ADVERTISEMENT
Effectiveness of Alcohol Septal Ablation in Obstructive Hypertrophic Cardiomyopathy With Versus Without Extreme Septal Hypertrophy
Abstract: Aims. Data on the effectiveness of alcohol septal ablation (ASA) in patients with hypertrophic cardiomyopathy (HCM) and extreme septal hypertrophy (ESH) are lacking. This study aimed to compare the effectiveness of ASA in patients with vs without ESH. Methods. Clinical profiles of 17 patients with ESH and 256 patients without ESH were compared. Results. Baseline pressure gradient and limiting symptoms were comparable between patients with and without ESH. At median 1.1 years of follow-up after ASA, pressure gradient was 48.5 ± 40.4 mm Hg in the ESH group and 40.9 ± 35.2 mm Hg in the non-ESH (N-ESH) group (P=.33). Patients with New York Heart Association class III/IV represented 5.9% of the ESH group and 16.9% of the N-ESH group (P=.39). Patients with Canadian Cardiovascular Society class III/IV represented 5.9% of the ESH group and 10.2% of the N-ESH group (P=.87). Conclusion. The effectiveness of ASA seems comparable between patients with and without ESH.
J INVASIVE CARDIOL 2016;28(3):99-103
Key words: alcohol septal ablation, hypertrophic cardiomyopathy, extreme septal hypertrophy
______________________________________
Left ventricular outflow tract (LVOT) obstruction occurs in about 70% of patients with hypertrophic cardiomyopathy (HCM).1 If this hemodynamic disorder leads to severe limiting clinical symptoms and persists despite optimal medical treatment, invasive treatments should be considered.2,3 Surgical septal myectomy is the first consideration for the majority of eligible patients with HCM with severe drug-refractory symptoms and LVOT obstruction in experienced centers. For patients who are not optimal surgical candidates (eg, because of comorbidities or advanced age) or have such a strong desire to avoid surgery, alcohol septal ablation (ASA) is an alternative treatment option.2-7 The effectiveness of this technique is deemed to be uncertain or less effective in patients with extreme septal hypertrophy (ESH), while data on the effectiveness of ASA in these patients are lacking.2,3 This study aimed to compare the effectiveness of ASA in patients with vs without ESH.
Methods
Study population. Both ASA and myectomy were available at our center. The choice of ASA or myectomy was made based on detailed discussion of the risks and benefits of each alternative for every patient. This study consecutively enrolled adult patients (≥18 years of age) who underwent ASA at our center between January 2002 and March 2014. HCM was defined as the presence of left ventricular maximum wall thickness ≥15 mm in the absence of diseases associated with this degree of hypertrophy.2ESH was defined as maximum septal thickness of ≥30 mm. Echocardiographic data and the degree of mitral regurgitation were obtained as previously described.8 LVOT pressure gradient was assessed using continuous-wave Doppler echocardiography and cardiac catheterization.4,8,9 ASA was performed using previously described techniques.10 Patients were classified into two groups based on maximal septal thickness: (1) the ESH group, comprising patients with ESH; and (2) the non-ESH (N-ESH) group, comprising patients without ESH. This study was approved by the local ethics committee with patient informed consent.
Statistical analysis. Continuous variables were expressed as mean ± standard deviation or median (interquartile range [IQR]), and differences between groups were analyzed by t-test or Mann-Whitney U-test, where appropriate. The Wilcoxon signed-rank test was used to assess differences in serial pressure gradient measures. Categorical variables were summarized as frequencies with percentages and were compared by Pearson chi-square test, Fisher’s exact test, McNemar test, or continuity correction chi-square test, where appropriate. All analyses were performed with SPSS statistical software, version 16.0 (SPSS, Inc). All tests were two-tailed, and statistical significance was defined as P<.05.
Results
Baseline clinical profiles. A total of 273 patients underwent ASA at our center from January 2002 to March 2014; all were enrolled in this study. The cited reasons for the selection of ASA over myectomy were: patient choice (262 patients); elderly age with frailty (5 patients); chronic obstructive pulmonary disease (4 patients); prior surgical wounds (1 patient); and Sheehan syndrome (1 patient). There were 17 patients (6.2%) with ESH and 256 patients (93.8%) without ESH. Patients with ESH were younger and had greater maximum septal and posterior wall thickness. No significant differences of limiting symptoms, baseline pressure gradient, and medications were observed between the two groups (Table 1).
