Evaluation of Cardiac Hemodynamic Modifications During Temporary Left Atrial Appendage Occlusion

Study Overview
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Brief Summary
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The left atrium appendage (LAA) is a remnant of the original embryonic left atrium formed during the third week of gestation. LAA is believed to function as a decompression chamber during left ventricular systole and other periods when left atrial pressure is elevated. The LAA is also a major endocrine organ and is the main producer of ANP (atrial natriuretic peptide) in the human heart. The ANP concentration is 40 times higher in the LAA walls than in the rest of the atrial wall. A study of patients having undergone the maze procedure and associated LAA removal found a significantly lower ANP secretion and an increase in salt and water retention. Whether this could eventually lead to hypertension or heart failure symptoms is not known. Removal of the LAA is routinely performed during antiarrhythmic surgical techniques (MAZE surgery) to reduce the risk of subsequent LAA thrombus. Furthermore, new percutaneous ablation techniques target LAA to reduce further risks of atrial fibrilation recurrences. However, in addition to effects on diastolic atrial function and atrial natriuretic peptide (ANP) secretion, this could potentially reduce stroke volume and cardiac output and may thus promote heart failure. Its removal could be particularly detrimental in patients with existing heart failure and high intraatrial pressure, as it would further promote pulmonary congestion and also reduce their cardiac output. The study will be conducted at the CHU Brugmann Hospital, with collaboration between cardiac surgery and cardiology wards. Subjects referred for non valvular cardiac surgery will be prospectively included during the first 6 months following the onset of the protocol. Echocardiographic and invasive data will be collected simultaneously. The goals of the study are: To evaluate the immediate impact of temporary closure of the LAA using a vascular clamp in the beating heart of human subjects during cardiac surgery. Impact of LAA occlusion will be measured using transesophageal echocardiography and hemodynamic measurement of the cardiac output. To correlate echocardiographic parameters with in situ hemodynamic data. A significant role of the LAA in the cardiac hemodynamic including the left ventricle outflow might have different clinical implications and will raise questions about: Appropriateness of LAA resection in antiarrhythmic surgery Importance of restoring sinus rhythm in atrial fibrilation patients Importance to spare LAA from ablation during atrial fibrilation ablation to avoid significant consequences on cardiac function. Appropriateness of the LAA occluding device in atrial fibrillation patients.

Official Title
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Evaluation of Cardiac Hemodynamic Modifications During Temporary Left Atrial Appendage Occlusion

Conditions
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Cardiac Surgery

Intervention / Treatment
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* Device: Transesophageal echocardiogram
* Device: Thermistor-tipped catheter
* Device: Pressure/volume catheter
* Device: Transthoracic echocardiography


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aortic valve stenosis suitable to surgery Left Atrium<50 mm in the parasternal long axis view Sinus rhythm at the time of patient's inclusion and during the procedure Exclusion Criteria: Hypertrophic cardiomyopathy (diastolic septal thickness > 15mm). Heart failure with Left Ventricule Ejection Fraction < 45%. Significant mitral regurgitation/stenosis Significant aortic regurgitation History of atrial fibrillation Presence of prosthetic valves Complex congenital heart disease

