Two‐Year Results of Percutaneous Endocardial Septal Radiofrequency Ablation for Hypertrophic Obstructive Cardiomyopathy

ABSTRACT

Background

Hypertrophic obstructive cardiomyopathy (HOCM) is a hereditary myocardial disease. Percutaneous endocardial septal radiofrequency ablation (PESA) is an innovative approach for treating HOCM. Consequently, we present the outcomes of the PESA for HOCM.

Methods

This study included 20 patients with HOCM who received PESA. The primary outcomes include the control rate of the left ventricular outflow tract gradient (LVOTG) at rest and following the Valsalva maneuver and changes in New York Heart Association (NYHA) function. Secondary outcomes include changes in interventricular septal thickness (IVST), left ventricular ejection fraction (LVEF), pulmonary artery systolic pressure (PASP), and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). In addition, this study assessed the incidence of complications during the perioperative period, the operation time of the PESA, and hospital stays.

Results

After 2 years, the LVOTG for patients decreased 54% at rest and 55% after the Valsalva maneuver. In addition, the NYHA functional index increased from 3.25 ± 0.55 to 1.95 ± 0.88, and 15 patients (75%) achieved NYHA Class I/Ⅱ. The LVEF of patients significantly increased from 63.95 ± 6.29% to 65.75 ± 3.39%, the PASP decreased from 32.50 (31.00, 40.50) mmHg to 23.50 (19.50, 28.50) mmHg, the NT‐proBNP decreased from 388.90 (278.80, 1039.00) ng/mL to 227.4 (121.6, 499.6) ng/mL, and the IVST decreased from 17.20 ± 3.72 mm to 15.80 ± 3.14 mm. Importantly, no patients needed pacemaker treatment. The operative time for the PESA was 186.63 ± 22.47 min, and the median postoperative hospital stay for patients was 10.00 days.

Conclusions

PESA could reduce the LVOTG with the advantages of a low risk of arrhythmias, minimal trauma, rapid postoperative recovery, and shorter hospital stays.

Abbreviations

HCM

Hypertrophic cardiomyopathy

HOCM

Hypertrophic obstructive cardiomyopathy

PESA

percutaneous endocardial septal radiofrequency ablation

LVOTG

left ventricular outflow tract pressure gradient

IVST

interventricular septal thickness

LVEF

left ventricular ejection fraction

1. Introduction

Hypertrophic cardiomyopathy (HCM) is an autosomal dominant genetic disorder characterized by unevenly increased left ventricular (LV) wall thickness (> 15 mm) in the absence of hypertension or significant valvular disease. Approximately 70% of HCM patients experience left ventricular outflow tract obstruction (LVOTO) at rest or upon exercise provocation, leading to hypertrophic obstructive cardiomyopathy (HOCM) [1]. Conventionally, HOCM is defined by an instantaneous Doppler‐measured left ventricular outflow tract gradient (LVOTG) of ≥ 30 mmHg, and invasive treatment is considered at a threshold of 50 mmHg or higher. HOCM patients with elevated LVOTG are at increased risk of developing progressive heart failure (HF) symptoms and HF‐related mortality [2]. Although current guidelines advocate for the use of medication therapy—including β‐blockers and non‐dihydropyridine calcium channel blockers as class I indications [3]—these treatments often fail to manage symptoms in most patients adequately [4]. For HOCM patients who present with symptoms despite receiving β‐blockers or nondihydropyridine calcium channel blockers, a myosin inhibitor, disopyramide, or septal reduction therapy [surgical myectomy (SM) or alcohol septal ablation (ASA)] is recommended to alleviate severe LVOTO. Nonetheless, SM involves significant risks, including an increased risk of atrioventricular block and extended patient recovery periods. Furthermore, the applicability of the ASA is limited by the septal coronary anatomy [5].

Radiofrequency ablation (RFA) has been widely used to treat cardiac arrhythmias for several decades [6]. Percutaneous endocardial septal radiofrequency ablation (PESA) represents an innovative approach that uses high‐temperature energy to create necrotic areas in the ventricular septum for a reduction in systolic excursion of the myocardium and septum, and its clinical application for HOCM has increased in recent years. In this study, we present the outcomes following PESA for HOCM.

2. Methods

2.1. Ethical Approval

This study was conducted according to the principles outlined in the Declaration of Helsinki and received ethical approval from the Ethics Committee of the First Affiliated Hospital of Soochow University (No. 2024180). Owing to the retrospective design of the study and the use of anonymized data, the requirement for informed consent was waived.

2.2. Study Design

This retrospective study included patients who diagnosed with HOCM and a resting LVOTG > 50 mmHg at the First Affiliated Hospital of Soochow University from May 2022 to May 2023. Initially, all patients received guideline‐directed medical therapy (GDMT), such as beta‐blockers and verapamil. After ≥ 3 months of maximally tolerated GDMT, all symptomatic patients with HOCM were evaluated by a multidisciplinary heart team comprising an interventional cardiologist, a cardiac surgeon, an imaging specialist, and an anesthesiologist. Surgical septal myectomy was considered the first‐line septal reduction therapy, whereas ASA was regarded as the second‐line option.

Exclusion from myectomy: Nine of the 20 patients were judged to be at prohibitive surgical risk because of advanced age (≥ 65 years; n = 4) or significant comorbidities such as severe chronic obstructive pulmonary disease or renal insufficiency (n = 5). A further 11 patients declined open‐heart surgery after counseling.

Exclusion from ASA: In eight patients, the first or second septal‐perforator artery measured ≤ 1.0 mm in diameter, precluding safe catheter engagement; in four patients, these vessels gave rise to extensive collateral branches to the right ventricular free wall. An additional eight patients declined ASA after counseling.

When either treatment was contraindicated or declined, PESA was offered as a bail‐out strategy, and written informed consent was obtained. No patient underwent PESA without first completing this structured assessment.

2.3. PESA Procedure

The PESA procedure was performed under local anesthesia using lidocaine. After sterile preparation, an 8 F sheath was inserted into the right femoral artery, and a pigtail catheter was used to measure the LVOTG. Patients with an LVOTG of less than 30 mmHg underwent a pharmacological provocation test through an intravenous infusion of isoprenaline. An 11 F sheath facilitated the introduction of an intracardiac echocardiography catheter. The ultrasound fan was adjusted on the CartoSound module platform of the Carto3 mapping system (Biosense Webster Inc., Diamond Bar, CA, USA) to reconstruct a three‐dimensional ultrasound anatomical image of the left ventricular cavity by scanning along both the long and short axes of the left ventricle. The area of obstruction, where the anterior motion of the mitral valve leaflet contacts the septum, was fully delineated in the three‐dimensional structure of the left ventricle and targeted for ablation (Figure 1). A red THERMOCOOL SMARTTOUCH catheter (Biosense Webster, Diamond Bar, CA, USA) was introduced into the left ventricle via the retrograde aortic approach, marking the conduction bundles within the left ventricle, including the His bundle, left bundle branches, and Purkinje fibers. Ablation was performed at sites on the endocardial surface of the septal obstruction area where no P potential was detected, with the energy setting at 45 W and the temperature maintained between 30°C and 35°C, complemented by a saline infusion rate of 22 mL/min. Each ablation point lasted for 90 s. Ablation was considered complete when the edematous bright band on the ultrasound interface reached a thickness of more than 5 mm and/or when the ablated area accounted for more than half of the obstruction area (Figure 2). A pigtail catheter was reintroduced to measure the LVOTG, and the procedure was terminated when the pressure gradient decreased by ≥ 50%. Dexamethasone was routinely administered at the end of the ablation to control edema. Close cardiac monitoring was maintained during the procedure to avoid damaging the conduction bundles. All patients underwent temporary cardiac pacemaker implantation for 3 days in the case of atrioventricular block.

FIGURE 1.

Three‐dimensional structural map of the left ventricle and aortic root constructed by ICE, with the brown area being the SAM area. [Color figure can be viewed at wileyonlinelibrary.com]

FIGURE 2.

Highlighted edema bands after ablation. [Color figure can be viewed at wileyonlinelibrary.com]

2.4. Outcome

The primary outcomes included the control rate of the LVOTG at rest and following the Valsalva maneuver and changes in the New York Heart Association (NYHA) function. Secondary outcomes include changes in interventricular septal thickness (IVST), left ventricular ejection fraction (LVEF), pulmonary artery systolic pressure (PASP), and N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP). This study assessed the incidence of complications during the perioperative period. Vivid™ ultrasound equipment was used to measure changes in left ventricular hemodynamic indicators. Measurements were taken with the patient in the lateral position, and an experienced sonographer performed the procedure. Additionally, this study evaluated the operation time of the PESA, and the length of hospital stay.

$$\text{The reduction rate of LVOTG}\frac{\text{LVOTG after}12\text{months}-\text{LVOTG at}\text{baseline}}{\text{LVOTG at}\text{baseline}}$$

2.5. Statistical Analysis

Statistical analyses in this study were conducted using SPSS 26.0 software. Continuous variables are presented as the mean ± SD for those with a normal distribution and as the median with interquartile range (IQR) for variables deviating from normality. Paired t‐tests and Wilcoxon signed‐rank tests were utilized to compare continuous variables paired on the basis of data distribution. Categorical variables are presented as cases. All tests were two‐tailed, with a p‐value < 0.05 indicating statistical significance. The P values presented in this report have not been adjusted for multiplicity, and therefore, inferences drawn from these statistics may not be reproducible.

