Hypertrophic cardiomyopathy is a condition characterized by primary left ventricular hypertrophy which can manifest with or without obstruction of the left ventricular outflow tract (LVOT). Historically patients with obstructive hypertrophic cardiomyopathy (oHCM) were managed with beta blockers, non-dihydropyridine calcium channel blockers, or disopyramide to reduce myocardial contractility and thus relieve LVOT obstruction. Patients with symptoms unresponsive to those first-line medical therapies could be referred for septal reduction therapy by means of either septal myectomy or alcohol septal ablation.
Since 2020 there have been numerous landmarks, randomized clinical trials demonstrating the efficacy of cardiac myosin inhibitors, mavacamten and aficamten, in the treatment of patients with oHCM, and cardiac myosin inhibitors now carry a class I recommendation from the ACC/AHA for treatment of patients with oHCM with persistent symptoms despite treatment with beta blockers or calcium channel blockers. Sub-studies from these trials have also provided important insights into structural cardiac remodeling associated with myosin inhibition. ,,
The EXPLORER-HCM trial demonstrated significant improvement in functional class, symptoms, and LVOT gradients in patients with oHCM who were randomized to mavacamten. Subsequent echocardiographic analysis of the EXPLORER-HCM trial revealed that mavacamten improved echocardiographic markers of left ventricular hypertrophy as well as diastolic function. , In that sub study, left ventricular mass index (LVMI) decreased by 7.4 g/m 2 over 30 weeks in the mavacamten arm compared to an increase in LVMI by 8.9 g/m 2 in the placebo arm for a between group difference of −15.5 g/m 2. SEQUOIA-HCM studied a second cardiac myosin inhibitor, aficamten, and showed a significant improvement in peak oxygen uptake in the patients who were randomized to aficamten compared to placebo. In a secondary analysis of changes in cardiac structure and function from the SEQUOIA-HCM trial, aficamten was also shown to reduce LVMI by a mean between group difference of 12.2 g/m 2 at 24 weeks of treatment compared to placebo. Presumably the effects of cardiac myosin inhibition on left ventricular mass are at least partially attributable to relief of the LVOT obstruction which was substantial in both trials. This relationship is consistent with LV mass regression observed in patients with aortic stenosis and left ventricular hypertrophy following aortic valve replacement.
While there is evidence of left ventricular mass regression with cardiac myosin inhibition in clinical trial data with predominantly white study participants, there is a paucity of real-world data in ethnically diverse populations. This study sought to analyze the effects of mavacamten on left ventricular mass index on a diverse group of patients with oHCM from our single center.
Using single-center data, this study identified 105 patients with oHCM initiated on mavacamten between January 2021 and August 2024. Of these, 41 patients had received uninterrupted treatment with mavacamten and had follow-up echocardiograms at 60 weeks. Demographic, clinical and genetic data were recorded from chart review. Three physicians independently reviewed baseline and 60 weeks echocardiograms, manually remeasuring the LVMI and related parameters using linear 2D-measurements, in accordance with American Society of Echocardiography guidelines. Standard statistical methods were employed to characterize the data, and changes in LVMI and other parameters were compared using paired t-tests.
Among the 41 patients with oHCM treated with mavacamten, the median age was 62 years, 54% were female and 49% were African-American ( Table 1 ). Common comorbidities included hypertension (80%) and coronary artery disease (27%). All patients had a provoked peak left ventricle outflow tract gradient of >50 mm Hg consistent with oHCM at baseline. After 60 weeks of mavacamten, the LVMI significantly decreased from 123 to 108 g/m 2 (average reduction of 15 g/m 2; p <0.001, Figure 1 ). The interventricular septal thickness significantly decreased from 1.69 to 1.54 cm (p <0.001). The LV internal diameter and posterior wall thickness remained unchanged at 60 weeks.
Table 1
Baseline characteristics
| Overall (n = 41) | |
|---|---|
| Age (years) | 62 (51 to 68) |
| Sex | |
| Female | 22 (54%) |
| Male | 19 (46%) |
| Race | |
| White | 20 (49%) |
| African-American | 20 (49%) |
| Other | 1 (2%) |
| History of hypertension | 33 (80%) |
| History of atrial fibrillation | 7 (17%) |
| History of coronary artery disease | 11 (27%) |
| Left ventricular ejection fraction (%) | 70 (65 to 70) |
| Left ventricular outflow tract (mm Hg) | 59 (51 to 80) |
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