LAUSR

Few things can be as much fascinating as finding a genetic determinant of symptoms and clinical outcomes in patients with heart failure (HF). Angermann et al. accomplished this. They analysed the polymorphism of the gene encoding for the neuropeptide S receptor in 924 patients with HF.1 The T-allele variant of this gene is associated with increased anxiety and overinterpretation of symptoms. In this study, TT genotype carriers had similar mortality but more re-hospitalizations and ambulatory visits and this association remained significant at multivariable analysis.1 The mechanisms of HF with preserved ejection fraction (HFpEF) are still debated. A landmark hypothesis is that it is caused by increased oxidative stress and reduced cGMP activity.2,3 The mechanistic study by Mátyás et al. supports this. The administration of the phosphodiesterase-5A (PDE5) inhibitor vardenafil to diabetic rats prevented the development of diastolic dysfunction and restored cGMP levels and protein-kinase G activity.4 These data also suggest that PDE5 inhibition may be effective at an earlier stage, before the development of symptomatic HFpEF.5