LAUSR

The treatment of heart failure (HF) has been transformed by the availability of new medical therapies and devices. However, many of these advances are only recommended for subsets of the broader HF community. Sacubitril/ valsartan and left ventricular assist devices, for example, are only recommended for patients with chronic HF with reduced ejection fraction and those with advanced HF, respectively. This leaves millions of patients with limited treatment options, including those with HF with preserved ejection fraction. Furthermore, approved therapies are not routinely adopted despite current guideline recommendations.1 The HF community maintains the need for further interventions that are cost-effective, high-impact, easily accessible, and applicable to the broad HF population. Given the close relationship between HF and respiratory illness, with >50% of HF decompensations thought to be triggered by respiratory infection,2 the role of vaccination in patients with HF is of growing interest. It is theorized that improved vaccination rates may reduce the incidence of respiratory infection, prevent HF decompensations, and alter the natural history of chronic HF.3 In particular, influenza vaccination, which is widely available at low cost, has been described as a potential disease-modifying intervention in HF. In addition to the inflammatory effects of influenza infection, which have been linked to increases in atherogenesis, the production of proinflammatory cytokines during acute infection may directly depress myocardial contractility.4,5 Experience from patients with coronary disease suggests that influenza vaccination reduces cardiovascular mortality.6,7 In patients with HF, nonrandomized data have found conflicting results. An analysis from the PARADIGM-HF trial (Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure) found that vaccination was associated with a 19% decrease in the relative risk of all-cause mortality,8 whereas an analysis from the Get With The Guidelines-HF registry found no such association.9 In this issue of Circulation, Modin et al10 expand our current understanding of the link between influenza vaccination and HF outcomes in a cohort of 134 048 patients from Denmark. Despite influenza vaccination being recommended by the Danish Health Authority and offered free of charge, vaccination rates remained low during the study period, ranging from 16% to 54%. Over a median follow-up of >3 years, the investigators found that, in patients with newly diagnosed HF, receiving ≥1 influenza vaccinations during the study period was associated with worse outcomes in an unadjusted analysis. After adjustment for potential confounders, however, vaccination was associated with an 18% relative risk reduction in both all-cause (hazard ratio, 0.82; 95% CI, 0.81–0.84) and cardiovascular mortality (hazard ratio, 0.82; 95% CI, 0.81–0.84). In addition, patients vaccinated each year after diagnosis had more favorable outcomes than those vaccinated less than once © 2019 American Heart Association, Inc.