Changes in Cardiac Deformation Following Physiologic Alterations and Inotropic Support.

What Are the Changes in Cardiac Deformation Variables and Hemodynamic Parameters Following Changes in Cardiac Loading Conditions and After Administration of Two Different Inotropic Drugs.

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.

Study Overview

• Status: Completed
• Conditions: Aortic Valve Stenosis; Heart Failure, Diastolic; Physiology; Monitoring, Physiologic
• Intervention / Treatment: Drug: Levosimendan; Drug: Milrinone

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Sweden
  • Göteborg, Sweden, 413 45
    • Thoraxoperation/TIVA, Sahlgrenska universitetssjukhuset

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Levosimendan; st dose: 12 µg/kg iv bolus for 10 min followed by 0,1 µg/kg/min for 20 min.; nd dose: 12 µg/kg iv bolus for 10 min followed by 0,2 µg/kg/min for 20 min.	Drug: Levosimendan; Data is collected at baseline as two controls. Three physiological interventions follows, and data is collected after each: Increasing heart rate in two steps by atrial pacing through a temporary pacemaker. Raising cardiac preload by increasing central venous pressure through leg elevation. Raising cardiac afterload by increasing systemic vascular resistance through administering of phenylephrine. Baseline is restored, and data is collected before drug adminstration as two controls, then after a first (half) dose, and finally after a second (full) dose.; Other Names: Simdax; Daxim
Experimental: Milrinone; st dose: 48 µg/kg iv bolus for 10 min followed by 0,4 µg/kg/min for 20 min.; nd dose: 48 µg/kg iv bolus for 10 min followed by 0,8 µg/kg/min for 20 min.	Drug: Milrinone; Data is collected at baseline as two controls. Three physiological interventions follows, and data is collected after each: Increasing heart rate in two steps by atrial pacing through a temporary pacemaker. Raising cardiac preload by increasing central venous pressure through leg elevation. Raising cardiac afterload by increasing systemic vascular resistance through administering of phenylephrine. Baseline is restored, and data is collected before drug adminstration as two controls, then after a first (half) dose, and finally after a second (full) dose.; Other Names: Primacor; Corotrop; Milicor

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Sahlgrenska University Hospital, Sweden
• Investigators: Principal Investigator: Sven-Erik Ricksten, Professor, Dept of Anesthesia and Intensive Care, University of Gothenburg

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2014
• Primary Completion (Actual): May 1, 2016
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: March 31, 2015
• First Submitted That Met QC Criteria: March 31, 2015
• First Posted (Estimate): April 3, 2015

Study Record Updates

• Last Update Posted (Actual): May 9, 2017
• Last Update Submitted That Met QC Criteria: May 8, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: Echocardiography; Levosimendan; Milrinone; Strain; Deformation; Transesophageal; Diastole; Afterload; Preload; Systole
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Aortic Valve Disease; Heart Valve Diseases; Ventricular Outflow Obstruction; Heart Failure; Aortic Valve Stenosis; Heart Failure, Diastolic; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Enzyme Inhibitors; Platelet Aggregation Inhibitors; Protective Agents; Cardiotonic Agents; Phosphodiesterase Inhibitors; Phosphodiesterase 3 Inhibitors; Simendan; Milrinone
• Other Study ID Numbers: Fredholm strain study

Plan for Individual participant data (IPD)

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