A retrospective cohort of 7,678 adults with congenital heart disease (ACHD) followed at Mayo Clinic from 2002–2023 reveals a 1.4% annual mortality rate over 78,768 patient-years, with cumulative all-cause mortality reaching 26.2% at 20 years. Severe CHD carried double the annual death rate (2.4%/year) versus mild or moderate forms (1.2%/year). Cyanotic heart disease (HR 3.9) and Fontan physiology (HR 3.2) emerged as the strongest anatomical predictors of death. Heart failure accounted for nearly half of cardiovascular deaths, with sudden cardiac death comprising another 22%.
This large registry fills a critical evidence gap: as surgical advances push ACHD patients into middle age, the field has lacked robust contemporary mortality data on acquired comorbidities layered atop congenital anatomy. The finding that hypertension, coronary artery disease, renal dysfunction, and smoking independently predict death signals that ACHD has shifted from a purely structural problem to a chronic multisystem disease requiring integrated cardiology, nephrology, and preventive medicine. Clinicians managing these patients should arguably apply cardiovascular risk-reduction strategies as aggressively as in any high-risk adult population.
Limitations include the retrospective, single-center design at a tertiary referral center, which likely overrepresents complex anatomy and skews toward sicker patients. Cause-of-death ascertainment was incomplete for some cases. As a preprint posted to medRxiv and not yet peer-reviewed, these effect estimates may be revised before publication. Still, the scale of the cohort makes this one of the more methodologically credible ACHD mortality datasets to date — confirmatory rather than paradigm-shifting, but clinically actionable.
