Clinical outcomes of radiofrequency catheter ablation of ventricular tachycardia in patients with hypertrophic cardiomyopathy

Abstract

Background

Monomorphic ventricular tachycardia (VT) is rare in patients with hypertrophic cardiomyopathy (HCM), management of which is challenging. Limited data exists on the utility of catheter ablation for the treatment of VT in this population.

Objectives

We aimed to assess clinical outcomes of catheter ablation for VT in HCM patients.

Methods

A systematic search, without language restriction, using PubMed, EMBASE, SCOPUS, Google Scholar, and ClinicalTrials.gov was performed. The meta‐analysis was performed using a meta‐package for R version 4.0/RStudio version 1.2 and Freeman Tukey double arcsine method to establish the variance of raw proportions. Outcomes measured included (1) acute procedure success (defined as noninducible for clinical VT), (2) freedom from VT at follow‐up, (3) mortality.

Results

This systematic review of six studies (three from the United States and three from Japan) incorporated a total of 68 drug‐refractory HCM patients who underwent VT radiofrequency catheter ablation (mean age 57.6 ± 13.3 years, mean LVEF 45.8 ± 15.4%, 85% men, maximum septal wall thickness 17.4 ± 4.6 mm, and 32.3% with an apical aneurysm). Acute procedural success was achieved in 84.5% patients (95% confidence interval [CI]: 70.6%–95.2%) with 27.9% patients had recurrent VT requiring multiple ablations (median 1, IQR 1–3). During the follow‐up period (18.3 ± 11.7 months), the pooled incidence of freedom from recurrent VT after index procedure was 70.2% (95% CI: 51.9%–86.2%), while after the last ablation was 82.8% (95% CI: 57%–99.2%). There were two deaths during follow‐up, one from heart failure and one from SCD 0.8% (95% CI: 0%–5.8%).

Conclusion

The results of our pooled analysis demonstrated that catheter ablation for VT in HCM patients was associated with high acute procedural success, and reduced VT recurrence—findings comparable to previously published reports in other disease substrates.

Sustained ventricular arrhythmias (VAs) are the primary cause of sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) patients. While HCM patients with a high risk of SCD require primary prevention implantable cardiac defibrillator (ICD), frequent VT and electrical storm can occur, resulting in multiple ICD shocks and poor quality of life. Therefore, we aimed to perform a systematic review of clinical outcomes of catheter ablation for VT in HCM patients. Electronic databases were searched from inception until January 15th, 2022, using the keyword‐“hypertrophic cardiomyopathy” and “ventricular tachycardia ablation.” Isolated case reports were excluded. This systematic review was performed according to the PRISMA guidelines (PROSPERO ID 309176). We used Freeman‐Tukey double arcsine method to establish the variance of raw proportions. Hartung–Knapp–Sidik–Jonkman method with the random‐effect model was used to combine transformed proportions. Finally, we then back‐transformed the pooled estimates and plotted the data on a forest plot. A two‐tailed p < .05 was considered statistically significant for all analyses. The meta‐analysis was performed using a meta‐package for R version4.0/RStudio version 1.2. Outcomes measured included (1) acute procedure success (defined as noninducible for clinical VT), (2) freedom from VT at follow‐up, (3) procedural complications, and (4) mortality. We also performed subgroup analysis for studies comparing outcomes of VT ablation in HCM patients with AA versus dilated‐phase. The outcomes studied—acute procedure success (defined as noninducible for clinical VT), and (2) freedom from VT at follow‐up.

