Common Genetic Variants Contribute to Risk of Transposition of the Great Arteries.

RATIONALE: Dextro-transposition of the great arteries (D-TGA) is a severe congenital heart defect which affects approximately 1 in 4,000 live births. While there are several reports of D-TGA patients with rare variants in individual genes, the majority of D-TGA cases remain genetically elusive. Familial recurrence patterns and the observation that most cases with D-TGA are sporadic suggest a polygenic inheritance for the disorder, yet this remains unexplored. OBJECTIVE: We sought to study the role of common single nucleotide polymorphisms (SNPs) in risk for D-TGA. METHODS AND RESULTS: We conducted a genome-wide association study in an international set of 1,237 patients with D-TGA and identified a genome-wide significant susceptibility locus on chromosome 3p14.3, which was subsequently replicated in an independent case-control set (rs56219800, meta-analysis P=8.6x10 CONCLUSIONS: This work provides support for a polygenic architecture in D-TGA and identifies a susceptibility locus on chromosome 3p14.3 nea

Umbilical vein catheter protruding through a pulmonary vein in a patient with an infracardiac type total abnormal pulmonary venous drainage

Developmen

Joint Modeling of Longitudinal Markers and Time-to-Event Outcomes: An Application and Tutorial in Patients After Surgical Repair of Transposition of the Great Arteries

BACKGROUND: Most patients with congenital heart disease survive into adulthood; however, residual abnormalities remain and management of the patients is life-long and personalized. Patients with surgical repair of transposition of the great arteries, for example, face the risk to develop neoaortic valve regurgitation. Cardiologists update the prognosis of the patient intuitively with updated information of the cardiovascular status of the patient, for instance from echocardiographic imaging. METHODS: Usually a time-dependent version of the Cox model is used to analyze repeated measurements with a time-to-event outcome. New statistical methods have been developed with multiple advantages, of which the most prominent one being the joint model for longitudinal and time-to-event outcome. In this tutorial, the joint modeling framework is introduced and applied to patients with transposition of the great arteries after surgery with a long-term follow-up, where repeated echocardiographic values of the neoaortic root are evaluated against the risk of neoaortic valve regurgitation. RESULTS: The data are analyzed with the time-dependent Cox model as benchmark method, and the results are compared with a joint model, leading to different conclusions. The flexibility of the joint model is shown by adding the growth rate of the neoaortic root to the model and adding repeated values of body surface area to obtain a multimarker model. Lastly, it is demonstrated how the joint model can be used to obtain personalized dynamic predictions of the event. CONCLUSIONS: The joint model for longitudinal and time-to-event data is an attractive method to analyze data in follow-up studies with repeated measurements. Benefits of the method include using the estimated natural trajectory of the longitudinal outcome, great flexibility through multiple extensions, and dynamic individualized predictions

Anomalous connection of the circumflex coronary artery to the pulmonary trunk in a patient with Taussig-Bing anomaly: a case report

Background: Coronary anomalies are present in one-third of all patients with transposition of the great arteries (TGA) and have been associated with increased risk of adverse outcomes after the arterial switch operation. Therefore, knowledge about coronary anatomy remains key. Case summary: A 5-day-old girl with prenatal diagnosis of Taussig-Bing anomaly (double outlet right ventricle with TGA and large subpulmonary ventricular septal defect) along with aortic arch hypoplasia and coarctation of the aorta underwent the arterial switch operation with closure of the ventricular septal defect and aortic arch repair. On preoperative echocardiography, the right (R) and left coronary artery (LCx) connected both to aortic sinus 1, suggesting 1RLCx coronary anatomy according to the Leiden Convention coronary coding system. However, intraoperative inspection led to a reclassification of the coronary anatomy: the right coronary artery and left anterior descending coronary artery connected to aortic sinus 1 (1RL) as had been observed on echocardiography, but - remarkably - the circumflex coronary artery (Cx) connected to the posterior sinus of the pulmonary trunk. As a consequence, cardioplegia was administered into both the aortic and pulmonary roots, and the circumflex coronary artery could stay in its native position without having to be transferred during the arterial switch operation. Discussion: Various disruptions during embryological development can lead to unusual coronary anatomy in TGA patients. While anomalous connection of a coronary artery to the pulmonary trunk remains exceedingly rare, care should be taken to identify this pattern when present as failure to do so may result in adverse outcomes

Four-dimensional flow cardiovascular magnetic resonance for the evaluation of the atrial baffle after Mustard repair

Cardiolog

Reoperation for right ventricular outflow tract obstruction after arterial switch operation for transposition of the great arteries and aortic arch obstruction

Cardiolog

Outcomes of the modified Yacoub aortocoronary flap technique for 'non-separable' single sinus coronary arteries with intramural course in the neonatal arterial switch operation

