Hypertrophic cardiomyopathy (HCM) affects approximately 1 in 500 individuals and is characterized by unexplained left ventricular hypertrophy. Its clinical spectrum ranges from an asymptomatic course to progressive heart failure and sudden cardiac death.^1,2 Moreover, atrial fibrillation (AF) is the most common arrhythmia in this population, with an incidence of 27 per 100 patient-years.³ This high incidence is driven by pathophysiological factors including diastolic dysfunction, mitral regurgitation, and left ventricular outflow tract obstruction, which promote atrial remodeling and predispose to AF. The development of AF in patients with HCM is associated with worse prognosis, significantly increasing the risks of thromboembolic stroke, heart failure decompensation, and all-cause mortality.⁴

Conventional antiarrhythmic drug (AAD) therapy has demonstrated only modest long-term success, with substantial rates of arrhythmia recurrence despite treatment. Consequently, catheter ablation (CA) has emerged as an important alternative for those who are refractory to drug therapy.⁵ Although observational series have suggested that CA may achieve superior rhythm control and clinical outcomes, these studies frequently lack contemporaneous control groups, thereby limiting definitive conclusions.⁶ Therefore, this meta-analysis aimed to synthesize the available controlled observational evidence to determine the long-term impact of CA, specifically on mortality, heart failure hospitalizations, and stroke, in patients with HCM and AF, as seen in the Central Figure.

This systematic review and meta-analysis were conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.⁷ Our protocol ID in PROSPERO database is: CRD42023451815.

The systematic search yielded four retrospective cohort studies that met all inclusion criteria.^10–13 The detailed screening and selection process is depicted in Figure 1, illustrating the numbers of articles identified, screened, and ultimately included in the review.

All four cohorts, comprising a total of 579 patients with long follow-up time (5.52 ± 0.91 years), were thoroughly characterized in Tables 1 to 3, which summarize study design, participant demographics, intervention details, and primary outcomes. Notably, multiple studies lacked data on substrate modification techniques during AF ablation procedures, baseline echocardiographic parameters, AF duration prior to CA, and preprocedural antiarrhythmic therapy. Nevertheless, quality assessment using the NOS returned high scores (8 or 9 out of 9; Table 4). The GRADE evaluations of evidence certainty, presented in Table 5, indicated a low to moderate reliability.

Across all studies, patients undergoing CA demonstrated significantly improved arrhythmia-free survival, particularly following repeat procedures (Table 3). In addition, the pooled meta-analysis revealed a statistically significant reduction in the composite adverse event rate among ablated patients (OR 0.22; 95% CI 0.08 to 0.60; p < 0.05), despite moderate heterogeneity (I² = 64%; Figure 2).

Although mortality tended to be lower in the CA group, this difference did not achieve statistical significance (Figure 3). Also, CA was associated with a significant decrease in heart failure hospitalizations (OR 0.32; 95% CI 0.13 to 0.82; p = 0.01), indicating a clear protective effect (Figure 4). While stroke incidence was lower in the CA cohort compared to controls, this reduction did not reach statistical significance (Figure 5; p > 0.05).

The complications rate related to AF-CA procedures were low (8 in total): fatal pneumothorax due to accidental subclavian vein: 1; cardiac tamponade: 3; complete atrioventricular block requiring permanent pacemaker: 1; femoral hematoma, pleural effusion, and hemidiaphragm paralysis: 3. Information about serious adverse drug effects in the control groups was not available.

This systematic review and meta-analysis demonstrate that AF-CA in patients with HCM was associated with a significant reduction in adverse clinical events, driven predominantly by fewer heart failure hospitalizations. This observation suggests that the mitigation of heart failure admissions is a primary mechanism through which AF-CA confers its overall clinical benefit in this high-risk cohort.

