Magalie Ladouceur1, Stephanie Baron2, Valérie Nivet-Antoine3, Gérard Maruani2, Gilles Soulat4, Helena Pereira5, Anne Blanchard6, Pierre Boutouyrie7, Jean Louis Paul8, Elie Mousseaux4. 1. Paris Descartes University, Sorbonne Paris Cité, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou and Necker Enfants Malades Hospital, Department of Cardiology, Adult Congenital Heart Disease Unit, Centre de référence des Malformations Cardiaques Congénitales Complexes, M3C, France; INSERM U970, PARCC, France. Electronic address: magalie.ladouceur@aphp.fr. 2. Paris Descartes University, Sorbonne Paris Cité, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou Physiology Department, France. 3. Paris Descartes University, Sorbonne Paris Cité, Paris, France; Faculty of Pharmacy, Inserm UMRS-1140, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Biochemistry, France. 4. Paris Descartes University, Sorbonne Paris Cité, Paris, France; INSERM U970, PARCC, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Cardiovascular Radiology, France. 5. Paris Descartes University, Sorbonne Paris Cité, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Clinical Research Unit and INSERM, CIC1418, Paris, France. 6. Paris Descartes University, Sorbonne Paris Cité, Paris, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Clinical Investigation center and INSERM, CIC-P 1418, Paris, France. 7. Paris Descartes University, Sorbonne Paris Cité, Paris, France; INSERM U970, PARCC, France; Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Pharmacology, Paris, France. 8. Assistance Publique-Hôpitaux de Paris, Hôpital Européen Georges Pompidou, Department of Biochemistry, France; Lip(Sys)2, EA 7357, Univ Paris-Sud, Université Paris-Saclay, Châtenay-Malabry, France.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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. RESULTS: Late gadolinium enhancement (LGE) was found in 35% of D-TGApatients, and the collagen degradation biomarker pro-MMP1:TIMP1 ratio was significantly increased in D-TGApatients 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. CONCLUSIONS: 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.