Changes in Cardiac Deformation Following Physiologic Alterations and Inotropic Support.

Not Applicable

Completed

• Conditions: Physiology; Aortic Valve Stenosis; Heart Failure, Diastolic; Monitoring, Physiologic
• Interventions: Drug: Levosimendan; Drug: Milrinone

• Registration Number: NCT02408003
• Lead Sponsor: Sahlgrenska University Hospital, Sweden

Brief Summary

The investigators want to compare the effects of two drugs, levosimendan and milrinone, on cardiac muscle, both in terms of contractility and relaxation. Half of the participants will be randomized to each drug. The effects will be measured through echocardiographic deformation analyses.

Since deformation analyses could be dependent on different loading conditions of the heart, a second purpose of the study is to investigate the changes on deformation parameters after applied changes in preload and afterload, but also heart rate.

Detailed Description

Aortic stenosis is associated with myocardial hypertrophy and diastolic dysfunction. In patients undergoing open aortic valve replacement surgery due to stenosis, the investigators want to compare the effect on myocardial relaxation between two commonly used drugs, levosimendan and milrinone, using catheter-based measurements in combination with echocardiographic evaluation.

Standard anaesthesia and surgical care for these patients is performed. After surgery is completed and the participant is transferred to the intensive care unit, the studies are performed during general anaesthesia and the participants still connected to a respirator with controlled ventilation.

Echocardiographic data will be collected simultaneously with hemodynamic parameters - first at two control measurements, then after each of two different doses of the drug. Preload, afterload and heart rate will be kept stable during this intervention. The echocardiographic data is later analyzed offline for strain and strain rate.

To further investigate the dependency of strain and strain rate on changes in preload, afterload, and heart rate, these variables are consecutively changed prior to drug administration. For this purpose, all patients first have their baseline data recorded, thereafter are paced at two different rates, then preload and afterload is altered by passive leg elevation and phenylephrine, respectively. Hemodynamic and echocardiographic data are collected simultaneously at baseline and after each intervention. Before administration of the drugs, baseline conditions are restored.

Study Timeline

• Study Start: 2014-03
• Study First Submitted: 2015-03-31
• Study First Submitted QC: 2015-03-31
• Study First Posted: 2015-04-03
• Primary Completion: 2016-05
• Status Verified: 2017-05
• Study Completion: 2017-05
• Last Update Submitted: 2017-05-08
• Last Update Posted: 2017-05-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Subject has aortic valve stenosis
• Subject is scheduled for open heart aortic valve replacement with or without simultaneous coronary artery bypass grafting

Exclusion Criteria

• Less than normal systolic function, defined as ejection fraction less than 0,5
• Non-sinus rhythm
• Any major surgical complication
• Problems understanding the informed consent

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Levosimendan	Levosimendan	1. st dose: 12 µg/kg iv bolus for 10 min followed by 0,1 µg/kg/min for 20 min. 2. nd dose: 12 µg/kg iv bolus for 10 min followed by 0,2 µg/kg/min for 20 min.
Milrinone	Milrinone	1. st dose: 48 µg/kg iv bolus for 10 min followed by 0,4 µg/kg/min for 20 min. 2. nd dose: 48 µg/kg iv bolus for 10 min followed by 0,8 µg/kg/min for 20 min.

Primary Outcome Measures

Name	Time	Method
Change in diastolic strain rate	After each physiologic intervention, and at 30 and 60 min after start of iv infusion of drug.	Diastolic strain rate defined as peak E wave strain rate as measured by 2D speckle tracking of the left ventricular wall.

Secondary Outcome Measures

Name	Time	Method
Change in systolic strain and strain rate	After each physiologic intervention, and at 30 and 60 min after start of iv infusion of drug.	Systolic strain and strain rate defined as their respective peak values during systole, measured by 2D speckle tracking of the left ventricular wall.
Change in cardiac output	After each physiologic intervention, and at 30 and 60 min after start of iv infusion of drug.	Measured through pulmonary artery thermodilution as liters per minute. A baseline measurement is done before infusion is started.

Trial Locations

Locations (1)

Thoraxoperation/TIVA, Sahlgrenska universitetssjukhuset; 🇸🇪 Göteborg, Sweden