Regadenoson-induced hyperemia for absolute
myocardial blood ﬂow quantitation by
ammonia PET and detection of cardiac allograft
R. Sevag Packard, MD, PhD,
and Jamshid Maddahi, MD, FACC,
Division of Cardiology, Department of Medicine, David Geffen School of Medicine, University
of California, Los Angeles, Los Angeles, CA
Ronald Reagan UCLA Medical Center, Los Angeles, CA
Veterans Affairs West Los Angeles Medical Center, Los Angeles, CA
Nuclear Medicine Clinic, Department of Molecular and Medical Pharmacology, David Geffen
School of Medicine, University of California, Los Angeles, Los Angeles, CA
Received Oct 4, 2016; accepted Oct 5, 2016
See related article, pp. 1134–1144
In this issue of the Journal of Nuclear CardiologyÒ,
Miguel H. Pampolini and associates report on non-in-
vasive quantitation of myocardial blood ﬂow (MBF) by
regadenoson positron emission tomography (PET)
imaging for assessing cardiac allograft vasculopathy
(CAV) in orthotopic heart transplantation (OHT)
Non-invasive detection of post-transplant
vasculopathy continues to be challenging, and PET
quantitation of MBF may be uniquely positioned to
address this challenge.
World-wide, there remains a large discrepancy
between the need for OHT in patients with end-stage
heart disease and available donors.
In the United States,
the yearly number of OHT has been stable over the past
2 decades at *2500 cases per year.
This paucity of
available organs has led to the rise of ventricular assist
devices implanted as destination therapy
and to a very
rigorous transplant recipient selection process.
lowing OHT, transplant recipients are exposed to a
stringent surveillance program periodically screening for
graft rejection, graft failure, infection, malignancy, and
CAV, or transplant vasculopathy,
accounts for *10% of deaths in OHT recipients starting
at 1–3 years post-transplant.
The pathophysiology of CAV involves activation of
both the innate and adaptive immune responses in an
attempt to reject the transplanted heart, leading to coro-
nary inﬂammation, endothelial dysfunction, and
migration and proliferation of vascular smooth muscle
Contrary to atherosclerotic disease, CAV is char-
acterized by the presence of an intact elastic lamina and a
diffuse disease affecting the entire coronary tree with
intimal hyperplasia composed of vascular smooth muscle
Risk factors for the development of CAV include
traditional risk factors associated with atherosclerosis,
and additional transplant-associated risk factors such as
donor-speciﬁc antibodies and cytomegalovirus infec-
The end-result of this disease process is the diffuse,
concentric, and ﬁbrotic intimal thickening of the coronary
arteries, leading to extensive coronary artery disease
(CAD) and myocardial ischemia.
Given the transplanted heart is denervated—
although not permanently—anginal symptoms are
and screening methods have to be utilized
for coronary artery assessment. The diffuse nature of
CAV often renders angiography insensitive and an
Funding Dr. Packard is supported by AHA Grant 16SDG30910007.
Dr. Maddahi is supported by a research grant from Lantheus Med-
Reprint requests: Jamshid Maddahi, MD, FACC, FASNC, Nuclear
Medicine Clinic, Department of Molecular and Medical Pharma-
cology, David Geffen School of Medicine, University of California,
Los Angeles, 100 Medical Plaza, Suite 410, Los Angeles, CA,
90095, USA; email@example.com
J Nucl Cardiol 2017;24:1145–48.
Copyright Ó 2017 American Society of Nuclear Cardiology.