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Catheter Ablation of Atrial Fibrillation in Hypertrophic Cardiomyopathy: A Proportional Meta-Analysis and Systematic Review of Single Arm Studies

Open AccessPublished:January 11, 2023DOI:https://doi.org/10.1016/j.hroo.2023.01.002

      Abstract:

      Background

      Atrial fibrillation (AF) is the most common arrhythmia in patients with hypertrophic cardiomyopathy (HCM). Limited data exist about the efficacy and clinical outcomes of AF ablation in HCM.

      Objective

      The purpose of this meta-analysis was to evaluate the role of catheter-based ablation for treatment of AF in patients with HCM.

      Methods

      PubMed, SCOPUS, Web of Science, Embase, Cochrane library, and Clinicaltrials.gov were searched for studies discussing outcomes of catheter-based ablation for AF in patients with HCM. Two reviewers independently screened studies and extracted relevant data. Incidence rate estimates from individual studies underwent logit transformation to calculate the weighted summary proportion under the random effect model.

      Results

      A total of 19 reports met the inclusion criteria (1,183 patients). Single ablation procedure was successful in 39% patients. Up to 34% patients underwent a repeat ablation. About 41% patients in normal sinus rhythm after successful AF ablation received post-procedure anti-arrhythmic drug (AAD) therapy. Patients undergoing successful AF ablation experienced a significant improvement in the NYHA functional class (SMD -1.03[-1.23- -0.83], p<0.00001).

      Conclusion

      AF Ablation appears to be safe and feasible in patients with HCM. Freedom from AF after undergoing successful ablation is associated with significant improvement in heart failure symptoms.

      Key words

      1. Introduction

      Atrial fibrillation (AF) is the most common sustained arrhythmia in patients with hypertrophic cardiomyopathy (HCM) with a prevalence of 22-32%
      • Dinshaw L.
      • Münkler P.
      • Schäffer B.
      • et al.
      Ablation of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy: Treatment Strategy, Characteristics of Consecutive Atrial Tachycardia and Long-Term Outcome.
      ,
      • Falasconi G.
      • Pannone L.
      • Slavich M.
      • Margonato A.
      • Fragasso G.
      • Spoladore R.
      Atrial fibrillation in hypertrophic cardiomyopathy: pathophysiology, diagnosis and management.
      . Most patients with HCM and new-onset AF experience clinical decompensation manifesting as the progression of heart failure, stroke, and mortality
      • MacIntyre C.
      • Lakdawala N.K.
      Management of Atrial Fibrillation in Hypertrophic Cardiomyopathy.
      ,
      • Rowin E.J.
      • Hausvater A.
      • Link M.S.
      • et al.
      Clinical Profile and Consequences of Atrial Fibrillation in Hypertrophic Cardiomyopathy.
      . Although antiarrhythmic drugs (AAD) are utilized in patients with AF, their effectiveness and durable rhythm control can be challenging in patients with HCM due to progressive atrial cardiomyopathy, dilatation, and scarring

      Calkins H, Hindricks G, Cappato R, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 10 2017;14(10):e275-e444. doi:10.1016/j.hrthm.2017.05.012

      ,
      • Chung M.K.
      • Refaat M.
      • Shen W.K.
      • et al.
      Atrial Fibrillation: JACC Council Perspectives.
      . AF ablation with isolation of the pulmonary veins (PVI) is implemented in many patients with symptomatic AF and is more effective rhythm control than AAD

      Calkins H, Hindricks G, Cappato R, et al. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of atrial fibrillation. Heart Rhythm. 10 2017;14(10):e275-e444. doi:10.1016/j.hrthm.2017.05.012

      ,
      • Cheung C.C.
      • Nattel S.
      • Macle L.
      • Andrade J.G.
      Management of Atrial Fibrillation in 2021: An Updated Comparison of the Current CCS/CHRS, ESC, and AHA/ACC/HRS Guidelines.
      . Several observational studies have shown that patients with HCM can safely undergo AF ablation with favorable outcomes
      • Zhao D.S.
      • Shen Y.
      • Zhang Q.
      • et al.
      Outcomes of catheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy: a systematic review and meta-analysis.
      • Ha H.S.
      • Wang N.
      • Wong S.
      • et al.
      Catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy patients: a systematic review.
      • Gaita F.
      • Di Donna P.
      • Olivotto I.
      • et al.
      Usefulness and safety of transcatheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy.
      . Meta-analysis performed by Providencia et al. in 2016 reported single ablation success rates of 38.7% in patients with HCM
      • Providencia R.
      • Elliott P.
      • Patel K.
      • et al.
      Catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy: a systematic review and meta-analysis.
      . However, little is known about symptomatic improvement, redo ablations, and the burden of AAD use following the first successful ablation. Thus, we conducted this meta-analysis to study the outcomes of AF ablation in patients with HCM.

