Impact of Levosimendan Preconditioning on Critical Care and In-hospital Lengths of Stay After Cardiac Surgery With Bypass Surgery (LevoCCV)

Levosimendan, a drug with inotropic, vasodilatory and myocardial protective properties, has been proposed for the prevention and treatment of postoperative low cardiac output syndrome in cardiac surgery. Despite preliminary studies with promising results, large randomized controlled trials aimed at demonstrating the benefits of levosimendan did not show superiority over placebo in this indication. However, in these studies, the infusion was neither performed at the maximum dosage nor during the 24 hours preceding the surgery, but mainly at the very beginning of the operation. However, post hoc analyses showed a reduction in mortality and in the occurrence of low cardiac output syndrome in the subgroup of patients who had undergone isolated coronary artery bypass grafting, in contrast to those who had undergone valvular or combined surgery. Another recent study suggests that under similar conditions, preconditioning with levosimendan started 48 hours before surgery reduces the length of stay in intensive care and the average cost of hospitalization. There are no formal recommendations on the prophylactic use of levosimendan in cardiac surgery for heart failure patients with impaired LVAS. However, the France-Levo registry, a multicenter observational study requested by the HAS, has shown that in real practice there is a place for preconditioning with levosimendan, which is used in this indication for 7% of the patients in the registry. The Cardiovascular Surgery and Transplantation Department of the Nancy Brabois University Hospital, which actively participated in the France-Levo registry, is one of the cardiac surgery centers that uses this practice, as is the University Hospital of Rouen. It is interesting to be able to evaluate retrospectively whether levosimendan preconditioning has a positive impact on the postoperative prognosis of patients and more particularly on the reduction of the length of stay in critical care and in hospital compared to standard management.

Study Overview

• Status: Recruiting
• Conditions: Cardiac Surgery; Cardiopulmonary Bypass; Levosimendan
• Intervention / Treatment: Drug: Levosimendan

• Study Type: Observational
• Enrollment (Anticipated): 120

Contacts and Locations

• Study Contact: Name: KLEIN Thomas, MD; Phone Number: +33383154045; Email: t.klein@chru-nancy.fr

Study Locations

• France
  • Meurthe Et Moselle
    • Vandœuvre-lès-Nancy, Meurthe Et Moselle, France, 54530
      • Recruiting
      • 'CHRU Nancy
      • Contact: KLEIN Thomas, MD; Phone Number: +33383154045; Email: t.klein@chru-nancy.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: N/A
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Preoperative heart failure patients with impaired LVEF who underwent left heart surgery (coronary artery bypass grafting and/or mitral and/or aortic valve replacement) under extracorporeal circulation from 01/09/2018 to 28/02/2022 at the CHRU de Nancy, CHRU de Rennes, CHRU de Rouen or CHRU d'Amiens.

Description

Inclusion Criteria:

• Patients with heart failure impaired LVEF (< 40%), who have undergone left heart surgery (coronary artery bypass grafting and/or mitral and/or aortic valve replacement) under extracorporeal circulation between 01/01/2018 and 28/02/2022 at the Nancy University Hospital or the University Hospital of Rennes, Rouen or Amiens

Exclusion Criteria:

• Initiation of levosimendan > 48 hours or < 24 hours before surgery
• ECMO pre- or post-op

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Levosimendan - Interventional; Major patients in heart failure with impaired LVEF (< 40%) who have undergone left heart surgery (coronary artery bypass grafting and/or mitral and/or aortic valve replacement) under extracorporeal circulation between 01/01/2018 and 28/02/2022 at the Nancy University Hospital or at the University Hospital of Rennes, Rouen or Amiens, and who have received Levosimendan preoperatively	Drug: Levosimendan; Initiation of levosimendan 48 hours before surgery; Other Names: Interventional
Non Levosimendan - Control; Major patients in heart failure with impaired LVEF (< 40%) who have undergone left heart surgery (coronary artery bypass grafting and/or mitral and/or aortic valve replacement) under extracorporeal circulation between 01/01/2018 and 28/02/2022 at the Nancy University Hospital or at the University Hospital of Rennes, Rouen or Amiens, and who have not received Levosimendan preoperatively

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of stay in ICU	To evaluate the impact of levosimendan preconditioning preoperatively for cardiac surgery on critical care length of stay in patients with heart failure with impaired preoperative LVAS.	date of start of intensive care hospitalization to date of discharge from intensive care hospitalization assessed up to 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
On 1-year mortality	To evaluate the impact of preconditioning with Levosimendan before cardiac surgery in patients with heart failure and impaired left ventricular dysfunction on 1-year mortality	1 year after Levosimendan exposure
the total length of hospital stay	To evaluate the impact of preconditioning with Levosimendan preoperatively for cardiac surgery in patients with heart failure with impaired preoperative left ventricular dysfunction on the total length of hospital stay	start date of hospitalization in intensive care to the date of discharge from conventional sectors evaluated up to 3 months
left ventricular systolic function at hospital discharge	To evaluate the impact of Levosimendan preconditioning before cardiac surgery in patients with heart failure and impaired on left ventricular systolic function at hospital discharge	date of start of intensive care hospitalization to date of discharge from intensive care hospitalization assessed up to 3 months
duration of catecholamine use after surgery	To evaluate the impact of preconditioning with Levosimendan before cardiac surgery in patients with heart failure and impaired left ventricular function before surgery on the duration of catecholamine use after surgery	date of start of intensive care hospitalization to date of discharge from intensive care hospitalization assessed up to 3 months
severity of postcardiotomy cardiogenic shock and/or postoperative vasoplegia using the score Vasoactive Inotropic Score (VIS)	To evaluate the impact of preconditioning with Levosimendan in preoperative cardiac surgery in patients with heart failure with impaired preoperative LVAS on the severity of postcardiotomy cardiogenic shock and/or postoperative vasoplegia	date of start of intensive care hospitalization to date of discharge from intensive care hospitalization assessed up to 3 months
acute renal failure postoperatively	To evaluate the impact of preconditioning with Levosimendan preoperatively for cardiac surgery in patients with heart failure with impaired left ventricular function preoperatively on the rate of acute renal failure postoperatively	on discharge from the intensive care unit
readmission rate for cardiac decompensation	To evaluate the impact of preconditioning with Levosimendan preoperatively for cardiac surgery in patients with heart failure and impaired LVAS preoperatively on the readmission rate for cardiac decompensation	within one year of Levosimendan administration

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Principal Investigator: KLEIN Thomas, MD, Intensive Care Unit

Publications and helpful links

General Publications

• Levin R, Degrange M, Del Mazo C, Tanus E, Porcile R. Preoperative levosimendan decreases mortality and the development of low cardiac output in high-risk patients with severe left ventricular dysfunction undergoing coronary artery bypass grafting with cardiopulmonary bypass. Exp Clin Cardiol. 2012 Sep;17(3):125-30.
• Cholley B, Caruba T, Grosjean S, Amour J, Ouattara A, Villacorta J, Miguet B, Guinet P, Levy F, Squara P, Ait Hamou N, Carillion A, Boyer J, Boughenou MF, Rosier S, Robin E, Radutoiu M, Durand M, Guidon C, Desebbe O, Charles-Nelson A, Menasche P, Rozec B, Girard C, Fellahi JL, Pirracchio R, Chatellier G; -. Effect of Levosimendan on Low Cardiac Output Syndrome in Patients With Low Ejection Fraction Undergoing Coronary Artery Bypass Grafting With Cardiopulmonary Bypass: The LICORN Randomized Clinical Trial. JAMA. 2017 Aug 8;318(6):548-556. doi: 10.1001/jama.2017.9973.
• Erb J, Beutlhauser T, Feldheiser A, Schuster B, Treskatsch S, Grubitzsch H, Spies C. Influence of levosimendan on organ dysfunction in patients with severely reduced left ventricular function undergoing cardiac surgery. J Int Med Res. 2014 Jun;42(3):750-64. doi: 10.1177/0300060513516293. Epub 2014 Apr 29.
• Sanfilippo F, Knight JB, Scolletta S, Santonocito C, Pastore F, Lorini FL, Tritapepe L, Morelli A, Arcadipane A. Levosimendan for patients with severely reduced left ventricular systolic function and/or low cardiac output syndrome undergoing cardiac surgery: a systematic review and meta-analysis. Crit Care. 2017 Oct 19;21(1):252. doi: 10.1186/s13054-017-1849-0.
• van Diepen S, Mehta RH, Leimberger JD, Goodman SG, Fremes S, Jankowich R, Heringlake M, Anstrom KJ, Levy JH, Luber J, Nagpal AD, Duncan AE, Argenziano M, Toller W, Teoh K, Knight JD, Lopes RD, Cowper PA, Mark DB, Alexander JH. Levosimendan in patients with reduced left ventricular function undergoing isolated coronary or valve surgery. J Thorac Cardiovasc Surg. 2020 Jun;159(6):2302-2309.e6. doi: 10.1016/j.jtcvs.2019.06.020. Epub 2019 Jun 21.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2022
• Primary Completion (Actual): December 15, 2022
• Study Completion (Anticipated): February 15, 2023

Study Registration Dates

• First Submitted: December 20, 2022
• First Submitted That Met QC Criteria: January 5, 2023
• First Posted (Estimate): January 16, 2023

Study Record Updates

• Last Update Posted (Estimate): January 16, 2023
• Last Update Submitted That Met QC Criteria: January 5, 2023
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Simendan
• Other Study ID Numbers: 2022_PI_118

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No