Incident atrial fibrillation and its risk prediction in patients developing COVID-19: A machine learning based algorithm approach

Background The elderly multi-morbid patient is at high risk of adverse outcomes with COVID-19 complications, and in the general population, the development of incident AF is associated with worse outcomes in such patients. We therefore investigated incident AF risks in a large prospective population of elderly patients with/without incident COVID-19 cases and baseline cardiovascular/non-cardiovascular multi-morbidities. We used two approaches: main-effect modeling and secondly, a machine-learning (ML) approach accounting for complex dynamic relationships. Methods We studied a prospective elderly US cohort of 280592 patients from medical databases in a 8-month investigation of new COVID19 cases. Incident AF outcomes were examined in relationship to diverse multi-morbid conditions, COVID-19 status and demographic variables, with ML accounting for the dynamic nature of changing multimorbidity risk factors. Results Multi-morbidity contributed to the onset of confirmed COVID-19 cases with cognitive impairment (OR 1.69; 95%CI 1.52-1.88), anemia (OR 1.41; 95%CI 1.32-1.50), diabetes mellitus (OR 1.35; 95%CI 1.27-1.44) and vascular disease (OR 1.30; 95%CI 1.21-1.39) having the highest associations. A main effect model (C-index value 0.718) showed that COVID-19 had the highest association with incident AF cases (OR 3.12; 95%CI 2.61-3.710, followed by congestive heart failure (1.72; 95%CI 1.50-1.96), then coronary artery disease (OR 1.43; 95%CI 1.27-1.60) and valvular disease (1.42; 95%CI 1.26-1.60). The ML algorithm demonstrated improved discriminatory validity incrementally over the statistical main effect model (training: C-index 0.729, 95%CI 0.718-0.740; validation: C-index 0.704, 95%CI 0.687-0.72). Calibration of ML based formulation was satisfactory and better than the main-effect model. Decision curve analysis demonstrated that the clinical utility for the ML based formulation was better than the ‘treat all’ strategy and the main effect model. Conclusion COVID-19 status has major implications for incident AF in a cohort with diverse cardiovascular/non-cardiovascular multi-morbidities. Our approach accounting for dynamic multimorbidity changes had good prediction for incident AF amongst incident COVID19 cases.