Alcohol septal ablation (ASA) is associated with greater all-cause long-term mortality than surgical septal myectomy in patients with obstructive hypertrophic cardiomyopathy (HCM), new real-world data suggest. The study, published online Monday and in the May 3 issue of the Journal of the American College of Cardiology, compared the long-term mortality of patients with obstructive HCM following septal myectomy or ASA – reporting a 68% higher hazard of mortality associated with ASA. The team, led by Hao Cui, MD, from the Mayo Clinic, Rochester, Minnesota, noted that left ventricular outflow tract (LVOT) obstruction is present in 70% to 75% of symptomatic patients with HCM. “For most patients, initial management is medical using beta-blockers, calcium-channel blocking agents, and/or disopyramide,” they noted, adding that septal reduction therapy by surgical myectomy can provide predictable, near-complete relief of LVOT obstruction in patients who do not tolerate or respond to maximal medical treatment. Indeed, they noted that septal myectomy has been shown to improve symptoms and survival similar to a normal population during the first decade after the operation. Cui and colleagues added that percutaneous ASA is an alternate septal reduction therapy (SRT) that reduces septal thickness by targeted myocardial infarction, noting that studies from several experienced centers have shown favorable outcomes with ASA regarding symptom relief and survival. “Over the past 2 decades, there has been an ongoing debate regarding the relative merits of septal myectomy vs ASA for obstructive HCM, but there are few studies that directly compare the outcomes of the 2 procedures,” said the authors.“Furthermore, randomized trials of SRT are unlikely to be undertaken in the near future, and actionable results regarding patient survival will require lengthy follow-up.” Study setup Cui and colleagues evaluated the outcomes of 3,859 patients who underwent ASA or septal myectomy in three specialized HCM centers: Mayo Clinic; Tufts Medical Center, Boston; and Fuwai Hospital, Beijing. The team noted that each participating center is highly experienced in both septal myectomy (cumulative volume: >300) and ASA (cumulative volume: >150). “We reviewed patients with obstructive HCM who underwent septal myectomy or ASA at each institution from 1998 through 2019. We excluded patients who had prior septal myectomy or ASA before their index septal reduction at the study center.” Also excluded were patients undergoing septal myectomy who had a major concomitant cardiovascular procedure such as coronary artery bypass grafting for coronary artery disease or mitral valve repair for associated degenerative valve regurgitation. All-cause mortality was the primary endpoint of the study, the team noted, adding that survival data were obtained through prospectively maintained databases at each center, and were supplemented by LexisNexis Accurint, which links data from several sources, including the Social Security Death Master File and state death records, in the United States. Key findings According to the team, the median age was 54.8 years (interquartile range [IQR]: 45.8-64.3 years), with 2,115 (54.8%) male participants. A total of 585 (15.2%) patients underwent ASA, while 3,274 (84.8%) underwent septal myectomy. Patients undergoing ASA were significantly older than those undergoing septal myectomy (63.0 years [IQR: 52.7-72.8 years] vs. 53.7 years [IQR: 44.9-62.8 years]; P < 0.001), said the authors, noting that those undergoing ASA also had more comorbidities, including renal failure, diabetes, hypertension, and coronary artery disease. Over a median follow-up of 6.4 years (IQR: 3.6-10.2 years), Cui and colleagues reported that the 10-year all-cause mortality rate was 26.1% in the ASA group and 8.2% in the myectomy group. After adjustment for age, sex, and comorbidities, the mortality rate remained greater in patients having septal reduction by ASA (hazard ratio [HR]: 1.68; 95% confidence interval [CI]: 1.29-2.19; P < 0.001). “We further analyzed whether the treatment effect (ASA vs myectomy) on long-term mortality varied according to specific variables of interest,” they said. “Despite some fluctuation in the HR of death for ASA vs myectomy across a wide age range, there was no statistical evidence of a differential treatment effect according to age (interaction P = 0.222).” They added that the relative risk of ASA compared to myectomy was generally stable over the range of LVOT gradients. “However, we did observe a significant difference in the treatment effect according to NYHA [New York Heart Association] functional class (interaction P = 0.003), in which the estimated risk for death associated with ASA was worse among NYHA functional class IV patients (HR: 7.64; 95% CI: 2.78-20.99).” “In patients with obstructive HCM, those undergoing ASA are older and have more comorbidities and less septal thickness compared to patients undergoing septal myectomy,” concluded the team. “ASA is associated with increased long-term all-cause mortality. This impact on survival is independent of other known clinical and echocardiographic variables but may be influenced by unmeasured confounding patient characteristics,” they noted, adding that further studies are needed to improve the selection of patients with obstructive HCM for one type of septal reduction procedure over the other. ASA ‘should not be considered’ in most patients Writing in an accompanying editorial, Mark V. Sherrid, MD; Daniele Massera, MD, MSc; and Daniel G. Swistel, MD, from the New York University School of Medicine, noted that prior retrospective comparisons focused on short-term outcomes from single centers had shown largely similar mortality, despite higher residual LVOT gradients and pacemaker implantation rates from ASA. “Myectomy, as now performed at expert centers, is a low-mortality undertaking, lower than virtually all other cardiac surgical procedures,” said the editorialists. They noted that the data from the study show that ASA yields suboptimal relief of gradient and symptoms, and “because, as shown, alcohol ablation is associated with higher mortality, it should not be considered a routine therapeutic choice for patients with medication-resistant obstructive HCM.” Indeed, the expert commentators recommend that ASA should be reserved for patients who have severe chronic obstructive pulmonary disease, frailty, other causes of increased surgical risk, or limited life expectancy. “The remaining large majority of patients should be referred to a center with surgical expertise,” they said. Sources: Cui H, Schaff HV, Wang S, et al. Survival Following Alcohol Septal Ablation or Septal Myectomy for Patients With Obstructive Hypertrophic Cardiomyopathy. J Am Coll Cardiol 2022;79:1647-1655. Sherrid MV, Massera D, Swistel DG. Surgical Septal Myectomy and Alcohol Ablation: Not Equivalent in Efficacy or Survival. J Am Coll Cardiol 2022;79:1656-1659. 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