Clinical trial NCT06800716: Impella Reverse Remodeling in End-Stage Heart Failure
Official title: A Prospective Study of Recovery Mechanisms in Heart Transplant Eligible Patients With Cardiogenic Shock on Impella 5.5 Support
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Heart Failure
Cardiomyopathy
Keywords: cardiogenic shock and transplant
impella
LVAD
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Abiomed Inc.
First posted: 2025-01-30
Enrollment: 50
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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 and neurocognitive testing, and to obtain blood and discarded heart tissue from for 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, hand grip strength test and questionnaire to evaluate neurocognitive status.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Left Ventricular Ejection Fraction (LVEF)
timeFrame: Baseline and approximately Day 40
measure: Change in Left Ventricular End-Diastolic Diameter (LVEDD)
timeFrame: Baseline and approximately Day 40
measure: Change in Cardiac Index
timeFrame: Baseline and approximately Day 40
measure: Change in Pulmonary Capillary Wedge Pressure
timeFrame: Baseline and approximately Day 40
Secondary outcomes:
measure: Transplant Waitlist Outcome
timeFrame: 14 months
measure: Number of Participants Escalated
timeFrame: 14 months
measure: Waitlist time on Impella Support
timeFrame: 14 months
measure: Change in aminoterminal pro B-type natriuretic peptide (NT-proBNP)
timeFrame: Baseline and approximately Day 40
measure: Change in Blood Urea Nitrogen (BUN)
timeFrame: Baseline and approximately Day 40
measure: Change in Estimated Glomerular Filtration Rate (eGFR)
timeFrame: Baseline and approximately Day 40
measure: Change in Cystatin C
timeFrame: Baseline and approximately Day 40
measure: Change in Total Bilirubin
timeFrame: Baseline and approximately Day 40
measure: Change in Aspartate Aminotransferase (AST)
timeFrame: Baseline and approximately Day 40
measure: Change in Alanine Aminotransferase (ALT)
timeFrame: Baseline and approximately Day 40
measure: Change in International Normalized Ratio (INR)
timeFrame: Baseline and approximately Day 40
measure: Change in Hemoglobin
timeFrame: Baseline and approximately Day 40
measure: Change in Platelet Count
timeFrame: Baseline and approximately Day 40
measure: Change in Lactate dehydrogenase (LDH)
timeFrame: Baseline and approximately Day 40
measure: Change in Plasma Free Hemoglobin
timeFrame: Baseline and approximately Day 40
measure: Change in Prealbumin
timeFrame: Baseline and approximately Day 40
measure: Change in Albumin
timeFrame: Baseline and approximately Day 40
measure: Change in C-Reactive Protein (CRP)
timeFrame: Baseline and approximately Day 40
measure: Change in Erythrocyte Sedimentation Rate (ESR)
timeFrame: Baseline and approximately Day 40
measure: Change in Procalcitonin
timeFrame: Baseline and approximately Day 40
measure: Change in HLA Allosensitization Profile
timeFrame: Baseline and approximately Day 40
measure: Change in Vasoactive-Inotropic Score (VIS)
timeFrame: Baseline and approximately Day 40
measure: Six Minute Walk Test (6MWT)
timeFrame: 14 months
measure: Change in Upper Extremity Hand Strength
timeFrame: 14 months
measure: Change in Montreal Cognitive Assessment (MoCA)
timeFrame: 14 months
measure: Units of Blood Used During Heart Transplant
timeFrame: Day of Transplant (Approximately Day 40)
measure: Primary Graft Failure
timeFrame: 14 months
measure: Early Transplant Rejection
timeFrame: 14 months
measure: AlloMap Score
timeFrame: After Transplant, approximately Day 40
measure: Allosure Score
timeFrame: After Transplant, approximately Day 40
measure: Post-Transplant Length of Stay
timeFrame: Up to 14 months (approximately 420 days)
Other outcomes:
Locations:
city: New York
country: United States
facility: Columbia University
state: New York
Study officials:
affiliation: Columbia University
name: Adil Yunis, MS
role: PRINCIPAL_INVESTIGATOR
References: