Key result
Mavacamten reduces Valsalva LVOT gradient by ~41 mm Hg at 1 year in latent oHCM.
Why the study?
Approximately one-third of patients with HCM have latent LVOT obstruction present only with physiological provocation, and this sub-analysis evaluated the real-world effectiveness and safety of mavacamten in these patients.
Does mavacamten improve LVOT gradients and NYHA functional class in patients with symptomatic obstructive hypertrophic cardiomyopathy with latent obstruction in a real-world setting?
Cohort (n=69)
Yes
Does mavacamten improve LVOT gradients and NYHA functional class in patients with symptomatic obstructive hypertrophic cardiomyopathy with latent obstruction in a real-world setting?
In a global real-world cohort, mavacamten provided meaningful haemodynamic and clinical symptom improvements in patients with symptomatic obstructive HCM who have latent LVOT obstruction.
Answers are grounded in this paper and cite their sources.
Mavacamten was associated with gradient reductions and NYHA improvement in latent obstructive HCM; extends trial data to real-world settings but leaves open randomized confirmation.
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.
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Paratz et al. (2026) conducted a cohort in Symptomatic obstructive hypertrophic cardiomyopathy with latent obstruction (n=69). Mavacamten was evaluated on Resting and Valsalva LVOT gradients and NYHA class improvement at 1 year (MD -40.9 mm Hg (Valsalva LVOT gradient)). Mavacamten reduced mean Valsalva LVOT gradient by 40.9 mm Hg and resting gradient by 10.1 mm Hg at 1 year, with 56.3% of latent obstructive HCM patients improving by ≥1 NYHA class.
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