By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
Dr. Zimmet reports no financial relationships relevant to this field of study.
SYNOPSIS: Current guidelines recommend surgical myectomy over septal ablation for younger hypertrophic cardiomyopathy patients. A new study bridges part of the data gap, showing safety and efficacy of the procedure in young patients.
SOURCE: Liebregts M, Faber L, Jensen MK, et al. Outcomes of alcohol septal ablation in younger patients with obstructive hypertrophic cardiomyopathy. JACC Cardiovasc Interv 2017;10:1134-1143.
For symptomatic patients with hypertrophic cardiomyopathy (HCM) who exhibit significant left ventricular outflow tract gradients despite medical therapy (negatively inotropic therapy with beta-blockers, non-dihydropyridine calcium channel blockers, and disopyramide), septal reduction therapy may be considered for symptom relief. Traditionally, this has meant surgical myectomy, which has demonstrated long-term safety and efficacy, at least in the hands of a few high-volume specialty centers. Alcohol septal ablation was developed as a percutaneous alternative to myectomy, and has grown markedly in use since its initial introduction in 1995. Although data supporting the longer-term safety of this procedure have been accumulating, data regarding septal ablation in younger patients have been relatively lacking. For this reason, guidelines have discouraged its use in younger patients for whom the more-established surgical procedure is an option. The most recent American College of Cardiology/American Heart Association guidelines give a class III harm designation to this subgroup, stating “alcohol septal ablation should not be done in patients with HCM who are < 21 years of age and is discouraged in adults < 40 years of age if myectomy is a viable option.” The European Society of Cardiology guidelines, while more permissive, nonetheless address the controversy over these patients by noting that “there are no long-term data on the late effects of a myocardial scar in these groups.”
Liebregts et al reported outcomes from an observational study of consecutive patients with HCM who underwent septal ablation at seven centers in four European countries. With 1,197 patients included, this is the largest cohort of septal ablation patients reported to date. All patients met established morphologic criteria for the procedure, and the majority had persistent New York Heart Association (NYHA) functional class III or IV dyspnea. For the purposes of this report, patients were divided into three age groups: young (< 50 years), middle-age (51-64 years), and older (> 65 years). The young group included 369 patients, which is a respectable number in this area. Compared with older patients, the younger patients were less likely to be in functional class III or IV, but more exhibited at least two conventional risk factors for sudden cardiac death. Septal thickness also was slightly, but statistically significantly, greater in the youngest group compared with the other two groups, which matches a previously reported inverse relationship in patients undergoing alcohol septal ablation between age and septal thickness. Compared with older patients, the youngest patients demonstrated overall better markers of periprocedural safety, with lower rates of periprocedural death (0.3% vs. 2%; P = 0.03), pericardial tamponade (0.3 vs. 3%; P < 0.01), and heart block requiring permanent pacemaker implantation (8% vs. 16%; P < 0.001). For longer-term outcomes, follow-up averaged a respectable 5.4 years for the entire study group, and was completed for more than 99% of patients. Overall, survival was very good, with one-, five-, and 10-year survival rates of patients in the youngest group reported to be 99%, 95%, and 91%, compared with 100%, 99%, and 97%, respectively, in the age- and sex-matched controls. Serious adverse arrhythmic events were similar among the age groups, occurring at rates of fewer than 1% per year. Despite the noted higher septal thickness in younger patients, functional outcomes were quite good: At last follow up, 95% of the young patients were in NYHA functional class I or II, compared with 81% of the older patients (P < 0.001).
Patients < 35 years of age were termed “very young” and were reported in a separate analysis in addition to their inclusion in the young group. Among these 82 patients, there were no periprocedural mortalities, and the rate of new permanent pacemaker implant was 5%. Functional class improvement was good, and all-cause mortality was low (0.3% per year). In this large observational cohort study of alcohol septal ablation patients, these authors reported that patients < 50 years of age who underwent this procedure demonstrated favorable long-term survival, effective symptom alleviation, and acceptably low rates of arrhythmic events. Periprocedural complications, including need for pacemaker implantation, were significantly lower in the young compared to the older groups. The authors concluded that the recognized indications for alcohol septal ablation may be safely broadened for younger patients.
This is the largest reported study of alcohol septal ablation outcomes involving younger patients. Although comparative data between myectomy and septal ablation still are lacking, the results of this study are reassuring in terms of both the safety and efficacy of this procedure in such patients. But will it be enough, as the authors and the accompanying editorial suggested, to change published guidelines?
The answer is a matter of perspective. The excellent surgical myectomy outcomes data on which current guidelines favoring myectomy are based come primarily from a handful of high-volume centers of excellence that treat large numbers of such patients. Real-world data are not nearly as clear-cut. A recent study showed that large numbers of centers in the United States perform very low volumes of myectomy (the median was approximately one case per year), and that procedural outcomes are demonstrably worse in these centers.1 In fact, the low-volume tertile in that paper demonstrated approximately a four-fold increase in mortality compared with the higher-volume centers. The same study did not demonstrate a similar volume-outcome relationship for the less-invasive septal ablation procedure.
Some have argued that the take-home point from these studies should be to refer all HCM patients requiring septal reduction to regional specialized centers. The reality is that high-volume centers are not available in many areas, and patients continue to be treated locally. All patients considered for septal reduction therapy should continue to be discussed by multidisciplinary teams, which now have better data regarding the outcomes of septal ablation in younger patients. Ablation undoubtedly will be offered to increasing numbers of younger patients, but time will tell whether guideline writers will agree with this trend.
- Kim LK, Swaminathan RV, Looser P, et al. Hospital volume outcomes after septal myectomy and alcohol septal ablation for treatment of obstructive hypertrophic cardiomyopathy: US Nationwide Inpatient Database, 2003-2011. JAMA Cardiol 2016;1:324-332.