial contraction
as the electrical impulses in the heart become disorganized (McCance & Huether, 2019; Ritter et
al., 2020).
Structural changes and electrical changes in the atria predispose the development and
maintenance of AF lead to atrial remodeling (Olshansky, 2019). Specifically, the pathological
features of AF include impaired diastolic dysfunction, causing elevated left ventricular enddiastolic pressure and increased left atrial pressure and volume (Staerk et al., 2017). Structural
and electrical changes may occur simultaneously, and can facilitate or create electrical re-entrant
circuits or triggers that can lead to AF (Olshansky, 2019). Atrial remodeling is associated with
slower and more varied atrial conduction and increased pulmonary vein firing, and the increased
left atrial mass supports multiple re-entry circuits (Staerk et al., 2017). Thus, the presence of AF
results in remodeling of the atrium over time, and thus AF begets AF (Olshansky, 2019).

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Classification. AF is the most common cardiac rhythm disorder (McCance & Huether,
2019). AF is a progressive condition that typically begins silently and undiagnosed, and is often
paroxysmal AF that occurs when episodes of the arrhythmia terminate spontaneously.
Classifications of AF include paroxysmal, as recurrent self-limiting episodes lasting < seven
days; persistent, or continuous arrhythmia lasting > seven days and < 12 months; long-standing
persistent, involving continuous arrhythmias lasting > 12 months; or permanent, as further
attempts to restore or maintain sinus rhythm should be discontinued as it is not achievable or
desirable (Golian & Klein, 2021). AF can also develop in individuals without any pathogenic
conditions or abnormalities (Calvo et al., 2016). For example, lone AF may occur without any
apparent reason or in response to transient factors, such as increased caffeine, alcohol, or dietary
intake (Jahangir et al., 2007). Lone AF may resolve spontaneously once the trigger is resolved or
removed The longer an individual has been in continuous AF, the less likely it is to terminate
spontaneously, making it more difficult to restore and maintain sinus rhythm (Olshansky, 2019).
Clinical Manifestations. Although symptoms of AF are nonspecific and often not
present, they may include palpitations, fatigue, dizziness, light headedness, and dyspnea (Buttaro
et al., 2013). On an electrocardiogram, AF appears as a normal P-wave replaced by fibrillatory
F-waves, which produces a wavy baseline (Buttaro et al., 2013). Lone AF is often asymptomatic,
however it may be captured by chance (Calvo et al., 2016). AF can also be associated with an
increased risk of stroke and transient ischemic attack, which is in turn linked to long-term
disability and mortality (Staerk et al., 2017). In some patients, AF may be asymptomatic and the
first indication of AF may occur following presentation with stroke or transient ischaemic attack
(Staerk et al., 2017).

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Epidemiology
AF is the most common sustained arrhythmia with a prevalence of one million
Canadians, with a substantial economic burden attributed to direct costs associated with
hospitalization and the provision of acute care (Andrade et al., 2020). As well, advanced age,
male sex, and European ancestry are prominent AF risk factors, which are non modifiable. Other
modifiable risk factors that predispose individuals to AF include hypertension, sedentary
lifestyle, tobacco, obesity, alcohol, diabetes mellitus, and obstructive sleep apnea (Staerk et al.,
2017).
Prevalent and Incidence. AF is the most common cardiac rhythm disorder in older
adults with a prevalence of 15 % for individuals aged 80 or older (Andrade et al., 2020). In
developed countries, AF is present in 3-6% of those admitted to hospitals with acute conditions
(McCance & Huether, 2019). The approximate global number of individuals with AF in 2010
was 33.5 million; specifically, 20.9 million men and 12.6 million women (Chugh et al., 2014). In
the United States of America (USA), three to six million people have AF, and the numbers are
projected to reach six to 16 million by 2050 (Kornej et al., 2020). In Europe, prevalent AF in
2010 was almost nine million among individuals older than 55 years, and is expected to reach 14
million by 2060 (Kornej et al., 2020). As well, it was estimated that by 2050, AF will be
diagnosed in approximately 72 million individuals in Asia (McCance & Huether, 2019). The rise
in prevalence and incidence of AF is largely due to an aging population, as the incidence doubles
with each decade of life and thus the rate of AF dramatically increases with advancing age
(Piccini et al., 2013). Other factors may include rising levels of chronic disease and obesity
(Staerk et al., 2017).

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Cost and Burden on the Healthcare System. AF creates a significant problem for
healthcare systems worldwide, as estimates suggest that AF accounts for 1% of the National
Health Service budget in the United Kingdom and $16-26 billion of annual USA expenses
(Chugh et al., 2014). In Canada, the annual direct cost of AF care in 2020 was $956 million,
which includes $66 million for emergency department visits for primary diagnosis of AF and $20
million with comorbid AF; $204 million for hospitalization with the primary diagnosis of AF and
$634 million with comorbid AF; and $32 million for day procedures related to AF (Andrade et
al., 2020). Thus, AF’s impact on healthcare expenditures is majorly due to hospitalizations
(Chugh et al., 2013). For example, in a study by Delaney et al. (2018), caring for patients with
AF was deemed costly in the USA healthcare system, majorly due to increase in prevalence of
HF, population longevity with cardiovascular disorders, and aging of the population. When
comparing older individuals with and without AF and a follow-up period of 1 year, the estimated
incremental hospital and clinical Medicare costs for patients with AF was $18,601.
Risk Factors. The risk factors of AF generally induce structural and electric remodeling
of the atria, and there are a variety of risk factors for developing AF (McCance & Huether,
2019). Cardiovascular disease risk factors, including advanced age, male sex, alcohol
consumption, smoking, and diabetes, contribute to the development of AF (McCance & Huether,
2019). Age is one of the most significant predictors of incident AF due to structural and
electrical remodelling. Sex is also a strong predictor of AF, as males have a 1.5-fold increased
risk for developing AF. Additionally, diabetes is associated with a 1.5 times increased risk due to
structural, electrical, and autonomic remodelling. However, dyslipidemia has an unclear
association with AF (Andrade et al., 2020).

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Lifestyle factors, such as tobacco use, alcohol consumption, and a sedentary lifestyle are
associated with an increased risk of developing AF (Andrade et al., 2020). Sedentary lifestyle is
linked to autonomic dysfunction and elevated sympathetic tone, thus enhancing
afterdepolarization triggering and AF susceptibility. Paradoxically, endurance athletes are also at
risk of AF, as they have increased vagal tone which may shorten and increase pulmonary vein
firing, as well as cause progressive cardiac remodeling, and atrial enlargement and fibrosis
(Staerk et al., 2017). Obesity is also a risk factor, as body mass index (BMI) and AF have a
linear relationship with AF incidence increasing 3-7% of unit increase in BMI (Andrade et al.,
2020). Obstructive sleep apnea is common in obese individuals and has been associated with
sedentary lifestyle and systematic inflammation causing atrial remodelling. Sleep apnea is highly
prevalent in those with AF, with a rate that is twice the general population (Staerk et al., 2017).
Hypertension is a strong independent risk factor, as it causes neurohormonal activation,
structural remodelling and thus atrial fibrosis, as well as electrical remodelling causing
conduction disturbances (Andrade et al., 2020). Additionally, valvular heart disease has been
implicated with a 1.8- to 3.4-fold increased risk for AF due to structural remodelling. For the
same reason, AF is associated with an increased complexity of rheumatic heart disease (Andrade
et al., 2020). Moreover, AF increases the severity of cardiomyopathy, or HF, symptoms. HF
causes structural and electrical remodelling, as well as neurohormonal activation due to
increased sympathetic activity and impairment of vagal tone (Andrade et al., 2020). The
prevalence of AF in patients with HF ranges from 13% to 27%, and the prevalence rises with
increased New York Heart Association (NYHA) functional class (Staerk et al., 2017). As well,
AF increases with hyperthyroidism due to neurohormonal activation, structural and electrical
remodelling, and promotion of the pulmonary vein automaticity (Andrade et al., 2020). Lastly,

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AF occurs more often in those with a family history of AF in a first-degree relative, specifically
due to cardiac ion channel alterations, alterations in cellular coupling, or increased susceptibility
to AF (Andrade et al., 2020).
AF is the most common sustained rhythm and is associated with a substantial economic
burden (Andrade et al., 2020). AF ranges from isolated electrophysiological disorder, or a
manifestation of a cardiac or noncardiac pathology. As individuals age, the contribution of
abnormal substrate predominates, including nonmodifiable risk factors related to age, sex, and
genetically determined factors, modifiable risk factors related to reversible risk factors, as well as
substrate induced by the AF episodes themselves. Thus, strategies targeting modifiable
cardiovascular risk factors and relevant comorbid conditions improve survival rates (Andrade et
al, 2020).
Management
The risk of developing AF increases with the severity and presence of modifiable
cardiovascular risk factors, including hypertension, diabetes mellitus, and obesity (Staerk et al.,
2017). Due to the complex and multifaceted nature of AF, a systematic approach of AF
management is required. The initial management of AF can be provided by PCPs, in addition to
the support of cardiologists, cardiac clinic NPs, and others engaged in cardiac care, to guide
management decisions for patients who develop difficulties during therapy. There are
multidisciplinary clinics that exist with a focus on AF care, which includes facilitating patient
and provider education, advanced treatment options, and evidence-based care centred on chronic
disease management (Andrade et al, 2020).
Treatment strategies include achieving a normal heart rate, restoring normal rhythm, and
reducing the risk of stroke (McCance & Huether, 2019). Considerations when deciding the type

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of management includes the efficacy and safety profile of the medication, as well as the patient’s
tolerability and preference (Andrade et al., 2020). As well, the causes of AF should be
considered, as it is important to determine whether treatment aims at attempting to restore and
maintain sinus rhythm through rhythm control, or manage ventricular rate control. Factors that
contribute to the decision include duration of the AF and left atrial size, as left atrial enlargement
and prolonged duration of AF can reduce the ability to be successful in maintaining normal sinus
rhythm. Additionally, restoration and maintenance of sinus rhythm aids in symptomatic relief,
prevention of embolism, and prevention of cardiomyopathy (Buttaro et al., 2013).
Pharmacological interventions, such as anticoagulation, rhythm control, and rate control, and
nonpharmacological interventions, such as catheter ablation and cardioversion, will be briefly
discussed.
Pharmacological Interventions. The primary decision of medical management in AF is
whether to choose rate control, thus leaving atrial arrhythmia as the permanent rhythm, or
rhythm control, thus actively pursuing a sinus rhythm (Ritter et al., 2020). There is also a goal
stroke prevention in the AF population (McCance & Huether, 2019).
Rhythm Control. Rhythm control is preferred for individuals with a diagnosis of AF
within a year. Long-term rhythm control is also recommended in patients with AF who remain
symptomatic with rate control, or where rate control therapy is unlikely to control symptoms.
Rhythm control may not completely suppress AF, thus the focus is on symptomatic management.
Commonly used AADs include propafenone, flecainide, sotalol, and amiodarone. The initial
choice is driven by safety and tolerability of the patient. Of the available AADs, only
amiodarone and dofetilide are recommended in patients with left ventricular dysfunction and/or
clinical HF. Amiodarone is the most effective AAD, however the potency is at most 60% at one

13
year. Dofetilide therapy is less effective, and its initiation requires a three-day hospitalization due
to its potential to prolong the QT interval and can cause torsades de pointes, a life threatening
arrhythmia (Thihalolipavan & Morin, 2015).
AF triggers and modifies AF substrates (McCance & Huether, 2019). Thus, rhythm
control should be pursued in patients with more than minimal symptoms, in asymptomatic young
patients, and in those with possible tachycardia-related cardiomyopathy. There are many
medications that may be used to control AF, however amiodarone is the most commonly used
drug (Ritter et al., 2020). Amiodarone is a class III AAD with complex pharmacological
properties, including a long half-life. Long-term use increases the risk for extracardiac toxicities
affecting the skin, thyroid, pulmonary, liver, and neurological systems (Andrade et al., 2020).
Thus, while amiodarone is more effective than sotalol or propafenone for the prevention of
recurrences of AF, it is associated with significant adverse and side effects. As a result,
amiodarone can be poorly tolerated and may be discontinued, and particularly stopping the drug
in up to 18% of patients (Ritter et al., 2020). As such, amiodarone should not be considered as
first-line therapy (Andrade et al., 2020).
Rate Control. Long-term rate control involves agents with negative chronotropic
properties, including beta blockers (BB), including metoprolol or bisoprolol, and
nondihydropyridine calcium chancel blockers (ND-CCB), such as verapamil and diltiazem.
These drugs act to modulate the activity of the sinoatrial and atrioventricular nodes, and are
recommended for initial control of heart rate (McCance & Huether, 2019; Ritter et al., 2020).
There are many different drugs that may be used, each with their own mechanisms of action, and
each drug is chosen based on the individualized patient’s needs. For example, patients without
significant left ventricular dysfunction, BBs and ND-CCBs are first line medications (Andrade et

14
al., 2020). In patients with significantly impaired left ventricular systolic function, BBs are the
first line for rate control (Andrade et al., 2020). Digoxin may also be used, which increases the
stability of cell membranes and should be considered only when response to first-line agents is
inadequate, since it is not very effective and has concerns of increased mortality (Ritter et al.,
2020). Although amiodarone is a class III AAD, it is also a multichannel blocker and a
nonselective BB. Thus, patients that are critically ill, or with side effects from first-line agents,
may benefit from amiodarone for rate control therapy (Andrade et al., 2020).
Stroke Prevention. In AF, the ineffective blood pumping raises the likelihood of
coagulation and thrombosis, causing an increased risk of stroke and often require preventative
oral anticoagulant therapy (McCance & Huether, 2019). Warfarin and acetylsalicylic acid (ASA)
have been used for many years in this population, although ASA is less effective than warfarin
AF (Ritter et al., 2020). Additionally, apixaban, dabigatran, edoxaban and rivaroxaban have been
approved for prevention of systemic embolism in patients with AF, which are the four direct oral
anticoagulants currently approved for use in Canada (Andrade et al., 2020; Ritter et al., 2020).
Additionally, utilizing a rhythm control strategy for patients newly diagnosed with AF is
associated with reduced cardiovascular death and reduced rates of stroke. It is also recommended
that patients with AF should undergo annual assessment of their risk of stroke and systemic
embolism, regardless of their type of AF (Andrade et al., 2020). Stroke prevention remains a
central focus for those living with AF.
Nonpharmacological Interventions. If medical therapy does not achieve the desired
results, cardiac interventions, such as catheter ablation, may be a feasible option. Ablation of AF
may also be the preferred therapy for patients with recurrent AF that desire long-term rhythm

15
control (Andrade et al., 2020). As well, breakthrough episodes of AF can be terminated by either
electrical or chemical cardioversion when significantly compromised (Ritter et al., 2020).
Catheter Ablation. Catheter ablation is the delivery of radiofrequency or cryothermal
energy by targeting tissue injury in the heart, with a goal of preventing recurrence of the
arrhythmia (Golian & Klein, 2021). Pulmonary veins have been shown to be the main trigger
source for AF. Thus, pulmonary vein isolation (PVI) is the primary treatment for symptomatic
patients with paroxysmal and persistent drug-refractory AF, however AF recurrence is common
(Rottner et al., 2020). Although radiofrequency-based PVI has been the mainstay treatment,
novel ablation techniques, particularly cryoballoon, has emerged as the most commonly used
alternative AF ablation tool (Rottner et al., 2020). Catheter ablation is often not an absolute cure
for AF, but can significantly reduce the arrhythmia burden (Ritter al., 2020).
The success rate for ablation of AF is high with a low rate of complications, varying from
50–80% depending on technique, AF subtype, and the extent of structural heart disease (Ritter
al., 2020). A quantitative, multi-centered, and randomized control trial by Di Biase et al. (2016)
demonstrated that the success rate of catheter ablation after a single procedure ranged from 29%
to 61% in patients with persistent AF, as well as it was associated with decreased hospitalizations
and mortality. Catheter ablation offers an opportunity to achieve sinus rhythm without the
adverse effects of AAD therapy. Treatment of catheter ablation for patients with HF should be
individualized by weighing the potential long-term benefits of successful ablation against the
risks of intra-procedural complications (Liang & Callans, 2018). Thus, if rate or rhythm control
cannot be achieved with medication, catheter ablation can be considered (Ritter et al., 2020);
particularly if patients are symptomatic and have failed or do not wish to remain on AAD
therapy long term (Golian & Klein, 2021).

16
Cardioversion. AF that produces hemodynamic compromise, acute coronary syndrome,
or pulmonary edema, and is resistant to prompt medical management, should be terminated
electrically (Andrade et al., 2020; Golian & Klein, 2021). The initial success rate of
cardioversion for AF is 70–90%, however approximately 20% of patients will remain in sinus
rhythm after a year (Golian & Klein, 2021). As such, cardioversion is recommended in
hemodynamically unstable and symptomatic AF individuals that require restoration of sinus
rhythm from a tachycardic heart rate (Stegmann & Hinkdricks, 2019). Cardioversion can also be
a useful adjunctive measure in patients with breakthrough episodes of AF (Golian & Klein,
2021). Specifically, AF breakthrough episodes can be terminated by either electrical or chemical
cardioversion. Options for chemical cardioversion include oral flecainide, or propafenone, in
addition to intravenous amiodarone, ibutilide, or procainamide (Ritter et al., 2020).
When AF is not responsive to medical therapy, nonpharmacological interventions may be
necessary (Golian & Klein, 2021). Although AF ablation is often not a complete cure for AF, it
significantly reduces the arrhythmia burden. Thus, it is a recommended option for patients that
would like to avoid long term AAD therapy (Golian & Klein, 2021).
Heart Failure
HF is a complex clinical syndrome with signs and symptoms of volume excess that range
from mild dyspnea on exertion caused by fluid retention, to cardiogenic shock and lethal
arrhythmias (Buttaro et al., 2013). HF affects approximately 37.7 million people worldwide (Hu
et al., 2021). HF is the result of cardiac dysfunction, or the “inability of the heart to meet the
body’s metabolic demands” (Buttaro et al., 2013, p. 537), resulting in reduced longevity. HF is
caused by a structural or functional cardiac disorder, which impairs the ventricles from filling or
ejecting properly (Buttaro et al., 2013). HF does not occur independently, as it is caused by an

17
underlying cardiac defect and has an increased prevalence with the aging population (Andrade et
al., 2020). The disease is one of the most common, costly, debilitating, and morbid conditions in
primary and secondary care (McMurray & Pfeffer, 2005). An increase in natriuretic peptide
concentrations, specifically B type natriuretic peptide, is a hallmark of HF (Mosterd & Hoes,
2007). Patients with HF often require frequent hospitalizations, in addition to experiencing a
significantly reduced QoL and exercise intolerance (De Denus & White, 2019).
Pathophysiology
HF is characterized by impaired LV function and reduced LV reserve, characterized by
signs and symptoms due to an excess amount of volume (De Denus & White, 2019). Generally
in HF, the heart is unable to generate a cardiac output to adequately perfuse tissues or causes
increased diastolic filling pressure of the left ventricle. Cardiac output depends on the heart rate
and stroke volume, and stroke volume is influenced by preload, afterload, and contractility.
Preload is the degree of myocardial fiber stretch at the end of ventricular filling. Afterload is the
amount of left ventricular wall tension that develops during systole, determined by the size of the
ventricular chamber and the dynamic vascular resistance which the heart must contract against
(Buttaro et al., 2013). Lastly, contractility of the myocardium is a change in tension at a given
resting fiber length, or the ability of the heart muscle to shorten (McCance & Huether, 2019).
Thus, the abnormal heart function causes signs and symptoms of reduced cardiac output and/or
pulmonary or systemic congestion at rest or during exercise (Ezekowitz et al., 2017).
Classification. The American College of Cardiology (ACC) and the American Heart
Association (AHA) have created an ACC/AHA HF Stages system to grade HF by stage,
including patients at risk for the development of HF (stage A) and those with end-stage,
advanced disease (stage D) (Buttaro et al., 2013). Complementary to the ACC/AHA staging, the

18
NYHA classification is used to classify severity of HF and indicate prognosis to help guide
management. Severity ranges from asymptomatic (NYHA I), which is well managed patients
without symptoms, to mild (NYHA II), which is slight limitation in physical activity, to
moderate (NYHA III), which is symptoms while walking, to severe (NYHA IV), which is
breathless at rest (Buttaro et al., 2013; Mosterd & Hoes, 2007).
HF a clinical syndrome with signs or symptoms caused by a structural and/or functional
cardiac abnormalities (Gibson et al., 2021), and is categorized on the basis of left ventricular
ejection fraction (LVEF) (Ezekowitz et al., 2017). Specifically, HFrEF is characterized by a
symptomatic decrease in the EF of ≤ 40%, in addition to cardiac output (Ezekowitz et al., 2017;
Gibson et al., 2021). HF with mildly reduced ejection fraction is considered symptomatic HF
with LVEF between 41 and 49%. HFpEF occurs with symptoms when the LVEF is ≥ 50%
(Ezekowitz et al., 2017; Gibson et al., 2021). A new classification of HF is HF with improved
ejection fraction, which is defined as symptomatic HF with a baseline of LVEF ≤ 40%, a ≥ 10point increase from baseline LVEF, and a second measurement of LVEF > 40%. As cardiac care
is a rapidly evolving field, new classifications and diagnostic guidelines are continually being
developed. Classifying HF by stage allows PCPs the opportunity to communicate with patients in
a more practical manner and provide explanations to allow for greater shared decision-making
(Gibson et al., 2021).
HFrEF. HFrEF is defined as a reduction in the ventricle’s contractility leading to an
inadequate cardiac output to perfuse vital tissues (De Denus & White, 2019). The three
determinants of ventricular function, which are preload, contractility, and afterload, are altered.
Increased preload occurs because the heart ejects insufficiently, resulting in an increased volume
of blood that remains in the ventricular chambers. The result is increased left ventricular end-

19
systolic volume, which leads to distention of the ventricles and increased interventricular
pressure at the onset of diastole. Normally, the heart is able to withstand a small increase of
volume and pressure, while continuing to maintain cardiac output. Inversely, in HF the
myocardial fibers are excessively overloaded and stretched beyond the limits of a normal reflexincreased force of contraction. The result is left ventricular remodelling with dilation and
impaired contractility, and activations of the sympathetic and renin-angiotensin-aldosterone
system (RAAS) (Buttaro et al., 2013).
Decreased contractility causes stroke volume to fall, and left ventricular end diastolic
volume increases, causing dilation of the heart and increased preload. Increases in left ventricular
end diastolic volume can temporarily improve cardiac output, however as preload continues to
rise, the myocardium stretches and eventually leads to dysfunction of the sarcomeres and
decreased contractility (McCance & Huether, 2019). Therefore, a decrease in myocardial
contractility, reduction in EF, and a reduction in stroke volume and cardiac output occurs.
Specifically, systolic blood pressure is closely related to afterload, and thus is a relevant clinical
indicator of myocardial load or afterload, and an afterload-dependent measure of contractility
(Buttaro et al., 2013). Contractility is reduced by diseases that disrupt myocyte activity, such as
myocardial infarction, myocarditis, and cardiomyopathies, which contribute to inflammatory,
immune, and neurohormonal changes that mediate ventricular remodeling. Ventricular
remodelling results in disruption of normal myocardial extracellular structure with resultant
dilation of the myocardium and causes progressive myocyte contractile dysfunction (McCance &
Huether, 2019). A prolonged increase in preload and afterload are implicated in HF, as they
contribute to ventricular dysfunction and enlargement, decreased myocardial contractility,
reduction in EF, and thus a reduced stroke volume and cardiac output (Buttaro et al., 2013).

20
A cardiac output that is insufficient to meet metabolic demands leads to an increase in
fluid volume due to increasing venous pressure, therefore leads to increased capillary pressure.
There is an increase formation of tissue fluid caused by reduced renal blood flow activates the
RAAS, causing sodium and water retention, which acts to increase pulmonary vascular
remodeling and plasma volume, thus increasing afterload and preload (McCance & Huether,
2019; Ritter et al., 2020). Specifically, the reduced cardiac output causes decreased renal
perfusion and trigger activation of the RAAS system, which increases peripheral vascular
resistance and plasma volume and further contributes to increased preload and afterload.
Additionally, the baroreceptors in the central circulation detect the decrease in perfusion and
stimulate the sympathetic nervous system to cause increased vasoconstriction, causing the
hypothalamus to produce antidiuretic hormone. Thus, increased preload, increased afterload, and
decreasing contractility also contributes to the progressive worsening of HF (McCance &
Huether, 2019).
HFpEF. HFpEF is defined as impairment of the ventricular filling and relaxation,
causing pulmonary congestion despite a normal stroke volume and cardiac output (Buttaro et al.,
2013; De Denus & White, 2019; McCance & Huether, 2019). It is caused by increased
ventricular stiffness and reduced compliance of the left ventricle, causing a rise in cardiac filling
pressures during ventricular relaxation. The distensibility of the left ventricular is reduced for all
or part of diastole, causing filling pressures to increase for maintenance of a constant ventricular
volume (Buttaro et al., 2013). The failure of a normal rise in cardiac output during periods of
exertion causes dyspnea, or difficult breathing, which is a classic symptom of HF. As such, the
heart will attempt to compensate for the impaired distensibility through left atrial contracting,
causing left atrial dilation overtime (Buttaro et al., 2013).

21
Epidemiology
HF is a deadly and disabling disease with signs and symptoms caused by cardiac
dysfunction (Mosterd & Hoes, 2007), which increases patients requiring hospital admission
(McMurray & Pfeffer, 2005). Specifically, 30 – 40% of patients die within a year of diagnosis
and 60 – 70% die within five years, majorly due to worsening heart failure or suddenly. As such,
there is a one in five risk for developing HF for a person aged 40 years, as well as a one in three
chance of dying within a year of diagnosis (McMurray & Pfeffer, 2005).
Prevalent and Incidence. HF is considered a global epidemic disease that affects
approximately 1% to 2% of adult population in the western world, and incidence approaches five
to 10 per 1000 persons annually (Mosterd & Hoes, 2007). Specifically, 5.7 million Americans
older than 20 years of age have HF, causing one in nine deaths in the USA (McCance & Huether,
2019), and the prevalence and incidence increase progressively over the age of 50 years
(Mosterd & Hoes, 2007). HF majorly affects the elderly, as 6-10% of people over the age of 65
years are diagnosed with the disease (McMurray & Pfeffer, 2005), and 80% of HF-related
hospitalizations and 90% of HF-related deaths occur among patients aged 65 years or older.
In a study by Lloyd-Jones et al. (2002), the incidence of HF doubled over each
consecutive decade of life, rising more with age in women than in men. The annual incidence in
men increased from two per 1000 at age 35 to 64 years to 12 per 1000 at age 65 to 94 years, and
the lifetime likelihood of developing HF is approximately 20% for individuals above the age of
40. A further rise in HF cases is expected due to a higher proportion of elderly people and better
survival rates of patients with risk factors for developing HF (Lesyuk et al., 2018).
Cost and Burden on the Healthcare System. HF is a significant and increasingly
prevalent medical and economic problem worldwide, as it encompasses 1-2% of the healthcare

22
budget. The prevalence of HF has increased over the past decades and is expected to continue to
raise due to the higher proportion of elderly in the western societies (Lesyuk et al., 2018). The
annual mortality rate of HF is 6-25% depending on the severity of symptoms (De Denus &
White, 2019). The Meta-Analysis Global Group in Chronic HF by Pocock et al. (2012) discusses
the development of a prognostic model in HF patients that readily quantifies individual patient
mortality risk. The results showed that for 39,372 patients with HF from 30 studies, 40.2% of
patients died during a median follow-up of 2.5 years. The study showed that the patient’s overall
prognosis is variable, however, the overall risk profile helps identify patients in need of intensive
monitoring and therapy, as well as the need of new therapies.
Patients diagnosed with HF have a poor prognosis and high hospitalization rates
(Heidenreich et al., 2013). In a literature review by Cook et al. (2012), the overall economic cost
of HF in 2012 was approximately $108 billion a year, with 60% accounting for direct costs and
40% accounting for indirect costs. The USA is attributed as the biggest contributor to the global
HF costs, as it accounts for 28.4% of the total global HF expenditure. A policy statement from
the American Heart Association by Heidenreich et al. (2013) states that costs related to the
treatment of HF is 2-3% of the total expenditure of healthcare systems in developed countries,
and are projected to increase by more than 200% in the next 20 years due to the aging
population. By 2030, more than eight million people in the USA will develop HF. Between 2012
and 2030, total direct medical costs of HF are projected to increase from $21 billion to $53
billion. Total costs, including indirect costs for HF, are estimated to increase from $31 billion in
2012 to $70 billion in 2030. If all costs of cardiac care for HF patients are attributable to HF and
not attributed to comorbid conditions, the 2030 projected cost estimates of treating patients with
HF will be three-fold higher, or $160 billion in direct costs.

