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(Circulation. 1995;91:1706-1713.)
© 1995 American Heart Association, Inc.
Articles |
Occult and Frequent Transmission of Atherosclerotic Coronary Disease With Cardiac Transplantation
Insights From Intravascular Ultrasound
From the Department of Cardiology, The Cleveland Clinic Foundation, Cleveland, Ohio.
Correspondence to E. Murat Tuzcu, MD, Department of Cardiology, The Cleveland Clinic Foundation, 9500 Euclid Ave, Desk F-25, Cleveland, OH 44195-5066.
 |
Abstract |
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 Top Abstract IntroductionMethods Results Discussion References |
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Background Transplant coronary artery disease is a major cause of morbidity and mortality after cardiac transplantation. However, limited data exist regarding the potential contribution of coronary atherosclerosis in the donor heart to cardiac-allograft vasculopathy.
Methods and Results We performed quantitative coronary
angiography and intravascular ultrasound imaging in 50 of 62
consecutive heart-transplant recipients (40 men, 10 women, mean age,
53±9 years) 4.6±2.6 weeks after transplantation. The donor
population
consisted of 30 men and 20 women (mean age, 32±12 years). Ultrasound
imaging visualized all three coronary arteries in 22 patients, two
coronary arteries in 23, and one coronary artery in 5. Ultrasound
imaging detected coronary atherosclerosis (intimal thickness 
0.5 mm)
in 28 patients (56%). However, the angiography was abnormal in only 13
patients (26%). The sensitivity and specificity of coronary
angiography were 43% and 95%, respectively. With ultrasound, the
average atherosclerotic plaque thickness was 1.3±0.6 mm and the
cross-sectional area narrowing was 34±16%. Atherosclerotic
involvement frequently was focal (85%), eccentric (mean eccentricity
index, 87±8), and near arterial bifurcations. Donors of the transplant
recipients with coronary atherosclerosis were older than those without
atherosclerosis (37±12 versus 25±10 years, P=.001).
Maximal intimal
thickness correlated with donor age (r=.54,
P=.0001). Multivariate analysis demonstrated that donor
age (P=.0001), male sex of donor (P=.0006),
and
recipient age (P=.03) were independent predictors of
atherosclerosis.
Conclusions Coronary atherosclerosis is frequently but inadvertently transmitted by means of cardiac transplantation from the donor to the recipient. Long-term outcomes of donor-transmitted coronary artery disease will require further evaluation.
Key Words: transplantation • coronary disease • ultrasonics
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Introduction |
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TopAbstractIntroductionMethods Results Discussion References |
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Survival rates after cardiac transplantation have improved steadily during the past 2 decades. Presently, 1-year survival rates average 80% to 90% at most active centers.1 2 After the first year after transplantation, cardiac-allograft vasculopathy represents the principal cause of death.3 4 Necropsy examinations have described cardiac-allograft vasculopathy as a diffuse, obliterative process characterized by concentric intimal proliferation.5 6 7 Prior reports8 9 have emphasized that the predominant mechanism for genesis of transplant vasculopathy is immune injury with resulting intimal hyperplasia. Transplant coronary disease eventually results in multiple myocardial infarctions, which lead to accelerated graft failure or sudden cardiac death.
Both postmortem and intravascular ultrasound imaging studies have demonstrated that angiography underestimates the extent and severity of transplant vasculopathy.10 11 12 13 Although most centers perform routine surveillance angiography at annual catheterization, this screening process often fails to detect coronary disease. There is limited information regarding the prevalence of atherosclerosis in donor hearts and its effect on coronary disease after transplantation. Accordingly, we examined this phenomenon by performing quantitative coronary angiography and intravascular ultrasound imaging soon after cardiac transplantation. We sought to determine the frequency and morphological patterns of atherosclerosis transmitted from heart donors to recipients.
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Methods |
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TopAbstractIntroductionMethods Results Discussion References |
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Patient Population
The study group consisted of patients who underwent cardiac transplantation between December 31, 1992, and February 14, 1994. Patients who were ineligible for cardiac catheterization, who died during hospitalization, or who did not give informed consent were excluded. The study protocol was approved by the Institutional Review Board of The Cleveland Clinic Foundation.
Cardiac Catheterization
Recipients were studied within 2
months after cardiac
transplantation. All patients underwent right and left heart
catheterization, endomyocardial biopsy, coronary angiography, and
intravascular ultrasound imaging. After nitroglycerin was administered
sublingually, coronary arteriography was performed with large-lumen 7F
coronary-guiding catheters.14 Multiple angiographic views
were obtained for optimal visualization of the coronary arteries.
Coronary Intravascular Ultrasound Imaging
Intravascular
ultrasound imaging was performed on the recipients
with a 30 MHz 3.5F ultrasound catheter (Boston Scientific) interfaced
with a dedicated scanner (Hewlett Packard). The ultrasound catheter
consisted of a 135-cm-long monorail device with a transducer enclosed
in an acoustically transparent housing that was 20 mm from the tip. A
driveshaft cable rotated the transducer at 1800 rpm to generate a
360° imaging plane angled 15° forward from perpendicular to the
long axis of the catheter. The axial resolution of the imaging system,
which varied with distance, averaged 80 to 100 µm, whereas lateral
resolution ranged from 150 to 200 µm. This device generated
ultrasound images at 30 frames per second, and continuously recorded
these images on 1/2-in Super-VHS videotape.
After coronary angiography, recipients were given 3000 to 5000 U IV heparin before being examined by intravascular ultrasound imaging. The operator used fluoroscopic guidance to place a 0.014-in high-torque angioplasty guide wire at a distal location in the target vessel. The ultrasound catheter was placed over the guide wire at the most distal site in the coronary artery to which it could be advanced safely. The ultrasound catheter was then withdrawn gradually from this distal location during continuous imaging. At sites of atherosclerosis and adjacent normal segments, pullback was paused for identification. A cineangiogram and an audio recording documented the location of the imaging probe and its proximity to branches and other anatomic landmarks at each of these sites. Proximal, mid, and distal segments of the three major epicardial coronary arteries, defined according to Coronary Artery Surgery Study (CASS) classifications, were targeted for imaging.15
Ultrasound Imaging Analysis
The intravascular ultrasound
images were analyzed by blinded
observers in the intravascular ultrasound imaging core laboratory. For
each site examined, a short segment (10 to 20 seconds) of videotape was
digitized at 30 frames per second into a 640x480-pixel matrix image
with a 24-bit gray scale. The full-motion sequence was examined frame
by frame to select for analysis the image with the most
atherosclerosis.
The selected frames were used to make the following
measurements: (1)
Maximal intimal thickness was measured as the greatest distance from
the intimal leading edge to media-adventitia border, (2) minimal
intimal thickness as the shortest distance from the intimal leading
edge to media-adventitia border, (3) minimal luminal diameter as the
shortest distance between opposing intimal leading edges, (4) lumen
area as the area within the boundaries of the intimal leading edge, (5)
vessel area as the area within the media-adventitia border, and (6)
plaque cross-sectional area as the difference between vessel and lumen
areas. Also, a relative measure of ultrasound percent area reduction
was computed as follows: lumen area divided by vessel area multiplied
by 100 (Fig 1
).
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Patients were divided into
atherosclerotic and nonatherosclerotic
subgroups that were stratified by the maximal intimal thickness of all
examined sites. The atherosclerotic group included patients with
intimal thickness 0.5 mm, whereas the nonatherosclerotic group
included those with a maximal intimal thickness <0.5 mm. The
distribution pattern of atherosclerosis was assessed longitudinally and
circumferentially. Diffuse disease was defined as intimal thickening of
the entire length of the artery, whereas focal disease consisted of
intimal thickening of isolated sites. The circumferential distribution
of atherosclerotic plaque was determined as follows.
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Angiographic Analysis
Cineangiograms were reviewed in the
core cineangiography
laboratory by an experienced angiographer blinded to the results of the
ultrasound imaging study. The angiograms were projected onto a screen
at a fixed distance with a rear-projection system (Tagarno 35AX). For
each coronary artery, the CASS segment classification system was used
to identify the most distal site imaged by ultrasound. Stenosis
severity at sites showing any luminal narrowing was measured with an
Atari digital caliper system (Sandhill Scientific, Inc). For each
identifiable lesion, the operator determined vessel diameter at the
stenosis and at an adjacent angiographically normal reference site to
quantify percent diameter stenosis.
Statistical Analysis
Normally distributed data were reported
as mean±SD.
