Treatment of Cardiac Conditions

Introduction to Levosimendan

Levosimendan is a calcium sensitizer that acts mainly through two mechanisms: sensitization to calcium and vasodilation, providing a hemodynamic profile intermediate between a pure vasodilator and a predominant inotropic agent, as noted by the European Society of Cardiology 1
The European Society of Cardiology and the American College of Cardiology recommend levosimendan as an alternative to dobutamine in patients with concomitant beta-blocker therapy 1, 2

Levosimendan is indicated for decompensated chronic heart failure, patients with systolic arterial pressure between 90-100 mmHg, and cardiogenic shock after fluid loading, if systolic arterial pressure remains <90 mmHg, as indicated by the American College of Cardiology 1
The recommended administration is at 0.1 μg/kg/min as a continuous infusion for 24 hours, with an optional loading dose of 12 μg/kg over 10 minutes in patients with adequate blood pressure (>100 mmHg) 2
Evaluate systolic blood pressure (SBP) before administration, and omit the loading dose in patients with SBP <100 mmHg 2
For patients with SBP >100 mmHg, an optional loading dose can be considered, followed by a maintenance infusion starting at 0.1 μg/kg/min, adjustable between 0.05-0.2 μg/kg/min based on response 2

Regular monitoring of blood pressure, heart rate, urine output, renal function, and electrolytes is essential during levosimendan administration 3
Close hemodynamic monitoring is recommended, especially in patients with low baseline blood pressure 2, 1
Levosimendan should be used with caution in patients with systolic blood pressure <100 mmHg or diastolic blood pressure <60 mmHg 2, 1
The most common adverse events associated with levosimendan include hypotension, headache, atrial fibrillation, hypokalemia, and tachycardia 2

The American Heart Association acknowledges that levosimendan has a primary active metabolite called OR-1896, which is responsible for the prolonged hemodynamic effects of the drug after infusion is stopped, with a half-life of 70-80 hours in patients with heart failure 4
The effects of levosimendan on filling pressure, ventricular function, and biomarkers such as BNP and NT-proBNP persist for at least 7 days after a 24-hour infusion, as noted by the American College of Cardiology 4
Levosimendan improves cardiac contractility by binding to troponin C in cardiomyocytes and causes vasodilation mediated by the opening of ATP-sensitive potassium channels in vascular smooth muscle, with a mild inhibitory action on phosphodiesterase 1, 2, 5

Its efficacy is maintained in patients with beta-blocker treatment, as its mechanism of action is independent of beta-adrenergic receptors 2
Levosimendan maintains its efficacy in patients on beta-blocker treatment and does not increase myocardial oxygen consumption or exacerbate ischemia, unlike adrenergic agents, as reported by the American Heart Association 1
Key hemodynamic effects of levosimendan include increased cardiac output and stroke volume, reduced pulmonary wedge pressure, and decreased systemic and pulmonary vascular resistance 2