
==== Front
JACC Adv
JACC Adv
JACC: Advances
2772-963X
Elsevier

S2772-963X(24)00441-1
10.1016/j.jacadv.2024.101210
101210
State-of-the-Art Review
Atrial Fibrillation in Hypertrophic Cardiomyopathy
Weissler-Snir Adaya MD, MSc adaya.weissler-snir@mountsinai.org
a∗
Saberi Sara MD b
Wong Timothy C. MD c
Pantazis Antonis MD d
Owens Anjali MD e
Leunig Alexander MD c
Alvarez Chikezie MD f
Rader Florian MD, MSc g
a Icahn School of Medicine at Mount Sinai Medical Center, New York, New York, USA
b Division of Cardiovascular Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
c Heart and Vascular Institute, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
d Cardiomyopathy Service, Royal Brompton Hospital, London, United Kingdom
e University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, USA
f Section of Cardiac Electrophysiology, Division of Cardiovascular Medicine, Stanford University, Stanford, California, USA
g Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
∗ Address for correspondence: Dr Adaya Weissler-Snir, Director of the Inherited Arrhythmia and Cardiomyopathy Program and Cardiac Electrophysiologist at Mount Sinai Heart, New York, New York 11766, USA. adaya.weissler-snir@mountsinai.org
20 8 2024
9 2024
20 8 2024
3 9 1012108 3 2024
21 6 2024
27 6 2024
© 2024 The Authors
2024
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Atrial fibrillation (AF) is common among patients with hypertrophic cardiomyopathy (HCM) with a prevalence greater than 25%. AF in HCM is associated with a high risk of stroke and can be a marker of more advanced cardiomyopathy. Although, it frequently results in cardiac hemodynamic changes which are poorly tolerated, it can be subclinical. Thus, prompt diagnosis and adequate management of AF are essential to minimizing AF-related adverse outcomes in HCM. All HCM patients should be screened for AF regularly, and those with high-risk features should be screened more frequently preferably with extended ambulatory monitoring. Once AF is detected, oral anticoagulation should be initiated. Both general and HCM-specific modifiable risk factors should be addressed and assessment for cardiomyopathy progression should be performed. Although no randomized controlled studies have compared rate versus rhythm control in HCM, early rhythm control could be considered to prevent further LA remodeling.

Central Illustration

Highlights

• AF is common in HCM with a prevalence above 25%.

• AF in HCM carries high-risk of stroke and can be a marker of advanced cardiomyopathy.

• Prompt diagnosis and adequate management are essential to minimizing AF-related adverse outcomes.

• Early rhythm control could be considered to prevent further LA remodeling.

Key words

hypertrophic cardiomyopathy
atrial fibrillation
rhythm control
rate control
anti-coagulation
Abbreviations and Acronyms

AAD anti-arrhythmic drug

AF atrial fibrillation

DOAC direct oral anticoagulants

ECG electrocardiogram

HCM hypertrophic cardiomyopathy

ICM insertable cardiac monitor

LA left atrium

LVOTO left ventricular outflow tract obstruction

OAC oral anticoagulation

OSA obstructive sleep apnea

PAF paroxysmal AF

PV pulmonary vein

PVI pulmonary vein isolation

SCAF subclinical AF

SCD sudden cardiac death
==== Body
pmcHypertrophic cardiomyopathy (HCM) is the most common monogenetic cardiomyopathy and causes a multitude of disease-related morbidities and symptoms. Cardiac arrhythmias are common in HCM, and while sustained ventricular arrhythmias are the most concerning, supraventricular arrhythmias and among those, particularly atrial fibrillation (AF) are far more common, occurring in approximately 25% of the HCM patients and are 4-6-fold more prevalent than in age-matched patients without HCM.1, 2, 3, 4 Several aspects of AF are problematic in HCM: 1) the stroke risk associated with AF in HCM surpasses that of AF in patients without HCM; 2) AF is a risk marker of more advanced cardiomyopathy and can indicate an adverse disease trajectory;1,5 3) AF-related changes in cardiac hemodynamics are poorly tolerated and frequently cause worsening heart failure symptoms due to loss of synchronized atrial contraction, decreased passive diastolic filling time, and worsening left ventricular outflow obstruction (LVOTO); and 4) AF can acutely cause tachycardia-mediated systolic heart failure, especially in the setting of cardiac myosin inhibitors.6 Therefore, screening, prompt recognition, and adequate treatment of AF are key to minimizing AF-related complications in HCM. In this review, we will discuss briefly the pathomechanisms of AF in HCM, approaches to screening for risk factors for the development of AF, and best-practice recommendations for medical and device-based therapies of AF in HCM patients.

Definition of AF IN HCM

AF can be classified as subclinical AF(SCAF) in asymptomatic patients or clinical in those who seek medical attention for symptoms caused by AF.7 This distinction becomes important due to an increasing number of HCM patients recognized to have SCAF as detected by internal and external cardiac devices and arrhythmia monitors.8,9

The further classification of AF that focuses on duration and length of clinical episodes in HCM patients follows the standard definitions in non-HCM patients, including categories of paroxysmal, persistent, long-standing persistent, and permanent AF.10 More specific to HCM patients, an additional category of postoperative AF (after surgical myectomy) can be considered.

Brief summary of underlying pathomechanisms in HCM

There is overlap of the putative mechanisms of AF among patients with and without HCM, such as cardiac changes associated with older age. The cardiac substrate for AF can be categorized in structural and electrical changes (ie, remodeling) of the left atrium (LA), which usually is the site of the origin and perpetuation of AF.11,12 Electrocardiographic markers for AF which may indicate those structural and electrical abnormalities include P-wave duration and P-wave dispersion.13 Activation of the sympathetic nervous system (especially in the setting of concomitant obstructive sleep apnea [OSA]),14 as well as inflammatory pathways, may also be involved in the generation of AF.14 Evidence for an HCM-related atrial myopathy with decreased atrial systolic function and excessive fibrosis has also been documented and may further contribute to the development of AF and the excess risk of associated thromboembolic stroke noted in HCM (Figure 1).12,15, 16, 17Figure 1 Anatomical Changes in HCM Contributing to AF Development

(A) Dilated left atrium with spontaneous echo contrast. (B) A marked reduction in all left atrium strain components in the 4-chamber view is seen. The reservoir strain is 14% (white double arrow) and contractile strain is -5% (yellow double arrow). (C) Atrial myopathy with low left atrium appendage emptying velocities.

Risk factors for AF IN HCM

Age is by far the most potent nonmodifiable risk factor for AF in the general population and is also an important risk factor in HCM patients.2 More limited data exist on the role of modifiable risk factors for AF specific to HCM: some reports suggest correlations between traditional modifiable risk factors and AF,3,18 while others have not found these correlations and surmise that AF in HCM is driven primarily by the cardiomyopathy itself, making it potentially a nonmodifiable risk factor.19 An overview of the existing studies is presented in Table 1 and supports at least some associations between modifiable risk factors and AF in HCM, albeit limited by their retrospective nature and sample size. Recognition of risk factors and concomitant disease present a complementary treatment approach for AF in the general and HCM patient population (Table 2), both from a primary as well as a secondary prevention perspective (Figure 2).Table 1 Prevalence of Modifiable Risk Factors in HCM

Group	Modifiable Risk Factor for AF	Prevalence in HCM Patients (Each Cell Is 1 Paper)	Prevalence in HCM (range)	Prevalence in the General Population	
Metabolic	Obesity	Preobese 39% Obesity 31.7% (Fumagalli, 201918)	Preobese 38% Obesity 37% (Olivotto, 201320)	Obesity 43% (Sridharan, 202219)		Preobesity 38%-39%
Obesity 31.7%-43%	42.4% (Hales, 202021)	
Diabetes mellitus	9.3% (Fumagalli, 201918)	Septal thickness 13-14 mm 13% ≥15 mm 0% (Lopes, 202122)	6% (Guttmann, 20173)	11% (Sridharan, 202219)	6%-13%	9.8% (Benjamin, 201923)	
Hyperlipidemia	39% (Sridharan, 202219)	Septal thickness 13-14 mm 31.7% ≥15 mm 26.5% (Lopes, 202122)	28% (Sorajja, 200324)		31%.7-39%	11.7% (Benjamin, 201923)	
Sleep	OSA	Nocturnal Hypoxia 71% (Eleid, 200925)	Sleep disordered breathing 33% (Konecny, 201026)	40% (Pedrosa, 201027)	44% (Prinz, 201128)	32%-71%	14.5% (Peppard, 201329)	
Cardiovascular	Hypertension	38.9% (Fumagalli, 201918)	46% (Cannan, 199530)	28% (Guttmann, 20173)	27% (Sridharan, 202219)	27%-46%	46% (Benjamin, 201923)	
Atherosclerotic disease	2% (Guttmann, 20173)	CAD 8% (Sridharan, 202219)	CAD severe 26% mild 27% (Sorajja, 200324)	17% Siontis et al.5	2%-17%		
Lifestyle	Smoking	Previous 48.5% current 6.1% (Lopes, 202122)	Current or prior 42% (Sorajja, 200324)	Current 20% (Reineck, 201331)			15.5% current (Benjamin, 201923)	
Physical exercise	Vigorous recreational activities 23% (Reineck, 201331)					Leisure-time aerobic and muscle-strengthening
22.5% (Benjamin, 201923)	
C2 consumption	Regular alcohol intake 45.5% (Lopes, 202122)	1.7 drinks/day (Reineck, 201331)					
AF = atrial fibrillation; CAD = coronary artery disease; HCM = hypertrophic cardiomyopathy; OSA = obstructive sleep apnea.

