In ccTGA, Early Anatomic Repair Edges Out Physiologic Repair in Long-Term Outcomes

Large Cleveland Clinic series underscores challenges of decision-making for this rare defect

anatomic illustration of heart with congenitally corrected transposition of the great arteries (ccTGA)

Patients with congenitally corrected transposition of the great arteries (ccTGA) who undergo early anatomic repair fare better than those who have physiologic repair, even with tricuspid valve interventions. That’s the lead finding among a group of insights from a Cleveland Clinic retrospective review of 240 patients with ccTGA that underscores the enduring complexity of this congenital heart defect.

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The study, one of the largest and most diverse series of ccTGA cases published to date, appears in the Journal of Thoracic and Cardiovascular Surgery (2021;161:1080-1093).

“Teasing out the best strategy for managing the extremely heterogeneous population with ccTGA poses enormous challenges,” says Cleveland Clinic pediatric and congenital heart surgeon Tara Karamlou, MD, MSc, corresponding author of the study. “This analysis, based on data from a large sample with long follow-up, does not provide a single best answer for every patient, but it can better inform decision-making for those faced with this rare anomaly.”

A diverse group with multiple treatment pathways

ccTGA is a rare defect — affecting 5,000 to 10,000 U.S. residents — that can present from birth to late adulthood. It is also associated with a wide variety of additional lesions, including ventricular septal defects, dextrocardia and valve abnormalities.

Treatment options include the following:

  • Anatomic repair, i.e., correcting the atrioventricular and ventriculoarterial discordance and associated defects and making the morphologic left ventricle the systemic ventricle
  • Physiologic repair, i.e., addressing associated defects while keeping the morphologic right ventricle as the systemic ventricle
  • Fontan palliation for select patients
  • Heart transplantation, which is regarded as a last resort
  • Expectant management

“Cleveland Clinic, with its large patient population and many decades of systematic clinical data collection, provides a good opportunity to glean best management practices for this diverse condition,” says study co-author Hani Najm, MD, MSc, Chair of Pediatric and Congenital Heart Surgery at Cleveland Clinic.

Study design and findings

The investigative team retrospectively reviewed 240 patients diagnosed with ccTGA between 1955 and 2020; all but three were managed since 1983. Patients’ median age at presentation was 8.5 years, with the 15th and 85th percentiles at 0.38 and 41 years. Patients were categorized by intervention, as follows:

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  • Anatomic repair, 79 patients (median age at presentation, 1.6 years; median age at procedure, 2.4 years)
  • Physiologic repair, 45 patients (presentation, 23 years; procedure, 25 years)
  • Fontan palliation, 24 patients (presentation, 0.08 year; procedure, 4.3 years)
  • Primary transplantation, 6 patients (presentation, 42 years; procedure, 46 years)
  • Nonsurgical/expectant management, 40 patients (presentation, 35 years)

Additionally, 46 patients had their main procedure elsewhere before presenting to Cleveland Clinic and were not included in the analysis.

Patients were followed for a median of 10 years. Highlights of clinical outcomes include the following:

  • Overall survival was 85% at 15 years.
  • Transplant-free survival at 15 years was 80% for anatomic repair and 71% for physiologic repair.
  • Patients managed expectantly had excellent long-term survival (88% at 20 years), but these results are not directly comparable with those of the other cohorts since some of these patients transitioned to intervention strategies over time and had their treatment failures captured in the physiologic repair or transplantation groups.
  • Five years after physiologic repair, morphologic right ventricular dysfunction increased from 68% to 85%.
  • Morphologic left ventricular function was stable after anatomic repair, especially if performed early.

Dr. Karamlou notes that the difference in survival rates between the anatomic repair and physiologic repair groups was not statistically significant. However, she believes the trend is likely important and that the dataset may not have been large enough to demonstrate significance.

Lessons from a complex study

Drs. Karamlou and Najm identify several key takeaways from this study.

Early anatomic repair is the preferred strategy for the large majority of children. Physiologic repair is compromised by progressive right ventricular dysfunction, despite tricuspid valve interventions, with survival becoming impacted 12 years after the primary intervention.

Fontan procedures are viable options for select patients. Patients with a single atrioventricular valve (i.e., tricuspid atresia) or a single ventricle who were treated with a Fontan procedure had excellent midterm outcomes.

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Tricuspid intervention among physiologic repair patients does not improve outcomes. The study found that it neither improved morphologic right ventricular function nor appreciably improved survival.

Optimal paradigms for pulmonary artery banding are still uncertain. Although the investigators reviewed echocardiographic data longitudinally with detailed image review, they were unable to define optimum criteria and gradient thresholds for pulmonary artery banding. They note that further defining this is especially important to help predict which patients will have maladaptive myocardial responses to afterload from a pulmonary artery band.

Nonintervention is a viable strategy.  Evidence indicated that this group did well, partially because they could transition to other pathways when they “failed” expectant management.  

“Identifying which patients can live their life without needing corrective surgery remains a challenge,” Dr. Najm notes. “A patient with a balanced anatomy and no evident dysfunction may be a good candidate for an expectant strategy.”

In an accompanying commentary on the study, pediatric cardiologist Joseph Clark, MD, of Penn State Children’s Hospital, observes: “Although anatomic repair has become a favored choice, and the supporting rationale is sensible, intuitive, and backed by accumulating experience, there remains some room for equipoise. As this study shows, there was no clear winner among the multiple treatment pathways for this complex and heterogeneous disease.”