Hemodynamic Effects of Mavacamten in Obstructive Hypertrophic Cardiomyopathy: An Echocardiography-Derived Pressure-Volume Analysis

J.-C. Reil (Bad Oeynhausen)¹, V. Sequeira (Würzburg)², C. Coppee (Bad Oeynhausen)¹, K. Peters (Bad Oeynhausen)¹, G.-H. Reil (Oldenburg)³, C. Maack (Würzburg)⁴, P. Steendijk (2333 ZA)⁵, V. Rudolph (Bad Oeynhausen)¹, S. Scholtz (Bad Oeynhausen)^6
1Herz- und Diabeteszentrum NRW Allgemeine und Interventionelle Kardiologie/Angiologie Bad Oeynhausen, Deutschland; ²Universitätsklinikum Würzburg Deutsches Zentrum für Herzinsuffizienz Würzburg, Deutschland; ³Klinikum Oldenburg AöR Klinik für Kardiologie Oldenburg, Deutschland; ⁴Universitätsklinikum Würzburg Deutsches Zentrum für Herzinsuffizienz/DZHI Würzburg, Deutschland; ⁵LUMC Leiden 2333 ZA, Niederlande; ⁶Herz- und Diabeteszentrum NRW Klinik für Kardiologie Bad Oeynhausen, Deutschland

Background: Obstructive hypertrophic cardiomyopathy (oHCM) is marked by left ventricular (LV) hypercontractility, diastolic dysfunction, and elevated energy demand from sustained LV outflow tract (LVOT) obstruction. This imposes substantial pressure load on the LV, which activates the Anrep effect, a compensatory increase in contractility to raised afterload. We investigated whether the myosin inhibitor mavacamten can reverse this hemodynamic state.

Methods: Twenty-nine symptomatic oHCM patients underwent echocardiography-derived pressure–volume (PV) analysis before and after 3 months’ mavacamten. Anrep-related indices, including afterload (LV end-systolic pressure [LVESP], effective arterial elastance [Ea]), contractility (end-systolic elastance [Ees], end-systolic volume at 150 mmHg [ESV₁₅₀]), and systolic duration (systolic ejection time [SET]), were quantified. Myocardial workload (stroke work [SW], potential energy [PE], pressure–volume area [PVA]) and diastolic indices (LV end-diastolic pressure [LVEDP], end-diastolic volume [EDV], and volume at 15 mmHg LVEDP [V₁₅]) were compared. NYHA class and cardiac biomarkers (NT-proBNP, hs-cTnI) were assessed.

Results: Mavacamten reduced LVOT gradients (resting: 66 to 10 mmHg; provoked: 104 to 45 mmHg), LVESP (201 to 139 mmHg), and Ea (3.52 to 2.5 mmHg/mL) (all p<0.0001). Contractility decreased (Ees: 5.2 vs. 3.9 mmHg/mL, p<0.0001; ESV₁₅₀: 18.0 vs. 34.6 mL, p<0.0001), and SET shortened (380 vs. 360 ms, p=0.0002). Myocardial workload declined (SW: 5618 vs. 5043 mmHg·mL, p=0.0181; PE: 2843 vs. 2169 mmHg·mL, p=0.0398; PVA: 8785 vs. 7305 mmHg·mL, p=0.0092), with preserved stroke volume and efficiency (SW/PVA). Diastolic compliance improved: increased EDV (76 vs. 80 mL, p=0.012) and V₁₅ (73.8 vs. 81.6 mL, p=0.0002), and lowered LVEDP (15.9 vs. 14.2 mmHg, p=0.0109). Biomarkers declined, and NYHA class improved, with 53% reaching class I and class III decreasing from 53% to 6%.

Conclusion: Chronic Anrep activation contributes to the hemodynamic and energetic burden in oHCM. Mavacamten reverses this state by lowering afterload, normalizing contractility and systolic duration, and improving diastolic function and clinical status.