23
Risk Factors. The etiology of HF is divided into three categories: 1) Anatomic or
functional abnormalities of the coronary vessels, myocardium, or cardiac vales; 2)
Neurohormonal overexpression of biologically active molecules, activating the adrenergic
nervous system and RAAS; and 3) Extracardiac factors, creating an increased demand on the
cardiovascular system (Buttaro et al., 2013). Many conditions are able to cause HF, such as age,
smoking, diabetes, renal failure, coronary artery disease, hypertension, cardiomyopathies,
valvular and congenital heart disease, arrhythmias, pericardial disease, myocarditis, pulmonary
hypertension, and cardiotoxic substances (McCance & Huether, 2019; Mosterd & Hoes, 2007).
As well, obesity doubles the risk of HF, which is increasingly prevalent in western societies
(Mosterd & Hoes, 2007). However, ischemic heart disease and hypertension are the most
significant predisposing risk factors, as 75% of HF cases occur in persons with hypertension
(McCance & Huether, 2019). Moreover, coronary artery disease is the most common cause of
HFrEF, whereas hypertension, AF, and diabetes are common causes of diastolic dysfunction
(Buttaro et al., 2013). Diabetes can produce HF independently of coronary artery disease by
causing a diabetic cardiomyopathy through promoting the development of myocardial fibrosis
and diastolic dysfunction, autonomic dysfunction, and worsened renal and endothelial function.
The incidence of HF was two- and four-fold higher in patients with diabetes than in those
without. Approximately 12% of patients with diabetes have HF, and older than the age of 64
years, the prevalence increases to 22% (Ezekowitz et al., 2017).
Management
The goal of therapy for patients diagnosed with HF includes treating modifiable risk
factors, avoiding exacerbating factors, preventing disease progression, improving symptoms,
improving exercise tolerance and QoL, and reducing morbidity and mortality (De Denus &

24
White, 2019). The prognosis is now much improved compared with previous eras, however
patients with advanced HF who fail to respond to disease modifying therapy have a poor
prognosis and impaired QoL. Thus, early referral for palliative care support might be considered
during the advanced stages of HF (Fine et al., 2020). As well, treatment strategies for HF
involves managing common risk factors for the development of HF, such as smoking, obesity,
alcohol use, sedentary behaviour, hypertension, diabetes, and dyslipidemia, which will be briefly
addressed below (Ezekowitz et al., 2017).
Pharmacological Interventions. HF requires sufficient diagnostic testing in order to
determine the specific cause. After a diagnosis is made, the goals of therapy are to relieve
congestion, treat specific reversible causes, and then management of the residual heart failure. It
is important to note that HF caused by diastolic dysfunction must be differentiated from that
caused by systolic dysfunction, as treatment options differ (Buttaro et al., 2013). Medications are
required to address symptoms and optimize cardiac function in HF, and as well as manage other
comorbidities. However, side effects may occur due to the polypharmacy nature of HF
management (Ezekowitz et al., 2017).
HFrEF. For patients diagnosed with HFrEF, therapy incorporates angiotensin receptorneprilysin inhibitor (ARNI) as first-line therapy or after angiotensin converting enzyme inhibitor
(ACEI)/angiotensin receptor blocker (ARB) titration, as well as BBs, mineralocorticoid receptor
antagonists (MRA), and sodium glucose transport 2 inhibitors (McDonald et al., 2021).
Sacubitril-valsartan is the only available ARNI in Canada, and dosing and titration is
individualized (McDonald et al., 2021). ARBs differ pharmacologically from ACEIs, however,
act similarly to ACE inhibitors. ACEIs have greater evidence than ARBs, reducing
cardiovascular morbidity and mortality compared with placebo in hypertension (Ritter et al.,

25
2020). BBs have cardio-depressant effects and decrease cardiac rate and force, whereas ACEIs
cause vasodilation and reduce cardiac load as well as arterial pressure (Ritter et al., 2020).
Diuretics are used to control signs and symptoms of hypervolemia and maintain
euvolemia. Thiazide diuretics can be used in patients with minimal fluid retention, however loop
diuretics, such as furosemide, are often required to control congestion and peripheral edema (De
Denus & White, 2019; Ezekowitz et al., 2017). Other therapies that improve HF outcomes
include sinus node inhibitors, soluble guanylate cyclase stimulators, hydralazine/nitrates in
combination, and/or digoxin (McDonald et al., 2021). Digoxin causes cardiac slowing and
reduces the ventricular rate of conduction, as well as increases the force of cardiac contraction.
Digoxin is used in HF for patients who remain symptomatic, despite use of diuretics and ACEIs
(Ritter et al., 2020).
HFpEF. For patients diagnosed with HFpEF, therapy involves controlling risk factors,
such as hypertension, diabetes mellitus, ventricular rate, regulatory volume status, and
decreasing heart rate to improve filling time. Although chronic use of RAAS modulators, such as
ACEIs, does not reduce the risk of mortality in this population, these agents should be used to
treat hypertension, left ventricular hypertrophy, nephropathy or coronary artery disease due to
their efficacy and end-organ protection. Additionally, MRAs are recommended with
symptomatic patients, serum potassium < 5 mmol/L and glomerular filtration rate ≥ 30 mL/min,
however close monitoring of potassium and creatinine is required. BBs, such as metoprolol, are
recommended for patients with coronary artery disease, previous myocardial infarction,
hypertension, or AF due to their ability to control ventricular rate in patients. Diuretics,
furosemide, are considered to optimize volume status. Calcium channel blockers (CCB), such as

26
verapamil or diltiazem, are considered to control the ventricular rate for those with angina or
unable to tolerate BBs (De Denus & White, 2019).
Comorbidities. HF guidelines state that dyslipidemia should be treated in patients with
evidence of vascular disease or diabetes with lipid lowering drugs, particularly statins
(Ezekowitz et al., 2017). The benefit of statins in the primary and secondary prevention of
coronary artery disease is well established, however the benefits of statins in patients with HF is
limited (Denus & White, 2019). As well, an intensive glycemic control strategy is not
recommended for all patients with diabetes, as they should be assessed for their optimal
glycemic target for the prevention of macrovascular events or HF. Metformin is still considered
first-line pharmacological therapy for type two diabetes, as it is effective with a known safety
profile, and is well tolerated in patients with HF. SGLT-2inhibitors, such as dapagliflozin and
empagliflozin, benefit patients with HF, with or without diabetes (McDonald et al., 2021).
Nonpharmacological Interventions. Nonpharmacological management involves a
variety of approaches. Clinical assessment should include an assessment of symptoms, volume
assessment, and monitoring of vital signs, renal function, electrolytes, and creatinine (Ezekowitz
et al., 2017.
Lifestyle Modification. Moderate, regular exercise as tolerated is recommended to
improve exercise capacity, symptoms, and QoL, and has shown to decrease hospital admissions
(Ezekowitz et al., 2017; Ritter et al., 2020). Sedentary lifestyle and obesity are risk factors for the
development of HF, as well as exacerbation of HF (Ezekowitz et al., 2017. Additionally, alcohol
reduction is advised for all patients with HF, or complete avoidance if it is responsible or
contributes to the syndrome due to the dose dependent effect and individual susceptibility to the
deleterious effects of alcohol. No more than one alcoholic drink per day is recommended in all

27
patients, and avoidance is recommended in alcoholic cardiomyopathy (Ezekowitz et al., 2017;
De Denus & White, 2019; Ritter et al., 2020). Importantly, smoking has been linked to the
progression of cardiovascular disease, and thus smoking cessation is encouraged. Nicotine
replacement therapy or other smoking cessation therapies are recommended (Ezekowitz et al.,
2017). As well, reduced dietary intake of sodium is associated with improved clinical outcome,
thus patients with HF should restrict their dietary salt intake between 2 to 3 g per day
(Ezekowitz et al., 2017).
Fluid Restriction. Fluid intake should be restricted to 2 L per day for patients with fluid
retention or congestion not controlled by diuretics. To monitor fluid retention and congestion,
daily morning weight should be taken for patients with HF and fluid retention or congestion, or
with significant renal dysfunction. Any rapid weight gain >1.5 or 2 kg warrants a rapid medical
visit (Ezekowitz et al., 2017; De Denus & White, 2019; Ritter et al., 2020).
Devices. There are multiple devices considered for HF patients based on their clinical
status. Due to their cost, devices are typically reserved for patients without significant
comorbidities that are expected to limit their survival. Implantable cardioverted defibrillators
(ICD) are recommended for NYHA class II-III and LVEF ≤35%, or NYHA class I and LVEF ≤
30% (De Denus & White, 2.019). The primary indication for ICD implantation in patients with
HF is the prevention of sudden death. ICD devices can also act as pacemakers and treat
ventricular arrythmias by delivering shocks via the coils on the lead and the generator. The ICD
is placed subcutaneously in the pectoral region where pacemakers are implanted, and the leads
are placed in the endocardium of the atria and the ventricle (Muthumala, 2017). Patients with
significant comorbidities may not benefit from an ICD for treatment of the arrythmia, and thus
resynchronization may be considered if they meet certain criteria (Muthumala, 2017).

28
Cardiac resynchronization therapy (CRT) is widely accepted as a significant component
of standard HF therapy. In most patients, CRT reduces clinical symptoms, improves exercise
tolerance, and reverses cardiac remodeling (Hu et al., 2021). CRT is appropriate for patients with
NYHA class II, III, and ambulatory NYHA class IV. The procedure is more complicated than for
an ICD, as there are right atrial and right ventricular leads as well as a pacing lead placed in a
branch of the coronary sinus (Muthumala, 2017).
Left ventricular assist devices are used at end-stage heart failure and can be considered as
a bridge to cardiac transplantation. Also, continuous positive airway pressure is considered in
patients with obstructive sleep apnea due to HF (De Denus & White, 2019). Lastly,
revascularization can be completed by either percutaneous coronary intervention or coronary
artery bypass surgery. These should be performed in patients that are symptomatic is ischemia,
or if reperfusion may improve dysfunctional myocardium (Ezekowitz et al., 2017).
Advanced HF. If devices cannot manage advanced HF, strategies include advanced
mechanical devices, transplantation, or palliative therapies (Ezekowitz et al., 2017). Mechanical
circulatory support (MCS) is a group of technologies that increase forward cardiac output in
patients through the use of ventricular assist devices that augment or replace the ventricle
(Ezekowitz et al., 2017). As well, if patients have severe refractory HF despite optimal therapy,
cardiac transplantation can be considered (De Denus & White, 2019). Lastly, palliative care can
be used in conjunction with other therapies that are intended to prolong life, including oral
pharmacotherapy, surgery, implantable device therapy, and MCS (Ezekowitz et al., 2017).
In summary, HF is a complex clinical syndrome involving abnormal heart function
causing, or increasing the subsequent risk of, clinical symptoms and signs of reduced cardiac
output and/or pulmonary or systemic congestion at rest or with stress (Ezekowits et al., 2017).

29
Optimal management for patients with HF presents many challenges to the patient, their family
or caregivers, and the health care system. An accurate and timely diagnosis is critical to initiate
treatment that will improve QoL, reduce hospitalizations, and prolong survival (Ezekowits et al.,
2017). AF and HF are two of the most common cardiac diseases and are intrinsically linked as
they share common risk factors (AlTurki et al., 2019). The disorders perpetuate each other and
create unique challenges to their management. The combined diseases lead to increased negative
health outcomes, such as morbidity, mortality, and hospitalization, thus contributing to financial
burdens on the healthcare system (AlTurki et al., 2019).
Atrial Fibrillation and Heart Failure
Although distinct, HF and AF are highly interrelated cardiovascular disorders. AF often
contributes to worsening HF symptoms, and the prevalence of AF can give rise to, and parallels
the severity of, HF ( Verbrugge & Mullens, 2014). The presence of AF is associated with a
worse prognosis for overall survival. AF exacerbates HF due to decreased cardiac output,
increased myocardial oxygen consumption, decreased coronary perfusion, and the development
of tachycardia-induced cardiomyopathy (Ezekowits et al., 2017). The occurrence of one
condition has implications for the treatment of the other, and the presence of one condition often
hinders treatment for the other (Verbrugge & Mullens, 2014). As the population ages, the
prevalence of AF and HF is expected to increase dramatically (Smigorowsky et al., 2017), and
together they have the potential to cause a critical increase in healthcare burden and adversely
impact patient experience or QoL (Andrade et al., 2018). The combination of HF and AF leads to
harmful hemodynamic and symptomatic consequences (Di Biase et al., 2016).

30
Epidemiology
AF and HF are two conditions that are predicted to dominate the next 50 years of
cardiovascular care, as they are increasingly prevalent and associated with high morbidity,
mortality, and healthcare costs. They are closely inter-related with similar risk factors, and
usually affects the elderly with a significant burden of comorbidity (Kotecha & Piccini, 2015).
Prevalent and Incidence. HF is three times more common among patients with AF
compared to patients without AF (Wandell et al., 2018). The prevalence of AF in the presence of
HF increases from < 10% in individuals with NYHA functional class I, to approximately 50% in
individuals with NYHA functional class IV. Both diseases increase in incidence and prevalence
with age and are associated with dramatic increases in mortality and morbidity, including
increased hospitalizations, decreased QoL, and considerable financial healthcare burdens (Maisel
& Stevenson, 2003). For example, a community based study by Chamberlain et al. (2011)
determined that individuals with AF prior to HF had a 29% increased risk of death, whereas
those who developed AF after HF exhibited a greater than two-fold increased risk of death. Thus,
demonstrating that the combined disorders contributes to a greater risk of mortality.
Cost and Burden on the Healthcare System. As it is evident that AF commonly
coexists with HF and worsens prognosis, the financial burden on the healthcare system is
substantially increased when both diseases occur together (Chugh et al., 2013). A Markov
decision analysis model by Perez et al. (2011) measured rate control versus rhythm control for
management of AF in the presence of HF. In 2009, costs were measured in U.S. dollars, and
clinical outcomes in quality-adjusted life-years (QALY). Pharmacological rate control was less
costly and more effective than rhythm control. Base case and probabilistic sensitivity analyses
cost and effectiveness values for rate control were $7231 and 2.395 QALYs, whereas those for

31
rhythm control were $16,291 and 2.197 QALYs (95% UI 2.155-2.237 QALYs) (Perez et al.,
2011). As such, the study demonstrates that rate control is less costly and more effective than
rhythm control, however both have financial implications on the healthcare system.
Risk Factors. AF and HF often coexist, and underlying heart disease associated with HF
tends to increase left atrial pressure, cause atrial dilation, and alter wall stress, which is an
example of structural abnormalities (January et al., 2014). Many disease processes that
predispose patients to HF, such as valvular heart disease, hypertension, diabetes, and coronary
artery disease, are also risk factors for AF (McCance & Huether, 2019). Risk factors for
developing AF include conditions that are found to promote atrial remodelling, which includes
heart failure, ischemic heart disease, hypertension, obesity, obstructive sleep apnea, and
rheumatic heart disease. Other classic cardiovascular disease risk factors, such as diabetes,
advanced age, male sex, alcohol consumption, and smoking, also contributes to AF (Andrade et
al., 2020; McCance & Huether, 2019). Additionally, echocardiographic findings that are
commonly found in patients with HF, such as left atrial enlargement, increased left ventricular
wall thickness, and reduced left ventricular fractional shortening, also predispose patients to the
development of AF (Maisel & Stevenson, 2003).
Pathophysiology
Causality of AF and HF are highly interconnected. The pathophysiology of combined AF
and HF involves alterations in neurohormonal activation, electrophysiologic parameters, and
mechanical factors that consequently cause HF to predispose AF, and inadvertently for AF to
exacerbate HF (Maisel & Stevenson, 2003). AF is a complication of many cardiopulmonary
disorders, such as HF, and causes increased afterload, elevated filling pressures, and left atrial
enlargement (Piccini et al., 2013). Specifically, AF causes reductions in cardiac output due to

32
shorter diastolic filling time, loss of atrial contractile function, and elevated filling pressures, in
addition to myocardial dysfunction caused by tachycardia (Andrade et al., 2020). As such, AF
results in structural abnormalities and electric remodeling changes that enhance susceptibility to
HF (January et al., 2014; Maisel & Stevenson, 2003; Piccini et al., 2013). Additionally, agerelated declines in vascular compliance, increased population longevity, and the increasing
prevalence of cardiovascular disease has led to a growing AF and HF epidemic (Piccini et al.,
2013). Tachycardia and shortening of diastolic filling time associated with irregular ventricular
activation with AF further impair diastolic relaxation and promote HF, which further induces
atrial remodeling leading to the preservation of AF (Staerk et al., 2017).
Management
Individuals with concomitant AF and HF respond differently to treatment than those with
HF or AF alone. As such, there is a need to identify and treat according to best evidence to
prevent adverse outcomes and reduce the burden that HF and AF are expected to have on global
healthcare systems in the future (Kotchea & Piccini, 2015). For AF, the main goals of therapy
are control of symptoms and prevent cardiac dysfunction with subsequent HF and/or
hemodynamic compromise, as well as prevent arterial thromboembolism, including stroke.
These goals are also appropriate in patients with HF, as symptoms are frequent and potentially
disabling due to the interaction between the two conditions (Olshansky, 2019).
There are two strategies used for medical therapy, including rate and rhythm control.
Rate control includes medications and atrioventricular node ablation with pacing, whereas
rhythm control includes AADs, as well as cardioversion and catheter ablation, which will be
briefly discussed (Olshansky, 2019).

33
Pharmacological Interventions. There are various types of pharmacological agents used
to treat AF and HF separately. Rhythm and rate control strategies are reasonable in patients with
HFpEF or HFrEF. Rate control includes BBs are first line therapy due to their favourable effect
on morbidity and mortality (January et al., 2014), as they prolong diastolic filling time, reduce
myocardial ischemia, control hypertension, and prevent arrhythmias (Ezekowitz et al., 2017;
Olshansky, 2019). While ND-CCBs, such as verapamil and diltiazem, should be avoided with
HFrEF. If a patient is unable to receive either medication, digoxin may be considered (Wandell
et al., 2018). Rhythm control therapy includes AAD therapy or ablation of AF to suppress the
recurrence of AF. Some AADs, such as amiodarone and dronedarone, are not well tolerated by
patients with HF due to adverse effects. These drugs have led to an increased risk of pump
failure and arrhythmic deaths. As such, pharmacological rhythm control is not necessarily
superior to rate control in influencing long term outcomes (Packer, 2020).
Nonpharmacological Interventions. Pharmacology of rhythm and rate control strategies
for AF are not always effective or tolerated in patients with HF (Andrade et al., 2020; Ezekowitz
et al., 2017). Electrical cardioversion can be performed to return patients to normal sinus rhythm
to help stabilize the patient and try HF management (Olshansky, 2019). Another management
strategy includes catheter ablation for patients with symptomatic AF who have HF and failure of
AAD therapy, rather than continued attempts with AAD therapy or no AAD therapy (Olshansky,
2019). Catheter ablation has be shown to be a superior management strategy compared to
pharmacotherapy, whether rate or rhythm control, for improving outcomes in patients with
concomitant AF and HF (AlTurki et al., 2019).
In summary, AF and HF are two epidemics of cardiovascular disease, and both diseases
share similar risk factors and pathophysiology (Andrade et al., 2020; McCance & Huether,

34
2019). Combined AF and HF are increasingly prevalent and associated with high morbidity,
mortality, and healthcare costs (Chugh et al., 2013). However, finding effective therapies for the
population of interest is challenging, as treatments shown to be effective in one or other of these
conditions alone have also been observed to have efficacy or safety concerns in patients with HF
and AF combined. As such, there is an evident clinical need to optimally manage the
concomitant diseases in order to prevent poor outcomes, as well as reduce the significant burden
the diseases are predicted to have on healthcare systems (Kotech & Piccini, 2015).
Primary Care Setting
As with many other chronic cardiovascular conditions, the complex nature of AF and HF
requires a systematic approach to management. Much of the initial management of AF can be
provided by PCPs, with the support of specialist cardiology input to guide management decisions
in selected AF patients who develop problems or complications (Andrade et al., 2020). While
with HF, specialist supports are valuable even at an early stage, and often require ongoing
partnerships between primary and speciality care providers.
Due to the increasing prevalence of chronic conditions, healthcare systems are challenged
to provide necessary care and enable patients to participate in their treatment plan (Watts et al.,
2009). As such, NPs play a key role in meeting these challenges and barriers to healthcare. NPs
are able to diagnose, prescribe and order treatments, as they are independent practitioners that
work collaboratively within a healthcare team (Smigorowsky et al., 2020). NPs are unique, as
they use select medicine and advanced nursing skills that may result in greater benefits to
patients and the healthcare system. As such, NPs are associated with decreased costs, increased
patient engagement with their care, and improved QoL (Smigorowsky et al., 2020). In the

35
context of AF and HF, the NP in primary care are well situated to support patient care and to
work alongside specialists, including cardiologists and NPs in the cardiac clinical setting.
Support for patient self‐management, by providing education and training, can facilitate
the long term care of patients with chronic diseases (Dennis et al., 2008). Specifically, selfmanagement involves daily management of chronic conditions over the course of an illness with
the goal of improving health outcomes by enabling individuals to effectively manage their own
illness (Andrade et al., 2020). The traditional provider-patient relationship shifts to shared
decision making, where the patient is responsible for guiding their care in partnership with their
health care providers. Key areas of focus include medical management by adherence to a
therapeutic regimen, behaviour modification, and development of strategies to provide emotional
and psychosocial support (Andrade et al., 2020).
NPs have a key role in supporting self‐management, as they provide patients with
essential tools to be successful in improving health outcomes (Watts et al., 2009). NPs possess
skills that have been shown to be harmonious with behavioral health specialists, and therefore
are qualified to manage patients with chronic diseases in outpatient settings (Watts et al., 2009).
Patient-centred care requires collaboration between clinicians and knowledgeable
patients, considering the best available evidence in addition to the patient’s values and
preferences (Andrade et al., 2020). As such, education is also vital to the concept of selfmanagement, as it necessary for the patient’s perceived understanding about the causes,
consequences, clinical manifestations, and controllability of their disease (Andrade et al., 2020).
Also, patient and family education have been shown to improve clinical outcomes (Ezekowitz et
al., 2017). Misalignment of the therapeutic interventions with the patient values and preferences
can lead to dissatisfaction with therapy, nonadherence of treatment, and thus therapy

36
discontinuation, resulting in an increased risk of adverse outcomes such as stroke (Andrade et al.,
2020). Unfortunately, patients with cardiovascular diseases, such as AF, often have a poor
understanding of the cause and consequences, such as risk of stroke (Andrade et al., 2020).
Therefore, individualized patient education is able to provide accurate illness representation,
improves compliance to treatment, manages therapeutic options and goals, relieves diseaseassociated anxiety and stress, and promotes self-management (Andrade et al., 2020). As well,
continuing medical education must be readily available for providers to help support knowledge
translation and help foster evidence based research into clinical practice and navigate patients
and providers between levels of care (Ezekowitz et al., 2017).
Nurse Practitioner Role
Management of AF in the presence of HF is relevant to NPs, as optimizing treatment of
the combined disorders involves incorporating broad expertise (Verbrugge & Mullens, 2014).
Addressing risk factors is a goal of therapy that can be effectively accomplished through a
multidisciplinary management approach using subspecialists of cardiologists, in addition to other
medical professionals, such as NPs (Andrade et al., 2018; Verbrugge & Mullens, 2014). NPs are
not specialized in a particular chronic disease, however they receive advanced, formal training in
primary care (Health Quality Ontario, 2013). For example, a study by Health Quality Ontario
(2013) aimed to determine the effectiveness of specialized nurses managing chronic disease in
patient care. Documents of various providers were assessed by reviewing patients’ charts in the
diabetes subgroup analysis. The study demonstrated that NPs were more likely to provide
education. As well, NPs provide a holistic approach to chronic illness management, including
medication concerns and barriers to adherence (Watts et al., 2009). Specifically, NPs are
competent in behavioral modification for chronically ill patients, which is valuable for practices

37
and approaches that related to self-management support. NPs coach patients to set goals and
provide assistant to achieve these goals (Jeon & Benavente, 2016). Particularly, health coaching
involves helping patients “gain the knowledge, skills, tools and confidence” (p. 24) to become
active participants in their care to be able to reach their health goals (Bennett et al., 2010). Health
coaching is emerging as an effective approach to improve patients’ behavior by empowering
them to be the center of their health care needs.
Physicians in primary care struggle to fit multiple agenda items into a 15-minute visit,
and thus may not be able to meet every need of their patients with chronic conditions. Thus, half
of patients leave primary care visits not understanding what was discuss, as only 9% of patients
participate in decisions, and average adherence rates for prescribed medications are about 50%,
and for lifestyle changes they are below 10% (Bennett et al., 2010). However, NPs are able to
provide care with improved outcomes when compared to family physicians (Sciamanna et al.,
2006). For example, patients with coronary heart disease who were randomized to receive care
from an NP with training to follow a treatment algorithm for one year were significantly more
likely to achieve low-density lipoprotein cholesterol levels than those patients who were
randomized to usual care with a family physician and/or cardiologist (Mundinger et a l., 2000).
Thus, by NPs involving patients in the decision-making process encourages self-determination,
self-responsibility, and ownership (Jeon & Benavente, 2016). As well, the NP and patient
relationship is a cost‐effective strategy to promote patients’ health (Hayes & Kalmakis, 2007).
In summary, NPs address major deficiencies in chronic illness management through
providing education and promoting self‐management to patients and their families (Watts et al.,
2009). NPs have been increasingly involved in providing pre-emptive care with an expanded
scope of practice through coaching patients to set and achieve goals, thus empowering them to

38
coordinate their own care (Jean & Venavente, 2016). Thus, management of chronic illness is a
longitudinal process where NPs play a key role, as NPs have unique skills that are well
positioned to foster patient‐centered care (Andrade et al., 2020). As such, the involvement of
NPs managing combined AF and HF leads to cost savings, thus reducing the burden on the
healthcare system by increasing adherence to treatment plans and improving clinical and patientreported outcomes (Smigorowsky et al., 2017).

