Excess Mortality and Hospitalizations Associated With Seasonal Influenza in Patients With Heart Failure

Background: Influenza virus may cause severe infection in patients with heart failure. It is known that influenza infection is associated with increased morbidity and mortality in patients with heart failure. However, less is known about the excess burden of morbidity and mortality caused by influenza infection in patients with heart failure at a population level. Objectives: The purpose of this study was to estimate the excess burden of morbidity and mortality as determined by annual excess number of deaths and hospitalizations associated with influenza infection in patients with heart failure in Denmark. Methods: We collected nationwide data on weekly number of deaths and hospitalizations among patients with heart failure in Denmark and weekly estimates of influenza circulation as determined by the proportion of positive influenza samples analyzed at all Danish Hospitals. These data were correlated in a time series linear regression model, and this model was used to estimate the annual excess number of deaths and hospitalizations attributable to influenza circulation among patients with heart failure in Denmark. The model also included data on weekly mean temperature and restricted cubic spline terms to account for seasonality and trends over time. Results: Data were available from 2010 to 2018 encompassing 8 influenza seasons with an annual mean of 25,180 samples tested for influenza at Danish hospitals. Among an annual mean of 70,570 patients with heart failure, our model estimated that influenza activity was associated with an annual excess of 250 all-cause deaths (95% CI: 144-489 deaths) corresponding to 2.6% of all all-cause deaths (95% CI: 1.5%-5.1%) in patients with heart failure. Similarly, influenza activity was associated with an annual excess of 115 cardiovascular deaths (95% CI: 62-244 deaths) corresponding to 2.9% of all cardiovascular deaths (95% CI: 1.5%-6.1%). Influenza activity was also associated with an annual excess of 251 hospitalizations for pneumonia or influenza (95% CI: 107-533 hospitalizations) corresponding to 5.0% of all hospitalizations for pneumonia or influenza. Conclusions: Our results indicate that influenza activity likely causes substantial morbidity and mortality among patients with heart failure. Notably, our study suggests that approximately 2.6% of all deaths and 5.0% of all hospitalizations with influenza or pneumonia may be attributed to influenza in patients with heart failure.