      2. Materials and Methods

      2.1 Data Sources and Search Strategy

      This review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines
      • Moher D.
      • Liberati A.
      • Tetzlaff J.
      • Altman D.G.
      • Group P.
      Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement.
      . The protocol for this meta-analysis is currently under review at PROSPERO, the international prospective register of systematic reviews. A systematic search, without language restriction, was performed through PubMed, Scopus, Web of Science, Embase, Cochrane library, and Clinicaltrials.gov from inception to July 31st, 2022 for studies reporting AF ablation in patients with HCM. The keywords used for searching include “atrial fibrillation”, “AF”, “hypertrophic cardiomyopathy”, “HCM”, “catheter ablation”, and “ablation”. In addition, we manually reviewed and searched references of related articles to identify additional relevant studies.

      2.2 Study Selection, data extraction, and quality assessment

      Studies were included if they met the following criteria: (1) randomized trials or observational studies that included adults aged ≥ 18 years, (2) studies that evaluated the efficacy and safety of AF ablation in HCM, and (3) Studies with primary reports of freedom from AF after ablation. We excluded review articles and case reports. Titles and abstracts were screened independently by the two authors (AL and MJA) for relevance. The full text of the potentially eligible studies was then retrieved and evaluated for eligibility through a full-text review. Any disagreements in the screening process were resolved through discussion and consensus among the authors. Two reviewers (SA and MJA) independently extracted data using a standardized data collection excel sheet. We assessed the study quality using the previously published version of quality assessment criteria for case series
      • Chambers D.
      • Rodgers M.
      • Woolacott N.
      Not only randomized controlled trials, but also case series should be considered in systematic reviews of rapidly developing technologies.
      .

      2.3 Outcomes of Interest

      Our primary outcome was (1) freedom from AF recurrence after single ablation. Other outcomes included: (2) patients undergoing redo ablation, (3) freedom from AF recurrence after redo ablation, (4) prevalence of AAD therapy use after successful ablation, and (5) pre- and post-ablation New York Heart Failure Association (NYHA) functional class.

      2.4 Statistical Analysis

      Meta-analysis was performed using the random-effects model. We used ‘metaprop’ command in Stata 17.0 (Stata Statistical Software: College Station, TX: Stata Corp LP) to perform the proportional meta-analysis. We used ‘ftt cimethod’ (method) for the transformation of incidence rate estimates from individual studies to calculate the weighted summary proportions. Statistical heterogeneity was assessed using Higgins and Thompson I2 statistics and the Galbraith graph. Publication bias was assessed using the funnel plot, Egger’s test, and Begg’s test. The trim-and-fill method of Duval and Tweedie was used to further detect and adjust for the small study effects. Review Manager software (version 5.4, The Nordic Cochrane Centre, The Cochrane Collaboration: Copenhagen, Denmark) was used to calculate the standardized mean difference (SMD) with a 95% confidence interval (CI) for the NYHA variable. P-value of less than 0.05 was considered statistically significant. Statistical analysis was performed by SA and reviewed by MJA.

