Angiotensin-Converting Enzyme Inhibition Early After Heart Transplantation

William F. Fearon, Kozo Okada, Jon A. Kobashigawa, Yuhei Kobayashi, Helen Luikart, Sean Sana, Tiffany Daun, Steven A. Chmura, Seema Sinha, Garett Cohen, Yasuhiro Honda, Michael Pham, David B. Lewis, Daniel Bernstein, Alan C. Yeung, Hannah A. Valantine, Kiran Khush

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


Background Cardiac allograft vasculopathy (CAV) remains a leading cause of mortality after heart transplantation (HT). Angiotensin-converting enzyme inhibitors (ACEIs) may retard the development of CAV but have not been well studied after HT. Objectives This study tested the safety and efficacy of the ACEI ramipril on the development of CAV early after HT. Methods In this prospective, multicenter, randomized, double-blind, placebo-controlled trial, 96 HT recipients were randomized to undergo ramipril or placebo therapy. They underwent coronary angiography, endothelial function testing; measurements of fractional flow reserve (FFR) and coronary flow reserve (CFR) and the index of microcirculatory resistance (IMR); and intravascular ultrasonography (IVUS) of the left anterior descending coronary artery, within 8 weeks of HT. At 1 year, the invasive assessment was repeated. Circulating endothelial progenitor cells (EPCs) were quantified at baseline and 1 year. Results Plaque volumes at 1 year were similar between the ramipril and placebo groups (162.1 ± 70.5 mm3 vs. 177.3 ± 94.3 mm3, respectively; p = 0.73). Patients receiving ramipril had improvement in microvascular function as shown by a significant decrease in IMR (21.4 ± 14.7 to 14.4 ± 6.3; p = 0.001) and increase in CFR (3.8 ± 1.7 to 4.8 ± 1.5; p = 0.017), from baseline to 1 year. This did not occur with IMR (17.4 ± 8.4 to 21.5 ± 20.0; p = 0.72) or CFR (4.1 ± 1.8 to 4.1 ± 2.2; p = 0.60) in the placebo-treated patients. EPCs decreased significantly at 1 year in the placebo group but not in the ramipril group. Conclusions Ramipril does not slow development of epicardial plaque volume but does stabilize levels of endothelial progenitor cells and improve microvascular function, which have been associated with improved long-term survival after HT.

Original languageEnglish (US)
Pages (from-to)2832-2841
Number of pages10
JournalJournal of the American College of Cardiology
Issue number23
StatePublished - Jun 13 2017
Externally publishedYes


  • cardiac allograft vasculopathy
  • coronary physiology
  • microcirculation

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


Dive into the research topics of 'Angiotensin-Converting Enzyme Inhibition Early After Heart Transplantation'. Together they form a unique fingerprint.

Cite this