Effectiveness of radiofrequency catheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy: long-term outcomes and predictors of recurrence

Introduction

Hypertrophic cardiomyopathy (HCM) is a phenotypic presentation of cardiomyopathy with asymmetric ventricular hypertrophy and may be associated with left ventricular outflow tract (LVOT) obstruction (1). The most common arrhythmia in patients with HCM is atrial fibrillation (AF), with a predicted prevalence of approximately 20% (2). HCM is often associated with mitral regurgitation (MR) and tricuspid regurgitation (TR) and can influence the outcome of catheter ablation and long-term survival, which suggests that left atrial (LA) size and functional regurgitation may have considerable implications for patient outcomes (1,2).

In addition to MR and TR, HCM significantly influences the prognosis of patients with AF, occurring in 1 in every 500 of these AF patients. A portion of patients may be asymptomatic, while others may experience dyspnea, syncope, and sudden cardiac death (SCD) (3). HCM is a progressive condition that leads to heart failure (HF), arrhythmias, and thromboembolic events. Arunachalam et al. (4) reported an AF incidence of 3.8% per 100 patient-years and a prevalence of 27.09% in patients with HCM and found that its presence increases mortality. While beta-blockers and amiodarone yield inconsistent drug effects, catheter ablation can reliably reduce symptoms; however, the rate of recurrence is high, and repeated ablation may be needed to improve outcomes (4). AF is present in 20% of patients with HCM, with this proportion increasing with age and disease severity (5). Its pathophysiology involves LA remodeling due to diastolic dysfunction, MR, LVOT obstruction, and atrial myopathy, with elevated left ventricular (LV) filling pressures and atrial stress promoting AF onset and recurrence (5,6). Episodes of AF are frequently precipitated by severe symptoms, e.g., hypotension, fatigue, and intolerance to exertion (2,5,7). Additionally, AF contributes significantly to adverse clinical outcomes, such as higher thromboembolic event rates, deterioration of HF, and inappropriate implantable cardioverter-defibrillator (ICD) discharge (2,5,7). The risk of thromboembolism, however, increases substantially in patients with HCM who acquire AF (8). Overall, these facts highlight the importance of effective AF management in patients with HCM.

The efficacy of radiofrequency catheter ablation (RFCA) in patients with HCM remains controversial. The unique pathological features of HCM, including extensive atrial fibrosis, hypertrophy, and remodeled atrial electrophysiological properties, present substantial challenges to preventing AF recurrence following RFCA (9). The evidence from one study consistently suggests that patients with HCM undergoing RFCA have higher rates of arrhythmia recurrence than do those without HCM. This increased recurrence rate often requires the administration of continuous antiarrhythmic drug therapy and subsequent ablation treatments, which reflects the challenge of rhythm control for these patients (10).

Despite these issues, RFCA remains beneficial for symptomatic, drug-refractory AF in patients with HCM, as it can restore sinus rhythm (SR), reduce the frequency of thromboembolic events, and improve outcomes (8,9). However, the long-term efficacy and safety of RFCA remain unclear due the small sample size, variable methodological designs, and inconsistent follow-up characteristics of the related research (3,11). Moreover, data concerning the impact of RFCA on the symptoms, AF burden, progression of HF, and prognosis of patients with HCM are limited (5). As AF’s interaction with the pathology of HCM is complex, further research needs to assess RFCA’s long-term utility, such as rhythm control, symptom reduction, and thromboembolic risk reduction (5,8,9). Identifying predictors of successful ablation and identifying those HCM subgroups that will most likely benefit can also further optimize treatment strategies (3,11). This study thus aimed to evaluate the effectiveness of RFCA in preventing AF recurrence and to clarify its impact on symptoms and prognosis in order to contribute to the evidence-based treatment of patients with HCM and AF. We present this article in accordance with the STROBE reporting checklist (available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-196/rc).

Methods

Study design and patient selection

This retrospective study was carried out by senior cardiac electrophysiology (EP) ablation experts with more than 10 years’ experience in EP procedures. Between January 2013 and January 2020, 5,712 first-time RFCA candidates for AF were consecutively screened in three hospitals (Department of Cardiology, The First Affiliated Hospital of Dalian Medical University; Department of Cardiology, Dalian University of Technology Affiliated Central Hospital; and Department of Cardiology, The Affiliated Zhongshan Hospital of Dalian University). A total of 153 consecutive patients with HCM and AF were enrolled, of whom 129 underwent follow-up. Patients were categorized into two groups based on whether or not they experienced arrhythmic recurrence following RFCA. The SR group consisted of patients who did not experience a recurrence of arrhythmia, while the recurrence group included those who did experience recurrence. For patients undergoing repeat ablation procedures, recurrence was defined as any arrhythmia recurrence occurring after the 3-month blanking period following the most recent ablation. The diagnosis of HCM was established according to the 2020 American Heart Association (AHA)/American College of Cardiology (ACC) guidelines (12). The exclusion criteria were as follows: the presence of other arrhythmias treated by catheter ablation [e.g., Wolf-Parkinson-White syndrome, supraventricular tachycardia, or ventricular tachycardia (VT)]; premaze process, hybrid surgery, or a history of surgical ablation; moderate-to-severe mitral stenosis and aortic stenosis, or congenital heart disease; history of septal myectomy, alcohol septal ablation, or valve surgery; severe noncardiac conditions (e.g., end-stage kidney disease or active cancer); cognitive loss; conditions that would render RFCA inappropriate (such as hematological issues or bleeding disorders); a thrombus in the left atrium or LA appendage; and refusal to sign informed consent. The flowchart of patient inclusion is shown in Figure 1.

Figure 1 Flowchart of patient inclusion. AAD, antiarrhythmic drug; AF, atrial fibrillation; AT, atrial tachycardia; HCM, hypertrophic cardiomyopathy; PSVT, paroxysmal supraventricular tachycardia; RFCA, radiofrequency catheter ablation; WPW, Wolff-Parkinson-White.

This retrospective study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and was approved by the Ethics Committee of The First Affiliated Hospital of Dalian Medical University. Informed consent was waived by the Ethics Committee due to the retrospective nature of the study. Dalian University of Technology Affiliated Central Hospital and The Affiliated Zhongshan Hospital of Dalian University were informed of and agreed to the study protocol.

RFCA procedure

Preoperatively, all patients underwent transesophageal echocardiography in order to rule out atrial thrombi. Venous access was obtained via the femoral vein, and transseptal puncture was performed under echocardiographic or fluoroscopic guidance. Ablation was performed with a CARTO system [Biosense Webster Inc., Johnson & Johnson (J&J) MedTech, Irvine, CA, USA] with sedation or general anesthesia. Pulmonary vein isolation (PVI) was performed in all patients and was the primary procedural endpoint. Additional ablation lines, including an LA roof line, posterior inferior line (posterior box lesion), and anterior line, were employed at the operator’s discretion. Left lateral isthmus ablation, right atrial isthmus ablation, and complex fractionated atrial electrogram (CFAE) ablation were applied as needed.

For repeat procedures, PVI remained the primary endpoint, and reisolation of the pulmonary veins (PVs) was required in the case of reconnection. Any additional ablation after PVI was determined at the discretion of the operator. Bidirectional conduction block was ensured following SR restoration through ablation or cardioversion.

Follow-up and endpoints

Patients were followed up at 1, 3, and 6 months after the procedure and every year thereafter. Follow-up testing included 12-lead electrocardiogram, 24-hour or 7-day Holter monitor, and cardiac implantable electronic device (CIED) interrogation as appropriate. The primary endpoint was AF or atrial tachycardia (AT) recurrence, defined as any reported event lasting ≥30 seconds after the 3-month blanking interval. Secondary endpoints included all-cause mortality, HCM-associated mortality, thromboembolic events, and rehospitalization for HF.

HCM-related mortality was operationally defined as the follows: (I) sudden death (i.e., death occurring with no symptoms or <1 hour after symptom onset in a previously fairly stable patient, including those resuscitated from cardiac arrest); (II) HF-related death occurring after progressive cardiac decompensation, particularly if complicated by pulmonary edema or evolution into end-stage HCM; and (III) embolic mortality resulting from a probable or proven embolic stroke. Exacerbation of HF hospitalization was defined as major unplanned inpatient admissions for severe HF symptoms [i.e., New York Heart Association (NYHA) functional classes III/IV]. Thromboembolism events were considered to be cerebrovascular accidents (strokes and transient ischemic attack) and peripheral embolism.

Statistical analysis

Statistical analyses were performed with SPSS 27.0 (IBM Corp., Armonk, NY, USA). A normal distribution of data was confirmed to determine whether to use parametric or nonparametric tests. Continuous variables are expressed as the mean ± standard deviation (SD) or as median and were compared via the paired t-test or Mann-Whitney test, respectively. Categorical variables are expressed as frequencies (percentages) and were compared via the Chi-squared test or Fisher’s exact test. Univariate Cox proportional hazards regression was used to examine possible determinants of AF/AT recurrence. Variables with P<0.15 in the univariate analysis were incorporated into the multivariable Cox regression model to establish independent predictors. Hazard ratios (HRs) with 95% confidence intervals (CIs) are presented. The discriminative power of CAAP-AF (coronary artery disease, age, sex, atrial diameter, type of AF, and prior antiarrhythmic drug failure) score, and APPLE score (age >65 years, persistent AF, impaired estimated glomerular filtration rate, LAD, and ejection fraction) was calculated via receiver operating characteristic curve analysis, with the area under the curve (AUC) being compared. Kaplan-Meier (K-M) survival plots were used to examine arrhythmia-free survival and secondary endpoints, and log-rank tests were used for group comparisons. Sankey plots were used to visualize the changes in the longitudinal burden of symptoms based on the modified European Heart Rhythm Association (mEHRA) (13) and the NYHA classification (14). A two-tailed P value of <0.05 was considered statistically significant.

Results

Baseline characteristics and predictors of arrhythmic recurrence in patients with AF

A total of 129 patients were included, and the baseline characteristics were compared (Table 1) between the SR (n=58) and recurrence groups (n=71). The mean age of the entire cohort was 62.8±9.5 years, and there was no significant age difference between the groups (P=0.70). However, the recurrence group had a greater proportion of females (50.7%) compared to the SR group (32.8%) (P=0.03). The average duration of AF was 4.7±4.6 years, with a similar distribution between groups (P=0.60). Long-term AF was more prevalent in the recurrence group than in the SR group (33.8% vs. 20.7%), but this did not represent a significant difference (P=0.10).

The comorbidities of hypertension (59.7%), diabetes (19.4%), and coronary artery disease (22.5%) were prevalent in both groups, without differences in their distributions. Both groups were similar in terms of thromboembolic events, renal disease, thyroid disease, and ventricular arrhythmia [including nonsustained VT (NSVT) and sustained VT]. Meanwhile, brain natriuretic peptide (BNP) levels were lower in the SR group (337.9±253.4 pg/mL) than in the recurrence group (482.4 ±339.3 pg/mL) but not significantly so. Echocardiographic findings revealed that the recurrence group, as compared to the SR group, had higher septal LV thickness (15.9±4.3 vs. 14.2±3.3 mm, P=0.006) and larger LAD (45.0±5.5 vs. 41.5±3.5 mm, P<0.001), which reflected more pronounced structural remodeling in these patients. In addition, moderate-to-severe MR was more common in the recurrence group than in the SR group (26.8% vs. 8.6%, P=0.008).

Other echocardiographic parameters, including posterior LV wall thickness, LV ejection fraction (LVEF), LV end-diastolic (LVED), and E peak deceleration time (EDT), were not significantly different between the groups. Functional assessment, including mEHRA and NYHA classifications, was also not significantly different. However, a higher proportion of patients in the recurrence group had NYHA III/IV symptoms (38.0% vs. 27.6%, P=0.21), indicating a possible correlation between greater functional impairment and arrhythmic recurrence.

