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Effect of cardiac resynchronization therapy on broad neurohormone biomarkers in heart failure

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Journal of Interventional Cardiac Electrophysiology Aims and scope Submit manuscript

Abstract

Background

Neurohormonal dysregulation contributes to heart failure (HF) progression. We sought to determine the effect of cardiac resynchronization therapy (CRT) on nerve growth factor (NGF), a biomarker that promotes the maturation and survival of sympathetic nerve endings, and amino-terminal propeptide of type III procollagen (PIIINP), a marker of type III collagen synthesis.

Methods

This prospective study consisted of 45 consecutive patients who received cardiac resynchronization therapy defibrillator for advanced HF and 20 healthy age-matched controls. New York Heart Association class, distance of 6-min walk, echocardiography and plasma concentrations of NGF, PIIINP, b-type natriuretic peptide (BNP), norepinephrine, and epinephrine were measured before and 6 months after CRT. Response to CRT was defined as 15% or greater reduction in left ventricular end-systolic volume index at 6-month follow-up.

Results

The baseline BNP (2.61 ± 0.51 vs. 1.53 ± 0.44 ug/L, P < 0.01) and PIIINP (0.88 ± 0.21 vs. 0.71 ± 0.14 μg/L, P = 0.01), but not other biomarkers, were elevated in HF compared to controls. Twenty-two of 45 patients (49%) responded to CRT. The responder group demonstrated significant decrease only in BNP level from 2.61 ± 0.51 to 2.31 ± 0.41 μg/L (P = 0.04) at 6-month follow-up, paralleling the clinical improvements. The baseline PIIINP, rather than the other biomarkers, was lower in CRT responders than non-responders (0.80 ± 0.20 vs. 0.96 ± 0.19 μg/L, P = 0.03). Univariate and multivariate analysis showed that less elevated plasma PIIINP level in HF might be an independent biomarker predicting better response to CRT (odds ratio = 0.20, 95% CI = 0.03–1.17, P = 0.07).

Conclusion

The less elevated PIIINP level in HF, which is suggestive of a lesser amount of cardiac fibrosis, has a trend in association with a favorable response to CRT. Contrary to previous reports, NGF levels are not reduced during HF with optimal medical therapy, and there is no NGF rebound in CRT responders.

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Abbreviations

ACE:

Angiotensin-converting enzyme

ARB:

Angiotensin II receptor blockers

AV:

Atrioventricular

BMI:

Body mass index

BNP:

B-type natriuretic peptide

CI:

Confidence interval

CRT:

Cardiac resynchronization therapy

CRT-D:

Cardiac resynchronization therapy defibrillator

CS:

Coronary sinus

EPI:

Epinephrine

HF:

Heart failure

LV:

Left ventricular

LVEF:

Left ventricular ejection fraction

LVEDV:

Left ventricular end-diastolic volume

LVESV:

Left ventricular end-systolic volume

NE:

Norepinephrine

NGF:

Nerve growth factor

NYHA:

New York Heart Association

OR:

Odds ratio

PIIINP:

Amino-terminal propeptide of type III procollagen

RV:

Right ventricular

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Acknowledgements

This study was supported by the Scientist Development Grant from AHA Greater Midwest Affiliate AHA 0435347Z and Award for Research in Cardiology Grant from the Mayo Foundation for Medical Education and Research.

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Authors and Affiliations

  1. Division of Cardiovascular Diseases, Department of Medicine, College of Medicine, Mayo Clinic, 200 First Street SW, Rochester, MN, 55905, USA

    Ying-xue Dong, John C. Burnett Jr, Horng H. Chen, Sharon Sandberg, Yan-zhong Yang & Yong-Mei Cha

  2. The Department of Cardiology, The First Affiliated Hospital of Dalian Medical University, Dalian, People’s Republic of China

    Ying-xue Dong & Yan-zhong Yang

  3. The Krannert Institute of Cardiology, Division of Cardiology, Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

    Yanhua Zhang & Peng-Sheng Chen

Authors
  1. Ying-xue Dong
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Correspondence to Yong-Mei Cha.

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Dong, Yx., Burnett, J.C., Chen, H.H. et al. Effect of cardiac resynchronization therapy on broad neurohormone biomarkers in heart failure. J Interv Card Electrophysiol 30, 241–249 (2011). https://doi.org/10.1007/s10840-011-9551-7

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  • DOI: https://doi.org/10.1007/s10840-011-9551-7

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