Acute heart failure with low cardiac output: can we develop a short-term inotropic agent that does not increase adverse events?
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.
Campia
Umberto
U
Center for Cardiovascular Quality and Outcomes, Northwestern University Feinberg School of Medicine, 645 North Michigan Avenue, Suite 1006, Chicago, IL 60611, USA.
Nodari
Savina
S
Gheorghiade
Mihai
M
D000208:Acute Disease; D000818:Animals; D002302:Cardiac Output / Q000502:physiology*; D002316:Cardiotonic Agents / Q000009:adverse effects / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D004077:Digoxin / Q000009:adverse effects / Q000494:pharmacology; D004280:Dobutamine / Q000009:adverse effects / Q000494:pharmacology; D005043:Etiocholanolone / Q000009:adverse effects / Q000031:analogs & derivatives / Q000494:pharmacology; D015316:Genetic Therapy / Q000379:methods; D006333:Heart Failure / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology; D006801:Humans; D006835:Hydrazones / Q000009:adverse effects / Q000494:pharmacology; D011724:Pyridazines / Q000009:adverse effects / Q000494:pharmacology; D019837:Ryanodine Receptor Calcium Release Channel / Q000187:drug effects; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000187:drug effects; D000077464:Simendan; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors; D014508:Urea / Q000031:analogs & derivatives / Q000494:pharmacology
D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D019837:Ryanodine Receptor Calcium Release Channel; C547293:omecamtiv mecarbil; D000077464:Simendan; D004280:Dobutamine; D004077:Digoxin; D014508:Urea; D005043:Etiocholanolone; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; C468128:Istaroxime