Hemodynamic, echocardiographic, and neurohormonal effects of istaroxime, a novel intravenous inotropic and lusitropic agent: a randomized controlled trial in patients hospitalized with heart failure

• Published in: Journal of the American College of Cardiology 2008-06, Vol.51 (23), p.2276-2285
• Main Authors: Gheorghiade, Mihai, Blair, John E A, Filippatos, Gerasimos S, Macarie, Cezar, Ruzyllo, Witold, Korewicki, Jerzy, Bubenek-Turconi, Serban I, Ceracchi, Maurizio, Bianchetti, Maria, Carminati, Paolo, Kremastinos, Dimitrios, Valentini, Giovanni, Sabbah, Hani N
• Format: Article
• Language: English
• Subjects: Acute coronary syndromes; Acute Disease; Adenosine triphosphatase; Adolescent; Adult; Aged; Aged, 80 and over; Blood pressure; Cardiac arrhythmia; Cardiology; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - pharmacology; Cardiotonic Agents - therapeutic use; Clinical trials; Diastole - drug effects; Etiocholanolone - administration & dosage; Etiocholanolone - analogs & derivatives; Etiocholanolone - pharmacology; Etiocholanolone - therapeutic use; Female; Heart attacks; Heart failure; Heart Failure - diagnostic imaging; Heart Failure - drug therapy; Heart Failure - physiopathology; Heart Rate - drug effects; Hemodynamics; Hospitalization; Humans; Infusions, Intravenous; Male; Middle Aged; Pain; Pulmonary arteries; Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors; Statistical analysis; Stroke; Stroke Volume - drug effects; Systole - drug effects; Ultrasonography
• ISSN: 0735-1097; 1558-3597
• DOI: 10.1016/j.jacc.2008.03.015

We examined the hemodynamic, echocardiographic, and neurohormonal effects of intravenous istaroxime in patients hospitalized with heart failure (HF). Istaroxime is a novel intravenous agent with inotropic and lusitropic properties related to inhibition of Na/K adenosine triphosphatase (ATPase) and stimulation of sarcoplasmic reticulum calcium ATPase. One hundred twenty patients admitted with HF and reduced systolic function were instrumented with a pulmonary artery catheter within 48 h of admission. Three sequential cohorts of 40 patients each were randomized 3:1 istaroxime:placebo to a continuous 6-h infusion. The first cohort received 0.5 microg/kg/min, the second 1.0 microg/kg/min, and the third 1.5 microg/kg/min istaroxime or placebo. All doses of istaroxime lowered pulmonary capillary wedge pressure (PCWP), the primary end point (mean +/- SD: -3.2 +/- 6.8 mm Hg, -3.3 +/- 5.5 mm Hg, and -4.7 +/- 5.9 mm Hg compared with 0.0 +/- 3.6 mm Hg with placebo; p < 0.05 for all doses). Istaroxime significantly decreased heart rate (HR) and increased systolic blood pressure (SBP). Cardiac index increased and left ventricular end-diastolic volume decreased significantly only with 1.5 microg/kg/min. On echocardiography, left ventricular end diastolic volume and deceleration time improved with 1.5 microg/kg/min. There were no changes in neurohormones, renal function, or troponin I. Adverse events were not life threatening and were dose related. In patients hospitalized with HF, istaroxime improved PCWP and possibly diastolic function. In contrast to available inotropes, istaroxime increased SBP and decreased HR. (A Phase II Trial to Assess Hemodynamic Effects of Istaroxime in Pts With Worsening HF and Reduced LV Systolic Function [HORIZON-HF]; NCT00616161).