      3. Results

      3.1 Systematic review and study population

      We identified 19 studies with 1,183 patients for our final analysis
      • Dinshaw L.
      • Münkler P.
      • Schäffer B.
      • et al.
      Ablation of Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy: Treatment Strategy, Characteristics of Consecutive Atrial Tachycardia and Long-Term Outcome.
      ,
      • Gaita F.
      • Di Donna P.
      • Olivotto I.
      • et al.
      Usefulness and safety of transcatheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy.
      ,
      • Kilicaslan F.
      • Verma A.
      • Saad E.
      • et al.
      Efficacy of catheter ablation of atrial fibrillation in patients with hypertrophic obstructive cardiomyopathy.
      • Di Donna P.
      • Olivotto I.
      • Delcrè S.D.
      • et al.
      Efficacy of catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy: impact of age, atrial remodelling, and disease progression.
      • Santangeli P.
      • Di Biase L.
      • Themistoclakis S.
      • et al.
      Catheter ablation of atrial fibrillation in hypertrophic cardiomyopathy: long-term outcomes and mechanisms of arrhythmia recurrence.
      • Derejko P.
      • Polańska M.
      • Chojnowska L.
      • et al.
      Catheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy: atrial fibrillation type determines the success rate.
      • Hayashi H.
      • Hayashi M.
      • Miyauchi Y.
      • et al.
      Left atrial wall thickness and outcomes of catheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy.
      • Wen S.
      • Liu N.
      • Li S.
      • et al.
      [Predictors of atrial fibrillation recurrence after catheter ablation in hypertrophic cardiomyopathy patients with atrial fibrillation].
      • Contreras-Valdes F.M.
      • Buxton A.E.
      • Josephson M.E.
      • Anter E.
      Atrial fibrillation ablation in patients with hypertrophic cardiomyopathy: long-term outcomes and clinical predictors.
      • Okamatsu H.
      • Ohara T.
      • Kanzaki H.
      • et al.
      Impact of left ventricular diastolic dysfunction on outcome of catheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy.
      • Bassiouny M.
      • Lindsay B.D.
      • Lever H.
      • et al.
      Outcomes of nonpharmacologic treatment of atrial fibrillation in patients with hypertrophic cardiomyopathy.
      • Müssigbrodt A.
      • Kosiuk J.
      • Koutalas E.
      • et al.
      Results of catheter ablation of atrial fibrillation in hypertrophied hearts - Comparison between primary and secondary hypertrophy.
      • Roh S.Y.
      • Kim D.H.
      • Ahn J.
      • et al.
      Long-Term Outcome of Catheter Ablation for Atrial Fibrillation in Patients With Apical Hypertrophic Cardiomyopathy.
      • Chen X.
      • Dong J.Z.
      • Du X.
      • et al.
      Long-term outcome of catheter ablation for atrial fibrillation in patients with apical hypertrophic cardiomyopathy.
      • Zheng S.
      • Jiang W.
      • Dai J.
      • et al.
      Five-year outcomes after catheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy.
      • Creta A.
      • Elliott P.
      • Earley M.J.
      • et al.
      Catheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy: a European observational multicentre study.

      Q. Yan JZD, D.Y. Long, R.H. Yu, R.B. Tang, X. Du, R. Bai, C.S. Ma, Catheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy, European Heart Journal , Volume 34, Issue suppl_1, 1 August 2013, P548, https://doi.org/10.1093/eurheartj/eht307.P548.

