Biomarkers to Predict the Response to Cardiac Resynchronization Therapy

Ward Heggermont; Angelo Auricchio; Marc Vanderheyden


Europace. 2019;21(11):1609-1620. 

In This Article

Epigenetic Alterations in Cardiac Resynchronization Therapy

In the last decennium, the number of publications on epigenetic regulation in the cardiovascular field has boomed. In particular microRNAs play various roles in controlling processes of cardiac hypertrophy, fibrosis, angiogenesis, apoptosis, among others. Sardu and co-workers investigated whether LV reserve remodelling after CRT was associated with changes of circulating microRNAs in patients with dyssynchronous HF.[37] In this prospective, non-randomized trial, 84 microRNAs levels were determined in 81 patients with HF eligible for CRT, against 15 healthy controls and 60 matched non-HF patients but with concomitant diseases. In the CRT population, 55 patients displayed a beneficial response, whereas the remaining 26 patients were non-responders at 12 months. At this follow-up period, the responders displayed a differential expression pattern than the non-responders: in the former group, microRNA-26b-5p, -145-5p, -92a-3p, 30e-5p, and -29a-3p (P < 0.01 for all microRNAs).

In 2015, the study of Melman[38] investigated the potential of 766 plasma-derived microRNAs at baseline in 12 CRT patients, with and without subsequent echocardiographic improvement at 6 months after CRT. After this pilot phase, candidate microRNAs were validated in 61 additional patients. Higher baseline microRNA-30d levels, expressed in cardiomyocytes and released in vesicles in response to mechanical stress, appeared to be associated with a beneficial CRT response, here defined as a relative increase in LVEF ≥15%. Although these results seem promising, a large validation study of microRNA-30d as a biomarker for CRT response is currently still lacking.

From these epigenetic data, it appears that the microRNA-30 cluster, consisting of microRNA-30a, -30 b, -30c1, -30c2, -30d, and -30e is critically involved in the remodelling of the left ventricle, potentially by its important role in the extracellular matrix,[39] angiogenesis,[40] and autophagy.[41] Further large validation data are eagerly awaited to confirm or refute the role of microRNAs in predicting the response to CRT.