Lowering heart rate may reduce mortality

Heart failure is a clinical syndrome in which the heart fails to maintain an adequate output to vital organs. The responses to the resultant low blood pressure and underperfusion of organs include activation of the renin-angiotensin system with retention of salt and water, structural change of the heart and blood vessels with altered arterial compliance, and increased sympathetic drive. These result in an increase in heart rate, peripheral resistance, and myocardial contractility. Although these compensatory mechanisms are effective in the short term, they eventually become harmful. The adverse compensatory activation of the renin-angiotensin system can be modified by inhibitors, which improve symptoms and reduce mortality. Is the long term sympathetic overdrive that occurs as a consequence of heart failure also harmful?

The effect of adrenergic stimulation on the myocyte is to increase contractility and improve cardiac function. This should be a beneficial effect, yet all clinical trials of positively inotropic drugs have either failed to improve symptoms or have increased mortality in heart failure. The long list of drugs includes the phosphodiesterase inhibitors,1 dopaminergic inodilators …