39
CHAPTER II: METHODOLOGY
The integrative review method is designed to summarize existing literature in a
systematic process, allowing for a more comprehensive understanding of a particular healthcare
problem (Whittemore & Knafl, 2005). By incorporating diverse methodologies, integrative
reviews contribute directly to nursing science, in addition to informing wider research, practice,
and policy initiatives, and are commonly used to support evidence-informed practice
(Whittemore & Knafl, 2005). The purpose of this integrative literature review is to identify
strategies to best manage and support patients with AF in the presence of HF in primary care
settings. As such, there is an opportunity to better understand the care of patients with these
challenging conditions, which in turn may inform initiatives that can improve patient outcomes,
reduce hospitalizations, and decrease healthcare costs.
Integrative Review Methods
Integrative reviews allow for various perspectives on an issue to be organized
systematically by incorporating diverse forms of literature. They capture the context, processes,
and subjective components of the topic, which aids in forming nursing science, as well as
informing research, practice, and policy initiatives (Whittemore & Knafl, 2005). In comparison,
systematic reviews have more of an emphasis on the formal assessment of the quality of the
study, as they combine the evidence of multiple studies focused on a specific clinical problem to
inform practice (Whittemore & Knafl, 2005).
Integrative reviews allow for the inclusion of diverse methodologies and are able to
contribute to evidence‐based practice for nursing. For example, a guideline by Andrade et al.
(2018) was developed through studies and literature, and provides periodic reviews of new
information and developed focused updates that discuss clinically relevant advances for the

40
management of AF. However, further opportunities exist to understand the management of
concomitant AF and HF, which in turn may help inform clinicians about the risks and benefits of
therapeutic options.
The literature review will follow the integrative review methodology as delineated by
Gray et al. (2017). In congruence with this approach, the following review stages were
undertaken: 1) Development of the research question, 2) Preliminary review of the literature and
focused search, and 3) Analysis and reporting
Development of the Research Question and Search Strategy
The impetus for this review was grounded in the professional experiences and interest of
the writer. Over four years, the writer has worked in critical care, providing direct care to those
living with cardiac disorders. It is these clinically-grounded experiences that has led her to
investigate the management of concomitant cardiac diseases, specifically combined AF and HF.
The high volume of patients seen in emergency departments with unmanaged AF, in addition to
a subset of HF, intrigued the writer to explore the most optimal approach to support patients and
avoid hospitalizations, thereby reducing the burden on the healthcare system. By exploring the
topic’s relevance and identification of the specific problem, the research question was developed
by following the population, intervention, and evaluation (PIE) approach (Gray et al., 2017). The
population consists of outpatients with HF. The intervention includes the management of AF
with a focus on arrythmia care. The effect is an improvement in outpatient management of AF in
the context of HF, and therefore a reduced burden on the healthcare system. The formulated
question is, “How can the NP best manage HF patients with AF in outpatient settings to help
reduce the burden on the healthcare system?” With the above in mind, the strategies for the
literature review is as follows, which was conducted as suggested in Gray et al. (2017).

41
Search Strategy
A health librarian at University of Northern British Columbia’s (UNBC) library (Dr. T.
Fyfe) was consulted during the literature review search. A preliminary literature search was
performed using electronic databases accessed through UNBC’s library, including Cumulative
Index of Nursing and Allied Health Literature (CINAHL [ESBCO]), MEDLINE (Ovid), and
Cochrane Reviews (EBM). The databases were selected as they provided access to full-text
articles and professional and academic literature. Specifically, CINAHL was chosen, as it
provides full text for more than 770 journals related to nursing and allied health journals.
Additionally, the Cochrane Database of Systemic Reviews was utilized, as it is the leading
database for systematic reviews in healthcare. Lastly, MEDLINE was selected, as it contains
citations from over 4, 8000 current biomedical journals pertaining to medicine, nursing, and the
health care system (Gray et al., 2017). As such, the above databases represent a wide range of
sources for primary research articles and systematic reviews that pertain to areas of medicine,
nursing, and healthcare, which are relevant to the topic of AF in the context of HF, with a focus
on arrythmia care.
Search Terms
Through searching the background literature and consulting with the health librarian,
selected search terms were selected. Search terms and MeSH terms were utilized and Boolean
operations, such as “AND”, “OR”, and “NOT,” were used to group or exclude keywords during
the search – see table 1. Additionally, the truncation (*) symbol was used to retrieve additional
articles related to HF and AF. See Appendix A for specific database searches.

42
Table 1
Search Terms and MeSH Terms for the Literature Review
Population
Outpatients with
HF
Intervention
Managing AF
Evaluation
Reduced burden
on the health care
system

“heart failure” OR “congestive heart failure” OR “cardiac failure” OR
“chf” OR “chronic heart failure” OR “congestive heart failure” AND
“atrial fibrillation” OR “afib” OR “af”
“antiarrhythmic drugs” OR “rate control” OR “rhythm control” OR
“catheter ablation” OR “physicians, family" OR "family nurse
practitioners" OR "primary health care” OR “family practice”
“health care costs” OR outcomes OR “preventative health care” OR
“readmission” OR “hospitalization”

Preliminary Review of the Literature and Focused Search
Each database was individually searched as found in Appendix A. Filters were applied,
including the English language. After the initial database search was completed, a total of 1326
articles were found and moved into Zotero (n.d.), which is a standard software that manages
references for bibliographic data and research materials. The duplicate articles were removed,
leaving 1237 articles remaining. These article’s titles were screened for relevance to the research
question, 221 articles remained. The 221 articles were read and also screened for relevance. The
remaining 32 articles were retrieved in full text and were read closely. These were then reviewed
according to the eligibility criteria. After a thorough review of the remaining 32 records by
considering the inclusion and exclusion criteria, a focused search was undertaken. The search
produced a more manageable body of literature for a focused review, resulting 20 eligible studies
included in the synthesis. See the Appendix B for a PRISMA flow diagram to help illustrate how
the applicable articles were screened.
Eligibility Criteria
Eligibility was established by applying predetermined inclusion and exclusion criteria,
which were monitored throughout the literature search and guided the selection process of the

43
articles included in the literature review. The inclusion and exclusion criteria were chosen to
reflect the diversity needed to address the clinical question, as well as support the literature
selection process to ensure the information would be translatable into a primary care setting.
Inclusion Criteria. References in the English language original research, such as
controlled studies, systematic reviews, and articles from peer-reviewed journals were included.
Studies from developed countries were chosen, as they are the most relevant documents that
relate to the Canadian healthcare system. Literature from 2015 to present were included with the
intention of capturing the most recent practices and recommendations, as the literature has been
rapidly evolving with major revisions to the AF and HF guidelines. Articles pertaining to both
AF and HF were included. Lastly, participants included were adults aged 18 years or older, as
AF and HF are problems in the aging population (Smigorowsky et al., 2017), and seldom studies
were found in the literature search with patients younger than 18 years of age.
Exclusion Criteria. Articles that focussed on teaching or education were excluded, as the
focus of the research question is on clinical content. Studies with a focus on acute
decompensated HF, rapid AF, and hemodynamically unstable samples were excluded from the
study, as the management for acute episodes are not implemented in a primary care setting.
Youth and children less than 18 years of age were excluded as this group is beyond the scope of
this literature review. Articles pertaining to only HF or AF alone were excluded, as there is
already a great body of research for managing both disease independently, and the focus was
managing both diseases together.
Analysis and Reporting
The review is guided by the integrative review approach and framework that directed the
initial literature analysis involved three different appraisal tools. Specifically, an abstraction

44
analysis was conduced using the Critical Appraisal Skills Programme (2013) appraisal tools for
the single studies. In addition, from Davies & Logan (2018) and a worksheet for appraising
systematic reviews was utilized for the eight systematic studies. A total of 20 articles were
critically appraised for content and then organized thematically. A matrix was developed to
document the key aspect of the studies and support the analysis of the articles. Articles were
reviewed in full and organized thematically in a matrix, which can be found in appendix (C).
Through analyzing the final articles in the integrative literature review, three key themes
emerged. The matrix was helpful in identifying areas of overlaps and focal topics. These were
found to reflect key health service outcomes, including areas that indicate burden and impacts for
both the patient and healthcare system. The themes include: 1) Catheter ablation is superior to
medical therapy, 2) Safety considerations, and 3) Differing treatment for HFrEF and HFpEF.
Themes were developed and reported descriptively, and key studies were highlighted and
a synthesis of the key outcomes provided. An integrative review approach was used to explore
the literature relating to concomitant AF and HF. A systematic search was undertaken and
relevant literature was captured and screened for eligibility. The final cohort of articles were
reviewed in detail and were analyzed thematically. Descriptive accounts of the key themes are
presented in detail in the following findings chapter.

45
CHAPTER III: FINDINGS
In the findings chapter, a critical review of the literature on the management of
concomitant AF and HF will be presented. This is supplemented by a literature review matrix of
the single studies, as well as the systematic reviews, and meta-analyses, which organizes the
findings of the abstracted documents and provides relevant research data for optimally managing
combined AF and HF. The matrix can be found in Appendix C.
The integrative literature review included a final cohort of eight systematic reviews
and/or meta-analyses and 12 single studies, dating from 2015 to present. Of the single studies,
four were conducted in the USA (Black-Maier et al., 2018; Di Biase et al., 2016; Kuck et al.,
2019; Marrouche et al., 2018), one in Korea (Yu et al., 2018), one in Germany (Eitel et al.,
2019), four in Japan (Fukui et al., 2020; Ichijo et al., 2018; Machino-Ohtsuka et al., 2019;
Saksena et al., 2018), and one in China (Geng et al., 2017). All articles were quantitative, with a
clinical focus on the treatment of combined AF and HF. Of the single studies, six studies focused
on a HFrEF (AlTurki et al., 2019; Di Biase et al., 2016; Eitel et al., 2019; Geng et al., 2017;
Kuck et al., 2019; Marrouche et al., 2018), two studies focused on HFpEF (Fukui et al., 2020;
Machino-Ohtsuka et al., 2019), and five studies compared the effects on HFrEF and HFpEF
(Black et al., 2018; Eitel et al., 2019; Hess et al., 2020; Ichijo et al., 2018; Sasken et al., 2018).
Four studies included patients with HF NYHA class ≥ two (Di Biase et al., 2016; Eitel et al.,
2019; Geng et al., 2017; Marrouche et al., 2018). Two studies did not specify ejection fraction or
NYHA class (Yu et al., 2018; Sasken et al., 2018). One study specified persistent type of AF (Di
Biase et al., 2016), one specified non-paroxysmal (Fukui et al., 2020), and one specified
paroxysmal (Ichijo et al., 2018). Seven studies included two or more types of AF, such as
paroxysmal, persistent, and/or permanent AF (Black-Maier et al., 2019; Eitel et al., 2019; Geng

46
et al., 2017; Kuck et al., 2019; Machino-Ohtsuka et al., 2019; Marrouche et al., 2018; Saksena et
al., 2018). One study did not specify any type of AF (Yu et al., 2018). There were also seven
single studies that were retrospective (Black-Maier et al., 2018; Fukui et al., 2020; Gene et al.,
2017; Ichijo et al., 2018; Machino-Ohtsuka et al., 2019; Sasken et al., 2018; Yu et al., 2018).
Despite attempts to capture literature of direct relevance to the primary care setting, there
was a lack of primary care specific studies, and thus complexities for generalizing the results to
an outpatient setting occurred. Likewise, synthesizing the articles within the review made it
evident that the body of literature is very diverse, therefore creating challenges for making
meaningful comparisons or robust recommendations. However, through analyzing the final
articles, three key themes emerged including: 1) Catheter ablation is superior to medical therapy,
2) Safety considerations, and 3) Differing treatment for HFrEF and HFpEF. The discussion of
the themes will be facilitated based on the data obtained through reviewing multiple studies with
a similar focus. As the topic is centered on the treatment of two dominant cardiovascular
conditions, the body of literature is also quantitative, meaning that the accounts of lived
experience are also not well addressed in the contemporary literature.
Catheter Ablation is Superior to Medical Therapy
When determining the best management strategy for AF in HF patients, it is important to
be aware of the therapies with the most optimal patient outcomes. There are clear guidelines for
how to manage AF and HF separately, however, there is a lack of a clear consensus for treating
the combined diseases. Thus, PCPs, in consultation with cardiac specialists, are often faced with
the need to determine therapeutic strategies without strong guidance. In the literature, various
studies were identified and reviewed that aimed to determine if catheter ablation was more
effective than medical therapy with outcomes of rehospitalizations, AF recurrence, mortality

47
rates, QoL and functional capacity, and/or improved LVEF. A total of fifteen studies addressed
the idea of catheter ablation being superior to medical therapy, eight of which were systematic or
meta-analyses (AlTurki et al., 2019; Chen et al., 2020; Ma et al., 2020; Ruzieh et al., 2019; Smer
et al., 2018; Turagam et al., 2019; Xu et al., 2019; Zhu et al., 2016), and seven of which were
single studies (Di Biase et al., 2016; Fukui et al., 2020; Geng et al., 2017; Ichijo et al., 2018;
Machino-Ohtsuka et al., 2019; Marrouche et al., 2018; Yu et al., 2018).
Through examining the literature, catheter ablation use led to significant improvements in
rehospitalization, AF recurrence, and morality rates, and suggested a strong association with an
improvement in QoL and functional capacity, as well as improved LVEF. The articles focused
on the use of tools to manage the arrhythmia, of which most were comparing newer catheter
ablation techniques to traditional medical regimes using rate and/or rhythm control. See table 2.
Table 2
Catheter Ablation is Superior to Medical Therapy for AF in Presence of HF

AlTurki et al. (2019)
Chen et al. (2020)
Di Biase et al. (2016)
Fukui et al. (2020)
Geng et al. (2017)
Ichijo et al. (2018)
Machino-Ohtsuka et al.
(2019)
Marrouche et al. (2018)
Ma et al. (2020)
Ruzieh et al. (2019)
Smer et al. (2018)
Turagam et al. (2019)
Xu et al. (2019)
Yu et al. (2018)
Zhu et al. (2016)

Rehospitalizations

AF
Recurrence

Mortality

X
X
X
X
X
X
X

X
X
X
X
X
X

X
X
X

X
X
X
X
X
X

X
X
X
X

X
X
X
X
X
X
X

QoL and
Functional
Capacity
X
X

LVEF

X
X

X
X
X

X
X
X
X

X
X
X
X

X

X

48
The theme of catheter ablation being superior to medical therapy will be discussed below.
It is important to emphasize that the Catheter Ablation versus Standard Conventional Therapy in
Patients with Left Ventricular Dysfunction and AF (CASTLE-AF) trial developed by Marrouche
et al. (2018) made a significant impact on the management of concomitant AF and HF. In
contrast to previous trials, the hard primary end point of death or hospitalization for HF was
evaluated. Participants were followed for up to 60 months to assess long-term outcomes, and the
mortality benefit of ablation in the trial did not arise until after three years. Patients with both
paroxysmal and persistent AF were both included, and both conditions were shown to benefit
from catheter ablation. There was no focus on a specific strategy, such as rate control compared
to rhythm control, or choice of AADs in the medical-therapy group, as previous studies had not
shown one strategy or drug to be superior to another. The study was evolutionary for the
subpopulation of interest, as it peaked other studies to examine the same, thus contributing to
major practice considerations and the inclusion of catheter ablation in guidelines.
Rehospitalizations
The analysis of the literature demonstrated that many studies sought to determine the
impact of different interventions, such as catheter ablation and pharmacotherapy of rhythm or
rate control, on rehospitalization rates for patients with concomitant AF and HF. Thirteen studies
discussed rehospitalization rates for patients with HF and AF undergoing catheterization as
compared to pharmacotherapy, of which seven were systematic studies and/or meta-analyses
(AlTurki et al., 2019; Chen et al., 2020; Ma et al., 2020; Ruzieh et al., 2019; Smer et al., 2018;
Turagam et al., 2019; Xu et al., 2019) and six were single studies (Di Biase et al., 2016; Fukui et
al., 2020; Geng et al., 2017; Ichijo et al., 2018; Machino-Ohtsuka et al., 2019; Marrouche et al.,

49
2018). The analysis of the studies vastly demonstrate that catheter ablation is associated with a
decrease, or freedom from, HF-related hospitalizations compared to pharmacotherapy.
A meta-analysis by Smer et al. (2018) was performed according to the Preferred
Reporting Items for Systematic Reviews and Meta‐Analyses statement. The methods of the
statistical analysis were rigorous and thorough, as two authors independently searched databases
from January 1966 to February 2018, and the selected manuscripts and review articles were
manually searched for additional studies. A total of 1,597 articles were screened, however only
six trials with a total of 775 patients met the inclusion criteria, which was considered to be a
small sample size and questions the potential generalizability of the findings. There were 388 in
the catheter ablation group and 387 in the medical therapy group, and a selection bias occurred
due to the type of patients offered to participate in the randomized control trials. Specifically,
those with advanced HF and NYHA class IV were mostly excluded from these studies due to the
likelihood of not having favourable outcomes. The patients included were younger males with
moderately decreased LVEF, shorter duration of persistent AF (mean 18.5 months), and less
likely to have coronary artery disease. Thus, the analysis results may not be useful for older
patients with severely depressed LVEF and/or longer duration of AF. The meta-analysis aimed to
compare catheter ablation to medical therapy in patients with AF and HFrEF, and determined
that ablation of AF was associated with significantly less HF hospital readmissions compared to
medical rate and/or rhythm control (CI 0.32‐0.78, p=0.002). Similar findings were also found in
systematic reviews and meta-analyses by AlTurki et al. (2019), Chen et al. (2020), Ma et al.
(2020), Ruzieh et al. (2019), and Turagam et al. (2019), demonstrating that the rate of HF-related
hospitalizations were significantly lower in catheter ablation groups than medical therapy groups.
In these studies, HF hospitalizations varied with ablation verses pharmacotherapy (95% CI 0.44-

50
0.71, p<0.0001; 95% 30.6% vs. 47.5%, p=0.003; 95% CI 0.46 - 0.66; 26.7% vs. 45.1%, 95% CI
0.29 – 0.64, p<0.001; 16.4% vs. 27.6%, CI 0.39 to 0.93, respectively).
A retrospective, non-randomized study by Ichijo et al. (2018) also discussed catheter
ablation and medical therapy, however, specifically compared freedom of HF-related unplanned
hospitalizations between HFrEF and HFpEF. The analysis of the study demonstrated that for
HFrEF patients, freedom of HF-related unplanned hospitalizations at 1, 2, 3, and 4 years after the
initial procedure was 97.6%, 97.6%, 97.6%, and 97.6%, respectively. For HFpEF patients, HFrelated hospitalizations were observed in 3.6% post-AF ablation, and at 1, 2, 3, and 4 years after
the initial procedure was 96.2%, 96.2%, 96.2%, and 96.2%, respectively.
Alike to the above single studies or systematic reviews/meta-analyses, Fukui et al. (2020)
conducted a retrospective study with a Kaplan‐Meier curve analysis that revealed significantly
more patients receiving ablation of AF were free from HF rehospitalization compared to
conventional pharmacotherapy of AADs and/or BBs in patients with HFpEF after a mean
follow‐up of 792 ± 485 days (p=0.0039). As well, catheter ablation of AF was the only
preventive factor of HF rehospitalization (OR = 0.15; 95% CI 0.04‐0.46; p <0.001), and all‐cause
rehospitalization was significantly lower in ablation group compared to the control group
(p=0.0284). The study also draws attention to the findings of Marrouche and colleagues (2018),
who found that fewer patients receiving catheter ablation compared to the medical therapy were
hospitalized for worsening HF (20.7% vs. 35.9%; 95% CI 0.37-0.83; p=0.004). While the
majority of the studies found statistically significant improvements in hospitalization, one
retrospective cohort study by Geng et al. (2017) investigated the relationship between catheter
ablation and medical therapy did not find a statistically significant association for unplanned
hospitalizations (16.1% vs. 10.0%, p=0.140).

51
Three studies explicitly discussed the types of medication given to manage AF and HF
together, all of which are in agreeance that medical therapy is associated with increased HFrelated hospitalizations. For example, the quantitative, multi-center, open labelled, randomized,
parallel-group study by Di Biase et al. (2016) aimed to determine if catheter ablation is more
effective than amiodarone for the treatment of persistent AF in patients with HF. In total, 866
patients were screened, 331 were eligible for inclusion. In total, 203 consented and were
included in the study and randomly assigned to receive catheter ablation (n=102) or amiodarone
therapy (n=101). Patients were randomly assigned by a 1:1 ratio to undergo catheter ablation for
AF or to receive amiodarone. Baseline characteristics in the catheter ablation group included
ages 62 ± 10, 77% male patients, and AF duration of 8.6 ± 3.2 months. In the amiodarone group,
baseline characteristics included ages 60 years ± 11, 74% male, and AF duration of 8.4 ± 4.1
months. A secondary end point was unplanned hospitalization rates, which was lower in the
catheter ablation group (31%) compared to the amiodarone group (57%) (p<0.001). The
methodology was rigorous, as a computerized central randomization scheme was undertaken
using block randomization, and sets of randomly selected blocks were provided to the sites. The
study also included 30% oversampling for attrition and sampling was based on 80% power
analysis. However, there was a lack of formal comparison with a rate control strategy or
followed up period longer than 24 months. Also, sotalol and dofetilide are alternative AAD
medications available for managing combined AF and HF, however were not tested in the trial.
In another retrospective observational study, Machino-Ohtsuka et al. (2019) investigated
if the maintenance of sinus rhythm was associated with better prognosis compared with rate
control in patients with concomitant HFpEF and AF in 283 patients with HFpEF and AF. Of
these, 107 patients achieved maintenance of sinus rhythm by catheter ablation and/or AADs

52
(rhythm control) and 176 were treated with rate control medications, such as BBs, CCBs, and
digoxin. The analysis of the study determined that the rhythm control group had a lower
incidence of hospitalization even after adjustment with propensity scoring (adjusted HR, 0.27;
95% CI 0.12–0.61; p=0.002). Lastly, a meta-analysis by Xu et al. (2019) aimed to investigate the
effects of BBs on outcomes in patients with chronic HF and AF. Six studies, including four posthoc analysis of randomized control trials and two observational studies, showed the effect of
BBs treatment on hospitalization for HF. Although not explicitly comparing BBs to catheter
ablation, the analysis of the data indicates that treatment with BBs was not associated with a
reduction of hospitalization for HF (RR = 1.03; 95% CI 0.89–1.21, P = 0.66), thus favouring
catheter ablation.
Overall, although one study did not demonstrate a strong correlation of ablation of AF in HF
patients and reduced hospitalization rates (Geng et al., 2017), the majority of the study analyses
demonstrated statistically significant evidence that catheter ablation is an important therapeutic
option. Particularly, catheter ablation has been proven to be superior to conventional
pharmacotherapy for reducing HF hospitalizations.
AF Recurrence
The literature explored the impact of interventions, including catheter ablation and
pharmacotherapy of rhythm or rate control, on recurrence of AF arrhythmia for patients with
combined AF and HF. In particular, ten studies analyzed the AF reoccurrence rate for patients
with HF undergoing catheter ablation of AF, as compared to pharmacotherapy. Five of the
captured studies were systematic reviews and/or meta-analyses (AlTurki et al., 2019; Chen et al.,
2020; Ma et al., 2020; Ruzieh et al., 2019; Smer et al., 2018) and five were single studies (Di
Biase et al., 2016; Fukui et al., 2020; Geng et al., 2017; Ichijo et al., 2018; Marrouche et al.,

53
2018). The analysis of the studies greatly demonstrate that catheter ablation is associated with a
decrease in AF recurrence compared to pharmacotherapy.
A systematic and meta-analysis study by Ruzieh et al. (2019) identified 1,884 studies, of
which seven full texts met inclusion criteria. A total of 856 patients were included, of which 429
patients were randomized to catheter ablation and 427 patients were randomized to medical
therapy alone. There was an average age of 63.4 years and a mean follow-up time of 15.2
months. The proportion of males ranged between 73% and 96%. Mean LVEF was 29.9%. The
vast majority of patients had persistent AF, and NYHA Functional Classification II-III. The aim
of the study was to determine if catheter ablation for AF is superior to medical therapy in
patients with coexisting AF and HF. The results confirmed that significantly more patients in the
AF ablation group were in sinus rhythm at the end of trials compared to the medical therapy
group (73.7% vs. 18.3%, 95% CI 10.2 – 111.7; p<0.001). To achieve this high success rate from
AF ablation, repeat intervention was allowed in all trials and the percentage of patients who
underwent repeat ablation ranged from 19% to 54%. Despite the rigorous methodology, a
limitation included patients not being blinded, as none of the trials had a placebo group. There
was also an overall representation of males, as the inclusion of women was relatively low.
Alike to Ruzieh and colleagues (2019), the analysis of the studies by Chen et al. (2020)
and Ma et al. (2020) determined that catheter ablation rhythm control was associated with
significantly lower arrhythmia recurrence. Specifically, Chen et al. (2020) determined that
catheter ablation rhythm control was associated with significantly lower arrhythmia recurrence
(29.6% vs. 80.1%; 95% CI 0.01–0.14, p< 0.00001). Similarly, Ma et al. (2020) concluded that
64.2% (95% CI 49.4% to 79.0%) of patients undergoing catheter ablation were free from AF
after the first procedure. As well, catheter ablation was repeated in patients with recurrent AF,

54
and at the end of follow-up 74.9% (95% CI 63.2% to 86.5%) of patients receiving catheter
ablation had freedom from AF, and AF burden was 14.2% (95% CI -10.7% to 39.1%).
Comparable to the above studies, the analysis of the CASTLE-AF trial by Marrouche et
al. (2018) determined that 63.1% of the patients receiving AF ablation and 21.7% receiving
medical-therapy (p<0.001) were in sinus rhythm at the 60-month follow-up period and had not
had recurrence of AF since the previous follow-up visit at 48 months. The adjudicated rate of
recurrence of AF in the ablation group among those who had actually undergone ablation and
who were followed for up to 60 months was 50.0%, with an average of 1.3 ± 0.5 ablation
procedures per treated patient. As well, a single center, retrospective non-randomized study by
Ichijo et al. (2018) aimed to determine the long-term effects of ablation of AF in patients with
HF. For patients with HFrEF, 92.1% of patients were free from any recurrent atrial arrhythmias,
and arrhythmia-free survival at 1, 2, 3, and 4 years after the last procedure was 95.3%, 88.7%,
88.7%, and 88.7%. For patients with HFpEF after 1.4 ± 0.5 procedures, 85.5% of patients
remained free from any recurrent atrial arrhythmias, and arrhythmia-free survival at 1, 2, 3, and 4
years after the last procedure was 90.0%, 84.6%, 79.3%, and 79.3%.
In contrast, a retrospective study by Fukui et al. (2020) attempted to determine the
relationship between catheter ablation and medical therapy in regards to the recurrence of AF,
however, insignificant results were generated. Although the analysis of study findings illustrates
that patients undergoing ablation of AF had advantages, such as lower rehospitalization rates, the
recurrence of AF did not differ compared to the control group receiving AADs and/or BBs after
a mean follow‐up of 703 ± 424 days (p=0.119).
Two studies addressed catheter ablation and medical therapy specific to patients with AF
and HFrEF. Systematic reviews by Smer et al. (2018) and AlTurki et al. (2019) compared

55
catheter ablation to medical therapy in patients with AF and HFrEF. Smer and colleagues (2018)
determined that ablation of AF was associated with freedom from AF higher in patients who had
underwent catheter ablation compared to medical therapy (CI 6.94‐84.41, p<0.00001). As well,
of the seven randomized control trials included in AlTurki et al. (2019)’s systematic review and
meta-analysis, six reported arrhythmia-free survival at the end of follow-up as the measure of
success of catheter ablation in maintaining sinus rhythm. In particular, one study reported an
arrhythmia free survival of 50%, whereas all other studies reported an arrhythmia free survival of
over 70% at the end of follow-up. The highest reported survival was 92% in one study, and in the
longest reported follow-up, which was 37 months in the CASTLE-AF trial, the arrhythmia freesurvival rate was 75% in patients who underwent catheter ablation.
Two studies examined the specific types of medication given to manage combined AF
and HF and compared the results to catheter ablation. In particular, the retrospective cohort study
by Geng et al. (2017) compared catheter ablation of AF in patients with HF compared to rate
control medical strategies, specifically BBs and/or digoxin. A total of 394 patients with AF and
HF were included. Of those, 90 patients received AF ablation and the rest received medical of
rate control therapy. Patients in the rate control group were older (73.0 ± 10.7 years vs. 64.7 ±
9.4 years, p<0.001) and had higher risk of stroke as determined by the CHA2DS2-Vasc score
(3.5 ± 1.5 vs.2.3 ± 1.5, p<0.001) when compared with those in catheter ablation group. There
were more patients with a previous histories of stroke (23.4% vs.13.3%, p=0.041) and with
persistent or long-standing persistent AF (81.2% vs.66.7%, p=0.003) in rate control group than
in catheter ablation group. The methodology was rigorous and thoroughly explained, and the
authors applied propensity score matching to adjust for potential confounding factors. Thus,
imbalanced baseline characteristics were added into a logistic regression model to help remove