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non valvular cardiac surgery<br>The study will be conducted at the CHU Brugmann Hospital, with collaboration between cardiac surgery and cardiology wards. Subjects referred for non valvular cardiac surgery will be prospectively included during the first 6 months following the onset of the protocol. | Device: Transesophageal echocardiogram<br>* All patients will undergo a standard surgical procedure by the surgical team of CHU Brugmann. A transesophageal echocardiogram (TEE) will be performed and the TEE probe will stay continuously during the entire procedure, to allow all necessary measurements.<br>Device: Thermistor-tipped catheter<br>* All patients will undergo a standard surgical procedure by the surgical team of CHU Brugmann.During the procedure, a thermistor-tipped catheter (model 93A-131-7F, Edwards, Santa Ana, CA) will be inserted into the pulmonary artery to measure right atrial pressure (Pra), pulmonary arterial pressure (Ppa), Ppao and thermodilution cardiac output. Ringer's lactate will be infused to maintain an occluded pulmonary arterial pressure (Ppao) of 8-10 mmHg.<br>Device: Pressure/volume catheter<br>* All patients will undergo a standard surgical procedure by the surgical team of CHU Brugmann.During the procedure, a pressure/volume catheter (CD Leicom, Zoetermeer, Netherland) will be placed in the left ventricle through a left superior pulmonary vein purse string, in order to measure alternatively LV pressure/volume loops and LA pressure.<br>Device: Transthoracic echocardiography<br>* A complete transthoracic echocardiography will be performed the day before the surgical procedure. It will establish the presence of the inclusion and exclusion criteria, as stipulated above. This will be done using a Philips IE33 echocardiograph (Koninklijke Philips Electronics N.V., Netherlands). During the surgical procedure, a transesophageal echocardiogram will be performed, using an Acuson Sequoia system (Siemens AG, Germany).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left atrium (LA) dP/dt max | Fluid-filled catheter-derived pressures will be zero-referenced at mid-chest level and processed using disposable transducers (Baxter-Bentley, Uden, the Netherlands) and a Sirecust 404 monitoring system (Siemens, Erlangen, Germany). Micromanometer-derived pressures and conductance catheter data will be processed using a Leicom INCA intracardiac monitor (CD Leycom, Zoetermeer, Netherlands). All pressures and volume signals will be digitalized at 200 Hz and stored in a PC for off-line analysis. | Baseline (before LAA clamping) | 
| Left atrium dP/dt max | Fluid-filled catheter-derived pressures will be zero-referenced at mid-chest level and processed using disposable transducers (Baxter-Bentley, Uden, the Netherlands) and a Sirecust 404 monitoring system (Siemens, Erlangen, Germany). Micromanometer-derived pressures and conductance catheter data will be processed using a Leicom INCA intracardiac monitor (CD Leycom, Zoetermeer, Netherlands). All pressures and volume signals will be digitalized at 200 Hz and stored in a PC for off-line analysis. | 5 minutes after LAA clamping | 
| Left atrium output | Fluid-filled catheter-derived pressures will be zero-referenced at mid-chest level and processed using disposable transducers (Baxter-Bentley, Uden, the Netherlands) and a Sirecust 404 monitoring system (Siemens, Erlangen, Germany). Micromanometer-derived pressures and conductance catheter data will be processed using a Leicom INCA intracardiac monitor (CD Leycom, Zoetermeer, Netherlands). All pressures and volume signals will be digitalized at 200 Hz and stored in a PC for off-line analysis. The cardiac output will be measured by thermodilution (REF-1 computer, Edwards, Irvine, CA). | Baseline (before LAA clamping) | 
| Left atrium output | Fluid-filled catheter-derived pressures will be zero-referenced at mid-chest level and processed using disposable transducers (Baxter-Bentley, Uden, the Netherlands) and a Sirecust 404 monitoring system (Siemens, Erlangen, Germany). Micromanometer-derived pressures and conductance catheter data will be processed using a Leicom INCA intracardiac monitor (CD Leycom, Zoetermeer, Netherlands). All pressures and volume signals will be digitalized at 200 Hz and stored in a PC for off-line analysis. The cardiac output will be measured by thermodilution (REF-1 computer, Edwards, Irvine, CA). | 5 minutes after LAA clamping | 
| Left atrium contractility index (dP/dt max)/P | Fluid-filled catheter-derived pressures will be zero-referenced at mid-chest level and processed using disposable transducers (Baxter-Bentley, Uden, the Netherlands) and a Sirecust 404 monitoring system (Siemens, Erlangen, Germany). Micromanometer-derived pressures and conductance catheter data will be processed using a Leicom INCA intracardiac monitor (CD Leycom, Zoetermeer, Netherlands). All pressures and volume signals will be digitalized at 200 Hz and stored in a PC for off-line analysis. | Baseline (before LAA clamping) | 
