Defining Clinically Meaningful Within-Patient Changes in Heart Failure

Heart failure (HF) clinical trials increasingly rely on diverse endpoints beyond mortality, including hospitalizations, imaging, hemodynamic status, biomarkers, functional capacity, and patient-reported outcomes. Although statistically significant differences between treatment groups are commonly reported, interpreting whether these changes are clinically meaningful for individual patients remains challenging. This JACC: Heart Failure position statement proposes a pragmatic framework for defining clinically meaningful within-patient change across commonly used HF outcomes by integrating measurement variability, prognostic associations, and patient-anchored evidence where available. Relative and absolute risk reductions should both inform interpretation of clinical events, while imaging, hemodynamic, biomarker, and functional measures require changes exceeding measurement variability and consideration of physiological context. Patient-reported health status measures, particularly the Kansas City Cardiomyopathy Questionnaire, currently have the strongest evidence supporting clinically meaningful thresholds. Many proposed cutpoints remain provisional, reflecting limited validation linking physiological changes to patient-perceived benefit or hard outcomes. Future work should prioritize anchor-based analyses and patient-centered validation to align trial results with shared decision-making.