Influenza vaccination in patients with heart failure: comprehensive review of evidence, challenges, and clinical implications.

Heart failure is a major global health burden, with high rates of hospitalization and mortality despite advances in medical therapy. Seasonal influenza is a well-established trigger for heart failure decompensation, acting through systemic inflammation, increased metabolic demand, endothelial dysfunction, prothrombotic states, and pulmonary congestion. These mechanisms contribute to higher risks of hospitalization, major adverse cardiovascular events, and death in patients with heart failure. Accordingly, major cardiovascular societies and public health organizations recommend annual influenza vaccination for all patients with heart failure. This review summarizes the biological rationale, clinical evidence, and implementation challenges surrounding influenza vaccination in heart failure. Observational studies consistently associate vaccination with lower mortality and reduced heart failure hospitalizations, though residual confounding remains a concern. More recent randomized and pragmatic trials, including large cardiovascular outcome studies and the dedicated PANDA-II trial, provide stronger evidence of benefit, demonstrating reductions in mortality and readmissions, particularly when vaccination is initiated during hospitalization for acute heart failure. Meta-analyses further support a protective effect against major cardiovascular events. Despite robust evidence and clear guideline endorsement, vaccination uptake remains suboptimal worldwide. Integrating influenza vaccination into routine and inpatient heart failure care represents a low-cost, scalable strategy with meaningful potential to improve clinical outcomes.