Hypertrophic obstructive cardiomyopathy and magnetic resonance imaging: exploring the impact of mavacamten
C Meledeth, H Rohringer, A Aigner, C Steinwender, C ReiterAbstract
Introduction
Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disorder characterized by abnormal thickening of the left ventricular myocardium, potentially leading to obstruction of the left ventricular outflow tract (LVOT), it is also associated with an increased risk of sudden cardiac death and arrhythmias (1). Recent advances in treatment include cardiac myosin ATPase inhibitors, such as mavacamten and aficamten, which significantly reduce LVOT gradients. Cardiac magnetic resonance imaging (CMR) has the ability to detect myocardial replacement fibrosis through late gadolinium enhancement (LGE). This focus on prognosis has been further refined by the development of the Cardiovascular Magnetic Resonance Late Gadolnium Enhancement (CMR-LGE) risk score, designed to predict all-cause mortality in HCM patients (3).
Methods
Patients underwent cardiac magnetic resonance imaging at baseline and were subsequently followed up after a minimum of 12 months of treatment with mavacamten. CMR was performed using 1.5T and 3T systems (Philips Medical Systems) using intravenous gadolinium contrast injection.
Results
At baseline the median left ventricular ejection fraction was 72,39%, and a significant LVOT jet could been seen in all patients, which was significantly reduced in the follow up imaging (Figure 1). The median left ventricular ejection fraction (EF) at baseline was 72.39%. Baseline cardiac laboratory assessment revealed NTproBNP ranging from 4ng/L to 352 ng/L, and high-sensitivity Troponin T (Troponin T-hs) ranging from 6.0ng/L to 16.5ng/L. Following 12 months of mavacamten treatment, key cardiac parameters demonstrated structural and functional changes. Left ventricular parameters showed a mean reduction in Ejection Fraction (EF) of 9.06%, while Stroke Volume (SV) also decreased on average by 8.38 ml/m2. Conversely, both End Diastolic Volume (EDV) and End Systolic Volume (ESV) increased, with mean changes of 8.11ml/m2 and 6.14 ml/m2, respectively, as seen in Figure 2. Most notably, Myocardial Mass showed a substantial structural benefit, with a mean reduction of 34.31g. Cardiac biomarkers also reflected the therapeutic effects: NTproBNP levels decreased from baseline (mean change: -193.31ng/L), and Troponin T-hs levels decreased (mean change: -3.47ng/L) at follow-up.
Discussion
The 12-month mavacamten therapy led to significant morphological and functional reverse cardiac remodelling in HOCM patients, quantified by CMR. The core finding was a substantial mean reduction in myocardial mass 34.31g, which correlated with the resolution of the LVOT obstruction. Functionally, the drug reduced hypercontractility, shown by a mean drop in EF 9.06% and SV 8.11ml/m2, while simultaneously increasing EDV and ESV, suggesting improved LV filling. Biomarker reductions in NT-proBNP and Troponin T-hs confirmed decreased myocardial stress and injury, validating that mavacamten effectively normalizes hemodynamic stress in HOCM.Baseline CMR (left) and follow-up CMRFor image description, please refer to the figure legend and surrounding text.Key CMR Parameters at Baseline and at FUFor image description, please refer to the figure legend and surrounding text.