2- test or Fisher's exact test was used to find
significant associations between categorical variables. An unpaired
t test was used to test for differences between the mean
values for continuous variables in subgroups. Pearson's correlations
were used to test for relations between continuous variables. Stepwise
linear regression was used to determine which factors (age, sex,
cytomegalovirus [CMV] virus titers for donors and recipients,
ischemic time for the donor heart, rejection episodes, donor family
history for coronary artery disease, smoking history, and hypertension)
were significantly related to atherosclerosis after adjustment for
other significant factors. A value of P.05 was considered
statistically significant.
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Results |
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TopAbstractIntroductionMethods Results Discussion References |
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Patient Characteristics
Sixty-two adult patients underwent cardiac transplantation between December 30, 1992, and February 14, 1994. All but 5 underwent cardiac catheterization within 2 months after transplantation. The 5 patients not examined included 4 who died soon after the operation (1 from multiorgan failure, 1 from cerebral hemorrhage, 1 from sepsis, and 1 from aortic rupture). One additional patient had severe medical problems precluding catheterization. Of the remaining 57 patients, 50 underwent successful intravascular ultrasound imaging. The 7 patients who did not undergo imaging included 3 patients with scheduling constraints, 2 with angiographically evident severe coronary artery disease, and 2 who experienced technical problems related to the equipment. The 50 cardiac transplant recipients were studied an average of 4.6±2.6 weeks after the operation. This cohort included 40 men and 10 women with a mean age of 53±9 years. Of the 50 recipients, 40 had positive CMV titers and 14 had experienced at least one episode of rejection requiring treatment before catheterization (Table 1
).
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The donor population consisted of 30 men and 20 women with a mean age
of 32±12 years. The ischemic time for the donor heart, defined as the
interval between removal of the donor heart and transplantation,
averaged 134±40 minutes. Of the 50 donors, 31 had positive CMV titers.
The medical and social histories of donors were not complete in some
cases. Twenty-four of 42 donors were known smokers, 4 of 42 were
hypertensive, and 3 of 24 had a family history of coronary artery
disease. Because most donors were identified after major trauma,
reliable basal lipid levels were not available (Table 1
).
All three major epicardial coronary arteries were imaged
successfully in 22 patients, two arteries were imaged in 23 patients,
and only one vessel was imaged in 5 patients (Table 2).
Thus, 117 first-order epicardial vessels were examined in the 50
patients. The right coronary artery was not imaged in 19 patients, the
left circumflex in 12, and the left anterior descending in 2. Arteries
were not imaged in 14 patients because of tortuosity, in 8 because of a
small-caliber vessel, in 5 because of a nondominant right coronary
artery, in 4 because of coronary spasm, and in 2 for technical reasons.
Of the 450 CASS segments targeted, 255 (112 proximal, 96 mid, and 47
distal) were imaged (Table 2), with no complications other than
reversible coronary spasm.
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Coronary Atherosclerosis
In 22 patients, the appearance of
the coronary arteries with
ultrasound imaging was normal, with maximal intimal thickness <0.5 mm
(Fig 2). By applying a criterion for atherosclerosis
requiring an intimal thickness 0.5 mm, it was determined that 28
patients (56%) had unequivocal evidence of disease (Fig 3). In
this subgroup, maximal intimal thickness averaged
1.3±0.6 mm; mean luminal diameter, 3.4±1.1 mm; and average
luminal
cross-sectional area, 11.8±5.8 mm2. The plaque
cross-sectional area averaged 5.5±2.4 mm2, which
represented a cross-sectional area reduction of 34±16%.
Thus, a significant amount of atherosclerosis was detected in more than
half the recipients studied early after transplantation.
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Distribution of Atherosclerosis
Atherosclerotic plaque
involvement was focal rather than diffuse
in 24 of 28 patients. In patients with focal disease, plaque was
observed most frequently near arterial bifurcation sites (Fig
4). In 14 patients (50%), atherosclerotic involvement
was evident near the left anterior descending–circumflex artery
bifurcation. Of the 14 patients, 9 had plaque on the left anterior
descending side of the bifurcation, 3 on the circumflex side, and 2 on
both sides. In all cases, the plaque was on the wall opposite the
arterial carina of the branching vessel. An atheroma was found near the
left anterior descending–diagonal artery bifurcation in 8 patients,
and plaque was seen at the circumflex-obtuse marginal bifurcation in 2
patients. One patient had a plaque in the right coronary artery at the
site of bifurcation in a right ventricular branch. These patterns
served to emphasize the focal nature of plaque distribution in patients
studied early after transplantation. Of the 28 patients with
atherosclerosis, 19 had an atherosclerotic plaque in more than one
arterial segment.
