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Cardiac Allograft Vasculopathy (cardiac + allograft_vasculopathy)
Selected AbstractsCoronary Flow Reserve by Transthoracic Echocardiography Predicts Epicardial Intimal Thickening in Cardiac Allograft VasculopathyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2010F. Tona Cardiac allograft vasculopathy (CAV) is the leading cause of morbidity and mortality in heart transplantation (HT). We sought to investigate the role of coronary flow reserve (CFR) by contrast-enhanced transthoracic echocardiography (CE-TTE) in CAV diagnosis. CAV was defined as maximal intimal thickness (MIT) assessed by intravascular ultrasound (IVUS) ,0.5 mm. CFR was assessed in the left anterior descending coronary artery in 22 HT recipients at 6 ± 4 years post-HT. CAV was diagnosed in 10 patients (group A), 12 had normal coronaries (group B). The mean MIT was 0.7 ± 0.1 mm (range 0.03,1.8). MIT was higher in group A (1.16 ± 0.3 mm vs. 0.34 ± 0.07 mm, p < 0.0001). CFR was 3.1 ± 0.8 in all patients and lower in group A (2.5 ± 0.6 vs. 3.7 ± 0.3, p < 0.0001). CFR was inversely related with MIT (r =,0.774, p < 0.0001). A cut point of ,2.9, identified as optimal by receiver operating characteristics analysis was 100% specific and 80% sensitive (PPV = 100%, NPV = 89%, Accuracy = 91%). CFR assessment by CE-TTE is a novel noninvasive diagnostic tool in the detection of CAV defined as MIT ,0.5 mm. CFR by CE-TTE may reduce the need for routine IVUS in HT. [source] Systemic Markers of Inflammation Are Associated with Cardiac Allograft Vasculopathy and an Increased Intimal Inflammatory ComponentAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2010S. Arora We evaluated an extensive profile of clinical variables and immune markers to assess the inflammatory milieu associated with cardiac allograft vasculopathy (CAV) assessed by intravascular ultrasound (IVUS) and virtual histology (VH). In total, 101 heart transplant (HTx) recipients were included and underwent IVUS/VH examination and measurement of plasma C-reactive protein (CRP), soluble tumor necrosis factor receptor-1, interleukin-6, osteoprotegerin, soluble gp130, von Willebrand factor, vascular cell adhesion molecule-1 (VCAM-1) and neopterin. Mean Maximal Intimal Thickness (MIT) was 0.61 ± 0.19 mm and mean fibrotic, fibrofatty, dense calcified and necrotic core components were 55 ± 15, 14 ± 10, 15 ± 13 and 17 ± 9%, respectively. In multivariate analysis, CRP > 1.5 mg/L (OR 4.6, p < 0.01), VCAM-1 > 391 ng/mL (adjusted OR 3.2, p = 0.04) and neopterin > 7.7 nmol/L (OR 3.8, p = 0.02) were independently associated with MIT > 0.5 mm. Similarly, CRP > 1.5 mg/L (OR 3.7, p < 0.01) and VCAM-1 > 391 (OR 2.7, p = 0.04) were independently associated with an increased intimal inflammatory component (dense calcified/necrotic core component > 30%). Advanced CAV is associated with elevated CRP, VCAM-1 and neopterin and the two former biomarkers are also associated with an increased intimal inflammatory component. Forthcoming studies should clarify if routine measurements of these markers can accurately identify HTx recipients at risk of developing advanced CAV and vulnerable lesions. [source] Macrophage Depletion Suppresses Cardiac Allograft Vasculopathy in MiceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2007W. H. Kitchens Cardiac allograft vasculopathy (CAV) is a major source of late posttransplant mortality. Although numerous cell types are implicated in the pathogenesis of CAV, it is unclear which cells actually induce the vascular damage that results in intimal proliferation. Because macrophages are abundant in CAV lesions and are capable of producing growth factors implicated in neointimal proliferation, they are leading end-effector candidates. Macrophages were depleted in a murine heterotopic cardiac transplant system known to develop fulminant CAV lesions. C57BL/6 hearts were transplanted into (C57BL/6 × BALB/c)F1 recipients, which then received anti-macrophage therapy with intraperitoneal carrageenan or i.v. gadolinium. Intraperitoneal carrageenan treatment depleted macrophages by 30,80% with minimal effects upon T, B or NK cells as confirmed by flow cytometry and NK cytotoxicity assays. Carrageenan treatment led to a 70% reduction in the development of CAV, as compared to mock-treated controls (p = 0.01), which correlated with the degree of macrophage depletion. Inhibition of macrophage phagocytosis alone with gadolinium failed to prevent CAV. Macrophages may represent the end-effector cells in a final common pathway towards CAV independent of T-cell or B-cell alloreactivity and exert their injurious effects through mechanisms related to cytokine/growth factor production rather than phagocytosis. [source] Coronary Flow Reserve by Contrast-Enhanced Echocardiography: A New Noninvasive Diagnostic Tool for Cardiac Allograft VasculopathyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5p1 2006F. Tona Noninvasive tests have proven unsatisfactory in cardiac allograft vasculopathy (CAV) diagnosis. We assessed coronary flow reserve (CFR) by contrast-enhanced transthoracic echocardiography (CE-TTE) in heart transplantation (HT). CFR was assessed in the left anterior descending coronary artery in 73 HT recipients (59 male, aged 50 ± 12 years at HT), at 8 ± 4.5 years post-HT. CFR measurements were taken blindly from coronary angiographies. CFR cut points were the standard value of ,2 and those defined by receiver operating characteristics (ROC) curve analysis. CFR was lower in patients with CAV (2.3 ± 0.7 vs. 3.2 ± 0.5, p < 0.0001). The ,2 cut point was 100% specific and 38% sensitive. The ,2.7 cut point, optimal by ROC analysis, was 87% specific and 82% sensitive. Accuracy rose from 71% with the standard ,2 cut point to 85% with the optimal cut point of ,2.7. CFR by CE-TTE may offer promise as a novel, easily repeatable and accurate noninvasive tool in CAV detection. However, further longitudinal studies in larger patient cohorts are warranted before widespread adoption can be advocated. [source] Impaired Left Ventricular Systolic Function Early After Heart Transplantation is Associated with Cardiac Allograft VasculopathyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2006I.A. Bolad Cardiac allograft vasculopathy (CAV) is a major cause of death more than 1 year after heart transplantation. We evaluated the role and possible predictive value of different etiological factors on development of CAV as diagnosed by quantitative coronary angiography (QCA). A total of 121 patients were studied with baseline QCA and 117 had a follow-up study at 1 year to assess the relationship of mean lumen diameter loss (MLDL) in main coronary arteries to immunological and non-immunological factors potentially affecting long-term survival. Out of them, 103 patients were males (85%), 114 (94%) patients were Caucasians and mean age was 48.5 ± 10 years. Univariate analysis showed that MLDL at 1 year was inversely related to echocardiographic fractional shortening (FS) measured within the first week after transplantation (p = 0.0098) and to intracranial hemorrhage as cause of donor death (p = 0.04) and was directly related to male donors (p = 0.0008), domino transplants (p = 0.037) and donor negative cytomegalovirus (CMV) status (p = 0.022). Multivariate analysis showed that initial FS (p = 0.006) and donor intracranial hemorrhage as a cause of death (p = 0.042) were inversely related to MLDL whereas donor male sex (p = 0.003) and prednisolone treatment throughout the first year (p = 0.012) were directly related. Thus, left ventricular systolic dysfunction early after heart transplantation was associated with subsequent development of CAV. [source] ,Rapping' up Cardiac Allograft VasculopathyCLINICAL CARDIOLOGY, Issue 6 2008Zain Khalpey M.R.C.S. No abstract is available for this article. [source] Coronary Flow Reserve by Transthoracic Echocardiography Predicts Epicardial Intimal Thickening in Cardiac Allograft VasculopathyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2010F. Tona Cardiac allograft vasculopathy (CAV) is the leading cause of morbidity and mortality in heart transplantation (HT). We sought to investigate