This systematic review of six studies (three from United States ¹ , ² , ³ and three from Japan  ⁴ , ⁵ , ⁶ ) incorporated a total of 68 drug‐refractory HCM patients who underwent VT radiofrequency catheter ablation (mean age 57.6 ± 13.3 years, mean LVEF 45.8 ± 15.4%, 85% men, maximum septal wall thickness 17.40 ± 4.6 mm, 32.3% with an apical aneurysm, and 79.4% had open‐irrigated catheter ablation). Sixty‐one (89.7%) patients were on at least one antiarrhythmic drug including amiodarone (69%), lidocaine (20%), mexiletine (17.5%), sotalol (17.5%), procainamide (5%), and disopyramide (2%). Combined epicardial‐endocardial ablation was performed in 41.2% of patients, while 50% and 9% underwent endocardial‐only and epicardial‐only ablation, respectively. Acute procedural success was achieved in 84.5% patients (95% CI: 70.6%–95.2%), with 27.9% of patients had recurrent VT requiring multiple ablations (median 1, IQR 1–3). During the follow‐up period (18.3 ± 11.7 months), the pooled incidence of freedom from recurrent VT after the index procedure was 70.2% (95% CI: 51.9%–86.2%); while after the last ablation was 82.8% (95% CI: 57.0%–99.2%) (Figure 1). In subgroup analysis, the pooled incidence of acute procedure success (96.45%; 95% CI: 87.9–100; I ² = 0% vs. 85%; 95% CI: 68.5–97.1; I ² = 0%; p _interaction = 0.02), and freedom from recurrent VT after last ablation (96.45%; 95% CI: 87.9–100; I ² = 0% vs. 79.7%; 95% CI: 51.3–98.9; I ² = 10%; p _interaction = 0.03) was significantly higher in HCM patients with AA compared to dilated‐phase HCM patients, respectively. Furthermore, ablation for VT in HCM patients with AA demonstrated a trend toward freedom from recurrent VT after index ablation compared to dilated‐phase HCM patients (88.6%; 95% CI: 53.1–100; I ² = 0% vs. 67.4%; 95% CI: 40.2–90.6; I ² = 8%; p _interaction = 0.11) (Figure 2). There were eight adverse events 9.1% (95% CI: 0%–28.9%), including two pericardial effusions requiring pericardiocentesis (one periprocedural while the other due to supratherapeutic INR at follow‐up), two complete atrioventricular block (one transient and one permanent), one left anterior descending artery occlusion, one transient phrenic nerve palsy, and two groin hematomas at follow‐up. There were two deaths during follow‐up, one from heart failure and one from SCD 0.8% (95% CI: 0%–5.8%) (Table 1).

Figure 1.

Outcomes of catheter ablation for ventricular tachycardia in patients with hypertrophic cardiomyopathy

Figure 2.

Outcomes of catheter ablation for ventricular tachycardia in hypertrophic cardiomyopathy—apical aneurysm versus dilated‐phase

Table 1.

Baseline characteristics of study population

First author	Dukkipati et al.	Igarashi et al.	Inada et al.	Naeemah et al.	Santangeli et al.	Ueda et al.
Population	Drug‐refractory HCM‐related VT undergoing VT ablation	HCM‐related VT with AA undergoing VT ablation	Apical HCM with HCM‐related VT undergoing VT ablation	Dilated‐phase HCM‐related VT undergoing VT ablation	Drug‐refractory HCM‐related VT undergoing VT ablation	Dilated‐phase HCM‐related VT undergoing VT ablation
Country of study	United States	Japan	United States	Japan	United States	Japan
N	9	15	4	13	22	5
Mean age (years)	57.8 ± 8.8	65.9 ± 8.8	46 ± 10	60 ± 11	50.4 ± 15.3	67 ± 8.1
Male	9	12	3	12	17	5
Mean LVEF (%)	53.8 ± 9.7	64.5 ± 10.1	54 ± 14	39 ± 9	34.3 ± 9.8	36.8 ± 7.2
Previously on any AAD	7	13	3	11	22	5
Amiodarone	4	13	3	11	14	2
Lidocaine	0	n/a	3	n/a	4	1
Mexiletine	4	n/a	0	n/a	2	1
Sotalol	3	n/a	2	n/a	0	2
Procainamide	0	n/a	1	n/a	0	1
Disopyramide	0	n/a	0	n/a	1	0
On AAD post ablation	6	13	3	11	16	4
Prior ICD implantation/previous shocks	7/7	7/7	3/2	7	18	5/5
VT/ICD storm	3	n/a	2	n/a	n/a	4
Apical aneurysm	3	15	2	0	2	0
Dilated‐phase HCM	4	1	1	13	22	5
Scar localization/VT
Substrate
Anterior				9		4
Septum				5	9	4
Apical				2	4
Lateral wall	7	15	3	3		1
Inferior	5			1
Other	1		1 (RVOT)		1 (BBR), 1 (ALPM)
Purkinje‐related VT	1	0	0	1	2	0
Maximum wall thickness (mm)	18.7 ± 5.1	18.8 ± 5.3	17.1 ± 0.5	14 ± 3.5	18 ± 4	n/a
Scar
Endocardial only	1		2	1	n/a	2
Epicardial only	3		0	4	n/a	0
Combined	5		2	4	n/a	3
No scar	0	n/a	0	2	4	0
Inducible VT	8	14	4	9	22	5
Open‐irrigated catheter	4	11	4	13	22	n/a
Procedural success
Complete	8	13	4	10	19	4
Partial	0	2	0	3	0	0
Failure	1	0	0	0	3	1
Procedural complications	3 (2 Groin hematoma, 1 pericardial effusion requiring pericardio centesis	1 (Cardiac tamponade)	0	3 (AV block requiring device upgrade, transient phrenic nerve palsy during epicardial ablation, LAD artery occlusion during bipolar ablation requiring drug‐eluting stent)	0	1 (Transient AV block during intracoronary ablation)
Follow‐up time (months)	37.4 ± 16.9	12	9.8 ± 5.8	12 ± 5	20 ± 9	19 ± 4
Underwent multiple ablation	2	1	2	8	6	1
Death	0	1	0	1	0	0