Table 2 Role of Modifiable Risk Factors for AF in HCM Patient Population

First Author, Year	Description	AF as Dependent or Independent Variable	Obesity	T2DM	Hyperlipidemia	OSA	Hypertension	Vascular Disease	Smoking	Physical Exercise	C2 Consumption	
Sridharan, 202219	n = 2,269 retrospective	Dependent	Yes, in univariate OR: 1.7	No	No		No	No	No		No	
Dejgaard, 201832	n = 187 small retrospective	Independent								No		
Saberi, 201733	n = 136 RCT moderate intensity exercise	Independent								No		
Fumagalli, 201918	n = 3,282 international retrospective cohort	Independent	Yes
Preobesity, HR: 1.067 (95% CI: 0.846-1.345) Obesity, HR: 1.416 (95% CI: 1.115-1.798)									
Guttmann, 20173	n = 4,907 international retrospective cohort	Dependent		Yes, in univariate			Yes
HR: 1.17	Yes
HR: 1.41				
Konecny, 201026	n = 91 prospective evaluation of OSA	Dependent				Yes						
Olivotto, 201320	n = 275 retrospective patients for Obesity. NB: small AF n = 30	Independent	No									
Pedrosa, 201027	n = 80 prospective OSA evaluation	Dependent				Yes
HR: 1.07						
Prinz, 201128	n = 113 prospective OSA evaluation. NB: small AF n = 10	Independent				No						
Siontis, 20145	n = 3,673 retrospective study	Dependent					No	Yes				
Wasserstrum, 201934	n = 937 retrospective study	Independent		Yes								
Zhang, 202235	n = 712 HCM patients undergoing septal myectomy	Dependent	Yes									
AF = atrial fibrillation; OSA = obstructive sleep apnea; RCT = randomized control trial; T2DM = type 2 diabetes mellitus.

Figure 2 Cardiac and Noncardiac Factors Driving AF Development and its Consequences

AF = atrial fibrillation; BNP = brain natriuretic peptide; HCM = hypertrophic cardiomyopathy; LA = left atrium; LAA = left atrium appendage; LVOTO = left ventricular outflow tract obstruction; LVEDP = left ventricular end-diastolic pressure; P/LP = pathogenic/likely pathogenic.

Lifestyle factors such as tobacco and alcohol use are associated with increased rates of AF in non-HCM cohorts,36 though few studies have investigated these relationships in HCM. Limited data suggest that HCM patients less commonly use tobacco and alcohol than the general population (Table 1),31 which may indicate that these factors are not principal AF risk factors in HCM, although minor contributions may still be at play.

Increased physical exercise appears to be associated with a decreased AF risk in the general population;36 however, one (underpowered) study did not find an association between physical activity and AF prevalence.32 As guidelines recommendations are evolving regarding exercise for HCM patients, it will become more evident from clinical observations and trials whether exercise protects or increases the risk for AF.

Although hypertension and diabetes mellitus are important AF risk factors in the general population, no clear data exist on their association with AF among HCM patients.3,5,19

Given that atherosclerotic disease is typically a comorbidity (rather than a driver) of HCM, it may represent an under-recognized modifiable AF risk factor in HCM. Two large retrospective studies suggest a correlation between atherosclerotic disease and AF in HCM,3,5 with one study estimating a hazard ratio of 1.41.3 Prevention and treatment of atherosclerotic disease according to recognized guidelines is recommended regardless of whether HCM is present or not.

Obesity is a risk factor for developing HCM and has been shown to affect disease severity.37 Mechanistically, there is likely an overlap between obesity and sleep apnea. As in the general population, obesity is also a risk factor for developing AF among those with HCM.18,19 In univariate analysis, the AF risk increases by 40% to 70% in obese patients, based on two large retrospective studies.18,19 In a study investigating the risk of AF after septal myectomy, obesity was associated with an odds ratio of 2.8.35 Weight loss reduces AF frequency and symptom burden and can even convert persistent to paroxysmal AF.36

OSA is associated with AF in general.36 OSA is more common among HCM patients (32%-71%) than in the general population (3%-49%) and may be associated with AF in HCM,38 albeit with some conflicting data.26 This association may be confounded by an interaction between OSA and LA size and diastolic dysfunction.26,27 Autonomic instability mediated by OSA may facilitate AF development in the pulmonary vein ostia, which are densely innervated by adrenergic and vagal neurons.39 While the benefits of continuous positive pressure treatment in OSA are well-established in the general population, with some association with a reduction in AF burden40 (but not consistently)36 in HCM, this treatment effect is not well studied.41

Beyond risk factors for AF identified in the general population, the contribution of LVOTO in HCM patients may be relevant. Sun et al. identified several risk factors associated with chronic LVOTO, including LA enlargement, which predicted AF incidence following septal myectomy.42

In addition, the assessment of biomarkers is useful to determine AF risk, specifically brain natriuretic peptide, and less so troponin levels are associated with incident AF.5,13

In summary, modifiable risk factors for AF specific to HCM have not been well characterized. However, treating obesity, OSA, and LVOTO appear to hold the greatest potential for AF prevention and management. Additionally, atherosclerotic disease may be an underappreciated modifiable risk factor. Given the high prevalence of AF in HCM and given that treating the comorbidities listed above has intrinsic merits, identification and treatment of these comorbidities should be incorporated into routine clinical HCM care pathways. However, further studies focusing on the impact of risk factor modification specific to HCM patients are needed.

AF as risk factor for premature mortality and sudden cardiac death

AF in HCM is associated with increased risk of heart failure and stroke as well as overall mortality in multiple studies.2,5,43 Olivotto et al. found AF to be an independent risk factor for cardiovascular death where the annual HCM-related mortality was 3% in HCM patients with AF, compared with 1% among those in sinus rhythm, driven by excess stroke and heart failure–related mortality. The risk was significantly higher in the presence of LVOTO and in patients who developed AF at a young age (<50 years).2 Consistent with these findings, a retrospective study of over 3,500 patients found AF to be an independent predictor for all-cause mortality.5 There are contradicting reports whether development of AF is associated with an increased risk of sudden cardiac death (SCD). In the aforementioned studies, AF was not associated with SCD.2,5 Conversely, two meta-analyses found AF to be associated with increased risk for SCD.44,45 In contrast to older studies, a recent report showed a more favorable clinical course with current management where AF was not associated with heart failure morbidity, SCD, or thromboembolism.46 Moreover, with anti-arrhythmic drugs (AADs) and/or catheter or surgical ablation, only 26% of patients with paroxysmal AF (PAF) developed permanent AF, where sinus restoration was abandoned.47 These observations suggest that with contemporary management, AF has a favorable course and outcomes.