the role of coronary flow reserve (CFR) by contrast-enhanced transthoracic echocardiography (CE-TTE) in CAV diagnosis. CAV was defined as maximal intimal thickness (MIT) assessed by intravascular ultrasound (IVUS) ,0.5 mm. CFR was assessed in the left anterior descending coronary artery in 22 HT recipients at 6 ± 4 years post-HT. CAV was diagnosed in 10 patients (group A), 12 had normal coronaries (group B). The mean MIT was 0.7 ± 0.1 mm (range 0.03,1.8). MIT was higher in group A (1.16 ± 0.3 mm vs. 0.34 ± 0.07 mm, p < 0.0001). CFR was 3.1 ± 0.8 in all patients and lower in group A (2.5 ± 0.6 vs. 3.7 ± 0.3, p < 0.0001). CFR was inversely related with MIT (r =,0.774, p < 0.0001). A cut point of ,2.9, identified as optimal by receiver operating characteristics analysis was 100% specific and 80% sensitive (PPV = 100%, NPV = 89%, Accuracy = 91%). CFR assessment by CE-TTE is a novel noninvasive diagnostic tool in the detection of CAV defined as MIT ,0.5 mm. CFR by CE-TTE may reduce the need for routine IVUS in HT. [source] Macrophage Depletion Suppresses Cardiac Allograft Vasculopathy in MiceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 12 2007W. H. Kitchens Cardiac allograft vasculopathy (CAV) is a major source of late posttransplant mortality. Although numerous cell types are implicated in the pathogenesis of CAV, it is unclear which cells actually induce the vascular damage that results in intimal proliferation. Because macrophages are abundant in CAV lesions and are capable of producing growth factors implicated in neointimal proliferation, they are leading end-effector candidates. Macrophages were depleted in a murine heterotopic cardiac transplant system known to develop fulminant CAV lesions. C57BL/6 hearts were transplanted into (C57BL/6 × BALB/c)F1 recipients, which then received anti-macrophage therapy with intraperitoneal carrageenan or i.v. gadolinium. Intraperitoneal carrageenan treatment depleted macrophages by 30,80% with minimal effects upon T, B or NK cells as confirmed by flow cytometry and NK cytotoxicity assays. Carrageenan treatment led to a 70% reduction in the development of CAV, as compared to mock-treated controls (p = 0.01), which correlated with the degree of macrophage depletion. Inhibition of macrophage phagocytosis alone with gadolinium failed to prevent CAV. Macrophages may represent the end-effector cells in a final common pathway towards CAV independent of T-cell or B-cell alloreactivity and exert their injurious effects through mechanisms related to cytokine/growth factor production rather than phagocytosis. [source] Impaired Left Ventricular Systolic Function Early After Heart Transplantation is Associated with Cardiac Allograft VasculopathyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 1 2006I.A. Bolad Cardiac allograft vasculopathy (CAV) is a major cause of death more than 1 year after heart transplantation. We evaluated the role and possible predictive value of different etiological factors on development of CAV as diagnosed by quantitative coronary angiography (QCA). A total of 121 patients were studied with baseline QCA and 117 had a follow-up study at 1 year to assess the relationship of mean lumen diameter loss (MLDL) in main coronary arteries to immunological and non-immunological factors potentially affecting long-term survival. Out of them, 103 patients were males (85%), 114 (94%) patients were Caucasians and mean age was 48.5 ± 10 years. Univariate analysis showed that MLDL at 1 year was inversely related to echocardiographic fractional shortening (FS) measured within the first week after transplantation (p = 0.0098) and to intracranial hemorrhage as cause of donor death (p = 0.04) and was directly related to male donors (p = 0.0008), domino transplants (p = 0.037) and donor negative cytomegalovirus (CMV) status (p = 0.022). Multivariate analysis showed that initial FS (p = 0.006) and donor intracranial hemorrhage as a cause of death (p = 0.042) were inversely related to MLDL whereas donor male sex (p = 0.003) and prednisolone treatment throughout the first year (p = 0.012) were directly