Pharmacologic Treatment of Heart Failure due to Ventricular Dysfunction by Myocardial Stunning

Abstract

The treatment of heart failure continues to pose a real challenge for clinicians. This condition is sometimes reversible and therapy should therefore pursue this outcome. In the context of coronary ischemic syndromes, myocardial stunning can cause heart failure and even cardiogenic shock, with important prognostic repercussions. Myocardial stunning is mainly due to calcium overload in the cytosol of myocardial cells, the loss of myofilaments and their reduced sensitivity to calcium. Enhanced immune activation with inflammatory phenomena also plays an important role in the pathophysiology of cardiac dysfunction. Increasing evidence has shown that the myocardial ATP-dependent potassium channel (K(ATP)) plays an important role in many myocardial cell functions and that it is involved in ischemia-reperfusion injury and myocardial stunning. K(ATP) is thus considered a therapeutic target in this setting. Currently used inotropic drugs improve contractility by increasing intracellular concentrations of free calcium, but they increase myocardial consumption of energy and even produce arrhythmia; therefore, in this clinical context, they do not seem to be 'pathophysiologically correct' drugs. Levosimendan, a new calcium-sensitizing agent, increases contractility by enhancing the sensitivity of myofilaments to calcium by binding to the C cardiac troponin in cardiac muscle in a calcium-dependent way. Levosimendan also exerts a coronary and systemic vasodilatory effect through its K(ATP) channel-opening properties and may exert other cardioprotective actions through this mechanism. Levosimendan produces positive hemodynamic effects without increasing myocardial oxygen demand or causing arrhythmias. Intravenous levosimendan is generally well tolerated and has been approved by several European countries, and recently recommended in European Society of Cardiology guidelines, as inotropic therapy for the short-term treatment of acute severe decompensated heart failure in adults. Randomized, double-blind trials have shown that levosimendan is not only more clinically and hemodynamically effective but also that it significantly reduces morbidity and mortality when compared with dobutamine or placebo. Clinical trials addressing the use and efficacy of intravenous levosimendan in acute heart failure in patients with systolic dysfunction or cardiogenic shock due to myocardial stunning are scarce. Beneficial effects on myocardial contractility in patients with myocardial stunning have only been shown in small clinical trials. A positive experience with levosimendan in a small series of patients with cardiogenic shock complicating ST-elevation myocardial infarction suggests that the use of this drug in cardiogenic shock should be further evaluated.

Effects of levosimendan versus dobutamine on left ventricular diastolic function in patients with cardiogenic shock after primary angioplasty

“…In previous studies from our group, we have found that levosimendan might be beneficial in cardiogenic shock, especially when it complicates acute myocardial infarction [4,8,9]. We observed that, in this type of patient, levosimendan improved cardiac reserve pumping and it increased both cardiac index and cardiac power [10] significantly more than dobutamine at the studied doses.…”

Levosimendan Improves Renal Outcome in Cardiac Surgery: A Randomized Trial

“…KEY WORDS: levosimendan, mitral valve surgery, cardiopulmonary bypass, serum creatinine, estimated glomerular filtration rate, ejection fraction T HE CORONARY AND PERİPHERAL vasodilatory properties of levosimendan recently have been investigated in patients with heart failure. [1][2][3][4] It is considered a promising alternative to conventional inotropic agents for patients with low left ventricular ejection fraction (LVEF). 5,6 However, the effects of levosimendan on renal function in patients undergoing cardiac surgeries with cardiopulmonary bypass (CPB) are not well studied in randomized clinical trials.…”

“…5,6 However, the effects of levosimendan on renal function in patients undergoing cardiac surgeries with cardiopulmonary bypass (CPB) are not well studied in randomized clinical trials. 3,7 One classification system, the risk, injury, failure, loss, and end-stage kidney (RIFLE) by the Acute Dialysis Quality Initiative, is based on changes in either serum creatinine or urine output from the baseline condition, and acute kidney injury (AKI) is defined as either an increase in serum creatinine by 0.3 mg/dL in o48 hours or an increase by 50% from baseline. The difference in the final serum creatinine reached with an episode of AKI using these two different criteria seems to be more marked when the baseline serum creatinine is higher.…”

The Effect of Erythropoietin on Potassium Levels During Ischemia Reperfusion Injury in Rats

“…This study demonstrates that resistance to myocardial IR injury is dependent on sarcolemmal K (ATP) activity during ischemia. Garcia Gonzalez et al [12] have shown that levosimendan exerts a coronary and systemic vasodilatory effect through its ATP-dependent K channel K (ATP) opening properties, as was experienced in patients with cardiogenic shock [12]. Bittner et al [13] used either Euro-Collinsaprotinin procurement solution (Apt-EC group) or aprotinin in combination with low-K dextran (LPD) flush solution (Apt-LPD group) for the procurement of donor lungs [13].…”