First in man right atrial appendage implantation of a Micra leadless pacemaker.

INTRODUCTION: Pacemaker implantation can be challenging in patients with congenital heart disease. METHODS AND RESULTS: In a patient with Ebstein disease and symptomatic sinus node dysfunction, despite multiple attempts, the Micra® pacemaker could not be implanted in the severely dilated right ventricle. In that context, and after iodine injection to confirm the appropriate location, the Micra® pacemaker was successfully implanted in the right appendage at the first attempt. CONCLUSION: Despite the recent development of dedicated dual-chamber leadless pacemaker, to the best of our knowledge, this case is the first off-label Micra® implantation in a right appendage.

Discordance between 2D and 4D flow in the assessment of pulmonary regurgitation severity: a right ventricular remodeling follow-up study.

OBJECTIVES: Pulmonary regurgitation (PR) is common in adult congenital heart disease (ACHD). 2D phase contrast MRI is the reference method for the quantification of PR and helps in the decision of pulmonary valve replacement (PVR). 4D flow MRI can be an alternative method to estimate PR but more validation is still needed. Our purpose was to compare 2D and 4D flow in PR quantification using the degree of right ventricular remodeling after PVR as the reference standard. METHODS: In 30 adult patients with a pulmonary valve disease recruited between 2015 and 2018, PR was assessed using both 2D and 4D flow. Based on the clinical standard of care, 22 underwent PVR. The pre PVR estimate of PR was compared using the post-operative decrease in right ventricle end-diastolic volume on follow-up exam as reference. RESULTS: In the overall cohort, regurgitant volume (Rvol) and regurgitant fraction (RF) of PR measured by 2D and 4D flow were well correlated but with moderate agreement in the overall cohort (r = 0.90, mean diff. -14 ± 12.5 mL; and r = 0.72, mean diff. -15 ± 13%; all p < 0.0001). Correlations between Rvol estimates and right ventricle end-diastolic volume decrease after PVR was higher with 4D flow (r = 0.80, p < 0.0001) than with 2D flow (r = 0.72, p < 0.0001). CONCLUSIONS: In ACHD, PR quantification from 4D flow better predicts post-PVR right ventricle remodeling than that from 2D flow. Further studies are needed to evaluate the added value of this 4D flow quantification for guiding replacement decision. KEY POINTS: • Using 4D flow MRI allows a better quantification of pulmonary regurgitation in adult congenital heart disease than 2D flow when taking right ventricle remodeling after pulmonary valve replacement as a reference. • A plane positioned perpendicular to the ejected flow volume as allowed by 4D flow provides better results to estimate pulmonary regurgitation.

Catheter ablation of atrial tachyarrhythmias in patients with atrioventricular septal defect.

AIMS: The incidence of atrial tachyarrhythmias is high in patients with atrioventricular septal defect (AVSD). No specific data on catheter ablation have been reported so far in this population. We aimed to describe the main mechanisms of atrial tachyarrhythmias in patients with AVSD and to analyse outcomes after catheter ablation. METHODS AND RESULTS: This observational multi-centric cohort study enrolled all patients with AVSD referred for catheter ablation of an atrial tachyarrhythmia at six tertiary centres from 2004 to 2022. The mechanisms of the different tachyarrhythmias targeted were described and outcomes were analysed. Overall, 56 patients (38.1 ± 17.4 years, 55.4% females) were included. A total of 87 atrial tachyarrhythmias were targeted (mean number of 1.6 per patient). Regarding main circuits involved, a cavo-annular isthmus-dependent intra-atrial re-entrant tachycardia (IART) was observed in 41 (73.2%) patients and an IART involving the right lateral atriotomy in 10 (17.9%) patients. Other tachyarrhythmias with heterogeneous circuits were observed in 13 (23.2%) patients including 11 left-sided and 4 right-sided tachyarrhythmias. Overall, an acute success was achieved in 54 (96.4%) patients, and no complication was reported. During a mean follow-up of 2.8 ± 3.8 years, 22 (39.3%) patients had at least one recurrence. Freedom from atrial tachyarrhythmia recurrences was 77.5% at 1 year. Among 15 (26.8%) patients who underwent repeated ablation procedures, heterogeneous circuits including bi-atrial and left-sided tachyarrhythmias were more frequent. CONCLUSION: In patients with AVSD, most circuits involve the cavo-annular isthmus, but complex mechanisms are frequently encountered in patients with repeated procedures. The acute success rate is excellent, although recurrences remain common during follow-up.