56
biases. Limitations to the study includes a short term follow-up period, and sixteen patients were
lost to follow-up. After a mean follow-up of 13.5 ± 5.3 months, 82.2% of patients in catheter
ablation group had total freedom from AF, whereas all patients in the rate control group
remained in paroxysmal and persistent or long-standing persistent AF. These findings were
consistent with the study by Di Biase et al. (2016), which aimed to determine if catheter ablation
is more effective than amiodarone for the treatment of persistent AF in patients. At the end of the
study, 70% of patients in the catheter ablation group did not have recurrence of AF after an
average of 1.4 ± 0.6 procedures, in comparison with 34% (95% CI 25% – 44%) in patients
receiving amiodarone.
Aside from Fukui et al. (2020)’s study results, the majority of captured studies
demonstrate statistical significance that ablation of AF in patients with HF reduced AF
recurrence rates, and the results are strong enough to have the therapeutic strategy as an option in
a clinical setting. Therefore, the assessments of the studies have determined catheter ablation is
superior to conventional pharmacotherapy for improving AF recurrence rates.
Mortality
The literature explored the impact of interventions, including catheter ablation and
pharmacotherapy of rhythm or rate control, on mortality rates for patients with concomitant AF
and HF. Thirteen studies discussed mortality rates for patients with HF undergoing
catheterization compared to pharmacotherapy, of which seven were systematic and/or metaanalyses (AlTurki et al., 2019; Chen et al.,2020; Ma et al., 2020; Ruzieh et al., 2019; Smer et al.,
2018; Turagam et al., 2019; Xu et al., 2019) and six were single studies (Di Biase et al., 2016;
Geng et al., 2017; Ichijo et al., 2018; Machino-Ohtsuka et al., 2019; Marrouche et al., 2018; Yu

57
et al., 2018). The analysis of the studies considerably demonstrated that catheter ablation of AF
in HF patients is associated with a decrease in mortality compared to pharmacotherapy.
Seven studies, including three systematic and/or meta-analyses and four single studies,
aimed to determine if catheter ablation was superior to medical therapy in terms of mortality in
patients with combined AF and HF. A stratified pooled analysis of randomized data by Turagam
et al. (2019) evaluated the benefits of medical therapy and catheter ablation of rhythm control for
the management of combined AF and HF. Six randomized control trials were included with a
total of 775 participants. The trials had at least a six month follow-up, adults aged 18 years or
older, compared AF ablation with standard drug therapy in patients with HF, and reported one or
more clinical outcomes. Retrospective studies, studies with no comparative group, nonrandomized trials, case reports, editorials, reviews, expert opinion, and studies published in a
language other than English were excluded. The authors developed and followed a protocol for
the systematic review and meta-analysis. The methodology was rigorous, as two investigators
independently performed searches of various databases without language restrictions for articles
and abstracts published between January 2005 and October 2018. Two investigators also
independently screened all titles and full-text versions of the relevant randomized control trials.
The purpose of the study was to compare benefits and harms between catheter ablation
and pharmacotherapy in adult patients with AF and HF. The analysis of the study determined
that compared with drug therapy, AF ablation reduced all-cause mortality (9.0% vs. 17.6%; 95%
CI 0.33 to 0.81). A limitation of the study includes the results being driven primarily by the
largest trial, CASTLE-AF, although there were six randomized control trials included. As well,
patient selection bias may have occurred, as patients selected for a randomized catheter ablation
trial may have been healthier than those who are receiving only medical management,

58
particularly patients included were relatively young (aged 55 to 64 years). Additionally, the
participants and physicians were not blinded to treatment assignment, thus, medical care and
follow-up may have differed after ablation. Alike to Turagam and colleagues (2019), two metaanalyses of randomized control trials by Ma et al. (2020) and Chen et al. (2020) aimed to
compare catheter ablation and pharmacotherapy in adult patients with AF and HF. The studies
demonstrated that catheter ablation was shown to be superior to conventional pharmacotherapy
for improving all-cause mortality (95% CI 0.35 – 0.76; 9.0% vs. 17.6%, risk ratio, 0.52 [95% CI
0.33 to 0.81]; 10.7% vs. 18.9%; p=0.0003, respectively).
In the CASTLE-AF trial by Marrouche et al. (2018), the purpose was to assess whether
catheter ablation lowers morbidity and mortality compared to medical therapy of rate or rhythm
control in patients with AF in the context of medically managed HF. The authors demonstrated
that rhythm control of catheter ablation is more beneficial than medical therapy in preventing
death, as significantly fewer patients in the catheter ablation group died from any cause (13.4%
vs. 25.0%; 95% CI 0.32- 0.86; p=0.01) or died from cardiovascular causes (11.2% vs. 22.3%;
95% CI 0.29-0.84; p=0.009), compared to medical therapy of rate or rhythm control for AF.
Similarly, the quantitative, multi-center, open labelled, randomized, parallel-group study by Di
Biase et al. (2016) had a secondary end point of mortality. The assessment of the study
demonstrated that mortality was significant lower in the catheter ablation group (8%) compared
to participants receiving amiodarone therapy (18%), with a P value of 0.037 determining
statistical significance. As well, a single center, retrospective non-randomized study by Ichijo et
al. (2018) aimed to address the long-term effects of ablation of AF in patients with HF. In the
HFrEF group, one patient died due to an acute myocardial infarction during the follow-up period.
Freedom from a composite endpoint (death, strokes, and HF-related unplanned hospitalizations)

59
at one, two, three, and fours years after the initial procedure was 97.6%, 97.6%, 97.6%, and
88.7%. Among the HFpEF patients, one (1.8%) patient died due to cancer during the follow-up
period. After 1.4 ± 0.5 procedures, 47 (85.5%) patients remained free from recurrent AF, and at
one, two, three, and fours years after the last procedure was 90.0%, 84.6%, 79.3%, and 79.3%.
Four studies, including three systematic reviews and/or meta-analysis and one single
study, aimed to compare catheter ablation to medical therapy in patients with AF and HFrEF
alone. Specifically, AlTurki and et al. (2019) retrieved and summarized seven randomized
controlled trials, enrolling 856 patients. The methodology was thorough, and the systematic
literature review was performed according to the PRISMA statement. The search was limited to
human studies in peer reviewed journals from inception to February 26, 2018. The authors hand
searched and cross referenced retrieved publications, review articles, and guidelines to ensure the
inclusion of all relevant studies. For each randomized control trial, two reviewers independently
reviewed the literature, and disagreements were resolved by consensus. The analysis of the study
concluded that compared with medical therapy, AF catheter ablation was associated with a
significant reduction in mortality (risk ratio 0.50; 95% CI 0.34 to 0.74; p=0.0005). Limitations
of the study included the absence of clinical trials with long term clinical outcome assessment
comparing catheter ablation with a pure rate control strategy, such as excluding amiodarone use
completely. As well, the number of included studies and sample size is relatively small,
preventing an effective analysis of publication bias and questions the generalizability of the
study results. Comparably to AlTurki and associates (2019), Smer et al. (2018) determined that
ablation of AF was associated with less HF-related death from any cause in patients with HFrEF
(95% CI 0.34-0.74, p=0.0005; OR 0.46, CI 0.29‐0.73, p=0.0009, respectively).

60
There were two studies captured that attempted to determine the relationship between
catheter ablation and medical therapy in terms of mortality rates, however demonstrated weak
evidence. The systematic and meta-analysis study by Ruzieh et al. (2019) results showed allcause mortality was significantly lower in the catheter ablation group (OR 0.49; 95% CI 0.31 –
0.77; p=0.002). However, the trials were not designed or powered to detect a mortality
difference, and thus the confidence in the outcome estimate derived from pooled data is low.
Additionally, the retrospective cohort study by Geng et al. (2017) aimed to determine the
associated adverse events of catheter ablation of AF in patients with HF compared to rate control
medical strategies, including BBs and/or digoxin. The study found that all-cause mortality was
higher in the rate control group compared to the catheter ablation group (7.9% vs. 3.3%,
p=0.126), however the results were not deemed statistically significant.
Three studies, including one meta-analysis and two single studies, discussed the
outcomes of medical therapy when treating patients with combined AF and HF. In particular, a
meta-analysis by Xu et al. (2019) identified 12 studies, including six post-hoc analysis of
randomized control trials and six observational studies, capturing data from a total of 38,133
patients. The aim was to investigate the effects of BBs on outcomes in patients with chronic HF
and AF. Although BBs were associated with significant decrease in all-cause mortality for
patients with combined AF and HF (95% CI 0.65-0.82, p<0.001), the analysis demonstrated that
treatment with BBs was not associated with a reduction of cardiovascular mortality (RR: 0.83;
95% CI 0.65 –1.06, p=0.14). Although the study does not specifically compare medical therapy
to catheter ablation, the analysis demonstrates that BBs are not the most optimal treatment
strategy for the subpopulation of interest. Similarly, a retrospective observational study by Yu et
al. (2018) assessed the efficacy of rate control medications in AF patients with HF. Patients were

61
identified with (n=2,441) or without (n=4,593) HF and assigned to a treatment group if they
received one type of medication, including BBs, CCBs, or digoxin. In patients without HF, there
was no significant difference in the risk of death among the medication subgroups. The risk of
death was lower in patients receiving BBs (adjusted hazard ratio 0.75, 95% CI 0.64-0.88;
p<0.001) and CCBs (adjusted HR 0.74, 95% CI 0.55-0.98; p=0.036) compared with those who
did not receive rate control medications in the patients with AF. However, there was no
significant difference between patients treated with digoxin or not being treated with rate control
medication (adjusted hazard ratio 1.01, 0.86 – 1.19; p=0.928). Also, the use of BBs reduced the
mortality rate for AF patients with HF, but not for those without HF. The analysis of the
retrospective observational study by Machino-Ohtsuka et al. (2019) determined that maintaining
sinus rhythm with catheter ablation and/or AADs compared to rate control medications, such as
BBs, CCBs, and digoxin, was associated with lower occurrence of a composite endpoint of
cardiovascular death or hospitalization for HF.
In summary, the analysis for the majority of the forementioned studies demonstrate
statistical significance in regards of ablation of AF in patient with HF and the association with
decreased mortality compared to medical therapy. As well, three articles addressed and studied
specific medications, determining that treatment with pharmacotherapy was not associated with a
reduction of cardiovascular mortality compared to catheter ablation. As such, the results are
robust enough to be clinically significant, and thus catheter ablation should be considered as an
option in clinical practice for the management of concomitant AF and HF.
QoL and Functional Capacity
The literature captured in this review also explored the impact of interventions, including
catheter ablation and pharmacotherapy of rhythm or rate control, on QoL and functional capacity

62
for patients with concomitant AF and HF. The analysis of the studies considerably demonstrate
that catheter ablation is associated with improved QoL and functional capacity compared to
pharmacotherapy in the management of patients with combined AF and HF. In particular, eight
studies discussed management of combined AF and HF pertaining to QoL and functional
capacity for individuals undergoing catheter ablation compared to pharmacotherapy, including
seven systematic and/or meta-analyses (AlTurki et al., 2019; Chen et al., 2020; Ma et al., 2020;
Ruzieh et al., 2019; Smer et al., 2018; Turagam et al., 2019; Zhu et al., 2016) and one single
study (Kuck et al., 2019). There are various ways QoL and functional capacity can be evaluated,
including 6-minute walk test distance, Minnesota Living with HF Questionnaire scores, and peak
oxygen consumption – see table 3 below.
Table 3
QoL and Functional Capacity
6-Minute Walking
Test
AlTurki et al. (2019)
Chen et al. (2020)
Ma et al. (2020)
Ruzieh et al. (2019)
Smer et al. (2018)
Turagam et al. (2019)
Zhu et al. (2016)

X
X
X
X
X

Minnesota Living
with HF
Questionnaire
X
X

Peak Oxygen
Consumption

X
X
X

X
X
X

Five systematic reviews or meta-analyses determined catheter ablation of AF in HF
patients significantly improved 6-minute walking test distances. Specifically, a meta-analysis by
Ma et al. (2020) included seven studies involving 856 patients with a mean age ranged from 55
to 64 years old. Baseline LVEF of all the patients was < 50% and NYHA class was II-IV in
participants. All of the participants in the catheter ablation group underwent pulmonary vein
isolation, most of who underwent additional linear and complex or fractionated electrograms

63
ablation. Medical rate control strategy was introduced to control group in four trials. The study
was performed according to recommendations from the guidelines of the Preferred Reporting
Items for Systematic Reviews and Meta-Analyses and Cochrane Handbook for Systematic
Reviews of Interventions. The methodology was extensive, as two investigators independently
searched the databases, including PubMed, Embase, and Cochrane Library enrolling patients
with AF and HF who were assigned to catheter ablation, and medical rhythm or rate control
groups. The studies included were published before February 27, 2018, and the language was
restricted to English. Cochrane collaboration’s tool was used to assess risk of bias, as well as the
quality of included studies. The items in the tool included random sequence generation,
allocation concealment, blinding of participants and personnel, blinding of outcome assessment,
incomplete outcome data, and selective reporting. Two reviewers independently extracted data
from the included studies.
The study aimed to evaluate the efficacy and safety of catheter ablation in patients with
concomitant AF and HF, with the goal of creating a comprehensive representation of therapeutic
strategies. The analysis of the study demonstrates catheter ablation had a longer 6-minute
walking test (MD 26.67, 95% CI 12.07 to 41.27) than the medical rhythm or rate control group.
Limitations of the study includes a lack of specified individual data to conduct subgroup analyses
based on age, sex, and baseline diseases. As well, baseline LVEF was measured under AF
rhythm in the included studies and echocardiography was used in 4 trials, thus there were
relatively low accuracy and poor repeatability. Alike to Ma and colleagues (2020), the analysis
of the studies by Turagam et al. (2019), AlTurki et al. (2019), Ruzieh et al. (2019), and Smer et
al. (2018) also determined that catheter ablation was shown to be superior to conventional
pharmacotherapy for improving 6-minute walking test (mean difference, 20.93 m [CI 5.91 to

64
35.95 m]; 30.15; 95% CI 10.47 to 49.84, p<0.0001; 29.3; 95% CI 11.8 – 46.8; p=0.001; 25.82,
CI 5.46-46.18, p=0.01).
Five systematic reviews and/or meta-analyses compared medical therapy and catheter
ablation to determine the effect on Minnesota Living with HF Questionnaire (MLWHFQ) score
in patients with combined AF and HF. In particular, AlTurki et al. (2019), assessed the efficacy
and safety of catheter compared to medical therapy in patients with AF and HFrEF. The
evaluation of the study results demonstrate that when compared with medical therapy, catheter
ablation was associated with significant improvements in MLWHFQ score (95% CI –14.67 to
− 4.38; p<0.0001) in the AF catheter ablation group compared to the medical therapy group.
Alike to AlTurki and associates (2019), the analysis of the studies by Ruzieh et al. (2019), Ma et
al. (2020), Chen et al. (2020), and Smer et al. (2018) determined that catheter ablation of AF in
HF patients showed an improvement in MLWHFQ than the control group (mean difference 12.1, 95% CI -20.9 to -3.3; p=0.007; -9.49, 95% CI -14.64 to − 4.34; 95% CI -15.7 to -2.5,
p=0.007; -9.01, CI -15.56, -2.45, p=0.007).
Lastly, four systematic reviews and/or meta-analyses compared medical therapy and
catheter ablation to determine the effect on peak oxygen consumption in patients with combined
AF and HF. Specifically, the systematic review of quantitative literature by Zhu et al. (2016)
demonstrated significant evidence that when compared to a medical rate control strategy,
catheter ablation of AF in HF patients significantly improves peak oxygen consumption (95% CI
0.78-4.85, p=0.007). Similarly to Zhu and colleagues (2016), Turagam et al. (2019), Ma et al.
(2020), and Smer et al. (2018) also determined catheter ablation was superior to conventional
pharmacotherapy for improving peak oxygen consumption (mean difference, 3.17 mL/kg per

65
minute [CI 1.26 to 5.07 mL/kg per minute]; 3.16, 95% CI 1.09 to 5.23); 3.16, CI 1.04 to 5.29,
p=0.004).
In contrast to the above studies, a multicenter, open label, and randomized control trial by
Kuck et al. (2019) attempted to determine the relationship between catheter ablation and medical
therapy pertaining to QoL, however, there was an inconclusive effect. Specifically, there were no
statistically significant differences between the ablation group and best medical therapy group in
the secondary end points of change in 6-minute walking test (+46 m vs. +81 m, P=0.07) and
QoL score (−11.2 vs. −8.9, p=0.42). The study was terminated due to ineffective study results.
Although Kuck and colleagues (2019) demonstrated weak evidence, the prior mentioned studies
associated catheter ablation in AF and HF patients with improved the 6-minute walking test,
Minnesota Living with HF Questionnaire score, and peak oxygen consumption, and thus overall
QoL and functional capacity in comparison to control strategies of medical therapy. Thus,
ablation of AF in the HF population should be considered as a therapeutic option.
LVEF
The literature explored the impact of interventions, including catheter ablation and
pharmacotherapy of rhythm or rate control, on LVEF for patients with concomitant AF and HF.
Eight studies discussed management of combined AF and HF pertaining to LVEF for individuals
undergoing catheter ablation compared to pharmacotherapy, including seven systematic and/or
meta-analyses (AlTurki et al., 2019; Chen et al., 2020; Ma et al., 2020; Ruzieh et al., 2019; Smer
et al.; 2018; Turagam et al., 2019; Zhu et al., 2016) and one single study (Kuck et al., 2019).
Seven studies determined catheter ablation significantly increases LVEF in patients with
combined AF and HF (AlTurki et al., 2019; Chen et al., 2020; Ma et al., 2020; Ruzieh et al.,
2019; Smer et al., 2018; Turagam et al., 2019; Zhu et al., 2016). In particular, a systematic

66
review of quantitative literature by Zhu et al. (2016) included three randomized controlled trials
with a total of 143 patients, in which the quality was assessed by Cochrane Collaboration tool.
The study was performed following the Preferred Reporting Items for Systematic Reviews and
Meta-Analyses guidelines. The methodology was thorough, as the databases were systematically
searched for articles until December 20, 2015. The references of the retrieved articles, relevant
reviews, and previous meta-analyses, were manually searched for applicable citations. The data
extraction and quality assessment were performed independently by two reviewers, and
disagreements were resolved by consensus. The primary outcome in the study was the change in
the LVEF after catheter ablation or medical rate control therapy relative to baseline. The analysis
of the study demonstrated significant evidence that when compared to a medical rate control
strategy, catheter ablation in AF and HF patients significantly improves the LVEF (95% CI 0.711.74, p=0.03). Limitations involved the small number of studies included, as well as a relatively
small sample size of participants. As well, follow-up lengths were short, with the longest being
12 months, and thus may have been insufficient for complications and recurrences to occur.
Thus, the analysis of the long-term results was underpowered.
Alike to Zhu and associates (2016), systematic reviews and/or meta-analyses by Smer et
al. (2018), Turagam et al. (2019), AlTurki et al. (2019), Ruzieh et al. (2019), Ma et al. (2020),
and Chen et al. (2020) determined that compared to medical therapy, catheter ablation has
significantly improved LVEF with the following results, mean difference 5.93, CI 3.59‐8.27,
p<0.00001, I2 = 87%; 6.95% (CI 3.0% to 10.9%); 95% CI 3.71-11.26, p<0.0001; 6.8%, 95% CI
3.5 – 10.1; p<0.001; 7.57, 95% CI 3.72 to 11.41; 95% CI −10.6% to −3%, p=0.0004,
respectively.

67
Dissimilarly to the above studies, the randomized control trial by Kuck et al. (2019) did
not reveal any benefit of catheter ablation in patients with AF and advanced HF. Specifically, at
one year, LVEF increased in ablation patients to a similar extent as in best medical therapy
patients. The increase in LVEF from baseline to one year was 8.8% (95% CI 5.8%–11.9%) in the
ablation group and 7.3% (4.3%–10.3%, p=0.36) in the best medical therapy group, thus both
groups improved similarly over one year. However, the study was terminated due to ineffective
study results. Although Kuck et al. (2019) did not determine statistically significant evidence, the
results of the other forementioned studies are all in agreeance that ablation of AF in HF patients
increases LVEF.
In summary, according to the majority of the study results addressed in this section of the
literature review, ablation of AF in HF patients significantly reduces re-hospitalization rates,
increases the maintenance rate of sinus rhythm, improves mortality rate, and improves QoL and
functional capacity, as well as LVEF, for AF patients complicated with HF, with statistically and
clinically significant evidence. As such, ablation of AF in the HF population is related to better
prognosis, as well as improved key health outcomes, and thus should be considered an initial
therapeutic treatment strategy.
Safety Considerations
Safety emerged as an important consideration when managing patients with concomitant
AF and HF. The literature around safety was centred on the application of common medical
therapies, including catheter ablation and pharmacotherapy. In total, five systematic reviews and
three single studies discussed the safety considerations of the diverse therapies for use in the
desired population. The main findings that will be further described below includes low

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complications rates of catheter ablation, as well as the comparison between the safety of catheter
ablation to medical therapy.
Low Complication Rates of Catheter Ablation
Complication rates of catheter ablation are important when considering management for
concomitant AF and HF and were a prominent feature of the included literature. In the literature
review, four studies demonstrated that there were low complication rates associated with catheter
ablation (AlTurki et al., 2019; Black-Maier et al., 2018; Ma et al., 2020; Zhu et al., 2016).
Specifically, a comprehensive review and meta-analysis by Zhu et al. (2016) explored the
efficacy and safety of restoring the sinus rhythm using catheter ablation in patients with AF and
HF. The study was performed following the Preferred Reporting Items for Systematic Reviews
and Meta-Analyses guidelines, and all analyses were based on previous published studies. The
data extraction and quality assessment were performed by two independent reviewers, and
disagreements were resolved by consensus. Three randomized control trials with 143 patients
were included, all of which had relatively low risks of bias, as the team followed a robust review
process guided by Cochrane Collaboration tool. However, the studies included were relatively
small with a short-term follow-up of 12 months, which may have been insufficient for
complications to occur. As well, although the interventions did not permit blinding, the assessors
of the follow-up data measurements were blinded. The analysis of the data revealed that although
compared with medical therapy, catheter ablation of AF is associated with significant risks due
to the nature of the invasive procedure, there was a relatively low complication rate observed in
the ablation-treated patients. Of the analyzed studies included in the systematic review by Zhu
and colleagues (2016), the procedural complication rates ranged from 7.7% to 15.4%. However,
the study did not explicitly mention the types or severity of complication rates or adverse effects.

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As such, the evaluation of the study demonstrated that catheter ablation is able to restore and
maintain the sinus rhythms of AF and HF patients with a relatively low risk of complications and
adverse effects, making the results clinically significant to the subpopulation of interest.
Similarly to Zhu et al. (2016), the study by Ma et al. (2020) included seven randomized
control trials enrolling 856 participants and aimed to evaluate the safety of catheter ablation in
patients with concomitant AF and HF. The analysis of the study determined a relatively low
procedural complication rate of catheter ablation at 6.4% (95% CI 2.7% to 10.1%), thus
indicating ablation of AF was safe in HF patients. Additionally, the evaluation of a systematic
review and meta-analysis of seven randomized control trials by AlTurki et al. (2019) showed that
catheter ablation is a safe procedure in patients with AF and HFrEF, as the number of adverse
events were relatively small, making this a feasible option for maintenance of sinus rhythm.
Finally, an observational, retrospective cohort study by Black-Maier et al. (2018) discussed
periprocedural adverse events for ablation of AF in HF patients, including access site bleeding
(p=0.24), stroke or transient ischemic accident (p=0.177), or acute HF (p=0.396). However, the
results were not statistically significant. Overall, when critically examining the studies to
determine the complications rates of catheter ablation, low procedural adverse effects were
found, and adverse events that did occur were not statistically significant.
Safety of Catheter Ablation
The management of concomitant AF and HF is a challenging task, and thus determining
the safety of catheter ablation compared to medical therapy helps guide treatment decisions. In
the literature review, four studies compared safety of catheter ablation and pharmacotherapy for
patients with concomitant AF and HF. The results of two studies demonstrated that when
compared to medical therapy, catheter ablation has similar safety rates. Specifically, the stratified

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pooled analysis of randomized data by Chen et al. (2020) compared rhythm control using AADs
and rate control (Subset A), or rhythm control using catheter ablation vs. medical therapy (Subset
B) in AF and HF patients. There were 11 randomized control trials with high methodological
quality included for a total of 3,598 patients enrolled (Subset A: 2486; Subset B: 1112) with a
mean age 67.0 ± 9.9 years, in which 78% were male patients. However, there were various small
sample-size studies included in the pooled analysis. For the purpose of the literature review,
Subset B is of interest, as it compares the safety of catheter ablation and medical therapy. The
study was performed in accordance with the Preferred Reporting Items for Systematic Reviews
and Meta-analyses statement. Also, clinically relevant comparisons and stratified analysis were
conducted for each subset group. The analysis of the findings demonstrate that catheter ablation
is safe in patients with AF and HF, as they evaluated the safety of rhythm control strategies in
patients with concomitant AF and HF. In this study, the authors compared catheter ablation
rhythm control vs. medical therapy. The analysis of the findings included the rate of overall
composite adverse events between the catheter ablation group and the medical therapy group,
including death, stroke, major bleeding, cardiac arrest, intracranial haemorrhage, myocardial
infarction, worsening HF, cardiac tamponade, pulmonary vein stenosis, and groin bleeding, were
similar (22.8% vs. 34%, 95% CI 0.33–1.34, p=0.25). In terms of the catheter ablation-related
adverse events, there were no procedure-related deaths, as the rate of tamponade during catheter
ablation was 1.3%, the rate of groin complications was 1.3%, and the rate of pulmonary vein
stenosis was 0.3%. Although there was a large sample size, based on the analysis of a total of 11
studies with a combined 3598 patients enrolled, some of the studies included did have a small
sample size, possibly affecting the generalizability of the study.

