(Circulation. 1998;98:2672-2678.)
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports |
Development of Transplantation Vasculopathy and Progression of Donor-Transmitted Atherosclerosis
Comparison by Serial Intravascular Ultrasound Imaging
From The Cleveland Clinic Foundation, Cleveland, Ohio.
Correspondence to E.M. Tuzcu, MD, The Cleveland Clinic Foundation, F25, 9500 Euclid Ave, Cleveland, OH 44195.
 |
Abstract |
|---|
 Top Abstract IntroductionMethodsResultsDiscussionReferences |
|---|
Background—Transplant coronary artery disease is a combination of atherosclerosis transmitted from the donor and new lesions of allograft vasculopathy. We sought to determine the morphological characteristics of allograft vasculopathy and differentiate it from donor-transmitted atherosclerosis with serial intravascular ultrasound.
Methods and Results—Intravascular ultrasound examination
was performed in 93 patients at 27.2±15.0 and 369.7±23.9 days after
transplantation. The maximally and minimally diseased sites were
selected in each segment as defined by Coronary Artery Surgery
Study classification. For each matched site, maximal plaque thickness
was measured. Lesions (maximum plaque thickness 
0.5 mm)
present at baseline examination were defined as donor lesions. On
follow-up, lesions that developed at previously normal sites were
defined as de novo lesions. The distribution and severity of donor and
de novo lesions were similar in proximal, mid, and distal segments. The
de novo lesions were less focal (43% vs 74%) and more circumferential
(69% vs 45%) compared with the donor lesions, but there was
significant morphological heterogeneity. Similar
numbers of patients with and those without donor lesions developed de
novo lesions. Moreover, progression of donor lesions was not associated
with the presence or absence of de novo lesions.
Conclusions—Differentiation between early allograft vasculopathy from conventional atherosclerosis by distribution and morphology of lesions alone is difficult. Serial intravascular ultrasound imaging with early baseline examination is necessary to make this distinction. This distinction is important because the progression of donor lesions and the development of de novo lesions are independent of each other.
Key Words: coronary artery disease • transplantation • ultrasonics • lesion
|
Introduction |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Transplant coronary artery disease is the leading cause of late mortality, limiting the long-term success of heart transplantation.1 2 3 Coronary artery disease in heart transplantation recipients often is a combination of atherosclerosis transmitted from the donor and de novo lesions that develop after transplantation. The latter have been called "allograft vasculopathy or transplant arteriopathy."4 5 The late stage of transplant coronary artery disease, as seen at necropsy, manifests as a severe diffuse obliterative process characterized by concentric intimal proliferation.6 7 8 However, the morphological characterization of early arteriopathy and its relation to donor lesions are not well defined.
Serial studies with intravascular ultrasound provide a unique opportunity to follow the natural history of the disease process.9 The sensitivity of intravascular ultrasound in identifying early changes in the transplanted heart is well documented.7 10 11 12 13 The measurements derived from intravascular ultrasound images have been validated with morphometric5 14 and angiographic15 16 17 measurements.
We sought to determine the morphology of early coronary lesions with serial intravascular ultrasound examinations. Our goal was to identify the lesions of allograft vasculopathy and differentiate them from atherosclerosis transmitted from the donor. We performed baseline intravascular ultrasound examination early after transplantation to identify donor lesions. One-year follow-up ultrasound examination was performed to identify the newly developed (de novo) lesions of transplant vasculopathy and to assess the changes in donor lesions.
|
Methods |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patient Population
The study group consisted of patients who underwent heart transplantation between December 1992 and October 1995. Patients who died during hospitalization, those who were not eligible for cardiac catheterization, and patients who did not give informed consent were excluded. The study protocol was approved by the hospital's Institutional Review Board.
Intravascular Ultrasound Imaging
The baseline intravascular ultrasound examination was done
within 2 months of transplantation. The repeat ultrasound imaging was
performed at 1 year. Effort was made to image all 3 major epicardial
vessels in all patients. Three arteries were imaged in 27 (29%)
patients, 2 arteries were imaged in 38 (41%) patients, and only 1
vessel was imaged in 28 (30%) patients. Thus, 185 first-order
epicardial vessels were examined in 93 patients. The right
coronary artery was imaged in 48 (52%) patients, the left
circumflex in 58 (62%) patients, and the left anterior descending in
79 (85%) patients.