      • Castagno D.
      • Di Donna P.
      • Olivotto I.
      • et al.
      Transcatheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy: Long-term results and clinical outcomes.
      • McCready J.W.
      • Smedley T.
      • Lambiase P.D.
      • et al.
      Predictors of recurrence following radiofrequency ablation for persistent atrial fibrillation.
      . All selected studies were observational (12 prospective and 7 retrospective), and single arm in design (Figure 1). Mean age across studies was 55 years, females were 29%. Baseline study and patient characteristics are summarized in table 1 and table 2, respectively.
      Figure thumbnail gr1
      Figure 1PRISMA flow chart depicting the screening process for included studies.
      Table 1Study Characteristics
      First author, yearStudy designCountry of originNumber of HCM patient (n)Mean follow-up durationCatheter Ablation TechniqueMethod of AF Detection
      Kilicaslan, 2006RetrospectiveUS, Brazil, Italy27341 + 237 daysRFRhythm transmitter, Holter monitor
      Gaita, 2007ProspectiveItaly2619 + 10 monthsRF12-lead EKG, 24-h Holter monitor
      Di Donna, 2010RetrospectiveItaly, France6129 + 16 monthsRF12-lead EKG,24-h Holter monitor
      McCready, 2011ProspectiveUK19113 + 9 monthsRF12-lead EKG, 1–7-day Holter monitor, cardiac device interrogation (if available)
      Derejko, 2013ProspectivePoland301.9 + 1.2 yearsRF12-lead EKG, 48-h Holter monitor
      Santangeli, 2013ProspectiveUS, Italy4342 [38-48] monthsRF12-lead EKG, 7-day Holter monitor
      Hayashi, 2014RetrospectiveJapan1726 + 14 monthsRFCardiac event recorder, 12-lead EKG, 24-h Holter monitor
      Bassiouny, 2015RetrospectiveUS7928 [9-51] monthsRFHolter monitor, cardiac device interrogation (if available)
      Contreras Valdes, 2015RetrospectiveUS4054 [22-67] monthsRFN/A
      Mussigbrodt, 2014ProspectiveGermany, Greece2212 + 11 monthsRF7-day Holter monitor, cardiac device interrogation (if available)
      Okamatsu, 2015ProspectiveJapan2221 + 12 monthsRF12-lead EKG, Holter monitor
      Wen, 2015ProspectiveChina3914.8 monthsRF12-lead EKG, 24-h Holter monitor
      Roh, 2016ProspectiveKorea3144.7 + 30.8 monthsRF12-lead EKG, 24-h Holter monitor
      Yan, 2017RetrospectiveChina253.39 + 1.17 yearsRFN/A
      Chen, 2018ProspectiveChina9744.3 + 29.6 monthsRF12-lead EKG, 24-h Holter monitor
      Castagno, 2020ProspectiveItaly, France1166 [3-8.9] yearsRF12-lead EKG, 24-h Holter monitor, cardiac device interrogation (if available)
      Zheng, 2020RetrospectiveChina12061.9 + 31.6 monthsRF12-lead EKG, 24-h Holter monitor
      Creta, 2021ProspectiveUK, Italy, France13743.8 + 37 monthsCryo or RF12-lead EKG, 24-h Holter monitor, cardiac device interrogation (if available)
      Dinshaw, 2021ProspectiveGermany6548.1 + 32.5 monthsCryo or RF24-h Holter monitor
      RF: Radiofrequency ablation, Cryo: Cryoablation, N/A: not available
      Table 2Baseline patient characteristics
      First author, yearAge (years)

      [Mean+/-SD]
      Female

      n(%)
      Non-paroxysmal AF n(%)AF duration (years) [Mean+/-SD]LA volume (ml)LA diameter (mm) [Mean+/-SD]Mitral regurgitation n(%)LVOT obstruction n(%)Previous myomectoy or septal ablation n(%)Interventricular Septum (mm) [Mean+/-SD]LVEF (%) [Mean+/-SD]No. of failed AAD’s [Mean+/-SD]
      Kilicaslan, 200655 +/- 108 (30%)13 (48%)5.4 +/- 3.6NR50 +/- 920 (74%)12 (44%)NR17 +/- 555 +/- 83.0 +/- 1.2
      Gaita, 200758 +/- 118 (31%)13 (50%)7.3 +/- 6.2170 +/- 4852 +/- 621 (81%)6 (23%)5 (19%)NR57 +/- 42.3 +/- 1.4
      Di Donna, 201054 +/- 1317 (28%)26 (43%)5.7 +/- 5.5140 [125-180]51 +/- 6.750 (86%)12 (20%)6 (10%)NR59 +/- 8NR
      McCready, 201158.2 +/- 12.940 (21%)168 (88%)4.0 +/- 3.7NR47 +/- 7NRNRNRNR57 +/- 11NR
      Derejko, 201348.7 +/- 1110 (33%)16 (53.3%)6 +/- 4.2180 +/- 47NRNR6/30 (20%)2 (7%)20.5 +/- 6.3NR1.8 +/- 1.2
      Santangeli, 201359 +/- 814 (33%)31 (72%)3NR50.8 +/- 6.8NRNRNRNR59 +/- 6NR
      Hayashi, 201463 +/- 125 (29%)9 (53%)3.5 +/- 3.5NR46 +/- 73 (18%)NR7 (41%)19 +/- 471 +/- 101.7 +/- 1.2
      Bassiouny, 201555.3 +/- 12.222 (28%)45 (57%)3 [1.4- 7.8]NR50.1 +/- 9.146 (58%)22 (28%)NR19.0 +/- 4.756.1 +/- 7.9NR
      Contreras Valdes, 201554.3 +/- 7.312 (30%)27 (67.5%)NRNRNRNR15 (37.5%)NRNRNRNR
      Mussigbrodt, 201457 +/- 87 (32%)12 (55%)NRNR46 +/- 83 (14%)NRNR19 +/- 460 +/- 7NR
      Okamatsu, 201565 +/- 1112 (54.5%)17 (77%)6.6 +/- 4.498 +/- 3848 +/- 65 (22.7%)3 (13.6%)NRNR57 +/- 14NR
      Wen, 201554.0 +/- 10.110 (25.6%)12 (31%)5.8 +/- 5.6NR45.8 +/- 6.710 (25.6%)NR0 (0%)NR64.9 +/- 8.6NR
      Roh, 201657.5 +/- 11.55 (16.1%)18 (58%)5.1NR47 +/- 102 (6.5%)NRNR15.560.5NR
      Yan, 201753.4 +/- 86 (24%)9 (36%)NRNR47.4 +/- 7.51NRNRNRNRNRNR
      Chen, 201857.628 (28.8%)41 (42.2%)2.5NR44.6NRNRNR14.265.2NR
      Castagno, 202053.6 +/- 11.434 (29%)73 (63%)5.0 +/- 5.6168 +/- 41NR100 (86%)25 (22%)22 (19%)21 +/- 557 +/- 6NR
      Zheng, 202061 +/- 9.843 (35.8%)60 (50%)NRNR47 +/- 6NR22 (18.3%)NR18 +/- 5.162 +/- 4.7NR
      Creta, 202155 +/- 13.439 (29.1%)57 (41.5%)3.3 +/- 3.1NR47 +/- 714 (12.2%)NR20 (14.9%)NR58 +/- 0NR
      Dinshaw, 202164.5 +/- 9.923 (35%)52 (80%)NR54.1 +/- 12.554.1 +/- 12.555 (84.5%)NR8 (12.3%)18.6 +/- 4.254.4 +/- 14.6NR

