Beyond outflow obstruction alleviation in HOCM: Role of CMR in monitoring cardiac myosin inhibitors.

Description of Clinical Presentation: A 61-year-old male with familial hypertrophic obstructive cardiomyopathy (HOCM) presented with exertional and post-prandial chest tightness due to a significant left ventricular outflow tract (LVOT) gradient. Standard treatments with beta-blockers and calcium channel blockers were ineffective at relieving his symptoms, leading to the consideration of Aficamten, a cardiac myosin inhibitor for symptom management. Aficamten is thought to improve symptoms by not only alleviating outflow obstruction, but by also improving myocardial oxygen and metabolic demands. This is the first case report highlighting Aficamten’s impact on myocardial metabolism and microstructure in humans and exploring its benefits beyond LVOT gradient reduction.

Diagnostic Techniques and Their Most Important Findings: In this open-label study, we performed comprehensive echocardiography and multiparametric CMR (3T Siemens Prisma) with 31-phosphorus magnetic resonance spectroscopy (31-P MRS) on the patient pre- and post-treatment with Aficamten. The CMR protocol included cine imaging to assess cardiac structure and function, diffusion tensor cardiac magnetic resonance (DT-CMR) to assess fractional anisotropy (FA), a marker of microstructural organization, adenosine blood oxygen level dependent (BOLD) imaging to assess myocardial oxygenation, adenosine stress perfusion imaging to assess myocardial blood flow (MBF), and 31-P MRS for cardiac energetics.
At baseline, the patient had significant resting and post-Valsalva LVOT gradients (peak 160 mm Hg). CMR revealed basal septal hypertrophy with a maximum wall thickness of 22 mm. Stress MBF was severely impaired at 0.89 ml/min/g. Myocardial energetics (phosphocreatine to ATP ratio) was reduced at 1.66 (normal range: 2.1 ± 0.41) as was myocardial stress oxygenation on BOLD CMR 5% ( normal range: 18±4%2 ). Additionally, FA was low at 0.38 (normal range 0.52 ± 0.033). After 12 weeks of Aficamten treatment, there was a significant improvement in resting and post-Valsalva gradient (peak 40 mmHg), stress MBF (1.88 ml/min/g), myocardial energetics (1.96), and stress myocardial oxygenation (13%). Compared to baseline, there was an increase in FA (0.53), suggesting more diastolic or relaxed configuration of cardiomyocytes. These changes were accompanied by significant improvements in exertional chest tightness.

Learning Points from this Case: This case demonstrates for the first time that in HOCM patients, the benefits of cardiac myosin inhibition extend beyond LVOT gradient reduction, improving myocardial metabolic and oxygen needs. Our findings highlight the potential utility of advanced multiparametric CMR to track the effects of disease-modifying treatments in inherited conditions like HOCM.

Figure 1. CMR images pre- and post-treatment with Aficamten demonstrates an increase in indexed left ventricular end-diastolic volume (LVEDVi), increase in myocardial perfusion (stress myocardial blood flow or MBF), increase in myocardial energetics (PCr/ATP), increase in oxygenation with vasodilator stress (stress oxygenation) and improvement in microstructural configuration (fractional anisotropy or FA).