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Similar findings were identified in a multicenter, open-label, and randomized controlled
trial by Kuck et al. (2019), which compared catheter ablation of AF and best medical therapy for
patients with HF. The study results showed that 64 patients in the ablation-group (65.3%) and 56
best medical therapy group patients (56.0%; p=0.19) experienced at least one serious adverse
event. Although, the percentage of patients experiencing adverse effects when undergoing
ablation of AF appears to be higher than in practice. Serious adverse events related to the
ablation procedure, including atrioesophageal fistula leading to death [n=1], cardiogenic shock
[n=1], pericardial tamponade [n=1], pleural effusion [n=1], suspected pericarditis [n=1], damage
of ICD system [n=1], and vascular access complications [n=2]), were observed in six patients.
There were no statistically significant differences between groups in the incidence (8.2% and
8.0%,), type of death (p=0.26), or in the incidence of serious cardiac disorders (48% and 43%,
p=0.57). The study was terminated early due to being ineffective, demonstrating weak evidence.
Another two studies reported on the safety of catheter ablation of AF in HF patients
compared to pharmacotherapy, however demonstrated weak evidence. In particular, the
observational, retrospective cohort study by Geng et al. (2017) included 394 patients with AF
and HF, where 90 patients had AF ablation and 304 received medical rate control therapy. The
study was conducted in three tertiary hospitals from January 2015 to 2016. Prior to enrollment,
all patients received catheter ablation or medical rate control treatment decided by experienced
doctors. The study was performed according to the STROBE statement, as well as followed a
registered protocol at Clinical trials.gov. There was a short-term follow up period of 13.5 ± 5.3
months, and sixteen patients were lost to follow-up. The study demonstrated the greater safety
profile of catheter ablation when compared to medical therapy, including BBs and/or digoxin.
Specifically, in patients with HF, catheter ablation for AF was associated with a lower risk of

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major adverse cardiac effects, as 29.3% patients in the rate control group had major adverse
cardiac events, which was significantly higher than in catheter ablation group (13.3%, 95% CI
0.32–0.82, p=0.005), however, the results were not deemed statistically significant, and thus the
relationship of catheter ablation for the treatment of combined AF and HF was not clear.
Additionally, a meta-analysis of randomized control trials by Turagam et al. (2019) demonstrated
weak evidence, as the results were driven primarily by one clinical trial. Thus, there was possible
patient selection bias in the ablation group, lack of patient-level data, open-label trial designs,
and heterogeneous follow-up length among trials. The study demonstrated that serious adverse
events were more common in the catheter ablation groups, which were 7.2% in the AF ablation
group and 3.8% in the standard pharmacotherapy group observed in the pooled analysis,
however, differences between groups were not statistically significant (7.2% vs. 3.8%; RR, 1.68
[CI 0.58 to 4.85]).
Overall, although there is a risk of complications with catheter ablation, the long term
benefits of all-cause mortality, HF hospitalizations, and overall clinical outcomes must be
considered in clinical decision making process (Turagam et al., 2019). However, although
compelling, the findings of the included articles do not definitively suggest that catheter ablation
is a safer than medical rate control therapy for the treatment of concomitant AF and HF.
Differing Treatment for HFrEF and HFpEF
HF comprises a wide range of patients, from those with HFpEF to those with a reduced
HFrEF, and the proportion of patients with HFpEF ranges from 22% to 73%. AF is present in up
to 50% of patients with HF regardless of the type of HF, and both are associated with several
common predisposing risk factors and a shared pathophysiology (Ichijo et al., 2018). Thus, it is
important to investigate the most optimal treatment strategy for these patients and to determine if

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the type of HF is a factor in the management. There are evolving ways to evaluate cardiac
function, and echocardiography is the most accessible method to evaluate LVEF (Ezekowitz et
al., 2017). The difficulty of establishing a standardized treatment regimen for patients with AF
and differing types of HF emerged as a key finding in the integrative literature review.
The literature explored the impact of interventions on different types of HF. In particular,
catheter ablation was heavily researched, as well as other modalities including pharmacotherapy,
strict and lenient rate control, and dual-site right atrial pacing as adjunct therapy. In particular,
five single studies addressed whether or not treatment strategies for patients diagnosed with AF
and HF differ based on a reduced or preserved ejection fraction. Specifically, three studies in the
literature review determined that treatment of HF in AF patients is not dependent on the type of
HF (Black-Maier et al., 2018; Hess et al., 2020; Ichijo et al., 2018). In contrast, two studies
determined that treatment of combined AF and HF is dependent on whether or not the ejection
fraction is reduced or preserved (Eitel et al., 2019; Saskena et al., 2018).
A total of 106 patients with HF were divided into two groups (51 with HFrEF and 55
with HRpEF) between 2010 and 2015, and were enrolled into a retrospective non-randomized
study by Ichijo et al. (2018). The mean age was 62 ± 10 years, and only 21% were females. The
follow-up period was 32.4 ± 18.6 months, which is a longer than majority of studies selected in
the literature review. As the study is a single center nature and there was a lack of randomization
of participants, there may have been biases in selecting healthier patients who were more suitable
candidates for an invasive procedure. The study aimed to determine the long term effects of
ablation of AF in patients with HF. At three years, freedom of AF recurrence, HF-related
hospitalizations, and composite endpoints of all-cause death, stroke, and HF-related
hospitalizations were examined. For HFrEF, the results were 88.7%, 97.6%, and 97.6%. For

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HFpEF patients, the results were 79.3%, 96.2%, and 91.8%. At the final follow-up, low dose
AADs were prescribed in 17 (33.3%) HFrEF and 12 (21.8%) HFpEF patients, and sinus rhythm
was maintained after AF ablation in the vast majority of the HF patients. Freedom from the
composite endpoint was approximately 90% after AF ablation during four years of follow-up,
regardless of HFpEF or HFrEF.
Similar to Ichijo and colleagues (2018), the analysis of the study by Black-Maier et al.
(2018) did not demonstrate significant differences between catheter ablation of AF for patients
with HFrEF compared to HFpEF. There was no statistically significant differences in
improvements in NYHA functional class (p=0.135), rates of AF recurrence (33.9% vs. 32.6%;
p=0.848), repeat ablation (6.0% vs. 3.1%; p=0.364), 12-month all-cause hospitalization (26.3%
vs. 32.0%; p=0.350), or cardiovascular hospitalization rates (21.1% vs. 22.7%; p=0.768) for
either HF type. Thus, ablation of AF has similar effectiveness in patients with HF, regardless of
presence of systolic dysfunction, as there were no significant differences in procedural types,
arrhythmia-free recurrence, or functional improvements between patients with HFpEF and
HFrEF. Moreover, an observational analysis by Hess et al. (2020) aimed to characterize heart
rates achieved at discharge in a current cohort of patients admitted with HF and AF. The study
demonstrated that compared with strict rate control (heart rate < 80 beats/min), lenient rate
control (heart rate < 110 beats/min) was associated with higher risks of death (95% CI 1.11 to
1.33, p<0.001), all-cause readmission (95% CI 1.03 to 1.15, p<0.002), and death or all cause
readmission (95% CI 1.05 to 1.18, p<0.001) at 90 days. As the analysis suggests that an elevated
heart rate is associated with adverse outcomes, the analysis of the study determined heart rate >
80 beats/min were associated with adverse outcomes, irrespective of LVEF. Thus, HF with the
presence or absence of reduced ejection fraction did not impact the magnitude of adverse effects.

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In contrast to the above, a retrospective observational analysis by Saksena et al. (2018)
discussed a different treatment strategy using dual-site right atrial pacing as adjunct therapy to
standard AAD therapy, determining if it would permit rhythm control and improve HF in
patients with AF. There was a total survival rate of 83.9% at three years and 72.6% at five years,
and 47% at 10 years in the combined HFrEF and HFpEF population. However, superior survival
rates occurred in patients with HFpEF compared to HFrEF at three, five, and 10 years (88.2 vs.
79.6%, 81.9 vs. 63.1%, and 59.9 vs. 33.6%); p=0.036). The authors concluded that it is feasible
to suggest very long term restoration of sinus rhythm or atrial paced rhythm in HF populations,
specifically in patients with HFpEF. Limitations of the study include small sample size with
strict inclusion criteria, which limits the generalizability of the study, as well as no control group
for alternative packing sites. The strengths of the study include a long follow-up period of
approximately 9.3 years, and the recommendations are supported by other evidence as
demonstrated in their discussion. As such, the novel finding of combining AADs and biatrial
resynchronization can improve survival for HFpEF more than survival for HFrEF on maximal
medical therapy, but requires further investigation.
Alike to Saksena et al (2018), Eitel and colleagues (2019) determined that differing
treatment strategies according to type of HF will produce similarly desirable outcomes. The
authors performed a multi-center German ablation registry aimed to assess ablation strategies in
patients with AF and HF, specifically comparing outcomes in patients with HFpEF, HF with
mid-range EF (HFmrEF), and HFrEF. Ablation strategies differed significantly between the
groups. The majority of patients with HFpEF (83.4%) and HFmrEF (78.4%) underwent
pulmonary vein isolation (PVI) and 48.9% of patients with HFrEF, of which 47.3% underwent
ablation of the atrioventricular node. The evaluation of the study determined that there were no

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significant differences in terms of symptoms or severe adverse events, such as myocardial
infarction, stoke, or major bleeding, between the three groups. The study also found that there
were no differences in hospitalizations for patients undergoing AV-node ablation compared to
PVI during follow-up. Additionally, arrhythmia recurrences occurred in 47.9% of HFpEF, 36%
in HFmrEF, and 39.8% in HFrEF with a P value of 0.036. Lastly, the mortality rate was
significantly higher in the HFrEF group (10.4%) compared to HFpEF (2.5%) and HFmrEF
(2.2%) with a P value <0.001.
In summary, it is unclear whether or not treatment of AF differs according to the type of
HF, as some analyses determined that therapy depends on the type of HF, and others
demonstrated desirable outcomes irrespective of HF type. Specifically, ablation was deemed to
be an important therapeutic option in the management of patients with HF combined with AF,
regardless of the HF type. As well, the presence of HFrEF and HFpEF did not affect clinical
outcomes when considering lenient or strict HF control. Dissimilarly, a report from a registry
study demonstrated that AF ablation strategies differed in patients based on the type of HF with
similar results. As well, when performing dual-site right atrial pacing as an adjunct therapy to
AAD therapy, the outcomes are more favourable in HFpEF compared to HFrEF. Thus, the
difficulty of establishing a standardized treatment regimen for patients with AF and differing
types of HF requires further exploration, and recommendations and guidelines should clearly
inform clinicians about the risks and benefits of therapeutic options for individual patients with
concomitant AF and differing types of HF.
Summary
There are clinical guidelines pertaining to the management of AF and HF alone, however,
there is more limited guidance regarding concomitant management of both diseases together.

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The current available therapeutic options for AF in patients with HF are diverse and current
guidelines do not provide a clear consensus regarding the best approach to management (Ruzieh
et al., 2019). The next chapter will include a discussion that synthesizes the evidence and
highlights gaps in the literature, as well as provides future recommendations for the concomitant
management of AF and HF.

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CHAPTER IV: DISCUSSION
The body of literature captured within the review is very diverse, making it difficult to
determine finite conclusions for treatment strategies and practices for combined AF and HF. The
chapter will consider the findings of the review and discuss the management of AF in HF
patients within a primary care setting. The key findings will be presented, including exploring
the benefits of catheter ablation compared to pharmacotherapy, the safety considerations in
treatment strategies, as well as discordant evidence and guidelines. Subsequently, a summary of
recommendations for practice, education, research, and policy will be provided, culminating with
a review of the strengths and limitations of the integrative literature review.
Catheter Ablation as an Alternative to Medical Therapy
The evidence appraised in the literature review demonstrates that catheter ablation is a
superior management strategy compared to pharmacotherapy, whether rate or rhythm control, for
improving outcomes in patients with concomitant AF and HF. There is clear evidence that
catheter ablation of AF is associated with improved QoL, functional capacity, and LVEF, as well
as reduced morbidity, mortality, and hospitalizations, thereby reducing the financial burden on
the healthcare system and improving patient outcomes. Fifteen studies addressed catheter
ablation being superior to medical therapy, eight of which were systematic or meta-analyses
(AlTurki et al., 2019; Chen et al., 2020; Ma et al., 2020; Ruzieh et al., 2019; Smer et al., 2018;
Turagam et al., 2019; Xu et al., 2019; Zhu et al., 2016), and seven of which were single studies
(Di Biase et al., 2016; Fukui et al., 2020; Geng et al., 2017; Ichijo et al., 2018; Machino-Ohtsuka
et al., 2019; Marrouche et al., 2018; Yu et al., 2018). The following subsection will discuss how
catheter ablation improves QoL and functional capacity, as well as the impact on the healthcare
system.

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Improved QoL and Functional Capacity
Catheter ablation remains a highly specialized procedure, and common reasons for
ablation include improving symptoms and QoL, maintenance of sinus rhythm, as well as a
medication-free lifestyle (Riahi, 2016). A strategy of sinus rhythm maintenance should be aimed
primarily at reduction of patient symptoms to improve QoL and reduce healthcare utilization
(Andrade et al., 2020). As discovered within the literature review, catheter ablation has been
shown to be significantly more efficacious at achieving long term sinus rhythm and freedom
from AF than medial therapy (Phillips, 2016).
Analyses of the various studies and systematic reviews within the literature review have
demonstrated clinically important improvements in QoL and functional capacity associated with
catheter ablation over pharmacological rate control or rhythm control strategies. In particular,
many studies examined in the literature review demonstrated that catheter ablation significantly
improves QoL and functional capacity, which can be evaluated based on 6-minute walking tests,
Minnesota Living with HF Questionnaire scores, and peak oxygen consumption. Six studies
demonstrated that catheter ablation improved QoL and functional capacity when compared to
conventional medical therapy (AlTurki et al.., 2019; Chen et al., 2020; Ma et al., 2020; Ruzieh et
al., 2019; Turagam et al., 2019; Zhu et al., 2016). As well, symptoms factor heavily on
determining whether AF ablation is worthwhile, as QoL scores demonstrate improvement after
ablation, which became evident in the literature review. As such, ablation of AF is accepted as an
alternative to pharmacologic treatment to prevent recurrent AF in symptomatic patients with
minimal or no left atrial enlargement. However, repeat ablations might be necessary, such as for
those with longstanding persistent AF compared to paroxysmal AF (Darby, 2016).

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Catheter ablation is an invasive procedure offered by specialists (Ezekowitz et al., 2017),
and has become an increasingly frequent procedure performed by electrophysiologists worldwide
(Darby, 2016). Consultation is the act of seeking advice for diagnosis and/or management from
specialists, including cardiologists and electrophysiologists. It is a widely used practice, and with
the increasing complexity of patients' illnesses, cardiology consultations have become more
frequent (Marques et al., 2014). Unfortunately, despite the evidence, underutilization of referrals
for ablation of AF in HF patients occur (Sinner et al., 2015). As such, PCPs must collaborate
with electrophysiologists, cardiologists, and cardiac clinic NPs associated with the management
of AF and HF in an appropriate timeframe for the most optimal success (Ezekowitz et al., 2017).
Providing PCPs with the knowledge of appropriate and timely referrals and consultation would
create better preparedness to work within the broader interdisciplinary team, which is necessary
for the optimal management of combined AF and HF in outpatient settings.
Reduced Healthcare Burden
AF and HF frequently coexist and increase the risk of stroke, HF-related hospitalizations,
and all-cause mortality, particularly recently after the clinical onset of AF (Verma et al., 2017).
Catheter ablation has been shown to be significantly more efficacious at achieving long term
sinus rhythm and freedom from AF than medial therapy (Phillips, 2016). Thus, when evaluating
ablation of AF in HF patients over a lifetime, the main finding encompasses catheter ablation
being an economically appealing alternative to medical therapy. Specifically, catheter ablation is
considered cost-effective intervention for the treatment of AF, and the most determining
variables are the impact on stroke and hospitalization rates (Barra & Fynn, 2015).
Various studies were evaluated in the literature review and determined catheter ablation is
a more effective strategy than medical therapy with outcomes of rehospitalizations, AF

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recurrence, mortality rates, and LVEF. Seven systematic and/or meta-analyses and six single
studies determined that catheter ablation of AF was associated with less HF hospital
readmissions compared to medical therapy (AlTurki et al., 2019; Chen et al., 2020; Di Biase et
al., 2016; Fukui et al., 2020; Ma et al., 2020; Geng et al., 2017; Ichijo et al., 2018; MachinoOhtsuka et al., 2019; Marrouche et al., 2018; Ruzieh et al., 2019; Smer et al., 2018; Turagam et
al., 2019; Xu et al., 2019). Five systematic and/or meta-analysis studies and five single studies
determined that catheter ablation of AF was associated with lower arrhythmia recurrences when
compared to pharmacotherapy in HF patients (AlTurki et al., 2019; Chen et al., 2020; Di Biase et
al., 2016; Fukui et al., 2020; Geng et al., 2017; Ichijo et al., 2018; Marrouche et al., 2018; Ma et
al., 2020; Ruzieh et al., 2019; Smer et al., 2018). Seven systematic and/or meta-analyses and six
single studies demonstrated that catheter ablation was associated with less deaths in patients with
concomitant AF and HF (AlTurki et al., 2019; Chen et al.,2020; Di Biase et al., 2016; Geng et
al., 2017; Ichijo et al., 2018; Machino-Ohtsuka et al., 2019; Marrouche et al., 2018; Ma et al.,
2020; Ruzieh et al., 2019; Smer et al., 2018; Turagam et al., 2019; Yu et al., 2018; Xu et al.,
2019). Lastly, seven systematic and/or meta-analyses studies determined catheter ablation
significantly increases LVEF in patients with combined AF and HF (AlTurki et al., 2019; Chen
et al., 2020; Ma et al., 2020; Ruzieh et al., 2019; Smer et al., 2018; Turagam et al., 2019; Zhu et
al., 2016).
The findings of the literature review are in alignment with the AF guidelines by Andrade
et al. (2020), as catheter ablation is recommended as a reasonable alternative to pharmacologic
rhythm or rate control therapy for patients with HF. The above recommendations are supported
by the Canadian Cardiovascular Society (CCS, 2017) HF guidelines, as catheter ablation of AF is

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considered a therapeutic strategy to achieve and maintain sinus rhythm if rhythm control is
indicated and AAD therapy has failed, or the patient is unable to tolerate AAD therapy.
NPs are highly trained and independent healthcare providers that work in collaboration
with other members of the healthcare team to manage the healthcare needs of patients. There are
several known benefits of NP-led care for chronic diseases, including AF and HF (Smigorowsky
et al., 2017). NPs are able to perform stroke risk assessment, re-evaluate patients with increasing
symptoms to adjust medication regimes, and arrange for interventions, such as cardioversion or
cardiac electrophysiology. Both interventions are able to improve patient outcomes, as well as
have a positive impact on the healthcare system, limiting emergency room visits and hospital
admissions. As well, earlier appropriate management produces fewer devastating, costly
complications of stroke and HF in AF patients (Smigorowsky et al., 2017). As such, PCPs,
including NPs, should be aware of the evidence based research behind the available options for
managing the combined diseases. NPs also have a responsibility to deliver effective education to
patients to make informed decisions, and recognize that their knowledge, or lack there of, could
impact their illness trajectory (Watts et al., 2009). Specifically, shared decision making that is
facilitated by decision aids could help patients choose an option that is compatible with their
values. With that, there is a decrease in patients remaining undecided, or who play a passive role
in the decision-making process, as well as improvement in patient knowledge, decisional
conflict, and patient-provider communication (Wieringa et al., 2019).
Safety Considerations
Pharmacologic rate and rhythm control are limited in the AF and HF population due to
variable efficacy, intolerance, and adverse reactions (Sinner et al., 2015). Ablation for AF in
patients with HF has resulted in a paradigm shift, as there is evidence to show superiority over

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medical therapy (Sinner et al., 2015). A main finding obtained from the literature review
includes low complication rates of catheter ablation in patients with concomitant AF and HF.
Three systematic studies and one single study determined that there is evidence for low
complication rates of catheter ablation (AlTurki et al., 2019; Black-Maier et al., 2018; Ma et al.,
2020; Zhu et al., 2016). As such, ablation of AF in the HF population is determined to be a safe
procedure due to the limited number of adverse events, making catheter ablation a feasible
option for maintenance of sinus rhythm (AlTurki et al., 2019).
The safety profile of most AADs, including amiodarone, is a concern as they may
provoke HF decompensation and other adverse effects (Ezekowitz et al., 2017). When
considering these medications, consulting with an electrophysiologist, or other relevant
specialists, in their use is highly encouraged for improved patient outcomes (Ezekowitz et al.,
2017; McDonald et al., 2021). One systematic study and one single study in the literature review
also determined that catheter ablation and medical therapy share similar safety profiles (Chen et
al., 2020; Kuck et al., 2019). The CCS Guidelines for the Management of HF recommend the use
of AAD therapy with concomitant AF to achieve and maintain sinus rhythm. However, if rhythm
control is indicated, it should be restricted to amiodarone (Ezekowitz et al., 2017). Most AADs,
including amiodarone, have significant concerns related to their safety profile, especially in
HFrEF. Although they are effective at suppressing cardiac arrhythmias, they might also provoke
HF decompensation and cause other adverse effects (Ezekowitz et al., 2017), including
proarrhythmia and multiorgan toxicity (Black-Maier et al., 2018). As such, due to the limitations
and safety profile of AAD medications, catheter ablation of AF is a reasonable alternative
therapeutic option for treating patients with associated HF.

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Self‐care research and clinical efforts have been hindered by the perceptions of both
patients and providers, with beliefs that pharmacological interventions are more effective than
lifestyle change. Given the lack of emphasis on self‐care in the healthcare system today, most
patients expect that PCPs hold the responsibility for their patients’ health (Riegel et al., 2017).
Both PCPs and patients need to alter their expectations about their respective roles in the
prevention for cardiovascular diseases. Patients are able to understand their risks and benefits of
treatment for their cardiovascular disease and treatment, first by having knowledge of their
health status and awareness. The “Know Your Numbers” campaign was designed to encourage
patients to determine their risk for cardiovascular disease, including five risk factors of blood
pressure, total cholesterol, high‐density lipoprotein cholesterol, blood glucose, and body mass
index being the focus. The goal is for patients to determine whether any of these factors are
abnormal, allowing them to monitor their cardiovascular health and be actively engaged in their
treatment plan and the decision making process (Riegel et al., 2017).
Discordant Evidence and Guidelines
Within the literature review, there were inconsistent management strategies that were
revealed for AF patients with HFrEF compared to HFpEF. The analyses of three studies in the
literature review determined that treatment of HF in AF patients is not dependent on the type of
HF (Black-Maier er al., 2018; Hess et al., 2020; Ichijo et al, 2018). Controversy, the evaluation
of two other studies determined that the treatment of AF and HF differs based on whether or not
the ejection fraction is reduced or preserved (Eitel et al., 2019; Saskena et al., 2018). BlackMaier et al. (2018) underwent an observational, retrospective cohort study that determined there
is no significant difference in the type or severity of EF when treating HFpEF or HFrEF patients
with ablation of AF. Specifically, catheter ablation of AF significantly improves NYHA

85
functional class and Mayo AF-Specific Symptom Inventory in patients with HFpEF and HFrEF.
In contrast, Eitel et al. (2019) underwent a multi-center ablation registry that compared various
ablation strategies in patients with HFpEF, HFmrEF, and HFrEF. Although treatment strategies
for concomitant AF and HF differed between patients and had similarly desirable outcomes,
there is a lack of randomized control trials in the literature review to truly identify whether or not
differing treatment strategies for HFrEF and HFpEF make a statistically and clinically significant
difference in patient outcomes. Although AF is common in patients with HF, most of the
available data are from patients with HFrEF, therefore evidence regarding HFpEF is less
established (Sartipy et al., 2017). Thus, further contributing to the conflicting, and thus unclear,
treatment recommendations for AF in the HF population.
A challenge for managing patients with more than one morbidity, such as combined AF
and HF, includes the presence of inadequate guidelines. Clinical practice guidelines often only
provide recommendations for disease-specific conditions, however, they do not guide prescribers
in managing patients with multiple comorbidities. The significant increase in medication options
for AF and HF patients further complicates the situation, as PCPs need to carefully deliberate the
suitability of each treatment option for a particular patient in terms of cost, effectiveness, and
adverse effects. These challenges may lead to inappropriate prescribing for patients with chronic
disease, leading to poor disease control. As the majority of patients with chronic diseases are
elderly who are at high risk for adverse events of medical therapy, and AF and HF are problems
in the aging population (Smigorowsky et al., 2017), the population needs more detailed and
conclusive guidelines. Lastly, inappropriate prescribing for chronic diseases also has a
significant economic impact due to increased hospitalization, number of outpatient visits and
medical costs (Sellappands et al., 2015). Thus, the above mentioned all contribute to a major

86
concern in the delivery of healthcare, and guidelines that encompass the management of multiple
diseases, including AF and HF, need to be further researched and developed to improve patient
outcomes and reduce financial burdens on the healthcare system.
AF and HF Guidelines
Multiple studies in the literature review demonstrated that catheter ablation was more
beneficial when compared to medical therapy for concomitant AF and HF. However, the
Focused Update of the CCS Guidelines for the Management of Atrial Fibrillation by Andrade et
al. (2018) did not add a new recommendation for catheter ablation of AF in HF patients, thus,
they recommend catheter ablation as a second-line treatment. As well, in the updated guideline,
the CCS/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of AF
by Andrade et al. (2018), catheter ablation of AF is recommended as an alternative approach to
pharmacologic therapy, thus continue to refrain from highlighting catheter ablation as first-line
therapy for AF in HF patients. Additionally, from the CCS (2017) HF guidelines, catheter
ablation of AF is considered as a therapeutic strategy to achieve and maintain sinus rhythm if
rhythm control is indicated and AAD therapy has failed or the patient is unable to tolerate AAD
therapy, however, they labeled it as a weak recommendation with low-quality evidence (CCS,
2017). As well, the updated HF guidelines from the CCS and Canadian Heart Failure Society is
limited to key pharmacologic therapies for patients with HFrEF and mention that the
management of comorbidities, including AF, have been addressed in previous guideline updates,
although they acknowledge that evidence is quickly evolving in many of these areas (McDonald
et al., 2021). As such, there is an absence of guidance for managing HF in the presence of AF, as
well as a lack of discussion concerning catheter ablation. Therefore, as AF ablations are
becoming more widespread in HF patients, standardized procedures across healthcare systems

87
are important in order to improve overall quality of the treatment strategy in HF patients, which
includes developing guidelines for the management of the combined diseases (Riahi, 2016).
Recommendations
Recommendations for areas of improvement in the PCP role, including education and
professional development, practice, and research, had been formulated from the results of the
integrative literature review. It is certain that PCPs, including NPs, will have some of the greatest
exposure to HF patients with AF in outpatient settings, thus, they are key stakeholders for
implementing the recommended improvements for managing the concomitant diseases.
Education and Professional Development
The increase in life expectancy and advances in surgical and anesthetic techniques have
allowed for surgical procedures to be performed in a broad population of patients, including
those with advanced age and multiple comorbidities, including AF and HF (Marques et al.,
2014). Catheter ablation has become an increasingly frequent procedure performed in
electrophysiology laboratories worldwide (Darby, 2016). Unfortunately, despite the evidence,
underutilization of referrals for ablation of AF in HF patients occurs (Sinner et al., 2015).
Although AAD therapy remains as the foundation of AF treatment, the role of AF ablation as a
therapeutic option has been well established. However, ablation of AF is only performed in a
small percentage of patients with AF (Tanner at al., 2011).
Throughout the literature review, it was made evident that catheter ablation of AF in HF
patients should be considered a therapeutic management strategy. Similarly to catheter ablation,
there is clear evidence that proves implantable defibrillators reduce mortality in high risk
patients, however are underutilized due to lack of provider knowledge (Bernier et al., 2017).
Sinner at al. (2015) studied the geographical variation of catheter ablation procedures among

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Medicare beneficiaries in the USA. Although the prevalence of AF was greatest in the major
metropolitan areas of the East and West Coasts, catheter ablation rates were higher in areas
where the prevalence of AF was relatively low. Thus, the low rate of catheter ablation referrals
was likely due to the uncertainty about safety, effectiveness, and benefit of catheter ablation. As
such, the lack of provider knowledge regarding catheter ablation leads to reduced referrals, and
therefore underutilization of catheter ablation for AF and HF patients.
New research and guidelines are frequently being created and updated regarding AF and
HF. As such, to address the underutilization of catheter ablation, PCPs should participate in
continuing education, as well as educate themselves on treating patients with combined AF and
HF. In Canada, there are resources available to education oneself on chronic disease
management pertaining to AF and HF diseases. For example, systematic studies from UpToDate,
the CCS/Canadian Heart Rhythm Society Comprehensive Guidelines for the Management of AF
(2020), as well as the Comprehensive Update of the CCS Guidelines for the Management of
Heart Failure (2017) and the CCS/CHFS Heart Failure Guidelines Update: Defining A New
Pharmacologic Standard Of Care For Heart Failure With Reduced Ejection Fraction (2021).
However, due to the discordant and difficult to interpret guidelines, PCPs should be comfortable
with local support opportunities, as well as how to access support when caring for patients with
concomitant AF and HF where complex decision making is apparent. For example, the British
Columbia (BC) Heart Failure Network makes accurate, relevant, and up-to-date information
regarding HF available to health care professionals in BC. As well, Rapid Access to Consultative
Expertise (RACE) program is a telephone service line that involves access to speciality services
for general practitioners. PCPs are able to consult a cardiologist tor review their treatment plan

