The Present and Future
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Allograft Vasculopathy: The Achilles’ Heel of Heart Transplantation

https://doi.org/10.1016/j.jacc.2016.04.033Get rights and content
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Abstract

Cardiac allograft vasculopathy (CAV) remains the Achilles’ heel of long-term survival after heart transplantation. Almost one-third of patients develop CAV by 5 years post-transplant and 1 in 8 deaths beyond a year are due to CAV. Abnormal vascular fibroproliferation in CAV occurs as a result of coronary endothelial inflammation, injury, and dysfunction triggered by immune and nonimmune insults. Surveillance methods for CAV have significant limitations, particularly for detecting early disease. Areas of investigation include myocardial and coronary blood flow quantification, and intracoronary imaging to detect early changes in the vessel wall and high-risk plaques. Treatment approaches continue to evolve, but prevention remains the focus. Newer mammalian target of rapamycin inhibitors can significantly delay the progression of CAV; however, their optimal use remains to be established. Further investigation is needed to understand the complex pathophysiology of CAV, improve surveillance techniques, and develop therapies to prevent and slow disease progression.

Key Words

coronary and myocardial flow reserve
endothelial injury
heart transplant
intimal hyperplasia
intravascular ultrasound
mammalian target of rapamycin inhibitors

Abbreviations and Acronyms

CAV
cardiac allograft vasculopathy
CFR
coronary flow reserve
DSE
dobutamine stress echocardiography
HLA
human leukocyte antigen
IVUS
intravascular ultrasound
MIT
maximal intimal thickness
mTORi
mammalian target of rapamycin inhibitor
OCT
optical coherence tomography
PET
positron emission tomography
SPECT
single-photon emission computed tomography

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Dr. Bhatt has served on the advisory board for Cardax, Elsevier Practice Update Cardiology, Medscape Cardiology, and Regado Biosciences; has served on the board of directors for Boston VA Research Institute and Society of Cardiovascular Patient Care; has served as the chair of the American Heart Association Quality Oversight Committee; has served on data monitoring committees for the Duke Clinical Research Institute, Harvard Clinical Research Institute, Mayo Clinic, and Population Health Research Institute; has received honoraria from the American College of Cardiology (senior associate editor, Clinical Trials and News, ACC.org), Belvoir Publications (Editor-in-Chief, Harvard Heart Letter), Duke Clinical Research Institute (clinical trial steering committees), Harvard Clinical Research Institute (clinical trial steering committee), HMP Communications (Editor-in-Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (guest editor, associate editor), Population Health Research Institute (clinical trial steering committee), Slack Publications (chief medical editor, Cardiology Today’s Intervention), Society of Cardiovascular Patient Care (secretary/treasurer), and WebMD (CME steering committees); has served as the deputy editor for Clinical Cardiology; has served as the vice-chair of the NCDR-ACTION Registry Steering Committee; has served as the chair of the VA CART Research and Publications Committee; has received research funding from Amarin, AstraZeneca, Bristol-Myers Squibb, Eisai, Ethicon, Forest Laboratories, Ischemix, Medtronic, Pfizer, Roche, Sanofi, and The Medicines Company; has received royalties from Elsevier (editor, Cardiovascular Intervention: A Companion to Braunwald’s Heart Disease); has served as a site coinvestigator for Biotronik, Boston Scientific, and St. Jude Medical; has served as a trustee for American College of Cardiology; and has conducted unfunded research for FlowCo, PLx Pharma, and Takeda. Dr. Beanlands has served as a consultant for and received grant support from Jubilant DraxImage, Lantheus Medical Imaging, and General Electric; and has received research grant support from GE Healthcare, Lantheus Medical Imaging, and Jubilant DraxImage. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Listen to this manuscript's audio summary by JACC Editor-in-Chief Dr. Valentin Fuster.