Frequency and tools for atrial fibrillation screening

There are no consistent and clear recommendations regarding the type and frequency of screening for AF in HCM patients. The current guidelines recommend extended ambulatory monitoring for HCM patients who have additional risk factors for AF, such as LA dilatation, advanced age, and NYHA functional class III-IV symptoms, and who are eligible for oral anticoagulation (OAC), as part of the initial evaluation and annually (Class I recommendation).7 The guidelines note that ambulatory monitoring may be considered also for patients without risk factors for AF beyond the diagnosis of HCM alone who are eligible for OAC (Class IIb recommendation). The 2014 European Society of Cardiology guidelines recommend 48-hour ambulatory electrocardiogram (ECG) monitoring every 6 to 12 months to detect AF in patients who are in sinus rhythm and have a LA diameter of 45 mm or more (Central Illustration).47Central Illustration Approach to AF Screening and Management in HCM Patients

AF = atrial fibrillation; CMR = cardiovascular magnetic resonance; CPET = cardiopulmonary exercise testing; DOAC = direct oral anticoagulants; FDA = Food and Drug Administration; HTN = hypertension; LA = left atrium; LVOTO = left ventricular outflow tract; OSA = obstructive sleep apnea.

The HCM-AF score is a novel predictive tool for the detection of HCM patients at risk for developing AF at 2 and 5 years, who will benefit from increased ambulatory monitoring. It was developed from a cohort of 1900 HCM patients and was externally validated in a cohort of 387 HCM patients. It includes four parameters: LA dimensions, current age, age at diagnosis, and heart failure symptoms. The HCM-AF score stratifies risk as low (<1.0%/y; score ≤17), intermediate (1.0%-2.0%/y; score 18-21), and high (>2.0%/y; score ≥22). The score has a higher yield for AF prediction than LA dimensions alone. The authors suggest that patients with low-risk scores are less likely to benefit from frequent monitoring for AF and should be reassured, whereas patients with high-risk scores require close ambulatory monitoring for the development of AF.48

A survey among international HCM experts found that most experts (87%) perform routine screening for AF, with the majority (61%) conducting it on an annual basis.49 A 24-to-48-hour Holter monitor was the preferred first-line tool (91%), followed by prolonged Holter monitoring. Consumer wearable devices were the third most-used screening tool (56%); but 91% of experts would not rely on these to start OAC and pursue further Holter or event monitor screening if a patient reports AF on these devices. LA dilatation was an important factor when considering screening for AF by most experts (78%). Additional factors that prompted increased frequency of screening included severe mitral regurgitation (61%), NYHA functional class III-IV (43%), and dynamic LVOTO (19%).

Whether extended ECG monitoring is more sensitive than the standard 24 to 48-hour Holter monitoring was examined in two small studies. Weissler-Snir et al. found newly diagnosed AF in 4 of 77 patients using 14-day ambulatory arrhythmia monitoring, none of which occurred during the first 48 hours of monitoring.50 The TEMPO-HCM study compared the yield of a 24-hour vs 30-day ambulatory arrhythmia monitoring in 100 HCM patients with a clinical indication for AF screening or for risk stratification for SCD. The 30-day monitoring detected 3 more cases of newly diagnosed AF than 24-hour monitoring. The difference was not statistically significant, likely due to the small sample size. However, the study suggests that extended ECG monitoring may have a role for AF screening in HCM.

Data regarding the yield of an insertable cardiac monitor (ICM) for AF detection in HCM are scarce. A prospective observational study of 30 unselected HCM patients detected AF using ICM in 7 patients (5 asymptomatic) without a prior diagnosis of AF during an 18-month follow-up period.51 An additional study of 25 HCM patients who received an ICM for either recurrent near-syncope, palpitations, myocardial fibrosis by cardiovascular magnetic resonance, or HCM Risk-SCD score ≥4 to <6% found newly diagnosed AF in 3 patients during a 30-month follow-up period. Only 1 of the 3 patients developed symptoms. No AF was diagnosed in the control group, who received conventional follow-up (ie, Holter monitoring every 6-24 months based on treating physician's discretion).52

Management of AF IN HCM

Rhythm vs rate control

There have been no randomized trials comparing rhythm vs rate control for AF in HCM. Moreover, most randomized trials comparing rhythm to rate control in the general population excluded HCM patients. Several registries included small numbers of HCM patients and found better outcomes for rhythm control; however, none performed a sub-analysis within the HCM subpopulation.53,54 As patients with AF and HCM tend to be quite symptomatic, particularly in the presence of rapid ventricular rates and LVOTO, a rhythm control strategy may be preferred. However, as AF can be a marker of advanced disease—especially in young people—progression of cardiomyopathy should be assessed (eg, repeat cardiovascular magnetic resonance, cardiopulmonary exercise test, right heart catheterization) and addressed prior to pursuing rhythm control. Furthermore, in the presence of high LVOT gradients, pursuing rhythm control is unlikely to be successful without treating the obstruction. If LVOTO is not present at rest, provocative maneuvers—or a stress echocardiogram to assess for latent obstruction—should be performed. Beta-blockers or nondihydropyridine calcium channel blockers such as verapamil and diltiazem are the preferred agents for rate control therapy with the avoidance of nondihydropyridine calcium channel blockers in patients with signs and symptoms of heart failure, cardiogenic shock, pre-excitation, and very high LVOT gradients.55 Rate control therapy should also be considered for those who are intolerant to AADs. Lastly, data on the efficacy of digoxin for rate control of AF in HCM are lacking, although there is a theoretical concern that digoxin can exacerbate LVOTO due to its positive inotropic effect. However, in the absence of LVOTO, it may be a reasonable option (Central Illustration).

Rhythm control: anti-arrhythmic drugs

Data on the use of various AADs in HCM are limited to small retrospective and observational studies. Amiodarone has the longest experience and until recently was considered the drug of choice for rhythm control in HCM. However, as many HCM patients with AF are relatively young, amiodarone should be avoided if possible due to its many potential long-term side effects and toxicities. Alternatives to amiodarone include the other class III agents sotalol and dofetilide and the relatively weak class Ia agent disopyramide. Several small retrospective studies have shown that both sotalol and dofetilide are safe in HCM and have moderate efficacy. A recent retrospective analysis of 98 HCM patients with AF compared the safety profile, efficacy, and side effects of sotalol (n = 45), amiodarone (n = 47), dofetilide (n = 20), and disopyramide (n = 18).56 No sudden deaths occurred with any agent. Overall, the use of AADs was relatively safe, with 4.6% of the total cohort experiencing serious side effects or safety events. The probability of remaining on a single AAD was 62% at 1 year and 42% at 3 years. Amiodarone demonstrated the lowest rate of discontinuation for inefficacy (8.5%), but the highest rate of discontinuation for side effects (19.1%). Documented inefficacy resulting in cessation occurred in 12 patients (8.7%) on sotalol, 5 patients (22%) on disopyramide, and 6 patients (15.8%) on dofetilide. Another single-center observational study of 72 HCM patients treated with dofetilide 31 and sotalol for either AF 57 or ventricular arrhythmia 18 found similar moderate efficacy for sotalol and dofetilide with 40 to 45% recurrence rate at 1 year.58 No patients developed sustained torsade de pointes. Moreover, QTc prolongation was infrequent and precluded dofetilide loading in only 10% of the patients and resulted in postloading sotalol discontinuation in 6%. In a retrospective study of 1,404 patients with AF treated with dofetilide, of whom 25 had HCM, dofetilide was well tolerated in HCM with 11/25 (52%) of the patients remaining on it after a median follow-up of 396 days.59

Disopyramide, a class Ia AAD, may be particularly beneficial in patients with symptomatic LVOTO and AF given its negative inotropic effects and proven efficacy in reducing LVOTO,60 although it should be combined with a beta-blocker or nondihydropyridine calcium channel blocker as it can potentially be pro-arrhythmic due to enhanced AV nodal conduction in the setting of rapid ventricular response during AF episodes. Adler et al. demonstrated in 168 patients that outpatient initiation of disopyramide was safe, with no cardiac events in the first 3 months of therapy at both the starting dose (300 mg daily) and subsequent uptitration (600 mg daily). Its excellent safety profile despite QT prolongation may be explained by its multichannel inhibitory effects and membrane stabilizing actions, which may be protective against ventricular as well as atrial arrhythmias.61 Yet, although in vitro studies show that disopyramide has promising antiarrhythmic properties, its clinical efficacy in the management of AF in HCM is not well established.