|
A distinctly eccentric pattern of atherosclerosis was
evident in these
28 patients (Fig 5). The mean eccentricity index was
87±8%, which demonstrated that nearly all of the plaque was located
on one side of the artery. Of the 28 recipients who had atherosclerotic
involvement, the eccentricity index was >50% in every patient and was
>75% in 26 of 28. In all cases, the surfaces of the coronary plaques
were smooth. There was no evidence of ulcerated plaque or plaque
dissection in any of the imaged arteries. Calcified elements occurred
in the plaques of 9 of 28 patients.
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Risk Factors for Atherosclerosis
Donor age and recipient age
were the only variables found to be
significantly different between the atherosclerotic and
nonatherosclerotic groups by univariate analysis. Although all
donors were relatively young, the donors for recipients who had
atherosclerotic involvement were significantly older (37±12 versus
25±10 years, P=.0003, Table 1).
Linear-regression
analysis revealed a moderate correlation between maximal plaque
thickness and donor age (r=.54, P=.0001, Fig
6). A less-significant difference existed between the
two subgroups with regard to recipient age (55±9 versus 49±10
years,
P=.02). Univariate analysis demonstrated no significant
differences for the remaining variables, including donor hypertension,
smoking history, family history of coronary disease, rejection
episodes, donor and recipient CMV titers, time between transplantation
and imaging, ischemic time, and number of vessels and segments
imaged.
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indicates male donors; 
, female
donors.
Multivariate analysis demonstrated that only donor age
(P=.0001), male donor sex (P=.0006), and
recipient age (P=.03) were independent predictors of
atherosclerosis. There was no correlation between recipient and donor
ages (r=.11, P=.43) to explain these findings.
However, when plaque thickness was analyzed with donor age and
recipient age as categorical variables (age <30 or 30) rather than
as continuous factors, only donor age (P=.0001) and donor
sex were significant factors for predicting atherosclerosis
(P=.008, Table 3).
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Angiographic Analysis
Quantitative coronary arteriography
revealed completely normal
coronary arteries in 37 of 50 patients (74%). In the other 13
patients, angiographic stenosis ranged from 10% to 38% (22±7%), and
ultrasound imaging confirmed the presence of a plaque in abnormal
segments in 12 of these patients. Thus, coronary angiography detected
atherosclerosis in only 12 of the 28 patients (43% sensitivity) who
had atherosclerosis but correctly identified 21 of 22 normal cases
(95% specificity, Fig 7). In 3 patients, angiography
detected more than one lesion; some of these lesions were in segments
not imaged by ultrasound. However, in all 3 of these patients,
ultrasound imaging identified atherosclerosis in more than one
segment.
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Discussion |
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TopAbstractIntroductionMethods Results Discussion References |
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Coronary artery disease represents the major cause of late death in patients after cardiac transplantation. Cardiac-allograft vasculopathy has been reported16 17 to be an immunologic process in which intimal injury leads to proliferation and, eventually, to arterial obstruction. The present study, which uses quantitative coronary arteriography and a new high-resolution intravascular ultrasound imaging device, demonstrates an alternative cause. In the first few weeks after transplantation, comprehensive imaging of multiple major epicardial coronary arterial segments revealed typical atherosclerotic plaque in 56% of recipients. Thus, unequivocal evidence of transmission of atherosclerosis from the donor to recipient was present in more than one half of the recipients.
These findings are particularly striking when one considers the
conservative definition that is used in the present study to
classify the presence or absence of atherosclerosis. Although the
normal intima in young subjects consists of only a few cell layers,
limited data are available to describe the range of normal intimal
thickness in adults. In a necropsy study, normal intimal thickness
averaged 0.21 mm (0.10 to 0.28 mm) in 21- to 25-year-old men and 0.25
mm (0.18 to 0.35 mm) in 36- to 40-year-old men.18 In a
comparative ultrasound-histology study, patients with no known coronary
artery disease had intimal thicknesses averaging 0.24±0.11
mm.19 An in vivo ultrasound imaging study20
reported mean intimal thickness in a "normal" population as 0.18
mm, with 95% confidence intervals of 0.06 and 0.30 mm. However, in
normal subjects, intimal thickness and echogenicity increases with age.
