Pathophysiology and clinical use of agents with vasodilator properties in acute heart failure. A scientific statement of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC).

Acute heart failure (AHF) affects millions of people each year and vasodilators have been a central part of treatment for over 25 years. The haemodynamic effects of vasodilators vary considerably among individual agents. Some vasodilators, such as nitrates, primarily act on the venous system by redistributing the circulating blood volume away from the heart towards the venous capacitance system. Other vasodilators, such as nesiritide, lead to balanced vasodilatation in the arteries and veins, decreasing left ventricular afterload and preload. Considering mechanisms of action, intravenous vasodilators are thought to be effective in patients with AHF, particularly in those with acute pulmonary oedema, where increased cardiac filling pressures and elevated systemic blood pressures occur in the absence of, or with minimal systemic fluid accumulation. However, the 2021 European heart failure guidelines have downgraded the use of vasodilators due to two recent studies and several contemporary meta-analyses failing to show benefit in terms of survival. Thus, there remains no firm recommendation suggesting the use of vasodilator treatment over usual care. In addition, despite repeated efforts to develop new vasodilatory agents, no novel therapy has outperformed traditional AHF management. In parallel with the development of novel vasodilators, changing the design of clinical trials for AHF to consider phenotype diversity of AHF patients remains an unmet need. New randomized clinical trials should particularly focus on subgroups that may mechanistically derive benefit from vasodilators, which may entail moving enrolment of patients to clinical settings close to moment of decompensation, such as the emergency department.