Rhythm control: catheter ablation

There are no prospective randomized controlled studies comparing catheter ablation to AADs in HCM. Acknowledging that the HCM population is underrepresented in clinical trials, the 2018 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement suggests that it is reasonable to use similar indications for AF ablation in selected HCM patients as in patients without HCM (Class IIa recommendation).57 All studies examining the short- and long-term success rate of catheter ablation in HCM are relatively small, yet they consistently show that the success rate of catheter ablation in HCM patients is substantially lower than in patients without HCM.62, 63, 64 The success rates are higher for patients with PAF than persistent AF, with most patients requiring more than one ablation and concurrent AADs. A recent meta-analysis of 25 studies with data on a total of 1817 HCM patients found a 1-year success rate following a single procedure of 61%.65 The success rate declined to only 34.7% at 4 years and 27.5% at 7 years. However, the success rates increased substantially following multiple ablations, with arrhythmia-free rates of 71.1%, 48.9%, and 46.8% at 1, 4, and 6 years, respectively. Similar to patients without HCM, the success rate was higher in those with PAF vs persistent AF, with a 12-month success rate of 63.7% in PAF compared to 46.1% in persistent AF after 1 procedure and 79.2% in PAF and 67.2% in persistent AF after multiple ablations. Notably, many patients were on concurrent AADs and the success rate at latest follow-up in patients without AADs was only 33.4%. Another meta-analysis found that HCM patients underwent ablation relatively late after the initial diagnosis of AF, with a median time from initial diagnosis to ablation of 5.9 years.62 Recent trials in non-HCM patients lend support to early catheter ablation for paroxysmal AF.66, 67, 68 Although it is unclear whether their results can be extrapolated to HCM patients, it can be postulated that early catheter ablation for HCM patients with PAF may decrease the atrial electrophysiological and structural remodeling, resulting in a decreased risk of progression to persistent AF.68 It is plausible that a significant delay in performing catheter ablation after onset of AF in HCM patients may contribute to the worse ablation success rates noted in HCM patients as compared with the general population. Hence, considering the advances in catheter ablation with shorter procedure time and same-day discharge on the one hand and the moderate success of AADs in maintaining sinus rhythm and the relatively young age of HCM patients with AF on the other hand, catheter ablation can be considered first-line strategy in selected HCM patients with PAF. With respect to persistent AF, a catheter ablation can also be considered as first-line strategy in selected patients with the expectation that several procedures and AADs may be needed for long-term sinus rhythm maintenance. A recent study by Haq et al. showed that genotype-positive patients undergoing AF ablation (n = 12) had more low-amplitude LA signals suggestive of fibrosis, than genotype-negative patients (n = 15), albeit with a greater number of procedures (1.67 ± 0.65 vs 1.20 ± 0.41, P = 0.03), they had similar 12-month freedom from AF (75% vs 73%, P = 0.92). It is noteworthy that a greater proportion of patients in the genotype-positive cohort had persistent AF (66.6% vs 50%, P = 0.09). Notably, all patients in the gene-positive cohort and 93% of the genotype-negative patients were on AADs post-ablation.69

Pulmonary vein isolation only vs substrate modification

As HCM patients may have non-pulmonary vein (PV) triggers for AF, an important question is whether there is any additional benefit to performing substrate modification and extensive ablation beyond PV isolation (PVI) during the first ablation. Some studies suggest that ablation beyond PVI may not be associated with improved efficacy outcomes in HCM,70 whereas others suggest that PVI and posterior wall isolation alone may be insufficient to maintain long-term freedom from recurrent arrhythmia despite achieving permanent isolation and that non-PV triggers may represent the dominant etiology for arrhythmia recurrence in HCM patients, with subsequent improvement in arrhythmia-free survival after targeted ablation of non-PV triggers.71 Zahid et al.72 observed that HCM patients and PAF have reduced atrial conduction velocity despite having normal bipolar voltage amplitude, suggesting that this might contribute to arrhythmia persistence after catheter ablation in HCM patients with PAF. Their observations also question the utility of the “conventional” methods to assess the atrial tissue (eg, voltage mapping) in deciding whether to perform further substrate modification in addition to PVI in HCM patients.

Radiofrequency and cryoballoon catheter ablation

In the general population, cryoballoon catheter ablation has emerged as an effective alternative to radiofrequency ablation, with similar efficacy reported in several studies.73, 74, 75, 76 This general theme does appear to be applicable to HCM patients. In an observational multicenter study of 137 HCM patients, cryoballoon ablation demonstrated similar efficacy and complication rates compared to radiofrequency ablation for both PAF and persistent AF.70 However, cryoballoon catheter is designed for PVI only, with emerging data that it can also be used safely for posterior wall isolation. Thus, many electrophysiologists prefer using radiofrequency over cryoballoon catheter ablation for HCM patients.

Pulsed-field ablation

Pulsed-field ablation has been shown to have similar outcomes to thermal ablation but with fewer complications due to its tissue selectivity.77 It is currently approved only for PVI. However, there are data from nonrandomized trials demonstrating its safety and efficiency for posterior wall as well as mitral isthmus and cavotricuspid isthmus isolation (with the use of intravenous nitrates).78 Thus, it will likely to be approved for ablation of non-PV triggers and substrate modification. Notably, no data are available on PFA in HCM patients. Yet, there is no reason to postulate that the safety profile of pulsed-field ablation will be lower in HCM patients.

Safety of catheter ablation

Two meta-analyses found similar complication rates of catheter ablation procedures in patients with and without HCM.62,63 In contrast, an observational multicenter study of 135 patients with 225 ablations reported a higher rate of major complications, with cardiac tamponade rates 4 times higher than the general population in the participating center.70 However, there was a significant reduction in the rate of complications over time. Notably, there was no significant difference in the overall complication rate between RF and cryoballoon ablation. The authors postulated possible explanations for the increase in complications, including a greater anatomical challenge with trans-septal punctures and decreased hemodynamic tolerance with a small increase in pericardial fluid due to worse diastolic function in HCM patients. The real-world safety of catheter ablation for AF in HCM was assessed in a large-scale study investigating the nationwide trends of 1,563 catheter ablation cases (47% female) during two time periods of 2003 to 2008 (“early years”) and 2009 to 2015 (“later years”).79 The authors found that at least 1 complication occurred in 16.1% of the cases, with an all-cause in-hospital mortality of 1%. However, similar to the abovementioned study, there was a decrease in complication rates from the “early years” to “later years” (20.9% vs 14%).79 The lower complication rates in the “later years” is likely due to improved operator experience, techniques, and equipment in more recent years.79

Rhythm control: surgical ablation during septal myectomy

Studies on surgical ablation for HCM patients are limited and have been mostly done on patients with drug-refractory AF undergoing concomitant septal myectomy. Most studies show lower rates of AF recurrence with surgical ablation than catheter ablation, with 70% to 85% and 50% to 70% freedom from AF at 1 and 3 years, respectively.46,80,81 As surgical ablation is not typically done as a stand-alone procedure and is usually performed at the time of septal myectomy, the results can be confounded by the relief of LVOTO. It is difficult to determine whether the better outcomes are due to increased efficacy of surgical ablation alone or the favorable effects that septal myectomy has on reducing the LVOT gradient, with subsequent reduction in mitral regurgitation and LA size and remodeling. A recent meta-analysis of over 600 patients (68% with PAF) found surgical AF ablation during septal myectomy to be safe and effective, with overall survival and freedom from recurrent AF at 7 years of 90.5% and 63.2%, respectively.82 Thus, the current guidelines recommend consideration of concomitant surgical AF ablation at the time of septal myectomy for patients with AF (class IIa recommendation).7 Whether patients with nonobstructive HCM might benefit from a stand-alone surgical AF ablation or the hybrid procedure of surgical and endocardial ablation has not been studied.

Pace and ablate

A substantial subset of patients who have failed medical therapy and/or ablation for AF are highly symptomatic due to rapid ventricular response and/or the irregular rhythm. For this group of patients, a pacemaker implantation and AV node ablation (ie, pace-and-ablate strategy) might offer an effective therapy option. Butcher et al83 have recently reported their experience with this approach in 42 patients, of whom 18 (43%) had undergone previous catheter ablation. Cardiac resynchronization therapy devices were implanted in 24 patients (57%). Most patients (83%) experienced improvement in symptoms, including those who underwent the procedure to regularize the rhythm. Left ventricular systolic function remained stable regardless of the type of device implanted. It is also noteworthy that the growing use of physiologic pacing (eg, left bundle branch area pacing, His-bundle pacing), which significantly reduces the risk for pacemaker-mediated cardiomyopathy, makes the option of pace-and-ablate even more attractive for this group of patients. However, more data are needed to confirm the feasibility and safety of conduction system pacing in HCM.