A new score for life-threatening ventricular arrhythmias and sudden cardiac death in adults with transposition of the great arteries and a systemic right ventricle.

AIMS: To investigate the incidence of major adverse ventricular arrhythmias and related events (MAREs) and to develop a stratification tool predicting MAREs in adults with a systemic right ventricle (sRV). METHODS AND RESULTS: In a multicentre approach, all adults (≥16 years old) with a sRV undergoing follow-up between 2000 and 2018 were identified. The incidence of MAREs, defined as sudden cardiac death, sustained ventricular tachycardia, and appropriate implantable cardioverter-defibrillator (ICD) therapy, was analysed. The association of MAREs with clinical, electrical, and echocardiographic parameters was evaluated. A total of 1184 patients (median age 27.1 years; interquartile range 19.9-34.9 years; 59% male; 70% with atrial switch repair for D-transposition of the great arteries) were included. The incidence of MAREs was 6.3 per 1000 patient-years. On multivariate analysis, age, history of heart failure, syncope, QRS duration, severe sRV dysfunction and at least moderate left ventricular outflow tract obstruction were retained in the final model with a C-index of 0.78 [95% confidence interval (CI) 0.72-0.83] and a calibration slope of 0.93 (95% CI 0.64-1.21). For every five ICDs implanted in patients with a 5-year MARE risk >10%, one patient may potentially be spared from a MARE. CONCLUSION: Sudden cardiac death remains a devastating cause of death in a contemporary adult cohort with a sRV. A prediction model based on clinical, electrocardiographic, and echocardiographic parameters was devised to estimate MARE risk and to identify high-risk patients who may benefit from primary prevention ICD implantation.

Long-Term Follow-Up of Patients With Tetralogy of Fallot and Implantable Cardioverter Defibrillator: The DAI-T4F Nationwide Registry.

BACKGROUND: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease, and sudden cardiac death represents an important mode of death in these patients. Data evaluating the implantable cardioverter defibrillator (ICD) in this patient population remain scarce. METHODS: A Nationwide French Registry including all patients with tetralogy of Fallot with an ICD was initiated in 2010 by the French Institute of Health and Medical Research. The primary time to event end point was the time from ICD implantation to first appropriate ICD therapy. Secondary outcomes included ICD-related complications, heart transplantation, and death. Clinical events were centrally adjudicated by a blinded committee. RESULTS: A total of 165 patients (mean age, 42.2±13.3 years, 70.1% males) were included from 40 centers, including 104 (63.0%) in secondary prevention. During a median (interquartile range) follow-up of 6.8 (2.5-11.4) years, 78 (47.3%) patients received at least 1 appropriate ICD therapy. The annual incidence of the primary outcome was 10.5% (7.1% and 12.5% in primary and secondary prevention, respectively; P=0.03). Overall, 71 (43.0%) patients presented with at least 1 ICD complication, including inappropriate shocks in 42 (25.5%) patients and lead dysfunction in 36 (21.8%) patients. Among 61 (37.0%) patients in primary prevention, the annual rate of appropriate ICD therapies was 4.1%, 5.3%, 9.5%, and 13.3% in patients with, respectively, 0, 1, 2, or ≥3 guidelines-recommended risk factors. QRS fragmentation was the only independent predictor of appropriate ICD therapies (hazard ratio, 3.47 [95% CI, 1.19-10.11]), and its integration in a model with current criteria increased the 5-year time-dependent area under the curve from 0.68 to 0.81 (P=0.006). Patients with congestive heart failure or reduced left ventricular ejection fraction had a higher risk of nonarrhythmic death or heart transplantation (hazard ratio, 11.01 [95% CI, 2.96-40.95]). CONCLUSIONS: Patients with tetralogy of Fallot and an ICD experience high rates of appropriate therapies, including those implanted in primary prevention. The considerable long-term burden of ICD-related complications, however, underlines the need for careful candidate selection. A combination of easy-to-use criteria including QRS fragmentation might improve risk stratification. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03837574.

Aorta-to-right ventricle neoshunt closure using an Amplatzer Duct Occluder II device.

We report the case of a 22-year-old female patient with complex congenital heart disease and multiple cardiac surgeries who came to our attention for right heart failure and hemolysis 3 years after aortic valve replacement surgery. She was diagnosed with aorta-to-right ventricle fistula and was efficiently treated with retrograde implantation of an Amplatzer Duct Occluder II device using three-dimensional multimodality fusion imaging.

