Aortic Valve Stenosis, Heart Failure, Diastolic, Monitoring, Physiologic, Physiology
Conditions
Keywords
Transesophageal, Echocardiography, Milrinone, Levosimendan, Strain, Deformation, Diastole, Afterload, Preload, Systole
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.
Interventions
DRUGLevosimendan
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.
DRUGMilrinone
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.
Sponsors
Sahlgrenska University Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
Sweden
Outcome results
None listed