title: Effect of levosimendan on ventricular arrhythmias and prognostic autonomic indexes in patients with decompensated advanced heart failure secondary to ischemic or dilated cardiomyopathy.
abstract: Positive inotropes used for the treatment of heart failure have been arrhythmogenic. Levosimendan is a novel calcium sensitizer with vasodilating properties and a complex mechanism of action. Its effect on ventricular arrhythmias and 24-hour Holter electrocardiographically derived prognostic autonomic nervous system-related markers, because it occurs in parallel with changes in cardiac function and neurohormonal response, has not been systematically assessed. Forty-five patients (mean age 65 +/- 1.3 years) with heart failure refractory to conventional therapy and a mean ejection fraction of 23 +/- 1.2%, randomized to levosimendan or placebo, were studied. After Holter electrocardiographic recording, 1 drug was infused for 24 hours (levosimendan at a dose of 0.1 mug/kg/min). During this period, another Holter recording was performed to assess changes in ventricular arrhythmogenesis, 24-hour heart rate variability indexes, QTc, QT variability, and QT/RR slope. Clinical evaluation, echocardiography, and B-type natriuretic peptide measurements were performed at baseline and after treatment. After levosimendan, clinical and echocardiographic improvement was observed, associated with beneficial neurohormonal modulation (mean B-type natriuretic peptide level after levosimendan 668 +/- 108 vs 1,009 +/- 122 pg/ml at baseline, p <0.05). Episodes of nonsustained ventricular tachycardia increased with levosimendan (21.9 +/- 9.6 vs 3.0 +/- 1.2, p <0.05). Levosimendan and placebo exerted a neutral effect on all autonomic markers assessed. In conclusion, levosimendan at low doses increases nonsustained ventricular arrhythmias, without affecting Holter-derived, prognostically significant autonomic markers. At the same time, it is associated with improvements in cardiac function and neurohormonal response. These findings may have important clinical and prognostic implications.
authors.affiliation: Second Department of Cardiology, Attikon University Hospital, Athens, Greece. pflevari@yahoo.com
authors.forename: Panayota
authors.initials: P
authors.lastname: Flevari
authors.forename: John T
authors.initials: JT
authors.lastname: Parissis
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Leftheriotis
authors.forename: Fotis
authors.initials: F
authors.lastname: Panou
authors.forename: Kallirrhoe
authors.initials: K
authors.lastname: Kourea
authors.forename: Dimitrios Th
authors.initials: DT
authors.lastname: Kremastinos
mesh_terms: D000368:Aged; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000150:complications / Q000188:drug therapy*; D001341:Autonomic Nervous System / Q000503:physiopathology*; D002311:Cardiomyopathy, Dilated / Q000150:complications*; D002316:Cardiotonic Agents / Q000627:therapeutic use*; D005260:Female; D006333:Heart Failure / Q000150:complications* / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D006801:Humans; D006835:Hydrazones / Q000627:therapeutic use*; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000378:metabolism; D011724:Pyridazines / Q000627:therapeutic use*; D000077464:Simendan; D013318:Stroke Volume; D014665:Vasodilator Agents / Q000627:therapeutic use*; D018487:Ventricular Dysfunction, Left / Q000503:physiopathology
chemical_list: D000889:Anti-Arrhythmia Agents; D002316:Cardiotonic Agents; D006835:Hydrazones; D011724:Pyridazines; D014665:Vasodilator Agents; D020097:Natriuretic Peptide, Brain; D000077464:Simendan