Cardiac allograft vasculopathy: advances in diagnosis

Cardiac allograft vasculopathy (CAV), characterized by diffuse intimal thickening and luminal narrowing in the arteries of the allograft, is the leading cause of morbidity and mortality in cardiac transplant recipients. Many transplant centers perform routine annual surveillance coronary angiography. However, angiography can underdiagnose or miss CAV due to its diffuse nature. Intravascular ultrasound (IVUS) is more sensitive than angiography. IVUS provides not only accurate information on lumen size, but also quantification of intimal thickening, vessel wall morphology, and composition. IVUS has evolved as a valuable adjunct to angiography and the optimal diagnostic tool for early detection. Noninvasive testing such as dobutamine stress echocardiography and nuclear stress test have shown considerable accuracy in diagnosing significant CAV. Computed tomographic imaging and cardiac magnetic resonance imaging are promising new modalities but require further study. This article reviews the diagnostic methods that are currently available.     

Vascular remodelling after cardiac transplantation: a 3-year serial intravascular ultrasound study.

AIMS: To assess the time-course of intimal hyperplasia and vascular remodelling, and their relative contributions on luminal narrowing in transplant coronary artery disease (TCAD) by a 3-year serial intravascular ultrasound (IVUS) study. METHODS AND RESULTS: Serial IVUS examinations were performed in 90 cardiac transplant recipients at 1.4+/-0.6 months after transplantation and again annually thereafter for 3 years. From 90 arteries, 304 sites were matched from baseline to the third year post-transplant. Based on the change in external elastic membrane (EEM) area +/-10% at 1 year, 304 sites were divided into three groups: sites with no remodelling (52%); early constrictive remodelling (26%); and early compensatory enlargement (22%). Greater intimal growth was seen at 1 year in sites with early compensatory enlargement, whereas there was no change in intimal area in sites with early constrictive remodelling. Over 3 years, the cumulative lumen loss was greater in sites with early constrictive remodelling than in sites with early compensatory enlargement or no remodelling (P<0.001). When luminal narrowing occurred for each annual interval, the contribution from the decrease in EEM area was greater than that due to intimal thickening (P<0.001). CONCLUSION: During the first 3 years post-transplant, the largest intimal growth occurs in the first year, mostly in sites with early compensatory enlargement. The contribution to luminal loss in TCAD is greater from constrictive remodelling than from intimal hyperplasia. The type of remodelling pattern that occurs in transplanted coronary arteries within the first year post-transplant may be a predictor of the progression of luminal narrowing during subsequent years.     

Multicenter intravascular ultrasound validation study among heart transplant recipients: outcomes after five years

OBJECTIVES: We sought to assess the validity of first-year intravascular ultrasound (IVUS) data as a surrogate marker for long-term outcome after heart transplantation. BACKGROUND: Cardiac allograft vasculopathy (CAV) is a major impediment to long-term graft survival. Intravascular ultrasound is more sensitive than coronary angiography and detects intimal thickening (early CAV) in the coronary arteries of the donor heart. Single-center studies have suggested first-year IVUS results might be a surrogate marker for long-term outcome. METHODS: First-year IVUS results and subsequent five-year clinical follow-up data were reviewed in 125 heart transplant recipients from five institutions. The IVUS tapes (at baseline and one year) were re-analyzed at a core IVUS laboratory. The change in maximal intimal thickness (MIT) from baseline to one year was recorded for several matched sites in the same coronary artery. Patients were classified into two groups: those with >/=0.5 mm in the MIT in any matched site (group 1) and those with MIT <0.5 mm (group 2). RESULTS: Group 1 patients compared with group 2 patients had a higher incidence of death or graft loss (D/GL, 20.8% vs. 5.9%; p = 0.007), had more nonfatal major adverse cardiac events and/or D/GL (45.8% vs. 16.8%; p = 0.003), and had more findings of newly occurring angiographic luminal irregularities (65.2% vs. 32.6%, p = 0.004). CONCLUSIONS: This multicenter study suggests that progression of intimal thickening >/=0.5 mm in the first year after transplantation appears to be a reliable surrogate marker for subsequent mortality, nonfatal major adverse cardiac events, and development of angiographic CAV through five years after heart transplantation.     