3. Results

3.1. Baseline Characteristics of Patients

Twenty patients were included in the study, with an average age of 56.29 ± 8.13 years, 70% of whom were male. Most patients had varying degrees of mitral regurgitation. More than half of the patients had hypertension, and the majority were receiving β‐blockers. Baseline characteristics are detailed in Table 1.

TABLE 1.

Baseline clinical characteristics.

n	20
Age, years	56.29 ± 8.13
Male, n (%)	14 (70.0)
Hypertension, n (%)	11 (55.0)
Diabetes, n (%)	3 (15.0)
Mild mitral regurgitation, n (%)	12 (60.0)
Moderate mitral regurgitation, n (%)	8 (40.0)
Severe mitral regurgitation, n (%)	0 (0.0)
Medications
β‐Blocker, n (%)	16 (80.0)
Calcium channel blocker, n (%)	7 (35.0)

3.2. Clinical and Hemodynamic Results

Both the LVOTG at rest and after the Valsalva maneuver declined progressively during postoperative follow‐up; the values at 12 months (p < 0.001) and 24 months (p < 0.001) were significantly lower than those recorded immediately after surgery. The LVOTG for patients decreased 54% at rest and 55% after the Valsalva maneuver. Expressed as absolute changes, the mean reduction in the LVOTG at rest was 6.86 ± 12.02 mmHg before discharge, 20.68 ± 13.20 mmHg at 3 months, 35.75 ± 16.32 mmHg at 12 months, and 39.75 ± 13.30 mmHg at 24 months, as shown in Table 3.

TABLE 3.

LVOTG at rest and following Valsalva during follow‐up, Mean ± SD, mmHg.

Times	LVOTG at rest	LVOTG following Valsalva
Baseline	73.00 ± 25.47	106.10 ± 24.47
Before discharged	66.14 ± 28.63a	87.51 ± 23.72a
3 months	52.32 ± 27.34a	71.24 ± 22.89a
12 months	37.25 ± 21.90a	52.55 ± 18.61a
24 months	33.25 ± 16.28a	47.25 ± 18.38a

^a p < 0.05, compared with the Baseline; LVOTG, left ventricular outflow tract pressure gradient.

Similarly, the changes in NYHA function significantly improved (p < 0.001), from 3.25 ± 0.55 to 1.95 ± 0.88. Specifically, after 24 months, seven patients achieved NYHA Class I, eight patients achieved NYHA Class II, and four patients remained NYHA Class III, as shown in Figure 3.

FIGURE 3.

NYHA heart function classification during follow‐up. [Color figure can be viewed at wileyonlinelibrary.com]

At 12 months, the LVEF was significantly greater than the preoperative value (p = 0.017); however, by 24 months, this difference was no longer significant (p = 0.128). The PASP score was significantly lower than the baseline score at both 12 and 24 months (p < 0.001), and the reduction plateaued after 12 months, with no further significant change between 12 and 24 months (p = 0.216). NT‐proBNP declined steadily over time, showing a significant decrease at 12 months relative to baseline (p < 0.001) and an additional reduction at 24 months (p < 0.001). The IVST showed only a mild downward trend that did not reach statistical significance (12 months: p = 0.272; 24 months: p = 0.110), as shown in Table 2.

TABLE 2.

Each outcome during follow‐up.

Outcome	Baseline	12 months	24 months	P1	P2	P3
LVOTG at rest, Mean ± SD, mmHg	73.00 ± 25.47	37.25 ± 21.90	33.25 ± 16.28	＜0.001	＜0.001	0.055
LVOTG following Valsalva, Mean ± SD, mmHg	106.10 ± 24.47	52.55 ± 18.61	47.25 ± 18.38	＜0.001	＜0.001	0.003
IVST, Mean ± SD, mm	17.20 ± 3.72	16.15 ± 3.53	15.80 ± 3.14	0.272	0.110	0.065
LVEF, Mean ± SD, %	63.95 ± 6.29	68.60 ± 3.55	65.75 ± 3.39	0.017	0.128	0.007
PASP, median (IQR), mmHg	32.50 (31.00, 40.50)	25.50 (21.80, 27.30)	23.50 (19.50, 28.50)	＜0.001	＜0.001	0.216
NT‐proBNP, median (IQR), ng/L	388.90 (278.80, 1039.00)	279.80 (199.30, 683.40)	227.4 (121.6, 499.6)	＜0.001	＜0.001	＜0.001

Note: P1: 12 months versus baseline; P2: 24 months versus baseline; P3: 24 months versus 12 months. *No corrections for multiple testing were applied.

