Changes in Cardiac Deformation Following Physiologic Alterations and Inotropic Support.

NCT ID: NCT02408003

Last Updated: 2017-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-03-31
• Study Completion Date: 2017-05-31

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.

Conditions

Heart Failure, Diastolic; Aortic Valve Stenosis; Monitoring, Physiologic; Physiology

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

Levosimendan

Intervention Type: DRUG

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.

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.

Group Type: EXPERIMENTAL

Milrinone

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Daxim; Simdax; Primacor; Corotrop; Milicor

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sahlgrenska University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Martin Fredholm

MD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sven-Erik Ricksten, Professor

Role: PRINCIPAL_INVESTIGATOR

Dept of Anesthesia and Intensive Care, University of Gothenburg

Locations

Thoraxoperation/TIVA, Sahlgrenska universitetssjukhuset

Gothenburg, , Sweden

Countries

Sweden

Other Identifiers

Fredholm strain study

Identifier Type: -

Identifier Source: org_study_id