Angiotensin Converting Enzyme (ACE) Inhibition and Cardiac Allograft Vasculopathy

2014-08-27 03:15:31 | BioPortfolio


Cardiac transplantation is the ultimate treatment option for patients with end stage heart failure.

Cardiac allograft vasculopathy remains a leading cause of morbidity and mortality after transplantation.

Angiotensin converting enzyme inhibitors are used in less than one half of transplant recipients. Preliminary data suggest that angiotensin converting enzyme inhibitors retard the atherosclerotic plaque development that is the hallmark of cardiac allograft vasculopathy. Moreover, this class of drug appears to increase circulating endothelial progenitor cell number and has anti-inflammatory properties, both of which improve endothelial dysfunction, the key precursor to the development of cardiac allograft vasculopathy.

The objective of this project is to investigate the role of an angiotensin converting enzyme inhibitor, ramipril, in preventing the development of cardiac allograft vasculopathy. During the first month after cardiac transplantation subjects will undergo coronary angiography with intravascular ultrasound measurements of plaque volume in the left anterior descending coronary artery. Using a coronary pressure wire, epicardial artery and microvascular physiology will be assessed. Finally, endothelial function and mediators of endothelial function, including circulating endothelial progenitor cells, will be measured. Subjects will then be randomized in a double blind fashion to either ramipril or placebo. After 1 year, the above assessment will be repeated. The primary endpoint will be the development of cardiac allograft vasculopathy based on intravascular ultrasound-derived parameters. The second aim will be to assess the effect of ramipril on endothelial dysfunction early after transplantation. The final aim is to determine the impact of ramipril on coronary physiology early after transplantation.


During the first 4 years of this study, we plan to recruit patients within the first month after OHT. As has become routine at Stanford, study subjects will undergo baseline coronary angiography and IVUS assessment of their left anterior descending coronary artery. Coronary endothelial function will be assessed as well transmyocardial levels of ADMA and other mediators of endothelial function. Blood samples will be obtained for analyzing circulating EPC number and function. Epicardial and microvascular coronary physiology in the left anterior descending coronary artery will be determined by measuring FFR and IMR with a coronary pressure wire(in the adults only). Subjects will then be randomized to either the ACE I(Ramipril), or to placebo, in addition to their usual medications. During years 2 through 5 of this project, study subjects will undergo the above routine invasive assessments at 1 year after OHT. During the 5th year of this project, data analysis and manuscript preparation will occur.

Table 2. Patient Flowchart Time post OHT Event 0-4 Weeks Recruitment and enrollment 4-6 Weeks Baseline angiogram, endothelial function, coronary physiology and IVUS studies 4-6 (at time of baseline)Weeks Baseline blood sampling for circulating EPC studies 4-6 Weeks Randomization to ramipril or placebo to begin one week after baseline studies 5-7 Weeks Titration up of ramipril or placebo Month 3 and month 6: blood sampling for EPC studies. 11-13 Months 1 year angiogram, endothelial function, coronary physiology and IVUS studies 11-13 Months 1 year blood sampling for circulating EPC studies The primary endpoint of the study will be change in plaque volume as determined by IVUS analysis at baseline and 1 year later, between those treated with ramipril compared to those treated with placebo.

Secondary endpoints will include change in circulating EPC number and function, change in ADMA levels,change in coronary endothelium-dependent vasodilation, and change in coronary physiology (FFR and IMR)from baseline to 1 year. Although there are multiple potential mechanisms by which ACE I might reduce CAV, evaluating each of these is beyond the scope of this project. For this reason, we will focus on the likely common final pathway of endothelial dysfunction mediated by dysregulation of ADMA and NOS, as well as changes in EPCs. If this study shows a benefit to ACE I therapy in this population, the goal of future studies will be to determine the exact mechanism by which this occurs and to perform a large, multicenter study comparing ACE I to placebo with hard clinical endpoints. Study visits include two major time points 1) baseline angiogram and IVUS which include recording of angiographic data, lab data, clinical data. 2)assessment at the usual follow up periods post transplant, and these data points will also be collected for research purposes. after base line which usually occurs one month post transplant plus or minus 2 weeks. F/u = q 2 weeks until two months out from tx, then once per month until six months out from TX, then every two months until the patient is 12 months out from TX. Each routine f/u visit includes a physical exam,vital signs, echocardiogram, chest x-ray, a complete metabolic panel ( contains a Creatinine), Complete blood count, immunosuppressant drug blood levels, and a heart biopsy (at the same intervals described above).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment


Cardiac Allograft Vasculopathy


Ramipril, Placebo


VA Palo Alto Health Care System
Palo Alto
United States


Enrolling by invitation


Stanford University

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:15:31-0400

Clinical Trials [1439 Associated Clinical Trials listed on BioPortfolio]

Cardiac Allograft Vasculopathy and Dobutamine Stress Echocardiography / Brain Natriuretic Peptide Coupling

Primary purpose :To early detect cardiac allograft vasculopathy and to identify patients with high risk of cardiac events, by coupling the analysis of the kinetics of the brain natriuretic...