      3.2 Freedom from AF recurrence after single ablation

      All 19 studies reported the success rate after single ablation as freedom from AF recurrence. Single-procedure freedom from AF in our pooled analysis (n=1,183) was 39% (95%CI: 35%-44%, I2 = 50%) (Figure 2). Meta-regression for the year of study (p = 0.48) and baseline NYHA score (p = 0.15) did not reveal any significant impact on single ablation success to prevent AF recurrence (Supplementary Figures 1A and 1B, Supplementary Material). Galbraith plot was constructed for heterogeneity that did not reveal any outlier studies (Supplementary Figure 2, Supplementary Material). Although publication bias was suggested by a visually asymmetric funnel plot (Supplementary Figure 3A, Supplementary Material) and Egger’s test (Egger’s test, p = 0.01; Begg’s test, p = 0.10), the trim-and-fill method (Supplementary Figure 3B, Supplementary Material) confirmed the stability of pooled analysis with no significant change in the imputed result.
      Figure thumbnail gr2
      Figure 2Forest plot for freedom from atrial fibrillation (AF) recurrence after single ablation.

      3.3 Prevalence of redo ablation

      Data regarding the use of a second ablation procedure in patients with HCM was provided by 15/19 studies. The pooled analysis (n=241) showed prevalence of repeat ablation as 34% ((95%CI: 28%-40%), I2 = 73%) (Figure 3).
      Figure thumbnail gr3
      Figure 3Forest plot for prevalence of redo ablation.

      3.4 Freedom from AF recurrence after redo ablation

      Total 11/19 studies reported outcome data regarding freedom from AF recurrence after the second ablation. Redo procedure freedom from AF in pooled analysis (n=241) was 52% ((95%CI: 36%-67%), I2 = 78%) (Figure 4).
      Figure thumbnail gr4
      Figure 4Forest plot for freedom from atrial fibrillation (AF) recurrence after redo ablation.

      3.5 Utilization of antiarrhythmic drug therapy after successful ablation

      Total 10/19 studies provided information about the long-term use of antiarrhythmic drugs in patients with HCM after successful ablation. This pooled analysis (n=425) result was 41% ((95%CI: 17%-66%), I2 = 98%) (Figure 5).
      Figure thumbnail gr5
      Figure 5Forest plot for utilization of anti-arrhythmic drug (AAD) therapy after successful ablation.

      3.6 Change in NYHA functional class after ablation

      5/10 studies reported baseline and post-procedural NYHA functional class in HCM patients undergoing AF ablation. One study
      • Bassiouny M.
      • Lindsay B.D.
      • Lever H.
      • et al.
      Outcomes of nonpharmacologic treatment of atrial fibrillation in patients with hypertrophic cardiomyopathy.
      did not report standard deviations, so 4/10 studies were included in the final analysis (n=223) that showed a significant improvement in NYHA status after successful AF ablation (SMD -1.03 (95%CI: -1.23- -0.83, p < 0.00001), I2 = 0%) (Figure 6).
      Figure thumbnail gr6
      Figure 6Forest plot showing change in NYHA functional class after successful ablation.