Intravascular ultrasound evidence of angiographically silent progression in coronary atherosclerosis predicts long-term morbidity and mortality after cardiac transplantation

OBJECTIVES: The aim of this study was to determine whether angiographically silent early coronary intimal thickening could predict long-term morbidity and mortality. BACKGROUND: Although intravascular ultrasound (IVUS) is widely used to detect early transplant coronary disease, its prognostic significance has not been well defined. METHODS: The study cohort consisted of 143 patients who underwent early multivessel (2.1 +/- 0.7 arteries/patient) IVUS examination 1.0 +/- 0.5 month and 12.0 +/- 1.0 month after transplantation. The change in intimal thickness was evaluated using paired analysis of 1,069 matched sites. Rapidly progressive vasculopathy was defined as the change in intimal thickness >/=0.5 mm. Patients were followed for a primary end point of all-cause mortality and a secondary composite end point of mortality and nonfatal myocardial infarction (MI). Angiographic disease, defined as any >/=50% diameter stenosis, was assessed in 126 patients. RESULTS: Intravascular ultrasound at one year demonstrated rapid progression in 54 (37%) of 143 patients and new lesions in 67 (47%) of 143 of patients. At a mean clinical follow-up of 5.9 years, more patients with rapidly progressive vasculopathy died, as compared with those without (26% vs. 11%, p = 0.03). Death and MI also occurred more frequently among those with rapid progression than in those without it (51% vs. 16%, p < 0.0001). There was no significant difference in outcome in patients with and without donor-transmitted lesions. Angiographic disease was found in 11 (22%) of 50 patients with and in 2 (2.1%) of 76 patients without (p = 0.003) rapidly progressive vasculopathy. The IVUS-defined rapid progression correlated highly with future development of angiographic disease (p = 0.0005). CONCLUSIONS: Rapidly progressive vasculopathy by IVUS, defined as an increase of >/=0.5 mm in intimal thickness within the first year after transplantation, is a powerful predictor of all-cause mortality, MI, and angiographic abnormalities. Accordingly, such patients may be candidates for more aggressive anti-atherosclerotic and/or immunosuppressive therapy.     

Low clinical utility of routine angiographic surveillance in the detection and management of cardiac allograft vasculopathy in transplant recipients

BACKGROUND: Cardiac allograft vasculopathy (CAV), a form of accelerated atherosclerosis, is the major cause of late death in heart transplant recipients. Routine annual coronary angiography has been used as the standard surveillance technique for CAV in most transplant centers. HYPOTHESIS: The aim of this study was to investigate the clinical utility of routine angiographic surveillance in the detection and management of CAV in transplant recipients. METHODS: We reviewed the case notes and angiograms of 230 patients who underwent cardiac transplantation in our unit between January 1986 and January 1996 and survived beyond the first year post transplantation. RESULTS: Significant complications secondary to angiography arose in 19 patients (8.2%). Cardiac allograft vasculopathy was present on none of angiograms performed 3 weeks post transplantation, but was identified in 9 patients (4%) at the first annual angiogram and an additional 25 patients by the fifth annual angiogram. A target lesion suitable for angioplasty was only identified in two patients, and only limited procedural success was achieved in both cases. Twenty-five patients (11%) died during the study period, and the most common cause of late death was graft failure which occurred in 10 patients. All patients who died from graft failure had significant CAV at autopsy, but the most recent coronary angiogram had been normal in eight of these patients. CONCLUSIONS: These data clearly illustrate the limited clinical utility of routine angiographic surveillance for CAV in heart transplant recipients and prompted us to abandon this method of surveillance in our unit.     

The impact of mode of donor brain death on cardiac allograft vasculopathy: an intravascular ultrasound study