The method of intravascular ultrasound imaging has been previously reported in detail.4 5 Briefly, a 30-MHz, 3.5F monorail ultrasound catheter (Boston Scientific) interfaced with a dedicated scanner (Hewlett-Packard) was passed over an angioplasty guide wire. The most distal transducer location was documented by cineangiography. Ultrasound images were recorded on S-VHS tape during a slow, distal-to-proximal manual pullback. Each vessel and its ultrasound landmarks (ie, branches, veins, pericardium) were identified during the pullback with the use of voice annotation. When needed, repeat imaging runs were performed and angiographic contrast injection was used to confirm the location of imaging sites, enabling precise matching of ultrasound images with angiographic segments. Before the 1-year examination, the cineangiograms and intravascular ultrasound images were reviewed by the operators to duplicate the imaging study.
Off-Line Intravascular Ultrasound Analysis
Baseline and follow-up ultrasound tapes were reviewed side
by side on 2 identical video monitors in an intravascular ultrasound
core laboratory. This simultaneous evaluation allowed
accurate matching of pullback sequences. Angiographic as well as
intravascular ultrasound landmarks such as side branches, pericardium,
and cardiac veins were used in matching the sites. An operator
digitized these full-motion ultrasound sequences (30 frames per second)
on a 640x480 pixel matrix with 24 bits per pixel, using an image
processing computer. Ultrasound images were considered suitable for
analysis if images were free from ultrasound artifacts such as
catheter angulation or nonuniform rotational distortion.
For each segment, defined according to Coronary Artery Surgery Study (CASS) classifications, all diseased sites at baseline examination were prospectively identified and included in the analysis. These sites were compared with the matching sites from the follow-up imaging. A different, retrospective methodology was used to capture the most severe de novo lesions of transplant vasculopathy. For this, from the 1-year examination, the normal or least diseased site and most diseased site from each segment were selected after excluding the sites with donor lesions.4 These sites were then identified from the baseline examination for measurement. In cases in which the entire segment was normal, 1 or 2 sites were selected from the segment. The operator examined the full-motion sequence before the selection of the single still frame to assist in optimal border delineation. The lumen and media-adventitial border of the selected still frames were manually traced, and direct measurements of cross-sectional area, circumference, minimum diameter, and maximum diameter were generated. Manual measurements of the minimum and maximum plaque thickness (Pmin and Pmax, respectively) were also performed.
The following definitions for lesion characteristics were used:
(1) Focal: Focality describes the longitudinal extent of a lesion.
The lesion was described as focal if there was at least 1 site in the
same CASS segment that was completely normal. If the entire segment was
involved by the disease process, the lesion was called diffuse. (2)
Circumferential: Circumferentiality describes the axial distribution of
a lesion. The lesion was circumferential if it involved the entire
(>270 degrees of the arc) circumference of the vessel and
noncircumferential if any arc of the vessel wall was free of disease
(Figure 1
). (3) Donor lesion: If Pmax was
0.5 mm at baseline examination, it was defined as a donor
lesion. (4) De novo lesion: If Pmax was 0.5 mm at follow-up, at
a previously normal site, it was defined as a de novo lesion. (5)
Progression of donor lesion: If the increase in maximal plaque
thickness of a donor lesion on follow-up was >0.3 mm, this term
was used.
|
We have used Pmax for the definition of lesions and their progression because this is the most commonly reported parameter in the literature. However, plaque area (Pcsa), calculated from lumen and external elastic membrane area measurement (Pcsa=external elastic membrane area-lumen area), can serve as a reliable alternative to the Pmax measurement. Therefore, we sought a correlation of these 2 measurements in our data set. Pmax closely correlates with Pcsa measurement at baseline as well as at follow-up examination (r=0.88, P<0.001 for baseline and r=0.90, P<0.001 for follow-up examination). Furthermore, the progression in donor lesions and development of de novo lesions identified by the increase in Pmax was confirmed by the statistically significant increase in Pcsa.
