title: Hemodynamic effects of Ivabradine in addition to dobutamine in patients with severe systolic dysfunction.
abstract: BACKGROUND
  Dobutamine induced tachycardia increases myocardial oxygen consumption and impairs ventricular filling. We hypothesized that Ivabradine may be efficient to control dobutamine induced tachycardia.
  
  
  METHODS
  We assessed the effects of Ivabradine in addition to dobutamine in stable heart failure (HF) patients (LVEF < 35%, n = 22, test population) and validated its effects in refractory cardiogenic shock patients (n = 9, validation population) with contraindication to cardiac assistance or transplant. In the test population (62 ± 17 years, LVEF = 24 ± 8%), systolic and diastolic function were assessed at rest and under dobutamine [10 γ/min], before and after Ivabradine [5mg per os]. In the validation population (54 ± 11 years, LVEF = 22 ± 7%), Ivabradine [5mg twice a day] was added to the dobutamine infusion.
  
  
  RESULTS
  In the test population, Ivabradine decreased heart rate [HR] at rest and during dobutamine echocardiography (-9 ± 8 bpm, P = 0.0004). The decrease in HR was associated with a decrease in cardiac power output and an increase in diastolic duration at rest (+ 74 ± 67 ms, P = 0.0002), and during dobutamine infusion (+ 75 ± 67 ms, P < 0.0001). Change in LVEF during dobutamine was greater after Ivabradine treatment than before (+ 7.2 ± 4.7% vs. + 3.6 ± 4.2%, P = 0.002). In the validation population, Ivabradine decreased HR (-18 ± 11 bpm, P = 0.008) and improved diastolic filling time (+ 67 ± 42 ms, P = 0.012) without decreasing cardiac output. At 24h, Ivabradine improved systolic blood pressure (+ 9 ± 5 mmHg, P = 0.007), daily urine output (+ 0.7 ± 0.5L, P = 0.008), oxygen balance (ΔScv02 = + 13 ± 15%, P = 0.010), and NT-pro BNP (-2270 ± 1912 pg/mL, P = 0.017). Finally, only 2/9 (22%) patients died whereas expected mortality determined from a historical cohort was 78% (P = 0.017).
  
  
  CONCLUSIONS
  This pilot study demonstrates the safety and potential benefit of a HR lowering agent in cardiogenic shock.
authors.affiliation: AP-HP - University Hospital Henri Mondor, Cardiovascular Department, INSERM U955 Team 3, Creteil, France. Electronic address: romain.gallet@yahoo.fr.
authors.forename: Romain
authors.initials: R
authors.lastname: Gallet
authors.affiliation: AP-HP - University Hospital Henri Mondor, Cardiovascular Department, INSERM U955 Team 3, Creteil, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Ternacle
authors.affiliation: AP-HP - University Hospital Henri Mondor, Cardiovascular Department, INSERM U955 Team 3, Creteil, France.
authors.forename: Thibaud
authors.initials: T
authors.lastname: Damy
authors.affiliation: AP-HP - University Hospital Henri Mondor, Cardiovascular Department, INSERM U955 Team 3, Creteil, France.
authors.forename: Soulef
authors.initials: S
authors.lastname: Guendouz
authors.affiliation: AP-HP - University Hospital Henri Mondor, Cardiovascular Department, INSERM U955 Team 3, Creteil, France.
authors.forename: Camille
authors.initials: C
authors.lastname: Bremont
authors.affiliation: AP-HP - University Hospital Henri Mondor, Cardiovascular Department, INSERM U955 Team 3, Creteil, France.
authors.forename: Aurélien
authors.initials: A
authors.lastname: Seemann
authors.affiliation: AP-HP - University Hospital Henri Mondor, Cardiovascular Department, INSERM U955 Team 3, Creteil, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Gueret
authors.affiliation: AP-HP - University Hospital Henri Mondor, Cardiovascular Department, INSERM U955 Team 3, Creteil, France.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Dubois-Rande
authors.affiliation: AP-HP - University Hospital Henri Mondor, Cardiovascular Department, INSERM U955 Team 3, Creteil, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lim
mesh_terms: D000368:Aged; D001552:Benzazepines / Q000008:administration & dosage*; D002316:Cardiotonic Agents / Q000008:administration & dosage; D004280:Dobutamine / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D054143:Heart Failure, Systolic / Q000175:diagnosis* / Q000188:drug therapy* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D000077550:Ivabradine; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012720:Severity of Illness Index; D016896:Treatment Outcome
chemical_list: D001552:Benzazepines; D002316:Cardiotonic Agents; D000077550:Ivabradine; D004280:Dobutamine
keywords: Cardiogenic shock; Dobutamine; Heart failure; Ivabradine; Oxygen consumption