OBJECTIVES: We evaluated the association of mode of brain death with cardiac allograft vasculopathy. BACKGROUND: Explosive brain death (EBD) is accompanied by a sudden increase in intracranial pressure, with recruitment of pro-inflammatory cytokines, as well as adhesion cell and co-stimulatory molecules. Whether these early events influence the later development of cardiac allograft vasculopathy following heart transplantation remains unknown. METHODS: An inception cohort of 61 consecutive heart transplant recipients between 1993 and 1995 who underwent intravascular ultrasound examination of the coronary arteries were evaluated. Based on the mode of donor brain death, this cohort was divided into either an EBD group (n = 27) or non-EBD (n = 34), and the development of intimal thickness and cardiac events (sudden cardiac death, myocardial infarction, and need for coronary revascularization via percutaneous techniques or surgical bypass) was assessed. RESULTS: Despite similar posttransplant survival and distribution of nonimmunological and immunological variables, heart transplant recipients with EBD demonstrated greater intimal thickening (0.59 +/- 0.1 vs. 0.32 +/- 0.2 mm; p = 0.02) and higher cardiac events (37% vs. 12%; p = 0.01) when compared to those with non-EBD donors. Hearts from donors with EBD had lower survival (63 +/- 19 vs. 72 +/- 17 months) than with non-EBD donors (p = 0.04). CONCLUSIONS: Explosive brain death is a significant determinant for the late development of cardiac allograft vasculopathy and influences long-term allograft survival. Thus, strategies focusing on limitation of vascular allograft injury in the pre-engraftment phase of cardiac transplantation are warranted.     

Intravascular ultrasound for assessment of coronary allograft vasculopathy

Summary Coronary allograft vasculopathy (CAV) is the major factor limiting the long-term survival after cardiac transplantation. Intravascular ultrasound (IVUS) markedly improved our knowledge about in vivo morphology of CAV by precise determination of vessel morphology. In vivo studies with IVUS demonstrated that transplant vasculopathy may present with a very hetereogeneous morphology suggesting a dual etiology of transplant coronary artery disease. The high incidence of donor-transmitted atherosclerosis and its role in further progression of CAV could be demonstrated by the use of IVUS. Beside intimal hyperplasia, adaptive remodeling processes of vessel and lumen geometry may have physiologic and prognostic importance. IVUS is so far the only method that allows the evaluation of compensatory enlargement and shrinkage of coronary vessels in CAV. IVUS investigations allow the assessment of CAV progression in early angiographically not visible stages. The influence of different medical treatment regimens on CAV progression can be quantified. Further studies showed that IVUS parameters may have prognostic impact on subsequent clinical events and angiographic progression of CAV. However, besides all the diagnostic information provided by IVUS, the main application of this method is currently in the field of clinical research.     

Impact of lipid abnormalities in development and progression of transplant coronary disease: a serial intravascular ultrasound study.

OBJECTIVES: We sought to determine the role of conventional atherosclerosis risk factors in the development and progression of transplant coronary artery disease (CAD) using serial intravascular ultrasound imaging. BACKGROUND: Transplant artery disease is a combination of allograft vasculopathy and donor atherosclerosis. The clinical determinants for each of these disease processes are not well characterized. Intravascular ultrasound imaging is the most sensitive tool to serially study these processes. METHODS : Baseline intravascular ultrasound imaging was performed 0.9 +/- 0.5 months after transplantation to identify donor atherosclerosis. Follow-up imaging was performed at 1.0 +/- 0.07 year to evaluate progression of donor atherosclerosis and development of transplant vasculopathy. Conventional risk factors for CAD included recipient age, gender, smoking history, diabetes mellitus, hypertension and hypercholesterolemia. RESULTS : Donor-transmitted atherosclerosis was present in 36 patients (39%). At follow-up, progression of donor lesions was seen in 15 patients (42%) and 42 patients (45%) developed transplant vasculopathy, leaving 35 patients (38%) without any disease. There was no difference in any conventional risk factors in patients with and without allograft vasculopathy. However, the severity of allograft vasculopathy was associated with a larger increase in low density lipoprotein (LDL) cholesterol from baseline (p = 0.02). High one-year posttransplant serum triglyceride level and pretransplant body mass index were the only significant predictors (p = 0.03) for progression of donor atherosclerosis. CONCLUSIONS: Conventional atherosclerosis risk factors do not predict development of allograft vasculopathy, but greater change in serum LDL cholesterol level during the first year after transplant is associated with more severe vasculopathy. Therefore, maintenance of LDL cholesterol as close to pretransplant values as possible may help to limit the rate of progression of acquired allograft vasculopathy.     