| Left atrium contractility index (dP/dt max)/P | Fluid-filled catheter-derived pressures will be zero-referenced at mid-chest level and processed using disposable transducers (Baxter-Bentley, Uden, the Netherlands) and a Sirecust 404 monitoring system (Siemens, Erlangen, Germany). Micromanometer-derived pressures and conductance catheter data will be processed using a Leicom INCA intracardiac monitor (CD Leycom, Zoetermeer, Netherlands). All pressures and volume signals will be digitalized at 200 Hz and stored in a PC for off-line analysis. | 5 minutes after LAA clamping | 
| Left ventricle (LV) dP/dt max | Fluid-filled catheter-derived pressures will be zero-referenced at mid-chest level and processed using disposable transducers (Baxter-Bentley, Uden, the Netherlands) and a Sirecust 404 monitoring system (Siemens, Erlangen, Germany). Micromanometer-derived pressures and conductance catheter data will be processed using a Leicom INCA intracardiac monitor (CD Leycom, Zoetermeer, Netherlands). All pressures and volume signals will be digitalized at 200 Hz and stored in a PC for off-line analysis. | Baseline (before LAA clamping) | 
| Left ventricle dP/dt max | Fluid-filled catheter-derived pressures will be zero-referenced at mid-chest level and processed using disposable transducers (Baxter-Bentley, Uden, the Netherlands) and a Sirecust 404 monitoring system (Siemens, Erlangen, Germany). Micromanometer-derived pressures and conductance catheter data will be processed using a Leicom INCA intracardiac monitor (CD Leycom, Zoetermeer, Netherlands). All pressures and volume signals will be digitalized at 200 Hz and stored in a PC for off-line analysis. | 5 minutes after LAA clamping | 
| Left ventricle output | Fluid-filled catheter-derived pressures will be zero-referenced at mid-chest level and processed using disposable transducers (Baxter-Bentley, Uden, the Netherlands) and a Sirecust 404 monitoring system (Siemens, Erlangen, Germany). Micromanometer-derived pressures and conductance catheter data will be processed using a Leicom INCA intracardiac monitor (CD Leycom, Zoetermeer, Netherlands). All pressures and volume signals will be digitalized at 200 Hz and stored in a PC for off-line analysis. The cardiac output will be measured by thermodilution (REF-1 computer, Edwards, Irvine, CA). | Baseline (before LAA clamping) | 
| Left ventricle output | Fluid-filled catheter-derived pressures will be zero-referenced at mid-chest level and processed using disposable transducers (Baxter-Bentley, Uden, the Netherlands) and a Sirecust 404 monitoring system (Siemens, Erlangen, Germany). Micromanometer-derived pressures and conductance catheter data will be processed using a Leicom INCA intracardiac monitor (CD Leycom, Zoetermeer, Netherlands). All pressures and volume signals will be digitalized at 200 Hz and stored in a PC for off-line analysis. The cardiac output will be measured by thermodilution (REF-1 computer, Edwards, Irvine, CA). | 5 minutes after LAA clamping | 
| LV contractility index (dP/dt max)/P | Fluid-filled catheter-derived pressures will be zero-referenced at mid-chest level and processed using disposable transducers (Baxter-Bentley, Uden, the Netherlands) and a Sirecust 404 monitoring system (Siemens, Erlangen, Germany). Micromanometer-derived pressures and conductance catheter data will be processed using a Leicom INCA intracardiac monitor (CD Leycom, Zoetermeer, Netherlands). All pressures and volume signals will be digitalized at 200 Hz and stored in a PC for off-line analysis. LV contractility will be estimated from the slope of the end-systolic pressure-volume relation. | Baseline (before LAA clamping) | 
| LV contractility index (dP/dt max)/P | Fluid-filled catheter-derived pressures will be zero-referenced at mid-chest level and processed using disposable transducers (Baxter-Bentley, Uden, the Netherlands) and a Sirecust 404 monitoring system (Siemens, Erlangen, Germany). Micromanometer-derived pressures and conductance catheter data will be processed using a Leicom INCA intracardiac monitor (CD Leycom, Zoetermeer, Netherlands). All pressures and volume signals will be digitalized at 200 Hz and stored in a PC for off-line analysis. LV contractility will be estimated from the slope of the end-systolic pressure-volume relation. | 5 minutes after LAA clamping | 
