The 30-Year Outcomes of Tetralogy of Fallot According to Native Anatomy and Genetic Conditions

The 30-Year Outcomes of Tetralogy of Fallot According to Native Anatomy and Genetic Conditions.

Blais S, Marelli A, Vanasse A, Dahdah N, Dancea A, Drolet C, Colavincenzo J, Vaugon E, Dallaire F.Can J Cardiol. 2021 Jun;37(6):877-886. doi: 10.1016/j.cjca.2020.10.002. Epub 2020 Oct 12.PMID: 33059007


Take Home Points:

  • Among all TOF subjects, ±20% have TOF-PA
  • The prevalence of genetic conditions is higher in the TOF-PA group compared to the cTOF group
  • In non-syndromic cTOF patients, long term survival is excellent
  • For both cTOF and TOF-PA, mortality before surgical correction is about 30%, but less frequent in the non-syndromic patients
  • The predicted survival for patients with TOF-PA and those with genetic conditions are considerably poorer

Dr Blanche Cupido

Commentary from Dr. Blanche Cupido (Cape Town, South Africa), chief section editor of ACHD Journal Watch:

Surgically corrected Tetralogy of Fallot (TOF) overall has an excellent survival – up to 97%. The variant group that has pulmonary atresia or genetic outcomes have been thought to subtend poorer outcomes. Long term data relating outcomes to these subgroups are lacking. The TRIVIA (Tetralogy of Fallot Research for Improvement of Valve Replacement Intervention: A Bridge across the Knowledge Gap) study, based in the Quebec Registry, Montreal, aimed to assess the long-term outcomes of TOF from birth to age 30, based on native anatomic subtype and the presence of genetic syndromes.


The primary outcome was all-cause mortality. Secondary outcomes included cardiovascular interventions and cardiovascular unplanned hospitalisations for adverse cardiac events. The TOF anatomic types were categorized as: 1. Classic stenotic TOF (cTOF), 2. TOF with pulmonary atresia (TOF-PA). The presence of genetic conditions were categorized as: 1. Trisomy 21, 2. 22q11 deletion, 3. Clinical or genetic diagnosis other than trisomy 21 or 22q11 deletion, 4. Non-syndromic subjects.


A total of 960 TOF patients were included in the final analysis, with a median follow-up period of 17.1 years. One-hundred and fifty-eight patients (16%) were followed up for >30 years. cTOF, as expected, was more prevalent than TOF-PA (78.5% vs 21.5%). The presence of a genetic condition was more frequently seen in those with TOF-PA compared to cTOF (28.2% vs 17.5%), mainly due to the prevalence of 22q11 deletions in the TOF-PA group. The proportion of patients with trisomy 21 was higher in the cTOF vs TOF-PA group (4.8% vs 2.4%). Figure 1 below shows the distribution of TOF clinical profiles:



A total of 142 deaths occurred. Causes of death was similar between the 2 groups. The majority of deaths were due to cardiovascular causes (64.8%) – mainly peri-operative complications. Nearly half of the deaths occurred before surgical correction – even across surgical eras.



The 30 year survival varied greatly between the 2 categories, with TOF-PA having a worse prognosis. Furthermore, genetic syndromes also resulted in a markedly varied outcome: Non-syndromic cTOF patients had the highest survival (95% at 30 years). The non-syndromic TOF-PA had an estimated 30 year survival of 78%. There was significant heterogeneity of the effect of genetic syndromes in each of the anatomic TOF types. 22q11 deletion had a similar outcome to non-syndromic patients, whereas trisomy 21 and other syndromes portended a worse prognosis.



Over 2000 (n=2305) cardiovascular interventions were recorded during follow-up. Surgical correction of TOF accounted for most. The second most frequent intervention was percutaneous pulmonary valvuloplasty (40% of all interventions in cTOF and TOF-PA).



The overall rate of unplanned hospitalisations for a cardiac event was low in both anatomic groups of TOF patients (mean rate <0.1 hospitalisations per patient year) with cardiac infections accounting for 40%, arrythmias for 25% and heart failure for 7%.