Novel Biomarkers in Cardiac Resynchronization Therapy: Hepatocyte Growth Factor Is an Independent Predictor of Clinical Outcome

Abstract Introduction and objectives Cardiac resynchronization therapy (CRT) is beneficial for selected heart failure (HF) patients, although nonresponse to therapy is still prevalent. We investigated a set of novel biomarkers associated with various pathophysiological pathways of HF. Our purpose was to assess their ability to predict clinical outcomes after CRT. Methods We studied 136 chronic HF patients undergoing CRT. We measured the plasma levels of fractalkine, pentraxin-3, hepatocyte growth factor (HGF), carbohydrate antigen-125, and matrix metalloproteinase-9 before and 6 months after CRT. The primary endpoint of the study was 5-year all-cause mortality, and we considered the absence of 6-month reverse remodelling (defined as at least a 15% decrease in end-systolic volume) as a secondary endpoint. Results Fifty-eight patients died during the 5-year follow-up period and 66 patients were categorized as nonresponders. In multivariable models, only an increased HGF was an independent predictor of both mortality (HR, 1.35; 95%CI, 1.11-1.64; P  = .003; per 1 standard deviation increase) and the absence of reverse remodelling (OR, 1.83; 95%CI, 1.10-3.04; P  = .01; per 1 standard deviation increase). Applying HGF to the basic multivariable model of both mortality (net reclassification improvement = 0.69; 95%CI, 0.39-0.99; P P  = .01; integrated discrimination improvement = 0.03; 95%CI, 0.00-0.06) resulted in a statistically significant reclassification and discrimination improvement. Conclusions Of the investigated biomarkers, only HGF predicted clinical outcomes following CRT independently of other parameters. Reclassification analyses showed that HGF measurements could be useful in refining patient selection.