Predictors of AF/AT recurrence after RFCA

The predictors of arrhythmic recurrences after multiple procedures, as determined in the univariable and multivariable Cox analyses, are listed in Table 2. Female sex was correlated with recurrence (HR =1.582; 95% CI: 0.990–2.526; P=0.055) in the univariate analysis, but not significantly so. Female sex was associated with arrhythmic recurrence (HR =1.842; 95% CI: 1.141–2.973; P=0.01) in the multivariate analysis. The LAD was strongly correlated with recurrence in the univariate and multivariate analyses (univariate: HR =1.111; 95% CI: 1.062–1.163; P<0.001; multivariate: HR =1.126; 95% CI: 1.073–1.181; P<0.001), as was moderate-to-severe MR (univariate: HR =1.922; 95% CI: 1.135–3.253; P=0.02; multivariate: HR =2.055; 95% CI: 1.212–3.485; P=0.008). Other variables, including age, AF duration, persistent AF, and comorbidities (hypertension, diabetes, and coronary artery disease), along with echocardiographic parameters such as septal LV thickness and LVEF, were not found to have any significant correlation with arrhythmic recurrence.

Arrhythmia-free survival was graphically presented on a Cox model survival curve in terms of the predictors’ effect (Figure 2A). The adjusted arrhythmia-free survival curve for other covariates indicated the significant effect of different predictors on AF recurrence-free survival (P=0.008 in Figure 2B; P=0.01 in Figure 2C). The optimal cutoff value for LAD, as determined by the receiver operating characteristic curve, was 45 mm. The arrhythmia-free cumulative survival rate was lower in those with LAD ≥45 mm than in those with LAD <45 mm after adjustments were made for AF type, sex, MR, and septal LV thickness (P<0.001), as shown in Figure 2D.

Figure 2 Arrhythmia-free cumulative survival of different predictors following the most recent procedure. (A) AF type, LAD, sex, moderate-to-severe MR, and septal LV thickness-adjusted arrhythmia-free cumulative survival following the most recent procedure. (B) Sex-adjusted arrhythmia-free cumulative survival stratified by the presence (MR+) or absence (MR−) of moderate-to-severe MR, adjusted for AF type, LAD, and sex. (C) Sex-adjusted arrhythmia-free cumulative survival by sex, adjusted for AF type, LAD, MR+, and septal LV thickness. (D) Arrhythmia-free cumulative survival stratified by LAD ≥45 and <45 mm, with adjustments for AF type, sex, MR+, and septal LV thickness. AF, atrial fibrillation; CI, confidence interval; HR, hazard ratio; LAD, left atrial diameter; LV, left ventricular; MR, mitral regurgitation; MR+, with moderate-to-severe mitral regurgitation; MR−, without moderate-to-severe mitral regurgitation.

Predictive value of clinical scores for atrial arrhythmia recurrence postablation

K-M curves were used to determine the predictive value of the CAAP-AF score for AF recurrence (Figure 3A). The CAAP-AF score (15) (ranging from 0 to 13), is a composite of known risk factors for recurrence of AF after ablation, including coronary artery disease, LAD, age, presence of persistent AF, number of anti-arrhythmic drugs failed, and female gender, and demonstrated excellent ability in predicting recurrence (concordance statistic =0.768; 95% CI: 0.685–0.850; P<0.001), whereas the predictive ability of APPLE score was moderate (concordance statistic =0.632; 95% CI: 0.536–0.729; P=0.01; Figure 3B).

Figure 3 Predictive ability of the CAAP-AF score for arrhythmic recurrence. (A) K-M plots of arrhythmia-free survival after last CA procedure based on the CAAP-AF score. (B) Receiver operating characteristic curve comparing the predictive ability of the CAAP-AF and APPLE scores for arrhythmic recurrence. AF, atrial fibrillation; APPLE, age >65 years, persistent AF, impaired estimated glomerular filtration rate, LAD, and ejection fraction; AUC, area under the curve; CA, catheter ablation; CI, confidence interval; CAAP-AF, coronary artery disease, age, sex, atrial diameter, type of AF, and prior antiarrhythmic drug failure; K-M, Kaplan-Meier; LAD, left atrial diameter.

Long-term follow-up outcomes

Three patients (2.3%) received cardiac resynchronization therapy with defibrillators due to deteriorating congestive HF at follow-up. Two (1.6%) patients were implanted with dual-chamber ICDs as a secondary indication for the prevention of sustained VT. Seven (5.4%) patients received dual-chamber pacemakers due to intractable bradycardia.

