Target population for a selective cardiac myosin inhibitor in hypertrophic obstructive cardiomyopathy: Real-life estimation from the French register of hypertrophic cardiomyopathy (REMY)

Alessandro Parodi; Tania Puscas; Patricia Réant; Erwan Donal; Dorra M'Barek Raboudi; Clarisse Billon; Anne Bacher; Mohamed El Hachmi; Karim Wahbi; Xavier Jeunemaître; Albert Hagège; REMY Working Group of the French Society of Cardiology

doi:10.1016/j.acvd.2024.04.001

Target population for a selective cardiac myosin inhibitor in hypertrophic obstructive cardiomyopathy: Real-life estimation from the French register of hypertrophic cardiomyopathy (REMY)

Arch Cardiovasc Dis. 2024 May 7:S1875-2136(24)00070-6. doi: 10.1016/j.acvd.2024.04.001. Online ahead of print.

Affiliations

¹ Département de cardiologie, hôpital européen Georges-Pompidou, AP-HP, 75015 Paris, France; Università del Piemonte Orientale Amedeo Avogadro, 13100 Vercelli, Italy.
² Département de cardiologie, hôpital européen Georges-Pompidou, AP-HP, 75015 Paris, France.
³ Département de cardiologie, hôpital Haut-Lévêque, CHU de Bordeaux, université de Bordeaux, Inserm 1045, IHU Lyric, CIC 1401, 33600 Pessac, France.
⁴ Service de cardiologie, hôpital Pontchaillou, CHU de Rennes, université de Rennes, Inserm, LTSI-UMR 1099, 35000 Rennes, France.
⁵ Département de génétique, hôpital européen Georges-Pompidou, AP-HP, 75015 Paris, France; Molecular Medicine, La Sapienza University, 00185 Rome, Italy.
⁶ Département de génétique, hôpital européen Georges-Pompidou, AP-HP, 75015 Paris, France; Inserm U970, Paris Cardiovascular Research Centre, Université Paris Cité, 75015 Paris, France.
⁷ Département de cardiologie, hôpital européen Georges-Pompidou, AP-HP, 75015 Paris, France; Inserm U970, Paris Cardiovascular Research Centre, Université Paris Cité, 75015 Paris, France. Electronic address: albert.hagege@aphp.fr.

PMID: 38762345
DOI: 10.1016/j.acvd.2024.04.001

Abstract

Background: The efficacy of current pharmacological therapies in hypertrophic cardiomyopathy is limited. A cardiac myosin inhibitor, mavacamten, has recently been approved as a first-in-class treatment for symptomatic hypertrophic obstructive cardiomyopathy.

Aims: To assess the profile and burden of cardiac myosin inhibitor candidates in the hypertrophic cardiomyopathy prospective Register of hypertrophic cardiomyopathy (REMY) held by the French Society of Cardiology.

Methods: Data were collected at baseline and during follow-up from patients with hypertrophic cardiomyopathy enrolled in REMY by the three largest participating centres.

Results: Among 1059 adults with hypertrophic cardiomyopathy, 461 (43.5%) had obstruction; 325 (30.7%) of these were also symptomatic, forming the "cardiac myosin inhibitor candidates" group. Baseline features of this group were: age 58±15years; male sex (n=196; 60.3%); diagnosis-to-inclusion delay 5 (1-12)years; maximum wall thickness 20±6mm; left ventricular ejection fraction 69±6%; family history of hypertrophic cardiomyopathy or sudden cardiac death (n=133; 40.9%); presence of a pathogenic sarcomere gene mutation (n=101; 31.1%); beta-blocker or verapamil treatment (n=304; 93.8%), combined with disopyramide (n=28; 8.7%); and eligibility for septal reduction therapy (n=96; 29%). At the end of a median follow-up of 66 (34-106) months, 319 (98.2%) were treated for obstruction (n=43 [13.2%] received disopyramide), 46 (14.2%) underwent septal reduction therapy and the all-cause mortality rate was 1.9/100 person-years (95% confidence interval 1.4-2.6) (46 deaths). Moreover, 41 (8.9%) patients from the initial hypertrophic obstructive cardiomyopathy group became eligible for a cardiac myosin inhibitor.

Conclusions: In this cohort of patients with hypertrophic cardiomyopathy selected from the REMY registry, one third were eligible for a cardiac myosin inhibitor.

Keywords: Cardiac myosin inhibitor; Hypertrophic cardiomyopathy; Obstruction; Registry.