Impact of Level and Quality of Immunosuppression on Onset and Pattern of Cardiac Allograft Vasculopathy Evaluated by OCT

The aim of this study is to use the high resolution of optical coherence tomography to assess the prevalence of different types of cardiac allograft vasculopathy (CAV) in cardiac transplan...

Cholesterol Lowering With EVOLocumab to Prevent Cardiac Allograft Vasculopathy in De-novo Heart Transplant Recipients

The main goal of this study is to evaluate the effect of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor evolocumab on cardiac allograft vasculopathy in de novo heart t...

Effect of Ivabradine on Exercise Capacity After Heart Transplantation

This study evaluates whether treatment with ivabradine compared to placebo can improve exercise capacity in long-term heart transplant recipients with cardiac allograft vasculopathy and el...

Early Post Transplant Cardiac Allograft Vasculopathy

Heart transplantation is an effective life-saving treatment for patients with end-stage heart disease. After a transplant, the new heart may develop narrowing in the arteries, causing hear...

PubMed Articles [4884 Associated PubMed Articles listed on BioPortfolio]

Semi-quantitative myocardial perfusion MRI in heart transplant recipients at rest: repeatability in healthy controls and assessment of cardiac allograft vasculopathy.

Cardiac Allograft Vasculopathy (CAV) is a major cause of chronic cardiac allograft failure. Invasive coronary angiography (ICA) and intravascular ultrasound (IVUS) are the current diagnostic methods. ...

Cardiac Allograft Vasculopathy: The Enduring Enemy of Cardiac Transplantation.

Cardiac allograft vasculopathy remains a major limiting factor in the long-term survival of the heart transplant recipient. Our understanding of its pathogenesis is continuously evolving as advances i...

Mild acute cellular rejection and development of cardiac allograft vasculopathy assessed by intravascular ultrasound and coronary angiography in heart transplant recipients - a SCHEDULE trial substudy.

To evaluate the association between mild acute cellular rejection (ACR) and the development of cardiac allograft vasculopathy (CAV) after heart transplantation (HTx).

Coronary computed tomographic angiography quantitative plaque analysis improves detection of early cardiac allograft vasculopathy: A pilot study.

Cardiac allograft vasculopathy (CAV) is an increasingly important complication following cardiac transplant. We assessed the additive diagnostic benefit of quantitative plaque analysis in patients und...

B cell clonal expansion within immune infiltrates in human cardiac allograft vasculopathy.

Cardiac allograft vasculopathy (CAV) is associated with intragraft B cell infiltrates. Here, we studied the clonal composition of B cell infiltrates using 4 graft specimens with CAV. Using deep sequen...

Medical and Biotech [MESH] Definitions

A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat.

Misunderstanding among individuals, frequently research subjects, of scientific methods such as randomization and placebo controls.

Visualization of the heart structure and cardiac blood flow for diagnostic evaluation or to guide cardiac procedures via techniques including ENDOSCOPY (cardiac endoscopy, sometimes refered to as cardioscopy), RADIONUCLIDE IMAGING; MAGNETIC RESONANCE IMAGING; TOMOGRAPHY; or ULTRASONOGRAPHY.

Striated muscle cells found in the heart. They are derived from cardiac myoblasts (MYOBLASTS, CARDIAC).

Precursor cells destined to differentiate into cardiac myocytes (MYOCYTES, CARDIAC).

More From BioPortfolio on "Angiotensin Converting Enzyme (ACE) Inhibition and Cardiac Allograft Vasculopathy"

Quick Search

Relevant Topics

Organ transplantation is the moving of an organ from one body to another or from a donor site to another location on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative ...

Cardiovascular disease (CVD)
Acute Coronary Syndromes (ACS) Blood Cardiovascular Dialysis Hypertension Stent Stroke Vascular Cardiovascular disease (CVD) includes all the diseases of the heart and circulation including coronary heart disease (angina...

Searches Linking to this Trial