Statistical evaluation demonstrated that RFCA significantly improved AF symptoms in patients with HCM. The mean mEHRA symptom classification significantly improved at follow-up as compared with baseline (1.9±1.0 vs. 2.9±0.7, P<0.001). mEHRA symptom classification improvement was evident in both the SR group (2.9±0.7 vs. 1.1±0.3, P<0.001) and the recurrence group (2.9±0.7 vs. 2.5±0.8, P<0.001) (Figure 4A).

Figure 4 Comparison of mean (A) mEHRA and (B) NYHA classes at baseline and follow-up in all patients and in the SR and recurrence groups. *, P≤0.05; **, P<0.01; ***, P<0.001; ns, not significant (P>0.05). mEHRA, modified European Heart Rhythm Association symptom classification; NYHA, New York Heart Association; SR, sinus rhythm.

No clinically relevant NYHA status improvement was observed in any patients at follow-up as compared with baseline (2.2±0.8 vs. 2.1±0.8, P=0.37). The SR group had improved NYHA class at follow-up compared with baseline (2.2±0.9 vs. 1.8±0.7, P=0.006) and also had a higher NYHA functional status at follow-up compared with the recurrence group (1.8±0.7 vs. 2.3±0.9, P=0.04) (Figure 4B). Sankey diagrams were used to visualize the mEHRA symptom classification and NYHA class change from baseline to follow-up (Figure 5).

Figure 5 Sankey plots of the change in (A) mEHRA symptom classification and (B) NYHA status from baseline to follow-up. mEHRA, modified European Heart Rhythm Association; NYHA, New York Heart Association.

Secondary outcomes

In terms of secondary outcomes, 13 (9.3%) patients developed new-onset acute thromboembolic events, with 11 occurring in the recurrence group and 2 in the SR group. The incidence was higher in the recurrence group than in the SR group (15.5% vs. 3.4%, log-rank P=0.009). Ten deaths from any cause occurred during follow-up, with four of these deaths in the SR group and six in the recurrence group (8.5% vs. 6.9%, log-rank P=0.22).

Four HCM-related deaths occurred in the recurrence group, while none were reported for the SR group (5.6% vs. 0%, log-rank P=0.01). Additionally, 23 patients (17.8%) were admitted for HF exacerbation, with 3 in the SR group and 20 in the recurrence group (28.2% vs. 5.2%, log-rank P<0.001). K-M curves were used to visualize the secondary outcome events in the SR group and the recurrence group (Figure 6).

Figure 6 JenyK-M curves for the comparison between the SR and recurrence groups for (A) thromboembolic event risk, (B) hospitalization as a consequence of HF exacerbation, (C) all-cause mortality, and (D) HCM-related mortality. HCM, hypertrophic cardiomyopathy; HF, heart failure; K-M, Kaplan-Meier; SR, sinus rhythm.

Impact of catheter ablation on SCD risk in patients with HCM

This study included 83 patients (40 in the SR group and 43 in the recurrence group) with full 1-, 3-, and 5-year follow-up echocardiographic data. Using the HCM-SCD risk calculator of the 2014 European Society of Cardiology guidelines, we calculated the risk of SCD at baseline, 1, 3, and 5 years for all individuals. High-risk individuals were defined as those with an HCM-SCD risk of ≥4% (10 patients), while low-risk individuals were those with a <4% risk (73 patients). All patients exhibited a notable decrease in SCD risk in postprocedure follow-up (Figure 7A). The change in SCD risk was particularly pronounced in the high-risk patients, further supporting the notion that catheter ablation can decrease the incidence of SCD (Figure 7B). The 5-year HCM-related mortality rate was significantly increased in the high-risk group as compared to the low-risk group (30% vs. 1.3%, log-rank P<0.001; Figure 7C). Of the 19 patients with CIEDs, 6 were in the high-risk category and 13 in the low-risk category. CIED data indicated that the prevalence of sustained VT, ventricular fibrillation (VF), and appropriate ICD therapy was significantly greater in the high-risk than in the low-risk group (50% vs. 0%, P=0.02).

