Mavacamten reduced resting LVOT gradient by 27.11 mmHg and with Valsalva by 56.8 mmHg at 24 weeks, improving NYHA class in 71.3% of patients with obstructive HCM.
Does mavacamten improve electrocardiographic parameters and LVOT gradients in adult patients with obstructive hypertrophic cardiomyopathy?
Mavacamten treatment in obstructive HCM is associated with early and sustained improvements in electrocardiographic voltage criteria and structural echocardiographic parameters, suggesting reverse electrical and structural remodeling.
Absolute Event Rate: 0% vs 0%
Abstract Background Hypertrophic cardiomyopathy (HCM) is a complex disorder deriving from excessive myosin–actin cross-bridging and increased sensitivity to calcium in the cardiac sarcomere, that clinically manifests with myocardial hypertrophy and diastolic dysfunction. Left ventricular outflow tract (LVOT) obstruction is present in nearly two-thirds of patients and significantly contributes to functional impairment and long-term prognosis. Mavacamten, a reversible allosteric inhibitor of cardiac myosin ATPase, is the first treatment able to act directly on the pathophysiological mechanism underlying this clinical phenotype. Purpose The aim of this study was to systematically evaluate electrocardiographic changes during Mavacamten treatment in patients with obstructive HCM. Methods In this multicenter, observational, retrospective study, 37 consecutive adult patients with obstructive HCM (mean age: 58.5±10 years, 59.5% male) were evaluated. All patients had been receiving Mavacamten for at least four weeks. At baseline, 70.3% of patients were classified as NYHA II, with a mean resting LVOT peak gradient of 45.2±29.7 mmHg. Clinical and instrumental parameters were assessed before therapy initiation and at each follow-up visit and correlated with response to therapy and potential adverse events. Results A significant reduction in LVOT gradients, both at rest and with Valsalva maneuver, was already evident after four weeks of therapy (-22.21 mmHg and -34.81 mmHg, respectively; p0.001). The maximum reduction was observed at 24 weeks, with a mean decrease of 27.11 mmHg at rest and 56.8 mmHg with Valsalva (p0.001). Overall, 71.3% of patients demonstrated an improvement of at least one NYHA class. After four weeks of therapy, 10 patients (27%) exhibited normalization of negative T waves in the inferolateral leads and one patient showed resolution of a complete left bundle branch block. At 24 weeks, a reduction in the Sokolow-Lyon index (-5.33±7.9 mm, p=0.011) and Cornell voltage criteria (-4.83±5.4 mm, p=0.001) was recorded, along with decreased interventricular septal thickness (-1.875±2.33 mm, p=0.006) and posterior wall thickness (-1.69±2.3 mm, p=0.011) on echocardiography. Three patients experienced an increase in systemic arterial pressure requiring antihypertensive therapy uptitration; these patients had higher Sokolow-Lyon index values at baseline (t-stat:2.85, p=0.013). No patient required permanent drug withdrawal. In three patients who experienced transient decline in left ventricular ejection below 50%, lower baseline Cornell voltage criteria values were recorded (t-stat: 3.43, p=0.002). Conclusions Mavacamten therapy resulted in a significant and sustained reduction in LVOT gradients, with marked improvements in all clinical and instrumental parameters. These early signs of electrical and structural remodeling support the hypothesis that the net beneficial effect of this therapy extends beyond the resolution of LVOT obstruction.
Marchionni et al. (Sat,) reported a other. Mavacamten reduced resting LVOT gradient by 27.11 mmHg and with Valsalva by 56.8 mmHg at 24 weeks, improving NYHA class in 71.3% of patients with obstructive HCM.