Statistical Analysis
Normally distributed data are reported as mean±SD. The
2 test or Fisher's exact test was used to
find significant differences between categorical variables. The
unpaired 2-tailed t test was used to compare mean values for
continuous variables.
|
Results |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Patient Characteristics
At our institution, 177 adult patients underwent heart transplantation between December 30, 1992, and October 30, 1995. Of these, 118 patients underwent cardiac catheterization early after transplantation. Hospital mortality, severe comorbid conditions, patient refusal, and scheduling constraints were reasons for not catheterizing the remaining 59 patients. At 1 year, 105 patients underwent catheterization. The causes of dropout were death (n=11) and technical considerations (n=2). Paired intravascular ultrasound data were available in 93 patients. Baseline and follow-up intravascular ultrasound examination were performed 27±15 and 370±24 days after transplantation, respectively. Donor and recipient characteristics are summarized in Table 1
.
|
Morphology of Lesions
At baseline examination, 36 (39%) patients were identified with
donor-transmitted atherosclerosis with involvement of
89 sites. These lesions involved proximal segments more frequently than
mid and distal segments (Figure 2). The
majority of the donor lesions were focal (74%), 55% were
noncircumferential, and 57% of them involved a vessel bifurcation.
|
At follow-up imaging, 107 de novo lesions were identified in 42 (45%)
patients. Similar to the donor-transmitted
atherosclerosis, most of the de novo lesions were
located in the proximal segments (Figure 2
). Involvement of the
bifurcation sites was also frequent (45%). Though the proportion of
lesions in each distribution (proximal, mid, and distal) is comparable
for donor and de novo lesions, more donor lesions are focal and
noncircumferential compared with the de novo lesions (Table 2).
|
Severity of Lesions
The maximal plaque thickness of donor and de novo lesions in
proximal, mid, and distal segments was similar (Figure 3). Moreover, there was no correlation
between vessel area and plaque thickness (r=0.13,
P=0.08). When the lesions involving different sites in the
same coronary artery (n=45) were analyzed, plaque
thickness of the more proximal lesions was similar to that of the
distal lesions (proximal=0.97±0.37 mm, distal=0.88±0.26 mm;
P=0.14). This was also the case for donor and de novo
lesions (inset of Figure 3).
|
Progression of Donor Lesions
Donor lesion progression was noted at 23 sites in 15 (42%) of 36
patients. Progression was seen in 22% of proximal, 38% of mid, and
20% of distal segments (P=0.7). Ten (15%) lesions that
were focal at baseline became diffuse on follow-up. Only 4 (8%) of the
noncircumferential lesions at baseline progressed to involve the entire
circumference of the coronary artery. However, the increase in
plaque thickness of donor lesions was significantly less than that for
the de novo lesions in the first year after transplantation (Figure 4).
|
Progression of donor-transmitted atherosclerosis was independent of the de novo lesion development. Of the 15 patients with progression, 6 (40%) had de novo lesions, and of the 21 patients without progression, 10 (48%) had de novo lesions (P=0.74). The converse was also true. Development of allograft vasculopathy was independent of donor-transmitted atherosclerosis. In 36 patients with donor lesions, 20 patients developed de novo lesions and 16 did not (P=0.11).
|
Discussion |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
Our findings indicate that at 1 year after transplantation, it is difficult to distinguish the lesions of donor-transmitted atherosclerosis from transplant vasculopathy by their morphological characteristics and distribution. Though the lesions of transplant vasculopathy tend to be more diffuse and circumferential than the atherosclerosis transmitted from donor lesions, both types of lesions have predilection for proximal segments and bifurcation sites. Despite these similarities, the development of de novo lesions and progression of donor-transmitted atherosclerosis are independent of each other.
Our understanding of the morphological aspects of transplant coronary artery disease is primarily based on necropsy studies, and to a lesser extent, on angiographic studies.18 19 20 In general, postmortem studies showed that transplant coronary artery disease involves distal vessels more than proximal, in a diffuse manner.21 22 23 However, necropsy studies allow assessment at one time point, usually at a late phase of the disease. These studies do not provide any information about the evolution of the disease process. On the other hand, annual angiographic examinations allow serial data collection. However, the insensitivity of coronary angiography in detecting early atherosclerotic changes limits its usefulness in understanding the development of transplantation coronary artery disease. Most of the previous morphological studies with intravascular ultrasound to study transplant coronary artery disease were done without serial examinations.24 25 A serial study with intravascular ultrasound has been published to establish feasibility, but morphology of lesions was not the focus of interest.26 This is the first serial intravascular ultrasound study that evaluates the morphology and distribution of transplant coronary artery disease.
