Mavacamten shows benefits in patients with symptomatic obstructive hypertrophic cardiomyopathy with latent obstruction: global evidence from COLLIGO-HCM
E Paratz, P Arora, E Maor, M Arad, O Bilen, R Bastiaenen, J P MacNamara, D Husser, G Arora, E Burford, M Gold, C Pruett, E Maksabedian Hernandez, A AdlerAbstract
Background/Introduction
Approximately one-third of patients with hypertrophic cardiomyopathy (HCM) have latent obstruction, defined as left ventricular outflow tract (LVOT) obstruction (LVOT gradient ≥30 mm Hg) that is present with physiological provocation but not at rest. Mavacamten, a cardiac myosin inhibitor, is approved in over 60 countries for the treatment of adults with symptomatic obstructive HCM. COLLIGO-HCM is an international, multicentre study evaluating the real-world effectiveness and safety of mavacamten in patients with symptomatic obstructive HCM.
Purpose
The aim of this sub-analysis of COLLIGO-HCM was to evaluate the effectiveness and safety of mavacamten treatment among a cohort of patients with symptomatic obstructive HCM with latent obstruction in the real world.
Methods
Patient-level data from 7 sites and 5 countries (Australia, Canada, Israel, UK, and USA) were analysed in a cohort of mavacamten-treated patients with latent obstruction, defined as a baseline LVOT gradient of <30 mm Hg at rest and ≥30 mm Hg following provocation (Valsalva manoeuvre or exercise). Patient characteristics, echocardiographic data, and safety outcomes were assessed at baseline and during follow-up. Analyses used observed data only.
Results
Among 307 mavacamten-treated patients, 69 (22.5%) had latent LVOT obstruction. In this cohort, mean age was 59.0 years, 55.1% were male, and 53.6% were White. Median follow-up time was 9 months (39.9 weeks). The most common comorbidities were hypertension (42/69 [60.9%]), hyperlipidaemia (19/69 [27.5%]), and a history of atrial fibrillation (12/69 [17.4%]). At baseline, mean resting and Valsalva LVOT gradients were 18.2 mm Hg and 66.2 mm Hg, respectively; 44/68 patients (64.7%) were New York Heart Association (NYHA) class II, and 24/68 (35.3%) were class III. Most of the patients (76.8% [53/69]) were receiving background therapy with beta-blockers, calcium-channel blockers, and/or disopyramide at baseline. At 1 year, mean resting LVOT gradient was 10.2 mm Hg (mean [standard deviation (SD)] change from baseline: −10.1 [7.8] mm Hg [N=17]) and mean Valsalva LVOT gradient was 17.4 mm Hg (mean [SD] change from baseline: −40.9 [36.2] mm Hg [N=16]) (Figure 1); all patients (100% [17/17]) had a resting LVOT ≤30 mm Hg and 81.3% (13/16) had a Valsalva LVOT ≤30 mm Hg. At 1 year, 56.3% (9/16 patients) experienced ≥1 NYHA class improvement. Mean left ventricular ejection fraction remained ≥61.5% through follow-up (Figure 2). The safety profile was consistent with previous clinical trials.
Conclusions
In this global real-world cohort, a substantial proportion of patients with HCM had latent obstruction; therefore, routine provocation assessments are critical to avoid misclassification as nonobstructive HCM. Mavacamten treatment was associated with meaningful clinical and haemodynamic benefits in these patients with HCM with latent obstruction.