Prognostic implications of atrial fibrillation in young patients without overt heart disease - an early marker of future cardiomyopathy ?

Abstract Background In the general population, atrial fibrillation (AF) is associated with adverse outcomes such as heart failure and stroke, especially in patients with comorbidities. However, the long-term prognostic implications in younger patients presenting with AF without overt cardiovascular disease is poorly understood Purpose To investigate the very long-term risk of heart failure, stroke, and mortality in young patients diagnosed with AF without evidence of coexisting cardiovascular disease. Methods Using Danish nationwide registers, we included young adult patients ( 18 and 45 years of age) with a first-time diagnosis of AF between 1999 and 2023. Patients were included 180 days after their AF diagnosis to allow for diagnostic procedures determining possible coexisting cardiovascular disease precipitating AF. As such, all patients with overt cardiovascular disease or other causes for AF (e.g. any structural heart disease, cardiomyopathy/heart failure, ischemic heart disease, other arrhythmias, congenital heart disease, cerebrovascular disease, hypertension, hyperthyroidism etc.) were excluded All AF patients were matched to a control group sampled from the background population without AF using exact density sampling. The absolute risk of heart failure, stroke, and all-cause mortality were estimated using the Aalen-Johansen estimator and relative rates were calculated using adjusted Cox models with estimates presented as hazard ratios (HR) with 95% confidence intervals (95% CI). Results A total of 7,252 young patients with AF, as well as 109,681 matched controls, were included in the study cohort. The majority were male (71%) with a median age of 39 years (interquartile range 33-43 years). Comorbidities were generally very infrequent (e.g.~ 1% for both diabetes and kidney disease) and balanced between the groups. In the most contemporary years, frequently used first treatments after AF diagnosis were beta-blockers (35%) and oral anticoagulants (34%) and to a lesser extent ablation (12%) (Figure 1) In the young AF cohort, we found clinically relevant very long-term risks of stroke (20-year risk 6.5%, 95% CI 5.6-7.5), heart failure, (20-year risk 6.3%, 95% CI 5.4-7.1), and mortality (20-year risk 7.0%, 95% CI 6.1-8.0). (Figure 2) Comparing patients with AF with a matched sample from the background population yielded increased rates for all outcomes in AF patients including stroke (HR 2.33, 95% CI 2.01-2.70), heart failure (HR 4.98, 95% CI 4.2 – 5.9), and all-cause mortality (HR 1.58, 95% CI 1.37-1.82). Conclusions AF in young patients without concomitant cardiovascular conditions confers clinically significant very long-term risks of cardiovascular adverse events. Importantly, AF is associated with a five-fold increase in the risk of a future heart failure diagnosis and is potentially an important marker of future cardiomyopathy and heart failure events in otherwise healthy young patients.Management and treatment of AF Long-term risks of cardiovascular events