Impella Reverse Remodeling in End-Stage Heart Failure

A Prospective Study of Recovery Mechanisms in Heart Transplant Eligible Patients With Cardiogenic Shock on Impella 5.5 Support

This observational study is being done to learn more about heart attack recovery in patients supported with the Impella 5.5 left ventricular assist device (LVAD) as part of their standard of care. There are three stages in this study: screening, treatment and post treatment. There will be two phases of enrollment: First phase will enroll 10 patients; second phase will enroll an additional 40 patients. Approximately 50 participants will take part in the study at Columbia University Irving Medical Center.

Participation in this research is expected to last approximately 14 months. This time estimate includes a screening period for about 1- 3 days, treatment period of 40 days and post treatment follow-up period for 1 year. Data will be collected through 1- year after heart transplant. Clinical data (medical history, vital signs, laboratory assessments) from medical records, to perform functional testing, and to obtain blood and discarded heart tissue fromfor the purpose of this research study.

Participants will be asked to share their records for echocardiography, right heart catheterization, laboratory data and clinical information. Participants are required to complete an assessment a 6-minute walk, and hand grip strength test.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Cardiomyopathy

Detailed Description

Percutaneous endovascular mechanical circulatory support (MCS) devices have been increasingly utilized in patients on the waitlist for heart transplantation in the new heart allocation system. However, the number of patients recovering from heart failure and delisted from cardiac transplantation has declined in the new heart allocation system. While significant research has been performed on myocardial recovery with durable left ventricular assist device (LVAD) support, natural course and mechanistic basis of reverse remodeling on percutaneous endovascular MCS remains unknown. The primary objective of this prospective, observational, single-center study is to evaluate whether mechanical circulatory support with Impella 5.5 LVAD in decompensated patients on the waitlist for heart transplantation results in left ventricular reverse remodeling and improvement in end-organ function within 14 days of initiating support. Phenotypic data including clinical information, echocardiography, and hemodynamics will be serially obtained in participants before and after Impella 5.5 LVAD placement. Paired serum samples (pre- and post- Impella support) will be obtained for proteomic analysis. Cardiac tissue samples will be collected at the time of cardiac transplantation for histopathological analysis as well as RNA-sequencing. Candidate genes and proteins of reverse remodeling will be validated using quantitative polymerase chain reaction (qPCR) and Western Blotting. This study will definitively establish the natural course of reverse remodeling in patients with chronically failing ventricles on Impella 5.5 support and determine molecular signals and novel biomarkers of myocardial recovery in this growing population. Data obtained from this study will help determine which patients should pursue recovery pathway as opposed to transplant.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Adil Yunis, MD; Phone Number: 212-305-0211; Email: aay2122@cumc.columbia.edu

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University
      • Contact: Kate Dalton, MS; Phone Number: 347-514-3366; Email: Keb2114@cumc.columbia.edu
      • Principal Investigator: Adil Yunis, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Inpatients at Columbia University Irving Medical Center, who are waitlisted for heart transplant with a clinical indication for Impella 5.5 left ventricular assist device (LVAD) placement.

Description

Inclusion Criteria:

• Age 18 years or older
• Dilated cardiomyopathy (LVEDD > 5.5 cm and LVEF <25%)
• Indication for temporary mechanical circulatory support therapy with Impella 5.5 LVAD as a bridge to transplant or bridge to transplant decision based on treating physician's discretion

Exclusion Criteria:

• Intra-aortic balloon pump (IABP) use for more than 7 days at the time of Impella 5.5 implantation
• Percutaneous mechanical circulatory support device, extracorporeal membrane oxygenation (ECMO) or paracorporeal ventricular assist device (VAD) support prior to Impella 5.5 implantation
• Congenital heart disease
• Restrictive or hypertrophic Cardiomyopathy including hypertrophic obstructive cardiomyopathy (HOCM) Amyloidosis, and Sarcoidosis
• Evidence of acute myocarditis by endomyocardial biopsy
• Prior heart transplantation
• Mechanical aortic / mitral valve
• Patient with known aortic diseases such as Marfan-Syndrome, Morbus Erdheim-Gsell or others
• Left Ventricular thrombus
• Left Ventricular rupture
• Cardiac tamponade
• Presence of an Atrial or Ventricular Septal Defect
• Severe right ventricular (RV) Failure requiring mechanical RV support
• Severe peripheral vascular disease precluding placement of the Impella System
• Recent stroke resulting in significant neurological deficit
• Hypercoagulable disease precluding device implantation
• Severe thrombocytopenia (<50,000)
• Contraindication to anticoagulation
• Suspected or known pregnancy or lactating women
• Subject belongs to a vulnerable population

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Decompensated patients on the waitlist for heart transplantation; Study participants will receive Impella 5.5 LVAD for treatment of cardiogenic shock and transplant listing as standard of care. Clinical data and serum laboratory including blood counts, end-organ function, nutritional parameters will be collected prospectively from medical records. Participants are required to complete an assessment a 6-minute walk, and hand grip strength test.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Left Ventricular Ejection Fraction (LVEF)	A change in echocardiographic index will be evaluated by measuring a change in LVEF before and after Impella support at minimal pump setting.	Baseline and approximately Day 40
Change in Left Ventricular End-Diastolic Diameter (LVEDD)	A change in echocardiographic index will be evaluated by measuring a change in LVEDD before and after Impella support at minimal pump setting.	Baseline and approximately Day 40
Change in Cardiac Index	A change in hemodynamics will be evaluated by measuring a change in cardiac index before and after Impella support at minimal pump speed setting (P2).	Baseline and approximately Day 40
Change in Pulmonary Capillary Wedge Pressure	A change in hemodynamics will be evaluated by measuring a change in Pulmonary Capillary Wedge Pressure before and after Impella support at minimal pump speed setting (P2).	Baseline and approximately Day 40