Vascular remodeling in transplant vasculopathy

As therapeutic strategies to prevent acute rejection progressively improve, transplant vasculopathy (TV) constitutes the single most important limitation for long-term functioning of solid organ allografts. In TV, allograft arteries characteristically develop severe, diffuse intimal hyperplastic lesions that eventually compromise luminal flow and cause ischemic graft failure. Traditional immunosuppressive strategies that check acute allograft rejection do not prevent TV; indeed 50% of transplant recipients will have significant disease within five years of organ transplantation, and 90% will have significant TV a decade after their surgery. TV can involve the entire length of the transplanted arterial bed, including penetrating intraorgan arterioles. Indeed, the luminal narrowing of such penetrating vessels may be the most functionally significant because arterioles represent the major contributors to tissue vascular resistance. Because of the diffuseness of TV involvement in the allograft vascular bed, the only currently definitive therapy requires re-transplantation. Nevertheless, as we better understand the pathogenesis and critical mediators of these lesions, pharmacological advances can be anticipated. Other articles in this thematic review series focus on the specifics of the inciting injury, the cytokines and chemokines that drive TV development, and the nature of the recruited cells in TV lesions, as well as the pathogenic similarities between TV and other vascular lesions such as atherosclerosis. This review focuses on the mechanisms of vascular wall remodeling in TV, including the intimal accumulation of smooth muscle-like cells and associated extracellular matrix, medial smooth muscle cell degeneration, and adventitial fibrosis. A brief overview highlights the aneurysmal changes that can accrue when vessel wall inflammation has a cytokine profile distinct from the typical proinflammatory interferon-gamma-dominated milieu.     

Endothelial Dysfunction and Cardiac Allograft Vasculopathy

Cardiac allograft vasculopathy remains a major challenge to long-term survival after heart transplantation. Endothelial injury and dysfunction, as a result of multifactorial immunologic and nonimmunologic insults in the donor and the recipient, are prevalent early after transplant and may be precursors to overt cardiac allograft vasculopathy. Current strategies for managing cardiac allograft vasculopathy, however, rely on the identification and treatment of established disease. Improved understanding of mechanisms leading to endothelial dysfunction in heart transplant recipients may provide the foundation for the development of sensitive screening techniques and preventive therapies.     

Long-term clinical outcomes in patients treated with drug-eluting compared to bare-metal stents for the treatment of transplant coronary artery disease

Objective : We aimed to compare the long‐term clinical outcomes of first‐vessel percutaneous coronary intervention (PCI) with drug‐eluting stents (DES) and bare metal stents (BMS) for the treatment of transplant coronary artery disease (TCAD). Background : TCAD is the leading cause of late death in orthotopic heart transplantation (OHT) recipients. PCI is associated with worse clinical outcomes compared with non‐OHT patients. Our institution previously reported superior angiographic outcomes with DES compared with BMS in OHT patients. However, long‐term clinical outcomes comparing PCI with DES versus BMS are lacking. Methods : The data on 105 OHT recipients who underwent first‐vessel PCI with DES (n = 58) or BMS (n = 47) at UCLA Medical Center between 1995 and 2009 were retrospectively analyzed. Results : Five‐year clinical outcomes were not significantly different with DES and BMS in terms of the composite of death, myocardial infarction (MI), or target vessel revascularization (TVR) [(40.8 ± 7.2)% vs. (59.6 ± 7.2)%, log‐rank P = 0.33], death [(31.8 ± 7.8)% vs. (40.4 ± 7.2)%, log‐rank P = 0.46], MI [(12.2 ± 6.2)% vs. (11.3 ± 5.4)%, log rank P = 0.98], TVR [(25.5 ± 6.9)% vs. (26.5 ± 7.3)%, log rank P = 0.76], and time to repeat OHT [(2.27 ± 1.79) vs. (3.22 ± 3.34), P = 0.98]. Conclusions : At long‐term follow‐up, PCI with DES and BMS provided similar clinical outcomes in OHT. Long‐term mortality remains high in OHT recipients after PCI with either DES or BMS. Randomized clinical trials are required to determine the optimal treatment strategy for OHT recipients with TCAD. © 2012 Wiley Periodicals, Inc.     