Procedural results. As shown in Table 2, more alcohol was used and more septal branches were ablated in patients with ESH. The level of peak creatine kinase of the ESH group was numerically higher than in the N-ESH group. Both groups got significant relief of LVOT obstruction. Residual pressure gradient of the ESH group was greater than in the N-ESH group. The proportions of patients with moderate-to-severe mitral regurgitation and systolic anterior motion of the mitral valve (SAM) decreased in both groups. Postprocedural limiting symptoms were evaluated at a median of 8.0 days (IQR, 4.0 days) after ASA. Both the ESH and N-ESH groups got significant improvements in limiting symptoms. No significant differences in postprocedural limiting symptoms were observed between the two groups. Two patients (0.8%) in the N-ESH group died from procedural complications of ASA, including 1 death caused by ventricular fibrillation and 1 death caused by hemorrhagic shock. No patient in the ESH group died from procedural complications. Complete atrioventricular block occurred in 117 patients (42.9%) of the total study population, including 7 patients (41.2%) in the ESH group and 110 patients (43.0%) in the N-ESH group (P=.88). Atrioventricular conduction was restored in all of these patients before discharge, and no new permanent pacemaker dependency occurred.
Follow-up. Follow-up was completed in 273 patients (100%). At a median of 1.1 years (IQR, 1.5 years) after ASA, residual pressure gradient was 48.5 ± 40.4 mm Hg in the ESH group and 40.9 ± 35.2 mm Hg in the N-ESH group (P=.33). One patient (5.9%) in the ESH group and 43 patients (16.9%) in the N-ESH group presented with New York Heart Association (NYHA) class III/IV (P=.39). One patient (5.9%) in the ESH group and 26 patients (10.2%) in the N-ESH group presented with Canadian Cardiovascular Society (CCS) class III/IV (P=.87). Maximum septal thickness reduced to 26.7 ± 4.0 mm in the ESH group and 19.3 ± 4.9 mm in the N-ESH group (P<.001) (Table 3). No significant differences in the utilization of medications were observed between the two groups. Serial pressure gradient measurements, NYHA class, and CCS class assessments are shown in Figure 1, Figure 2, and Figure 3, respectively.
After a median follow-up of 4.9 years (IQR, 4.3 years), a total of 11 patients died, all in the N-ESH group. The 5-year survival rate of the total study population was 95.7% (95% confidence interval [CI], 93.0%-98.4%). There was no significant difference in survival between the ESH group and the N-ESH group (log-rank P=.29). Two of the 11 deaths in the N-ESH group were sudden cardiac death. No patient in the ESH group experienced ventricular fibrillation or sustained ventricular tachycardia (P>.99). Two patients (0.8%) in the N-ESH group underwent permanent pacemaker implantation for sinus bradycardia. No patient in the ESH group developed new permanent pacemaker dependency (P>.99). During the follow-up period, a total of 17 patients underwent a second invasive therapy to treat LVOT obstruction-related limiting symptoms, including 1 patient (5.9%; myectomy) in the ESH group and 16 patients (6.3%; 11 myectomy, 4 ASA, and 1 dual-chamber pacing) in the N-ESH group (P>.99). The follow-up data on limiting symptoms, residual pressure gradient, mitral regurgitation, SAM, maximum septal thickness, and medications of these patients were all obtained before the second invasive therapy was performed.
Discussion
This study compared the effectiveness of ASA in obstructive HCM patients with ESH vs without ESH. The main findings of this study are: (1) the residual pressure gradient in the acute phase after ASA was higher in patients with ESH vs without ESH, while it was comparable between the two groups at 1.1 years of follow-up; (2) no significant differences in severe limiting symptoms were observed after ASA between the two groups; and (3) no significant differences in the incidence rates of serious complications (mainly complete heart block and ventricular fibrillation/sustained ventricular tachycardia) were observed between the two groups.