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direction or reassurance is required to aid in their decision making. As such, cardiac clinics are
able to provide ongoing support for primary care practice (BC Ministry of Health, 2015).
NPs are competent in coaching patients to make and accomplish their goals, educating to
make informed decisions, and promoting decision aids to allow for more active participation in
their patient’s care and improved shared decision making (Jeon & Benavente, 2016). The NP
role engages patients with chronic diseases to participate in their treatment plan by selfmanaging their conditions. As such, PCPS with proper training, materials, and resources are able
to do so more effectively. However, it is difficult for PCPs, especially in small practices with
limited resources, to know where to find information that will help them provide effective selfmanagement strategies to their patients. There are a variety of web-based tools that exist and can
be easily updated and disseminated to PCPs in various ways. For example, the Prevention and
Chronic Care Program at Agency for Healthcare Research and Quality authorized the
development of a searchable library of actionable, free resources to aid PCPs in coaching
patients on self-management strategies, including motivational interviewing (LeRoy et al., 2014).
As AF and HF management strategies have convoluted and limited guidance, PCPs must seek
out the expertise of their colleagues. As well, they must partake in ongoing educational courses
and stay up to date with research and guidelines pertaining to the most optimal treatment
strategies for the population of interest.
Practice
The management of concomitant AF and HF is a therapeutic challenge (Batul &
Gopinathannair, 2017). By conducting the literature review from the perspective of a PCP,
recommendations for practice became evident. There is uncertainty of AF’s independent role of
HF in predicting the response to therapy, whether pharmacological therapy or catheter ablation

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(Andrade et al., 2020). Even though guidelines for pharmacological therapy for HF is evident,
there are various treatment modalities for AF, and as such there is no clear consensus on how to
best to treat AF in the presence of HF (Verma et al., 2017). Based on the findings of the review,
the main area for practice support revolves around the use of catheter ablation of AF in HF
patients. There is also a need for a multidisciplinary approach for optimal management of
concomitant AF and HF for improved patient outcomes. Also, as HF prevention among patients
with AF involves identifying the patients at highest risk for the disease, self-management should
be included in the treatment plan (Pandey et al., 2017).
Catheter Ablation. The long term control of AF in HF patients has been significantly
enhanced by catheter ablation of AF (Phillips, 2016). As a shorter interval of time between initial
AF diagnosis and AF ablation is associated with an increased probability of procedural success,
there is a need for early ablation for optimal outcomes (Chew et al., 2020a). As well, part of the
mission to improve long term control of AF, or limit AF burden, should include the role of
adjunctive interventions (Phillips, 2016).
Catheter ablation is an evidenced based and established therapeutic option with
reasonable safety and efficacy. However, success rates for persistent AF ablation are
significantly lower than paroxysmal AF, despite a large spectrum of ablation strategies (Kocyigit
et al., 2015). Individuals with paroxysmal AF have the highest success rates for AF ablation,
whereas patients with long-standing persistent AF lasting more than three to five years have
much lower success rates (Golian & Klein, 2021). The longer an individual has been in
continuous AF, the less likely it is to terminate spontaneously, creating difficulties for restoring
and maintaining sinus rhythm (Olshansky, 2019). As such, late referrals for ablation are
associated with worse outcomes in patients with structural heart disease due to arrhythmia

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recurrence and acute complications (Romero et al., 2018). A meta-analysis by Romero et al.
(2018) demonstrated that early referral was associated with a statistically significant reduction in
acute complications compared with the late referrals (CI 0.27 to 0.93; p=0.03). As well,
paroxysmal AF has been shown to have increased annual elimination rates (approximately 75 to
80%) than persistent AF (approximately 60 to 70%), and repeat ablations for AF result in higher
effectiveness rates. These differing ablation success rates support the observation that the longer
AF is present, the more the left atrium is altered to promote and perpetuate AF (Shapira, 2009).
Although there is limited data on timing of catheter ablation of AF in HF patients, it is
recognized that AF in a population with left ventricular systolic dysfunction should be regarded
with relative urgency as not just a prognostic marker for poor outcomes, but as an effective
treatment target prompting early referral (Phillips, 2016). As such, when catheter ablation is
approached as a first-line strategy, it should generally be performed at an earlier stage of the
disease for a significantly higher success rate and a decreased need for repeat procedures (Tanner
et al., 2011). The collaboration between the referring PCP and cardiac specialists is essential,
which includes appropriate and timely utilization of catheter ablation (Ezekowitz et al., 2017).
Thus, educating PCPs, including NPs, regarding the appropriate timing of catheter ablation in the
presence of AF and HF is necessary for the success of ablation and patient outcomes. Evidenced
based research should be incorporated into education programs, including medical school and
NP curriculum, that addresses the impact of AF and HF together as opposed to lone conditions.
Collaboration. Consultation is the act of seeking advice for diagnosis and/or
management. It is a widely used practice, and with the increasing complexity of patients'
illnesses, cardiology consultations have become more frequent (Marques et al., 2014). PCPs act
as gatekeepers to evidence-informed interventions, thus, their understanding of the challenge and

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interaction of HF and AF could ensure that patients receive appropriate and timely treatment
(Ezekowitz et al., 2017). As such, PCPs should collaborate with specialists to consider catheter
ablation in an appropriate timeframe for the most optimal success (Ezekowitz et al., 2017).
Adherence to Recommendations. The effectiveness of cardiology referrals involves
many variables, including knowledge of medical management and effective communication
between the consultant and PCP. The success primarily depends on adherence to suggestions
provided by the cardiology team (Marques et al., 2014). Recommendations from cardiologists
involves complex and aggressive treatments, thus the recommendations from cardiologists may
be ignored or denied by PCPs (Marques et al., 2014). Poor adherence to cardiology referral
recommendations is associated with unfavorable clinical outcomes (Marques et al., 2014).
Specifically, there is a 43% reduction in unfavorable outcomes, including clinical worsening or
death, in patients in the adherence group (6.3% of events) compared with patients in the nonadherence group (11.1% of events) (Marques et al., 2014). To improve the effectiveness of
cardiology referrals, identifying the factors that are correlated with compliance to
recommendations is necessary. Adherence depends on the presence of follow-up notes in the
medical chart, verbal reinforcement of recommendations, the number of cardiology suggestions,
as well as the patient's age. A successful cardiology consultation includes effective
communication with referring PCPs. It is apparent that variables representing effective
communication, including follow-up visits and verbal reinforcement, is the most important
predictor of adherence (Marques et al., 2014). As such, a multidisciplinary approach is necessary
for optimal management of concomitant AF and HF to reduce acute care utilization and mortality
(Ezekowitz et al., 2017). There is a need to educate PCPs surrounding the importance of
appropriate and timely referrals as well as educate specialists, including cardiologists and

93
electrophysiologists, on the importance of optimal communication strategies when providing a
consultation to the referring PCP.
Self-Management and Risk Factor Reduction. Patients that understand their current
health status and their risk for future conditions are more capable of engaging in adequate self‐
care with improved outcomes (Reigel et al., 2017). Self‐care is defined as a decision‐making
process that addresses the prevention and management of chronic illness, with a focus on self‐
care maintenance, monitoring, and management (Reigel et al., 2017). NPs are well positioned to
provide education and promote self‐management to patients and their caregivers, as well as assist
in navigating their care and the healthcare system to be more engaged in their own treatment plan
(Watts et al., 2009). Implementation of self-management interventions can improve patients’
lifestyle with AF, as well as prevent physical, psychological, and social problems that negatively
affect patients and their daily life. Crucial areas of focus for the subpopulation include medical
management by adherence to the treatment strategy, as well as behaviour modification (Andrade
et al., 2020). By targeting modifiable risk factors for AF and HF, including obesity and tobacco
smoking, there is potential to significantly reduce individual risk of mortality and morbidity, and
thus reduce the healthcare burden (Chatterjee et al., 2017). Particularly, timely follow up
appointments should address adherence to medications, coagulation tests, blood pressure and
heart rate monitoring, smoking cessation, alcohol abuse, diet, as well as techniques for stress
reduction (Rakhshan et al., 2019). The target population is able to be properly managed by NPs
within an outpatient setting, as they are competent in behavioral modification for chronically ill
patients, including coaching patients to establish and accomplish their goals (Jeon & Benavente,
2016). Additionally, NPs are able to create linkages and refer patients to cardiac clinics to
optimize the delivery of education, support for self-management, and improve patient outcomes.

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Research
Catheter ablation has provided healthcare with major advances for managing patients
with AF (Al-Khatib et al., 2020). The literature review has demonstrated significant evidence
that benefits exists within the setting of the HF population, as ablation of AF reduces
cardiovascular hospitalizations, AF recurrence, and mortality rates, as well as improves QoL and
functional capacity, and LVEF. However, due to the discordant guidelines and conflicting
research for managing AF and HF, PCPs and specialists do not have standardized protocols or
guidelines to follow. There remains a need for updated AF and HF guidelines, in addition to
combined guidelines as both diseases share common risk factors and frequently co-exist (CCS,
2017). The patient experience should be considered and further explored when developing
guidelines, as catheter ablation is an invasive procedure with risks (Kocyigit et al., 2015).
Catheter Ablation. The therapeutic success of ablation is high for paroxysmal AF,
however it may be suboptimal in persistent AF (Batul & Gopinathannair, 2017). In older
individuals with significant atrial enlargement, left ventricular dysfunction, and comorbidities,
AF ablation may be inappropriate, as many of these individuals are already in permanent AF at
the time of referral (Verma et al., 2017). There is a lack of studies for appropriate timing of
ablation of AF in HF patients. Although it has been shown that earlier ablation of AF is required
to increase likelihood of success, further studies are required to explore implementation of earlier
catheter AF ablation and patient outcomes (Chew et al., 2020a). As well, future research is
needed to examine whether long term adjunctive AAD therapy can further improve the response
rates and reduce recurrences of AF after catheter ablation in the HF population (Phillips, 2016).
As catheter ablation is a specialized procedure, PCPs must be informed of the most up to date

95
and evidence based research to inform their referral practice, ensuring appropriate and timely
consultations.
Patient decision aids include interventions to be used independently by patients, before or
after a clinical encounter. They are designed to increase patient knowledge and increase shared
decision making without increasing encounter duration (Scali et al., 2019). PCPs are able to help
patients navigate self-management interventions to significantly improve lifestyle for patients
with AF (Andrade et al., 2020). Decision aids could be developed for patients with AF and HF to
better educate patients on their treatment options, and to promote the active engagement of
patients in the decision-making process (Wieringa et al., 2019).
HFrEF and HFpEF. There are several knowledge gaps regarding the potential effect of
cardiac structure and function on the likelihood of AF ablation success. For example, some
studies have shown that the reduction in AF burden that results from AF ablation improves
LVEF and HF symptoms in patients with reduced ejection fraction attributed to ischemic or
nonischemic cardiomyopathy (Al-Khatib et al., 2020). However, it is uncertain whether similar
benefits might be observed in patients with HFpEF (Al-Khatib et al., 2020). Specifically,
ablation of AF may cause, or worsen, left atrial non-compliance, which may result in a reduction
of blood flow as well as pulmonary hypertension, right ventricular dysfunction, tricuspid
insufficiency, and right atrial enlargement (Al-Khatib et al., 2020). This is clinically important,
as incident HF in stable patients with AF is more commonly HFpEF, and is associated with poor
long term outcomes (Pandey et al., 2017). As majority of the available data for AF and HF are
focused on HFrEF compared to HFpEF, there is a need for further research and literature around
the differing types of HF in the AF population (Sartipy, Dahlstrom, Fu, & Lund, 2017).
Specifically, further studies are needed to determine the role and safety profile of AF ablation in

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patients with HFpEF (Al-Khatib et al., 2020). As well, retrospective and observational studies
were included, and thus there is a need for randomized control trials to help determine a
consensus for treatment of AF in the presence of HF with differing ejection fractions.
Patient Experiences. There are significant gaps in AF patient’s knowledge about their
condition, as well as knowledge of the risks and benefits of the treatment they are currently
taking for their AF despite their disease being treated for several years. Patients often wish for
more information about their treatment options (Seaburg et al., 2014). Particularly, some older
patients with AF may prefer less invasive treatment strategies, whereas others might choose
catheter ablation with goals of maintaining an active lifestyle free of AF symptoms or in an
attempt to avoid further medical therapy (Sinner et al., 2015). There is a need for further
qualitative studies to explore the lived experiences of patients with AF and HF to assist with
guiding therapeutic management strategies. As well, there is also a need for further research
developed into resources available to PCPs for providing education to patients for managing
concomitant AF and HF.
Generic patient reported outcome measures, such as the SF-36 and EQ-5D
questionnaires, have been developed with an advantage of allowing comparison of QoL in
patients with different diseases. However, these tools are less sensitive to the effects of a single
disease on QoL. Thus, with the growing burden of combined AF and HF, the relatively high cost
of treatment, and the appreciation of QoL as a treatment objective, there has been substantial
interest in the development of AF-specific patient reported outcome measures for use in both
clinical research and routine practice (Kotecha et al., 2016). Specific patient-reported outcome
measures should be developed and utilized in practice to help guide the approach to managing
AF in the presence of HF.

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Policy
Policy development is required for guidelines around concomitant AF and HF that include
the PCP, demonstrating care across the continuum and within the context of interdisciplinary
care. For example, catheter ablation has emerged as an effective therapy in patients with
coexistent AF and HF. However, the CCS/Canadian Heart Rhythm Society Comprehensive
Guidelines for the Management of AF (2020), as well as the Comprehensive Update of the CCS
Guidelines for the Management of Heart Failure (2017), have similar recommendations for
catheter ablation of AF in HF patients. However, neither guideline emphasizes catheter ablation
as first line therapy, despite significant beneficial evidence. Both guidelines only briefly mention
the other disease and do not mention the role of the NP for managing patients with both disease,
as well as neglect guidance for referral practices.
As presented in the previous chapter, the findings of the integrative review strongly
support the use of catheter ablation as a first line option for patients with concomitant AF and
HF. However, there is a clear need for policy surrounding clearer guidelines for the treatment of
the two diseases together. Due to the challenged nature of managing patients with more than one
morbidity, such as concomitant AF and HF, clinical practice guidelines need to focus on
providing recommendations for multiple diseases to help guide prescribers in prescribing for
patients with multiple comorbidities. With the significant increase in medication options, the
guidelines need to be diligent in advising prescribers to carefully deliberate the suitability of
medications in terms of cost, effectiveness, and adverse effects (Sellappans et al., 2015). The
goal is easier management of combined diseases, as well as increased confidence in PCPs
prescribing medications for patients with more than one chronic disease. More advanced
guidelines have the potential to significantly decrease hospitalization, number of outpatient

98
visits, and medical costs, thus reducing the economic burden on the healthcare system. As well,
patients with chronic diseases often receive care from multiple practitioners and institutions,
which requires a high level of coordination (Sellappans et al., 2015). There is a need for policy
that strengthens shared care and interdisciplinary care to allow PCPs to be an instrumental part of
the patient’s journey.
Limitations
The review of the literature on managing AF in HF patients has provided key insight and
recommendations for education, practice, and research. A strength of the review include the
development of a comprehensive literature search strategy, as well as the systematic process for
extracting and analyzing the data. Specifically, the literature review contains multiple study
designs, including systematic studies and meta-analysis, as well as retrospective, observational,
multi-centered, and single-centered studies, which allowed for a comprehensive overview of the
management of concomitant AF and HF, including identifying actionable recommendations that
could be implemented to support improved patient and health system outcomes.
Despite many strengths of the literature review, there are relevant limitations to consider.
The literature obtained from the review was limited to quantitative studies, thus, the experiences
of the patient are not well established. The lack of patient experiences poses a challenge to
understand the full picture of HF and AF care, as there is a lack of patient perspective and
preference. There is a need for the patient’s experience and perspective when considering
treatment options. As well, other methodological considerations may impact the assessment of
the evidence and the application into practice. For example, there was an overall lack of ability to
randomize participants, and as the studies majorly did not employ randomizations, the results of
all studies are limiting the potential generalizability to the population of interest. Another

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limitation involves most of the available studies being retrospective. As there is an absence of
prospective or randomized control studies to determine causality and as a result, completely
evaluating the best management for the concomitant disorders is difficult. In addition, challenges
emerged when reviewing the studies, as it was difficult to clearly identify the various methods of
managing the combined diseases.
Another notable limitation of the literature review included catheter ablation being the
focal point of treatment strategies. Some studies mentioned the types of medical therapy,
whether rate or rhythm control, however many combined both strategies into a conventional
medical therapy without thorough explanation. As such, there is a lack of available evidence
pertaining to the best medical therapy of AF in HF patients, and thus, a thorough comparison was
not able to be completed. Additionally, none of the articles specifically focused on the primary
care setting, or mentioned the NP as a primary care provider. Instead, majority of the studies
referred to physicians and specialists, including cardiologists and electrophysiologists. As such,
there is a lack of NP perspective when managing concomitant AF and HF. However, literature
was discussed that captured the NP practice, including coaching and educating patients, as well
as having a similar scope of practice to primary care physicians. Thus, the recommendations will
apply to NP practice and assist PCPs to best manage AF in the HF population.
Conclusion
The combination of AF and HF has a worse prognosis than either of the conditions alone,
thus determining effective therapies is of paramount importance (Batul & Gopinathannair, 2017).
The burden of the diseases on the healthcare system is expected to increase in the future, as both
disproportionately affect the older population. As such, there are associated considerable implied
healthcare costs, as well as morbidity and mortality (Batul & Gopinathannair, 2017).

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The research question that guided the integrative literature review is, “How can the NP
best manage HF patients with AF in outpatient settings to help reduce the burden on the
healthcare system?” In the review, a search of key search terms in various databases and applied
eligibility criteria yielded a final cohort of 20 articles, including nine systematic reviews and/or
meta-analyses and 12 single studies from dates 2015 to present. The review highlighted three key
themes, including catheter ablation being superior to pharmacotherapy, safety considerations of
catheter ablation, and discordant guidelines for managing patients with AF in the presence of HF.
The review of the available evidence clearly supports the benefits of catheter ablation as
an alternative to pharmacotherapy due to improved QoL and functional capacity, and LVEF, as
well as reduced hospital readmissions, AF recurrence, and mortality in concomitant AF and HF.
However, the AF and HF guidelines are contradictory, as they refrain from recommending
catheter ablation as a first line strategy. Although catheter ablation for AF has resulted in a
paradigm shift with evidence indicating superiority over medical therapy (Batul &
Gopinathannair, 2017), underutilization of referrals for ablation of AF in HF patients remains
evident (Sinner et al., 2015). Therefore, next steps include education to increase PCPs utilization
of appropriate and timely cardiology consults and referrals in patients with concomitant AF and
HF, as success rates for persistent AF ablation are significantly lower than paroxysmal AF,
despite a large spectrum of ablation strategies (Kocyigit et al., 2015). There is also a need for
policy development concerning conclusive guidelines around the treatment of the concomitant
AF and HF, as there are inconsistent and conflicting management strategies found within the
literature. The information found within the literature review is valuable to PCPs, including NPs,
as they are well equipped to manage these patients in outpatient settings with a collaborative
approach.

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119
Appendix A: Database Searches
CINHAL (EBSCO)
Search
Search Term/Key Words
Results
1
MH Heart Failure
43,140
2
AB heart failure OR chf OR congestive heart
55,027
failure
3
S1 AND S2
36,738
4
MH Atrial Fibrillation
25,542
5
atrial fibrillation OR afib OR af
21,330
6
S4 AND S5
13,178
7
antiarrhythmic drugs OR rate control OR rhythm
33,148
control
8
MH "Physicians, Family" OR MH "Family Nurse 100,467
Practitioners" OR MH "Primary Health Care" OR
MH "Family Practice"
9
10

11
12

MH "Readmission" OR MH "Hospitalization+"
MH "Health Care Costs+" OR MH "Outcomes
(Health Care)+" OR MH "Preventive Health
Care+"
S7 OR S8 OR S9 OR S10
S3 AND S6 AND S11

COCHRANE (EBM)
Search
Search Term/Key Words
1
heart failure or chf* or congestive heart failure
2
atrial fibrillation or afib* or af*
3
antiarrhythmic drugs or rate control or rhythm
control or catheter ablation or physicians, family
or family nurse practitioners or primary health
care or family practice
4
health care costs OR outcomes OR preventative
health care OR readmission OR hospitalization
5
1 and 2 and 3 and 4
MEDLINE (Ovid)
Search
Search Term/Key Words
1
heart failure or chf* or congestive heart failure
2
atrial fibrillation or afib* or af*
3
antiarrhythmic drugs or rate control or rhythm
control or catheter ablation or physicians, family
or family nurse practitioners or primary health
care or family practice
4
health care costs OR outcomes OR preventative
health care OR readmission OR hospitalization
5
1 and 2 and 3 and 4

117,477
806,999

992,493
363
Results
35006
212614
17097

290309
311
Results
215272
7477977
212320

1246093
703

120
Appendix B: PRSIMA Flow Diagram

Databases searched: CINHAL (EBSCO) (n = 363),
COCHRANE (EBM) (n=311), MEDLINE (Ovid) (n=703)

Records after duplicates removed
(n=1237)

Inclusion/Exclusion
Criteria Applied

Records excluded after
title and abstract screen
(n=1016)

221 Articles Retrieved

Inclusion/Exclusion
Criteria Applied

Articles included
(n=20)

Full-text articles excluded,
with reasons
(n=201)

Author,
Date,
Title,
Journal
BlackMaier,
E., Ren,
X.,
Steinber
g, B. A.,
Green,
C. L.,
Barnett,
A. S.,
Rosa, N.
S., AlKhatib,
S. M.,
Atwater,
B. D.,
Daubert,
J. P.,
FrazierMills, C.,
Grant, A.
O.,
Hegland,
D. D.,
Observational,
retrospective
cohort study
performed within
the Duke Center
for AF.

The purpose
of the study
was to
evaluate
outcomes of
catheter
ablation of
AF in
patients with
HFpEF
compared to
HFrEF.

Symptoms were
assessed using
NYHA functional
class and Mayo
AF Symptom
Inventory

AF ablation
procedures were
performed from
January 1, 2007,
to June 30, 2013,
in adult patients
and were
retrospectively
screened for
inclusion.

Research Type/
Background/
Methods

Purpose/
Hypothesis

Single Studies

Exclusion Criteria:
patients with
baseline
measurement of
LVEF without
follow-up data, or
with catheter
ablation other than
radiofrequency
ablation (surgical,
cryoballoon, or laser
balloon).

Inclusion Criteria:
patients undergoing
first-time ablation of
AF.

230 patients with HF
underwent AF
ablation (97 with
HFrEF and 133 with
HFpEF).

Sample

After catheter ablation
of AF, both groups had
significant
improvements in
NYHA function class.
However, no
statistically significant
difference in
improvements in

No significant
differences in AF
recurrence
(33.9% vs. 32.6%;
p0.848), repeat ablation
(6.0% vs.
3.1%; P= 0.364), or 12month all-cause
hospitalization (26.3%
vs. 32.0%; p=0.350)
and cardiovascular
hospitalization (21.1%
vs. 22.7%; P= 0.768)
between groups.

Key Findings

Appendix C: Literature Review Matrix

The
radiofrequency
ablation
procedure was

Manually
screening of
operative
reports were
done to
determine
radiofrequency
and
fluoroscopy
time, ablation
lesion sets, and
procedural
duration.

Approved by
the Duke
University
Institutional
Review Board.

Strengths

The
generalizabili
ty of the
findings
may be
limited by the
single-center,
retrospective,
observational
approach. It
might also be
limited, as
the patients

Median
follow up
was short,
specifically
10.3 months
in the HFpEF
group and
10.6 months
in the HFrEF
group.

Limitations

121

Catheter
ablation
of atrial
fibrillatio
n in
patients
with
heart
failure
and
preserve
d
ejection
fraction.

2018.

Jackson,
K. P.,
Jackson,
L. R.,
Koontz,
J. I.,
Lewis,
R. K.,
Sun, A.
Y.,
Thomas,
K. L.,
Bahnson,
T. D., &
Piccini,
J. P.
Symptom burden
and adverse
events
were determined
by telephone at 1
week, and 3, 6,
and 12
months after the
procedure.

checklist
(MAFSI).

An on treatment
analysis compared
NYHA functional class
in HFpEF and HFrEF
patients with freedom
of AF at 12 months and
showed a greater trend
towards better
improvements in
HFpEF patients (-0.42
vs. -0.24; P= 0.083).

Baseline
characteristics
found to be
statistically
significant
between HF
groups were
used to adjust
each endpoint
using
an appropriate
multivariable
regression
model. ??

After catheter ablation
of AF, there were
significant
improvements for both
groups in MAFSI.
In the HFpEF compared
to the HFrEF, there
were greater
improvements in
MAFSI symptom
severity (-0.23 vs. 0.09; P= 0.116) and
frequency (-0.105 vs. 0.74; P=0.116),
however results were
not statistically
significant.
There was no
significant
difference
among AADs
prescribed at
discharge
(80.4% of
patients were
given a III
AADs).

thoroughly
described and
the same for
all participants.

NYHA function class (0.32 vs. -0.19; P=
0.135) between groups.

The sample
size was
relatively
small.

are a selected
cohort and
are treated in
highly
experienced
centers.

122

Di Biase,
L.,
Mohanty
, P.,
Mohanty
, S.,
Santange
li, P.,
Trivedi,
C.,
Lakkired
dy, D.,
Reddy,
M.,
Jais, P.,
Themisto
clakis,
S., Dello
Russo,
A.,
Casella,
M.,
Pelargon
io, G.,
Narducci

Heart
Rhythm.

The purpose
was to
determine if
catheter
ablation is
more
effective than
amiodarone
for the
treatment of
persistent AF
in patients
with HF.

Follow-up period
of 24 months.

Patients were
randomly
assigned by a 1:1
ratio to undergo
catheter ablation
for AF or to
receive
amiodarone.

Quantitative,
multi-center, open
labelled,
randomized,
parallel-group
study.

Exclusion Criteria:
AF from a reversible
etiology, valvular or
coronary heart
disease requiring
surgery, early
postoperative AF,
life expectancy ≤ 2
years, prolonged QT

Inclusion Criteria: ≥
18 years of age,
persistent AF, dualchamber implantable
cardioverter
defibrillator or
cardiac
resynchronization
therapy defibrillator,
NYHA class II to III,
LVEF < 40%.

CA (group 1) n=102.
amiodarone (group
2) n=101.

Significantly lower
mortality rates were
observed in catheter
ablation group (8% in
group 1 and 18% in
group 2; P=0.037).

Unplanned
hospitalization rate was
31% in the catheter
ablation group and 57%
in amiodarone group
(P<0.001, 95% CI 0.390.76).

Ablation outcomes for
HFpEF and HFrEF of
access site bleeding,
stroke or transient
ischemic accident, or
acute HF were not
statistically significant.
70% of patients (95%
CI 60%–78%) patients
in group 1 did not have
recurrence of AF after
an average of 1.4±0.6
procedures, in
comparison with 34%
(95% CI 25%–44%) in
patients receiving
amiodarone.

Sampling
based on 80%
power
analysis.

The study
included 30%
oversampling
for attrition.

Computerized
central
randomization
scheme was
done using
block
randomization.
Sets of
randomly
selected blocks
were provided
to the sites.

Patients were
followed up
for 24
months,
however a

Sotalol and
dofetilide are
alternative
AADs
available for
managing
combined AF
and HF,
however
were not
tested in the
trial.

No formal
comparison
with a rate
control
strategy was
done.

123

Ablation
versus
amiodaro
ne for
treatment
of
persisten
t atrial
fibrillatio
n in
patients
with
congesti
ve heart
failure

2016.

, M. L.,
Schweik
ert, R.,
Neuzil,
P.,
Sanchez,
J.,
Horton,
R.,
Beheiry,
S.,
Hongo,
R., …
Natale,
A.

interval,
hypothyroidism,
severe pulmonary
disease, liver failure,
≥ 200 mg of
amiodarone a day.

longer
follow-up
would be
desirable.

