Author + information
- Received October 8, 2009
- Revision received July 8, 2010
- Accepted July 13, 2010
- Published online February 1, 2011.
- Thorsten Lawrenz, MD⁎,†,⁎ (, )
- Bianca Borchert, MD⁎,
- Christian Leuner, MD⁎,
- Markus Bartelsmeier, MD⁎,
- Jens Reinhardt, MD⁎,
- Claudia Strunk-Mueller, MD⁎,
- Dorothee Meyer Zu Vilsendorf, MD⁎,
- Marc Schloesser, MD⁎,
- Gerald Beer, MD⁎,
- Frank Lieder, MD‡,
- Christoph Stellbrink, MD⁎ and
- Horst Kuhn, MD⁎
- ↵⁎Reprint requests and correspondence:
Dr. Thorsten Lawrenz, Klinikum Bielefeld, Department of Cardiology, Teutoburger Strasse 50, Bielefeld D-33604, Germany
Objectives The purpose of this study was to examine the efficacy and safety of endocardial radiofrequency ablation of septal hypertrophy (ERASH) for left ventricular outflow tract (LVOT) gradient reduction in hypertrophic obstructive cardiomyopathy (HOCM).
Background Anatomic variability of the vessels supplying the obstructing septal bulge can limit the efficacy of transcoronary ablation of septal hypertrophy in HOCM. Previous studies showed that inducing a local contraction disorder without reducing septal mass results in effective gradient reduction. We examined an alternative endocardial approach to transcoronary ablation of septal hypertrophy by using ERASH.
Methods Nineteen patients with HOCM were enrolled; in 9 patients, the left ventricular septum was ablated, and in 10 patients, the right ventricular septum was ablated. Follow-up examinations (echocardiography, 6-min walk test, bicycle ergometry) were performed 3 days and 6 months after ERASH.
Results After 31.2 ± 10 radiofrequency pulses, a significant and sustained LVOT gradient reduction could be achieved (62% reduction of resting gradients and 60% reduction of provoked gradients, p = 0.0001). The 6-min walking distance increased significantly from 412.9 ± 129 m to 471.2 ± 139 m after 6 months, p = 0.019); and New York Heart Association functional class was improved from 3.0 ± 0.0 to 1.6 ± 0.7 (p = 0.0001). Complete atrioventricular block requiring permanent pacemaker implantation occurred in 4 patients (21%); 1 patient had cardiac tamponade.
Conclusions ERASH is a new therapeutic option in the treatment of HOCM, allowing significant and sustained reduction of the LVOT gradient as well as symptomatic improvement with acceptable safety by inducing a discrete septal contraction disorder. It may be suitable for patients not amenable to transcoronary ablation of septal hypertrophy or myectomy.
Transcoronary ablation of septal hypertrophy (TASH) is an accepted option and alternative to surgery in patients with hypertrophic obstructive cardiomyopathy (HOCM) (1–7). However, owing to variability of septal branch anatomy, approximately 5% to 8% of patients are not suitable for TASH (4,5). Previous studies showed that inducing a local septal contraction disorder without reducing septal mass by using only small alcohol dosages for TASH results in effective gradient reduction (8,9). Thus, we hypothesized that such localized contraction disorders could also be induced by endocardial radiofrequency (RF) ablation of septal hypertrophy (ERASH) in HOCM.
We enrolled 19 patients (age 60.7 ± 12 years) with typical HOCM and left ventricular outflow tract (LVOT) gradients of ≥50 mm Hg at rest or after provocation and severe symptoms (New York Heart Association [NYHA] functional class III) despite adequate medication in the study (Table 1); 8 patients were receiving beta-blockers (162.5 ± 52 mg metoprolol), and 11 patients, verapamil (294.5 ± 63 mg). In 1 patient (no. 8), dual-chamber pacing for gradient reduction had been ineffective for 18 months; and in 8 patients, previous TASH treatment had been ineffective (gradient reduction <50%). Reasons for TASH inefficacy were either inadequate septal branch anatomy (6 of 8 patients), or a high spillover of contrast medium into collateral branches (2 of 8 patients). Surgical myectomy was offered to all patients with failed TASH; only patients refusing myectomy were enrolled in the study. The study protocol was approved by the local ethics committee of the University of Muenster, Muenster, Germany. All patients gave written, informed consent to participate in the study.
Echocardiographic measurements of the LVOT gradients were performed under resting conditions and after provocation (bicycle exercise, 75 W, for 5 min) before ERASH, 3 days after ERASH, and at 6 months of follow-up. At each follow-up, the 6-min walking distance was measured twice on 2 separate days. Cardiac magnetic resonance imaging (MRI) was performed in a subgroup of 5 randomly chosen patients (Figs. 1 and 2). After the procedure, continuous electrocardiographic monitoring was performed for 8 days.
Invasive measurements and ablation technique
The LVOT gradients at rest and post-extrasystolic were measured invasively. A catheter was placed at the bundle of His. Radiofrequency ablation was performed with a 4-mm irrigated-tip ablation catheter (CoolFlow Irrigation Pump, Biosense Webster, Diamond Bar, California) 30 ml/min. In the first 2 patients, left ventricle (LV) ablation was chosen under the assumption that the LV gradient reduction would be best achievable by ablating the LV septal myocardium (10,11). Because of some catheter instability, a right ventricle (RV) approach was attempted in the next 5 patients. With more experience, we again switched to a LV approach to test whether that could further improve the efficacy of ERASH. The decision regarding which approach to use was then made on a case-by-case basis for the remaining patients.
