AN INTERPLAY OF GENETICS AND INFLAMMATION AFFECTING LEFT VENTRICULAR REVERSE REMODELLING IN DILATED CARDIOMYOPATHY

Recent-onset dilated cardiomyopathy (RODCM) is a disease of heterogeneous aetiology including genetic, inflammatory, toxic and metabolic causes. The interplay between genetic background and myocarditis is still poorly understood and could improve risk stratification of patients with RODCM.

We aimed to determine the genetic background of RODCM by whole-exome sequencing (WES), evaluate the inflammation by endomyocardial biopsy (EMB) and correlate these findings with left ventricular reverse remodelling (LVRR) in the 12-month follow-up.

This single-centre prospective observational study enrolled 83 RODCM patients who underwent whole-exome sequencing, EMB and 12-month clinical and echocardiographic follow up. LVRR was defined as an absolute increase in LV ejection fraction and a relative decrease of LV end-diastolic diameter at 12 months. Inflammation was defined according to TIMIC immunohistochemical criteria.

WES identified disease-related gene variants (ACMG class 3-5) in 45 (54%) patients. Majority of the 28 detected genes were represented by variants of titin (TTN) in 9 (11%), other cardiomyopathic genes in 36 (43%) and none in 38 (46%) patients. EMB analysis uncovered inflammation in 28 (34%) cases. LVRR at 12 months occurred in 28 (34%) of all cases. Carriers of non-titin gene variants heralded a lower probability of 12-month LVRR (19%), followed by patients with a negative genetic result (42%). Interestingly, LVRR occurred most often in carriers of isolated TTN variants (56%) P=.041. In contrast, inflammation positively predicted LVRR (P=.019). Combination of genetic and EMB findings did not predict LVRR in 12 months. 

In concusion, carriers of non-titin disease-related variants are less likely to reach LVRR, while myocardial inflammation and isolated titin variants predict favourable remodelling in 12 months.