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Transplant Waitlist Outcome	The transplant waitlist outcome will be evaluated and the number of participants who die, are delisted due to worsening clinical condition, are transplanted, or are delisted for recovery will be reported.	14 months
Number of Participants Escalated	Number of participants escalated to extracorporeal membrane oxygenation (ECMO) or other temporary/durable mechanical circulatory support (MCS).	14 months
Waitlist time on Impella Support	Waitlist time on Impella support measured in days from the date of Impella insertion to heart transplantation or other waitlist end-point.	14 months
Change in aminoterminal pro B-type natriuretic peptide (NT-proBNP)	Change in NT-proBNP levels collected from blood samples and measured in pg/mL.	Baseline and approximately Day 40
Change in Blood Urea Nitrogen (BUN)	Change in BUN levels collected from blood samples and measured in mg/dL.	Baseline and approximately Day 40
Change in Estimated Glomerular Filtration Rate (eGFR)	Change in eGFR collected from blood samples and measured in mL/min/1.73m^2.	Baseline and approximately Day 40
Change in Cystatin C	Change in Cystatin C collected from blood samples and measured in mg/L.	Baseline and approximately Day 40
Change in Total Bilirubin	Change in Total Bilirubin collected from blood samples and measured in mg/dL.	Baseline and approximately Day 40
Change in Aspartate Aminotransferase (AST)	Change in AST collected from blood samples and measured in U/L.	Baseline and approximately Day 40
Change in Alanine Aminotransferase (ALT)	Change in ALT collected from blood samples and measured in U/L.	Baseline and approximately Day 40
Change in International Normalized Ratio (INR)	Change in INR collected from blood samples. INR is a ratio and has no units of measure.	Baseline and approximately Day 40
Change in Hemoglobin	Change in hemoglobin levels collected from blood samples and measured in g/L.	Baseline and approximately Day 40
Change in Platelet Count	Change in platelet count collected from blood samples and measured in pl/μL.	Baseline and approximately Day 40
Change in Lactate dehydrogenase (LDH)	Change in LDH collected from blood samples and measured in U/L.	Baseline and approximately Day 40
Change in Plasma Free Hemoglobin	Change in plasma free hemoglobin collected from blood samples and measured in mg/dL.	Baseline and approximately Day 40
Change in Prealbumin	Change in prealbumin collected from blood samples and measured in mg/dL.	Baseline and approximately Day 40
Change in Albumin	Change in albumin collected from blood samples and measured in mg/dL.	Baseline and approximately Day 40
Change in C-Reactive Protein (CRP)	Change in CRP collected from blood samples and measured in mg/L.	Baseline and approximately Day 40
Change in Erythrocyte Sedimentation Rate (ESR)	Change in ESR collected from blood samples and measured in mm/hr.	Baseline and approximately Day 40
Change in Procalcitonin	Change in procalcitonin collected from blood samples and measured in ng/mL.	Baseline and approximately Day 40
Change in HLA Allosensitization Profile	Change in the HLA allosensitization profile. Allosensitization is the presence of circulating antibodies against human leukocyte antigens and nonhuman leukocyte antigens.	Baseline and approximately Day 40
Change in Vasoactive-Inotropic Score (VIS)	Vasoactive-Inotropic Score (VIS) is calculated with the following formula: VIS = dopamine (µg/kg/min) + dobutamine (µg/kg/min) + 100 × epinephrine (µg/kg/min) + 100 × norepinephrine (µg/kg/min) + 10 × milrinone (µg/kg/min) + 10,000 × vasopressin (units/kg/min). Scores range from 0 to no upper limit, with a higher score indicating a worse outcome.	Baseline and approximately Day 40
Six Minute Walk Test (6MWT)	The 6MWT is a measure of performance that assesses the distance walked in six minutes measured in meters. the 6MWT will be conducted in the Cardiac Care Unit (CCU) on device support.	14 months
Change in Upper Extremity Hand Strength	Change in upper extremity strength measured by Handgrip dynamometry in kilograms.	14 months
Units of Blood Used During Heart Transplant	Units of red blood cells, cryoprecipitate, fresh frozen plasma, and platelets used during transplant.	Day of Transplant (Approximately Day 40)
Primary Graft Failure	The number of participants with primary graft failure after heart transplantation. Graft failure defined as left ventricular ejection fraction of <40%.	14 months
Early Transplant Rejection	The number of participants with early transplant rejection. Early transplant rejected defined as an episode of rejection within the first 3 months of transplant.	14 months
AlloMap Score	AlloMap score after heart transplantation. AlloMap measures the risk of acute cellular rejection. Scores range from 0 - 40 with higher score indicating a worse outcome.	After Transplant, approximately Day 40
Allosure Score	Allosure score after heart transplantation. Allosure measures the risk of rejection in heart transplant recipients. Scores range from a lower limit of < 0.04 and above with a higher score indicating a worse outcome.	After Transplant, approximately Day 40
Post-Transplant Length of Stay	Post-transplant length of hospital stay measured in days and assessed for up to 14 months.	Up to 14 months (approximately 420 days)

Collaborators and Investigators

• Sponsor: Columbia University
• Collaborators: Abiomed Inc.
• Investigators: Principal Investigator: Adil Yunis, MS, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): December 4, 2024
• Primary Completion (Estimated): November 1, 2026
• Study Completion (Estimated): November 1, 2027

Study Registration Dates

• First Submitted: January 8, 2025
• First Submitted That Met QC Criteria: January 28, 2025
• First Posted (Actual): January 30, 2025

Study Record Updates

• Last Update Posted (Actual): July 31, 2025
• Last Update Submitted That Met QC Criteria: July 29, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: LVAD; impella; cardiogenic shock and transplant
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Cardiomyopathies
• Other Study ID Numbers: AAAV1201

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes