Changing Comorbidity Clusters in Patients With Congenital Heart Disease Across the Lifespan

BACKGROUND: Benefiting from advances in medical care, patients with congenital heart disease (CHD) now survive to adulthood but face elevated risks of cardiac and noncardiac complications. Understanding how comorbidity evolves across the lifespan is the cornerstone to improving long-term outcomes. We hypothesized that comorbidity occurs in clusters that change over time in patients with CHD. METHODS: ) coded comorbidities. Observed sequences of comorbidities were mapped using median ages of onset. Associations between disease pairs were quantified using hazard ratios from Cox proportional hazard models adjusting for age, sex, genetic syndrome, competing risks of death, and time-varying predictor diseases. RESULTS: The cohort comprised 9764 individuals with severe CHD and 127 728 with nonsevere CHD. Patients with severe CHD demonstrated higher cumulative probabilities of developing comorbidities than those with nonsevere CHD from birth to older adulthood. By age 40 years, cumulative probabilities for developing cardiac, vascular, endocrine/metabolic, digestive, infectious, renal, and neurological disease were ≥2-fold higher in severe versus nonsevere CHD. Median ages of onset for most comorbidities occurred below age 40 in severe CHD, 2 to 3 decades earlier than patients with nonsevere CHD where peak comorbidity onsets occurred between their 60s and 80s. Disease progression in severe CHD began with childhood cardiovascular diseases, progressing to early-adulthood metabolic, hepatic, renal diseases, and later heart failure and dementia. CONCLUSIONS: Distinct multimorbidity clusters were observed by CHD severity, with earlier clustering in severe CHD, highlighting the need for early risk characterization and preventive strategies.