Tetralogy of Fallot (TOF) is one of the most common cyanotic congenital heart defects, with an incidence of 5 cases per 10,000 live births. A late complication of TOF includes progressive aortic root dilatation and AR. The prevalence of this complication varies widely, depending on the population studied, follow-up protocols, and the stage of life during evaluation. Additionally, the prevalence is influenced by whether measurements are reported as absolute values, indexed values, or z-scores; the specific region of the aorta assessed; and the imaging modality used. Consequently, aortic dilatation prevalence in this population ranges from 7% to 88% depending on these factors. The clinical significance of this dilatation is debatable, as aortic dissection in these patients is exceedingly rare. A study evaluating 18,000 emergency department admissions of adults with TOF reported aortic dissection in only 0.06% of cases. In fact, the literature documents only five deaths due to aortic dissection in this population. This study aims to establish a foundational understanding of the natural history of this late complication, leveraging six decades of institutional experience.

All medical records of patients with TOF repair at Boston Children’s Hospital from 1960 to 2022 were reviewed. Patients were categorized into two groups: those with TOF and pulmonary stenosis (TOF-PS) and those with TOF variants, which included TOF with pulmonary atresia with or without major aortopulmonary collateral arteries (MAPCAs). Variants such as double-outlet right ventricle, TOF with atrioventricular canal, and TOF with absent pulmonary valve syndrome were excluded. Echocardiograms performed preoperatively and during follow-up were analyzed. Measurements of the aortic annulus, sinuses of Valsalva, and sinotubular junction were collected, and z-scores were calculated. Longitudinal trends in these parameters were evaluated using linear mixed-effects models.

A total of 2,205 patients underwent TOF repair at a median age of 4.9 months. Among them, 72.9% (1,608 patients) had TOF-PS, while 27.1% (597 patients) had TOF variants. With a median follow-up of 14.4 years (range, 0.1–62.6 years), 313 patients (14.2%) developed mild or greater AR, and 34 patients (1.5%) required interventions involving the aortic valve or root. The mean growth rates of the aortic annulus, sinuses of Valsalva, and sinotubular junction were 0.5 mm/year, 0.6 mm/year, and 0.7 mm/year, respectively, while z-scores remained stable over time. Patients with TOF variants exhibited larger aortic root dimensions compared to those with TOF-PS (p < .05). During follow-up, TOF variants demonstrated greater growth of the aortic annulus (p = .02), sinuses of Valsalva (p < .001), and sinotubular junction (p < .001).

High-risk patients, defined as those with measurements above the 75th percentile, had increased incidence rates of mild or greater AR (p < .001), moderate or greater AR (p < .001), and higher rates of aortic valve intervention (p = .045). No cases of aortic dissection or rupture were observed in the entire cohort.

COMMENTARY:

The pathophysiology of aortic dilatation in conotruncal anomalies remains unclear. Early studies attributed the condition to hemodynamic stress on the aortic wall prior to surgical repair. However, intrinsic abnormalities in the aortic wall—including defects in smooth muscle, elastic fibers, and collagen—have also been observed in neonates undergoing early repair, suggesting that prolonged hemodynamic stress is not the sole factor. Regardless of the timing of complete repair, all TOF patients exhibit intrinsic aortic root abnormalities exacerbated by hemodynamic factors that increase stiffness and reduce distensibility, leading to focal smooth muscle loss, cystic medial degeneration, and elastic fiber fragmentation. It is now believed that TOF-related aortic dilatation arises from a combination of hemodynamic and genetic factors contributing to asymmetric development of conotruncal structures.

Applying standard aortopathy guidelines to TOF-related dilatation can lead to misguided clinical decisions. The natural history of TOF-associated aortic pathology differs significantly from conditions like bicuspid aortic valve disease or Marfan syndrome. For instance, TOF variants with pulmonary atresia—representing extreme cases of obstruction—are associated with greater aortic root dimensions due to sustained volume overload and longer periods of hemodynamic stress, as these patients typically undergo palliative procedures before definitive repair.

Despite being an excellent study with the longest longitudinal follow-up of TOF patients to date, this research has limitations. It is a single-center retrospective study with inherent selection biases, particularly as it originates from a quaternary care hospital. Measurement reliability varied over decades as echocardiographic technology evolved. Additionally, z-scores were analyzed only up to the age of 20 years, as these scores are not validated beyond this age.

The study by Sengupta et al. sheds light on the natural history of aortic dilatation and AR in TOF. It highlights the importance of differentiating high-risk variants that require closer surveillance. Most notably, the rarity of dissection and rupture emphasizes the need to avoid over-treatment and to tailor follow-up strategies based on individualized risk profiles.

REFERENCE:

Sengupta A, Lee JM, Gauvreau K, Colan SD, Del Nido PJ, Mayer JE Jr, Nathan M. Natural history of aortic root dilatation and pathologic aortic regurgitation in tetralogy of Fallot and its morphological variants. J Thorac Cardiovasc Surg. 2023 Dec;166(6):1718-1728.e4. doi: 10.1016/j.jtcvs.2023.04.014.