Survival Over the First Few Decades Following Tetralogy of Fallot Repair A Study From the Pediatric Cardiac Care Consortium

A study published in JAMA cardiology has shown that long-term survival after simple Tetralogy of Fallot (TOF) repair is excellent. Staged repair and non–valve-sparing operations were negatively associated with survival in the early post repair phase but not the late post repair phase. The study, led by Dr. Clayton A. Smith, Emory University School of Medicine is important for patients with repaired TOF and their caretakers and may guide surgical strategies for optimizing the long-term outcomes of this population.

Tetralogy of Fallot (TOF) is a surgically repairable form of cyanotic congenital heart disease and is the most common form of cyanotic heart disease, with an incidence of 4 of 10000 live births. Surgical repair for TOF was first reported in 1954 for a cohort of 106 patients, with a 30-year survival of 77%. Long-term outcome data for patients with repaired TOF that have been derived from single-center series are not representative of the survival experience of TOF patients in the United States owing to selection biases, differences in treatment strategies, techniques, or variation in population or health care systems. In the light of this, Smith et al. aimed to evaluate the long-term transplant-free survival of TOF by surgical strategy adjusted for era and patient characteristics.

The Pediatric Cardiac Care Consortium (PCCC) is the oldest and one of the largest clinical registries for interventions for congenital heart disease in the United States. Linkage of the PCCC to the registries of the National Death Index (NDI) and the Organ Procurement and Transplantation Network (OPTN) extends the follow-up time of PCCC-enrolled persons for major outcomes with nearly 90% sensitivity and almost 100% specificity for death and transplant events. In this study, the investigators used the linked PCCC-NDI-OPTN dataset to evaluate long-term transplant-free survival and causes of death (COD) of a large multicenter US-based cohort following TOF repair. The cohort included patients with adequate identifiers for linkage with the National Death Index and the Organ Procurement and Transplantation Network who were enrolled in the PCCC registry between 1982 and 2003 and survived surgical repair of simple TOF. Data were analyzed between September 2015 and April 2018. Patient-associated and surgery-associated risk factors affecting survival were assessed. The primary outcome analyzed was the transplant-free survival during early (<6 years) and late (≥6 years) phase after TOF surgical repair.

The study results showcased that of the 3283 patients who survived repair for simple TOF and met the study’s inclusion criteria, 56.4%were male, and 43.6%were female. Twenty-five–year survival following TOF repair was 94.5%. Moreover, multivariable analysis demonstrated an increased risk of early mortality with staged repair (HR, 2.68; 95%CI, 1.59-4.49) and non–valve-sparing operation (HR, 3.76; 95%CI, 1.53-9.19). Furthermore, the presence of a genetic abnormality was associated with increased risk of death both in the early (HR, 3.64; 95%CI, 2.05-6.47) and late postoperative phase (HR, 4.41; 95%CI, 2.62-7.44). Survival following complete repair was 98.6%, 97.8%, 97.1%, 95.5%, and 94.5%for 1-year, 5-year, 10-year, 20-year, and 25-year survival, respectively, with an early peaking hazard of mortality shortly after repair. Statistically significant associations with decreased long-term survival included staged repair, non–valve-sparing operation, repair in an earlier surgical era, and presence of a genetic abnormality.

The authors deduced that overall long-term transplant-free survival in repaired tetralogy of Fallot was excellent, with several factors affecting survival, some of which could be modifiable such as planning of the surgical strategy. The authors claimed that the primary strengths of their study included a large number of patients and participating centers as well as the length of follow up. They stated, “Our study provides important information about the long-term outcomes of patients with repaired TOF in the United States. The data highlight the shortcomings of early repair, staged, and non–valve-sparing approaches in the early period following repair. Long-term transplant-free survival beyond the first 6 years following repair is excellent and influenced primarily by the coexistence of an associated genetic condition. Within the 25-year follow-up period, most deaths were associated with the underlying diagnosis of TOF and mediated by arrhythmias and congestive heart failure.” However, “Continuous surveillance of this cohort is important in identifying additional risks resulting from the interaction of underlying conditions with cardiovascular morbidities expected with aging,” they advised. Commenting on the significance of this study, Dr. Roger Andrew de Freitas remarked, “Understanding the effect of surgical strategy on many different types of outcomes, such as neurodevelopmental and functional outcomes, will ultimately allow us to determine optimal strategies for infantile surgical repair. A fundamental first step in this assessment is to understand the effects of different Strategies on long-term survival. Smith et al suggest that survival over the first few decades after TOF repair has largely been determined by residual morbidity present after discharge. This is consistent with clinical experience that patients with repaired TOF typically do well for their first several decades of life. Their work highlights the value of teams that provide intensive post-discharge care, a growing trend in congenital cardiology. This robust analysis of a large, contemporary, multicenter database answers an important question about how surgical factors affect mortality over the first several decades of life, an essential outcome to be considered along with functional outcomes in evaluating the long-term value of any surgical strategy.”