Putting it all Together: Utility of LGE and Circumferential Strain in Clinical Trials
With the understanding that LGE is a precursor to development of LVEF abnormality and circumferential strain is abnormal before development of LGE suggest that both are early indicator of DMD-CM. Circumferential strain is a sensitive index of DMD-CM and can occur in young DMD patients 54, 128. The combination of circumferential strain and LGE can be a sensitive tool to detect occult cardiomyopathy before LVEF abnormality is evident. This data along with preclinical animal study demonstrating the impact of aldosterone inhibition in cardiac function in mice was evident that we have a tool to assess efficacy of therapy. We used CMR with LGE and circumferential strain as endpoints in one of the first randomized, double-blinded placebo-controlled trial in a cohort of DMD patients with known LGE but relatively preserved LGE. The decline in circumferential strain magnitude was lower in treatment compared to placebo group with stable LGE. The studied concluded that in DMD patients the additional of an aldosterone inhibitor (Eplerenone) to background afterload reducer attenuated DMD-CM compared to placebo after 12 months of therapy129. A two-year follow-up extension study in a smaller of DMD patients showed continued attenuation of DMD-CM progression compared to an age-match group of patients from an established CMR database130. The utility of circumferential strain and LGE further validated in a follow-up multi-center trial of aldosterone inhibition and demonstrated attenuation of DMD-CM with no difference in circumferential strain magnitude decline between the two therapy but less than reported in patients on standard therapy in a multicenter double-blinded study82, 131.