The experimental evidence in support of the role of tumor necrosis factor in heart failure stems from the observations that tumor necrosis factor exerts negative inotropic effects and is capable of promoting fibrosis, hypertrophy, and cardiomyopathy in animal models. More importantly, cardiac specific tumor necrosis factor levels are regulated by pressure and volume load in animals and in humans. Therefore, a series of clinical small trials were conducted with etanercept, a highly specific anti‐tumor necrosis factor‐blocking agent that indicated a potential therapeutic role. However, two large randomized clinical trials powered to determine the effect of etanercept and infliximab on mortality have demonstrated no clinical benefit. The explanation of those findings are not clear; however, based on the strength of the experimental evidence one can conclude that perhaps other nonspecific approaches to manipulate the immune system may be of benefit.

Heart failure is not a simple defect in the pumping function of cardiac muscle, but rather a complex systemic inflammatory disease affecting many organ systems. Recognition of this fact has led to new therapeutic interventions such as angiotensin-converting enzyme inhibitors and beta-blockers, which have a significant impact on the quality of life and survival of patients with heart failure. During the course of heart failure, the steps involved in the activation of inflammation are now better understood. As a result, new therapies will develop that block, modify, or prevent these inflammatory changes, and supplement our armamentarium for providing better and longer lives for patients.

Acute heart failure in adults is the unfolding of heart failure in minutes, hours or a few days. Low output heart failure describes a form of heart failure in which the heart pumps blood at a rate at rest or with exertion that is below the physiological range and the metabolizing tissues extract their required oxygen from blood at a lower rate, causing a proportionately smaller oxygen amount remaining in the blood. Therefore, a widened arterial-venous oxygen difference occurs. High output heart failure is characterized by pumping blood with a rate above the physiological range at rest or during exertion, resulting in an arterial-venous oxygen difference, which is normal or low. This may be caused by peripheral vasodilatation during sepsis or thyrotoxicosis, blood shunting, or reduced blood oxygen content/viscosity (Fig. 1). The differentiation between low output heart failure versus high output heart failure is of highest importance for the choice of therapy and therefore the information and the monitoring of the systemic vascular resistance. Patients who present with acute heart failure suffer from a severe complication of different cardiac disorders. Most often they have an acute injury that affects their myocardial performance (eg, myocardial infarction) or valvular/chamber integrity (mitral regurgitation, ventricular septal rupture), which leads to an acute rise in left-ventricular filling pressures resulting in pulmonary edema.