Cardiac myosin inhibitors

Cardiac myosin inhibitors (eg mavacamten, aficamten) are a novel class of agents which decreases the cardiac hypercontractility by reducing the actin–myosin interactions in the cardiomyocytes. The effects of these agents on the incidence and severity of AF in HCM are currently uncertain. As these agents alleviate LVOTO and improve diastolic dysfunction, they are expected to favorably affect the frequency of new-onset or recurrent AF. However, in randomized clinical trials, AF represented an adverse event in 2%–4% of the patients randomized to mavacamten.84,85 In a “real world” cohort of 67 patients with oHCM from the Mayo clinic, the incidence of newly recognized AF after mavacamten initiation was 11%.86 In a large, randomized double-blinded trial of aficametn in patients with symptomatic oHCM, there was no observed increase in the incidence or recurrence of AF within the aficamten arm.87 Thus, further studies are needed to understand the effects of cardiac myosin inhibitors on AF in HCM.

Stroke prophylaxis

The risk of systemic embolization associated with AF is high in HCM patients. A meta-analysis that included 33 studies and 7,381 patients revealed an overall prevalence of thromboembolism in HCM patients and AF of 27.1% and an incidence of 3.75 per 100 patients.4 The stroke risk cannot be predicted by CHA2DS2-VASc score88,89—a significant number of strokes are observed in HCM patients with a score of 0.

No randomized controlled trials have compared direct oral anticoagulants (DOACs) with warfarin; however, observational data demonstrate that DOACs are at least as effective as warfarin in reducing the risk of stroke in this population, with the added benefits of increased patient satisfaction and reduction of major bleeding complications and death.90, 91, 92

The numbers of HCM patients included in the trials of LA appendage occlusion devices are very limited, thus the role of these devices in thromboembolic risk reduction in HCM patients is largely unknown. One pilot study of 36 HCM patients and AF who underwent LA appendage closure procedure showed the safety and feasibility of this approach in primary and secondary stroke prevention, with no thromboembolic events or deaths during a mean follow-up time of 28.4 months and 97.2% of patients remaining free of anticoagulation during that time.93 Conversely, an analysis of the National Readmissions Database of patients undergoing LA appendage closure between 2016 to 2019 showed that HCM was independently associated with increased odds of in-hospital mortality (OR: 5.44) and peripheral vascular complications (OR: 4.18).94 Additionally, a recent analysis of HCM patients with AF from 2015 to 2024, using the TriNetX Global Research Network, found that HCM patients treated with LA appendage occlusion devices had higher rates of ischemic stroke (13% vs 8%, HR 1.9, P = 0.006) and systemic embolism (14% vs 9%, HR 1.8, P = 0.006), but no difference in mortality compared to matched HCM patients on OAC.95

Anticoagulation is recommended for all HCM patients and clinical (symptomatic) AF.55 While the relationship of SCAF to stroke has not been investigated in a specific HCM population, in a meta-analysis of seven studies and 15,353 patients, SCAF was associated with a 2.4-fold increased risk of stroke, with an absolute annual rate of 1.89 per 100 person-years in the general population.96,97 The definitions of episodes that predicted stroke varied significantly between studies, reported as episodes as short as 5 and 6 minutes97 or episodes >5.5 hours within the past 30 days.98

However, subsequent studies show that most events occurred in patients with >24 hours of SCAF.99 Another recent study showed that short AF episodes (<20 seconds) were not associated with clinical events.100 These data suggest that the risk of events is dependent on AF burden (duration and frequency). Similar risk stratification is unavailable in HCM; however, these data can likely be extrapolated to HCM patients. If a very short duration of SCAF is detected by device or monitor, patients should have ongoing monitoring as increasing burden is likely to occur over time.

Conclusions

AF is common and poses a significant clinical dilemma for HCM patients as a major cause for stroke, trigger for heart failure symptoms, and indicator of progressive cardiomyopathy with an increased mortality risk. Modifiable and nonmodifiable risk factors for AF in HCM are obesity, OSA, and LVOTO, and age as well as myocardial fibrosis, respectively. These risk factors should be addressed to avoid the development of AF, and patients with a higher AF risk profile require more frequent arrhythmia surveillance. We recommend yearly AF screening in most patients who are eligible for OAC. Once detected, stroke prophylaxis—preferably with a DOAC—should be initiated in patients without contraindication to such therapy. With the increased use of wearable devices that can detect subclinical (ie, asymptomatic) AF, the AF burden may be a consideration before starting anticoagulation; however, short of more definitive data, we recommend erring on the side of treatment rather than ignoring brief AF episodes. Data on the efficacy and safety of LA appendage occluder devices are very limited but they seem to be a reasonable alternative for patients with high bleeding risk. Similarly, whether rhythm control is superior to rate control in patients with AF is not well studied. However, especially in symptomatic PAF, the former may be preferable. Reduction of risk factors for recurrent AF should be addressed. Both AADs and catheter ablation are reasonable approaches to rhythm control, although weighing effectiveness and side effects of AADs and a possibly higher ablation-related complication rate in HCM patients compared to their counterparts without HCM must be considered. Surgical Cox-Maze in conjunction with septal myectomy lowers the risk for recurrent AF and thus is recommended in current HCM guidelines.

Funding support and author disclosures

Dr Weissler-Snir has received speaker fees from Bristol Myer Squibb; and fees for publication steering committee participation for Cytokinetics and research grants from 10.13039/100004374 Medtronic . Dr Rader has received consultant and speaker fees from Bristol Myer Squibbs, Medtronic, Recor Medical, and Cytokinetics. Dr Saberi has received consultant/advisor fees from Bristol Myers Squibb; and has received research grants from Bristol Myers Squibb, 10.13039/100014941 Cytokinetics , 10.13039/100004336 Novartis , and 10.13039/100005646 Actelion Pharmaceuticals . Dr Wong is the site principal investigator for clinical trials sponsored by Bristol Myers Squibb, Cytokinetics, and Tenaya Therapeutics; and discloses unpaid advisory board participation for Bristol Myers Squibb and Cytokinetics. Dr Owens has received consulting/research support from 10.13039/100014941 Cytokinetics , MyoKardia/Bristol Myers Squibb, Pfizer, Lexicon Pharmaceuticals, Tenaya Therapeutics, Stealth BioTherapeutics, Renovacor, Edgewise Therapeutics, BioMarin Pharmaceuticals, and Lexeo Therapeutics.

The authors attest they are in compliance with human studies committees and animal welfare regulations of the authors’ institutions and Food and Drug Administration guidelines, including patient consent where appropriate. For more information, visit the Author Center.
==== Refs
References

