Role of myocardial collagen degradation and fibrosis in right ventricle dysfunction in transposition of the great arteries after atrial switch

• Published in: International journal of cardiology Vol. 258; pp. 76 - 82
• Main Authors: Ladouceur, Magalie, Baron, Stephanie, Nivet-Antoine, Valérie, Maruani, Gérard, Soulat, Gilles, Pereira, Helena, Blanchard, Anne, Boutouyrie, Pierre, Paul, Jean Louis, Mousseaux, Elie
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.05.2018; Elsevier
• Subjects: Adult; Arterial Switch Operation; Biomarkers; Collagen; Cross-Sectional Studies; Female; Fibrosis; Follow-Up Studies; Humans; Life Sciences; Male; Myocardium; Prospective Studies; Right ventricle; Transposition of Great Vessels; Transposition of the great arteries; Ventricular Dysfunction, Right; Biomarkers; Transposition of the great arteries; Collagen; Right ventricle; Fibrosis
• ISSN: 0167-5273; 1874-1754; 1874-1754
• DOI: 10.1016/j.ijcard.2018.01.100

Heart failure is a serious event in patients with transposition of the great arteries (D-TGA) after atrial redirection surgery. We aimed to determine the association between myocardial fibrosis and systolic and diastolic systemic right ventricle (sRV) dysfunction. Diastolic and systolic function of sRV was prospectively assessed using echocardiography and cardiac magnetic resonance imaging (CMR) in 48 patients with atrially switched D-TGA and 26 healthy subjects. Diastolic function of the subaortic ventricle was assessed by echocardiography Doppler and DTI. In CMR, ejection fraction of sRV and wall stress defined as the product of the systolic blood pressure and volume/mass ratio were assessed. Fibrosis extent within sRV myocardium was evaluated using gadolinium-enhanced magnetic resonance and serum collagen turnover biomarkers. Late gadolinium enhancement (LGE) was found in 35% of D-TGA patients, and the collagen degradation biomarker pro-MMP1:TIMP1 ratio was significantly increased in D-TGA patients compared to healthy subjects (1.0 × 10−2vs. 2.5 × 10−2, p = 0.04). Increase in sRV wall stress was significantly associated with LGE (p = 0.01) and pro-MMP1:TIMP1 ratio (r = 0.77, p < 0.01). After adjustment for age, sex, BMI, blood pressure and cardiac treatment, pro-MMP1:TIMP1 ratio was the strongest determinant of sRVEF (R2 = 0.85, p < 0.01). Pro-MMP1:TIMP1 ratio was also significantly correlated with the early diastolic filling parameter E/E′ (r = 0.53, p = 0.02), but this was not anymore the case after adjustment. Diastolic and systolic sRV dysfunction is related to myocardial collagen degradation and fibrosis. Research in medical therapies that reduce systemic sRV afterload and limit collagen degradation is warranted in this setting. •Systemic RV failure is a severe complication in adults with D-TGA.•Myocardial collagen degradation and fibrosis are associated with sRV dysfunction.•Myocardial collagen degradation and fibrosis are related to sRV pressure overload.•Therapies reducing systemic afterload and collagen degradation may prevent sRV failure.