Valsalva-induced systolic blood pressure drop as a real-time marker of dynamic left ventricular outflow tract obstruction in hypertrophic cardiomyopathy

Background Obstructive hypertrophic cardiomyopathy (oHCM) requires provocable gradient measurement for diagnosis and dose optimisation of myosin inhibitors, but current provocation methods are resource-intensive. We hypothesized that the systolic blood pressure decrease during a standardized Valsalva manoeuvre (SBPd) would mirror dynamic left-ventricular outflow-tract gradient (ΔLVOTG) and serve as a bedside biomarker. Methods Two prospective cohorts were studied: a exploration set (n = 173) to derive and a validation set (n = 161) to test a SBPd threshold for diagnosing oHCM. Beat-by-beat SBP measurement and simultaneous Doppler echocardiography quantified the SBPd–ΔLVOTG relationship (Figure 1). A longitudinal cohort (n = 87) receiving mavacamten was followed for 10 months to assess SBPd as a pharmacodynamic endpoint. Primary outcomes were diagnostic accuracy and cumulative incidence of measurement-definedtreatment-response. Results SBPd and ΔLVOTG were virtually collinear (r = 0.94; slope 0.96 mmHg mmHg⁻¹). A SBPd >13 mmHg threshold identified oHCM with AUC 0.99 (sensitivity 100 %, specificity 95 %) in the exploration cohort and AUC 0.93 (sensitivity 90 %, specificity 88 %) in the validation cohort, independent of age, sex, hypertension or drugs. During mavacamten therapy, monthly SBPd tracked Valsalva-LVOTG (r = 0.97) and achieved response criteria earlier than resting gradient or NYHA class. Patients reaching SBPd >13 mmHg parallels Valsalva-LVOTG (log-rank p = 0.71) as a sensitive indicator of treatment response. No serious adverse events in 574 sequential Valsalva maneuvers. Conclusions SBPd >13 mmHg during Valsalva is a universally available, real-time surrogate for dynamic obstruction that matches invasive precision, accelerates diagnosis, guides myosin-inhibitor titration and predicts survival—offering a pragmatic tool to decentralize management of obstructive hypertrophic cardiomyopathy (Figure 1).Figure 1Figure 2