Surgical strategies, genetics affect tetralogy of Fallot survival

Almost 95 percent of patients survived 25 years after discharge for surgical repair of tetralogy of Fallot without requiring a transplant, according to a U.S. registry study published in JAMA Cardiology. While this statistic highlights the “excellent” outcomes for this congenital heart condition, the report’s authors also identified areas for further improvement.

Tetralogy of Fallot (TOF) is the most common form of cyanotic heart disease, affecting roughly four newborns in every 10,000 live births. Previous data regarding long-term outcomes of patients undergoing surgical repair of TOF have been limited to single-center studies, which may not reflect the differences in treatment strategies, techniques or patient populations present throughout the U.S., noted lead author Clayton A. Smith, MD, and colleagues.

To provide a more complete picture of contemporary outcomes associated with these operations, the researchers used the Pediatric Cardiac Care Consortium (PCCC) to analyze a cohort of 3,283 patients who survived repair of TOF from 1982 to 2003. They also linked these individuals with the National Death Index and the Organ Procurement and Transplant Network, enabling them to accurately assess transplant-free survival.

Overall, in-hospital mortality was 4.1 percent, occurring more often in patients weighing less than 5.5 pounds (reflecting prematurity) and those treated in earlier surgical eras. But among those who survived to discharge, transplant-free survival was 98.6 percent at one year and 94.5 percent at 25 years. Smith et al. found mortality after repair peaked early, declined rapidly to a low point around six years post-operation and then increased slowly beyond that with an acceleration around the 20-year mark.

“In the PCCC cohort, the late-phase survival and (causes of death) have not substantially changed over time,” wrote Smith, with Emory University School of Medicine in Atlanta, and coauthors. “These findings suggest that residual morbidity remains a major factor affecting survival of these individuals despite improvements in acute and midterm treatment. Not surprisingly, coexistence of a genetic anomaly remains a risk factor for mortality in both early and late postoperative phases.”

Specifically, the researchers found genetic abnormalities were associated with a 3.64-fold risk of death in the early postoperative phase, defined as within six years of surgical repair. Those abnormalities were also tied to a 4.41-fold risk of mortality beyond that timepoint—the only factor that was independently associated with death in the late postoperative phase after multivariable adjustment.

Other factors that were linked to an early risk of death included a staged repair (hazard ratio: 2.68) and a non-valve-sparing operation (HR: 3.76). Smith and colleagues said these observations may guide surgical strategies in the future, although they acknowledged the clinical decision-making may have been impacted by more severe pathologies or comorbidities in those patients. Those characteristics, along with medication use and socioeconomic factors, aren’t completely captured in the PCCC registry.

“Those undergoing … (staged repair) may also have residual deleterious effects related to the initial palliative shunt (eg, pulmonary artery distortion, excessive pulmonary blood flow, and left heart overload),” the authors wrote. “Patients with non-valve-sparing approach are exposed to higher likelihood for subsequent reoperation and perioperative complications. Potentially, pulmonary insufficiency associated with non-valve-sparing operation has an adverse association with early ventricular hemodynamics affecting survival.”

Unsurprisingly, most of the deaths in the young cohort were related to the TOF diagnosis but “mediated by arrhythmias and congestive heart failure,” Smith et al. noted.

“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 wrote.