Abstract
BACKGROUND: Currently, there is no patient-reported outcome (PRO) instrument specifically designed to evaluate hypertrophic cardiomyopathy (HCM). OBJECTIVE: We present the development and psychometric validation of a novel PRO measure, the HCM Symptom Questionnaire version 1.0 (HCMSQv1.0). METHODS: Cognitive debriefing interviews and a card-sorting task were conducted in 33 patients with HCM to support development of the HCMSQv1.0, showing the scale to be interpretable and relevant to patients' experiences. Baseline blinded data from two trials (EXPLORER-HCM and MAVERICK-HCM) were pooled (N = 299) to develop the scoring algorithm of HCMSQv1.0. Measurement properties were examined, followed by a meaningful-change analysis to interpret scores. Rasch modeling, mixed-model repeated measures, exploratory factor analysis, confirmatory factor analysis, and missing-data simulation analysis informed the number of domains and the items in each domain. RESULTS: The scoring algorithm for HCMSQv1.0 consists of four domains: shortness of breath, tiredness, cardiovascular symptoms, and syncope; plus a total score, with higher scores indicating more severe symptoms. Item characteristics, internal consistency, test-retest reliability, construct validity, and responsiveness were acceptable. A clinically meaningful responder definition of 1-2 points on the HCMSQv1.0 score for shortness of breath and total score, and approximately 1 point on the tiredness and cardiovascular symptom scores, was calculated based on distribution- and anchor-based methods. CONCLUSION: Our findings support the HCMSQv1.0 as a fit-for-purpose PRO instrument for assessing treatment benefit in patients with HCM. Studies in larger patient populations are ongoing to confirm responder definition and scoring approaches encompassing key HCM symptoms.