      3.7 Quality assessment of included studies

      We assessed the study quality using the previously published version of quality assessment criteria for case series. We used a quality assessment tool for case series to evaluate single arm studies included in our meta-analysis
      • Chambers D.
      • Rodgers M.
      • Woolacott N.
      Not only randomized controlled trials, but also case series should be considered in systematic reviews of rapidly developing technologies.
      . We have reported the detailed outline of the risk of bias (supplementary Table 1).

      4. Discussion

      The systematic review and meta-analysis on the outcomes of AF ablation in patients with HCM suggest that catheter ablation is safe but less effective in HCM patients compared to the general AF ablation population. Many HCM patients required repeat ablations and post-procedure AAD therapy to maintain sinus rhythm. There was a significant improvement in heart failure symptoms after successful AF ablation. This study included 19 studies with 1,183 patients when compared to previous meta-analyses with a sample size of 531 patients which furthered the evidence of catheter ablation for AF in HCM patients.
      • Zhao D.S.
      • Shen Y.
      • Zhang Q.
      • et al.
      Outcomes of catheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy: a systematic review and meta-analysis.
      ,
      • Providencia R.
      • Elliott P.
      • Patel K.
      • et al.
      Catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy: a systematic review and meta-analysis.
      . In addition, we have studied a new outcome consisting of the degree of improvement in NYHA functional status after successful AF ablation in HCM patients, which has not been reported in prior meta-analyses
      • Zhao D.S.
      • Shen Y.
      • Zhang Q.
      • et al.
      Outcomes of catheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy: a systematic review and meta-analysis.
      ,
      • Providencia R.
      • Elliott P.
      • Patel K.
      • et al.
      Catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy: a systematic review and meta-analysis.
      .
      HCM is an inheritable cardiomyopathy that globally affects every 1 in 500 adults with an incidence of device-detected, de-novo AF in up to 50% of patients
      • Wilke I.
      • Witzel K.
      • Münch J.
      • et al.
      High Incidence of De Novo and Subclinical Atrial Fibrillation in Patients With Hypertrophic Cardiomyopathy and Cardiac Rhythm Management Device.
      ,
      • Abdelazeem B.
      • Abbas K.S.
      • Ahmad S.
      • Raslan H.
      • Labieb F.
      • Savarapu P.
      The Effect of Angiotensin II Receptor Blockers in Patients with Hypertrophic Cardiomyopathy: An Updated Systematic Review and Meta-analysis of Randomized Controlled Trials.
      . Given high preload dependence in patients with HCM, loss of atrial kick with new-onset AF results in decreased ventricular filling, resulting in reduced cardiac output. This reduction in cardiac function is often poorly tolerated in patients with HCM and is associated with worsening heart failure symptoms and impaired quality of life
      • Rowin E.J.
      • Hausvater A.
      • Link M.S.
      • et al.
      Clinical Profile and Consequences of Atrial Fibrillation in Hypertrophic Cardiomyopathy.
      ,
      • Maron B.J.
      • Desai M.Y.
      • Nishimura R.A.
      • et al.
      Management of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review.
      . Maintenance of sinus rhythm is associated with a marked reduction in cardiovascular events in the general population
      • Chung M.K.
      • Refaat M.
      • Shen W.K.
      • et al.
      Atrial Fibrillation: JACC Council Perspectives.
      ,
      • Wyse D.G.
      • Waldo A.L.
      • DiMarco J.P.
      • et al.
      A comparison of rate control and rhythm control in patients with atrial fibrillation.
      . Although prior randomized trials revealed no significant difference in major cardiovascular outcomes between rate and rhythm control strategies, some randomized studies, including the AFFIRM trial, did not account for patient crossover from rate to rhythm control groups due to heart failure and uncontrolled symptoms with a rate control only strategy

      Camm AJ, Naccarelli GV, Mittal S, et al. The Increasing Role of Rhythm Control in Patients With Atrial Fibrillation: JACC State-of-the-Art Review. J Am Coll Cardiol. 05 17 2022;79(19):1932-1948. doi:10.1016/j.jacc.2022.03.337