Figure 7 Effect of catheter ablation on SCD risk in patients with HCM. (A) Evolution of SCD risk after RFCA, with comparisons of baseline to follow-up in all patients and stratified by recurrence status. Both recurrence and nonrecurrence groups showed reduced SCD risk, with the greatest improvement observed in the high-risk patients. (B) Reduction of SCD risk in high-risk patients: SCD risk changed over time in the high-risk patients (HCM-SCD ≥4%) according to the 2014 European Society of Cardiology HCM-SCD risk calculator. SCD risk markedly decreased in the high-risk patients after catheter ablation. (C) Five-year follow-up of HCM-related mortality and CIED data: the high-risk, as compared to the low-risk group had higher HCM-related mortality (30% vs. 1.3%; P<0.001) and a higher prevalence of ICD therapy (50% vs. 0%, P=0.02). The green line indicates HCM-related deaths in patients with low HCM-SCD risk that occurred during follow-up. The red line indicates HCM-related deaths in patients with high HCM-SCD risk that occurred during follow-up. *, P<0.05. CIED, cardiac implantable electronic device; HCM, hypertrophic cardiomyopathy; ICD, implantable cardioverter-defibrillator; RFCA, radiofrequency catheter ablation; SCD, sudden cardiac death; SVT, sustained ventricular tachycardia; VF, ventricular fibrillation.

Discussion

The principal findings of our study were the following: (I) RFCA was an efficacious long-term rhythm control regimen for AF in patients with HCM. (II) To the best of our knowledge, this study is the first to identify MR as a predictor of AF recurrence in patients with HCM. Moreover, the CAAP-AF score was confirmed to be capable of forecasting the risk of AT/AF recurrence in this population. (III) RFCA was associated with substantial improvement in AF-related symptoms in patients with HCM. Those who maintained SR had a significantly better NYHA class, a reduced rate of worsening HF-related hospitalization, a reduced risk of thromboembolic events, and lower HCM-related mortality as compared to those who experienced recurrence in follow-up.

The reported rates of success for RFCA in AF among patients with HCM are extremely varied, ranging from 22.6% to 70% (16-19). Success from a single procedure occurs in approximately 30% of patients, and success rates can increase to around 50% after repeated procedures (20). A number of factors intrinsic to HCM are responsible for this heterogeneity, including increased LA volume, dysfunctional LA, and high prevalence of atrial fibrosis, which are well-documented predictors of the onset and perpetuation of AF in these patients (21,22). Hypertrophy of the myocardial sleeves that conduct PV triggers into the left atrium, and the higher prevalence of non-PV triggers also contribute to the risk of AF recurrence.

Gertz et al. found that MR increased LA size and AF persistence, which could lead to higher recurrence after ablation (61% vs. 46%, P=0.04). The size of left atrium was the only independent predictor of recurrence [odds ratio (OR) =2.9 per cm; P=0.005], indicating that MR is the cause of AF recurrence due to LA remodeling (23). Okada et al. examined functional MR (FMR) in AF patients with LVEF <50%. At 6 months after ablation, 66% and 3.6% of patients improved and worsened in FMR, respectively. FMR resolution correlated with larger LA ejection fraction (OR =3.55 per 10% increment; P<0.001) and lower LVED volume index (P<0.05). Residual moderate-to-severe FMR was linked to increased HF hospitalization and cardiovascular death (30.5% vs. 4.6%, P<0.001) (24). Cichoń et al. examined the effect of FMR on PVI in patients with ejection fraction ≥50%. FMR was identified in 74.3% of these patients with by transthoracic echocardiography and in 94.9% by transesophageal echocardiography. Additionally, severe FMR predicted reduced success at 3 months of PVI (P=0.012), and moderate-to-severe FMR had worse long-term outcomes (P=0.041) (25).

Genetic factors have also been recognized as key risk determinants of AF in patients with HCM. They include sarcomeric mutations such as MYH7 and MYBPC3, which are associated with the initiation and reinitiation of AF. It is likely that individuals with these mutations not only carry a heightened risk of developing AF but also possess typical electroanatomical changes. Electroanatomical mapping has demonstrated that patients with MYH7 and MYBPC3 mutations have more diffuse low-voltage electrographic activity of the left atrium, reflecting severe fibrosis. This fibrosis creates a pathologic substrate for atrial arrhythmogenesis, which explains why these patients have an increased rate of AF recurrence following catheter ablation in comparison to that in patients without disease-generating genetic variants (26,27).