Outcomes in cardiac transplant recipients using allografts from older donors versus mortality on the transplant waiting list; Implications for donor selection criteria

OBJECTIVES: This study investigates the outcomes of cardiac transplantation using older donors. BACKGROUND: Despite high mortality rates on waiting lists, transplanting hearts from older donors remains a relative contraindication. METHODS: We retrospectively reviewed data on 479 adult heart transplant recipients, 352 status I patients, and 534 status II patients enrolled on a waiting list between 1992 and 1999. The Cox proportional hazards model was used for statistical analysis. RESULTS: Of all donors, 20% were 40 to 50 years old and 8% were > or =50 years old. The risk of six-month mortality on the waiting list for patients who were not transplanted (status I: relative risk [RR] 8.5; status II: RR 3.7) significantly outweighed the risk of transplanting patients with a heart from donors >40 years old (status I: RR 1.6; status II: RR 2.1). Recipients of cardiac allografts from donors <40 years old had a one-month mortality rate of 5%, in contrast to 13% and 22% in those receiving allografts from donors 40 to 50 years old and > or =50 years old, respectively. Donor age did not influence long-term survival or frequency of rejections; however, it did correlate with the early presence of transplant-related coronary artery disease (TCAD). By the first annual angiogram, only 17% of recipients with donors <20 years old developed TCAD, in contrast to 26% to 30% and 34% of recipients who received allografts from donors age 20 to 40 years and >40 years, respectively. CONCLUSIONS: Despite a strong association between older donor age and increased post-operative mortality and TCAD, it is more beneficial in terms of patient survival to receive an allograft from a donor >40 years old than to remain on the waiting list.     

The role of vitronectin receptor (alphavbeta3) and tissue factor in the pathogenesis of transplant coronary vasculopathy

OBJECTIVES: This study was undertaken to test the hypothesis that transplant coronary vasculopathy (CV) is associated with increased myocardial protein expression of both tissue factor (TF) and integrin alphavbeta3. BACKGROUND: The vitronectin receptor (integrin alphavbeta3) and TF have recently been found to play a key role in apoptotic cell death and vascular endothelial cell injury. METHODS: A total of 77 heart transplant recipients underwent simultaneous endomyocardial biopsy and intravascular ultrasound (IVUS) at one year of transplant. Patients with pre-existing donor coronary atherosclerosis (n = 35) or with acute rejection (grade >1A, n = 10) at the time of the IVUS were excluded from the analysis. The remaining 32 patients constitute the cohort of the present study. A computerized biopsy score was derived based on the duration and severity of cellular rejection. Both TF and alphavbeta3 expression in the heart biopsy specimens were evaluated by immunoperoxidase histochemistry and Western blot analysis. RESULTS: Patients with CV (n = 24) had increased expression of alphavbeta3 (2.7-fold, p = 0.003) and TF (7.9-fold, p = 0.04) compared with patients without evidence of vasculopathy (n = 8). In the absence of myocardial fibrosis, alphavbeta3 expression correlated significantly with the cellular rejection score (r = 0.58, p = 0.02). CONCLUSIONS: Transplant vasculopathy is associated with increased expression of both TF and alphavbeta3. The significant correlation of alphavbeta3 with cellular rejection suggests an important role for this integrin in serving as a mechanistic link between cellular rejection and vasculopathy.     

Increased incidence of atrial flutter associated with the rejection of heart transplantation

Atrial fibrillation (AF) and atrial flutter (Afl) are common dysrhythmias that occur after orthotopic heart transplantation (OHT); however, their etiology and clinical significance have not been defined. To determine the precise incidence of sustained AF and Afl and their association with cardiac rejection, 892 consecutive patients who underwent OHT were studied. A total of 104 patients had 113 episodes of Afl; 102 patients had 117 episodes of AF. The incidence of Afl (12.7%) was the same as AF (13.1%). Sixty-nine AF episodes occurred in first 2 weeks after transplantation, and 22 of which were associated with rejection. In contrast, only 20 Afl episodes occurred the first 2 weeks after OHT, 10 of which were associated with rejection. Fifty-two episodes of Afl occurred during from the third week to 6 months after transplantation, 34 of which were associated with moderate to severe cellular or humoral rejection and/or transplant coronary artery disease (TCAD). All 41 Afl episodes that occurred 6 months after transplantation were associated with cellular and humoral rejection, and/or TCAD. The prevalence of Afl was significantly higher in biatrial than bicaval anastomosis. Atrial conduction defect, manifested by the increase of terminal force of the P wave in lead V(1) of the surface electrocardiogram, predicted the occurrence of Afl and AF associated with rejection in OHT with a sensitivity of 89% and specificity of 92%. These results demonstrate that the incidence of Afl increased after OHT, which might be a consequence of cellular and humoral rejection, and coronary vasculopathy of the transplanted hearts.     

