Inotropic therapy is unsuccessful: wrong conceptual target or wrong therapeutic tools?
Since a depressed contractility has long been considered the primary defect in patients with heart failure, the use of inotropic agents has been regarded as a logical approach to treat this syndrome. Despite this conceptual framework, these drugs have not yet established themselves in the treatment of chronic heart failure and their long-term use was associated with an excessive mortality while the short-term intravenous administration in critically ill patients produced only acute hemodynamic results without a stable clinical improvement. At least four mechanisms could explain this discrepancy: their arrhythmogenicity, their direct cardiotoxic effects, the downregulation of the beta-adrenoreceptors, and the energetic cost of inotropic intervention. Moreover, in many patients with ischemic cardiomyopathy the reduction in contractility could be considered as a compensatory mechanism since hibernation is able to decrease the metabolic requirements of the heart. The contractile force of the heart can be augmented not only by an increased availability of intracellular calcium for troponin C but also by an increased sensitivity of the contractile proteins to calcium. A new class of inotropes working with this mechanism is now available and could represent a real improvement in this challenging therapeutic area.
Rapezzi
Claudio
C
Institute of Cardiology, University of Bologna, Bologna, Italy. crapezzi@orsolamalpigh.med.unibo.it
Perugini
Enrica
E
Santi
Michela
M
Bracchetti
Giovanni
G
Branzi
Angelo
A
D002316:Cardiotonic Agents / Q000627:therapeutic use*; D006333:Heart Failure / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D008508:Medication Errors; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology; D018570:Risk Assessment; D013577:Syndrome; D017211:Treatment Failure
D002316:Cardiotonic Agents