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Joren C Madsen - One of the best experts on this subject based on the ideXlab platform.

  • b cell clonal expansion within immune infiltrates in human Cardiac Allograft Vasculopathy
    American Journal of Transplantation, 2020
    Co-Authors: Michael M Givertz, Carolina Moore, Baoshan Gao, Krishna M Roskin, Elenarodica Vasilescu, Linda J Addonizio, Joren C Madsen
    Abstract:

    Cardiac Allograft Vasculopathy (CAV) is associated with intragraft B cell infiltrates. Here, we studied the clonal composition of B cell infiltrates using 4 graft specimens with CAV. Using deep sequencing, we analyzed the immunoglobulin heavy chain variable region repertoire in both graft and blood. Results showed robust B cell clonal expansion in the graft but not in the blood for all cases. Several expanded B cell clones, characterized by their uniquely rearranged complementarity-determining region 3, were detected in different locations in the graft. Sequences from intragraft B cells also showed elevated levels of mutated rearrangements in the graft compared to blood B cells. The number of somatic mutations per rearrangement was also higher in the graft than in the blood, suggesting that B cells continued maturing in situ. Overall, our studies demonstrated B cell clonal expansion in human Cardiac Allografts with CAV. This local B cell response may contribute to the pathophysiology of CAV through a mechanism that needs to be identified.

  • depletion of t regulatory cells promotes natural killer cell mediated Cardiac Allograft Vasculopathy
    Transplantation, 2014
    Co-Authors: Tsutomu Hirohashi, Catharine M Chase, P Dellapelle, Divya Sebastian, Evan Farkesh, Robert B Colvin, P S Russell, Alessandro Alessandrini, Joren C Madsen
    Abstract:

    Background A role for NK cells in Cardiac Allograft Vasculopathy (CAV) was suggested by our earlier observation that CAV arises even in the absence of detectable anti-donor T or B cell reactivity in parental to F1 mouse heart grafts. However, prevention of CAV in this setting required the depletion of both NK and CD4+ T cells.

  • international society for heart and lung transplantation working formulation of a standardized nomenclature for Cardiac Allograft Vasculopathy 2010
    Journal of Heart and Lung Transplantation, 2010
    Co-Authors: Mandeep R Mehra, J A Kobashigawa, Joren C Madsen, Randall C Starling, Maria G Crespoleiro, Anne I Dipchand, Stephan M Ensminger, N E Hiemann, Jayan Parameshwar, Patricia A Uber
    Abstract:

    The development of Cardiac Allograft Vasculopathy remains the Achilles heel of Cardiac transplantation. Unfortunately, the definitions of Cardiac Allograft Vasculopathy are diverse, and there are no uniform international standards for the nomenclature of this entity. This consensus document, commissioned by the International Society of Heart and Lung Transplantation Board, is based on best evidence and clinical consensus derived from critical analysis of available information pertaining to angiography, intravascular ultrasound imaging, microvascular function, Cardiac Allograft histology, circulating immune markers, non-invasive imaging tests, and gene-based and protein-based biomarkers. This document represents a working formulation for an international nomenclature of Cardiac Allograft Vasculopathy, similar to the development of the system for adjudication of Cardiac Allograft rejection by histology.

  • macrophage depletion suppresses Cardiac Allograft Vasculopathy in mice
    American Journal of Transplantation, 2007
    Co-Authors: William H Kitchens, Robert B Colvin, P S Russell, C M Chase, Shuichiro Uehara, Lynn D Cornell, Joren C Madsen
    Abstract:

    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 x BALB/c)F(1) 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.

  • effects of mycophenolate mofetil on Cardiac Allograft survival and Cardiac Allograft Vasculopathy in miniature swine
    The Annals of Thoracic Surgery, 2005
    Co-Authors: Margaret L Schwarze, Stuart L Houser, M E Maloney, Ashok Muniappan, James S Allan, Matthew T Menard, Isabel M Mcmorrow, Joren C Madsen
    Abstract:

