‘Targeting the cardiac myocyte and fibrosis’ in heart failure

A previously healthy 38-year-old man was referred to our cardiology department with exertional dyspnoea. Echocardiography demonstrated left ventricular (LV) dilatation and global systolic dysfunction with normal wall thickness (Panel A and Supplementary material online, Video S1). Cardiovascular magnetic resonance (CMR) demonstrated diffusely and markedly high myocardial native T1 and extracellular volume fraction (ECV) values, and predominant septal involvement on multi-parametric mapping (1470 ms and 34%, respectively) (Panels B and C). Coronary angiography revealed that normal coronary arteries and histological samples taken from the interventricular septum depicted myocyte degeneration, increased extracellular space component, and moderate-to-severe interstitial fibrosis, resulting in the diagnosis of non-ischaemic dilated cardiomyopathy (Panel D). One year after receiving guideline-directed medical therapy, native T1 and ECV mapping demonstrated markedly reduced native T1 and ECV values (1389 ms and 32%, respectively), but there was a progressively dilated LV cavity, wall thinning, and declining LV ejection fraction (Panels E–G and Supplementary material online, Video S2). To determine the aetiology and guide therapy, endomyocardial biopsy was obtained at the 1-year follow-up. Consistent with CMR parametric mapping results, there was a substantial reversal of the cardiac myocyte and extracellular matrix abnormalities (Panel H). Six months later, there was significant improvement in LV function and reduction in LV volumes on follow-up echocardiography (Supplementary material online, Video S3), and the patient is asymptomatic without device therapy. This case describes the new promise of CMR-based myocardial substrate trajectory in predicting future LV functional recovery. A decrease in native T1 may mean therapeutic reversal of both myocyte degeneration and diffuse myocardial fibrosis (reference values at our institution; native T1: 1314 ± 29 ms, ECV: 26 ± 4%).