Cardiovascular events in perimembranous ventricular septal defect with left ventricular volume overload: a French prospective cohort study (FRANCISCO).

The long-term prospective multi-centre nationwide (French) observational study FRANCISCO will provide new information on perimembranous ventricular septal defect with left ventricular overload but no pulmonary hypertension in children older than 1 year. Outcomes will be compared according to treatment strategy (watchful waiting, surgical closure, or percutaneous closure) and anatomic features of the defect. The results are expected to provide additional guidance about the optimal treatment of this specific population, which is unclear at present. BACKGROUND: The management of paediatric isolated perimembranous ventricular septal defect (pmVSD) with left ventricle (LV) volume overload but no pulmonary arterial hypertension (PAH) remains controversial. Three therapeutic approaches are considered: watchful waiting, surgical closure, and percutaneous closure. We aim to investigate the long-term outcomes of these patients according to anatomic pmVSD characteristics and treatment strategy. METHODS: The Filiale de Cardiologie Pediatrique et Congénitale (FCPC) designed the FRANCISCO registry, a long-term prospective nationwide multi-centre observational cohort study sponsored by the French Society of Cardiology, which enrolled, over 2 years (2018­2020), patients older than 1 year who had isolated pmVSD with LV volume overload. Prevalent complications related to pmVSD at baseline were exclusion criteria. Clinical, echocardiographic, and functional data will be collected at inclusion then after 1, 5, and 10 years. A core lab will analyse all baseline echocardiographic data to depict anatomical pmVSD features. The primary outcome is the 5-year incidence of cardiovascular events (infective endocarditis, sub-aortic stenosis, aortic regurgitation, right ventricular outflow tract stenosis, tricuspid regurgitation, PAH, arrhythmia, stroke, haemolysis, heart failure, or death from a cardiovascular event). We plan to enrol 200 patients, given the 10% estimated 5-year incidence of cardiovascular events with a 95% confidence interval of ±5%. Associations linking anatomical pmVSD features and treatment strategy to the incidence of complications will be assessed. CONCLUSIONS: The FRANSCICO study will provide the long-term incidence of complications in patients older than 1 year with pmVSD and LV volume overload. The results are expected to improve guidance for treatment decisions.

Transbaffle/transconduit puncture using a simple CARTO-guided approach without echocardiography in patients with congenital heart disease.

INTRODUCTION: Catheter ablation (CA) of atrial tachyarrhythmias (ATs) in patients with complex congenital heart disease (CHD) often requires technically challenging transbaffle or transconduit puncture. The aim was to assess the feasibility and safety of transbaffle/transconduit puncture based on computed tomography (CT) three-dimensional (3D) reconstruction merged with electro-anatomical mapping (EAM) without per-procedure echocardiographic guidance. METHODS AND RESULTS: We included 18 consecutive CHD patients in two centers who had atrial-switch or Fontan surgery and underwent CA of AT by an antegrade approach requiring intracardiac puncture. Twelve patients with atrial-switch surgery and six patients with extracardiac Fontan surgery were referred for CA of AT. Cardiac CT with 3D reconstruction was performed before the procedure. The 3D volume of the systemic venous atrium or extracardiac conduit acquired by EAM was merged with the corresponding CT 3D reconstruction. The ablation catheter was positioned at the optimal puncture site. Under fluoroscopic guidance, the needle was positioned next to the ablation and the puncture was performed. Balloon expansion of the puncture site was performed in every case of transconduit puncture and in two (17%) cases of transbaffle puncture. Overall, 17 intra-atrial reentrant tachycarrythmias and 9 focal ATs were successfully ablated, with no acute complications. The median time to access the pulmonary atrium was 78.5 minutes (range, 55-185) and total median fluoroscopy time was 23 minutes (range, 7-53). CONCLUSIONS: Transbaffle and transconduit punctures can be performed safely in CHD patients by using a simple technique relying on CT 3D reconstruction and EAM.

Neopulmonary Outflow Tract Obstruction Assessment by 4D Flow MRI in Adults With Transposition of the Great Arteries After Arterial Switch Operation.

