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Multicenter Study
. 2024 Oct 22;150(17):1377-1390.
doi: 10.1161/CIRCULATIONAHA.124.069378. Epub 2024 Oct 2.

Long-Term Outcomes After Septal Reduction Therapies in Obstructive Hypertrophic Cardiomyopathy: Insights From the SHARE Registry

Niccolò Maurizi  1   2 , Panagiotis Antiochos  2 , Anjali Owens  3 , Neal Lakdawala  4 , Sara Saberi  5 , Mark W Russell  6 , Carlo Fumagalli  1   7 , Ioannis Skalidis  2 , Kimberly Y Lin  8 , Ashwin S Nathan  3 , Alejandro De Feria Alsina  3 , Nosheen Reza  3 , John C Stendahl  9 , Dominic Abrams  10 , Christopher Semsarian  11   12   13 , Brian Clagget  14 , Rachel Lampert  8 , Matthew Wheeler  15 , Victoria N Parikh  15 , Euan Ashley  15 , Michelle Michels  16 , Joseph Rossano  8 , Thomas D Ryan  17 , Jodie Ingles  18 , James Ware  19 , Carolyn Y Ho  4 , Adam S Helms  5 , Sharlene M Day #  3 , Iacopo Olivotto #  1   20
Affiliations
Multicenter Study

Long-Term Outcomes After Septal Reduction Therapies in Obstructive Hypertrophic Cardiomyopathy: Insights From the SHARE Registry

Niccolò Maurizi et al. Circulation. .

Abstract

Background: Septal reduction therapy (SRT) provides substantial symptomatic improvement in patients with obstructive hypertrophic cardiomyopathy (HCM). However, long-term disease course after SRT and predictors of adverse outcomes have not been systematically examined.

Methods: Data from 13 high clinical volume HCM centers from the international SHARE (Sarcomeric Human Cardiomyopathy Registry) were analyzed. Patients were followed from the time of SRT until last follow-up or occurrence of heart failure (HF) composite outcome (cardiac transplantation, implantation of a left ventricular assist device, left ventricular ejection fraction <35%, development of New York Heart Association class III or IV symptoms), ventricular arrhythmias composite outcome (sudden cardiac death, resuscitated cardiac arrest, or appropriate implantable cardioverter defibrillator therapy), or HCM-related death. Cox proportional hazards models were used to identify predictors of outcome.

Results: Of the 10 225 patients in SHARE, 1832 (18%; 968 [53%] male) underwent SRT, including 455 (25%) with alcohol septal ablation and 1377 (75%) with septal myectomy. The periprocedural 30-day mortality rate was 0.4% (8 of 1832) and 1499 of 1565 (92%) had a maximal left ventricular outflow tract gradient <50 mm Hg at 1 year. After 6.8 years (range, 3.4-9.8 years; 12 565 person-years) from SRT, 77 (4%) experienced HCM-related death (0.6% per year), 236 (13%) a composite HF outcome (1.9% per year), and 87 (5%) a composite ventricular arrhythmia outcome (0.7% per year). Among adults, older age at SRT was associated with a higher incidence of HCM death (hazard ratio, 1.22 [95 CI, 1.1-1.3]; P<0.01) and the HF composite (hazard ratio, 1.14 [95 CI, 1.1-1.2] per 5-year increase; P<0.01) in a multivariable model. Female patients also had a higher risk of the HF composite after SRT (hazard ratio, 1.4 [95 CI, 1.1-1.8]; P<0.01). De novo atrial fibrillation occurred after SRT in 387 patients (21%). Among pediatric patients followed for a median of 13 years after SRT, 26 of 343 (16%) developed the HF composite outcome, despite 96% being free of recurrent left ventricular outflow tract obstruction.

Conclusions: Successful short- and long-term relief of outflow tract obstruction was observed in experienced multidisciplinary HCM centers. A subset of patients progressed to develop HF, but event-free survival at 10 years was 83% and ventricular arrhythmias were rare. Older age, female sex, and SRT during childhood were associated with a greater risk of developing HF.

Keywords: cardiomyopathy, hypertrophic; heart failure; hypertrophy, left ventricular; myectomy.