OBJECTIVES: Coronary transfer remains the most crucial part of the arterial switch operation (ASO); yet, certain coronary anatomies prohibit the use of button or trap-door transfer techniques. In the rare setting of 'non-separable' single sinus coronary arteries with intramural course, the modified Yacoub aortocoronary flap technique is a viable option. The aim of this study is to describe this operative technique and review its early- and mid-term outcomes. METHODS: This retrospective analysis included all cases with 'non-separable' single sinus coronary arteries with intramural course where the modified Yacoub aortocoronary flap technique served as a bail-out option. RESULTS: Of 516 patients who underwent ASO at our institution between January 1977 and April 2022, 14 underwent the modified Yacoub aortocoronary flap technique. The median age at ASO was 10 (interquartile range 7-19) days. Hospital mortality occurred in 3 patients (21.4%), all being related to coronary complications. All hospital survivors were still alive at a median of 9.1 (interquartile range 4.2-18.3) years after the ASO. None of them developed complaints of ischaemia, ventricular arrhythmias, ventricular dysfunction or exercise intolerance. Surveillance computed tomography angiography showed stable aortocoronary relationships free from stenosis, compression and kinking. No reoperations for coronary artery problems and/or neoaortic valve or root problems were needed. CONCLUSIONS: Although close monitoring of early coronary events seems crucial to prevent perioperative mortality, the modified Yacoub aortocoronary flap technique may serve as a viable bail-out option in patients with 'non-separable' single sinus coronary anatomy with intramural course, with excellent results among hospital survivors

Persistent neo-aortic growth during adulthood in patients after an arterial switch operation

After the arterial switch operation (ASO), disproportional neo-aortic growth during childhood has been reported. Even though it has been suggested neo-aortic dilation will stabilise in adulthood, data are lacking. The aim of this study was to assess the change in neo-aortic dimensions, prevalence of neo-aortic dilation >40 mm and long-term outcome in adults who underwent ASO in childhood. All 116 ASO patients operated in a tertiary referral centre and born before 1995 were included. Of these, 83 (72%) survived to adulthood (>17 years) and six were lost to follow-up. Neo-aortic measurements performed in adulthood were collected from available echocardiographic, cardiovascular magnetic resonance and CT images. The time trend was analysed using a mixed model, adjusted for imaging modality. Clinical data with at least one measurement of the neo-aortic diameter were available in 77 (93%) adult patients and serial measurements in 65 (78%). At baseline (median age 18.1 years), mean neo-aortic diameter was 36±5 mm. Mean neo-aortic growth was 0.31 mm/year (p <0.001 compared with normal value 0.08 mm/year) and was linear over time. Freedom from neo-aortic dilation beyond a diameter of 40 mm was 23% at 28 years of age. During a mean clinical follow-up in adulthood of 7.2 years (IQR 4.0 to 10.1), 3 (4%) patients underwent neo-aortic replacement. No other neo-aortic complications occurred. In early adulthood, neo-aortic growth was on average linear and did not stabilise over tim

Oxygen Uptake Efficiency Slope is Strongly Correlated to VO2peak Long-Term After Arterial Switch Operation

After the arterial switch operation (ASO) for transposition of the great arteries (TGA), many patients have an impaired exercise tolerance. Exercise tolerance is determined with cardiopulmonary exercise testing by peak oxygen uptake (VO 2peak). Unlike VO 2peak, the oxygen uptake efficiency slope (OUES) does not require a maximal effort for interpretation. The value of OUES has not been assessed in a large group of patients after ASO. The purpose of this study was to determine OUES and VO 2peak, evaluate its interrelationship and assess whether exercise tolerance is related to ventricular function after ASO. A cardiopulmonary exercise testing, assessment of physical activity score and transthoracic echocardiography (fractional shortening and left/right ventricular global longitudinal peak strain) were performed to 48 patients after ASO. Median age at follow-up after ASO was 16.0 (IQR 13.0–18.0) years. Shortening fraction was normal (36 ± 6%). Left and right global longitudinal peak strain were reduced: 15.1 ± 2.4% and 19.5 ± 4.5%. This group of patients showed lower values for all cardiopulmonary exercise testing parameters compared to the reference values: mean VO 2peak% 75% (95% CI 72–77) and mean OUES% 82(95% CI 77–87); without significant differences between subtypes of TGA. A strong-to-excellent correlation between the VO 2peak and OUES was found (absolute values: R = 0.90, p < 0.001; normalized values: R = 0.79, p < 0.001). No correlation was found between cardiopulmonary exercise testing results and left ventricle function parameters. In conclusion, OUES and VO 2peak were lower in patients after ASO compared to reference values but are strongly correlated, making OUES a valuable tool to use in this patient group when maximal effort is not achievable