BACKGROUND: The main complication in adult patients with transposition of the great arteries (TGA) treated by an arterial switch operation (ASO) is neopulmonary outflow tract stenosis (NPOTS). However, pulmonary flow velocity measurements cannot always be performed with transthoracic echocardiography (TTE) due to complex anatomical features. 4D flow MRI allows detection, quantification, and location of the obstruction site along the NPOTS. PURPOSE AND HYPOTHESIS: To investigate the accuracy of 4D flow for the diagnosis of NPOTS in adults with TGA corrected by ASO. STUDY TYPE: Prospective. POPULATION: Thirty-three adult patients with TGA treated by ASO (19 men, mean age 25.5 years old). FIELD STRENGTH/SEQUENCE: Accelerated 4D flow research sequence at 3T. ASSESSMENT: Maximum NPOTS velocities on TTE and 4D flow MRI done the same day. STATISTICAL TESTS: Pearson correlation coefficient, paired t-test, and Bland-Altman analysis were used to investigate the relationship between TTE and MRI data. RESULTS: In 16 patients (48.5%), evaluation of NPOTS anatomy was not obtained by TTE, while it was always possible by 4D flow. Peak flow velocity (PV) measurements in Doppler and 4D flow were highly correlated (r = 0.78; P < 0.001). PV >350 cm.s-1 was detected in only one patient (3%) by TTE vs. five patients (15%) by 4D flow. Moreover, a high correlation was found between PV and the right ventricle (RV) mass index to body surface area when using 4D flow (r = 0.63; P < 0.001). The location of NPOTS was determined in all patients using 4D flow and concerned the main pulmonary artery in 42%. DATA CONCLUSION: Compared to TTE, 4D flow MRI provides better sensitivity to detect and locate NPOTS in patients with TGA treated by ASO. 4D flow PV measurements in NPOTS were well correlated with TTE PV and RV mass. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2020;51:1699-1705.

Administrative health databases for addressing emerging issues in adults with CHD: a systematic review.

The need for population-based studies of adults with CHD has motivated the growing use of secondary analyses of administrative health data in a variety of jurisdictions worldwide. We aimed at systematically reviewing all studies using administrative health data sources for adult CHD research from 2006 to 2016. Using PubMed and Embase (1 January, 2006 to 1 January, 2016), we identified 2217 abstracts, from which 59 studies were included in this review. These comprised 12 different data sources from six countries. Of these, 55% originated in the United States of America, 28% in Canada, and 17% in Europe and Asia. No study was published before 2007, after which the number of publications grew exponentially. In all, 41% of the studies were cross-sectional and 25% were retrospective cohort studies with a wide variation in the availability of patient-level compared with hospitalisation-level episodes of care; 58% of studies from eight different data sources linked administrative data at a patient level; and 37% of studies reported validation procedures. Assessing resource utilisation and temporal trends of relevant epidemiological and outcome end points were the most reported objectives. The median impact factor of publication journals was 4.04, with an interquartile range of 3.15, 7.44. Although not designed for research purposes, administrative health databases have become powerful data sources for studying adult CHD populations because of their large sample sizes, comprehensive records, and long observation periods, providing a useful tool to further develop quality of care improvement programmes. Data linkage with electronic records will become important in obtaining more granular life-long adult CHD data. The health services nature of the data optimises the impact on policy and public health.

Temporal trends and changing profile of adults with congenital heart disease undergoing heart transplantation.

AIMS: To investigate the temporal trends in profile and outcomes of adults with congenital heart disease (ACHD) undergoing heart transplantation (HT). METHODS AND RESULTS: Out of a multi-institutional series of 2257 HT from 1988 to 2012, 100 HT were performed in 97 ACHD. We evaluated clinical characteristics, underlying defect, surgical history, perioperative issues, and outcomes. We compared two eras: era 1 (1988-2005, n = 48) and era 2 (2006-2012, n = 49). Mean age at HT was 30.3 ± 10.5 years. Twenty-five patients (25.8%) had biventricular physiology with a systemic right ventricle and 43 patients (44%) had univentricular physiology. Adults with congenital heart disease severity were classified as great complexity (74.2%), moderate (21.7%), and simple (4.1%). During a median follow-up of 28.7 months [0-282], 44 patients died. Early mortality was high (34%; 95% CI 0.2536-0.4390). Survival was 63.9% at 1 year. The proportion of univentricular patients did not change. Biventricular patients with systemic right ventricle significantly increased in era 2 (16.7  vs. 34.7%, P = 0.04) due to increasing number of transposition of the great arteries with atrial switch. Although the proportion of great complexity ACHD did not change significantly in era 2 (81.6%  vs. and 66.7% in era 1, P = 0.09), ACHD recipients have more advanced disease, being more likely hospitalized (P = 0.03), receiving intravenous inotropes (P = 0.01), under assist devices (P = 0.04), or UNOS status 1 (P = 0.02) at the time of HT. Survival rates were comparable. CONCLUSION: Despite a worse risk profile, mortality after HT in ACHD did not increase. Improving survival of complex CHD will probably amplify the proportion of complex ACHD recipients with more advanced disease.

