Acute Heart Failure With Low Cardiac Output: Can We Develop a Short-term Inotropic Agent That Does Not Increase Adverse Events?

Abstract

Acute heart failure represents an increasingly common cause of hospitalization, and may require the use of inotropic drugs in patients with low cardiac output and evidence of organ hypoperfusion. However, currently available therapies may have deleterious effects and increase mortality. An ideal inotropic drug should restore effective tissue perfusion by enhancing myocardial contractility without causing adverse effects. Such a drug is not available yet. New agents with different biological targets are under clinical development. In particular, istaroxime seems to dissociate the inotropic effect exerted by digitalis (inhibition of the membrane sodium/potassium adenosine triphosphatase) from the arrhythmic effect and to ameliorate diastolic dysfunction (via sarcoendoplasmic reticulum calcium adenosine triphosphatase activation). Additionally, the myosin activator omecamtiv mecarbil appears to have promising characteristics, while genetic therapy has been explored in animal studies only. Further investigations are needed to confirm and expand the effectiveness and safety of these agents in patients with acute heart failure and low cardiac output.

Haemodynamic monitoring of cardiac status using heart sounds from an implanted cardiac device

“…27 In most patients with cardiac decompensation and low perfusion, the depressed cardiac function is a consequence of impaired myocardial contractility coupled with abnormal preload and afterload conditions. 28 Compensatory mechanisms triggered to restore contractility following a primary event of myocardial infarction or cardiomyopathy result in a downward spiral of worsening preload and afterload conditions, myocardial injury, and further decrease in contractility, culminating in a low cardiac output and impaired organ perfusion. 28 Prior studies have demonstrated the acute relationship of S1 amplitude with LV dP/dt max as a surrogate for LV contractility.…”

“…28 Compensatory mechanisms triggered to restore contractility following a primary event of myocardial infarction or cardiomyopathy result in a downward spiral of worsening preload and afterload conditions, myocardial injury, and further decrease in contractility, culminating in a low cardiac output and impaired organ perfusion. 28 Prior studies have demonstrated the acute relationship of S1 amplitude with LV dP/dt max as a surrogate for LV contractility. 11 Our study suggests that the haemodynamic association is preserved in spite of the unconventional sensor location and the use of accelerometer embedded within an implanted cardiac device to measure HSs.…”

On the Differences Between Ouabain and Digitalis Glycosides

“…75,76 A better understanding of its mode of action might help to reposition this drug in therapeutic regimens. Decades of intensive research have not yet solved the enigma surrounding the exact mechanism of action.…”

Omecamtiv Mecarbil: A Myosin Motor Activator Agent with Promising Clinical Performance and New in vitro Results

“…The ideal inotropic agent (1) should enhance cardiac pumping selectively without altering other parameters of cardiac function, (2) should not increase substantially cardiac energy consumption, and (3) should not increase the incidence of cardiac arrhythmias [16]. Since these requirements can hardly be met with interactions upstream to the contractile machinery, the downstream steps came into the focus of the research.…”