Valsartan for Attenuating Disease Evolution In Early Sarcomeric HCM

⁃ All subjects must have a Pathogenic or Likely Pathogenic HCM Sarcomere Mutation

‣ a. The following categories of mutations are considered acceptable for subjects who have previously undergone clinical genetic testing. If results are ambiguous, they will be reviewed by the Clinical Coordinating Center to determine eligibility.

• Laboratory for Molecular Medicine (Pathogenic, Likely Pathogenic)

• Transgenomics/ PGXHealth (Class I)

• GeneDx (Disease causing; Variant; likely disease-causing; Published, disease-causing mutation; Novel, likely disease-causing, mutation)

• Correlagen (Associated; Probably Associated)

‣ Group 1 (Overt HCM Cohort)

⁃ LV wall thickness ≥12 mm and ≤25 mm or z score ≥3 and ≤18 as determined by rapid assessment by the echocardiographic core laboratory

⁃ NYHA functional class I or II; no perceived or only slight limitations in physical activities

⁃ No resting or provokable LV obstruction (peak gradient ≤ 30 mmHg) on clinically-obtained Exercise Tolerance Test (ETT)-echo within the past 24 months or transthoracic echo with Valsalva maneuver within the past 12 months

⁃ Age 8-45 years

⁃ Able to attend follow-up appointments, complete all study assessments, and provide written informed consent

‣ Group 2 (Preclinical HCM Cohort (G+/LVH-))

⁃ LV Wall Thickness \<12 mm and z score \<3 , as determined by rapid assessment by the echocardiographic core laboratory

⁃ Age 10-25 years

⁃ E' z score ≤ -1.5 OR ECG abnormalities other than NSSTW changes (Q waves, T wave inversion, repolarization changes) OR LV wall thickness z-score 1.5-2.9 combined with LV thickness to dimension ratio ≥0.19 (as determined by rapid assessment by the echocardiographic core laboratory)

⁃ Able to attend follow-up appointments, complete all study assessments, and provide written informed consent