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Rev Esp Cardiol (Engl Ed). 2019 Jan;72(1):48-55. doi: 10.1016/j.rec.2017.12.015. Epub 2018 Mar 23.

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

[Article in English, Spanish]

Author information

1
Heart and Vascular Center, Semmelweis University, Budapest, Hungary.
2
Third Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
3
Heart and Vascular Center, Semmelweis University, Budapest, Hungary. Electronic address: merkely.bela@kardio.sote.hu.

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<.0001; integrated discrimination improvement=0.06; 95%CI, 0.02-0.11) and reverse remodelling (net reclassification improvement=0.39; 95%CI, 0.07-0.71; 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.

KEYWORDS:

Biomarcadores; Biomarkers; Cardiac resynchronization therapy; Clinical response; Factor de crecimiento hepatocitario; Hepatocyte growth factor; Mortalidad; Mortality; Respuesta clínica; Terapia de resincronización cardiaca

PMID:
29580749
DOI:
10.1016/j.rec.2017.12.015

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