Establishing Physiologic Outcomes for Ventricular Unloading on VA ECMO

Study Overview
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Brief Summary
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Aim 1: Prospective, observational analysis of the association between echocardiographic measures of cardiac function and left ventricular unloading on VA ECMO. Aim 2: Prospective, observational analysis of the association between clinical laboratory biomarkers and left ventricular unloading on VA ECMO.

Detailed Description
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Mechanical circulatory support (MCS) is increasingly utilized as a means of hemodynamic support among cardiogenic shock (CS) patients refractory to optimal medical management. MCS modalities include using either an intra-aortic balloon pump (IABP), Impella®, or ECMO, each with unique benefit/harm profiles. Among the various MCS devices, extracorporeal membrane oxygenation (ECMO) is described as the highest level of support, capable of providing 5+ liters per minute of oxygenated blood flow but is the most invasive. Despite the benefit of maximal cardiopulmonary support, ECMO increases afterload in a failing heart. Left ventricular (LV) unloading or decompression (using simultaneous IABP or Impella®) has been suggested as potential improvement. Observational studies suggest a benefit with LV unloading during VA ECMO for CS, but the mechanisms underlying the association are poorly understood. Prior to trials, a mechanistic understanding of the effect of different LV unloading strategies on key physiologic abnormalities in CS is needed, as the physiologic effects of LV unloading during VA ECMO for CS remain insufficiently defined. The objective of this study is to define serial changes in common clinical variables routinely obtained during management of patients in CS. These clinical variables are readily accessible to clinicians, but are not typically collected in a sufficiently granular serial manner to characterize their utility as clinical biomarkers. By obtaining scheduled assessments, repeated in a prospective cohort over the clinical course of CS, the investigators will define the physiologic effects of different LV unloading strategies in cardiogenic shock. We will examine a) echocardiographic measures of ventricular distension, and b) blood biochemical measures of peripheral perfusion.

Official Title
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Establishing Physiologic Outcomes for Ventricular Unloading on VA ECMO

Conditions
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Cardiogenic Shock

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who are 18 years of age or older Patients with cardiogenic shock Patients with mechanical circulatory support, specifically veno-arterial extracorporeal membrane oxygenation (VA ECMO) inserted peripherally Exclusion Criteria: None

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| With LV Unloading<br>Adults (18+) who are in cardiogenic shock and being treated with mechanical circulatory support (veno-arterial ECMO) inserted peripherally. The patients in this group will also have an additional device, such as an Impella or an intra-aortic balloon pump (IABP) for left ventricular unloading. The decision whether or not to unload the patient will be purely clinical. Data will be collected from the patient's chart and entered into a secure database. A standard complete transthoracic echocardiogram will be completed at enrollment and then again 7 days from enrollment (+/- 2 days). Additional blood tests will be ordered for the 7 days after enrollment. All tests will be ordered on Day 1 (patient on ECMO, prior to any LV unloading) and additionally as follows: Troponin: Daily for 7 days NT-proBNP: Daily for 7 days PCO2 gap (in blood gas analysis): Every 6 hours for 3 days Lactate (in blood gas analysis): Every 12 hours for 3 days cBIN1: Twice in 7 days | |
| Without LV Unloading<br>Adults (18+) who are in cardiogenic shock and being treated with mechanical circulatory support (veno-arterial ECMO) inserted peripherally. The patients in this group will not have any LV unloading device in addition to the ECMO support. The decision not to do LV unloading will be purely clinical. Data will be collected from the patient's chart and entered into a secure database. A standard complete transthoracic echocardiogram will be completed at enrollment and then again 7 days from enrollment (+/- 2 days). Additional blood tests will be ordered for the 7 days after enrollment. All tests will be ordered on Day 1 (patient on ECMO, prior to any LV unloading) and additionally as follows: Troponin: Daily for 7 days NT-proBNP: Daily for 7 days PCO2 gap (in blood gas analysis): Every 6 hours for 3 days Lactate (in blood gas analysis): Every 12 hours for 3 days cBIN1: Twice in 7 days | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Left ventricular function (ejection fraction) | Ejection fraction will be measured via echocardiogram and compared between time points and between groups | Day 1/Enrollment | 
| Left ventricular function (ejection fraction) | Ejection fraction will be measured via echocardiogram and compared between time points and between groups | After LV unloading (within the first week of ECMO treatment; no specific day as this is a clinical decision) | 
| Left ventricular function (ejection fraction) | Ejection fraction will be measured via echocardiogram and compared between time points and between groups | Day 5 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Distension | Left ventricular end-diastolic dysfunction (LVEDD) will be measured via echocardiogram and compared between groups and between time points. | Day 1/Enrollment | 
| Distension | Left ventricular end-diastolic dysfunction (LVEDD) will be measured via echocardiogram and compared between groups and between time points. | After LV unloading (within the first week of ECMO treatment; no specific day as this is a clinical decision) | 
| Distension | Left ventricular end-diastolic dysfunction (LVEDD) will be measured via echocardiogram and compared between groups and between time points. | Day 5 | 
| Peripheral perfusion per lactate | Measurements of lactate will indicate differences in peripheral perfusion between time points and between groups | Daily (days 1-7) | 
| Peripheral perfusion per CO2 gap | Measurements of carbon dioxide (CO2) gap will indicate differences in peripheral perfusion between time points and between groups | Daily (days 1-7) | 
| Cardiac injury per troponin | Measurements of troponin will indicate levels of cardiac injury between time points and between groups. | Daily (days 1-7) | 
| Cardiac injury per BNP | Measurements of B-type natriuretic peptide (BNP) will indicate levels of cardiac injury between time points and between groups. | Daily (days 1-7) | 
| Cardiac injury per cBIN1 | Measurements of cardiac BIN1 (cBIN1) will indicate levels of cardiac injury between time points and between groups. | Daily cBIN1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mechanical circulatory support