External validation of a risk score model for predicting major clinical events in adults after atrial switch operation for transposition of the great arteries

Background A risk model has been proposed to provide a patient individualized estimation of risk for major clinical events (heart failure, ventricular arrhythmia, all-cause mortality) in patients with transposition of the great arteries (D-TGA) repaired by an atrial switch operation. The aim of this study was to externally validate the model. Methods A retrospective, multicentric, longitudinal cohort of 417 patients with D-TGA (median age 24 years at baseline [interquartile range 18-30], 63% male) independent of the model development and internal validation cohort was studied. Data on risk model predictors (age >30 years, prior ventricular arrhythmia, age >1 year at atrial switch, moderate or severe right ventricular dysfunction, severe tricuspid regurgitation and at least mild left ventricular (LV) dysfunction) were collected from the time of baseline clinical evaluation. The performance of the prediction model in predicting risk at 5 years was assessed. Results Twenty-five patients (5.9%) met the major clinical events endpoint within 5 years. Model validation showed a good discrimination between high and low 5-year risk patients (Harrell’s C-index of 0.73 (95% CI 0.65–0.81)) but tended to overestimate this risk (calibration slope of 0.20 (95% CI 0.03–0.36)). We separately evaluated predictors of major clinical events in our cohort. History of heart failure and at least mildly impaired sub pulmonary LV function remained the strongest predictors of major clinical events in this population. Conclusions We reported the first external validation of a major clinical events risk model in a large D-TGA patient population. Although a good discrimination, the model tends to overestimate the absolute 5-year risk. Subpulmonary LV dysfunction appears to be a key marker in the prognosis of patients with Senning and Mustard. Further optimizing risk models are needed to individualize risk predictions in D-TGA patients. Clinical Perspective What is new? This is the first external validation of a risk model for major clinical events in D-TGA patients after atrial switch and the largest study emphasizing the importance of assessing subpulmonary left ventricle (LV) function in these patients. What are clinical implications? Risk model for major clinical events can be used to discriminate patients at low from those at intermediate and high risk. This tool helps determine follow-up intensity, and support management decisions specifically for intermediate- and high-risk patients with a history of heart failure and at least mild sub pulmonary left ventricle (LV) dysfunction. Sub-pulmonary LV, which can be the “forgotten chamber” in these patients with a systemic right ventricle, should be carefully and regularly surveyed. Patients from the intermediate/high-risk group with history of heart failure, and subpulmonary LV dysfunction have a poor prognosis and should be referred for consideration of advanced therapies