Abbreviations: LVOTG, left ventricular outflow tract gradient; IVST, interventricular septal thickness; LVEF, left ventricular ejection fraction; NT‐proBNP, N‐terminal pro‐B‐type natriuretic peptide; PASP, pulmonary artery systolic pressure.

Furthermore, no pericardial effusions were observed postoperatively. However, two patients experienced complications related to femoral vein punctures, which were resolved following treatment. One patient developed an incomplete right bundle branch block. Additionally, four patients exhibited occasional premature ventricular contractions that resolved within 2 years, as confirmed by follow‐up Holter monitoring.

The mean operative time for the PESA procedure was 186.63 ± 22.47 min. The median postoperative hospital stay for patients was 10.00 days, with an interquartile range of 7.00–14.00 days.

4. Discussion

This study describe the clinical and echocardiographic outcomes observed after PESA for HOCM, and the results of the study indicate that (1) the PESA could reduce the LVOTG at rest or following the Valsalva maneuver and improve cardiac function; (2) while medication can alleviate clinical symptoms such as chest tightness and dyspnea, its efficacy is limited in patients with severe obstruction; and (3) the PESA shows no acute ventricular arrhythmia or risk of heart block.

The 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR guidelines for diagnosing and treating patients with hypertrophic cardiomyopathy β‐blockers and calcium channel blockers are standard class I indications [3]. For patients with significant symptoms and severe obstruction who respond poorly to β‐blockers and calcium channel blockers, myosin inhibitors or disopyramide may be added to reduce LVOTG and improve symptoms [3]. Mavacamten is a selective cardiac‐myosin inhibitor that produces clinically meaningful benefits in symptomatic HOCM; 37% of treated patients achieved a composite response, whereas 17% achieved a placebo, with mean Valsalva LVOT gradients falling by 36 mmHg [7]. The subsequent VALOR‐HCM study showed that adding mavacamten to maximally tolerated therapy lowered the proportion of patients proceeding to septal reduction therapy by 82% and further improved the NYHA class, exercise capacity, and NT‐proBNP over 16–56 weeks [8].

Lawrenz first reported in 2004 that Endocardial radiofrequency ablation of septal hypertrophy (ERASH) provided an alternative treatment for patients with severe HOCM [9]. Sreeram et al. assessed the efficacy of radiofrequency ablation for treating children with HOCM and reported that after radiofrequency catheter ablation, the LVOTG decreased from 96.9 ± 27.0 mmHg to 32.7 ± 27.1 mmHg [10]. Subsequently, numerous studies have demonstrated that PESA can reduce the LVOTG and improve clinical outcomes [11, 12].

In this study, the LVOTG for patients decreased 54% at rest and 55% after the Valsalva maneuver, respectively, after 2 years. In addition, 3 days after the PESA procedure, six patients presented a paradoxical increase in the LVOTG compared with the baseline values. In addition, the levels of highly sensitive cardiac troponin T and creatine kinase‐MB were significantly greater than the baseline levels, increasing from 13.23 pg/mL and 3.42 ng/mL to 324.61 pg/mL and 9.23 ng/mL, respectively. These findings suggest that PESA may induce myocardial tissue edema, temporarily exacerbating the LVOTG. All patients in the PESA group received dexamethasone for 3 days after the PESA procedure, and echocardiography before discharge revealed a reduction in myocardial edema, with a decrease in the LVOTG compared with that in the immediate postoperative period.

Furthermore, the LVOTG at rest decreased by 6.86 ± 12.02 mmHg before discharge, 20.68 ± 13.20 mmHg at 3 months, 35.75 ± 16.32 mmHg at 12 months, and 39.75 ± 13.30 mmHg at 24 months. This finding indicates that PESA might induce myocardial edema, temporarily worsening LVOTO, but the efficacy of PESA in reducing the LVOTG has become more pronounced over time. Some possibilities could explain these results: the PESA reduces LVOTO by partially ablating myocardial tissue. This procedure provides immediate relief from obstruction and induces fibrosis over time, which may further reduce the degree of outflow tract obstruction. Additionally, as the heart gradually adapts to the new hemodynamic state, the pressure in the left ventricular outflow tract is further alleviated.