Several predictors of AF recurrence after catheter ablation have been identified, such as greater LA volume, a characteristic of atrial remodeling in patients with HCM (28,29). Other predictors that have been associated with higher recurrence risks include female sex (20,21), obesity (18), nonapical HCM (21), persistent AF (30), diabetes mellitus, thyroid disease, LV apical aneurysm (14), and LVOT obstruction (31). These factors form a complex clinical profile, which demands individualized strategies be implemented to achieve rhythm control in these patients. Our study confirmed several of the previously reported predictors of AF recurrence, such as LAD, persistent AF, and female sex, emphasizing their important role in patient risk stratification. A novel finding was that moderate-to-severe MR was independently predictive of AF recurrence in patients with HCM undergoing RFCA. This highlights the interaction between hemodynamic factors, atrial remodeling, and rhythm control outcomes.

RFCA is a minimally invasive procedure that ameliorates arrhythmias via the ablation of targeted myocardial areas and has the advantages of precise lesion deposition, low tissue damage, and rapid recovery. However, even when treated with RFCA, a portion of patients with HCM may continue to experience MR. This may occur for several reasons: the typical myocardial hypertrophy of HCM may lead to LVOT obstruction and systolic anterior motion (SAM) of the mitral valve, which recur after RFCA; myocardial fibrosis, which impairs mitral valve function and may restrict valve closure; structural mitral valve disease (e.g., leaflet thickening or elongation of the chordae); and postoperative change in the cardiac electrophysiological environment, which indirectly impairs ventricular function and mitral valve performance. Therefore, RFCA, which focuses mainly on arrhythmias, might not treat the root pathological characteristics of HCM, leading to sustained MR (32-34).

MR, due it its contribution to increased LA volume and pressure, exacerbates atrial structural and functional derangements, thereby creating a proarrhythmic substrate (35). MR in patients with HCM may be caused by the SAM of mitral valve leaflets, annular remodeling, leaflet abnormalities, or alterations in the structure of the mitral apparatus (36). Experimental models suggest that MR increases LA reservoir strain and contractility, leading to increased interstitial atrial fibrosis (37). In addition, extensive LA fibrosis is related to increased LA size and reduced LA ejection fraction, indicating that the left atrium is not a neutral factor in MR but is actively involved in its pathophysiology (38).

In patients with HCM, severe MR correlates with LA myopathy regardless of LV diastolic function, systolic function, and LA size (39). The pathophysiology between atrial myopathy and AF is complex in the sense that atrial remodeling is both the cause and the effect of AF and hence constitutes a self-perpetuating process (40). Previous studies have established that MR severity correlates directly with AF recurrence in patients undergoing ablation for long-standing persistent AF and that patients with FMR have a lower rate of recurrent AF (41). In our study, moderate-to-severe MR was found to the strongest predictor of AF recurrence (HR =2.055; 95% CI: 1.212–3.485; P=0.008), which, to our knowledge, has not been reported elsewhere.

The European Society of Cardiology HCM-SCD 2014 risk calculator includes several high-risk factors for HCM, such as LV wall thickness, LA diameter, LVOT gradients, family history of SCD, and NSVT. The risk of SCD in these patients is usually considered high if the HCM risk exceeds 4% according to the HCM-SCD 2014 risk calculator, the point at which ICD is often warranted (42,43). This attests to the positive effects of RFCA for AF and SCD on the symptoms of patients with HCM, especially in reducing risk. However, despite risk reduction, the HCM-associated mortality is greater in high-risk patients, and thus close monitoring is advised (42,43). Patients with high-risk HCM tend to require CIEDs due to the persistence of VT and VF. Proper infection prevention and management strategies are of paramount concern in these patients (44,45). In our study, 19 patients required CIEDs, and augmented VT/VF and ICD therapy was administered in high-risk patients. In our study, there was a significant decrease in the mean mEHRA and NYHA class after ablation, especially for high-risk patients (≥4%). The SR and recurrence groups equally showed extreme risk reductions. The potential reasons for the decreased risk in SCD after RFCA may be as follows: (I) after catheter ablation in patients, the type and frequency of AF attacks decrease, resulting in improved cardiac function and reduced episodes of nonpersistent VT; (II) after catheter ablation, atrial remodeling occurs, and the anteroposterior and posterior diameters of the left atrium decrease compared with the anterior ones; and (III) the pressure decreases due to the obstruction in the outflow tract. Although ICD may be a confounding factor in the treatment of SCD, RFCA still effectively minimized SCD risk, especially among high-risk patients. These findings support the implementation of continuous monitoring and intervention to prevent fatal arrhythmic events.