A retrograde transaortic approach was used for LV ablation, an inferior caval approach for RV ablation; in 1 case, the LV septum was ablated after trans-septal puncture.
We delivered RF current strictly to the most proximal parts of the septum in immediate vicinity to the LVOT. To prevent induction of complete heart block, we navigated the tip of the ablation catheter as far as possible away from the His-bundle region, marked by the electrode catheter or additionally by a “tag” in the CARTO (Biosense Webster) map (Fig. 1). To produce a myocardial defect comparable to that of TASH, we ablated a region of approximately 2 cm2 (Fig. 3). The therapeutic end point for ERASH was a gradient reduction of >50%.
Statistical analysis was performed using commercial software (SPSS version 10.0, SPSS, Chicago, Illinois). Paired data were analyzed with the Wilcoxon signed-rank test; unpaired data were analyzed with the Mann-Whitney U test. All p values <0.05 were considered significant. No corrections for multiple comparisons were made.
A total of 14 to 40 RF pulses (90 s, 40 to 70 W, procedure time 139 ± 47 min) were delivered to either the RV septum (n = 10) or the LV septum (n = 9) (Table 1). Significant elevation of myocardial serum markers was noticeable in all patients (Table 2). We observed a sustained reduction of the LVOT gradient at rest (62%) or after provocation (60%) (Tables 3 and 4,Figs. 4 and 5). Only patients with a remaining resting gradient >50 mm Hg after ERASH (n = 4) received their pre-procedural medication (verapamil or beta-blockers) at the time of hospital discharge.
After 6 months, NYHA functional class improved from 3.0 ± 0.0 to 1.6 ± 0.7 (p < 0.01); the 6-min walking distance improved by 58 m (413 ± 129 m at baseline; 458 ± 108 m immediately after ERASH; 471 ± 139 m after 6 months, p < 0.019) (Fig. 6).
Gadolinium-contrast MRI exhibited a subaortic septal zone of late enhancement with a maximal penetration depth of 28 mm (Fig. 2). Early after ERASH, this zone was localized surrounding the ablation site with a low signal core and a homogenous late enhancement after 6 months. There was only a minor, albeit significant, reduction of the septal diameter after 6 months compared with baseline (21.4 ± 3.4 mm vs. 22.6 ± 3.7 mm, p = 0.046), but both echocardiography and MRI showed a circumscribed region of reduced contraction at the ablation site (visual interpretation of regional wall motion).
During RF ablation, complete heart block occurred in 4 patients with permanent pacemaker dependency (patient nos. 2, 6, 11, and 14). All patients received a dual-chamber pacemaker and were still pacemaker dependent after 6 months. One patient (no. 6) had acute pericardial tamponade during RV ablation caused by perforation of the RV pacing lead, requiring surgical revision.
Catheter-based treatment of HOCM initially aimed for reduction of septal myocardial mass to relieve LVOT obstruction, and required injection of relatively large amounts of ethanol (3 to 5 ml) (2–7). However, evidence has grown that injection of smaller amounts of ethanol (1 to 2 ml) may be equally effective as higher dosages (8,9). Thus, relief of obstruction may be more dependent on induction of a localized reduction in contractility responsible for the dynamic obstruction. Early studies on the behavior of LVOT obstruction during temporary balloon occlusion of septal branches without alcohol injection by Gietzen et al. (12) support this hypothesis, as transient ischemia already led to an acute, reversible LVOT gradient reduction. The present study aimed to prove that endocardial RF ablation could create a myocardial scar comparable to that of a “low-dose” TASH procedure (Figs. 2 and 3). Although we did not observe a significant reduction of septal mass after ERASH, gadolinium-contrast MRI showed a nearly transmural scar, >2 cm deep in some patients (Fig. 2).
Our data indicate that ERASH is safe and effective in reducing LVOT gradients and resulted in a significant improvement of exercise capacity and NYHA functional class after 6 months. Although our study does not indicate a significant difference in gradient reduction of a left-sided versus right-sided approach, our data do not yet allow a recommendation for which approach (LV vs. RV) should be chosen.
Except for 1 case of pericardial tamponade, no severe complications occurred. The percentage of patients requiring additional pacemaker implantation (21%) was similar to that of the early learning phase of TASH and about twice that expected after contemporary TASH treatment (1–9).
Comparing results of ERASH in this study to TASH or myectomy, the extent of gradient reduction appears to be lower after ERASH (3–9). In only 7 of 19 patients was a residual gradient <100 mm Hg after provocation achieved. However, the patients included in our study represent a subset of very severely affected patients with HOCM, including many with previously failed TASH attempts. Therefore, a comparison in terms of the effectiveness mandates further prospective investigations.
It is a limitation that we did not measure maximum oxygen consumption or additional echocardiographic parameters (diastolic function, systolic anterior motion phenomenon).
Endocardial radiofrequency ablation of septal hypertrophy allows significant and sustained gradient reduction and symptomatic improvement of patients with severe HOCM. It may be suitable for patients who are not suitable for TASH or myectomy.
The study was supported by a grant from the Franz Loogen Foundation, Düsseldorf, Germany. The authors have reported that they have no relationships to disclose.
- Abbreviations and Acronyms
- endocardial radiofrequency ablation of septal hypertrophy
- hypertrophic obstructive cardiomyopathy
- left ventricle
- left ventricular outflow tract
- magnetic resonance imaging
- New York Heart Association
- right ventricle
- transcoronary ablation of septal hypertrophy
- Received October 8, 2009.
- Revision received July 8, 2010.
- Accepted July 13, 2010.
- American College of Cardiology Foundation
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