Pressure gradient reduction occurs immediately after alcohol injection.4,11-13 The rebound of pressure gradient occurs several days later.14,15 Both the ESH group and N-ESH group experienced this course in this study. The acute reduction of pressure gradient is associated with the decrease of myocardial contractility and changes in left ventricular ejection dynamics following alcohol injection.14,16,17 Pressure gradient will rebound with the recovery of myocardial contractility several days later. As time went on, the thinning of septal myocardium occurred, which results in the widening of LVOT and the further reduction of pressure gradient. As the markers of dynamic outflow tract obstruction, mitral regurgitation and SAM will decrease with the relief of obstruction.
The residual pressure gradient in the acute phase after ASA was significantly higher in patients with ESH vs without ESH. This raised the concern that ASA may be less effective in patients with ESH. However, as previously reported,18 the follow-up pressure gradient and limiting symptoms of the ESH group were comparable with the N-ESH group. This suggested that long-term effect of ASA was comparable between patients with ESH and without ESH.
The effect of ESH on all-cause mortality after ASA is controversial. Jensen et al reported that all-cause mortality after ASA was higher in patients with vs without ESH,19 whereas this phenomenon was not observed by Veselka et al.18 There was no difference in survival between patients with ESH vs without ESH in this study, which was in line with Veselka et al.
As no significant differences in the incidence rates of serious complications were observed between the ESH and N-ESH groups, it seems likely that ASA for patients with ESH was as safe as for patients without ESH. However, higher doses of alcohol and multiple septal branches are associated with greater potential arrhythmogenic myocardial damage of the septum.20 It is recommended to minimize the dose of alcohol and the number of septal branches. Further studies are needed to investigate the minimum effective dose of alcohol and the minimum number of septal branches in patients with ESH.
As discussed above, ASA appeared safe and effective in patients with ESH. This raises the possibility that ASA is also an alternative to myectomy in patients with ESH. However, before head-to-head comparisons of ASA and myectomy in patients with ESH to validate this conjecture, myectomy should be recommended first for patients with ESH and eligible for surgery. ASA should be limited to patients who are not suitable for surgery or have a desire to avoid the myectomy procedure.
Study limitations. There are several limitations of this study. First, like most studies on HCM, this is a retrospective, non-randomized study, which have common inherent limitations of this type of study. Second, as the number of patients with ESH is limited in the current study, further studies are needed to validate the safety and efficacy of ASA in patients with ESH. Finally, as disopyramide is not available in China, no patients in our study were treated with this medication.
Conclusion
In summary, although the effectiveness of ASA in relieving LVOT obstruction in patients with ESH was not as good as in patients without ESH in the acute phase after ASA, the decrease of pressure gradient happened during follow-up and the residual pressure gradient will finally be comparable between patients with ESH vs without ESH. The improvements of limiting symptoms after ASA are similar. The effectiveness of ASA seems comparable between patients with ESH vs without ESH.
References
1. Maron MS, Olivotto I, Zenovich AG, et al. Hypertrophic cardiomyopathy is predominantly a disease of left ventricular outflow tract obstruction. Circulation. 2006;114:2232-2239.
2. Gersh BJ, Maron BJ, Bonow RO, et al. 2011 ACCF/AHA guideline for the diagnosis and treatment of hypertrophic cardiomyopathy: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;58:e212-e260.
3. Elliott PM, Anastasakis A, Borger MA, et al. 2014 ESC guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC). Eur Heart J. 2014;35:2733-2779.
4. Sigwart U. Non-surgical myocardial reduction for hypertrophic obstructive cardiomyopathy. Lancet. 1995;346:211-214.
5. Sorajja P, Valeti U, Nishimura RA, et al. Outcome of alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Circulation. 2008;118:131-139.
6. Sorajja P, Ommen SR, Holmes DJ, et al. Survival after alcohol septal ablation for obstructive hypertrophic cardiomyopathy. Circulation. 2012;126:2374-2380.
7. Veselka J, Zemanek D, Tomasov P, Duchonova R, Linhartova K. Alcohol septal ablation for obstructive hypertrophic cardiomyopathy: ultra-low dose of alcohol (1 mL) is still effective. Heart Vessels. 2009;24:27-31.