Resting echocardiography and quantitative dipyridamole technetium-99m sestamibi tomography in the identification of cardiac allograft vasculopathy and the prediction of long-term prognosis after heart transplantation.

AIMS: To evaluate the accuracy of echocardiography in conjunction with quantitative high-dose dipyridamole technetium-99m sestamibi tomography (SPECT) in detecting coronary allograft vasculopathy. METHODS AND RESULTS: Seventy-eight consecutive heart transplant recipients underwent echocardiography while at rest and high-dose dipyridamole SPECT within 48 h of a yearly angiogram. Resting wall motion abnormalities were considered significant if present in two or more segments. SPECT was considered abnormal in the presence of reversible/fixed defects. The coronary angiogram was normal in 53, showed non-significant coronary allograft vasculopathy in 13 and significant (> or = 50% stenosis) coronary allograft vasculopathy in 12 cases. Resting wall motion abnormalities were observed in nine cases and perfusion defects in 20. Echocardiography and SPECT were concordant in 59 cases (five positive and 54 negative); in these, accuracy was 100% for significant coronary allograft vasculopathy and 83% for any coronary allograft vasculopathy. Over 6.5+/-2 years, 17 patients suffered coronary allograft vasculopathy-related events, including death in six and retransplantation in three. Resting wall motion abnormalities, SPECT perfusion defects and angiographic coronary allograft vasculopathy were significant predictors of cardiac events. CONCLUSION: Normal resting wall motion at echocardiography coupled to normal stress myocardial perfusion, rules out the presence of significant coronary allograft vasculopathy in many heart transplant recipients. Conversely, resting wall motion abnormalities and perfusion defects strongly predict cardiac events. Therefore, a strategy which reserves angiography for patients with resting wall motion abnormalities and/or perfusion defects may be safe and cost-effective.     

Volumetric remodeling of the proximal left coronary artery: early versus late after heart transplantation.

OBJECTIVES: The aim of this study was to characterize progression of cardiac allograft vasculopathy (CAV) with special respect to coronary artery geometry. BACKGROUND: As previously shown by intravascular ultrasound (IVUS), CAV is characterized by a multifocal intimal hyperplasia. Little is known, however, about vascular remodeling processes influencing vessel geometry and luminal narrowing. METHODS: In 30 heart transplant recipients serial IVUS studies were performed at baseline (BL) and after a mean follow-up period of 12.5+/-2.5 months. Changes in plaque, lumen and vessel volume were assessed in the proximal left anterior descending artery. Pattern of remodeling was analyzed in patients "early" (n = 15, BL study 1.4+/-0.7 months after heart transplantation [HTX]) compared with "late" after HTX (n = 15, BL 46.1+/-29.1 months). RESULTS: Plaque volume was found to increase by a mean of 23.8+/-25.9 mm3, not significantly different within and beyond the 1st year after HTX. Significant differences, however, were observed in changes in vessel volume with a mean decrease of -52.8+/-70.9 mm3 in the early group, whereas late follow-up group presented with an enlargement of 32.3+/-46.0 mm3. Based on these changes, lumen volume decreased by -73.2+/-69.8 mm3 early, in contrast to a slight increase of 5.2+/-32.6 mm3 in the late group. CONCLUSIONS: Progression of CAV is a complex process, modified by changes in the vascular geometry. Especially within the 1st year after HTX, luminal loss is influenced not only by an increase in plaque area but by a decrease in total vessel volume as well.     

Coronary Artery Spasm during Angiography in a Pediatric Heart Transplant Recipient: Subsequent Prevention by Intracoronary Nitroglycerin Administration

Coronary artery spasm can occur during coronary angiography in pediatric heart transplant recipients. The angiographic appearance can suggest allograft vasculopathy. We report coronary artery spasm in a pediatric heart transplant recipient in whom intracoronary nitroglycerin administration prevented a repetition of spasm upon subsequent diagnostic coronary angiography. Additional studies of dose response, particularly in cardiac transplant recipients, may help determine whether lower doses of intracoronary nitrates, such as that administered to our patient, can be effective in preventing coronary artery vasospasm in pediatric heart transplant recipients.Key words: Child, coronary angiography, coronary vasospasm/etiology/pathology/radiography, graft survival, heart transplantation, male, postoperative complications/radiographyCoronary artery spasm has been reported to occur in 4.9% of adult heart transplant recipients during subsequent coronary angiography,¹ but its frequency in children during coronary angiography after heart transplantation is unreported. Because coronary artery spasm can produce generalized luminal narrowing, such spasm can be difficult to distinguish angiographically from cardiac allograft vasculopathy, although this last is morphologically different and at times distinguishable from coronary spasm.²We describe a case wherein coronary spasm resulted from coronary angiography and produced temporary cardiac compromise, leading to a provisional diagnosis of graft vascular disease. Subsequent angiography, preceded by the intracoronary administration of nitroglycerin, showed the affected vessels to be closer to normal in appearance and had no adverse effects, which suggested that transient vasospasm had been responsible for the angiographic appearance of diffuse luminal narrowing.     