Our study was prospectively designed to investigate transplant coronary artery disease with an early baseline intravascular imaging followed by a 1-year imaging. This approach allowed us to define donor-transmitted atherosclerosis from transplant vasculopathy. Moreover, multivessel, multisegment imaging was performed to maximize sampling and to minimize errors in detecting and characterizing patterns of transplant coronary artery disease. This is distinct from other studies in which investigators have concentrated on 1 or 2 proximal segments of a single vessel. Our study population is representative of the heart transplantation population in general. Although some transplantation recipients were excluded, 79% of the hospital survivors and 89% of those who had catheterization were imaged by ultrasound. The 89% of patients who had a baseline study also had follow-up examination at 1 year.
Our findings demonstrate that though the early de novo lesions are more likely to be diffuse and concentric, a significant number of these are focal and noncircumferential. Besides, the distribution of de novo lesions throughout the length of the coronary arteries and predilection for bifurcation sites are similar to the donor-transmitted atherosclerosis. Even the severity of the de novo lesions in the proximal, mid, and distal segments is comparable. Thus the lesions of allograft vasculopathy at 1 year are indistinguishable from conventional atherosclerosis. This finding underscores the importance of serial examination and highlights the difficulty in interpretation of studies with cross-sectional design. These findings also suggest a role of local rheological factors in the development and progression of transplant vasculopathy as in conventional atherosclerosis.27 28 29 30
The importance of donor-transmitted atherosclerosis in the genesis and progression of transplant vasculopathy is not known. In a predominantly angiographic study, preexisting coronary artery disease was found to be associated with accelerated allograft coronary artery disease.31 This finding was valid for angiographically evident coronary artery disease but not for intravascular ultrasound-detected atherosclerosis. In this study, the progression of preexisting lesions was not differentiated from de novo lesions. Our observations demonstrate that atherosclerotic plaques in the transplanted heart does not predispose to allograft vasculopathy. It is also not known whether transplant vasculopathy leads to the progression of donor-transmitted atherosclerosis. We did not find any association between the progression of preexisting atherosclerosis and the development of allograft vasculopathy; however, the number of patients in each category is relatively small. Moreover, in the first year after transplantation, the rate of progression of donor lesions is slower than that of de novo lesions. Thus, despite many morphological similarities in the lesions of mild conventional atherosclerosis and early allograft vasculopathy, lack of interaction between the 2 disease processes and different rates of progression suggest the presence of independent biological determinants affecting their development and progression. However, there was predilection for the more proximal and bifurcation sites in both disease processes. These similarities in distribution can be explained by factors such as high shear forces that may contribute to the development of conventional atherosclerosis as well as transplant vasculopathy.
In this study, plaque thickness is defined as the distance from the intimal leading-edge to the external elastic membrane (adventitial leading edge). This is the standard method of measuring plaque thickness by intravascular ultrasound.32 The measurement of intima only (leading edge to trailing edge) requires delineating the internal elastic membrane, which can be difficult and imprecise. For all ultrasound techniques, the trailing edge location is often determined by ultrasound beam properties, not anatomic location. This latter method has been shown to be less accurate than the measurement technique that we used, which is based on delineating and tracing the external elastic membrane.32 33 The differences between definitions should be kept in mind while comparing the results of this study with other studies.