Our results further emphasized the utility of the CAAP-AF score for the prediction of AT/AF recurrence in patients with HCM. This score, originally developed for the general AF population, demonstrated good predictive power in our HCM cohort (with a concordance statistic of 0.768; 95% CI: 0.685–0.850; P<0.001). A score ≥5 predicted AF recurrence with a sensitivity and specificity of 84.5% and 56.9%, respectively, a positive predictive value of 71.1%, and a negative predictive value of 58.9%, confirming the CAAP-AF score as a valuable tool for clinicians in patient counseling and procedure planning (15). These findings are particularly relevant given the challenge of achieving long-term SR in patients with HCM with extensive atrial fibrosis and non-PV triggers. One recent study reported that catheter ablation was able to maintain SR and delay the time to permanent AF as compared to medical treatment. It did not, however, significantly influence severe adverse cardiac events (46). Our study provided further evidence for the benefits of maintaining SR in patients with HCM. The mEHRA symptom classification score, as a measure of symptom severity, notably increased at follow-up as compared to baseline. Although no participants had improvement in the NYHA functional class, patients in the SR group had significant improvement and had better NYHA status than those in the recurrence group. Moreover, there were fewer thromboembolic events and hospitalizations for HF exacerbation in the SR group than in the recurrence group. These findings emphasize the clinical merits of maintaining SR in patients with HCM. Chronic SR promotes symptom burden reduction, decreases the thromboembolic risk, and reduces in HF-related hospitalizations due to improved filling in the SR. Our study supports the value of effective rhythm control strategies, such as RFCA, for the treatment of patients with HCM and AF.

Limitations

Certain limitations of this study should be addressed. First, the sample size was small, and our findings should be validated in larger prospective cohorts. Second, selection bias might have influenced the baseline characteristics and outcomes. Third, not all patients received CIEDs or underwent 7-day Holter monitoring, and thus, the AF recurrence rates might have been underestimated. Fourth, LA voltage mapping was not completed in all patients, and its relationship with AF recurrence could not be evaluated. Fifth, 19 patients in the study required CIEDs, with augmented VT/VF and ICD therapy being applied in high-risk patients, which may be a confounding factor for the results concerning SCD incidence. Finally, genetic testing for sarcomeric mutations was not conducted in any of the patients, and thus, data on the genetic factors of AF recurrence were not examined.

Conclusions

RCA was found to provide effective rhythm control for AF in patients with HCM. The predictors of recurrence of AF were identified to female gender, large LAD, and moderate-to-severe MR. The CAAP-AF score demonstrated excellent predictive power for AF recurrence. In addition to aiding in rhythm control, RFCA also ameliorated the symptoms related to AF. The patients with SR had better NYHA functional class than did those with recurrence, and thus emphasizing the benefits of clinical long-term rhythm control. Overall, RFCA reduces the risk of SCD, exacerbation of HF, and death due to HCM predominantly in high-risk patients requiring close follow-up.

Acknowledgments

None.

Footnote

Reporting Checklist: The authors have completed the STROBE reporting checklist. Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-196/rc

Data Sharing Statement: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-196/dss

Peer Review File: Available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-196/prf

Funding: This research was supported by the Noncommunicable Chronic Diseases-National Science and Technology Major Project (No. 2023ZD0504500).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://cdt.amegroups.com/article/view/10.21037/cdt-2025-196/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. This retrospective study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments and was approved by the Ethics Committee of The First Affiliated Hospital of Dalian Medical University. Informed consent was waived by the Ethics Committee due to the retrospective nature of the study. Dalian University of Technology Affiliated Central Hospital and The Affiliated Zhongshan Hospital of Dalian University were also informed of and agreed to the study protocol.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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(English Language Editor: J. Gray)