Elsevier

American Heart Journal

Volume 164, Issue 4, October 2012, Pages 530-537
American Heart Journal

Clinical Investigation
Congestive Heart Failure
Serum markers of deranged myocardial collagen turnover: Their relation to malignant ventricular arrhythmias in cardioverter-defibrillator recipients with heart failure

https://doi.org/10.1016/j.ahj.2012.07.006Get rights and content

Background

Pathologic collagen remodeling has been involved in the occurrence of ventricular arrhythmias and sudden cardiac death in heart failure. The aim of the study was to investigate the relationship between malignant ventricular arrhythmias and cardiac collagen turnover indexes, expressing specific types of derangement in collagen physiology, in stable patients with an implantable cardioverter-defibrillator (ICD).

Methods

Seventy-four patients with an ICD and heart failure were studied. They had coronary artery disease (n = 42) or dilated cardiomyopathy, New York Heart Association classes I and II, and left ventricular ejection fraction 29% ± 1%. An ICD had been implanted for secondary (n = 36) or primary prevention of sudden cardiac death. We assessed (1) markers of collagen types I and III synthesis and their ratio: procollagen type I carboxyterminal peptide (PICP), procollagen type III aminoterminal peptide (PIIINP), and PICP/PIIINP; (2) markers of collagen degradation, degradation inhibition, and their ratio: matrix metalloproteinase 9 (MMP-9), tissue inhibitor of matrix metalloproteinase (TIMP) 1 (TIMP-1), and MMP-9/TIMP-1. Patients were prospectively followed up for 1 year. The number of episodes necessitating appropriate interventions for ventricular tachyarrhythmias (>170 beat/min) was related to the assessed parameters.

Results

Multivariate analysis revealed a significant relation between the number of tachyarrhythmic episodes and MMP-9/TIMP-1 (P = .007), PICP/PIIINP (P = .007), and ejection fraction (P = .04). No other significant relation was observed between arrhythmias and the remaining parameters.

Conclusion

In heart failure, biochemical markers indicative of a deranged equilirium in myocardial collagen deposition/degradation and collagen I/III synthesis are related to ventricular arrhythmogenesis. Further studies are needed to investigate their predictive ability.

Section snippets

Patient selection

The initially assessed study population consisted of 84 patients with clinically stable heart failure, due either to idiopathic dilated cardiomyopathy (n = 39) or coronary artery disease (n = 45) and an ICD. Patients with angina or signs of significant ischemia, as assessed by thallium scintigraphy or coronary angiography, were not included. Conditions known to alter collagen turnover or inflammatory status, such as renal impairment, liver disease, history of atrial fibrillation, pulmonary

Patient characteristics

During the 1-year follow-up, fast ventricular arrhythmias related to unstable angina or to heart failure deterioration were observed in 4 patients with dilated cardiomyopathy and in 6 with coronary artery disease; thus, these 10 patients were not included in the analysis. The data of the remaining 74 patients were eventually analyzed. No patient died or withdrew during the study period. Their baseline characteristics are depicted in Table I.

Arrhythmic episodes and collagen turnover markers

During the follow-up period, appropriate device

Main findings

In this study, we have shown that, in stable patients with heart failure and an ICD, the biochemical markers indicative of specific derangements in the balance of collagens I and III synthesis as well as in the equilibrium of myocardial deposition and degradation are related to the frequency of ensuing malignant ventricular arrhythmias, occurring in the 12-month period after ICD implantation. These indexes seem to be related to arrhythmic episodes as strongly as ejection fraction.

Fibrosis and ventricular arrhythmias

Several

References (27)

  • R.N. Vest et al.

    Risk stratification of ventricular arrhythmias in patients with systolic heart failure

    Curr Opin Cardiol

    (2010)
  • R. Tung et al.

    A critical appraisal of implantable cardioverter-defibrillator therapy for the prevention of sudden cardiac death

    J Am Coll Cardiol

    (2008)
  • A.E. Buxton et al.

    Left ventricular ejection fraction for sudden death risk stratification and guiding implantable cardioverter-defibrillator implantation

    J Cardiovasc Electrophysiol

    (2010)
  • Cited by (0)

    View full text