Several lines of evidence suggest that a strategy of utilizing high-dose influenza vaccine in at risk cardiovascular patients would reduce morbidity and mortality. Immune responses to influenza vaccine, normally subject to variability by age and concomitant medical conditions, are substantially reduced in patients with heart failure evidenced by lower vaccine-induced antibody titers compared to healthy controls. In a randomized trial, antibody responses in patients with heart failure were augmented by using a higher dose of influenza vaccine. In a meta-analysis, higher dose influenza vaccination was associated with a 27% reduced risk for MACE compared to standard dose vaccine. A randomized study of high dose versus standard dose influenza vaccine in medically-stable patients over age 65 showed that participants receiving high dose vaccine had a 24% reduced risk of laboratory-confirmed influenza associated with protocol-defined influenza-like-illness, and had a low risk for adverse events. High dose influenza vaccine is FDA approved for use in medically stable adults over the age of 65, but has not been studied for patients under the age of 65 or in those with unstable, high risk medical conditions. The CDC does not preferentially recommend one influenza vaccine over another, and the optimal vaccine formulation that offers the most clinical protection in these high risk patients is unknown.