Myocardial fibrosis and its relation to adverse outcome in transposition of the great arteries with a systemic right ventricle

Background: Myocardial dysfunction has been implicated in gradual heart failure in transposition of the great arteries (TGA) with a systemic right ventricle (RV). Fibrosis can be assessed using the extracellular volume fraction (ECV). Our aim was to measure ECV and determine its associations with clinical findings and outcomes. Methods: We prospectively measured ECV in systemic RV subjects (either D-loop after atrial switch or L-loop) and healthy controls. T ₁ measurements for a single mid-ventricular short-axis plane before and 3, 7, and 15 min after gadolinium contrast were used to quantify systemic ventricular ECV. Individuals with elevated ECV were compared to those without. Results: In 53 TGA subjects (age 34.6 ± 10.3 years, 41% female) the mean ECV for the systemic RV (28.7 ± 4.4%) was significantly higher than the left ventricle in 22 controls (26.1 ± 2.8%, P = 0.0104). Those with an elevated ECV (n = 15, 28.3%) had a higher b-type natriuretic peptide (BNP) (P < 0.011) and a longer 6-min walk distance (P = 0.021), but did not differ by age, arrhythmia history, ventricular volume, function, or circulating collagen byproducts. At follow-up (median 4.4 years), those experiencing major cardiovascular endpoints (new arrhythmia, arrhythmia device, heart failure hospitalization, listing for transplantation, mechanical support, or cardiovascular death, n = 14) had a higher ECV. ECV, age, and BNP were independent predictors of cardiac events in Cox-proportional hazard models. Conclusions: Myocardial fibrosis is common in the systemic RV and associated with a higher BNP. Elevated CMR-derived ECV was associated with adverse clinical outcome. The findings suggest a role of diffuse myocardial fibrosis in clinical deterioration of the systemic RV.