Left ventricular reverse remodeling is not related to biopsy-detected extracellular matrix fibrosis and serum markers of fibrosis in dilated cardiomyopathy, regardless of the definition used for LVRR

Left ventricular reverse remodeling (LVRR) is reported in dilated cardiomyopathy (DCM) patients (pts). However, numerous definitions of LVRR exist. Measurements of serum markers of fibrosis provide insight into myocardial fibrosis. The relationship between LVRR and fibrosis is poorly understood. From July 2014 until October 2015, we included 63 consecutive DCM pts (48 +/- 12.1 years, EF 24.4 +/- 7.4%) with completed baseline and 3-month follow-up echocardiograms. LVRR was assessed on the basis of four differing definitions. Procollagens type I and III carboxy- and amino-terminal peptides (PICP, PINP, PIIICP, and PIIINP), collagen 1, ostepontin, tumor growth factor beta-1, connective tissue growth factor, and matrix metalloproteinases (MMP-2, MMP-9), and their tissue inhibitor (TIMP-1) were measured in serum. In addition, all pts underwent right ventricular endomyocardial biopsy. Depending on the definition chosen, LVRR could be diagnosed in between 14.3 and 50.8% pts. Regardless of the LVRR definition used, the frequency of LVRR was similar in fibrosis negative and positive DCM. Minor differences of markers of fibrosis were detected between pts with and without LVRR. For every LVRR definition, adjusted and unadjusted models were constructed to evaluate the predictive value of serum fibrosis parameters. Only an increase of TIMP-1 by 1 ng/ml was found to independently increase the probability of LVRR by 0.016%. The choice of a particular definition of LVRR determines the final diagnosis, and this has a profound impact on subsequent management. LVRR is unrelated to biopsy-detected ECM fibrosis. Serum markers of fibrosis are only weakly related to LVRR, and are not of use in the prediction of LVRR.