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Abstract
Heart failure is a global problem with an estimated prevalence of 38 million patients
worldwide, a number that is increasing with the ageing of the population. It is the
most common diagnosis in patients aged 65 years or older admitted to hospital and
in high-income nations. Despite some progress, the prognosis of heart failure is worse
than that of most cancers. Because of the seriousness of the condition, a declaration
of war on five fronts has been proposed for heart failure. Efforts are underway to
treat heart failure by enhancing myofilament sensitivity to Ca(2+); transfer of the
gene for SERCA2a, the protein that pumps calcium into the sarcoplasmic reticulum of
the cardiomyocyte, seems promising in a phase 2 trial. Several other abnormal calcium-handling
proteins in the failing heart are candidates for gene therapy; many short, non-coding
RNAs--ie, microRNAs (miRNAs)--block gene expression and protein translation. These
molecules are crucial to calcium cycling and ventricular hypertrophy. The actions
of miRNAs can be blocked by a new class of drugs, antagomirs, some of which have been
shown to improve cardiac function in animal models of heart failure; cell therapy,
with autologous bone marrow derived mononuclear cells, or autogenous mesenchymal cells,
which can be administered as cryopreserved off the shelf products, seem to be promising
in both preclinical and early clinical heart failure trials; and long-term ventricular
assistance devices are now used increasingly as a destination therapy in patients
with advanced heart failure. In selected patients, left ventricular assistance can
lead to myocardial recovery and explantation of the device. The approaches to the
treatment of heart failure described, when used alone or in combination, could become
important weapons in the war against heart failure.