related. Thus, left ventricular systolic dysfunction early after heart transplantation was associated with subsequent development of CAV. [source] Low clinical utility of routine angiographic surveillance in the detection and management of cardiac allograft vasculopathy in transplant recipientsCLINICAL CARDIOLOGY, Issue 6 2001FRCPI, Jonathan R. Clague M.D. Abstract 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. [source] Systemic Markers of Inflammation Are Associated with Cardiac Allograft Vasculopathy and an Increased Intimal Inflammatory ComponentAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2010S. Arora We evaluated an extensive profile of clinical variables and immune markers to assess the inflammatory milieu associated with cardiac allograft vasculopathy (CAV) assessed by intravascular ultrasound (IVUS) and virtual histology (VH). In total, 101 heart transplant (HTx) recipients were included and underwent IVUS/VH examination and measurement of plasma C-reactive protein (CRP), soluble tumor necrosis factor receptor-1, interleukin-6, osteoprotegerin, soluble gp130, von Willebrand factor, vascular cell adhesion molecule-1 (VCAM-1) and neopterin. Mean Maximal Intimal Thickness (MIT) was 0.61 ± 0.19 mm and mean fibrotic, fibrofatty, dense calcified and necrotic core components were 55 ± 15, 14 ± 10, 15 ± 13 and 17 ± 9%, respectively. In multivariate analysis, CRP > 1.5 mg/L (OR 4.6, p < 0.01), VCAM-1 > 391 ng/mL (adjusted OR 3.2, p = 0.04) and neopterin > 7.7 nmol/L (OR 3.8, p = 0.02) were independently associated with MIT > 0.5 mm. Similarly, CRP > 1.5 mg/L (OR 3.7, p < 0.01) and VCAM-1 > 391 (OR 2.7, p = 0.04) were independently associated with an increased intimal inflammatory component (dense calcified/necrotic core component > 30%). Advanced CAV is associated with elevated CRP, VCAM-1 and neopterin and the two former biomarkers are also associated with an increased intimal inflammatory component. Forthcoming studies should clarify if routine measurements of these markers can accurately identify HTx recipients at risk of developing advanced CAV and vulnerable lesions. [source] Viral Infection Induces De Novo Lesions of Coronary Allograft Vasculopathy Through a Natural Killer Cell-Dependent PathwayAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009J. A. Graham Viral infections including those due to cytomegalovirus have been associated with accelerated cardiac allograft vasculopathy (CAV) in clinical trials and some animal models. Evidence demonstrating a direct causal relationship between such infections and de novo formation of coronary vascular lesions is lacking. Heterotopic murine cardiac transplants were performed in a parental to F1 combination in animals lacking both T- and B-lymphocytes (RAG,/,). Coronary vasculopathy developed almost exclusively in the presence of recipient infection with lymphocytic choriomeningitis virus but not in uninfected controls. This process was also dependent upon the presence of natural killer (NK) cells as depletion of NK cells abrogated the process. These data show that a viral infection in its native host, and not previously implicated in the production of CAV, can contribute to the development of advanced coronary vascular lesions in cardiac allotransplants in mice. These data also suggest that virus-induced CAV can develop via an NK-cell-dependent pathway in the absence of T- and B-lymphocytes. [source] Strain-Encoded Cardiac Magnetic Resonance for the Evaluation of Chronic Allograft Vasculopathy in Transplant RecipientsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009G. Korosoglou The aim of our study was to investigate the ability of Strain-Encoded magnetic resonance imaging (MRI) to detect cardiac allograft vasculopathy (CAV) in heart transplantation (HTx)-recipients. In consecutive subjects (n = 69), who underwent cardiac catheterization, MRI was performed for quantification of myocardial strain and perfusion reserve. Based on angiographic findings subjects were classified: group A including patients with normal vessels; group B, patients with stenosis <50%; and group C, patients with severe CAV (stenosis , 50%). Significant correlations were observed between myocardial perfusion reserve with peak systolic strain (r =,0.53, p < 0.001) and with mean diastolic strain rate (r = 0.82, p < 0.001). Peak systolic strain and strain rate were significantly reduced only in group C, while mean diastolic strain rate and myocardial perfusion reserve were already reduced in group B and A. Myocardial perfusion reserve and mean diastolic strain rate had higher accuracy for the detection of CAV (AUC = 0.95, 95% CI = 0.87,0.99 and AUC = 0.93, 95% CI = 0.84,0.98, respectively) and followed peak systolic strain and strain rate (AUC = 0.80, 95% CI = 0.69,0.89 and AUC = 0.78, 95% CI = 0.67,0.87, respectively). Besides the quantification of myocardial perfusion, the estimation of the diastolic strain rate is a useful parameter for CAV assessment. In combination with the clinical evaluation, these parameters may be effective tools for the routine surveillance of HTx-recipients. [source] Lack of Effect of MICA Antibodies on Graft Survival Following Heart TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009J. D. Smith Little is known about the effect of MICA antibodies (Abs) on cardiac allograft function and survival. Pretransplant and posttransplant serum from 491 and 196 adult cardiac allograft recipients, respectively, has been investigated for MICA Abs, donor specificity and the effect of MICA Abs on graft survival, acute rejection episodes (AR) and cardiac allograft vasculopathy (CAV). Patients with HLA Abs (11.6%) were excluded from the analysis. A total of 11.8% of patients had MICA Abs, without HLA Abs, before their transplant. Actuarial graft survival demonstrated slightly better survival of patients with donor-specific MICA Abs at 1 and 5 years (88.9% and 83.3%) than patients negative for MICA Abs (72% and 63.7%, p = 0.051). After transplantation, 15.8% of patients produced MICA Abs, and in 17 patients these were produced de novo. There was no effect of pretransplant or posttransplant production of MICA Abs on numbers of AR episodes in year 1, or CAV assessed at years 3 and 5. Immunocytochemistry of cardiac biopsies from 11 patients did not demonstrate a presence of MICA. Sera from only 4/69 patients with MICA Abs fixed complement prior to transplantation and from 7/38 patients following transplantation. In conclusion, this study suggests that MICA Abs do not adversely affect the outcome of cardiac transplantation. [source] Coronary Flow Reserve by Contrast-Enhanced Echocardiography: A New Noninvasive Diagnostic Tool for Cardiac Allograft VasculopathyAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5p1 2006F. Tona Noninvasive tests have proven unsatisfactory in cardiac allograft vasculopathy (CAV) diagnosis. We assessed coronary flow reserve (CFR) by contrast-enhanced transthoracic echocardiography (CE-TTE) in heart transplantation (HT). CFR was assessed in the left anterior descending coronary artery in 73 HT recipients (59 male, aged 50 ± 12 years at HT), at 8 ± 4.5 years post-HT. CFR measurements were taken blindly from coronary angiographies. CFR cut points were the standard value of ,2 and those defined by receiver operating characteristics (ROC) curve analysis. CFR was lower in patients with CAV (2.3 ± 0.7 vs. 3.2 ± 0.5, p < 0.0001). The ,2 cut point was 100% specific and 38% sensitive. The ,2.7 cut point, optimal by ROC analysis, was 87% specific and 82% sensitive. Accuracy rose from 71% with the standard ,2 cut point to 85% with the optimal cut point of ,2.7. CFR by CE-TTE may offer promise as a novel, easily repeatable and accurate noninvasive tool in CAV detection. However, further longitudinal studies in larger patient cohorts are warranted before widespread adoption can be advocated. [source] Low clinical utility of routine angiographic surveillance in the detection and management of cardiac allograft vasculopathy in transplant recipientsCLINICAL CARDIOLOGY, Issue 6 2001FRCPI, Jonathan R. Clague M.D. Abstract 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. [source] | ||||||||||