Table 1.

Inclusion and exclusion criteria of EXPLORER-HCM and SEQUOIA-HCM clinical trials [4,5].

EXPLORER-HCM clinical trial investigating Mavacamten
Key inclusion criteria	Key exclusion criteria
Aged at least 18 years	History of syncope or sustained ventricular tachyarrhythmia with exercise within the past 6 months
Diagnosed with obstructive HCM (LV hypertrophy with max LV wall thickness ≥15 mm or ≥13 mm if familial HCM)	QT interval corrected >500 ms using Fridericia’s formula
Peak LVOT gradient at least 50 mmHg (at rest, after Valsalva manoeuvre or exercise)	Paroxysmal or intermittent atrial fibrillation present on screening ECG
Left ventricular ejection fraction (LVEF) at least 55%	Persistent or permanent atrial fibrillation not on anticoagulation for 4 weeks+ or not adequately rate-controlled within the past 6 months
NYHA class II–III symptoms and able to perform upright CPET	Patients were allowed to continue standard hypertrophic cardiomyopathy medical therapy except disopyramide, including monotherapy with β blockers or calcium channel blockers, if dosing remained stable for at least 2 weeks before screening and no changes were anticipated during the study.
SEQUOIA-HCM clinical trial investigating Aficamten
Key inclusion criteria	Key exclusion criteria
Adults between 18 and 85 years of age at screening	Moderate-severe valvular aortic stenosis and/or regurgitation. Moderate-severe mitral regurgitation not caused by systolic anterior motion of the mitral valve
BMI <35 kg/m2	Known or suspected infiltrative, genetic, or storage disorder causing cardiac hypertrophy that mimics HOCM (e.g., Noonan syndrome, Fabry disease, amyloidosis)
Has an end-diastolic LV wall thickness as measured by the echocardiography core laboratory of • ≥15 mm in ≥1 myocardial segment OR • ≥13 mm in ≥1 wall segment and a known-disease-causing gene mutation or positive family history of HCM	History of LV systolic dysfunction (LVEF <45%) or stress cardiomyopathy at any time during the clinical course of the disease
RER ≥1.05 and pVO2 ≤90% predicted on the screening CPET per the core laboratory	Inability to exercise on a treadmill or bicycle (e.g., orthopedic limitations)
Resting LVOT gradient ≥30 mmHg AND post-Valsalva LVOT-G ≥50 mmHg	Has been treated with septal reduction therapy (surgical myectomy or percutaneous alcohol septal ablation) or plans for either treatment during the study period
LVEF ≥60% at screening	History of syncope or sustained ventricular tachyarrhythmia with exercise within 6 months before screening
NYHA functional class II or III at screening.	Has received prior treatment with aficamten or mavacamten
Patients on beta-blockers, verapamil, diltiazem, or disopyramide should have been on stable doses for >6 weeks prior to randomization and anticipate remaining on the same medication regimen during the study. Patients treated with disopyramide must also be concomitantly treated with a beta-blocker and/or calcium-channel blocker	Paroxysmal atrial fibrillation documented during the screening period
Hemoglobin ≥10 g/dL at screening	Paroxysmal or permanent atrial fibrillation requiring rhythm restoring treatment (e.g., direct-current cardioversion, atrial fibrillation ablation procedure, or antiarrhythmic therapy) ≤6 mo before screening (This exclusion does not apply if atrial fibrillation has been treated with anticoagulation and adequately rate-controlled for >6 mo).

CPET, cardiopulmonary exercise stress testing; ECG, electrocardiogram; HOCM, hypertrophic obstructive cardiomyopathy; NYHA, New York Heart Association; LVEF, left ventricular ejection fraction; LVOT, left ventricular outflow tract; HCM, hypertrophic cardiomyopathy; LV, left ventricular.