Abstract
BACKGROUND: Hypertrophic cardiomyopathy (HCM) symptoms include shortness of breath (SOB), fatigue, chest pain, palpitations, dizziness, and fainting. The HCM Symptom Questionnaire (HCMSQ), the only patient-reported outcome instrument designed to specifically measure HCM symptoms, yields four domain scores (SOB, tiredness, cardiovascular symptoms, syncope) and a total score. We evaluated the longitudinal psychometric properties of the HCMSQ using baseline to week 30 data from the phase III EXPLORER-HCM trial (NCT03470545). METHODS: Test-retest reliability was assessed via intraclass correlation of patients with stable Patient Global Impression of Change (PGIC) and Patient Global Impression of Severity (PGIS) responses. Sensitivity to change was assessed via Spearman correlations with the Kansas City Cardiomyopathy Questionnaire (KCCQ-23) and the EuroQoL visual analogue scale (EQ VAS), and via one-way ANOVA comparing change groups defined on clinical (New York Heart Association [NYHA] class, left ventricular outflow tract [LVOT] gradient, peak oxygen consumption [pVO(2)]) and patient-reported (PGIS, PGIC) variables. Meaningful change thresholds were established via PGIC/PGIS. RESULTS: All HCMSQ scores showed strong evidence of test-retest reliability (intraclass correlation coefficient > 0.70). Sensitivity to change was demonstrated with mostly strong/moderate correlations with KCCQ-23 and EQ VAS, and significant differences (p ≤ 0.05) in PGIS, PGIC, pVO(2), and NYHA (except tiredness domain) change categories, but not LVOT gradient. Clinically meaningful score reductions were ≥1 point for tiredness and cardiovascular symptoms domains, ≥ 2.5 points for SOB domain, and ≥2 points for total score. CONCLUSIONS: Results suggest that HCMSQ is fit for purpose in capturing HCM symptoms and may provide evidence of treatment benefit from the patients' perspectives.