Angiotensin II receptors from peritransplantation through first-year post-transplantation and the risk of transplant coronary artery disease

OBJECTIVES: We evaluated whether the angiotensin II (Ang II) receptors from perioperation through one-year post-transplantation predict the transplant coronary artery disease (TCAD) progression. BACKGROUND: The role of Ang II receptors (type 1: AT(1)R; type 2: AT(2)R) in TCAD is uncertain. METHODS: We investigated 28 heart donors and the corresponding recipients. The levels of AT(1)R and AT(2)R messenger ribonucleic acid (mRNA) were examined in lymphocytes from the donor spleen and in the donor heart at one-week and one-year posttransplantation to determine their association with the progression of TCAD, measured as changes in maximal intimal thickness (CMIT) and plaque volume (CPV) by intravascular ultrasound (IVUS) examinations. RESULTS: The AT(1)R mRNA in lymphocytes from the donor spleen (CMIT: r = 0.73, p < 0.0001; CPV: r = 0.69, p < 0.0001) and in the donor hearts at one-week (CMIT: r = 0.52, p = 0.005; CPV: r = 0.56, p = 0.002) and at one-year (CMIT: r = 0.63, p < 0.0001; CPV: r = 0.43, p = 0.004) post-transplantation along with AT(2)R mRNA in the donor hearts at one-year post-transplantation (CMIT: r = 0.3, p < 0.0001; CPV: r = 0.53, p = 0.009) were univariate predictors, whereas AT(1)R mRNA in lymphocytes and in the donor hearts at one-year post-transplantation proved to be multivariate predictors of the progression of TCAD. CONCLUSIONS: These data suggest a role for Ang II receptors in the pathogenesis of TCAD and support a novel concept that TCAD may have its origin in the donor per se and may be modulated by the recipient's inherent biological factors.     

Interaction between donor and recipient age in determining the risk of chronic renal allograft failure

OBJECTIVES: Donor age is a known risk factor for chronic allograft failure (CAF) in renal transplant recipients. We have recently shown that advanced recipient age is also a risk factor for CAF. To investigate the interaction between donor and recipient age, we analyzed 40,289 primary solitary Caucasian adult renal transplants registered at the United States Renal Data System (USRDS) from 1988 to 1997. DESIGN: CAF was defined as allograft loss beyond 6 months posttransplantation, censored for death, recurrent disease, acute rejection, thrombosis, noncompliance, infection, or technical problems. Cox proportional hazards models were used to investigate the risk of allograft loss secondary to CAF. All models were corrected for 15 covariates including donor and recipient demographics, ischemic time, and human leukocyte antigen match. Donor and recipient age were categorized, and relative risk for allograft loss of the interaction between the obtained categorical covariates was evaluated. SETTING: Retrospective data analysis using the USRDS. PARTICIPANTS: All primary Caucasian renal transplant recipients from 1988 to 1997. RESULTS: Patients aged 55 and older who received donor kidneys had a 110% increased risk of CAF (relative risk (RR) = 2.1, 95% confidence interval (CI) = 1.9-2.3, P< .001) and recipients aged 65 and older had a 90% increased risk for CAF (RR = 1.9, 95% CI = 1.61-2.1, P< .001), compared with the youngest reference groups. In addition, there was an additive and, in the long term, synergistic interaction between donor and recipient age in determining allograft loss. CONCLUSIONS: Donor and recipient age had an independent, equivalently detrimental effect on renal allograft survival. An overall additive and, in the long term (beyond 36 months posttransplant), synergistic deleterious effect on renal allograft survival was observed for the interaction of donor and recipient age.