Albertini M, Santens B, Fusco F, Sarubbi B, Gallego P, Rodriguez-Puras MJ, Prokselj K, Kauling RM, Roos-Hesselink J, Labombarda F, Van De Bruaene A, Budts W, Waldmann V, Iserin L, Woudstra O, Bouma B, Ladouceur M. J Am Heart Assoc. 2024 May 7;13(9):e032174. doi: 10.1161/JAHA.123.032174. Epub 2024 Apr 30. PMID: 38686874
Take Home Points:
- This study demonstrates the external validation of a risk stratification model specifically designed to predict major adverse events in patients with D-transposition of the great arteries (D-TGA).
- Despite demographic variations between the study populations, the model proved to be generalizable and effective in stratifying risk levels.
- Although the model performed well overall, it tended to overestimate the occurrence of events, particularly within the highest risk categories.

Commentary from Dr. David Leone (Ohio, USA), section editor of ACHD journal watch
Introduction:
Most patients with D-transposition of the great arteries (D-TGA) who have undergone an atrial switch are entering the 4th and 5th decade of life which has been associated with a dramatic increase in major adverse events such as atrial arrhythmias, ventricular arrhythmias, heart failure, and death. This study aimed to assess and validate a D-TGA risk stratification tool to predict major adverse events in D-TGA patients.
Study Design:
This was a validation study of a previously published model/risk score completed by Woudstra et al. (2021). This group examined a cohort of patients with D-transposition of the great arteries (D-TGA) following an atrial switch procedure (Senning or Mustard). The validation cohort included patients over 16 years of age from seven large European centers enrolled in the Major Adverse Ventricular Arrhythmia and Related Events (MAREs) registry (NCT03833843). The original cohort was from a Dutch registry at five large medical centers (CONCOR) that included D-TGA patients aged ≥18 years.
The investigators assigned a score to everyone (n = 417) in the MAREs registry: 1 for age > 30 years, 1.5 for repair > 1 year, 1 for prior ventricular arrhythmias, 1 for ≥ moderate right ventricular (RV) dysfunction, 1.5 for severe tricuspid regurgitation, and 1.5 for ≥ mild left ventricular (LV) dysfunction (see Table 1).
The primary outcomes for the study were: (1) heart failure (HF) events defined as hospitalization for HF, heart transplantation, ventricular assist device implantation, or HF as the cause of death; (2) ventricular arrhythmias; and (3) all-cause mortality. Data were censored after five years of follow-up.
Table 1. Major Clinical Event Score Developed by Woudstra et al.
Criteria | Score points |
---|---|
Age >30 y | 1 |
Repair at >1 y | 1.5 |
Prior ventricular arrhythmia | 1 |
≥Moderate RV dysfunction | 1 |
Severe tricuspid regurgitation | 1.5 |
≥Mild LV dysfunction | 1.5 |
A risk score between 0 and 2 corresponded to the low‐risk group, with a predicted 5‐year risk <5%, a score between 2.5 and 3.5 to the intermediate‐risk group with a predicted risk of 5–20%, and a score between 4 and 7.5 to the high‐risk group with a predicted risk >20%. LV indicates left ventricle, and RV, right ventricle.
Key Finding
Figure 3. Kaplan‐Meier curves showing survival free of major clinical events by risk category at 5 years. Shaded areas correspond to 95% CIs.
Strengths:
- External validation of this D-TGA risk model on an independent, large, validated cohort.
- Good event-free survival differentiation between risk groups
- Identification of new features that may be important in the evaluation of a patient with D-TGA, such as sub-pulmonary left ventricular function.
Limitations:
- Many of these features are known to clinicians as being indicative of chronic progression of the disease.
- What can be done to prevent the deterioration and progression of heart failure in these patients.
- Congenitally correct transposition patients were not included.
Discussion:
The study represents external validation of a significant clinical events risk model applied to a substantial cohort of adults diagnosed with D-TGA. Utilizing this model, researchers were able to effectively categorize patients into distinct risk groups, distinguishing those at low risk from those classified as intermediate to high risk for major clinical events. Key prognostic indicators identified in the study include a history of previous heart failure episodes and dysfunction of the subpulmonary left ventricle. These factors emerged as significant markers for 5-year outcomes in the cohort.
The findings highlight the model’s capability to stratify patients based on their risk profiles accurately, thereby aiding clinicians in identifying individuals who may require more intensive monitoring and tailored therapeutic interventions. However, the study also emphasizes the necessity for further refinement and optimization of risk models. Future directions should be aimed at clinical applications of this tool.
Conclusion:
This study represents a significant advancement in managing patients with D-TGA. The risk stratification tool enables appropriate medication selection, efficient resource allocation, and guides future research priorities. Future investigations should evaluate the impact of heart failure treatments, including angiotensin receptor-neprilysin inhibitors (ARNI) and sodium-glucose cotransporter-2 (SGLT2) inhibitors, in high-risk D-TGA groups.