| Occluded pulmonary arterial pressure (Ppao) | Fluid-filled catheter-derived pressures will be zero-referenced at mid-chest level and processed using disposable transducers (Baxter-Bentley, Uden, the Netherlands) and a Sirecust 404 monitoring system (Siemens, Erlangen, Germany). Micromanometer-derived pressures and conductance catheter data will be processed using a Leicom INCA intracardiac monitor (CD Leycom, Zoetermeer, Netherlands). All pressures and volume signals will be digitalized at 200 Hz and stored in a PC for off-line analysis. | Baseline (before LAA clamping) | 
| Occluded pulmonary arterial pressure (Ppao) | Fluid-filled catheter-derived pressures will be zero-referenced at mid-chest level and processed using disposable transducers (Baxter-Bentley, Uden, the Netherlands) and a Sirecust 404 monitoring system (Siemens, Erlangen, Germany). Micromanometer-derived pressures and conductance catheter data will be processed using a Leicom INCA intracardiac monitor (CD Leycom, Zoetermeer, Netherlands). All pressures and volume signals will be digitalized at 200 Hz and stored in a PC for off-line analysis. | 5 minutes after LAA clamping | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area fractional shortening (AFS) of the left atrium appendage (LAA) | Transesophageal echocardiography data (Acuson Sequoia system - Siemens AG, Germany). Computed with the following formula: AFS 2CME90°= (Amax-Amin)/Amax. | Baseline (before LAA clamping) | 
| Area fractional shortening (AFS) of the left atrium appendage (LAA) | Transesophageal echocardiography data (Acuson Sequoia system - Siemens AG, Germany). Computed with the following formula: AFS 2CME90°= (Amax-Amin)/Amax. | 5 minutes after LAA clamping | 
| Ejection volume of the LAA (left atrium appendage) | Transesophageal echocardiography data (Acuson Sequoia system - Siemens AG, Germany). Computed with the following formula: LAA ejection volume= 3,14*D1*D2*TVI PW LAA/4, where D1 and D2 are the diameters of the opening of the LAA at 0° and 90° | Baseline (before LAA clamping) | 
| Ejection volume of the LAA (left atrium appendage) | Transesophageal echocardiography data (Acuson Sequoia system - Siemens AG, Germany). Computed with the following formula: LAA ejection volume= 3,14*D1*D2*TVI PW LAA/4, where D1 and D2 are the diameters of the opening of the LAA at 0° and 90° | 5 minutes after LAA clamping | 
| Stroke volume | Transesophageal echocardiography data (Acuson Sequoia system - Siemens AG, Germany). Computed with the following formula: Stroke volume= 3,14D²*Aortic PW TVI /4, where D is the LVOT (left ventricular outflow tract)diameter in A3C. | Baseline (before LAA clamping) | 
| Stroke volume | Transesophageal echocardiography data (Acuson Sequoia system - Siemens AG, Germany). Computed with the following formula: Stroke volume= 3,14D²*Aortic PW TVI /4, where D is the LVOT (left ventricular outflow tract) diameter in A3C. | 5 minutes after LAA clamping | 
| Amplitude of the emptying pulse wave of the LAA (left atrium appendage) | Transesophageal echocardiography data (Acuson Sequoia system - Siemens AG, Germany). 2C ME 90° measure | Baseline (before LAA clamping) | 
| Amplitude of the emptying pulse wave of the LAA (left atrium appendage) | Transesophageal echocardiography data (Acuson Sequoia system - Siemens AG, Germany). 2C ME 90° measure | 5 minutes after LAA clamping | 
| TVI (Aortic Time-Velocity Integral) of the emptying pulse wave of the LAA (left atrium appendage) | Transgastric or deep transgastric aortic Pulse Wave Doppler. 2C ME 90° measure | Baseline (before LAA clamping) | 
| TVI (Aortic Time-Velocity Integral) of the emptying pulse wave of the LAA (left atrium appendage) | Transgastric or deep transgastric aortic Pulse Wave Doppler. 2C ME 90° measure | 5 minutes after LAA clamping | 
| Amplitude of the mitral A wave | Amplitude A wave: measured with DTI (Tissue Doppler ) 4C ME 0° lateral ring | Baseline (before LAA clamping) | 
| Amplitude of the mitral A wave | Amplitude A wave: measured with DTI (Tissue Doppler ) 4C ME 0° lateral ring | 5 minutes after LAA clamping | 
| TVI (Aortic Time-Velocity Integral) of the left upper pulmonary vein (LUPV) | Measured by aortic Pulse Wave (PW) Doppler flow | Baseline (before LAA clamping) | 
| TVI (Aortic Time-Velocity Integral) of the left upper pulmonary vein (LUPV) | Measured by aortic Pulse Wave (PW) Doppler flow | 5 minutes after LAA clamping | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Left atrium appendage (LAA) occlusion, Transesophageal echocardiography, Cardiac output hemodynamic measurement, Leycom Pressure/Volume Combination Catheter