Mavacamten reduced global work index from 2098 ± 700 to 1610 ± 440 mmHg% (p<0.001) at 3 months and to 1538 ± 402 mmHg% at 12 months in symptomatic oHCM patients.
Does Mavacamten improve myocardial work indices and reduce LVOT gradients in symptomatic patients with obstructive hypertrophic cardiomyopathy?
Mavacamten therapy significantly reduces LVOT gradients and improves myocardial energetics by decreasing wasted work in patients with symptomatic obstructive hypertrophic cardiomyopathy.
Effect estimate: P<0.001 for GWI reduction at 3 months
Absolute Event Rate: 1538% vs 2098%
p-value: p=<0.001
Abstract Background Mavacamten is the first approved myosin inhibitor for symptomatic obstructive hypertrophic cardiomyopathy (oHCM), addressing hypercontractility and left ventricular outflow tract (LVOT) obstruction. Objectives This study evaluates left ventricular performance by non-invasive measurements of pressure–strain loops in patients treated with Mavacamten. Methods In 36 symptomatic oHCM patients, pressure–strain analysis was performed prior to 3 and 12 months after Mavacamten therapy. Echocardiographic measurements included LVOT gradient, left ventricular ejection fraction (LVEF), global longitudinal strain (GLS), left atrial strain (LAS), peak strain time dispersion (PSD), and myocardial work parameters (global work index (GWI), global constructive work (GCW), global wasted work (GWW), and global work efficiency (GWE)). Clinical status was evaluated using the New York Heart Association (NYHA) class and stress biomarkers (NTproBNP and high-sensitivity troponin I). Results Mavacamten therapy significantly reduced LVOT gradients at rest and under provocation. Gradients decreased from 69 ± 36 to 24 ± 27 mmHg ( p < 0.001) at 3 months and further to 11 ± 6 mmHg ( p = 0.003) at 12 months. Provoked gradients decreased from 113 ± 33 to 50 ± 31 mmHg ( p < 0.001) at 3 months and to 31 ± 19 mmHg ( p = 0.01) at 12 months. Clinical symptoms also improved. LVEF was 68 ± 6% at baseline and decreased mildly to 62 ± 5% ( p = 0.003), while GLS and LAS remained unchanged. PSD decreased mildly from 116 ± 56 to 97 ± 36 ms and further to 93 ± 38 ms, but this was not statistically significant ( p = 0.07). Under Mavacamten, GWE remained stable. In contrast, GWI, GCW, and GWW decreased significantly from baseline to 3 months (GWI, 2098 ± 700 to 1610 ± 440 mmHg%, p < 0.001; GCW, 2514 ± 776 to 1951 ± 466 mmHg%, p < 0.001; GWW, 312 ± 163 to 249 ± 177 mmHg%, p = 0.003), with only mild, non-significant further reductions at 12 months (1538 ± 402, 1901 ± 380, and 207 ± 124 mmHg%, respectively; p = 0.67, p = 0.74, p = 0.30). Conclusion Myocardial work indices derived from non-invasive pressure–strain analysis were feasible to obtain in patients with oHCM in this study. Mavacamten therapy decreases workload index, constructive and wasted work, and synchronizes myocardial contractility, reflecting normalization of myocardial energetics. These findings reinforce the role of Mavacamten as a targeted therapy in oHCM. Graphical Abstract
Scholtz et al. (Thu,) conducted a other in Symptomatic adult patients (mean age 61.2 years, 52.8% female) with obstructive hypertrophic cardiomyopathy (oHCM) with resting or provoked LVOT gradient ≥50 mmHg and NYHA class II or III despite optimal medical therapy (n=36). Mavacamten vs. None (pre-post design) was evaluated on Change in myocardial work indices (global work index [GWI], global constructive work [GCW], global wasted work [GWW], global work efficiency [GWE]) derived from non-invasive pressure–strain loop analysis (P<0.001 for GWI reduction at 3 months, p=<0.001). Mavacamten reduced global work index from 2098 ± 700 to 1610 ± 440 mmHg% (p<0.001) at 3 months and to 1538 ± 402 mmHg% at 12 months in symptomatic oHCM patients.