Usefulness of maximal oxygen pulse in timing of pulmonary valve replacement in patients with isolated pulmonary regurgitation.

Patients with pulmonary regurgitation after tetralogy of Fallot repair have impaired aerobic capacity; one of the reasons is the decreasing global ventricular performance at exercise, reflected by decreasing peak oxygen pulse. The aims of our study were to evaluate the impact of pulmonary valve replacement on peak oxygen pulse in a population with pure pulmonary regurgitation and with different degrees of right ventricular dilatation and to determine the predictors of peak oxygen pulse after pulmonary valve replacement. The mean and median age at pulmonary valve replacement was 27 years. Mean pre-procedural right ventricular end-diastolic volume was 182 ml/m2. Out of 24 patients, 15 had abnormal peak oxygen pulse before pulmonary valve replacement. We did not observe a significant increase in peak oxygen pulse after pulmonary valve replacement (p=0.76). Among cardiopulmonary test/MRI/historical pre-procedural parameters, peak oxygen pulse appeared to be the best predictor of peak oxygen pulse after pulmonary valve replacement (positive and negative predictive values, respectively, 0.94 and 1). After pulmonary valve replacement, peak oxygen pulse was well correlated with left ventricular stroke and end-diastolic volumes (r=0.67 and 0.68, respectively). Our study confirms the absence of an effect of pulmonary valve replacement on peak oxygen pulse whatever the initial right ventricular volume, reflecting possible irreversible right and/or left ventricle lesions. Pre-procedural peak oxygen pulse seemed to well predict post-procedural peak oxygen pulse. These results encourage discussions on pulmonary valve replacement in patients showing any decrease in peak oxygen pulse during their follow-up.

Coronary artery compression during intention to treat right ventricle outflow with percutaneous pulmonary valve implantation: incidence, diagnosis, and outcome.

OBJECTIVES: Evaluate the incidence, diagnosis, and outcome of coronary compression (CC) during right-ventricular outflow tract interventions. BACKGROUND: The incidence, risk factors, diagnosis, and outcomes of CC during percutaneous pulmonary valve implantation are poorly defined. METHODS: One-hundred consecutive patients (May 2008 to January 2012) undergoing transcatheter right-ventricular outflow tract treatment in two institutions were studied. RESULTS: CC occurred in six patients (6%) with a right ventricular outflow conduit stenosis, at a median age of 24.5 (13-49) years. It involved the left main coronary artery in four and the right coronary artery originating from the left anterior descending coronary artery in two patients. Conduit types were homograft (n = 3), bioprosthesis (n = 2), and a pericardial patch (n = 1). Median diameter was 23 (17-24) mm at surgical implantation. CC was diagnosed through a selective coronary angiogram during balloon dilation of the conduit in the first three patients and through an aortic root angiogram for the three next cases because we recognized that proximal compression could be masked during coronary artery cannulation. It was suspected on pre-procedure imaging (magnetic resonance imaging and/or computed tomography) in three cases. Patients with abnormal coronary anatomy tend to be at increased risk of CC (P = 0.0504). One institution had a higher incidence of CC (P = 0.04). CC resolved after balloon deflation. No patient underwent conduit stenting. Four patients underwent surgical reconstruction of right ventricular outflow tract. CONCLUSIONS: CC is accurately diagnosed during right-ventricular outflow tract interventions. We recommend an aortic root angiogram during dilation with a non-compliant balloon matching the diameter and length of the intended conduit implant.

Long-term outcomes after heart transplantation in adult patients with univentricular versus biventricular congenital heart disease.

