39 SEX- AND AGE SPECIFIC ASSOCIATION OF AF WITH MORTALITY IN COVID-19 FIGURE 2: RISK OF IN-HOSPITAL MORTALITY BY SEX, AGE AND THE DEVELOPMENT OF NEW-ONSET ATRIAL FIBRILLATION AND/OR ATRIAL FLUTTER DURING HOSPITALISATION IN COVID-19 PATIENTS. Development of atrial fibrillation and/or atrial flutter during hospitalisation: The plots in Figure 2 are developed with the interaction between a cubic spline function for age with four knots (on the percentiles 0.05, 0.035, 0.65, and 0.95) and the development of new-onset AF and/or AFL during hospitalisation. Occurrence of AF and/or AFL during hospitalisation for COVID-19 was associated with a poorer prognosis exemplified by an increased in-hospital mortality in males aged 60–72 years, while this effect was not observed in female patients and largely attenuated in older male patients. Arrhythmogenesis in COVID-19 and the effect of AF on mortality Several mechanisms may contribute to arrhythmogenesis in the setting of COVID19. Pre-existing cardiovascular pathologies, such as heart failure and coronary artery disease, may increase the likelihood of myocardial ischaemia in the setting of hypoxemia. Indeed, in our cohort, heart failure, hypertension, and prior myocardial infarction were frequently present and apparently associated with an increased likelihood of developing AF and/or AFL. In addition, SARS-CoV-2 has been linked to a pro-thrombotic and hypercoagulability state in patients, which by itself may promote the development and propagation of AF and/or AFL.17 Furthermore, the virus may also directly affect the cardiomyocytes through expression of angiotensinconverting enzyme 2, inducing arrhythmogenic conditions such as intracellular ionic dysregulation, apoptosis, and possibly myocarditis.18 Additionally, potentially proarrhythmic therapeutics (including vasopressors and (hydroxy)chloroquine) and electrolyte disturbances in COVID-19 patients can all contribute to arrhythmogenesis.19 Irrespective of the underlying mechanism, our findings indicate that development of AF and/or AFL might be prognostically unfavourable in COVID-19 patients. 3
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