The threshold of plaque thickness (0.5 mm) used to define
a lesion is based on the information provided by several
histological and ultrasound studies. In a necropsy
study, normal intimal thickness (not including media) averaged
0.21 mm (0.10 to 0.28 mm) in 21- to 25-year-old subjects,
0.22 mm (0.12 to 0.28 mm) in 26- to 30-year-old subjects, and
0.25 mm (0.18 to 0.35 mm) in 36- to 40-year-old
subjects.34 Similarly, in a comparative
ultrasound-histology study, patients with no known coronary
artery disease, intimal thickness (without including media) was
0.24±0.11 mm.35 In this study, the medial
thickness was 0.23±0.6 mm and did not vary significantly with
intimal proliferation. Accordingly, the thickness of the normal intima
and media in young and middle-aged humans ranges from 0.45 to 0.50
mm. Therefore, we have traditionally used the threshold of 0.5
mm to define a lesion.4 Clinical studies
evaluating the risk factors for transplant vasculopathy commonly use
this threshold.36 37
Although the definitions used by us are rational and in
accordance with most of the previous literature, we wanted to
analyze the data by using a less stringent set of definitions
to further validate our interpretations. Thus for addressing the
concern that the use of the 0.5 mm threshold may underestimate
donor atherosclerosis, we also analyzed our
data using >0.3 mm threshold to define donor lesions. To exclude
any influence of early donor atherosclerosis on
development of transplant vasculopathy, de novo lesions were defined as
lesions with baseline plaque thickness <0.15 mm and follow-up
plaque thickness >0.3 mm. To capture even the minimal
progression, we used a difference of >0.15 mm to define donor
lesion progression. Using these definitions, the severity,
distribution, and morphological aspects of the lesions were similar to
the original analysis. The lack of interaction between the de
novo lesions and donor disease was also evident in this
analysis. However, with the use of the 0.3 mm threshold,
the prevalence of donor-transmitted atherosclerosis was
higher than previously reported.5 31 38
The differences between definitions and methodology should also be kept in mind while comparing our findings with previous studies in the literature. In histological studies, intramural arteries and arterioles are referred to as distal vessels. Angiography can identify distal vessels as small as 0.5 to 1.0 mm in diameter. We have defined the distal vessel according to CASS classification. Thus the distal vessels in this study do not represent very-small-caliber arteries and in this respect are not comparable with histological studies. Further, while interpreting the focality of a lesion, it should be recognized that the exact length of a lesion was not analyzed in this study because manual pullback was used for imaging.
This serial study points to the pitfalls of the morphological observations made at a single point in time with cross-sectional design and demonstrates that by morphological analysis it is impossible to distinguish donor-transmitted atherosclerosis from allograft arteriopathy. This finding underscores the role of serial intravascular ultrasound examination with early baseline study to make this distinction. It is meaningful to separate these two disease processes because they appear to behave independently despite their morphological similarities. In the future, to understand the pathophysiology of these diseases, it will be important to investigate potential clinical determinants separately for each disease process.
|
Received January 30, 1998; revision received August 18, 1998; accepted August 31, 1998.
|
References |
|---|
|
TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Bieber CP, Hunt SA, Schwinn DA, Jamieson SA, Reitz BA, Oyer PE, Shumway NE, Stinson EB. Complications in long-term survivors of cardiac transplantation. Transplant Proc. 1981;13:207–211.[Medline] [Order article via Infotrieve]
2. Unos. Annual report of the US Scientific Registry for Organ Transplantation and the Organ Procurement and Transplantation Network. US Department of Health and Human Services. 1990.
3. Ventura HO, Mehra MR, Smart FW, Stapleton DD. Cardiac allograft vasculopathy: current concepts. Am Heart J. 1995;129:791–799.[Medline] [Order article via Infotrieve]
4.
Tuzcu EM, Hobbs RE, Rincon G, Bott-Silverman C, De
Franco AC, Robinson K, McCarthy PM, Stewart RW, Guyer S, Nissen SE.
Occult and frequent transmission of atherosclerotic coronary
disease with cardiac transplantation: insights from intravascular
ultrasound. Circulation. 1995;91:1706–1713.
5.
St. Goar FG, Pinto FJ, Alderman EL, Fitzgerald PJ,
Stinson EB, Billingham ME, Popp RL. Detection of
coronary atherosclerosis in young adult hearts
using intravascular ultrasound. Circulation. 1992;86:756–763.
6. Johnson DE, Gao SZ, Schroeder JS, DeCampli WM, Billingham ME. The spectrum of coronary artery pathologic findings in human cardiac allografts. J Heart Transplant. 1989;8:349–359.[Medline] [Order article via Infotrieve]
7. Billingham ME. Cardiac transplant atherosclerosis. Transplant Proc. 1987;19:19–25.[Medline] [Order article via Infotrieve]
8. Billingham ME. Graft coronary disease: the lesions and the patients. Transplant Proc. 1989;21:3665–3666.[Medline] [Order article via Infotrieve]
9.
