Establishing Physiologic Outcomes for Ventricular Unloading on VA ECMO

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.

Study Overview

• Status: Withdrawn
• Conditions: Cardiogenic Shock

Detailed Description

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.

• Study Type: Observational

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2N2
      • University of Toronto
• United States
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients presenting to our facility in cardiogenic shock.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Only
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
With LV Unloading; 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; 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?

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.	Twice in 7 days

Collaborators and Investigators

• Sponsor: University of Utah

Publications and helpful links

General Publications

• Rao P, Khalpey Z, Smith R, Burkhoff D, Kociol RD. Venoarterial Extracorporeal Membrane Oxygenation for Cardiogenic Shock and Cardiac Arrest. Circ Heart Fail. 2018 Sep;11(9):e004905. doi: 10.1161/CIRCHEARTFAILURE.118.004905.
• Hitzeman TC, Xie Y, Zadikany RH, Nikolova AP, Baum R, Caldaruse AM, Agvanian S, Melmed GY, McGovern DPB, Geft DR, Chang DH, Moriguchi JD, Hage A, Azarbal B, Czer LS, Kittleson MM, Patel JK, Wu AHB, Kobashigawa JA, Hamilton M, Hong T, Shaw RM. cBIN1 Score (CS) Identifies Ambulatory HFrEF Patients and Predicts Cardiovascular Events. Front Physiol. 2020 May 25;11:503. doi: 10.3389/fphys.2020.00503. eCollection 2020.
• Nikolova AP, Hitzeman TC, Baum R, Caldaruse AM, Agvanian S, Xie Y, Geft DR, Chang DH, Moriguchi JD, Hage A, Azarbal B, Czer LS, Kittleson MM, Patel JK, Wu AHB, Kobashigawa JA, Hamilton M, Hong T, Shaw RM. Association of a Novel Diagnostic Biomarker, the Plasma Cardiac Bridging Integrator 1 Score, With Heart Failure With Preserved Ejection Fraction and Cardiovascular Hospitalization. JAMA Cardiol. 2018 Dec 1;3(12):1206-1210. doi: 10.1001/jamacardio.2018.3539.
• Eckman PM, Katz JN, El Banayosy A, Bohula EA, Sun B, van Diepen S. Veno-Arterial Extracorporeal Membrane Oxygenation for Cardiogenic Shock: An Introduction for the Busy Clinician. Circulation. 2019 Dec 10;140(24):2019-2037. doi: 10.1161/CIRCULATIONAHA.119.034512. Epub 2019 Dec 9.
• Combes A, Price S, Slutsky AS, Brodie D. Temporary circulatory support for cardiogenic shock. Lancet. 2020 Jul 18;396(10245):199-212. doi: 10.1016/S0140-6736(20)31047-3.
• Kim D, Jang WJ, Park TK, Cho YH, Choi JO, Jeon ES, Yang JH. Echocardiographic Predictors of Successful Extracorporeal Membrane Oxygenation Weaning After Refractory Cardiogenic Shock. J Am Soc Echocardiogr. 2021 Apr;34(4):414-422.e4. doi: 10.1016/j.echo.2020.12.002. Epub 2020 Dec 13.
• Aissaoui N, Luyt CE, Leprince P, Trouillet JL, Leger P, Pavie A, Diebold B, Chastre J, Combes A. Predictors of successful extracorporeal membrane oxygenation (ECMO) weaning after assistance for refractory cardiogenic shock. Intensive Care Med. 2011 Nov;37(11):1738-45. doi: 10.1007/s00134-011-2358-2. Epub 2011 Oct 1.
• Tonna JE, Selzman CH, Bartos JA, Presson AP, Ou Z, Jo Y, Becker L, Youngquist ST, Thiagarajan RR, Johnson MA, Rycus P, Keenan HT. The Association of Modifiable Postresuscitation Management and Annual Case Volume With Survival After Extracorporeal Cardiopulmonary Resuscitation. Crit Care Explor. 2022 Jul 25;4(7):e0733. doi: 10.1097/CCE.0000000000000733. eCollection 2022 Jul.

Study record dates

Study Major Dates

• Study Start (Actual): December 15, 2023
• Primary Completion (Actual): March 1, 2024
• Study Completion (Actual): March 1, 2024

Study Registration Dates

• First Submitted: October 31, 2022
• First Submitted That Met QC Criteria: December 12, 2022
• First Posted (Actual): December 20, 2022

Study Record Updates

• Last Update Posted (Estimated): November 12, 2024
• Last Update Submitted That Met QC Criteria: November 8, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Mechanical circulatory support
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Infarction; Necrosis; Myocardial Ischemia; Myocardial Infarction; Ischemia; Shock; Shock, Cardiogenic
• Other Study ID Numbers: 142543 (JapicCTI)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Undecided at this time.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No