A Prospective Study of Recovery Mechanisms in Heart Transplant Eligible Patients With Cardiogenic Shock on Impella 5.5 Support
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Change in Left Ventricular Ejection Fraction (LVEF)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Change in Left Ventricular Ejection Fraction (LVEF)
时间窗: Baseline and approximately Day 40
A change in echocardiographic index will be evaluated by measuring a change in LVEF before and after Impella support at minimal pump setting.
Change in Left Ventricular End-Diastolic Diameter (LVEDD)
时间窗: Baseline and approximately Day 40
A change in echocardiographic index will be evaluated by measuring a change in LVEDD before and after Impella support at minimal pump setting.
Change in Cardiac Index
时间窗: Baseline and approximately Day 40
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).
Change in Pulmonary Capillary Wedge Pressure
时间窗: Baseline and approximately Day 40
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).
次要结局
- Change in Vasoactive-Inotropic Score (VIS)(Baseline and approximately Day 40)
- Six Minute Walk Test (6MWT)(14 months)
- Change in Upper Extremity Hand Strength(14 months)
- Units of Blood Used During Heart Transplant(Day of Transplant (Approximately Day 40))
- Primary Graft Failure(14 months)
- Early Transplant Rejection(14 months)
- AlloMap Score(After Transplant, approximately Day 40)
- Allosure Score(After Transplant, approximately Day 40)
- Post-Transplant Length of Stay(Up to 14 months (approximately 420 days))
- Transplant Waitlist Outcome(14 months)
- Number of Participants Escalated(14 months)
- Waitlist time on Impella Support(14 months)
- Change in aminoterminal pro B-type natriuretic peptide (NT-proBNP)(Baseline and approximately Day 40)
- Change in Blood Urea Nitrogen (BUN)(Baseline and approximately Day 40)
- Change in Estimated Glomerular Filtration Rate (eGFR)(Baseline and approximately Day 40)
- Change in Cystatin C(Baseline and approximately Day 40)
- Change in Alanine Aminotransferase (ALT)(Baseline and approximately Day 40)
- Change in Total Bilirubin(Baseline and approximately Day 40)
- Change in Aspartate Aminotransferase (AST)(Baseline and approximately Day 40)
- Change in International Normalized Ratio (INR)(Baseline and approximately Day 40)
- Change in Hemoglobin(Baseline and approximately Day 40)
- Change in Platelet Count(Baseline and approximately Day 40)
- Change in Lactate dehydrogenase (LDH)(Baseline and approximately Day 40)
- Change in Plasma Free Hemoglobin(Baseline and approximately Day 40)
- Change in Albumin(Baseline and approximately Day 40)
- Change in Prealbumin(Baseline and approximately Day 40)
- Change in C-Reactive Protein (CRP)(Baseline and approximately Day 40)
- Change in Erythrocyte Sedimentation Rate (ESR)(Baseline and approximately Day 40)
- Change in Procalcitonin(Baseline and approximately Day 40)
- Change in HLA Allosensitization Profile(Baseline and approximately Day 40)
- Change in Alanine Aminotransferase (ALT)(Baseline and approximately Day 40)
- Change in Hemoglobin(Baseline and approximately Day 40)
- Change in Vasoactive-Inotropic Score (VIS)(Baseline and approximately Day 40)
- Six Minute Walk Test (6MWT)(14 months)
- Change in Upper Extremity Hand Strength(14 months)
- Units of Blood Used During Heart Transplant(Day of Transplant (Approximately Day 40))
- Primary Graft Failure(14 months)
- Early Transplant Rejection(14 months)
- AlloMap Score(After Transplant, approximately Day 40)
- Allosure Score(After Transplant, approximately Day 40)
- Post-Transplant Length of Stay(Up to 14 months (approximately 420 days))
- Change in Aspartate Aminotransferase (AST)(Baseline and approximately Day 40)
研究者
Adil A Yunis, MD
Assistant Professor of Medicine
Columbia University