Interest of Levosimendan Preconditioning for Cardiac Surgery Under CEC in Heart Failure Patients With Impaired Ejection Fraction (LevoCV)

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; Heart Failure With Reduced Ejection Fraction; Levosimendan
• Intervention / Treatment: Drug: Levosimendan; Drug: No Levosimendan

• Study Type: Observational
• Enrollment (Estimated): 300

Contacts and Locations

• Study Contact: Name: Thomas KLEIN, MD; Phone Number: +3383154045; Email: t.klein@chru-nancy.fr
• Study Contact Backup: Name: Thomas KLEIN, MD; Phone Number: ++33154045; 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: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• 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 different University Hospital in France

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 different University Hospital in France

Exclusion Criteria:

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

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Levosimendan; 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 different French Hospital, and who have received Levosimendan preoperatively	Drug: Levosimendan; Initiation of levosimendan 48 hours before surgery; Other Names: Interventional
Control - No Levosimendan; 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 different French Hospital and who have not received Levosimendan preoperatively	Drug: No Levosimendan; Without Levosimendan Infusion; Other Names: Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Major Adverse Cardiac Events (MACE) criteria at 30 days	to evaluate the impact of preconditioning with Levosimendan prior to scheduled cardiac surgery with extracorporeal circulation in patients with heart failure and impaired LVEF on the rate of cardiovascular events at 30 days post-op.	30 days after Levosimendan exposure

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
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
major renal events (MAKE) at 30 days from the date of surgery	to evaluate the impact of preconditioning with Levosimendan prior to scheduled cardiac surgery under extracorporeal circulation in patients with heart failure and impaired LVEF on the rate of renal events at 30 days post cardiac surgery.	30 days after Levosimendan exposure
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
Measurement of left ventricular ejection fraction by cardiac ultrasound 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 (measured by cardiac ultrasound) at hospital discharge	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. High VIS was empirically defined as ≥ 20. Maximum VIS≥20 predicts an increased likelihood of a poor composite clinical outcome	date of start of intensive care hospitalization to date of discharge from intensive care hospitalization assessed up to 3 months

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2023
• Primary Completion (Actual): July 2, 2023
• Study Completion (Estimated): October 10, 2023

Study Registration Dates

• First Submitted: July 26, 2023
• First Submitted That Met QC Criteria: August 30, 2023
• First Posted (Actual): September 1, 2023

Study Record Updates

• Last Update Posted (Actual): September 1, 2023
• Last Update Submitted That Met QC Criteria: August 30, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Cardiac Surgery; Cardiopulmonary Bypass; Levosimendan; Heart Failure With Reduced Ejection Fraction
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; 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: 2023_PI_084

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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