To answer that question, SCOUT-HCM enrolled symptomatic adolescents aged 12 to < 18 years with obstructive HCM [9]. Other key inclusion criteria included a Valsalva-provoked LVOT gradient ≥ 30 mmHg, maximal LVOT gradient ≥ 50 mmHg at rest, during Valsalva or after exercise, left ventricular ejection fraction (LVEF) ≥ 60%, and New York Heart Association (NYHA) functional class II or III symptoms. This trial excluded patients with HCM phenocopies, such as Noonan syndrome and Fabry disease.

Patients were stratified by age and beta-blocker use and randomised 1:1 to mavacamten or placebo for a 28-week double-blind treatment period [9]. Mavacamten was started once daily according to body weight and titrated based on echocardiographic assessment of Valsalva LVOT and LVEF. The primary endpoint was the change in Valsalva-provoked LVOT gradient from baseline to week 28 [9]. Key secondary endpoints were change in resting and post-exercise LVOT gradients, maximal LV wall thickness, E/e’ ratio, and patient-reported Hypertrophic Cardiomyopathy Symptom Questionnaire (HCMSQ) Shortness-of-breath score, peak oxygen uptake, NYHA class and mitral regurgitation. Exploratory endpoints included NT-proBNP and high-sensitivity cardiac troponins [9]. Since SCOUT-HCM was built around a haemodynamic primary endpoint in a small trial; the symptom, exercise, imaging and biomarker measures help interpret the results, but should not carry the same weight as the primary endpoint.

In total, 65 patients were screened, and 44 patients underwent randomisation to mavacamten (23 patients) or placebo (21 patients) [9]. The trial period was completed by all, but 1 patient: one placebo-treated patient requested unblinding and underwent myectomy due to symptom persistence. Baseline demographics and clinical characteristics were largely similar between the two cohorts, including baseline LVOT gradients (78.4 ± 34.1 mmHg in the mavacamten group vs. 80.8 ± 47.4 mmHg in the placebo group). Slight imbalances were observed in body mass index, NT-proBNP and high-sensitivity cardiac troponin I, with higher median biomarker concentrations in the mavacamten group at baseline [9]. Most patients were already receiving background HCM therapy, including beta-blockers in 83% and 86% of the mavacamten and placebo groups, respectively. In the mavacamten group, 91% of patients received an initial dose of 5 mg mavacamten daily and demonstrated ≥ 80% dose adherence [9].

Treatment with Mavacamten resulted in significant improvements in Valsalva-provoked LVOT gradients compared to placebo at week 28 [9]. The least-squares mean change in Valsalva LVOT gradient was − 48.5 mmHg with mavacamten and − 0.5 mmHg with placebo, corresponding to a between-group difference of − 48.0 mmHg (95% CI, − 67.7 to − 28.3; P < 0.001). Descriptive secondary analyses supported the primary endpoint, including reductions in resting and post-exercise LVOT gradients, maximal LV wall thickness and E/e′ ratio, and higher proportions of patients with NYHA class and mitral regurgitation improvement [9]. However, the HCMSQ Shortness-of-Breath score showed only a small between-group difference. Exploratory biomarker analyses showed lower NT-proBNP and high-sensitivity troponin concentrations with mavacamten compared to placebo, supporting a possible reduction in myocardial stress and injury [9]. Similar adverse event rates were seen in mavacamten and placebo groups (18 patients [78%] vs. 17 patients [81%], respectively). Two patients in each group had serious adverse events. No deaths occurred and no patient had an LVEF reduction to < 50%.

The most robust finding from SCOUT-HCM is the reduction in Valsalva-provoked LVOT gradient, while the symptom and exercise findings require more careful interpretation. Despite the marked haemodynamic improvement, the between-group difference in HCMSQ Shortness-of-Breath score was small, and the peak VO₂ data were not definitive. This is perhaps not surprising in adolescents, where symptoms and exercise capacity are influenced by more than LVOT obstruction alone, including physical conditioning, anxiety, school and sports participation, placebo response, short follow-up, small numbers, and the limitations of symptom tools not developed specifically for paediatric oHCM. The changes in wall thickness, E/e′, NT-proBNP and high-sensitivity troponin are encouraging and biologically plausible but should be viewed as signals of reduced myocardial stress and possible early remodelling, rather than evidence that durable disease modification has been achieved.