Thus, in very young subjects, a distinct laminar structure often is not
evident by intravascular ultrasound.19 20 To avoid
potential controversy regarding interpretation of this study, we used a
high threshold (0.5 mm) for abnormal intimal thickness. This value
represents intimal thicknesses at least three SDs greater than
any published range of normal values.
The pattern of atherosclerotic plaque in these patients was typical of atherosclerosis and distinctly different from immune-mediated transplant vasculopathy. Most atheromas were highly eccentric, with >87% of plaque on one side of the vessel. In addition, the lesions showed a predilection for sites of major bifurcations. Experimental studies suggest that low shear stress along the non–flow-dividing wall might be an important localizing force, in contrast to the high shear stress along the flow-dividing wall (carina at vessel bifurcation).21 The morphological characteristics of the plaques are typical of conventional atherosclerosis and dissimilar to vasculopathy as described in the transplant population.22 Indeed, features characteristic of transplant vasculopathy, particularly diffuse, concentric intimal thickening, were absent in our study group. Thus, it is evident that the atherosclerotic changes were present in the donor hearts and transmitted to the recipients at cardiac transplantation.
This study highlights the limitations of standard coronary arteriography for detecting early transplant coronary disease. Quantitative coronary angiography was relatively insensitive, revealing less than half the lesions identified by intravascular ultrasound imaging. An important explanation for the discrepancy between angiography and ultrasound imaging is provided by the anatomic pattern of early atherosclerosis. As originally described by Glagov et al,23 early coronary disease is characterized by remodeling of the coronary artery, which protects against luminal encroachment of the atherosclerotic plaque. Thus, segments with major intimal thickening retain a lumen size virtually identical to adjacent, uninvolved sites. In the absence of luminal narrowing, angiography fails to detect early disease.
Few demographic characteristics were useful for predicting the likelihood of donor atherosclerosis. Multiple-regression analysis showed only donor age, recipient age, and donor sex to be independent predictors. The strongest predictor was donor age, which correlated significantly with intimal thickness. Although donor sex was not (univariately) associated with maximal intimal thickness, it became a significant factor after adjusting for donor age. It is not surprising that hearts from older men tended to have a higher prevalence of atherosclerosis, since age and male sex are well-known risk factors for coronary disease. It is more difficult to explain the unfavorable effect of recipient age on atherosclerosis early after transplantation. Acute rejection,24 25 CMV infection,26 27 and conventional risk factors have been suggested to be possible contributors to the development of chronic transplant coronary disease, but were not significant in this study. However, information about donor hypertension, smoking, family history, and hypercholesterolemia was incomplete. Thus, a full understanding of the relation between donor risk factors and early atherosclerosis cannot be stated conclusively.
In a recent report from St Goar et al,28 with a larger (4.3F) earlier-generation intravascular ultrasound catheter, 25 patients were studied within 1 month of cardiac transplantation. Imaging was limited to segments extending from the ostium of the left main coronary artery to the midportion of the left anterior descending coronary artery. In 5 of 25 patients, there was eccentric intimal thickening >0.5 mm. The difference in the prevalence of atherosclerosis between the study by St Goar et al and ours is explained by several factors. In the present study, imaging was more extensive and an improved, low-profile 3.5F ultrasound probe was used. This permitted examination of multiple segments from major epicardial coronary arteries in 86% of patients. At least two of the three major coronary arteries were imaged in 90% of recipients. In addition, our study population was larger and donors were older (32±12 versus 28±8 years old).
These in vivo findings provide strong evidence as to the high prevalence of coronary atherosclerosis in young and middle-aged Americans. These findings are consistent with autopsy studies performed on large populations of trauma victims during the Korean and Vietnam wars.29 30 During the Korean War, atherosclerotic plaques with a wide range of stenoses (10% to 90%) were found in 117 of 300 young soldiers.29 Autopsy studies on American soldiers killed in Vietnam revealed that 45% had some coronary atherosclerosis.30 In both necropsy studies, all the deceased were men and mean subject age was 22 years old, whereas in our study, 40% of the donors were women and the mean donor age was 32±12 years. Furthermore, necropsy studies, which often examine explanted vessels not distended by physiological pressures, represent only estimations of the severity of coronary disease.
This intravascular ultrasound imaging study provides direct in vivo evidence of occult, but rather extensive, atherosclerosis in a young and presumably healthy population. Without high-resolution intravascular ultrasound imaging, detection and quantification of atherosclerosis would not have been possible in living humans. Ultrasound imaging provides unique cross-sectional information that is analogous to pathology and that cannot be obtained in coronary arteries from any other imaging technique.