OBJECTIVES: Heart transplantation (HT) is the only life-extending therapy in adults with congenital heart disease (CHD) and end-stage heart failure. HT is considered at high risk in complex CHD given the anatomical complexity and past medical history. Little is known about long-term outcomes after HT in these patients. We aimed to evaluate early and long-term outcomes after HT in adult patients with univentricular versus biventricular CHD. METHODS: This multicentre retrospective cohort study included all adult CHD patients who underwent HT between 1988 and 2021 in 3 tertiary centres. Factors associated with early (<30 days) and conditional long-term survival were assessed in the entire cohort. RESULTS: Over a mean follow-up of 10.1 ± 7.8 years, 149 patients were included, of whom 55 (36.9%) had univentricular CHD. Sixty-four patients died during follow-up including 47 deaths before discharge from hospital. In multivariable analysis, univentricular physiology and female recipient gender were independently associated with a higher risk of early mortality (odds ratio 2.99; 95% confidence interval [1.33-6.74] and odds ratio 2.76; 95% confidence interval [1.23-6.20], respectively). For patients who survived the early period, conditional long-term survival was excellent for both groups and was not different between 2 groups (P = 0.764). CONCLUSIONS: Adult CHD patients have a high incidence of overall mortality due to a high rate of early mortality. Univentricular physiology was associated with a significant increased risk of early death compared to biventricular physiology. However, late mortality was excellent and no longer different between the 2 physiologies.

Increased aortic pressures and pulsatile afterload components promote concentric left ventricular remodeling in adults with transposition of the great arteries and arterial switch operation.

BACKGROUND: Functional abnormalities of the ascending aorta (AA) have been mainly reported in young patients who underwent arterial switch operation (ASO) for transposition of the great arteries (TGA). OBJECTIVES: To compare systolic, diastolic brachial and central blood pressures (bSBP, bDBP, cSBP, cDBP), aortic biomechanical parameters, and left ventricular (LV) afterload criteria in adult ASO patients with healthy controls and to assess their relationships with LV remodeling and aortic size. MATERIALS AND METHODS: Forty-one prospectively enrolled patients (16.8 to 35.8 years) and 41 age- and sex-matched healthy volunteers underwent cardiac MRI to assess LV remodeling with simultaneous brachial BP estimation. After MRI, carotid-femoral tonometry was performed to measure pulse wave velocity (cfPWV), cSBP and cDBP for further calculation of pulse pressure (cPP), AA distensibility (AAD), and AA and LV elastance (AAE, LVE). RESULTS: bSBP, bDBP, cSBP,cDBP and cPP were all significantly higher in ASO group than in controls: cSBP (116.5 ± 13.8 vs 106.1 ± 12.0, p < 0.001), cDBP (72.5 ± 6.9 vs 67.1 ± 9.4, p = 0.002), cPP (44.0 ± 12.1 vs 39.1 ± 8.9, p = 0.003) and not related to aortic size. AAD were decreased in ASO patients vs controls (4.70 ± 2.72 vs 6.69 ± 2.16, p < 0.001). LV mass was correlated with bSBP, cSBP, cPP (ρ = 0.48; p < 0.001), while concentric LV remodeling was correlated with AAE (ρ = 0.60, p < 0.001) and LVE (ρ = 0.32, p = 0.04), but not with distensibility. CONCLUSION: Even without reaching arterial hypertension, aortic sBP and PP are increased in the adult TGA population after ASO, altering the pulsatile components of afterload and contributing to LV concentric remodeling.

External Validation of a Risk Score Model for Predicting Major Clinical Events in Adults After Atrial Switch.

BACKGROUND: A risk model has been proposed to provide a patient individualized estimation of risk for major clinical events (heart failure events, ventricular arrhythmia, all-cause mortality) in patients with transposition of the great arteries and atrial switch surgery. We aimed to externally validate the model. METHODS AND RESULTS: A retrospective, multicentric, longitudinal cohort of 417 patients with transposition of the great arteries (median age, 24 years at baseline [interquartile range, 18-30]; 63% men) independent of the model development and internal validation cohort was studied. The performance of the prediction model in predicting risk at 5 years was assessed, and additional predictors of major clinical events were evaluated separately in our cohort. Twenty-five patients (5.9%) met the major clinical events end point within 5 years. Model validation showed good discrimination between high and low 5-year risk patients (Harrell 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]). In our population, the strongest independent predictors of major clinical events were a history of heart failure and at least mild impairment of the subpulmonary left ventricle function. CONCLUSIONS: We reported the first external validation of a major clinical events risk model in a large cohort of adults with transposition of the great arteries. The model allows for distinguishing patients at low risk from those at intermediate to high risk. Previous episode of heart failure and subpulmonary left ventricle dysfunction appear to be key markers in the prognosis of patients. Further optimizing risk models are needed to individualize risk predictions in patients with transposition of the great arteries.