Pinto FJ, Chenzbraun A, Botas J, Valantine HA,
St. Goar FG, Alderman EL, Oesterle SN, Schroeder JS, Popp RL.
Feasibility of serial intracoronary ultrasound imaging for
assessment of progression of intimal proliferation in cardiac
transplant recipients. Circulation. 1994;90:2348–2355.
10.
Waller BF, Pinkerton CA, Slack JD. Intravascular
ultrasound: a histological study of vessels during
life: the new "gold standard" for vascular imaging.
Circulation. 1992;85:2305–2310.
11. Ventura HO, White CJ, Jain SP, Smart FW, Jain A, Stapleton DD, Collins TJ, Ramee SR. Assessment of intracoronary morphology in cardiac transplant recipients by angioscopy and intravascular ultrasound. Am J Cardiology. 1993;72:805–809.[Medline] [Order article via Infotrieve]
12. Klauss V, Rieber J, Uberfuhr P, Theisen K, Mudra H. Qualitative and quantitative assessment of cardiac allograft vasculopathy by intravascular ultrasound. Transplant Proc. 1995;27:1975–1976.[Medline] [Order article via Infotrieve]
13. Miller LW. Role of intracoronary ultrasound for the diagnosis of cardiac allograft vasculopathy. Transplant Proc. 1989;27:1989–1992.
14.
Tobis JM, Mallery J, Mahon D, Lehmann K, Zalesky P,
Griffith J, Gessert J, Moriuchi M, McRae M, Dwyer ML, Greep N, Henry,
WL. Intravascular ultrasound imaging of human coronary arteries
in vivo: analysis of tissue characterizations with comparison
to in vitro histological specimens.
Circulation. 1991;83:913–926.
15.
Nissen SE, Gurley JC, Grines CL, Booth DC, McClure R,
Berk M, Fischer C, DeMaria AN. Intravascular ultrasound assessment of
lumen size and wall morphology in normal subjects and patients with
coronary artery disease. Circulation. 1991;84:1087–1099.
16. St. Goar FG, Pinto FJ, Alderman EL, Fitzgerald PJ, Stadius ML, Popp, RL. Intravascular ultrasound imaging of angiographically normal coronary arteries: an in vivo comparison with quantitative angiography. J Am Coll Cardiol. 1991;18:952–958.[Abstract]
17. Lowry RW, Kleiman NS, Raizner AE, Young JB. Is intravascular ultrasound better than quantitative coronary arteriography to assess cardiac allograft arteriopathy? Cathet Cardiovasc Diagn. 1994;31:110–115.[Medline] [Order article via Infotrieve]
18. Park SJ, Pifarre R, Sullivan H, Montoya A, Kim SY. Natural history of allograft coronary arteriopathy: a retrospective study of 54 patients over an 81/2-year period. Cardiovasc Surg. 1996;4:37–41.[Medline] [Order article via Infotrieve]
19. Billingham ME. Histopathology of graft coronary disease. J Heart Lung Transplant. 1992;11:S38–S44.[Medline] [Order article via Infotrieve]
20. Young JB, Smart FM, Lowry RL, Kleiman NS. Coronary angiography after heart transplantation: should perioperative study be the "gold standard"? J Heart Lung Transplant. 1992;11:S65–S68.[Medline] [Order article via Infotrieve]
21. Alderman EL, Wexler L. Angiographic implications of cardiac transplantation. Am J Cardiol. 1989;64:16E–21E.[Medline] [Order article via Infotrieve]
22. Gao SZ, Alderman EL, Schroeder JS, Silverman JF, Hunt SA. Accelerated coronary vascular disease in the heart transplant patient: coronary arteriographic findings. J Am Coll Cardiol. 1988;12:334–340.[Abstract]
23. Lin H, Wilson JE, Kendall TJ, Radio SJ, Cornhill FJ, Herderick E, Winters GL, Costanzo MR, Porter T, Thieszen SL, McManus BM. Comparable proximal and distal severity of intimal thickening and size of epicardial coronary arteries in transplant arteriopathy of human cardiac allografts. J Heart Lung Transplant. 1994;13:824–833.[Medline] [Order article via Infotrieve]
24.