The older age of the donor population in this study reflects an
important trend in cardiac transplantation. The limited availability of
suitable donors and the long waiting lists for transplantation have
increased the use of older donors.31 However, the presence
of atherosclerosis in more than 80% of our donors who are 30 years
old indicates a potential hazard to this approach. The presence of
coronary atherosclerosis in so many transplant recipients raises an
important clinical question. Does disease transmitted from the donor
increase the risk of accelerated transplant vasculopathy? This
important clinical question cannot be answered until angiographic,
ultrasound, and clinical follow-up studies determine the long-term
prognostic significance of transmitted coronary disease.
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Acknowledgments |
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We thank James Thomas, MD, for the review of the manuscript and Karen Howell for her valuable assistance in the preparation of this article.
Received July 27, 1994; revision received October 17, 1994; accepted October 30, 1994.
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 H. Li, K. Tanaka, H. Anzai, B. Oeser, D. Lai, J. A. Kobashigawa, and J. M. Tobis Influence of Pre-Existing Donor Atherosclerosis on the Development of Cardiac Allograft Vasculopathy and Outcomes in Heart Transplant Recipients J. Am. Coll. Cardiol., June 20, 2006; 47(12): 2470 - 2476. [Abstract] [Full Text] [PDF]
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S. R.F.F. Pedra, C. A.C. Pedra, A. A. Abizaid, S. L.N. Braga, R. Staico, R. Arrieta, J. R. Costa Jr, V. D. Vaz, V. F. Fontes, and J. E. R. Sousa Intracoronary Ultrasound Assessment Late After the Arterial Switch Operation for Transposition of the Great Arteries J. Am. Coll. Cardiol., June 21, 2005; 45(12): 2061 - 2068. [Abstract] [Full Text] [PDF]
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E. M. Tuzcu, S. R. Kapadia, R. Sachar, K. M. Ziada, T. D. Crowe, J. Feng, W. A. Magyar, R. E. Hobbs, R. C. Starling, J. B. Young, et al. Intravascular Ultrasound Evidence of Angiographically Silent Progression in Coronary Atherosclerosis Predicts Long-Term Morbidity and Mortality After Cardiac Transplantation J. Am. Coll. Cardiol., May 3, 2005; 45(9): 1538 - 1542. [Abstract] [Full Text] [PDF]
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M. Yousufuddin, D. J. Cook, R. C. Starling, A. Abdo, P. Paul, E. M. Tuzcu, N. B. Ratliff, P. M. McCarthy, J. B. Young, and M. H. Yamani Angiotensin II receptors from peritransplantation through first-year post-transplantation and the risk of transplant coronary artery disease J. Am. Coll. Cardiol., May 5, 2004; 43(9): 1565 - 1573. [Abstract] [Full Text] [PDF]
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 M. J. Quinones, M. Hernandez-Pampaloni, H. Schelbert, I. Bulnes-Enriquez, X. Jimenez, G. Hernandez, R. De La Rosa, Y. Chon, H. Yang, S. B. Nicholas, et al. Coronary Vasomotor Abnormalities in Insulin-Resistant Individuals Ann Intern Med, May 4, 2004; 140(9): 700 - 708. [Abstract] [Full Text] [PDF]
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M. Yousufuddin, S. Haji, R. C. Starling, E. M. Tuzcu, N. B. Ratliff, D. J. Cook, A. Abdo, Y. Saad, S. S. Karnik, D. Wang, et al. Cardiac angiotensin II receptors as predictors of transplant coronary artery disease following heart transplantation Eur. Heart J., March 1, 2004; 25(5): 377 - 385. [Abstract] [Full Text] [PDF]
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S. E. Nissen Pathobiology, not angiography, should guide managementin acute coronary syndrome/non-ST-segment elevation myocardial infarction: The non-interventionist's perspective J. Am. Coll. Cardiol., February 19, 2003; 41(4_Suppl_S): 103S - 112S. [Abstract] [Full Text] [PDF]
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A. Nair, B. D. Kuban, E. M. Tuzcu, P. Schoenhagen, S. E. Nissen, and D. G. Vince Coronary Plaque Classification With Intravascular Ultrasound Radiofrequency Data Analysis Circulation, October 22, 2002; 106(17): 2200 - 2206. [Abstract] [Full Text] [PDF]