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Conflict of interest statement

Dr Ho is supported by funding from the National Institutes of Health (National Heart, Lung, and Blood Institute grant R01HL155568). Dr Day is supported by funding from the National Institutes of Health (National Heart, Lung, and Blood Institute grants R01 HL167524, R01 HL168841, and R61/R33 HL164376), Lexicon Pharmaceuticals, and the American Heart Association. Dr Ware is supported by the Wellcome Trust (grant 107469/Z/15/Z) and the UK Medical Research Council. Dr Scemsarian is the recipient of a National Health and Medical Research Council investigator grant (grant 2016822) and a New South Wales Health cardiovascular disease clinician scientist grant. Dr Ingles is the recipient of a National Heart Foundation of Australia future leader fellowship grant (grant 106732) and receives research grant support from Bristol Myers Squibb. Dr Reza is supported by funding from the National Institutes of Health (National Heart, Lung, and Blood Institute grant K23HL166961). Dr I. Olivotto has received grants from Bristol Myers Squibb, Cytokinetics, Amicus, Genzyme, Shire, Bayer, Boston Scientific, and Menarini International; fees (honoraria or consulting) from Bristol Myers Squibb, Cytokinetics, Amicus, Genzyme, Shire, and Boston Scientific; and served or is serving as principal investigator for EXPLORER‐HCM (Clinical Study to Evaluate Mavacamten [MYK-461] in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy), MAVA‐LTE (A Long-Term Safety Extension Study of Mavacamten in Adults Who Have Completed EXPLORER-HCM), REDWOOD‐HCM (Randomized Evaluation of Dosing With CK-3773274 in Obstructive Outflow Disease in HCM), REDWOOD‐OLE (REDWOOD‐HCM Open Label Extension), and SEQUOIA‐HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic oHCM). Dr Maurizi has received fees (honoraria or consulting) from Bristol Myers Squibb. Dr Ho receives research funding from the National Institutes of Health and has received unrestricted research funding or consulting fees from Bristol Myers Squibb, Cytokinetics, Pfizer, Tenaya, Biomarin, viz.AI, and Lexicon Pharmaceuticals. Dr Lakdawala receives research funding from BMS and Pfizer and modest consulting incomes from BMS, Pfizer, Alexion, Tenaya, Akros, Neuvocor, and Cytokinetics. Dr Stendahl serves or has served as site principal investigator for MAVA-LTE, PIONEER-OLE (Phase 2 Open-label Pilot Study Evaluating Mavacamten in Subjects With Symptomatic Hypertrophic Cardiomyopathy and Left Ventricular Outflow Tract Obstruction Open-Label Extension), and VALOR-HCM (A Study to Evaluate Mavacamten in Adults With Symptomatic Obstructive Hypertrophic Cardiomyopathy Who Are Eligible for Septal Reduction Therapy), and serves or has served as site subinvestigator for ACACIA-HCM (Phase 3 Trial to Evaluate the Efficacy and Safety of Aficamten Compared to Placebo in Adults With Symptomatic nHCM), FOREST-HCM (Follow-Up, Open-Label, Research Evaluation of Sustained Treatment with Aficamten in HCM), MAPLE-HCM (Metoprolol vs Aficamten in Patients with LVOT Obstruction on Exercise Capacity in HCM), and SEQUOIA-HCM.

Figures

Figure 1.
Figure 1.
Sex-stratified symptomatic classification of patients with Obstructive Hypertrophic Cardiomyopathy
Figure 2.
Figure 2.
Clinical outcomes after Septal Reduction Therapy in HCM and the impact of sex. Kaplan Meyer analysis of HCM-related deaths over follow-up and stratified per sex (Panel A), heart failure composite outcome occurrence stratified per sex (Panel B) and VA composite outcome stratified per sex (Panel C). Abbreviations: HF = heart failure; VA = ventricular arrhythmias; HCM = Hypertrophic Cardiomyopathy.
Figure 3.
Figure 3.
Event free survival for HCM related mortality, HF and VA outcomes after Septal Reduction Therapy. Kaplan Meyer analysis of HCM-related deaths, HF and VA outcomes over follow-up.
Figure 4.
Figure 4.
Incidence of LV EF < 50% and occurrence of NYHA Class III/IV after Septal Reduction Treatments Kaplan Meyer analysis of occurrence of LV EF < 50% and occurrence of NYHA III/IV stratified per procedure type (Panel A), sex (Panel B) and genotype (Panel C). Abbreviations: LV EF = Left Ventricular Ejection fraction.
Figure 5
Figure 5
Forest Plot depicting multivariable risk predictors of HCM-related death, HF composite outcome and for VA composite outcome. Abbreviations: HF = heart failure; HCM = Hypertrophic Cardiomyopathy. ASA: Alcohol Septal Ablation; SRT: Septal Reduction Therapy; SARC: sarcomere; VA: Ventricular arrhythmias.
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References

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