      ,
      • Kirchhof P.
      • Camm A.J.
      • Goette A.
      • et al.
      Early Rhythm-Control Therapy in Patients with Atrial Fibrillation.
      . The recently published EAST-AFNET 4 trial supports early rhythm control with either AAD therapy or AF ablation
      • Kirchhof P.
      • Camm A.J.
      • Goette A.
      • et al.
      Early Rhythm-Control Therapy in Patients with Atrial Fibrillation.
      ,
      • Willems S.
      • Borof K.
      • Brandes A.
      • et al.
      Systematic, early rhythm control strategy for atrial fibrillation in patients with or without symptoms: the EAST-AFNET 4 trial.
      . Rhythm control may be preferred early in the disease course in high-risk patients with HCM to potentially prevent progressive atrial remodeling with uncontrolled AF
      • Rowin E.J.
      • Hausvater A.
      • Link M.S.
      • et al.
      Clinical Profile and Consequences of Atrial Fibrillation in Hypertrophic Cardiomyopathy.
      ,
      • Maron B.J.
      • Desai M.Y.
      • Nishimura R.A.
      • et al.
      Management of Hypertrophic Cardiomyopathy: JACC State-of-the-Art Review.
      .
      Rhythm control using pharmacologic strategies has been successfully used in patients without HCM. AADs have limited efficacy in patients with HCM due to the presence of abnormal electrophysiologic substrate and are associated with increased hospitalizations for drug titration and long-term adverse effects
      • Di Donna P.
      • Olivotto I.
      • Delcrè S.D.
      • et al.
      Efficacy of catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy: impact of age, atrial remodelling, and disease progression.
      ,
      • Sivalokanathan S.
      • Zghaib T.
      • Greenland G.V.
      • et al.
      Hypertrophic Cardiomyopathy Patients With Paroxysmal Atrial Fibrillation Have a High Burden of Left Atrial Fibrosis by Cardiac Magnetic Resonance Imaging.
      . The STOP-AF trial reported that cryoablation as initial therapy had better outcomes as compared to AAD therapy in patients with paroxysmal AF
      • Wazni O.M.
      • Dandamudi G.
      • Sood N.
      • et al.
      Cryoballoon Ablation as Initial Therapy for Atrial Fibrillation.
      . In previous studies, single catheter ablation AF carries a success rate of up to 75%

      Camm AJ, Naccarelli GV, Mittal S, et al. The Increasing Role of Rhythm Control in Patients With Atrial Fibrillation: JACC State-of-the-Art Review. J Am Coll Cardiol. 05 17 2022;79(19):1932-1948. doi:10.1016/j.jacc.2022.03.337