Although AF-CA has been an established therapy in the last decades, observational series consistently report lower arrhythmia-free success rates in HCM compared with non-HCM populations, often necessitating repeat procedures and ongoing AAD therapy to maintain sinus rhythm. Indeed, single-procedure AF recurrence rates in HCM range from 38.7% to 49.8%, rising to 51.8% to 71.2% after multiple procedures.¹⁴ A more recent meta-analysis documented post-CA AF recurrence rates from 13.3% to 92.9%, and patients with HCM required more redo procedures and AADs than controls without HCM.¹⁵ We also observed a high recurrence rate of AF and atrial tachycardia following a single CA procedure in all four studies, with recurrence rates ranging from 63.7% to 74%, underscoring the challenges of durable rhythm control in this population. The distinct pattern of atrial remodeling in HCM, particularly asymmetric left atrial dilation observed on computed tomography imaging, likely contributes to these suboptimal outcomes.¹⁶ Moreover, emerging therapies such as mavacamten, which promotes reverse remodeling, and sodium-glucose cotransporter-2 inhibitors, which have demonstrated arrhythmia-reducing and cardioprotective effects in patients with heart failure, offer promising adjunctive approaches to enhance CA efficacy in HCM-associated AF.^17,18

Advances in ablation technology, including cryoballoon ablation and pulsed-field ablation, have yielded encouraging results in general AF cohorts, yet their specific utility in HCM remains under-investigated. Retrospective data suggest comparable efficacy between cryoballoon and radiofrequency contact-force ablation for pulmonary vein isolation in HCM.¹⁹ However, inconsistent reporting of mapping systems, catheter technology, and non-pulmonary vein targets limits definitive conclusions in our study. Given the frequent need for repeat procedures in HCM, comprehensive lesion sets and advanced mapping to address complex atrial substrates may be necessary for sustained sinus rhythm in patients with HCM.

While AF in HCM is linked to increased mortality, partly due to hemodynamic compromise from loss of atrial contractility, and carries a markedly higher stroke risk than in non-HCM AF populations, maintenance of sinus rhythm remains a biologically plausible strategy to improve survival. In our analysis, although mortality and stroke incidence showed lower trends in the CA group, only the reduction in heart failure hospitalizations reached statistical significance. Some studies suggest that reverse atrial remodeling and reduced progression to persistent AF after CA may underlie these improved outcomes by decreasing overall AF burden.²⁰ As we know, left atrial size is a critical determinant of AF risk in HCM, and persistent or permanent AF has been linked to worse prognosis.^21–23 Furthermore, large trials have demonstrated mortality benefits with AAD therapy and improved outcomes with early rhythm control, reinforcing the importance of sinus rhythm maintenance, especially when initiated early.²⁴

In our study, the only individual clinical outcome that was statistically significant and determined by CA intervention was heart failure hospitalization (7.28% versus 18.50%). AF is poorly tolerated by the HCM population and has an important negative impact on their quality of life. There are interplaying conditions, such as diastolic dysfunction, outflow tract obstruction, and mitral regurgitation, that interact with one another and collaborate to initiate AF and heart failure in HCM. In these cases, any AF recurrence determines a great chance of heart failure decompensation and hospitalization. This may explain the multiple procedures realized in the cohort studies to maintain better rhythm control and reduce serious hemodynamic consequences resulting from AF. Overall, the marked reduction in heart failure hospitalizations suggests that AF-CA may improve clinical stability in HCM by restoring ventricular filling and enhancing cardiac output through sustained sinus rhythm. To confirm and extend these findings, future investigations should prioritize large, prospective, randomized controlled trials directly comparing CA with contemporary medical therapy in this population. Moreover, incorporating advanced imaging modalities, such as cardiac magnetic resonance with late gadolinium enhancement, to quantify pre-ablation atrial fibrosis may enhance patient selection and procedural planning. Such imaging could identify arrhythmogenic substrates that voltage mapping alone may overlook in HCM atria, thereby optimizing lesion sets and improving long-term rhythm control.²⁵

This study suggests that CA may reduce adverse outcomes in patients with AF and HCM, particularly by lowering heart failure-related hospitalizations. While these findings are promising, they underscore the necessity for further clinical trials with more robust methodologies to validate these results, since this systematic review includes only four retrospective studies.