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European Heart Journal Advance Access originally published online on March 10, 2008
European Heart Journal 2008 29(7):898-906; doi:10.1093/eurheartj/ehn098
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Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2008. For permissions please email: journals.permissions@oxfordjournals.org

Impact of collagen type I turnover on the long-term response to cardiac resynchronization therapy

Ignacio García-Bolao1, Begoña López2, Alfonso Macías1, Juan J. Gavira1, Pedro Azcárate1 and Javier Díez1,2,*

1 Department of Cardiology and Cardiovascular Surgery, University Clinic, School of Medicine, University of Navarra, Pamplona, Spain
2 Division of Cardiovascular Sciences, Centre for Applied Medical Research, University of Navarra, Pamplona, Spain

Received 20 April 2007; revised 16 January 2008; accepted 14 February 2008; online publish-ahead-of-print 10 March 2008.

* Corresponding author: Area de Ciencias Cardiovasculares, Edificio CIMA, C/ Pío XII, 55, 31008 Pamplona, Spain. Tel: +34 948 194700, Fax: +34 948 194716, Email: jadimar{at}unav.es

Aims: We investigated whether collagen type I turnover influences the long-term response to cardiac resynchronization therapy (CRT).

Methods and results: Serum carboxy-terminal propeptide of procollagen type I or PICP (a marker of collagen type I synthesis) and carboxy-terminal telopeptide of collagen type I or CITP (a marker of collagen type I degradation) were measured in heart failure patients at baseline and after 1 year of CRT. Patients were categorized as responders or non-responders if they increased the distance walked in 6 min by > or <10%, respectively. At baseline, the PICP:CITP ratio, an index of the degree of coupling between collagen type I synthesis and degradation was higher (P = 0.006) in responders than in non-responders. Whereas the PICP:CITP ratio decreased (P= 0.000) after treatment in responders, it remained unchanged in non-responders. Thus, at 1-year, the PICP:CITP ratio was similar in the two groups of patients. A direct correlation (r = 0.289, P = 0.037) was found between the baseline PICP:CITP ratio and the change in the distance walked in 6 min in all patients. Receiver operating characteristics curves showed that a cut-off value of 14.4 for the PICP:CITP ratio provided 70% specificity and 63% sensitivity for the predicting response to CRT with a relative risk of 2.07 (95% confidence interval, 0.98–4.39).

Conclusion: Collagen type I turnover influences the long-term response to CRT. In addition, the ability of CRT to restore the balance between collagen type I synthesis and degradation is associated with a beneficial response.

Key Words: Collagen • Heart failure • Resynchronization


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