124

Atrial
fibrillatio
n

2019.

Circulati
on.
Eitel, C.,
Ince, H.,
Brachma
nn, J.,
Kuck,
K.-H.,
Willems,
S.,
GerdsLi, J.-H.,
Tebbenjo
hanns, J.,
Richardt,
G.,
Hochade
l, M.,
Senges,
J., &
Tilz, R.
R.

and an
implante
d
device.

The purpose
of the study
was to assess
ablation
strategies in
patients with
AF and HF,
specifically
comparing
outcomes in
patients with
HFpEF, HF
with midrange EF
(HFmrEF),
and HFrEF.

Patients were
divided into three
groups according to
LVEF: HFpEF
From January
(n=333), HFmrEF
2007 to January
(n=207), and HFrEF
2010, 728 patients (=188).
with HF and AF
were enrolled
Ablation strategies
prior to catheter
differed significantly
ablation of AF.
between the groups.
The majority of
A total of 51
patients with HFpEF
German centers
(83.4%) and
collected
HFmrEF (78.4%)
data of
underwent
consecutive
pulmonary vein
patients ≥ 18
isolation (PVI) and
years of age.
48.9% of patients
with HFrEF, of
Choice of catheter which 47.3%
ablation strategy
underwent ablation
(PVI vs. AV-node of the
ablation) was at
atrioventricular (AV)
the discretion of
node.
the center.

Multi-center
German ablation
registry.

The mortality rate was
significantly higher in
the HFrEF group
(10.4%) compared to
HFpEF (2.5%) and
HFmrEF (2.2%), with a

Arrhythmia recurrences
occurred in 47.9% of
HFpEF, 36% in
HFmrEF, and 39.8% in
HFrEF with a p value
of 0.036.

Follow-up was
completed in 97% with
HFpEF, 99% HfmrEf,
and 97.3% with HFrEF.
There were no
significant differences
in terms of symptoms
or severe adverse
events, such as
myocardial infarction,
stoke, or major
bleeding.

Large sample
size compared
to other studies
in the literature
review.

Assessed
ablation
strategies for
patients with
three different
types of
ejection
fraction.

Follow up was
completed in
100% of the
patients in the
AV-node
group and
94.9% in the
PVI group.

Patient
characteristic
between
groups
differed.
Specifically,
Patients
undergoing
AV-node
ablation were
older, more
often female,
and had
lower LVEF
and a higher
NYHA class,
as compared
to patients
undergoing
left atrial
catheter
ablation.

The study
was not
randomized.

125

Fukui,
A.,
Tanino,
T.,
Yamagu
chi, T.,
Hirota,
K., Saito,
S.,
Okada,
N.,
Akioka,

Clinical
Research
in
Cardiolo
gy.

ablation
strategies
and
outcome
in
patients
with
heart
failure:
Insights
from the
German
ablation
registry.

The purpose
was to
determine if
catheter
ablation of
AF reduces
HF
rehospitalizat
ion compared
with
conventional
pharmacother
The study
included 85
patients with
HFpEF (EF ≥
50% and a history
of HF
hospitalization),
and were
diagnosed with

Retrospective
study.

Follow up was 12
months.

A centralized,
prospective 1year follow-up
focused on
complications,
medication, AF
symptoms, repeat
hospitalizations,
arrhythmia
recurrences and
12-lead ECGs.

Exclusion criteria: >
85 years old, cancer,
hemodialysis, left

A total of 85
patients: 35 had
drug‐refractory AF
and received CA,
and the control
group that had 50
patients treated with
AADs and/or BBs.

A total of 734
procedures were
done. 47.3% with
HFrEF, and 7.5% of
patients with HFpEF
and 12.6% of
patients with
HFmrEF, underwent
ablation of the AV
node.

Inclusion Criteria:
patients with
structural heart
disease and HF
NYHA class ≥ 2.

Significantly more
patients in the ablation
group were free from
HF rehospitalization
(P = 0.0039), and
catheter ablation of AF

Sinus rhythm was
maintained in
approximately 70% of
patients who underwent
ablation of AF.

There were no
differences in
rehospitalizations for
patients undergoing
AV-node ablation vs.
PVI during follow-up.

P value <0.001, and
thus statistically
significant.

Patient
characteristics
did not differ
between the
two groups
including, age,
female sex,
mean plasma
BNP, mean
LVEF, and
type of AF.

The sample
size was not
sufficient
enough to
reach a

Follow up
period of 12
months.
The study
was not
randomized
or a
multicenter
study.

Recurrences
might also
have been
missed due to
lack of
systematic
rhythm
follow-up
with HolterECGs. Thus,
follow up
was done at
the discretion
of the
treating
center.

126

Journal
of
Cardiova

Catheter
ablation
of atrial
fibrillatio
n reduces
heart
failure
rehospita
lization
in
patients
with
heart
failure
with
preserve
d
ejection
fraction.

2020.

H.,
apy in
Shinohar patients with
a, T.,
HFpEF.
Yufu, K.,
&
Takahas
hi, N.

Follow‐up period
was 792 ± 485
days and was
performed by
direct contact
with patients in
the institute or
questioning to

A 12‐lead ECG
was obtained at
each visit for at
least 1, 3, 6, and
then every 6
months for up to
2 years. Also, a
24‐hour Holter
monitor was
performed 3, 6,
12, and 24
months after the
procedure.

AADs were
discontinued for
at least five half‐
lives before AF
ablation, except
amiodarone.

AF by 12‐lead
electrocardiogram
atrial diameter
greater than 55 mm,
and severe valvular
disease.

was the only preventive
factor of HF
rehospitalization
(OR = 0.15; 95% CI
0.04‐0.46; P < .001).

The study
thoroughly
discussed the
study
methodology.
The followup of AF
recurrence
was not strict,
particularly
in patients
with rhythm
control by
AADs.

definite
conclusion.

127

Catheter
ablation
versus
rate
control
in
patients
with
atrial
fibrillatio
n and
heart
failure:
A

2017.

scular
Electrop
hysiolog
y.
Geng, J.,
Zhang,
Y.,
Wang,
Y., Cao,
L., Song,
J., Wang,
B., Song,
W., Li,
J., & Xu,
W.

The purpose
was to
determine if
catheter
ablation of
AF is
associated
with a low
risk of
adverse
events in
patients with
HF,
compared to
rate control
medical
strategies.
Prior to
allocation, all
patients were
hospitalized due
to HF and treated
with angiotensinconverting
enzyme
inhibitors/angiote
nsin receptor
blockers, BBs,

Prior to
enrollment, all
patients received
catheter ablation
or medical rate
control treatment
decided by
experienced
doctors.

Retrospective
cohort study
conducted in
three tertiary
hospitals from
January 2015 to
May 2016.

their private
physicians.

All-cause mortality,
stroke, and unplanned
hospitalization were
higher in the rate
control group than in
catheter ablation group
(7.9% vs.3.3%,
[p=0.126] 9.9% vs.4.4
[P=0.103], and 16.1%
vs.10.0% [p=0.140]),
but not statistically
significant.
In the catheter ablation
group, 82.2% had
freedom from AF. In
the rate control group,
all patients remained in
paroxysmal and

Inclusion Criteria:
aged >18 years,
documented AF
(paroxysmal,
persistent and longstanding persistent
AF), symptomatic
HF (NYHA class II
to IV), and left
ventricular systolic
dysfunction (ejection
fraction <50%).
Exclusion Criteria:
reversible causes of
AF and/or HF,
previous ablation,
postoperative AF,
contraindications to
CA, anticoagulation

CA group had a
significant decreased
risk of major adverse
cardiac events
Ninety patients had
compared with rate
AF ablation and 304 control group (13.3%
received medical rate vs. 29.3%, 95% CI
control therapy.
0.32–0.82, p=0.005).

A total of 394
patients with AF and
HF were included.

The authors
applied
propensity
score matching
to adjust
potential
confounding
factors. Thus,
imbalanced
baseline
characteristics
were added
into a logistic
regression
model to help
remove biases.

The
methodology
of the study
was
thoroughly
explained.

Short term
follow-up
period.

Sixteen
patients were
lost to
follow-up.

The authors
did not
evaluate the
change in
LVEF, 6minute test,
NYHA class,
or QoL.

The authors
did not find
statistical
differences of
death, stroke,
and
unplanned
hospitalizatio
ns between
the groups.

128

Medicine
.

multicent
er study.

Patients were
evaluated from
the discharged
day until death or
December 2016.

For the catheter
ablation group, if
AF reoccurred
after pulmonary
vein isolation,
electrical
cardioversion was
done with
amiodarone (150
mg) until AF
converted to sinus
rhythm.

The goal of
treatment with
rate control
strategies (BBs
and/or digoxin)
was to achieve the
target heart rate of
<80 beats per
minute.

and other
medications for at
least 1 month.

or AADs, and
malignancy.
The mean heart rate at
rest was 73.5 ± 14.5
beats per minute in rate
control group, and 71.7
± 15.8 beats per minute
in catheter ablation
group (p=0.312).

persistent or longstanding persistent AF.

129

Hess, P.
L.,
Sheng,
S.,
Matsoua
ka, R.,
DeVore,
A. D.,
Heidenre
ich, P.
A.,
Yancy,
C. W.,
Bhatt,
D. L.,
Allen, L.
A.,
Peterson,
P. N.,
Ho, P.
M.,
Lewis,
W. R.,
Hernand
ez, A. F.,
Fonarow
, G. C.,
&

The study
characterized
heart rates
achieved at
discharge in a
current
cohort
of patients
admitted with
HF. The
study aimed
to explore
potential
associations
between rate
control and
death, allcause
readmission,
and
cardiovascula
r
readmission;
and to
evaluate
whether
the relation
between rate
control and
Majority of the study
population were
women and white.

Median age of the
study population
observational
analysis, the
possibility of
unmeasured or
residual confounding
exists
was 82 years.

Total of 13,981
patients from 199
sites with AF and
HF: 9,100 (65.0%)
had strict rate
control, 4,617
(33.0%) had lenient
rate control, and 264
(1.9%) had poor rate
control by resting
heart rate on the day
of discharge.

Median ejection
A total of 186,449 fraction was 50%.

Categorized
lenient rate
control as resting
heart rate <110
beats/min), strict
rate control as
resting heart rate
<80 beats/min,
and poor rate
control was
considered a
resting heart rate
>110 beats/min).

Dates: July 1,
2011, to
September 30,
2014.

Data from the Get
with The
Guidelines-HF
Program linked
with Medicare.

The mean followup period was
13.5 ± 5.3
months.
Observational
analysis.
Compared with strict
rate control, lenient rate
control was associated
with higher risks of
death (HR 1.21, 95% CI
1.11 to 1.33, p <0.001),
all-cause readmission
(HR 1.09, 95% CI 1.03
to 1.15, p, P <0.002),
death or all cause
readmission (HR 1.11,
95% CI 1.05 to 1.18, p
<0.001), however not
cardiovascular
readmission (HR1.08,
95% CI 1.00 to 1.16,
p=0.051) at 90 days.

Cox model
using inverse
probabilityweighting
was fitted to
examine
associate
between rate
control and
outcomes.

The sample
size of
patients
attaining poor
rate control
goals is
modest, and
correspondin
g confidence
intervals are
wide

Due to the
nature of an
observational
study,
residual and
unmeasured
confounding
may have
yielded false
findings.

130

The
America
n Journal
of

Strict
versus
lenient
versus
poor rate
control
among
patients
with
atrial
fibrillatio
n and
heart
failure
(from the
Get With
The
Guidelin
es—
Heart
Failure
Program)
.

2020.

Piccini,
J. P.

outcomes
differs by
ejection
fraction.

P value <0.05 was
considered
statistically
significant.

patients were
admitted to 309
hospitals with HF
and 107,031
patients were
excluded for
various reasons.

131

Impact
of
catheter
ablation
of atrial
fibrillatio
n on
longterm
clinical
outcome
s in
patients
with

2018.

Cardiolo
gy.
Ichijo,
S.,
Miyazaki
, S.,
Kusa, S.,
Nakamur
a, H.,
Hachiya,
H.,
Kajiyam
a, T., &
Iesaka,
Y.

The purpose
of the study
was to
determine the
long-term
effects
ablation of
AF in
patients with
HF.

The procedure
was pulmonary
vein antrum
isolation, and a
substrate
modification was
added in 22
(43.1%) HFrEF
and 16 (29.1%)
HFpEF patients.

HF and AF were
defined according
to the latest
guidelines.

All participants
were patients with
HF that
underwent
catheter ablation
for AF between
2010 and 2015 for
the first time.

Single center
retrospective nonrandomized
study.

At 3 years, freedom of
AF recurrence, HFrelated hospitalizations,
and composite
endpoints of all-cause
death, stroke, HFrelated hospitalizations
occurred. For HFrEF
the results were 88.7%,
97.6%, and 97.6%. For
HFpEF patients, the
results were 79.3%,
96.2%, and 91.8%.

HFpEF patients
more often had
paroxysmal AF, a
higher LVEF, a
smaller LV diastolic
diameter, and a
lower N-terminal pro
brain natriuretic
HFrEF:
peptide.
After 1.4 ± 0.3
procedures, 47 (92.1%)
In total, 11 (21.6%)
patients were free from
HFrEF and 15
any recurrent atrial
(27.3%) HFpEF
arrhythmias. The
patients had a history arrhythmia-free
of a hospitalization
survival at 1, 2, 3, and 4
due to HF prior to
years after the last
the procedure.
procedure was 95.3%,
88.7%, 88.7%, and
88.7%.
One patient died due to
an acute myocardial
infarction. Freedom
from the composite
endpoint (death,

A total of 106
patients with HF
were divided into
two groups (51 with
HFrEF and 55 with
HRpEF).
Detailed
statistical
analysis, as
data was
compared
using a Student
t test or MannWhitney U
test.

Longer followup period than
majority of
other studies in
the literature
review.

Some
patients
continued
low-dose
AADs after
ablation of
AF, as the
purpose was
to assess the
outcomes and
LV reverse
remodelling
after

Limited
intensity of
monitoring,
thus
asymptomati
c recurrent
events would
have been
missed.

The study
involved a
single center
and
participants
were not
randomized.

132

Journal
of
Cardiolo
gy.

heart
failure.

Follow up period
of 32.4 ± 18.6
months.

Patients were on
optimal medical
therapy for HF,
including ACE-I,
ARB, BB,
diuretics, digoxin,
if appropriate.

AADs were
discontinued for
at minimum of
five half-lives
prior to CA.
Patients were
anticoagulated for
more than one
month.

HFpEF:
After 1.4 ± 0.5
procedures, 47 (85.5%)
patients remained free
from recurrent atrial
arrhythmias – at 1, 2, 3,
and 4 years after the
last procedure was
90.0%, 84.6%, 79.3%,
and 79.3%.
1 (1.8%) patient died
due to cancer during the
follow-up period.
HF-related
hospitalizations were
observed in 2 (3.6%)
post-AF ablation – at 1,
2, 3, and 4 years after

strokes, and HF-related
unplanned
hospitalizations) at 1, 2,
3, and 4 years after the
initial procedure was
97.6%, 97.6%, 97.6%,
and 88.7%
Freedom from HFrelated unplanned
hospitalizations at 1, 2,
3, and 4 years after the
initial procedure was
97.6%, 97.6%, 97.6%,
and 97.6%
Biases
occurred in
selecting
healthier
patients, as
they were
more suitable
to undergo
CA.

restoring
sinus rhythm,
rather than
efficacy of
catheter
ablation as an
alone strategy
for AF.

133

Catheter
ablation
versus
best
medical
therapy
in

2019.

Kuck,
K.-H.,
Merkely,
B., Zahn,
R.,
Arentz,
T., Seidl,
K.,
Schlüter,
M., Tilz,
R. R.,
Piorkows
ki, C.,
Gellér,
L.,
Kleeman
n, T., &
Hindrick
s, G.

The authors
hypothesized
that the
catheter
ablation
group would
have a 15%
LVEF
increase after
1 year,
whereas the
BMT group

The purpose
of the study
was to prove
that catheter
ablation of
AF was
superior to
best medical
therapy
(BMT) in
regards to the
absolute
increase in
LVEF from
baseline to 1
year.
Inclusion Criteria:
need for an ICD or a
CRT-D, a LVEF ≤
35%, have optimal
medical treatment
for HF for at least 1
month.

A total of 140
patients were
included in the
primary efficacy and
end point analysis
(68 in the catheter
ablation group and
72 in the BMT
group).

Exclusion Criteria:
left atrial diameter of
Between January >60 mm in
2008 and June
parasternal
2016, 202 patients axis, underlying
were enrolled at
valvular heart
17 study sites in
disease without
Germany,
correction,
Hungary, and
and previous PV
Spain.
isolation procedures.

Randomization
with a 1:1 ratio
was completed
using a webbased application
computergenerated lists of
numbers in a
block design,
arranged by
device type (ICD
or CRT-D),
severity of AF,
and study site.

Multicenter,
open-label,
controlled,
randomized trial.

Least-squares mean
absolute increase in
LVEF from
baseline to 1 year was
8.8% (95% CI 5.8%–

There were no
statistically significant
differences between
treatment groups in the
secondary end points.
Differences between
catheter ablation and
BMT groups: change in
6-minute walk distance
(+46 m vs. +81 m,
P=0.07), quality-of-life
score (−11.2 and −8.9,,
P=0.42), and change in
NT-proBNP level
(−891 and −419 pg/mL,
P=0.60).

After 1 year, the
catheter ablation group
patients spent
significantly more time
in sinus rhythm than
BMT.

the initial procedure
was 96.2%, 96.2%,
96.2%, and 96.2%

Randomization
using a 1:1
ratio and black
design.

Multi-center
study,
including 17
study sites.

Lack of
statistical
significance.

Short term
follow-up
period of 1
year.

The study
was
terminated
early due to
being
ineffective.

134

Circulati
on:
Arrhyth
mia &
Electrop
hysiolog
y.

patients
was expected
with
to have a 5%
persisten increase.
t atrial
fibrillatio
n and
congesti
ve heart
failure:
The
randomiz
ed
AMICA
Trial.

Minnesota living
with HF
questionnaire
total

BMT consisted of
rate or rhythm
control followed
by the American
College of
Cardiology/Ameri
can Heart
Association/Euro
pean Society of
Cardiology 2006
Practice
Guidelines for the
Management of
Patients with AF.

Pulmonary vein
isolation was the
primary ablation
approach.

Patients with
persistent or
chronic AF and
LVEF ≤ 35%
were randomly
allocated to
catheter ablation
of AF or BMT.

11.9%) in the ablation
group and 7.3% (4.3%–
10.3%,
P=0.36) in the BMT
group.

135

Machino
Ohtsuka,
T., Seo,
Y.,
Ishizu,
T.,
Yamamo
to, M.,
HamadaHarimur
a, Y.,
Machino
, T.,
Yamasak
i, H.,
Sekiguch

The aim of
the study was
to determine
if
maintaining
sinus rhythm
was
associated
with an
improved
prognosis
compared to
a rate control
strategy in
patients with
combined
A total of 283
patients with
HFpEF and AF.
There were 107
patients that
maintained sinus
rhythm by

Utilized data from
11 institutions
between Jun 2012
and December
2015.

Follow up visits
occurred at 1, 3,
6, and 12 months.
Follow up was
done in July
2017.
Retrospective,
observational
study.

score of 21
questions with
answers graded
from 0 (no effect
on HF/condition)
to 5 (strong effect
on HF/condition)
was used to assess
QoL scores.

The 283 patients met
criteria for HFpEF
and had AF,
including 106
patients with
paroxysmal AF, 56
with persistent AF,
and 121 with longstanding persistent
AF.

Rhythm control
group (n = 107) and
rate control group (n
= 176).

The composite outcome
included events of CV

All-cause mortality was
lower in the rhythm
control group than in
the rate control group
(95% CI 0.03–0.59; p=
0.007). However, the
difference between
groups was not
significant after
adjustment with
propensity score
matching (adjusted HR,
0.31; 95% CI 0.07–
1.39; p=0.13).

The authors
identified the
important
confounding
factors, which
were taking
into account in
the study
design.
Specifically,
the exposure
was accurately
measured to
minimise bias
by utilizing the
propensity

Treatment
strategies
decisions are
made at the
attending
physician’s

The results
for primary
outcomes
were not
statistically
significant
after
propensity
score
matching.

136

Relations
hips
between
maintena
nce of
sinus
rhythm
and
clinical
outcome
s in
patients
with
heart
failure
with
preserve
d
ejection
fraction
and atrial
fibrillatio
n.

2019.

i, Y.,
Nogami,
A.,
Aonuma,
K., &
Ieda, M.

HFpEF and
AF.

The treatment
strategy for
rhythm or rate
control was
determined by
the attending
physician's

Rate control
medications used
were BBs
(bisoprolol,
carvedilol), CCBs
(diltiazem,
verapamil), and
digoxin.
Additional
medication for
HF included
diuretics, MRA,
angiotensinconverting
enzyme
inhibitors, or
angiotensin II
receptor blockers.

catheter ablation
and/or AADs, and
176 patients were
treated with rate
control.

Exclusion Criteria:
LVEF <50%, age
<20 years, history of
pacemaker
implantation,
valvular heart
disease requiring
surgical intervention,
active ischemic heart
disease, severe
pulmonary disease
or liver failure, and
lack of informed
consent.
In total, 172 patients
underwent attempts to
restore SR, 105
achieved successful
rhythm control and 67
experienced recurrence
of AF.

deaths or worsening HF
that required
hospitalization. OF
which, the rhythm
control group had a
lower incidence even
after adjustment with
propensity scoring
(adjusted HR, 0.27;
95% CI 0.12–0.61;
p=0.002).

Strong
statistical
analysis and
transparency
of study
results.

The study
included
participants
from 11
institutions.

The results, or
composite
endpoints,
were measured
objectively.

scoring
process.

Changes in
the
prescribed
medication,
other than
AADS, were
not recorded.

Regardless of
propensity
score
matching,
biases may
limit the
findings.

The study
had a
relatively
small sample
population.

The study
was nonrandomized.

discretion,
making the
comparisons
biased and
challenging.

137

Marrouc
he, N. F.,
Brachma
nn, J,
Andrese
n, D.,
Siebels,
J.,
Boersma
, L.,
Jordaens,
L.,
Merkely,
B.,
Pokushal
ov, E.,
Sanders,
P., Proff,
J.,

Journal
of
Cardiolo
gy.

The purpose
was to assess
whether
catheter
ablation
lowers
morbidity
and mortality
compared to
medical
therapy of
rate or
rhythm
control in
patients with
AF in the
context of
medically
managed HF.

Quantitative,
CA group (n=179)
multicenter, open- and medical therapy
labeled, RCT.
of rate or rhythm
control group
A total of 3013
(n=184).
patients were
assessed for
Inclusion Criteria:
eligibility and 398 paroxysmal or
were enrolled at
persistent AF;
33 sites in
absence of response
Europe, Australia, to, unacceptable side
and the USA.
effects from, or
unwillingness to take
Patients assigned AAD; NYHA class
in a 1:1 ratio by a II, III, or IV HF;
computerized
LVEF of ≤ 35%.
central
randomization
Exclusion Criteria:
design and
Heart transplantation

Follow up period
of 24 months.

All events were
investigated in the
outpatient clinic
and by telephone
and reported by
the primary site
investigators.

preference for
each patient.

The number needed to
treat to prevent death or

Significantly fewer
patients in the catheter
ablation group
compared to the control
group died from any
cause (13.4% vs.
25.0%; 95% CI 0.320.86; P=0.01), were
hospitalized for
worsening HF (20.7%
vs. 35.9%; 95% CI
0.37-0.83; P=0.004), or
died from
cardiovascular causes
(11.2% vs. 22.3%; 95%
CI 0.29-0.84; P=0.009).

The trial
avoided a
specific
strategy of

Treatment
groups were
compared on a
modified

Strong
statistical
analysis of
results.

Unclear
allocation
concealment
and the study
was
unblinded,
which could
have led to
bias in
decisions for
admitting a
patient for
worsening
HF.

Multicentre
study in
developed
countries, thus
the results are
generalizable
and applicable
to clinical
practice.

The results
are not robust
enough to
recommend
changes to
clinical
practice.

138

Saksena,
S., Slee,

The aim of
the study was
to determine

The Catheter
Ablation
versus
Standard
Conventional
Therapy in
Patients with
2018.
Left
Ventricular
Catheter Dysfunction
ablation
and Atrial
for atrial Fibrillation
fibrillatio (CASTLEn with
AF) trial was
heart
initiated to
failure.
address the
above.
The New
England
Journal
of
Medicine
.

Schunker
t, H.,
Christ,
H., Vogt,
J., &
Bansch,
D.

Retrospective
observational
analysis.

Follow up period
of mean 38
months.

At five weeks,
medication
adjustments for
HF were done. At
the baseline
evaluation,
patients were
referred for
catheter ablation
or medical
therapy for AF
based on the
randomization
design.

arranged
according to
center, type of
AF, type of
implantable
device, and
implantable
cardioverterdefibrillator
indication.

In total, 38 patients
with refractory AF
and HFpEF, and 35

Dates: January 2008
to January 2016.

or planned
cardiovascular
resynchronization
therapy.

After DAP, 87%
maintained rhythm
control with

hospitalization for
worsening HF at 36
months was 8.3.

Recommendati
ons are
supported by

Sampling
based on 80%
power
analysis.

Median
follow-up
duration of
37.8 months,
which is longer
compared to
other studies in
the literature
review.

Small sample
size with
strict

rate control
versus
rhythm
All outcomes
control, or
were judged by choice of
an independent AADs, in the
committee, and medical
members were therapy
unaware of
group.
treatment
assignments.

intention to
treat basis.

139

Journal
of
Intervent
ional
Cardiac

if using dualsite right
atrial pacing
2018.
(DAP) as
adjunct
Atrial
therapy to
resynchr standard
onization AAD therapy
therapy
would permit
in
rhythm
patients
control and
with
improve HF
atrial
in patients
fibrillatio with AF.
n and
heart
failure
with and
without
systolic
left
ventricul
ar
dysfuncti
on: A
pilot
study.

A., &
Saad, M.

Mean follow-up
period for
survival was 9.3
years and similar
across subgroups
(P=0.127).

A total of 73
patients with HF
(mean NYHA
class of 2.5) and
AF refractory to
AADs and/or
ablation were
implanted with
dual-site right
atrial pacing
(DAP) systems to
achieve biatrial
electrical and
mechanical
resynchronization
(ART) and
rhythm control.

improvement in NYHA
HF class (mean 1.8)
after 3 years.

Rhythm control was
similar in the HFpEF
group compared to
HFrEF (98 vs. 85%, p
value was not
significant). Long-term
Inclusion Criteria:
rhythm control was not
drug refractory AF,
statistically different in
bradycardia,
the HFpEF and HFrEF
symptomatic HF,
subgroups (83.3 vs.
and hospitalization
93.6% at 5 years;
for HF and/or AF in p = 0.444), in addition
the past 3 months;
to patients with
requiring pacemaker, paroxysmal and
ICD implant, or HF/ persistent AF (90.0 vs.
tachyarrhythmia
83.3%; p = 0.51).
prophylaxis or
treatment; refractory Long-term survival
to 2 or more AAD
rates were superior in
trials for restoring
HFpEF than HFrEF
rhythm control in
(75% in HFpEF vs.
AF; persistent AF
45% in HFrEF at 5
and HF with AF
years, and 60% in
refractory to prior
HFpEF vs. 34% in
cardioversion
HFrEF at 10 years,
therapy, paroxysmal p=0.036).
or persistent AF and
HF recurrence after
Total survival rate of
CA; written
83.9% occurred at

Patients with HFpEF
had higher LVEF
than HFrEF (53 ± 5
vs.
31 ± 10%; p< 0.001).

patients with HFrEF
were included in the
study.

Very long term
follow-up
period.

other evidence,
as
demonstrated
in the
discussion
section.

