Prevention of worsening heart failure: future focus.

For decades heart failure therapy has focused on symptomatic treatment, whereas preventive aspects have received less attention. However, 10 years of large controlled trials has provided insight into the potential of certain agents to prevent or delay the onset or worsening of heart failure. Such agents include ACE inhibitors and, in addition to the former beta-blockade, the vasodilator beta-blocking agent carvedilol, which possesses additional properties such as antioxidant effects. In contrast, drugs which typically are used to improve heart failure symptoms, such as diuretics, do not necessarily lead to prevention of (worsening) heart failure. Multiple mechanisms underlie worsening of left ventricular dysfunction and heart failure and have been, or may well be, instrumental in the development of novel preventive therapies of this syndrome. Principal mechanisms include: cardiac and vascular remodelling; neurohormonal and cytokine activation; hibernation and stunning; ischaemia-induced free radical formation; apoptosis; abnormalities in the cardiac membrane receptor, downstream signalling pathways, in intracellular calcium homeostasis, and sensitivity. As these mechanisms interact, leading to progression of heart failure, they provide opportunities for novel pharmacotherapeutic approaches. It is to be expected that many drugs currently in development will be added to the list of accepted heart failure therapy. As polypharmacy is likely to result and is to some extent unavoidable, the future challenge will be to detect the usefulness of alternative treatments to currently accepted therapy to prevent worsening of heart failure, enabling a more individualized and hence effective approach in each patient.