LVOTO is caused primarily by (1) the systolic anterior movement (SAM) of the mitral valve, which is in contact with the hypertrophic interventricular septum [13], and (2) the strong contraction force [14]. Although the change in IVST was minimal after 12 months, this study also revealed a significant decrease in the LVOTG. These results align with prior research, indicating that the efficacy of the PESA in reducing LVOTO appears to be independent of IVST changes. Moreover, Li et al. reported that radiofrequency ablation could induce mid‐wall necrosis in IVST, diminishing radial and circumferential contractile functions in the ablated area and reducing the LVOTG [15]. In addition, the short‐term reduction in the LVOTG in the PESA group was associated with decreased left ventricular wall motion resulting from radiofrequency ablation. The sustained reduction in the LVOTG may be linked to myocardial fibrosis and remodeling induced by the procedure [16]. Radiofrequency ablation can improve myocardial perfusion and alleviate microvascular ischemia; however, this perfusion does not correlate directly with the sustained reduction in the LVOTG [17].

More than half of patients with HCM have pulmonary hypertension (PH) [18], and PH is associated with an unfavorable clinical outcome [19]. In this study, all patients experienced a reduction in the PASP score. In addition, after 2 years, the LVEF increased from 63.95 ± 6.29% to 65.75 ± 3.39%, which is consistent with the findings of published studies [20]. Two possibilities could explain these results. First, the PESA can reduce the LVOTO. This alleviation decreases the afterload on the heart, allowing it to pump more efficiently, thus improving the LVEF. Second, the PESA can reduce septal thickness and LVOTO, alleviating SAM and decreasing mitral regurgitation. This improvement in mitral valve function contributes to better overall cardiac output. Moreover, after PESA surgery, most patients experienced significant improvement in clinical symptoms, such as chest tightness and shortness of breath, with improvement in NYHA function.

A previous study reported that approximately 21% of patients who undergo RFA will develop third‐degree atrioventricular block, which requires pacemaker treatment [21]. However, Li et al. reported that the myocardium located beneath the endocardium and extending longitudinally remained undamaged after RFA [15]. In this study, none of the patients experienced significant conduction block during the procedure. This can be attributed to the precise mapping of the left ventricular conduction bundle by the catheter before ablation, ensuring that ablation was not performed at the site where the P potential was recorded. During the ablation process, if sustained ventricular tachycardia or frequent ventricular premature beats lasting more than 2 seconds (s) occurred, the ablation was immediately stopped. These measures maximize the protection of the cardiac conduction bundle from damage. Notably, although there is no evidence that PESA increases the risk of short‐term postoperative arrhythmias, it is essential to remain vigilant about the risk that necrotic cardiac scarring induced by ablation could disrupt electrical conduction or serve as ectopic foci, potentially leading to arrhythmia.

The ablation parameters of the PESA significantly influences its efficacy. Sreeram et al. adjusted the ablation energy to 60 watts (W) and timed individual lesions between 60 and 120 s; each patient received between 10 and 63 lesions, resulting in a significant reduction in the LVOTG from 96.9 ± 27.0 mmHg to 32.7 ± 27.1 mmHg [10]. Kong et al. adjusted the ablation energy between 40 and 60 W, with each site ablated for 60–180 s [12]. The LVOTG was subsequently significantly reduced after 12 months of follow‐up. Our study set the ablation energy to 45 W and the temperature to 33°C–37°C, with the duration of ablation set to 90 s, with 35–60 points for each patient. The LVOTG significantly decreased in most patients after 12 months of follow‐up. However, a few patients still experienced severe left ventricular outflow tract obstruction. We suggest repeating the PESA or the SM procedure for these patients. Future studies should aim to establish optimal ablation parameter settings.

This study was a single‐center retrospective analysis limited by a short follow‐up period and a relatively small sample size. A large‐scale, prospective, multicenter, randomized controlled trial should further verify the long‐term efficacy and safety of PESA in treating patients with HOCM.

5. Conclusion

In summary, PESA may be a potential option for patients who are considered at high risk for surgical myectomy surgery due to age, comorbidities, or other factors.

Ethics Statement

This study was conducted according to the principles outlined in the Declaration of Helsinki and received ethical approval from the Ethics Committee of the First Affiliated Hospital of Soochow University (No. 2024180). Owing to the retrospective design of the study and the use of anonymized data, the requirement for informed consent was waived.

Consent

Written informed consent was obtained from the participant included in the study. Consent for publication was obtained for the patient's data included in the study.

Conflicts of Interest

The authors declare no conflicts of interest.