1 Maron B.J. Olivotto I. Bellone P. Clinical profile of stroke in 900 patients with hypertrophic cardiomyopathy J Am Coll Cardiol 39 2 2002 301 307 10.1016/S0735-1097(01)01727-2 11788223
2 Olivotto I. Cecchi F. Casey S.A. Dolara A. Traverse J.H. Maron B.J. Impact of atrial fibrillation on the clinical course of hypertrophic cardiomyopathy Circulation 104 21 2001 2517 2524 10.1161/HC4601.097997 11714644
3 Guttmann O.P. Pavlou M. O’Mahony C. Predictors of atrial fibrillation in hypertrophic cardiomyopathy Heart 103 9 2017 672 678 10.1136/HEARTJNL-2016-309672 27794017
4 Guttmann O.P. Rahman M.S. O’Mahony C. Anastasakis A. Elliott P.M. Atrial fibrillation and thromboembolism in patients with hypertrophic cardiomyopathy: systematic review Heart 100 6 2014 465 472 10.1136/HEARTJNL-2013-304276 24014282
5 Siontis K.C. Geske J.B. Ong K. Nishimura R.A. Ommen S.R. Gersh B.J. Atrial fibrillation in hypertrophic cardiomyopathy: prevalence, clinical correlations, and mortality in a large high-risk population J Am Heart Assoc 3 3 2014 e001002 10.1161/JAHA.114.001002
6 Rader F. Oręziak A. Choudhury L. Mavacamten treatment for symptomatic obstructive hypertrophic cardiomyopathy: interim results from the MAVA-LTE study, EXPLORER-LTE cohort JACC Heart Fail 12 1 2024 164 177 10.1016/J.JCHF.2023.09.028 38176782
7 Ommen S.R. Ho C.Y. Asif I.M. 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR guideline for the management of hypertrophic cardiomyopathy: a report of the American heart association/American college of Cardiology joint committee on clinical practice guidelines J Am Coll Cardiol 83 23 2024 2324 2405 10.1016/J.JACC.2024.02.014 38727647
8 Wilke I. Witzel K. MÜnch J. High incidence of de novo and subclinical atrial fibrillation in patients with hypertrophic cardiomyopathy and cardiac rhythm management device J Cardiovasc Electrophysiol 27 7 2016 779 784 10.1111/JCE.12982 27060297
9 van Velzen H.G. Theuns D.A.M.J. Yap S.C. Michels M. Schinkel A.F.L. Incidence of device-detected atrial fibrillation and long-term outcomes in patients with hypertrophic cardiomyopathy Am J Cardiol 119 1 2017 100 105 10.1016/J.AMJCARD.2016.08.092 28247846
10 January C.T. Wann L.S. Alpert J.S. 2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American college of Cardiology/American heart association task force on practice guidelines and the heart rhythm society J Am Coll Cardiol 64 21 2014 e1 e76 10.1016/J.JACC.2014.03.022 24685669
11 Casaclang-Verzosa G. Gersh B.J. Tsang T.S.M. Structural and functional remodeling of the left atrium: clinical and therapeutic implications for atrial fibrillation J Am Coll Cardiol 51 1 2008 1 11 10.1016/J.JACC.2007.09.026 18174029
12 Debonnaire P. Joyce E. Hiemstra Y. Left atrial size and function in hypertrophic cardiomyopathy patients and risk of new-onset atrial fibrillation Circ Arrhythm Electrophysiol 10 2 2017 10.1161/CIRCEP.116.004052
13 Ozdemir O. P-wave durations as a predictor for atrial fibrillation development in patients with hypertrophic cardiomyopathy Int J Cardiol 94 2–3 2004 163 166 10.1016/j.ijcard.2003.01.001 15093974
14 Sengupta P.P. Sorajja D. Eleid M.F. Hypertrophic obstructive cardiomyopathy and sleep-disordered breathing: an unfavorable combination Nat Clin Pract Cardiovasc Med 6 1 2009 14 15 10.1038/NCPCARDIO1401 19015644
15 Geske J.B. Sorajja P. Nishimura R.A. Ommen S.R. The relationship of left atrial volume and left atrial pressure in patients with hypertrophic cardiomyopathy: an echocardiographic and cardiac catheterization study J Am Soc Echocardiogr 22 8 2009 961 966 10.1016/J.ECHO.2009.05.003 19524402
16 Maron B.J. Haas T.S. Maron M.S. Left atrial remodeling in hypertrophic cardiomyopathy and susceptibility markers for atrial fibrillation identified by cardiovascular magnetic resonance Am J Cardiol 113 8 2014 1394 1400 10.1016/J.AMJCARD.2013.12.045 24589281
17 Pagourelias E. Boulmpou A. Evangeliou A. Prevalence of atrial myopathy among hypertrophic cardiomyopathy patients without atrial fibrillation Eur Heart J 43 Supplement_2 2022 10.1093/EURHEARTJ/EHAC544.152
18 Fumagalli C. Maurizi N. Day S.M. Association of obesity with adverse long-term outcomes in hypertrophic cardiomyopathy JAMA Cardiol 5 1 2020 65 72 10.1001/JAMACARDIO.2019.4268 31693057
19 Sridharan A. Maron M.S. Carrick R.T. Impact of comorbidities on atrial fibrillation and sudden cardiac death in hypertrophic cardiomyopathy J Cardiovasc Electrophysiol 33 1 2022 20 29 10.1111/JCE.15304 34845799
20 Olivotto I. Maron B.J. Tomberli B. Obesity and its association to phenotype and clinical course in hypertrophic cardiomyopathy J Am Coll Cardiol 62 5 2013 449 457 10.1016/j.jacc.2013.03.062 23643593
21 Hales C.M. Carroll M.D. Fryar C.D. Ogden C.L. Prevalence of obesity and severe obesity among adults: United States, 2017-2018 2020 National Center for Health Statistics Hyattsville, MD NCHS Data Brief, no 360
22 Lopes L.R. Aung N. van Duijvenboden S. Munroe P.B. Elliott P.M. Petersen S.E. Prevalence of hypertrophic cardiomyopathy in the UK Biobank population JAMA Cardiol 6 7 2021 852 854 10.1001/jamacardio.2021.0689 33851951
23 Benjamin E.J. Muntner P. Alonso A. Heart disease and stroke statistics-2019 update: a report from the American Heart Association Circulation 139 2019 e56 e528 10.1161/CIR.0000000000000659 30700139
24 Sorajja P. Ommen S.R. Nishimura R.A. Gersh B.J. Berger P.B. Tajik A.J. Adverse prognosis of patients with hypertrophic cardiomyopathy who have epicardial coronary artery disease Circulation 108 19 2003 2342 2348 10.1161/01.CIR.0000097110.55312.BF 14581405
25 Eleid M.F. Konecny T. Orban M. High prevalence of abnormal nocturnal oximetry in patients with hypertrophic cardiomyopathy J Am Coll Cardiol 54 19 2009 1805 1899 10.1016/j.jacc.2009.07.030 19874995
26 Konecny T. Brady P.A. Orban M. Interactions between sleep disordered breathing and atrial fibrillation in patients with hypertrophic cardiomyopathy Am J Cardiol 105 11 2010 1597 1602 10.1016/J.AMJCARD.2010.01.023 20494669
27 Pedrosa R.P. Drager L.F. Genta P.R. Obstructive sleep apnea is common and independently associated with atrial fibrillation in patients with hypertrophic cardiomyopathy Chest 137 5 2010 1078 1084 10.1378/CHEST.09-2335 20154076
28 Prinz C. Bitter T. Oldenburg O. Horstkotte D. Faber L. Incidence of sleep-disordered breathing in patients with hypertrophic cardiomyopathy Congest Heart Fail 17 2011 19 24 21272223
29 Peppard P.E. Young T. Barnet J.H. Palta M. Hagen E.W. Hla K.M. Increased prevalence of sleep-disordered breathing in adults Am J Epidemiol 177 9 2013 1006 1014 10.1093/aje/kws342 23589584
30 Cannan C.R. Reeder G.S. Bailey K.R. Melton L.J. 3rd Gersh B.J. Natural history of hypertrophic cardiomyopathy. A population-based study, 1976 through 1990 Circulation 92 9 1995 2488 2495 10.1161/01.cir.92.9.2488 7586349
31 Reineck E. Rolston B. Bragg-Gresham J.L. Physical activity and other health behaviors in adults with hypertrophic cardiomyopathy Am J Cardiol 111 7 2013 1034 1039 10.1016/J.AMJCARD.2012.12.018 23340032
32 Dejgaard L.A. Haland T.F. Lie O.H. Vigorous exercise in patients with hypertrophic cardiomyopathy Int J Cardiol 250 2018 157 163 10.1016/J.IJCARD.2017.07.015 29169752
33 Saberi S. Wheeler M. Bragg-Gresham J. Effect of moderate-intensity exercise training on peak oxygen consumption in patients with hypertrophic cardiomyopathy: a randomized clinical trial JAMA 317 13 2017 1349 1357 10.1001/jama.2017.2503 28306757