8. Rakowski H, Sasson Z, Wigle ED. Echocardiographic and Doppler assessment of hypertrophic cardiomyopathy. J Am Soc Echocardiogr. 1988;1:31-47.
9. Sasson Z, Yock PG, Hatle LK, Alderman EL, Popp RL. Doppler echocardiographic determination of the pressure gradient in hypertrophic cardiomyopathy. J Am Coll Cardiol. 1988;11:752-756.
10. Yuan J, Qiao S, Zhang Y, et al. Follow-up by cardiac magnetic resonance imaging in patients with hypertrophic cardiomyopathy who underwent percutaneous ventricular septal ablation. Am J Cardiol. 2010;106:1487-1491.
11. Knight C, Kurbaan AS, Seggewiss H, et al. Nonsurgical septal reduction for hypertrophic obstructive cardiomyopathy: outcome in the first series of patients. Circulation. 1997;95:2075-2081.
12. Seggewiss H, Gleichmann U, Faber L, Fassbender D, Schmidt HK, Strick S. Percutaneous transluminal septal myocardial ablation in hypertrophic obstructive cardiomyopathy: acute results and 3-month follow-up in 25 patients. J Am Coll Cardiol. 1998;31:252-258.
13. Lakkis NM, Nagueh SF, Kleiman NS, et al. Echocardiography-guided ethanol septal reduction for hypertrophic obstructive cardiomyopathy. Circulation. 1998;98:1750-1755.
14. Carasso S, Woo A, Yang H, et al. Myocardial mechanics explains the time course of benefit for septal ethanol ablation for hypertrophic cardiomyopathy. J Am Soc Echocardiogr. 2008;21:493-499.
15. Veselka J, Duchonova R, Prochazkova S, et al. The biphasic course of changes of left ventricular outflow gradient after alcohol septal ablation for hypertrophic obstructive cardiomyopathy. Kardiol Pol. 2004;60:133-136.
16. van Ramshorst J, Mollema SA, Delgado V, et al. Relation of immediate decrease in ventricular septal strain after alcohol septal ablation for obstructive hypertrophic cardiomyopathy to long-term reduction in left ventricular outflow tract pressure gradient. Am J Cardiol. 2009;103:1592-1597.
17. Nagueh SF, Ommen SR, Lakkis NM, et al. Comparison of ethanol septal reduction therapy with surgical myectomy for the treatment of hypertrophic obstructive cardiomyopathy. J Am Coll Cardiol. 2001;38:1701-1706.
18. Veselka J, Lawrenz T, Stellbrink C, et al. Early outcomes of alcohol septal ablation for hypertrophic obstructive cardiomyopathy: a European multicenter and multinational study. Catheter Cardiovasc Interv. 2014;84:101-107.
19. Jensen MK, Prinz C, Horstkotte D, et al. Alcohol septal ablation in patients with hypertrophic obstructive cardiomyopathy: low incidence of sudden cardiac death and reduced risk profile. Heart. 2013;99:1012-1017.
20. Kuhn HJ. Optimizing catheter-based therapy of hypertrophic obstructive cardiomyopathy: does alcohol dose matter? Can J Cardiol. 2011;27:668-670.
___________________________________________
From the 1Key Laboratory of Clinical Trial Research in Cardiovascular Drugs, Ministry of Health; 2Department of Cardiology; and 3Department of Echocardiography, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Funding: This work was supported by the National Key Clinical Specialty Project and the National Science and Technology Major Project (No. 2012ZX09303008-001) from the Ministry of Science and Technology of China.
Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. The authors report no conflicts of interest regarding the content herein.
Manuscript submitted July 14, 2015, provisional acceptance given July 31, 2015, final version accepted August 21, 2015.
Addresses for correspondence: Chao-Mei Fan, 167 Beilishi Rd, Xi Cheng District, Beijing, China 100037. Email: fancm2004@126.com; and Jin-Qing Yuan, 167 Beilishi Rd, Xi Cheng District, Beijing, China 100037. Email: yuanjinqing2013@yeah.net