Abbreviations: AA, apical aneurysm; AAD, antiarrhythmic drug; ALPM, left anterolateral papillary muscle; AV, atrioventricular; BBR, bundle branch re‐entry; HCM, hypertrophic cardiomyopathy; ICD, implantable cardioverter defibrillation; LAD, left anterior descending; LVEF, left ventricular ejection fraction; RVOT, right ventricular outflow tract; VT, ventricular tachycardia.

The mechanism of VA in HCM differs according to the subtypes. In young patients with no apparent fibrosis, the predominant arrhythmia responsible for SCD is polymorphic VT or VF due to myocyte cellular disarray and increased LV mass; while sustained monomorphic VT is rare. In contrast, elderly patients who have dilated‐phase HCM or HCM with AA, the presence of fibrosis intermingled with abnormal cardiomyocytes increase the vulnerability of scar‐related reentrant VT. ⁷ , ⁸ In these cases, the arrhythmogenic milieu for VT in HCM patients is often at the aneurysmal neck, or from islands of viable myocardium within the dense apical scar. VT circuits may be located in the basal septum, anterobasal to anterolateral aspect of the LV (predominantly without apical hypertrophy/apical aneurysm or dilated “burnt‐out” HCM). As such, these arrhythmogenic substrates exist not only endocardial but also epicardial and mid‐myocardial. Rarely patients can have Purkinje‐related VT, or the Purkinje network can be the origin of premature ventricular complex triggering VF. ⁹ Six percent of patients (n = 4) in our study had Purkinje‐related VAs and underwent successful endocardial ablation. ¹ , ³ , ⁵

VT is a poor predictor of adverse clinical outcomes, with increased efficacy with radiofrequency catheter ablation (compared to antiarrhythmic drugs) in patients with structural heart disease. Among patients with predominantly epicardial substrate, as is true for patients with HCM, endocardial‐only ablation has been limited in terms of durable success. In some studies, adjunctive epicardial mapping and ablation in HCM patients has seemed to offer an added benefit, despite the potentially increased risk of complications associated with epicardial access. Our pooled analysis demonstrated that combined epicardial‐endocardial ablation was safe and was associated with high acute procedural success, and reduced VT recurrence—findings comparable to previously published reports in other disease substrates.

Even though acute procedural success was approximately 90%, at least 20% of patients developed recurrent VT and required repeat ablations. The elimination of VT is challenging because of the diffuse and heterogeneous disease process (from myocardial disarray), failure to achieve transmural lesions (increased wall thickness and scar insulation), and anatomical difficulties (AA), thereby making catheter manipulation difficult) related to the procedure. Additionally, ablation outcomes largely depend on the clinical subtypes ‐ with improved clinical outcomes in HCM patients with AA compared to dilated phase‐HCM (Figure 2). Nevertheless, alternate strategies such as transcoronary ethanol ablation can be pursued, especially in patients with septal scar in patients who failed the combined epicardial‐endocardial approach.

The high rate of acute procedural success, freedom from recurrent VT, and low periprocedural complications is a convincing to consider epicardial–endocardial ablation in HCM patients with recurrent VT as the initial ablation strategy. Several limitations include a small number of participants, operator‐patient selection bias, operator's experience with complex ablations, and heterogeneity in HCM phenotype. Therefore, we postulate an international registry to provide additional insights into the arrhythmia mechanism and long‐term outcomes following catheter ablation in HCM patients.

CONFLICT OF INTEREST

The authors declare no conflict of interest.

Garg J, Kewcharoen J, Shah K, et al. Clinical outcomes of radiofrequency catheter ablation of ventricular tachycardia in patients with hypertrophic cardiomyopathy. J Cardiovasc Electrophysiol. 2023;34:219‐224. 10.1111/jce.15739