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 P. Schoenhagen and S. Nissen Understanding coronary artery disease: tomographic imaging with intravascular ultrasound Heart, July 1, 2002; 88(1): 91 - 96. [Full Text] [PDF]
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M. H. Yamani, S. A. Haji, R. C. Starling, E. M. Tuzcu, N. B. Ratliff, D. J. Cook, A. Abdo, T. Crowe, M. Secic, P. McCarthy, et al. Myocardial ischemic-fibrotic injury after human heart transplantation is associated with increased progression of vasculopathy, decreased cellular rejection and poor long-term outcome J. Am. Coll. Cardiol., March 20, 2002; 39(6): 970 - 977. [Abstract] [Full Text] [PDF]
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C. Di Mario Vulnerable plaques: let's stop sinking on submerged icebergs? Eur. Heart J., March 1, 2002; 23(5): 349 - 351. [Full Text] [PDF]
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H. Tsutsui, K. M. Ziada, P. Schoenhagen, A. Iyisoy, W. A. Magyar, T. D. Crowe, J. D. Klingensmith, D. G. Vince, G. Rincon, R. E. Hobbs, et al. Lumen Loss in Transplant Coronary Artery Disease Is a Biphasic Process Involving Early Intimal Thickening and Late Constrictive Remodeling: Results From a 5-Year Serial Intravascular Ultrasound Study Circulation, August 2, 2001; 104(6): 653 - 657. [Abstract] [Full Text] [PDF]
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S. R. Kapadia, S. E. Nissen, K. M. Ziada, G. Rincon, T. D. Crowe, N. Boparai, J. B. Young, and E. M. Tuzcu Impact of lipid abnormalities in development and progression of transplant coronary disease: a serial intravascular ultrasound study J. Am. Coll. Cardiol., July 1, 2001; 38(1): 206 - 213. [Abstract] [Full Text] [PDF]
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E. M. Tuzcu, S. R. Kapadia, E. Tutar, K. M. Ziada, R. E. Hobbs, P. M. McCarthy, J. B. Young, and S. E. Nissen High Prevalence of Coronary Atherosclerosis in Asymptomatic Teenagers and Young Adults : Evidence From Intravascular Ultrasound Circulation, June 5, 2001; 103(22): 2705 - 2710. [Abstract] [Full Text] [PDF]
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P. J. Hauptman, K. J. O'Connor, R. E. Wolf, and B. J. McNeil Angiography of potential cardiac donors J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1252 - 1258. [Abstract] [Full Text] [PDF]
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G. S. Mintz, S. E. Nissen, W. D. Anderson, S. R. Bailey, R. Erbel, P. J. Fitzgerald, F. J. Pinto, K. Rosenfield, R. J. Siegel, E. M. Tuzcu, et al. American College of Cardiology clinical expert consensus document on standards for acquisition, measurement and reporting of intravascular ultrasound studies (ivus): A report of the american college of cardiology task force on clinical expert consensus documents developed in collaboration with the european society of cardiology endorsed by the society of cardiac angiography and interventions J. Am. Coll. Cardiol., April 1, 2001; 37(5): 1478 - 1492. [Full Text] [PDF]
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S. Sdringola, D. Patel, and K. L. Gould High Prevalence of Myocardial Perfusion Abnormalities on Positron Emission Tomography in Asymptomatic Persons With a Parent or Sibling With Coronary Artery Disease Circulation, January 30, 2001; 103(4): 496 - 501. [Abstract] [Full Text] [PDF]
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S. E. Nissen and P. Yock Intravascular Ultrasound : Novel Pathophysiological Insights and Current Clinical Applications Circulation, January 30, 2001; 103(4): 604 - 616. [Abstract] [Full Text] [PDF]
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 M. Sharifi, Y. Siraj, J. O'Donnell, and V. J. Pompili Coronary Angioplasty and Stenting in Orthotopic Heart Transplants: A Fruitful Act or a Futile Attempt? Angiology, October 1, 2000; 51(10): 809 - 815. [Abstract] [PDF]
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F. D. Knollmann, W. Bocksch, S. Spiegelsberger, R. Hetzer, R. Felix, and M. Hummel Electron-Beam Computed Tomography in the Assessment of Coronary Artery Disease After Heart Transplantation Circulation, May 2, 2000; 101(17): 2078 - 2082. [Abstract] [Full Text] [PDF]