Heroux AL, Silverman P, Costanzo MR, O'Sullivan EJ,
Johnson MR, Liao Y, McKiernan TL, Balhan JE, Leya FS,
Mullen GM, Kao WG, Johnson SA. Intracoronary ultrasound
assessment of morphological and functional abnormalities associated
with cardiac allograft vasculopathy. Circulation. 1994;89:272–277.
25.
St. Goar FG, Pinto FJ, Alderman EL, Valantine HA,
Schroeder JS, Gao SZ, Stinson EB, Popp RL. Intracoronary
ultrasound in cardiac transplant recipients: in vivo evidence of
"angiographically silent" intimal thickening.
Circulation.. 1992;85:979–987.
26. Pinto FJ, Chenzbraun A, Botas J, Valantine HA, St. Goar FG, Alderman, El, Oesterle SN, Schroeder JS, Popp RL. Feasibility of serial intracoronary ultrasound imaging for assessment of progression of intimal proliferation in cardiac transplant recipients. Circulation. 1994;90:2348–2355.
27. Dressler FA, Miller LW. Necropsy versus angiography: how accurate is angiography? J Heart Lung Transplant. 1992;11:S56–S59.[Medline] [Order article via Infotrieve]
28. O'Neill BJ, Pflugfelder PW, Singh NR, Menkis AH, McKenzie FN, Kostuk WJ. Frequency of angiographic detection and quantitative assessment of coronary arterial disease one and three years after cardiac transplantation. Am J Cardiol. 1989;63:1221–1226.[Medline] [Order article via Infotrieve]
29. Strong JP, Eggen DA, Tracy RE. The geographic pathology and topography of atherosclerosis and risk factors for atherosclerotic lesions. Adv Exp Med Biol. 1978;104:11–31.[Medline] [Order article via Infotrieve]
30. Velican D, Velican C. Atherosclerotic involvement of the coronary arteries of adolescents and young adults. Atherosclerosis. 1980;36:449–460.[Medline] [Order article via Infotrieve]
31. Gao HZ, Hunt SA, Alderman EL, Liang D, Yeung AC, Schroeder JS. Relation of donor age and preexisting coronary artery disease on angiography and intracoronary ultrasound to later development of accelerated allograft coronary artery disease. J Am Coll Cardiol. 1997;29:623–629.[Abstract]
32. Metz JA, Yock PG, Fitzgerald PJ. Intravascular ultrasound: basic interpretation. Cardiol Clin. 1997;15:1–15.[Medline] [Order article via Infotrieve]
33.
Wong M, Edelstein J, Wollman J, Bond MG.
Ultrasonic-pathological comparison of the human arterial
wall: verification of intima-media thickness.
ArteriosclerThromb. 1993;13:482–486.
34. Velican D, Velican C. Comparative study on age-related changes and atherosclerotic involvement of the coronary arteries of male and female subjects up to 40 years of age. Atherosclerosis. 1981;38:39–50.[Medline] [Order article via Infotrieve]
35.
Fitzgerald PJ, St. Goar FG, Connolly AJ, Pinto FJ,
Billingham ME, Popp RL, Yock PG. Intravascular ultrasound imaging of
coronary arteries: is three layers the norm?
Circulation. 1992;86:154–158.
36. Escobar A, Ventura HO, Stapleton DD, Mehra MR, Ramee SR, Collins TJ, Jain SP, Smart FW, White CJ. Cardiac allograft vasculopathy assessed by intravascular ultrasonography and nonimmunologic risk factors. Am J Cardiol. 1994;74:1042–1046.[Medline] [Order article via Infotrieve]
37. Mehra MR, Ventura HO, Stapleton DD, Smart FW, Collins TC, Ramee SR. Presence of severe intimal thickening by intravascular ultrasonography predicts cardiac events in cardiac allograft vasculopathy. J Heart Lung Transplant. 1995;14:632–639.[Medline] [Order article via Infotrieve]
38.
McNamara JJ, Molot MA, Stremple JF, Cutting RT.
Coronary artery disease in combat casualties in Vietnam.
JAMA. 1971;216:1185–1187.
