Research Article: Collagen turnover biomarkers and systemic right ventricle remodeling in adults with previous atrial switch procedure for transposition of the great arteries

Date Published: August 2, 2017

Publisher: Public Library of Science

Author(s): Magdalena Lipczyńska, Piotr Szymański, Magdalena Kumor, Anna Klisiewicz, Piotr Hoffman, Zaccaria Ricci.

http://doi.org/10.1371/journal.pone.0180629

Abstract

Myocardial fibrosis is a potential pathophysiological mechanism leading to systemic right ventricular (SRV) deterioration. We hypothesize that circulating levels of collagen deposition markers are elevated in patients with SRV remodeling and this elevation may have a predictive value.

We prospectively evaluated 56 patients with D-TGA after the atrial switch procedure (mean age 25.6 ± 4.8, range 18–37 years; 67% males). Serum levels of procollagen type III amino-terminal propeptide (PIIINP), collagen type I carboxy-terminal telopeptide (CITP), procollagen type I N-terminal propeptide (PINP), matrix metalloproteinase (MMP 1, MMP 9) and a tissue inhibitor of matrix metalloproteinase (TIMP 1) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) were measured and compared with healthy controls. The relationship between these serum markers, echocardiographic and cardiac magnetic resonance parameters and the outcome at a follow-up of 61 months (range, 24–85 months) was determined.

Compared with the healthy control group, the study group had significantly higher levels of TIMP1, PIIINP, CITP, PINP and NT-pro-BNP (p<0.05, each). The levels of PIIINP and CITP were significantly higher among patients with an SRV mass index above the mean value. The level of PIIINP was significantly higher among patients with an SRV EDV index above the mean value. CITP was significantly elevated in SRV late gadolinium enhanced (LGE) positive patients, compared to patients without SRV LGE. MMP9 and TIMP1 predicted an adverse clinical outcome on univariate Cox proportional hazard survival analysis in addition to well proven predictors of outcome (SRV EF and NYHA). We demonstrated a pattern of altered collagen turnover adversely related with the indices of SRV remodeling and an adverse clinical outcome in patients with SRV.

Partial Text

D-transposition of the great arteries (D-TGA) is one of the most common, severe cyanotic congenital heart diseases. [1] The arterial switch operation is currently the procedure of choice. [2] Before the introduction of anatomical correction, D-TGA was repaired with the atrial switch procedure by using the Mustard or Senning technique, which revolutionized the outcome, allowing patients to survive well into adulthood. [3, 4] Importantly, in this type of operation the right ventricle (RV) is in the systemic position and subjected to significant pressure overload. [5] The cumulative survival rate after the atrial switch is about 80% after 25 years. [6, 7, 8] Now, a considerable number of these surviving patients are adults and provide a challenge to clinicians. There are some specific long-term complications associated with increased mortality and morbidity. [9, 10] Systemic right ventricular (SRV) dysfunction has been identified as a leading problem in the long term, suggesting the limited capacity of the morphologically RV while coping with systemic circulation. [11]

Fifty-six patients with D-TGA following the atrial switch procedure and 29 healthy age and sex matched controls were prospectively evaluated. The basic clinical characteristics as well as the results of the CMR and the echocardiographic evaluation of the SRV in D-TGA patients are presented in Table 1.

This is the second paper concerning CTB among patients with D-TGA after the atrial switch operation. [20] In a prospective study with a larger group and a wider profile of collagen turnover markers, we demonstrated an increased fibrotic signal (PIIINP, PINP, CITP) as well as an increased matrix turnover signal (MMP9, TIMP1) in these patients, as compared to age- and gender-matched healthy controls. The data suggest that some of CTB may have a predictive value in this group of patients.

In summary, while our cohort of patients with D-TGA was in good clinical condition, we demonstrated a pattern of altered collagen turnover and neurohormonal activation adversely correlated with indices of systemic right ventricular function and remodeling and assessed both by echocardiography and CMR. Even more importantly some of CTB were associated with an adverse clinical outcome in these patients.

 

Source:

http://doi.org/10.1371/journal.pone.0180629

 

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