34 Wasserstrum Y. Barriales-Villa R. Fernández-Fernández X. The impact of diabetes mellitus on the clinical phenotype of hypertrophic cardiomyopathy Eur Heart J 40 21 2019 1671 1677 10.1093/eurheartj/ehy625 30358878
35 Zhang J. Zhu C. Nie C. Impact of body mass index on postoperative atrial fibrillation in patients with hypertrophic cardiomyopathy undergoing septal myectomy J Am Heart Assoc 11 3 2022 10.1161/JAHA.121.023152
36 Elliott A.D. Middeldorp M.E. Van Gelder I.C. Albert C.M. Sanders P. Epidemiology and modifiable risk factors for atrial fibrillation Nat Rev Cardiol 20 6 2023 404 417 10.1038/S41569-022-00820-8 36600003
37 Adalsteinsdottir B. Obesity as a modifiable risk factor for hypertrophic cardiomyopathy Eur J Prev Cardiol 27 17 2020 1846 1848 10.1177/2047487319897164 31928363
38 Philipson D.J. Rader F. Siegel R.J. Risk factors for atrial fibrillation in hypertrophic cardiomyopathy Eur J Prev Cardiol 28 6 2021 658 665 10.1177/2047487319828474 30727760
39 Dimitri H. Ng M. Brooks A.G. Atrial remodeling in obstructive sleep apnea: implications for atrial fibrillation Heart Rhythm 9 3 2012 321 327 10.1016/J.HRTHM.2011.10.017 22016075
40 Neilan T.G. Farhad H. Dodson J.A. Effect of sleep apnea and continuous positive airway pressure on cardiac structure and recurrence of atrial fibrillation J Am Heart Assoc 2 6 2013 10.1161/JAHA.113.000421
41 Pedrosa R.P. Lima S.G. Drager L.F. Sleep quality and quality of life in patients with hypertrophic cardiomyopathy Cardiology 117 3 2010 200 206 10.1159/000321718 21150200
42 Sun D. Schaff H.V. Nishimura R.A. Patient-reported atrial fibrillation after septal myectomy for hypertrophic cardiomyopathy Ann Thorac Surg 113 6 2022 1918 1924 10.1016/J.ATHORACSUR.2021.08.081 34655566
43 Zegkos T. Efthimiadis G.K. Parcharidou D.G. Atrial fibrillation in hypertrophic cardiomyopathy: a turning point towards increased morbidity and mortality Hellenic J Cardiol 58 5 2017 331 339 10.1016/J.HJC.2017.01.027 28219794
44 Masri A. Kanj M. Thamilarasan M. Outcomes in hypertrophic cardiomyopathy patients with and without atrial fibrillation: a survival meta-analysis Cardiovasc Diagn Ther 7 1 2017 36 44 10.21037/CDT.2016.11.23 28164011
45 Liao M.T. Wu C.K. Juang J.M.J. Lin T.T. Wu C.C. Lin L.Y. Atrial fibrillation and the risk of sudden cardiac arrest in patients with hypertrophic cardiomyopathy - a nationwide cohort study EClinicalMedicine 34 2021 100802 10.1016/J.ECLINM.2021.100802 33997728
46 Rowin E.J. Hausvater A. Link M.S. Clinical profile and consequences of atrial fibrillation in hypertrophic cardiomyopathy Circulation 136 25 2017 2420 2436 10.1161/CIRCULATIONAHA.117.029267/-/DC1 28916640
47 members A.F. Elliott P.M. Anastasakis A. 2014 ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: the task force for the diagnosis and management of hypertrophic cardiomyopathy of the European society of Cardiology (ESC) Eur Heart J 35 39 2014 2733 2779 10.1093/EURHEARTJ/EHU284 25173338
48 Carrick R.T. Maron M.S. Adler A. Development and validation of a clinical predictive model for identifying hypertrophic cardiomyopathy patients at risk for atrial fibrillation: the HCM-AF score Circ Arrhythm Electrophysiol 14 6 2021 E009796 10.1161/CIRCEP.120.009796
49 Cheung M. Husain A. Du D. International practice patterns in the detection and management of arrhythmias in patients with hypertrophic cardiomyopathy J Am Heart Assoc 11 19 2022 e027385 10.1161/JAHA.122.027385
50 Weissler-Snir A. Chan R.H. Adler A. Usefulness of 14-day holter for detection of nonsustained ventricular tachycardia in patients with hypertrophic cardiomyopathy Am J Cardiol 118 8 2016 1258 1263 10.1016/J.AMJCARD.2016.07.043 27567133
51 Magnusson P. Mörner S. EvaLuation using cardiac insertable devices and TelephonE in hypertrophic cardiomyopathy (ELUCIDATE HCM): a prospective observational study on incidence of arrhythmias J Cardiovasc Electrophysiol 32 1 2021 129 135 10.1111/JCE.14792 33108031
52 Sakhi R. Huurman R. Theuns D.A.M.J. Incremental value of an insertable cardiac monitor in patients with hypertrophic cardiomyopathy with low or intermediate risk for sudden cardiac death Cardiology 146 2 2021 207 212 10.1159/000512656 33477163
53 Kim D. Yang P.S. You S.C. Comparative effectiveness of early rhythm control versus rate control for cardiovascular outcomes in patients with atrial fibrillation J Am Heart Assoc 10 24 2021 10.1161/JAHA.121.023055
54 Purmah Y. Proietti M. Laroche C. Rate vs. rhythm control and adverse outcomes among European patients with atrial fibrillation EP Europace 20 2 2018 243 252 10.1093/EUROPACE/EUW421 28160483
55 Ommen S.R. Mital S. Burke M.A. 2020 AHA/ACC guideline for the diagnosis and treatment of patients with hypertrophic cardiomyopathy: executive summary: a report of the American college of Cardiology/American heart association joint committee on clinical practice guidelines J Am Coll Cardiol 76 25 2020 3022 3055 10.1016/J.JACC.2020.08.044 33229115
56 Miller C.A.S. Maron M.S. Estes N.A.M. Safety, side effects and relative efficacy of medications for rhythm control of atrial fibrillation in hypertrophic cardiomyopathy Am J Cardiol 123 11 2019 1859 1862 10.1016/J.AMJCARD.2019.02.051 30922542
57 Calkins H. Hindricks G. Cappato R. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation EP Europace 20 1 2018 e1 e160 10.1093/EUROPACE/EUX274
58 Chen C. Lal M. Burton Y. Ecacy and safety of dofetilide and sotalol in patients with hypertrophic cardiomyopathy Commun Med 3 2023 99 10.21203/rs.3.rs-2391095/v1 37468544
59 Moore J.E.C. Trager L. Anzia L.E. Dofetilide for suppression of atrial fibrillation in hypertrophic cardiomyopathy: a case series and literature review Pacing Clin Electrophysiol 41 4 2018 396 401 10.1111/PACE.13310 29450893
60 Sherrid M.V. Barac I. McKenna W.J. Multicenter study of the efficacy and safety of disopyramide in obstructive hypertrophic cardiomyopathy J Am Coll Cardiol 45 8 2005 1251 1258 10.1016/J.JACC.2005.01.012 15837258
61 Coppini R. Ferrantini C. Pioner J.M. Electrophysiological and contractile effects of disopyramide in patients with obstructive hypertrophic cardiomyopathy: a translational study JACC Basic Transl Sci 4 7 2019 795 813 10.1016/J.JACBTS.2019.06.004 31998849
62 Providencia R. Elliott P. Patel K. Catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy: a systematic review and meta-analysis Heart 102 19 2016 1533 1543 10.1136/HEARTJNL-2016-309406 27234160
63 Zhao D.S. Shen Y. Zhang Q. Outcomes of catheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy: a systematic review and meta-analysis EP Europace 18 4 2016 508 520 10.1093/EUROPACE/EUV339 26612881
64 Dinshaw L. Münkler P. Schäffer B. Ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy: treatment strategy, characteristics of consecutive atrial tachycardia and long-term outcome J Am Heart Assoc 10 2021 e017451 10.1161/JAHA.120.017451 33455428
65 Faraz F. Rehman M.E.U. Sabir B. Efficacy of catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy: a systematic review and meta-analysis Curr Probl Cardiol 48 3 2023 101524 10.1016/J.CPCARDIOL.2022.101524 36455792
66 Wazni O.M. Dandamudi G. Sood N. Cryoballoon ablation as initial therapy for atrial fibrillation N Engl J Med 384 4 2021 316 324 10.1056/NEJMOA2029554/SUPPL_FILE/NEJMOA2029554_DATA-SHARING 33197158
67 Andrade J.G. Wells G.A. Deyell M.W. Cryoablation or drug therapy for initial treatment of atrial fibrillation N Engl J Med 384 4 2021 305 315 10.1056/NEJMOA2029980/SUPPL_FILE/NEJMOA2029980_DATA-SHARING 33197159
68 Kirchhof P. Camm A.J. Goette A. Early rhythm-control therapy in patients with atrial fibrillation N Engl J Med 383 14 2020 1305 1316 10.1056/NEJMOA2019422/SUPPL_FILE/NEJMOA2019422_DATA-SHARING.PDF 32865375