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P. Schoenhagen, K. M. Ziada, S. R. Kapadia, T. D. Crowe, S. E. Nissen, and E. M. Tuzcu Extent and Direction of Arterial Remodeling in Stable Versus Unstable Coronary Syndromes : An Intravascular Ultrasound Study Circulation, February 15, 2000; 101(6): 598 - 603. [Abstract] [Full Text] [PDF]
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D. A. Rossignol, B. Kipreos, K. Akosah, and P. K. Mohanty Accelerated Transplant Coronary Artery Disease and Massive Silent Acute Myocardial Infarction in a Heart Transplant Patient: A Case Report and Brief Review of Literature Angiology, November 1, 1999; 50(11): 947 - 953. [Abstract] [PDF]
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C. H. Spes, V. Klauss, H. Mudra, S. D. Schnaack, A. R. Tammen, J. Rieber, U. Siebert, K.-H. Henneke, P. Uberfuhr, B. Reichart, et al. Diagnostic and Prognostic Value of Serial Dobutamine Stress Echocardiography for Noninvasive Assessment of Cardiac Allograft Vasculopathy : A Comparison With Coronary Angiography and Intravascular Ultrasound Circulation, August 3, 1999; 100(5): 509 - 515. [Abstract] [Full Text] [PDF]
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P. J. Scanlon, D. P. Faxon, A.-M. Audet, B. Carabello, G. J. Dehmer, K. A. Eagle, R. D. Legako, D. F. Leon, J. A. Murray, S. E. Nissen, et al. ACC/AHA guidelines for coronary angiography: A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Coronary Angiography) developed in collaboration with the Society for Cardiac Angiography and Interventions J. Am. Coll. Cardiol., May 1, 1999; 33(6): 1756 - 1824. [Full Text] [PDF]
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S. R. Kapadia, S. E. Nissen, K. M. Ziada, V. Guetta, T. D. Crowe, R. E. Hobbs, R. C. Starling, J. B. Young, and E. M. Tuzcu Development of Transplantation Vasculopathy and Progression of Donor-Transmitted Atherosclerosis : Comparison by Serial Intravascular Ultrasound Imaging Circulation, December 15, 1998; 98(24): 2672 - 2678. [Abstract] [Full Text] [PDF]
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A VARNAVA Coronary artery remodelling Heart, February 1, 1998; 79(2): 109 - 110. [Full Text]
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 P. Holvoet, J.-M. Stassen, J. Van Cleemput, D. Collen, and J. Vanhaecke Oxidized Low Density Lipoproteins in Patients With Transplant-Associated Coronary Artery Disease Arterioscler Thromb Vasc Biol, January 1, 1998; 18(1): 100 - 107. [Abstract] [Full Text] [PDF]
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M. Weis and W. von Scheidt Cardiac Allograft Vasculopathy : A Review Circulation, September 16, 1997; 96(6): 2069 - 2077. [Abstract] [Full Text]
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 P. J. Hauptman and K. J. O'Connor Procurement and Allocation of Solid Organs for Transplantation N. Engl. J. Med., February 6, 1997; 336(6): 422 - 431. [Full Text] [PDF]
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E. Aptecar, P. Dupouy, C. Benvenuti, J.-P. Mazzucotelli, E. Teiger, H. Geschwind, A. Castaigne, D. Loisance, and J.-L. Dubois-Rande Sympathetic Stimulation Overrides Flow-Mediated Endothelium-Dependent Epicardial Coronary Vasodilation in Transplant Patients Circulation, November 15, 1996; 94(10): 2542 - 2550. [Abstract] [Full Text]
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M. J. Davies Stability and Instability: Two Faces of Coronary Atherosclerosis: The Paul Dudley White Lecture 1995 Circulation, October 15, 1996; 94(8): 2013 - 2020. [Full Text]
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J. M. Mann and M. J. Davies Vulnerable Plaque: Relation of Characteristics to Degree of Stenosis in Human Coronary Arteries Circulation, September 1, 1996; 94(5): 928 - 931. [Abstract] [Full Text]
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E. J. Topol and S. E. Nissen Our Preoccupation With Coronary Luminology : The Dissociation Between Clinical and Angiographic Findings in Ischemic Heart Disease Circulation, October 15, 1995; 92(8): 2333 - 2342. [Abstract] [Full Text]
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