      ,
      • Packer D.L.
      • Piccini J.P.
      • Monahan K.H.
      • et al.
      Ablation Versus Drug Therapy for Atrial Fibrillation in Heart Failure: Results From the CABANA Trial.
      . For patients with HCM, our pooled analysis showed a much lower single ablation success rate of 39%, which is similar to previously performed meta-analyses
      • Zhao D.S.
      • Shen Y.
      • Zhang Q.
      • et al.
      Outcomes of catheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy: a systematic review and meta-analysis.
      ,
      • Providencia R.
      • Elliott P.
      • Patel K.
      • et al.
      Catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy: a systematic review and meta-analysis.
      . In addition, to assess if the improving ablation technology and operator experience over the years had any significant impact on the first ablation success rate, we performed meta-regression analysis using the study year as covariate that did not reveal any significant association.
      Given the increased AF recurrence in HCM patients, a significant proportion of patients undergo repeat ablation procedures and maintenance AAD therapy. McCready et al., 2011 reported a second ablation procedure in 71% of HCM patients followed by a third and fourth procedure in 14% and 7% of HCM patients, respectively
      • McCready J.W.
      • Smedley T.
      • Lambiase P.D.
      • et al.
      Predictors of recurrence following radiofrequency ablation for persistent atrial fibrillation.
      . Similarly, long-term use of AAD to maintain sinus rhythm is higher in the HCM population as compared to the general population
      • Pokushalov E.
      • Romanov A.
      • De Melis M.
      • et al.
      Progression of atrial fibrillation after a failed initial ablation procedure in patients with paroxysmal atrial fibrillation: a randomized comparison of drug therapy versus reablation.
      . This increased frequency of AF recurrence, redo ablation, and AAD therapy use has been linked to the presence of multiple arrhythmogenic foci outside pulmonary vein territory, cellular level mutations in the sarcomere proteins, mitral regurgitation, progressive atrial dilatation, and atrial scarring in patients with HCM
      • Wen S.
      • Liu N.
      • Li S.
      • et al.
      [Predictors of atrial fibrillation recurrence after catheter ablation in hypertrophic cardiomyopathy patients with atrial fibrillation].
      ,
      • Okamatsu H.
      • Ohara T.
      • Kanzaki H.
      • et al.
      Impact of left ventricular diastolic dysfunction on outcome of catheter ablation for atrial fibrillation in patients with hypertrophic cardiomyopathy.
      .
      Data regarding symptomatic improvement after successful catheter ablation of AF patients with HCM is scarce. Therefore, we looked at the pre-ablation and post-ablation NYHA functional status of the included patients. Although only four studies reported this data, there is a clear signal toward the improvement of symptoms after undergoing successful ablation. This can be explained by HCM patients with the successful restoration of atrial kick in sinus rhythm leading to the better filling of the less compliant left ventricular chamber and improved cardiac output. Better cardiac function is associated with symptomatic improvement in patients with HCM. Interestingly, Di Donna et al., 2010 reported significant improvement in NYHA class even in patients with recurrence of AF
      • Di Donna P.
      • Olivotto I.
      • Delcrè S.D.
      • et al.
      Efficacy of catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy: impact of age, atrial remodelling, and disease progression.
      . However, it was less marked than in patients who were in sinus rhythm
      • Di Donna P.
      • Olivotto I.
      • Delcrè S.D.
      • et al.
      Efficacy of catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy: impact of age, atrial remodelling, and disease progression.
      . Conversely, Gaita et al., 2007 demonstrated no change in functional in patients who failed AF ablation
      • Gaita F.
      • Di Donna P.
      • Olivotto I.
      • et al.
      Usefulness and safety of transcatheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy.
      .
      Our meta-analysis provides valuable insight into outcomes of AF ablation in a high-risk patient population with HCM. Our study reported single ablation success rate of 39% that is in line with prior meta-analyses by Zhao et al and Providencia et al with reported single ablation success rate of 45% and 39%, respectively
      • Zhao D.S.
      • Shen Y.
      • Zhang Q.
      • et al.
      Outcomes of catheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy: a systematic review and meta-analysis.
      ,
      • Providencia R.
      • Elliott P.
      • Patel K.
      • et al.
      Catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy: a systematic review and meta-analysis.
      . In addition, our study reports significant improvement in patients’ heart failure functional class after successful ablation, an outcome that has not been studied in prior meta-analyses
      • Zhao D.S.
      • Shen Y.
      • Zhang Q.
      • et al.
      Outcomes of catheter ablation of atrial fibrillation in patients with hypertrophic cardiomyopathy: a systematic review and meta-analysis.
      ,
      • Providencia R.
      • Elliott P.
      • Patel K.
      • et al.
      Catheter ablation for atrial fibrillation in hypertrophic cardiomyopathy: a systematic review and meta-analysis.
      . This study also has several limitations. First, there is heterogeneity in reported outcomes due to variability among included studies in terms of follow-up duration, method of AF detection, and non-uniform criterion for redo ablation and AAD use after ablation procedures. Given the heterogeneity of included studies, we generated the Galbraith plot and conducted regression analysis that did not show any outlier studies or significant covariates. Second, publication bias is present in included studies, but the trim-and-fill method confirmed the stability of our results. Third, although most studies were good quality single-arm studies on our quality assessment, a few studies had limited data recruitment and follow up. Lastly, given the lack of control cohorts in included studies, we could not compare the success rate for AF ablation in HCM patients with those without HCM.

      5. Conclusions

      Although many HCM patients undergoing catheter ablation for AF may require redo ablations and AAD therapy to prevent AF recurrence, this updated analysis with significantly more patients continues to suggest that AF ablation in HCM appears safe and is associated with improvement in symptoms. In the future, randomized studies with longer follow-up duration should be conducted to establish higher quality evidence to better inform patient selection, procedural complications, and long-term outcomes associated with catheter ablation for AF in patients with HCM.

      Supplementary Material

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