69 Haq I.U. Akhiyat N. Al-Shakarchi N. Atrial fibrillation substrate and catheter ablation outcomes in MYBPC3- and MYH7-mediated hypertrophic cardiomyopathy JACC Clin Electrophysiol 10 2024 1380 1391 10.1016/J.JACEP.2024.03.026 38819352
70 Creta A. Elliott P. Earley M.J. Catheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy: a European observational multicentre study EP Europace 23 9 2021 1409 1417 10.1093/EUROPACE/EUAB022
71 Santangeli P. Di Biase L. Themistoclakis S. Catheter ablation of atrial fibrillation in hypertrophic cardiomyopathy: long-term outcomes and mechanisms of arrhythmia recurrence Circ Arrhythm Electrophysiol 6 6 2013 1089 1094 10.1161/CIRCEP.113.000339 24114776
72 Zahid S. Malik T. Peterson C. Conduction velocity is reduced in the posterior wall of hypertrophic cardiomyopathy patients with normal bipolar voltage undergoing ablation for paroxysmal atrial fibrillation J Intervent Card Electrophysiol 67 2023 1 8 10.1007/S10840-023-01533-9/FIGURES/5
73 Cardoso R. Mendirichaga R. Fernandes G. Cryoballoon versus radiofrequency catheter ablation in atrial fibrillation: a meta-analysis J Cardiovasc Electrophysiol 27 10 2016 1151 1159 10.1111/JCE.13047 27422848
74 Linhart M. Bellmann B. Mittmann-Braun E. Comparison of cryoballoon and radiofrequency ablation of pulmonary veins in 40 patients with paroxysmal atrial fibrillation: a case-control study J Cardiovasc Electrophysiol 20 12 2009 1343 1348 10.1111/J.1540-8167.2009.01560.X 19656254
75 Schmidt M. Dorwarth U. Andresen D. Cryoballoon versus RF ablation in paroxysmal atrial fibrillation: results from the German Ablation Registry J Cardiovasc Electrophysiol 25 1 2014 1 7 10.1111/JCE.12267 24134539
76 Luik A. Radzewitz A. Kieser M. Cryoballoon versus open irrigated radiofrequency ablation in patients with paroxysmal atrial fibrillation: the prospective, randomized, controlled, noninferiority FreezeAF study Circulation 132 14 2015 1311 1319 10.1161/CIRCULATIONAHA.115.016871 26283655
77 Verma A. Haines D.E. Boersma L.V. Pulsed field ablation for the treatment of atrial fibrillation: PULSED AF pivotal trial Circulation 147 19 2023 1422 1432 10.1161/CIRCULATIONAHA.123.063988 36877118
78 Davong B. Adeliño R. Delasnerie H. Pulsed-field ablation on mitral isthmus in persistent atrial fibrillation: preliminary data on efficacy and safety JACC Clin Electrophysiol 9 7 Pt 2 2023 1070 1081 10.1016/J.JACEP.2023.03.021 37354173
79 Rozen G. Elbaz-Greener G. Marai I. Utilization and complications of catheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy J Am Heart Assoc 9 13 2020 15721 10.1161/JAHA.119.015721
80 Lapenna E. Pozzoli A. De B.M. Mid-term outcomes of concomitant surgical ablation of atrial fibrillation in patients undergoing cardiac surgery for hypertrophic cardiomyopathy Eur J Cardio Thorac Surg 51 6 2017 1112 1118 10.1093/EJCTS/EZX017
81 Bogachev-Prokophiev A.V. Afanasyev A.V. Zheleznev S.I. Concomitant ablation for atrial fibrillation during septal myectomy in patients with hypertrophic obstructive cardiomyopathy J Thorac Cardiovasc Surg 155 4 2018 1536 1542.e2 10.1016/J.JTCVS.2017.08.063 28947201
82 Kharbanda R.K. Misier N.L.R. Van den Eynde J. Outcomes of concomitant surgical ablation in patients undergoing surgical myectomy for hypertrophic obstructive cardiomyopathy: a systematic review and meta-analysis Int J Cardiol 0 0 2023 131099 10.1016/J.IJCARD.2023.05.049
83 Wadid M. White M. Silver J.S. PO-02-158 pace and ablate IS an effective management strategy for atrial fibrillation in patients with hypertrophic cardiomyopathy Heart Rhythm 20 5 2023 S292 S293 10.1016/J.HRTHM.2023.03.1552
84 Olivotto I. Oreziak A. Barriales-Villa R. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial Lancet 396 10253 2020 759 769 10.1016/S0140-6736(20)31792-X 32871100
85 Desai M.Y. Owens A. Geske J.B. Myosin inhibition in patients with obstructive hypertrophic cardiomyopathy referred for septal reduction therapy J Am Coll Cardiol 80 2 2022 95 108 10.1016/J.JACC.2022.04.048 35798455
86 Castrichini M. Alsidawi S. Geske J.B. Incidence of newly recognized atrial fibrillation in patients with obstructive hypertrophic cardiomyopathy treated with Mavacamten Heart Rhythm S1547-5271 2024 02382 02388 10.1016/J.HRTHM.2024.04.055
87 Maron M.S. Masri A. Nassif M.E. Aficamten for symptomatic obstructive hypertrophic cardiomyopathy N Engl J Med 390 20 2024 10.1056/NEJMOA2401424
88 Guttmann O.P. Pavlou M. O’Mahony C. Prediction of thrombo-embolic risk in patients with hypertrophic cardiomyopathy (HCM Risk-CVA) Eur J Heart Fail 17 8 2015 837 845 10.1002/EJHF.316 26183688
89 Tsuda T. Hayashi K. Fujino N. Effect of hypertrophic cardiomyopathy on the prediction of thromboembolism in patients with nonvalvular atrial fibrillation Heart Rhythm 16 6 2019 829 837 10.1016/J.HRTHM.2018.11.029 30503962
90 Lee H.J. Kim H.K. Jung J.H. Novel oral anticoagulants for primary stroke prevention in hypertrophic cardiomyopathy patients with atrial fibrillation Stroke 50 9 2019 2582 2586 10.1161/STROKEAHA.119.026048 31340730
91 Jung H. Yang P.S. Jang E. Effectiveness and safety of non-vitamin K antagonist oral anticoagulants in patients with atrial fibrillation with hypertrophic cardiomyopathy: a nationwide cohort study Chest 155 2 2019 354 363 10.1016/J.CHEST.2018.11.009 30472021
92 Dominguez F. Climent V. Zorio E. Direct oral anticoagulants in patients with hypertrophic cardiomyopathy and atrial fibrillation Int J Cardiol 248 2017 232 238 10.1016/J.IJCARD.2017.08.010 28811092
93 Mo B.-F. Zhang R. Yuan J.-L. Left atrial appendage closure for primary and secondary stroke prevention in patients with hypertrophic cardiomyopathy and atrial fibrillation: a pilot study Front Cardiovasc Med 8 2021 719755 10.3389/FCVM.2021.719755 34722657
94 Agarwal S. Munir M.B. DeSimone C.V. Deshmukh A. Alkhouli M.A. Asad Z.U.A. Outcomes of patients with hypertrophic cardiomyopathy undergoing percutaneous left atrial appendage occlusion J Intervent Card Electrophysiol 67 2024 851 854 10.1007/S10840-024-01772-4
95 Aglan A. Fath A.R. Maron B.J. Percutaneous left atrial appendage closure for stroke prevention in hypertrophic cardiomyopathy patients with atrial fibrillation Heart Rhythm S1547-5271 24 2024 02632 02638 10.1016/J.HRTHM.2024.05.038
96 Mahajan R. Perera T. Elliott A.D. Subclinical device-detected atrial fibrillation and stroke risk: a systematic review and meta-analysis Eur Heart J 39 16 2018 1407 1415 10.1093/EURHEARTJ/EHX731 29340587
97 Healey J.S. Connolly S.J. Gold M.R. Subclinical atrial fibrillation and the risk of stroke N Engl J Med 366 2 2012 120 129 10.1056/NEJMOA1105575 22236222
98 Glotzer T.V. Hellkamp A.S. Zimmerman J. Atrial high rate episodes detected by pacemaker diagnostics predict death and stroke: report of the Atrial Diagnostics Ancillary Study of the MOde Selection Trial (MOST) Circulation 107 12 2003 1614 1619 10.1161/01.CIR.0000057981.70380.45 12668495
99 Van Gelder I.C. Healey J.S. Crijns H.J.G.M. Duration of device-detected subclinical atrial fibrillation and occurrence of stroke in ASSERT Eur Heart J 38 17 2017 1339 1344 10.1093/EURHEARTJ/EHX042 28329139
100 Swiryn S. Orlov M.V. Benditt D.G. Clinical implications of brief device-detected atrial tachyarrhythmias in a cardiac rhythm management device population: results from the registry of atrial tachycardia and atrial fibrillation episodes Circulation 134 16 2016 1130 1140 10.1161/CIRCULATIONAHA.115.020252 27754946