This article has been cited by other articles:
 |
|
 |
|
  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]
|
|
|
|
|
|
M.-K. Hong, G. S. Mintz, C. W. Lee, B.-K. Lee, T.-H. Yang, Y.-H. Kim, J.-M. Song, K.-H. Han, D.-H. Kang, S.-S. Cheong, et al. The Site of Plaque Rupture in Native Coronary Arteries: A Three-Vessel Intravascular Ultrasound Analysis J. Am. Coll. Cardiol., July 19, 2005; 46(2): 261 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Kato, M. C. Y. Chan, S.-Z. Gao, J. S. Schroeder, M. Yokota, T. Murohara, M. Iwase, A. Noda, S. A. Hunt, and H. A. Valantine Glucose intolerance, as reflected by hemoglobin a1c level, is associated with the incidence and severity of transplant coronary artery disease J. Am. Coll. Cardiol., March 17, 2004; 43(6): 1034 - 1041. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. J. Eisen, E. M. Tuzcu, R. Dorent, J. Kobashigawa, D. Mancini, H. A. Valantine-von Kaeppler, R. C. Starling, K. Sorensen, M. Hummel, J. M. Lind, et al. Everolimus for the Prevention of Allograft Rejection and Vasculopathy in Cardiac-Transplant Recipients N. Engl. J. Med., August 28, 2003; 349(9): 847 - 858. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Mancini, S. Pinney, D. Burkhoff, J. LaManca, S. Itescu, E. Burke, N. Edwards, M. Oz, and A. R. Marks Use of Rapamycin Slows Progression of Cardiac Transplantation Vasculopathy Circulation, July 8, 2003; 108(1): 48 - 53. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. Vassalli, A. Gallino, M. Weis, W. von Scheidt, L. Kappenberger, L.K. von Segesser, J.-J. Goy, and on behalf of the Working Group Microcirculation of Alloimmunity and nonimmunologic risk factors in cardiac allograft vasculopathy Eur. Heart J., July 1, 2003; 24(13): 1180 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Weis, S. Pehlivanli, B. M. Meiser, and W. von Scheidt Simvastatin treatment is associated with improvement in coronary endothelial function and decreased cytokine activation in patients after heart transplantation J. Am. Coll. Cardiol., September 1, 2001; 38(3): 814 - 818. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
P. Schoenhagen, K. M. Ziada, D. G. Vince, S. E. Nissen, and E. M. Tuzcu Arterial remodeling and coronary artery disease: the concept of "dilated" versus "obstructive" coronary atherosclerosis J. Am. Coll. Cardiol., August 1, 2001; 38(2): 297 - 306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
 |
|
 S. Tsimikas, W. Palinski, and J. L. Witztum Circulating Autoantibodies to Oxidized LDL Correlate With Arterial Accumulation and Depletion of Oxidized LDL in LDL Receptor-Deficient Mice Arterioscler Thromb Vasc Biol, January 1, 2001; 21(1): 95 - 100. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Pethig, V Klauss, B Heublein, H Mudra, A Westphal, C Weber, K Theisen, and A Haverich Progression of cardiac allograft vascular disease as assessed by serial intravascular ultrasound: correlation to immunological and non-immunological risk factors Heart, November 1, 2000; 84(5): 494 - 498. [Abstract] [Full Text]
|
|
|
|
|
|
S. Fateh-Moghadam, W. Bocksch, A. Ruf, T. Dickfeld, M. Schartl, G. Pogatsa-Murray, R. Hetzer, E. Fleck, and M. Gawaz Changes in Surface Expression of Platelet Membrane Glycoproteins and Progression of Heart Transplant Vasculopathy Circulation, August 22, 2000; 102(8): 890 - 897. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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]
|
|
|
|
|
|
S. P. Schwarzacher, N. G. Uren, M. R. Ward, A. Schwarzkopf, N. Giannetti, S. Hunt, P. J. Fitzgerald, S. N. Oesterle, and A. C. Yeung Determinants of Coronary Remodeling in Transplant Coronary Disease : A Simultaneous Intravascular Ultrasound and Doppler Flow Study Circulation, March 28, 2000; 101(12): 1384 - 1389. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. B. Young Allograft Vasculopathy : Diagnosing the Nemesis of Heart Transplantation Circulation, August 3, 1999; 100(5): 458 - 460. [Full Text] [PDF]
|
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||