One-year functional and structural effects of mavacamten in obstructive hypertrophic cardiomyopathy: A comprehensive CMR study

Background: Mavacamten can improve clinical and functional outcomes in obstructive hypertrophic cardiomyopathy (oHCM). However, its long-term effects on myocardial function and structure remain unclear. This study aims to evaluate the one-year remodeling effects of mavacamten using comprehensive cardiovascular magnetic resonance (CMR).

Methods: In this prospective single-center study, consecutive oHCM patients underwent 1.5T-CMR at first referral (baseline) and one-year later. After baseline, patients remained on negative inotropic therapy (control group) or were treated additionally with mavacamten according to patient`s discretion (mavacamten group). CMR assessment comprised volumetric, functional, and strain analysis of all chambers and left ventricular (LV) tissue characterization.

Results: Twenty-two patients were enrolled, of whom 15 (68.2%) received mavacamten. Compared to controls, mavacamten treatment was associated with a significant reduction in left ventricular (LV) mass index (mean change from baseline: -26.5 g/m² [95% CI -37.6 to -12.6 g/m²]; p< 0.001), maximal LV wall thickness (-4.5 mm [-3.2 to -5.7 mm]; p< 0.001), right ventricular (RV) wall thickness (-0.9 mm [-0.3 to -1.4 mm]; p=0.017), and left atrial volume index (-16.1 mL/m² [-6.9 to -25.3 mL/m²]; p=0.005). LV ejection fraction (-11.4% [-5.3 to -17.4%]; p< 0.001) and RV ejection fraction (-9.1% [-4.5 to -13.7%]; p=0.001) decreased, while LV global circumferential strain increased towards more positive values (+7.5% [+3.8 to +11.3%]; p< 0.001), indicating attenuation of the hyperdynamic state. Although mavacamten had no significant effect on late gadolinium enhancement mass, native T1 (-30.4 ms [-21.7 to -39.1 ms]; p< 0.001) and indexed extracellular volume (-4.0 mL/m² [-1.7 to -6.0]; p=0.004) showed a significant reduction.

Conclusion: One-year mavacamten therapy resulted in favourable remodeling with normalization of hyperdynamic state and regression of measures of interstitial fibrosis, all associated with worse outcome in oHCM.

I: Baseline characteristics, LVOT gradient with Valsalva of mavacamten and control groups as well as CMR parameters of mavacamten and control groups at baseline with respective changes at follow-up. II: CMR-derived significant effects of mavacamten treatment on cardiac structure, function, and LV interstitial fibrosis in obstructive HCM as shown in scatter plots with mean and 95% CI error bars. Data are given as mean (95% CI) between-group difference. Compared to controls, mavacamten resulted in reduction of LVMI, maximal LV wall thickness, LVEF, LV GCS, and LAVI. Furthermore, maximal RV wall thickness decreased with increase in RVESVI, accompanied by a decrease in RVEF. Additionally, mavacamten resulted in reduction of global native T1 and indexed ECV [calculated using the following equation: (ECV% x indexed LV mass) / (myocardial density x 100)]. For comparison of continuous variables, the student’s t-test or Mann-Whitney U-test were employed, as appropriate. For statistical analysis of longitudinal data, paired t-test or non-parametric related-samples Wilcoxon signed rank test, were applied, as appropriate. Categorical variables were compared using contingency tables and application of the chi-square test or Fisher’s exact test. III: CMR images of obstructive HCM in a forty-year-old male (A-D) receiving mavacamten and a 54-year-old female of the control group (E-H). Short-axis images depict the end-diastolic (ED), 4-chamber images the end-systolic (ES) moment of the cardiac circle. After mavacamten treatment (B, D), a decrease of maximal LV wall thickness, LVMI, LAVI, and RVEF can be observed while RVEDVI and RVESVI increase. On the contrary, a slight progression of disease is observed in follow-up CMR of the patient of the control group (F, H) with increase of LVEF, LVMI, and LAVI with RVEF and RV volumes remaining widely unchanged. Arrowheads delineate adjacent trabeculae and papillary muscles, which were not included in the measurement of maximal LV wall thickness. Abbreviations: BMI, body mass index; CCB, calcium channel blockers; CMR, cardiovascular magnetic resonance; CI, confidence interval; COPD, chronic obstructive pulmonary disease; ECV, extracellular volume; GCS, global circumferential strain; HCM=hypertrophic cardiomyopathy; IQR, interquartile range; LAVI, left atrial volume index; LV=left ventricle; LVEF, left ventricular ejection fraction; LVMI, left ventricular mass index; LVOT, left ventricular outflow tract; NYHA, New York Heart Association; NT-proBNP, N-terminal pro-B-type natriuretic peptide; RVEF, right ventricular ejection fraction; RVEDVI, right ventricular end-diastolic volume index; RVESVI, right ventricular end-systolic volume index; SD, standard deviation.
I: Baseline characteristics, LVOT gradient with Valsalva of mavacamten and control groups as well as CMR parameters of mavacamten and control groups at baseline with respective changes at follow-up. II: CMR-derived significant effects of mavacamten treatment on cardiac structure, function, and LV interstitial fibrosis in obstructive HCM as shown in scatter plots with mean and 95% CI error bars. Data are given as mean (95% CI) between-group difference. Compared to controls, mavacamten resulted in reduction of LVMI, maximal LV wall thickness, LVEF, LV GCS, and LAVI. Furthermore, maximal RV wall thickness decreased with increase in RVESVI, accompanied by a decrease in RVEF. Additionally, mavacamten resulted in reduction of global native T1 and indexed ECV [calculated using the following equation: (ECV% x indexed LV mass) / (myocardial density x 100)]. For comparison of continuous variables, the student’s t-test or Mann-Whitney U-test were employed, as appropriate. For statistical analysis of longitudinal data, paired t-test or non-parametric related-samples Wilcoxon signed rank test, were applied, as appropriate. Categorical variables were compared using contingency tables and application of the chi-square test or Fisher’s exact test. III: CMR images of obstructive HCM in a forty-year-old male (A-D) receiving mavacamten and a 54-year-old female of the control group (E-H). Short-axis images depict the end-diastolic (ED), 4-chamber images the end-systolic (ES) moment of the cardiac circle. After mavacamten treatment (B, D), a decrease of maximal LV wall thickness, LVMI, LAVI, and RVEF can be observed while RVEDVI and RVESVI increase. On the contrary, a slight progression of disease is observed in follow-up CMR of the patient of the control group (F, H) with increase of LVEF, LVMI, and LAVI with RVEF and RV volumes remaining widely unchanged. Arrowheads delineate adjacent trabeculae and papillary muscles, which were not included in the measurement of maximal LV wall thickness. Abbreviations: BMI, body mass index; CCB, calcium channel blockers; CMR, cardiovascular magnetic resonance; CI, confidence interval; COPD, chronic obstructive pulmonary disease; ECV, extracellular volume; GCS, global circumferential strain; HCM=hypertrophic cardiomyopathy; IQR, interquartile range; LAVI, left atrial volume index; LV=left ventricle; LVEF, left ventricular ejection fraction; LVMI, left ventricular mass index; LVOT, left ventricular outflow tract; NYHA, New York Heart Association; NT-proBNP, N-terminal pro-B-type natriuretic peptide; RVEF, right ventricular ejection fraction; RVEDVI, right ventricular end-diastolic volume index; RVESVI, right ventricular end-systolic volume index; SD, standard deviation.