No
standardized
medical
regimen
occurred for

Unable to
assess HF
metrics, such
as
hospitalizatio
ns for HF.

No control
group for
alternative
pacing sites
to DAP.

inclusion
criteria, thus
limiting the
generalizabili
ty of the
study. The
evidence is
also not
robust
enough to
recommend
changes to
clinical
practice.

140

Yu, H.
T., Yang,
P.-S.,
Lee, H.,
You, S.
C., Kim,

Electrop
hysiolog
y.

The purpose
of the study
was to assess
the efficacy
of ratecontrol
From January
2002 to

Retrospective
observational
study.

Exclusion Criteria:
HFrEF and not on
stable triple drug
therapy for HF or
HFpEF and had not
received diuretic and
vasodilatory therapy;
patients with QRS >
120 ms and
intraventricular
conduction defects;
new to AAD
therapy, coronary
revasculation
procedures in <3
months; heart
transplant or left
ventricular assist
device candidates or
cardiac surgery in <3
months;
Cerebrovascular
accident in <3
months.
Of the total 7,034
patients, they
identified ones with
(n=2,441) or without
(n=4,593) HF.
Patients were

informed consent for
device system.

In patients without HF,
there was no significant
difference in the risk
of death among the 4
medication subgroups

Survival was better in
patients with rhythm
control compared to
those without (75 vs.
54% at 5 years;
p=0.13).

3 years and 72.6% at
5 years, and 47% at 10
years in the combined
HFrEF and HFpEF
population.
Superior survival rates
occurred in patients
with HFpEF compared
to HFrEF at 3, 5, and
10 years (88.2 vs.
79.6%, 81.9 vs. 63.1%,
and 59.9 vs.
33.6%); p = 0.036).

The authors
included
patients with
AF only when
it was a
discharge

The study
was
retrospective
and
observational
.

BNP results
from patients
were not
required for
enrollment.

HFpEF,
which was
left to the
discretion of
the treating
cardiologist.

141

Circulati
on
Journal :
Official

Outcome
s of ratecontrol
treatment
in
patients
with
atrial
fibrillatio
n and
heart
failure—
a
nationwi
de cohort
study.

2018.

T.-H.,
Uhm, J.S., Kim,
J.-Y.,
Pak, H.N., Lee,
M.-H., &
Joung,
B.

medications
in AF
patients with
HF.

Statistical
significance was
P<0.05.

Follow-up period
of 12 years.

December 2008, a
total of 7,034 AF
patients with a
single type of
rate-control drug
or without ratecontrol treatment
were enrolled
from the Korea
National Health
Insurance Service
(NHIS)
database. The
participants were
followed up until
December 2013.

Exclusion Criteria:
patients receiving
multiple types of
rate-control
medications.

Use of BBs reduced the
mortality rate for AF
patients with HF, but
not for those without
HF.

The risk of death was
lower in patients
receiving BBs (adjusted
hazard ratio 0.75, 95%
CI 0.64-0.88; p<0.001)
and calcium-channel
blockers (adjusted HR
0.74, 95% CI 0.55-0.98;
p=0.036) compared
There were 1,307
with those who did not
(18.6%), 331 (4.7%), receive rate-control
and 685 (9.7%)
medications in the
patients enrolled in
patients with AF.
the groups receiving
BBs, CCBs, and
There was no
digoxin.
significant difference
between patients treated
Inclusion Criteria: ≥ with digoxin or not
20 years old,
being treated with ratereceiving single type control medication
of rate control drug
(adjusted hazard ratio
or without rate
1.01 (0.86-1.19;
control treatments.
p=0.928).

assigned to each
treatment group if
they received 1 type
of medication (BBs,
CCBs, or digoxin)
for >90 days within
the 6 months after
enrollment.

Propensityscore matched
analysis was
done and
calculated by
multivariate
logistic
regression
analyses.

Analysis of
categorical
variables was
performed
with the Chisquare test.

Student’s t-test
was used to
compare
variables.

diagnosis or
confirmed
more than
twice in an
outpatient
setting.
Clinical
information,
such as blood
pressure,
heart rate,
type of AF,
or ejection
fraction, were
not available
from the
NHIS
database.

142

Catheter
ablation
for atrial
fibrillatio
n in heart
failure

2019.

Authors,
Title,
Journal
AlTurki,
A.,
Proietti,
R.,
Dawas,
A.,
Alturki,
H.,
Huynh,
T.,
Essebag,
V.
A systematic
review and metaanalysis of RCTs
was completed
using the
Preferred
Reporting Items
for Systematic
Reviews and
Meta-Analyses
guidelines.

To assess the
efficacy and
safety of
catheter
ablation
compared to
medical
therapy in
patients with
AF and HF
with a
reduced
ejection
fraction
(HFrEF).
Total of 856 patients
enrolled. catheter
ablation group
(n=429) and medical
therapy group
(n=427).

Results = 1897,
duplicates removed
= 1868, abstracts
screened = 1868,
full-text articles
reviewed = 46,
studies included = 7.

Sample

Electronic
databases
searched:
PubMed, Embase, Inclusion Criteria:
and Cochrane.
All languages,
human studies in
Search terms:
peer-reviewed
“atrial
journals, RCTs,
fibrillation,”
control group and

Research Type
and Methods

Purpose

Systematic Reviews and Meta-Analyses

Journal
of the
Japanese
Circulati
on
Society.

Six of the seven trials
reported arrhythmiafree survival at the end
of follow-up as the
measure of success of
catheter ablation in

Compared with medical
therapy (including
AADs), catheter
ablation was associated
with a significant
reduction in mortality
(95% CI 0.34-0.74,
P=0.0005), HF-related
hospitalizations (95%
CI 0.440.71, P<0.0001), and
improvements in LVEF
(95% CI 3.71-11.26,
P<0.0001).

Key Findings

Evaluation of
the quality of

Conflicts were
resolved by
consensus and
additional
discussion
with a third
author.

Two
investigators
independently
performed
screening of
titles and
abstracts to
identify
relevant
articles.

Strengths

Absence of
clinical trials
with longterm outcome
assessment
comparing
catheter

Larger trials
are required
to confirm
whether
rhythm
control with
catheter
ablation is
superior to
rate control
in patients
with AF and
HF.

Limitations

143

BioMedi
cal
Central
Cardiova
scular
Disorder
s.

with
reduced
ejection
fraction:
A
systemati
c review
and
metaanalysis
of
randomiz
ed
controlle
d trials.

Retrieved
references were
hand searched to
determine
relevance for
inclusion.

“persistent atrial
fibrillation,”
“ablation,”
“catheter
ablation,”
“pulmonary vein
isolation,” “heart
failure,” “heart
failure with
reduced ejection
fraction,”
“congestive heart
failure,” “left
ventricular
dysfunction,”
“impaired left
ventricular
systolic function,”
“reduced left
ventricular
systolic function,”
“low ejection
fraction,”
“functional
capacity,” and
“QoL.”
Date: documents up
to February 26th,
2018.

medical therapy
group, follow-up
duration 6-12
months.

Significant
improvement in 6
minute walking test
performance (weighted
mean difference, 30.15;
95% CI 10.47 to 49.84;
P < 0.0001) and
Minnesota living with
heart failure
questionnaire scores
(weighted mean
difference, − 9.53; 95%
CI –14.67 to − 4.38;
P < 0.0001) in the AF
catheter ablation group
compared to the
medical therapy group.

CA is a safe procedure
in patients with AF and
HFrEF. The number of
adverse events were
relatively small and are
comparable to those
seen in patients with
paroxysmal AF.

maintaining sinus
rhythm.

All studies
were
multicenter
trials
completed
according to
the intention to
treat principle.

RCTs was
done with the
Risk of Bias
Tool
developed by
the Cochrane
Collaboration.
Variation in
follow-up
duration, as
only two
studies had
more than a
one year of
follow-up.
Therefore,
the benefit of
catheter
ablation
beyond oneyear followup could not
be evaluated.

ablation with
a rate control
strategy.

144

Rhythm
control
for
patients
with
atrial
fibrillatio
n
complica
ted with

(2020).

Chen, S.,
Pürerfell
ner, H.,
Meyer,
C.,
Acou,
W.-J.,
Schratter
, A.,
Ling, Z.,
Liu, S.,
Yin, Y.,
Martinek
, M.,
Kiuchi,
M. G.,
Schmidt,
B.,
& Chun,
K. R. J.

The aim of
the study was
to evaluate
the efficacy
and safety of
rhythm
control
strategies in
patients with
concomitant
AF and HF.

A total of 11 studies
involving 3598
patients were
enrolled.

Compared to medical
rate control:
AADs had similar allcause mortality
Data was taken
(P = 0.65), higher rate
from up-to-date
Trials:
of re-hospitalization
randomized data. RACE-HF 2005
(P = 0.01), and similar
(n=261; mean age
rate of stroke and
Pooled data was
69 ± 9), AFFIRMthromboembolic events
taken from up-to- HF 2007 (n=788;
(P = 0.76,).
date randomized
mean age 70 ± 9),
CA had lower all-cause
data, which was
AF-CHF 2008
mortality (10.7% vs.
stratified into two (n=1376; mean age
18.9%; P = 0.0003),
subsets based on
67 ± 11), CAFÉ-II
reduced rethe profile of the
2009 (n=61; mean
hospitalization rate
intervention for
age 72.4 ± 7.1).
(30.6% vs. 47.5%;
patients with AF
P = 0.003), similar rate
and HF: Subset
Inclusion Criteria:
of stroke events (2.8%
A: AADs for
randomized trial,
vs. 4.7% P = 0.27),
medical rhythm
double blinded, and
greater improvement in
control vs. rate
clear definition of
LVEF (P = 0.0004),
control; Subset B: the study population, lower arrhythmia
catheter ablation
study comparison,
recurrence (29.6% vs.
rhythm control vs. and outcomes
80.1%; P < 0.00001),
medical therapy.
assessment, as well
and greater
as appropriate
improvement in QoL
All comparisons
statistical method, no (P = 0.007).
were estimated on selective loss of data
an intention-toanalysis, and
The rate of overall
treat basis.
important
composite adverse
confounders
events between groups
All P values were identified.
was similar [22.8% vs.
two-tailed, and
34%; P = 0.25).

Stratified pooled
analysis of
randomized data.

Wide array of
hard endpoints
were
comprehensive
ly evaluated.

Clinically
relevant
comparisons
and stratified
analysis were
conducted for
both subsets.

Enhanced
statistical
power, as all
studies were
randomized
trials with high
methodologica
l quality.

Large sample
size.

Intrinsic
heterogeneity
from
different
studies
cannot be
fully ruled
out.

A number of
small sample
size studies
were
included.

145

Catheter
ablation

2018.

Europea
n Heart
Journal.
Ma, Y.,
Bai, F.,
Qin, F.,
Li, Y.,
Tu, T.,
Sun, C.,
Zhou, S.,
& Liu,
Q.

heart
failure in
the
contemp
orary era
of
catheter
ablation:
A
stratified
pooled
analysis
of
randomiz
ed data.

The study
aimed to
evaluate the
efficacy and
safety of
catheter
ablation in
patients with
concomitant
AF and HF,
with the goal
of creating a
comprehensi
ve
Databases
searched:
PubMed, Embase
and Cochrane
Library.

LVEF of all the
participants was

Mean age ranged
from 55 to 64 years
old.

Performed using
random-effect
models.

Key words:
“atrial

Of 2803 articles
found after the
search process, 7
RCTs were included,
enrolling 856
participants.

Meta-analysis.

the statistical
significance was
set at 0.05.

In the catheter ablation
group, 64.2% (95% CI
49.4% to 79.0%) were
free from AF after the
first procedure. catheter
ablation was repeated in

Compared to control
groups:
CA reduced the risks of
all-cause mortality
(95% CI 0.35 - 0.76)
and HF readmission
(95% CI 0.46 - 0.66).

Cochrane
collaboration’s
tool for
assessing risk
of bias was
used to assess
study quality.

Relatively
low accuracy

Lacked
individual
data to
conduct
subgroup
analyses
based on age,
sex, and
baseline
diseases.

146

BMC
Cardiova
scular
Disorder
s.

for
treatment
of
patients
with
atrial
fibrillatio
n and
heart
failure:
A metaanalysis
of
randomiz
ed
controlle
d trials.

representatio
n of
therapeutic
strategies.

fibrillation”,
< 50% and NYHA
“heart failure”,
class was II-IV.
catheter ablation”.
RCTs enrolling
Two researchers
patients with AF and
independently
HF who were
searched the
assigned to CA, rate
databases and
control or medical
extracted data
rhythm control
from the studies.
groups we included.

CA group had an
increase in peak oxygen
consumption (MD 3.16,
95% CI 1.09 to 5.23),
longer 6MWT (MD
26.67, 95% CI 12.07 to
41.27), and reduced
Minnesota Living with
Heart Failure

CA improved LVEF
(MD 7.57, 95% CI 3.72
to 11.41), left
ventricular end systolic
volume (MD -14.51,
95% CI -26.84 to
− 2.07), and left
ventricular end diastolic
volume (MD -3.78,
95% CI -18.51 to
10.96) compared to
control groups.

patients with recurrent
AF, and at the end of
follow-up 74.9% (95%
CI 63.2% to 86.5%) of
patients receiving
catheter ablation had
freedom from AF. AF
burden was 14.2%
(95% CI -10.7% to
39.1%).

and poor
repeatability.

147

Ruzieh,
M., Foy,
A. J.,
Aboujam
ous, N.
M.,
Moroi,
M. K.,
Naccarel
li, G. V.,
Ghahram
ani, M.,
Kanjwal,
S.,
Marine,
J. E., &
Kanjwal,
K.

The aim of
the study was
to determine
if catheter
ablation for
AF is
superior to
medical
therapy alone
in patients
with
coexisting
HF.

Systematic review The search identified
and meta1884 studies, and 7
analysis.
full texts met
inclusion criteria,
Searched:
including 856
PubMed, Google patients (429
Scholar, the
patients randomized
Cochrane Central to catheter ablation
Register for RCTs and 427 patients
and
randomized to
ClinicalTrials.gov medical therapy
for studies that
alone).
evaluated AF
catheter ablation
The average age was
in patients with
63.4 years.
HF.
Inclusion Criteria:
studies that

All-cause mortality was
significantly lower in
the catheter ablation
group (OR 0.49; 95%

Compared with control,
catheter ablation was
associated with
improved NYHA class
(MD -0.74, 95% CI 0.83 to − 0.64) and
lower B-type natriuretic
peptide levels (MD 105.96, 95% CI -230.56
to 19.64).
Significant increase in
LVEF (mean difference
6.8%; 95% CI 3.5 –
10.1; p<0.001) and
6MWT (mean
difference 29.3; 95% CI
11.8 – 46.8; p=0.001),
and improvement in
MLWHFQ (mean
difference -12.1; 95%
CI -20.9 – -3.3;
p=0.007).

Questionnaire scores
(MD -9.49, 95% CI 14.64 to − 4.34) than
the control group.

Patients were
not blinded,
as none of the
trials had a
sham arm.
There were
low risks of
selective
reporting,
attrition bias,
detection and
selection bias
in all trials.

Randomization
was performed
using random
number
generation in
all trials.
Similar
baseline
characteristics
for patients in
the ablation
and the control
groups.

148

Cardiova
scular
Therape
utics.

MetaAnalysis
of Atrial
Fibrillati
on
Ablation
in
Patients
with
Systolic
Heart
Failure.

2019.

Two authors
independently
reviewed all

The study
protocol was
drafted by three
of the authors and
revised by all
coauthors.

Search terms:
“atrial
fibrillation”,
“catheter
ablation”,
“pulmonary
venous isolation”,
“heart failure”,
“left ventricular
dysfunction”,
“low ejection
fraction”,
“functional
capacity”, “QoL”,
“stroke”,
“hospitalization”,
“mortality”, and
“death”.

Latest search
date: October 1,
2018.

randomized patients
with AF and systolic
HF to either catheter
ablation, medical
therapy, or
atrioventricular-node
ablation with
pacemaker
implantation.

The rate of HF- related
hospitalizations was
significantly lower in
the ablation group
(26.7% vs. 45.1%, 95%
CI 0.29 – 0.64; p<
0.001).

Significantly more
patients in the AF
ablation group were in
sinus rhythm at the end
of trials (73.7% vs.
18.3%, 95% CI 10.2 –
111.7; P< 0.001). To
achieve this high
success rate from AF
ablation, repeat
intervention was
allowed in all trials and
the percentage of
patients who underwent
repeat ablation ranged
from 19% to 54%.

CI 0.31 – 0.77;
p=0.002).

149

2018.

Smer,
A., Salih,
M.,
Darrat,
Y. H.,
Saadi,
A.,
Guddeti,
R.,
Mahfood
Haddad,
T.,
Kabach,
A.,
Ayan,
M.,
Saurav,
A.,
Abuissa,
H., &
Elayi, C.
S.

The aim of
the study was
to compare
catheter
ablation to
medical
therapy in
patients with
AF and
HFrEF.

Search terms:
“atrial
fibrillation”,

Dates: January
1966 through
February 2018

Searched
databases:
PubMed, Web of
Science,
CINAHL, and
Cochrane Library
databases.

Performed
according to the
Preferred
Reporting Items
for Systematic
Reviews and
Meta‐Analyses.

Mean follow-up
time of 15.2
months.
Systematic
review.

articles and
abstracts for
inclusion.

Inclusion Criteria:
history of AF with a
diagnosis of HF;
RCT to treat AF
with catheter
ablation vs. medical
therapy (rate or
rhythm control);
reported mean
differences and/or
number of events for
LVEF, HF-related
hospital admission,
6‐minute walk test
distance, and overall
mortality; adult

The mean age was
62.2 ± 7.8 years,
mostly males (83%)
with mean LVEF of
31.2 ± 6.7%.

Six trials with a total
of 775 patients were
included.

The selected
manuscripts
and review
articles were
manually
searched for
additional
studies.

Two authors
separately
searched the
databases.

Shorter
follow‐up
duration in
the majority
of the
included
studies.

Relatively
small number
of patients.

Selection bias
due to the
Titles and
type of
abstracts were patients
CA has less HF hospital screened to
offered to
readmissions (OR 0.5,
identify studies participate in
CI 0.32‐0.78, p=0.002). for full text
these RCTs.
review.
CA has less HF death
CA
from any cause (OR
procedures
0.46, CI 0.29‐0.73,
were done on
p=0.0009).
oral
anticoagulant
s, however no

Compared to medical
therapy, catheter
ablation has
significantly improved
LVEF by 5.9% (Mean
difference 5.93, CI
3.59‐8.27,
p< 0.00001, I2 = 87%),
QoL, (mean difference
−9.01, CI −15.56,
−2.45, P = 0.007, I2 = 4
7%), and functional
capacity (mean
difference 25.82, CI
5.46‐46.18, p=0.01).

150

Clinical
Cardiolo
gy.
Turagam
, M. K.,
Garg, J.,
Whang,
W.,
Sartori,
S.,
Koruth,
J. S.,

Metaanalysis
of
randomiz
ed
controlle
d trials
on atrial
fibrillatio
n
ablation
in
patients
with
heart
failure
with
reduced
ejection
fraction.

The aim of
the study was
to compare
catheter
ablation and
pharmacother
apy in adult
patients with
AF and HF,

Inclusion Criteria:
RCTs published in

Out of 24, 960
records, a total of 6
RCTs met the
inclusion criteria,
and 775 patients
were included.

Exclusion Criteria:
published abstract
without full text
publication; studies
assessing the impact
of catheter ablation
on AF without
medical treatment
group; studies
lacking endpoint
measures.

A two sided P
value of <0.05
was considered
statistically
significant for all
analyses

Randomized
control trials that
compared clinical
outcomes of
catheter ablation
versus drug
therapy in adults
with AF and HF

subjects (> 18 years
of age).

“ablation”, and
“heart failure”.

Compared with drug
therapy, AF ablation
reduced all cause
mortality (9.0% vs.
17.6%; risk ratio, 0.52
[95% CI 0.33 to 0.81])
and HF hospitalizations
(16.4% vs. 27.6%; risk

Freedom from AF was
higher in patients who
had catheter ablation
(OR 24.2, CI 6.94‐
84.41, p< 0.00001).

Two
investigators
independently
screened all
titles, extracted
data, and
assessed study
quality.

Possible
patient
selection bias

The results
were
predominatel
y from 1
clinical trial.

anticoagulant
details were
available in
most studies.

151

Annals
of
Internal
Medicine
.

Catheter
ablation
of atrial
fibrillatio
n in
patients
with
heart
failure.

2019.

Miller,
M. A.,
Langan,
N., Sofi,
A.,
Gomes,
A.,
Choudry,
S.,
Dukkipat
i, S. R.,
&
Reddy,
V. Y.

The quality
of individual
studies were
assessed
using the
Cochrane
Risk of Bias
Tool.

to determine
the benefits
and harms.

Search terms:
“atrial
fibrillation”,
“catheter
ablation”, “heart

Two investigators
independently
performed
searches.

Data sources were
searched from
January 2005 to
October 2018.

English, a minimum
of 6 months of
follow-up,
Data sources:
comparing clinical
ClinicalTrials.gov outcomes of catheter
, PubMed, Web of ablation and drug
Science, EBSCO therapy in adults
Information
with AF and HF.
Services,
Cochrane Central
Register of
Controlled Trials,
Google Scholar,
and various
scientific
conference
sessions.

were included in
the study.

Serious adverse events
were more common in
the catheter ablation
groups, however
differences between
groups were not
statistically significant
(7.2% vs. 3.8%; RR,
1.68 [CI 0.58 to 4.85]).

CA of AF improved
LVEF (mean
difference, 6.95% [CI
3.0% to 10.9%]), 6minute walk test
distance (mean
difference, 20.93 m [CI
5.91 to 35.95 m]), peak
oxygen consumption
(VO2max) (mean
difference, 3.17 mL/kg
per minute [CI 1.26 to
5.07 mL/kg per
minute]), and QoL
(mean difference in
Minnesota Living with
Heart Failure
Questionnaire score,
9.02 points [CI 19.75 to
1.71 points]).

ratio, 0.60 [CI 0.39 to
0.93]).

Utilization of
the Cochrane
Risk of Bias
Tool for
assessing the
studies.

No funding
was receive
for the study.

Heterogenous
follow-up
length among
trials.

Open-label
trial designs.

Lack of
patient-level
data.

occurred in
the catheter
ablation
group.

152

βblockers
and risk
of allcause
mortality
in

2019.

Xu, T.,
Huang,
Y.,
Zhou,
H., Bai,
Y.,
Huang,
X., Hu,
Y., Xu,
F.,
Zhang,
Y, &
Zhang, J.

To
investigate
the effects of
BBs on
outcomes in
patients with
chronic HF
and AF.

Key words:
“atrial
fibrillation” and
“heart failure” or
“cardiac

Databases
searched:
PubMed,
MEDLINE and
Embase databases
until 30, 2017.

Search was
performed
according to the
recommendations
of the MetaAnalysis of
Observational
Studies in
Epidemiology
Group.

failure”, “left
ventricular
ejection fraction”,
“hospitalizations”
, “functional
capacity”, “peak
oxygen
consumption”,
and “QoL”.

BBs were not
associated with a
reduction of
cardiovascular
mortality (RR = 0.83;
95% CI 0.65–
1.06, P = 0.14).

Results = 2,826, 46
duplicates removed,
potentially relevant
articles = 2,780,
2,741 articles were
excluded based on
title and abstract,
full-text articles
reviewed = 39,
studies based on BBs
in patients if HF and
AF = 12 included in
the synthesis.

BBs treatment was not
associated with a
reduction of
hospitalization for HF
(RR = 1.03; 95% CI
0.89–1.21, P = 0.66).

BBs were associated
with significant
decrease in all-cause
mortality for patients
with combined AF and
HF (95% CI 0.65-0.82,
P < 0.001).

Twelve studies (6
post-hoc analysis of
RCTs and 6
observational
studies) enrolled
38,133 patients with
chronic HF and AF.

The risk of
bias was
assessed with
the Cochrane
Collaboration’
s risk of bias
tool for
randomized
control trials
and the risk of

Two
investigators
independently
completed
literature
searches,
reviewed
relevant
articles, and
abstracted data
from eligible
studies.

Post-hoc
analysis of
RCTs were
included,
which were
originally
designed for
chronic HF
patients
which can
limit the
understandin
g of the effect
of BBs on
patients with

There was a
lack of
individual
data on
patients in
the studies.

153

Zhu, M.,
Zhou,
X., Cai,
H.,
Wang,
Z., Xu,
H.,
Chen, S.,
Chen, J.,
Xu, X.,
Haibin,
S., &
Mao, W.

BMC
Cardiova
scular
Disorder
s.

patients
with
chronic
heart
failure
and atrial
fibrillatio
n–a
metaanalysis.

Inclusion Criteria:
prospective studies,
diagnosed with AF
and CHF, ages ≥18
years, data on allcause mortality or
cardiovascular
mortality or
hospitalization for
HF associated with
BBs.

Exclusion Criteria:
not diagnosed with
HF, no control
group, no available
data for clinical
outcomes, data
derived from the
same study.
To explore
Systematic review Results = 1614,
the efficacy
of quantitative
duplicates/not
and safety of literature was
relevant articles
restoring the
performed using
removed = 1539,
sinus rhythm the Preferred
full-text articles
using catheter Reporting Items
reviewed = 75,
ablation in
for Systematic
studies included = 3.
patients with Reviews and
AF and HF
Meta-Analyses
Sample sizes ranged
compared
guidelines.
from 41 to 52
with the
(n=143).
efficacy and
Databases
safety of
searched:
Inclusion Criteria:

dysfunction” or
“heart
dysfunction” or
“cardiac failure”
or “heart
weakness”, and
“beta blockers” or
“adrenergic beta
antagonists” or
“bisoprolol” or
“nebivolol” or
“carvedilol” or
“bucindolol” or
“metoprolol” or
“atenolol” or
“metoprolol
CR/XL”

Compared with medical
rate control therapy, the
restoration of the sinus
rhythm by catheter
ablation resulted in a
significant
improvement in the
LVEF (95% CI 0.711.74, p=0.03) and
peak oxygen
consumption
(95% CI 0.78-4.85,
P=0.007).

Did not
include all
possible
studies, as
they excluded
studies not
Clear research
method was
established.
The data
extraction and

Limited
number of
studies and
small sample
sizes.

Did not
include
unpublished
articles.

combines HF
and AF.

Search terms
and inclusion
and exclusion
criteria were
thoroughly
explained.

bias
assessment
tool for nonrandomized
studies.

154

Medicine
.

Catheter
ablation
versus
medical
rate
control
for
persisten
t atrial
fibrillatio
n in
patients
with
heart
failure.

2016.

pharmacologi
cal rate
control
therapy.

A manual search
of the references
of the retrieved
studies was
completed to find
relevant citations.

Search terms:
“atrial
fibrillation,”
“persistent atrial
fibrillation,”
“heart failure,”
“left ventricular
systolic
dysfunction,”
“reduced left
ventricular
systolic function,”
“catheter
ablation,”
“pulmonary vein
isolation.”

Databases were
searched until
December 20,
2015.

Embase, Pubmed,
Cochrane Library,
and
ClinicalTrials.gov

Exclusion Criteria:
not published in
English, AF with
diastolic HF or
diastolic
dysfunction,
restoration of the
sinus rhythm by
surgical ablation,
and rate control
through
atrioventricular node
ablation.

English language,
RCT, more than 10
patients, follow-up
was at least 6
months, and
outcomes of interest.
Procedural
complication rates of
catheter ablation ranged
from 7.7% to 15.4%

No significant
beneficial effect of BBs
was found for chronic
HF patients with AF.

The quality of
the RCTs was
assessed by
Cochrane
Collaboration
tool.

quality
assessment
were
performed
independently
by 2 reviewers.

Symptomatic
AF patients
were not
included.

Short-term
follow up
period of 6 to
12 months.

published in
English.

155

156