YEAR IN REVIEW HEART FAILURE IN 2013
Continue what we are doing to treat HF, but do it better Jay N. Cohn
In 2013, clinical trials in heart failure focused on drugs and devices that might improve treatment of symptomatic patients beyond standard therapy. None achieved this aim. Therefore, future efforts should emphasize increased adherence to current, evidence-based therapy, and trials might better address efforts to prevent, rather than treat, heart failure. Cohn, J. N. Nat. Rev. Cardiol. 11, 69–70 (2014); published online 24 December 2013; doi:10.1038/nrcardio.2013.212
The principles of managing heart failure (HF) became apparent decades ago. When the left ventricle is dilated and under going the process of remodelling,1 function can be improved with vasodilatory drugs that reduce impedance to left ventricular ejection. These drugs augment the favour able effect of diuretics on symptoms and exercise tolerance in patients with HF. Life prolongation, however, is dependent on inhibition of the remodelling, which can be accomplished by neurohormone inhibitors,1 with or without vasodilatory properties, by drugs that enhance nitric oxide activity, and by electrical resynchronization of the ven tricles.2 However, the therapies used to treat HF with reduced ejection fraction (HFrEF) exhibit little benefit when the ventricle is not dilated—a syndrome now called HF with preserved ejection fraction (HFpEF). Trials conducted in the past few years have been devoted to efforts to improve strategies for using effective treatments in HFrEF, and to find a treatment for HFpEF that can reduce symptoms or improve out comes. Commercial sponsors have sought new drugs or devices, or expanded the use of existing interventions for HFrEF, whereas government sponsors have tried to document the best methods for employ ing existing treatments. New mechanistic breakthroughs have been scarce. In 2013, this pattern was dramatically apparent. Dissatisfaction with current loop diuretic therapy for acute decompensated HF has generated a number of studies to replace or supplement such drugs. These efforts have generally failed to reveal a more-effective alternative. The Heart Failure
Clinical Research Network, funded by the National Heart, Lung, and Blood Institute in the USA, addressed the possibility that lowdose dopamine or low-dose nesiritide could safely augment the diuresis induced by loop diuretics in patients with decompensated HF. The trial, in 360 patients, showed no evidence that diuresis or decongestion was enhanced by such combined therapy or that renal function was better preserved. 3 The conclusion is that we should continue what we are doing—maintain an aggressive approach to diuretic therapy, and perhaps concern ourselves less when renal function transiently worsens. Cardiac resynchronization therapy (CRT) has been remarkably effective in improv ing quality of life and prolonging survival in patients with HFrEF and an electro cardiogram (ECG)-measured prolongation of the QRS complex.2 The assumption has been that the ECG abnorma lity served as a crude surrogate for ventricular dys synchrony that could be used to distin guish responders from nonresponders. The EchoCRT Study Group, 4 funded by
Biotronik and GE Healthcare, conducted an international trial at 115 centres in 809 patients with HFrEF and demonstrable ventricular dyssynchrony despite a QRS duration
Continue what we are doing to treat HF, but do it better Jay N. Cohn
In 2013, clinical trials in heart failure focused on drugs and devices that might improve treatment of symptomatic patients beyond standard therapy. None achieved this aim. Therefore, future efforts should emphasize increased adherence to current, evidence-based therapy, and trials might better address efforts to prevent, rather than treat, heart failure. Cohn, J. N. Nat. Rev. Cardiol. 11, 69–70 (2014); published online 24 December 2013; doi:10.1038/nrcardio.2013.212
The principles of managing heart failure (HF) became apparent decades ago. When the left ventricle is dilated and under going the process of remodelling,1 function can be improved with vasodilatory drugs that reduce impedance to left ventricular ejection. These drugs augment the favour able effect of diuretics on symptoms and exercise tolerance in patients with HF. Life prolongation, however, is dependent on inhibition of the remodelling, which can be accomplished by neurohormone inhibitors,1 with or without vasodilatory properties, by drugs that enhance nitric oxide activity, and by electrical resynchronization of the ven tricles.2 However, the therapies used to treat HF with reduced ejection fraction (HFrEF) exhibit little benefit when the ventricle is not dilated—a syndrome now called HF with preserved ejection fraction (HFpEF). Trials conducted in the past few years have been devoted to efforts to improve strategies for using effective treatments in HFrEF, and to find a treatment for HFpEF that can reduce symptoms or improve out comes. Commercial sponsors have sought new drugs or devices, or expanded the use of existing interventions for HFrEF, whereas government sponsors have tried to document the best methods for employ ing existing treatments. New mechanistic breakthroughs have been scarce. In 2013, this pattern was dramatically apparent. Dissatisfaction with current loop diuretic therapy for acute decompensated HF has generated a number of studies to replace or supplement such drugs. These efforts have generally failed to reveal a more-effective alternative. The Heart Failure
Clinical Research Network, funded by the National Heart, Lung, and Blood Institute in the USA, addressed the possibility that lowdose dopamine or low-dose nesiritide could safely augment the diuresis induced by loop diuretics in patients with decompensated HF. The trial, in 360 patients, showed no evidence that diuresis or decongestion was enhanced by such combined therapy or that renal function was better preserved. 3 The conclusion is that we should continue what we are doing—maintain an aggressive approach to diuretic therapy, and perhaps concern ourselves less when renal function transiently worsens. Cardiac resynchronization therapy (CRT) has been remarkably effective in improv ing quality of life and prolonging survival in patients with HFrEF and an electro cardiogram (ECG)-measured prolongation of the QRS complex.2 The assumption has been that the ECG abnorma lity served as a crude surrogate for ventricular dys synchrony that could be used to distin guish responders from nonresponders. The EchoCRT Study Group, 4 funded by
Biotronik and GE Healthcare, conducted an international trial at 115 centres in 809 patients with HFrEF and demonstrable ventricular dyssynchrony despite a QRS duration