    Background Chronic rejection, as manifested by Cardiac Allograft Vasculopathy, remains the leading cause of late graft failure in heart transplant recipients. Despite recent clinical trials, the efficacy of mycophenolate mofetil in preventing human Cardiac Allograft Vasculopathy remains controversial. We investigated whether mycophenolate mofetil would prevent Cardiac Allograft Vasculopathy and prolong Cardiac Allograft survival in our well-established miniature swine model of heart transplantation. Methods Hearts disparate at the major histocompatibility complex class I locus were heterotopically transplanted into miniature swine recipients treated with a 12-day course of mycophenolate mofetil (n = 3) or cyclosporine A (n = 3). Allograft survival, acute rejection, and chronic rejection were monitored in the two groups. Results Hearts transplanted with 12 days of cyclosporine were rejected between 46 and 61 days, whereas two of the three hearts transplanted with mycophenolate mofetil remained beating beyond 120 days ( p = 0.02). At necropsy, there was a 4.9% mean prevalence of Cardiac Allograft Vasculopathy in the mycophenolate mofetil group as compared with 16.6% in the cyclosporine group ( p = 0.03). Cardiac Allograft rejection and Vasculopathy in the cyclosporine-treated group was associated with prominent myocardial interferon-γ gene expression, a finding absent in two thirds of the mycophenolate mofetil-treated swine. Moreover, the mycophenolate mofetil-treated swine failed to develop IgM or IgG alloantibodies. Conclusions A short course of mycophenolate mofetil resulted in a longer Allograft survival than a similar course of cyclosporine. Moreover, mycophenolate mofetil reduced the prevalence of Cardiac Allograft Vasculopathy as compared with cyclosporine-treated controls. The salutary effect of mycophenolate mofetil may be related to its ability to decrease interferon-γ expression in the myocardium and prevent the generation of alloantibodies.

William F Fearon - One of the best experts on this subject based on the ideXlab platform.

  • Cardiac Allograft Vasculopathy a review
    Catheterization and Cardiovascular Interventions, 2018
    Co-Authors: Michael S Lee, Ajay J Kirtane, William F Fearon, Rigved V Tadwalkar, Amisha Patel, Chetan B Patel, Ziad A Ali, Sunil V Rao
    Abstract:

    Cardiac Allograft Vasculopathy (CAV) is a complex disease that remains a significant cause of morbidity and mortality after orthotopic heart transplantation (OHT). Originating as a result of inflammatory response, the development and progression of CAV is attributed to endothelial dysfunction, cellular infiltration, and a wide-range of genetic and patient factors. The detection of CAV remains a diagnostic challenge, as symptoms can be variable or absent. While coronary angiography remains the initial test of choice for the diagnosis and surveillance of CAV, intravascular imaging (either by ultrasound or optical coherence tomography) and physiologic assessments are useful adjuncts in the Cardiac catheterization laboratory. Positron emission tomography, computed tomographic, and magnetic resonance imaging may have a role increasing the time interval between invasive screening tests for prognosis. Medical management should include a statin, vasodilator, and tailored immunosuppressive regimen that maximally decrease Allograft rejection and CAV progression while causing minimal side effects. Patients that are less responsive to pharmacotherapy should be considered for invasive management with percutaneous coronary intervention. Although surgical revascularization is a poor option, repeat OHT is the only definitive treatment option but given its morbidity should be reserved for a highly selected patient population.

  • impact of endothelin 1 on Cardiac Allograft Vasculopathy late mortality and re transplantation following heart transplantation
    Journal of the American College of Cardiology, 2018
    Co-Authors: Rushi V Parikh, Alan C Yeung, Hannah A Valantine, Kiran K Khush, Helen Luikart, David Grimm, William F Fearon
    Abstract:

    Cardiac Allograft Vasculopathy (CAV) is a leading cause of mortality and re-transplantation late after heart transplantation (HT). Endothelin-1 (ET-1) has been implicated in the development of CAV, but has not been well-studied after HT. In 90 HT patients, plasma ET-1 was assayed within 8 weeks of

  • coronary endothelial dysfunction and the index of microcirculatory resistance as a marker of subsequent development of Cardiac Allograft Vasculopathy
    Circulation, 2017
    Co-Authors: Jang Hoon Lee, Alan C Yeung, Hannah A Valantine, Kiran K Khush, Helen Luikart, Kozo Okada, Yuhei Kobayashi, Seema Sinha, Yasuhiro Honda, William F Fearon
    Abstract:

    Cardiac Allograft Vasculopathy (CAV) is a leading cause of long-term morbidity and mortality after heart transplantation.1 Conventional methods for monitoring for CAV detect CAV after it has developed, which may be too late to modify its course. Endothelial dysfunction and the index of microcirculatory resistance (IMR) assessed soon after transplantation have both been shown in separate studies to predict development of CAV and long-term adverse outcome.2,3 The purpose of this study (URL: http://clinicaltrials.gov. Unique identifier: NCT01078363) is to quantify the combined impact of early endothelial dysfunction and elevated microvascular resistance as a marker of subsequent development of CAV at 1 year after Cardiac transplantation. Forty-four heart transplant recipients underwent intracoronary acetylcholine injection (50–100 µg over 30 seconds), coronary physiology assessment, and volumetric intravascular ultrasound analysis performed in the left anterior descending coronary artery within 8 weeks after transplantation (baseline) and at 1 year. Endothelial dysfunction was defined as ≥20% change in diameter of the left anterior descending coronary artery as measured by quantitative angiography after acetylcholine and in comparison with baseline angiography.2 Elevated microvascular resistance was defined as an IMR≥20.3 IMR was assessed with a coronary pressure/thermistor-tipped wire …

  • comparison of drug eluting versus bare metal stents in Cardiac Allograft Vasculopathy
    American Journal of Cardiology, 2011
    Co-Authors: Jennifer A Tremmel, Fumiaki Ikeno, Sharon A Hunt, David P Lee, Alan C Yeung, William F Fearon
    Abstract:

    Although not a definitive treatment, percutaneous coronary intervention offers a palliative benefit to patients with Cardiac Allograft Vasculopathy. Given the superior outcomes with drug-eluting stents (DESs) over bare metal stents (BMSs) in native coronary artery disease, similar improvements might be expected in transplant patients; however, the results have been mixed. Consecutive Cardiac transplantation recipients at a single center receiving a stent for de novo Cardiac Allograft Vasculopathy from 1997 to 2009 were retrospectively analyzed according to receipt of a DES versus a BMS. The angiographic and clinical outcomes were subsequently evaluated at 1 year. The baseline clinical and procedural characteristics were similar among those receiving DESs (n = 18) and BMSs (n = 16). Quantitative coronary angiography revealed no difference in the reference diameter, lesion length, or pre-/postprocedural minimal luminal diameter. At the 12-month angiographic follow-up visit, the mean lumen loss was significantly lower in the DES group than in the BMS group (0.19 ± 0.73 mm vs 0.76 ± 0.97 mm, p = 0.02). The DES group also had a lower rate of in-stent restenosis (12.5% vs 33%, p = 0.18), as well as a significantly lower rate of target lesion revascularization (0% vs 19%, p = 0.03). At 1 year, DESs were associated with a lower composite rate of Cardiac death and nonfatal myocardial infarction (12% vs 38%, p = 0.04). In conclusion, DESs are safe and effective in the suppression of neointimal hyperplasia after percutaneous coronary intervention for Cardiac Allograft Vasculopathy, resulting in significantly lower rates of late lumen loss and target lesion revascularization, as well as a reduced combined rate of Cardiac death and nonfatal myocardial infarction.

Hans Eiskjær - One of the best experts on this subject based on the ideXlab platform.

  • cholesterol lowering with evolocumab to prevent Cardiac Allograft Vasculopathy in de novo heart transplant recipients design of the randomized controlled evolvd trial
    Clinical Transplantation, 2020
    Co-Authors: Kaspar Broch, E Gude, K Karason, Goran Dellgren, Finn Gustafsson, Jyri Lommi, Hans Eiskjær, Grunde Gjesdal, Goran Radegran, Karl Lemstrom
    Abstract:

    BACKGROUND: Cardiac Allograft Vasculopathy (CAV) is characterized by diffuse thickening of the arterial intima. Statins reduce the incidence of CAV, but despite the use of statins, CAV remains one of the leading causes of long-term death after heart transplant. Inhibitors of proprotein convertase subtilisin-kexin type 9 (PCSK9) substantially reduce cholesterol levels but have not been tested in heart transplant recipients. METHODS: The Cholesterol lowering with EVOLocumab to prevent Cardiac Allograft Vasculopathy in De-novo heart transplant recipients (EVOLVD) trial (ClinicalTrials.gov Identifier: NCT03734211) is a randomized, double-blind trial designed to test the effect of the PCSK9 inhibitor evolocumab on coronary intima thickness in heart transplant recipients. Adults who have received a Cardiac transplant within the past 4 - 8 weeks are eligible. Exclusion criteria include an estimated glomerular filtration rate < 20 mL/min/1.73 m2 , renal replacement therapy, or contraindications to coronary angiography with intravascular ultrasound. 130 patients will be randomized (1:1) to 12-months' treatment with evolocumab or matching placebo. The primary endpoint is the coronary artery intima thickness as measured by intravascular ultrasound. CONCLUSION: The EVOLVD trial is a randomized clinical trial designed to show whether treatment with the PCSK9 inhibitor evolocumab can ameliorate CAV over the first year after heart transplant.

  • layered fibrotic plaques are the predominant component in Cardiac Allograft Vasculopathy systematic findings and risk stratification by oct
    Jacc-cardiovascular Imaging, 2017
    Co-Authors: Tor Skibsted Clemmensen, Hans Eiskjær, Niels Ramsing Holm, Brian Bridal Logstrup, Evald Hoj Christiansen, Jouke Dijkstra, Trine Orhoj Barkholt, Christian Juhl Terkelsen, Michael Maeng, Steen Hvitfeldt Poulsen
    Abstract:

    Abstract Objectives The aims of this study were to characterize Cardiac Allograft Vasculopathy (CAV) phenotypes using optical coherence tomography (OCT) and to evaluate the prognostic significance of OCT-determined CAV severity. Background Intravascular OCT enables in vivo characterization of CAV microstructure after heart transplantation. Methods Sixty-two patients undergoing heart transplantation were enrolled at routine angiography from September 2013 through October 2015 and prospectively followed until censoring on May 27, 2016. Optical coherence tomographic acquisitions aimed for the longest possible pull-backs, including proximal segments of all 3 major vessels. Plaques and bright spots were analyzed by delineating circumferential borders and measuring the angulation of total circumference. Layers were contoured for absolute and relative estimates. Nonfatal CAV progression (NFCP) during follow-up was registered. NFCP included occluded vessels or severe (≥70%) new angiographic coronary stenosis or percutaneous coronary intervention. Results A total of 172 vessels were categorized as follows: no CAV, n = 111; mild to moderate CAV ( Conclusions OCT enables the detection of CAV-associated plaque compositions and allows early detection and differentiation of vessel wall disease not visible on angiography. LFP was the most prevalent plaque component, was strongly associated with NFCP, and may be associated with stepwise CAV progression caused by organizing mural thrombi. (The GRAFT Study: Evaluation of Graft Function, Rejection and Cardiac Allograft Vasculopathy in First Heart Transplant Recipients; NCT02077764)

  • virtual histology assessment of Cardiac Allograft Vasculopathy following introduction of everolimus results of a multicenter trial
    American Journal of Transplantation, 2012
    Co-Authors: Satish Arora, Hans Eiskjær, Vilborg Sigurdardottir, Thor Ueland, Hans Erik Botker, Bjorn Ekmehag, I Erikstad, Kristina Jansson, Sa Mortensen
    Abstract:

    In this 12-month multicenter Scandinavian study, 78 maintenance heart transplant (HTx) recipients randomized to everolimus with reduced calcineurin inhibitor (CNI) exposure or continued standard CNI-therapy underwent matched virtual histology (VH) examination to evaluate morphological progression of Cardiac Allograft Vasculopathy (CAV). Parallel measurement of a range of inflammatory markers was also performed. A similar rate of quantitative CAV progression was observed in the everolimus (n = 30) and standard CNI group (n = 48) (plaque index 1.9 ± 3.8% and 1.6 ± 3.9%, respectively; p = 0.65). However, VH analysis revealed a significant increase in calcified (2.4 ± 4.0 vs. 0.3 ± 3.1%; p = 0.02) and necrotic component (6.5 ± 8.5 vs. 1.1 ± 8.6%; p = 0.01) among everolimus patients compared to controls. The increase in necrotic and calcified components was most prominent in everolimus patients with time since HTx >5.1 years and was accompanied by a significant increase in levels of von Willebrand (vWF) factor (p = 0.04) and vascular cell adhesion molecule (VCAM) (p = 0.03). Conversion to everolimus and reduced CNI is associated with a significant increase in calcified and necrotic intimal components and is more prominent in patients with a longer time since HTx. A significant increase in vWF and VCAM accompanied these qualitative changes and the prognostic implication of these findings requires further investigation.

  • effect of everolimus introduction on Cardiac Allograft Vasculopathy results of a randomized multicenter trial
    Transplantation, 2011
    Co-Authors: Satish Arora, Hans Eiskjær, Thor Ueland, Bertil Wennerblom, Vilborg Sigurdadottir, Hans Erik Botker, Bjorn Ekmehag, Kjell Jansson, Svendaage Mortensen, Kari Saunamaki
    Abstract:

    Background. Everolimus reduces the progression of Cardiac Allograft Vasculopathy (CAV) in de novo heart transplant (HTx) recipients, but the influence on established CAV is unknown. Methods. In thi ...

Michael S Lee - One of the best experts on this subject based on the ideXlab platform.

  • Cardiac Allograft Vasculopathy a review
    Catheterization and Cardiovascular Interventions, 2018
    Co-Authors: Michael S Lee, Ajay J Kirtane, William F Fearon, Rigved V Tadwalkar, Amisha Patel, Chetan B Patel, Ziad A Ali, Sunil V Rao
    Abstract:

    Cardiac Allograft Vasculopathy (CAV) is a complex disease that remains a significant cause of morbidity and mortality after orthotopic heart transplantation (OHT). Originating as a result of inflammatory response, the development and progression of CAV is attributed to endothelial dysfunction, cellular infiltration, and a wide-range of genetic and patient factors. The detection of CAV remains a diagnostic challenge, as symptoms can be variable or absent. While coronary angiography remains the initial test of choice for the diagnosis and surveillance of CAV, intravascular imaging (either by ultrasound or optical coherence tomography) and physiologic assessments are useful adjuncts in the Cardiac catheterization laboratory. Positron emission tomography, computed tomographic, and magnetic resonance imaging may have a role increasing the time interval between invasive screening tests for prognosis. Medical management should include a statin, vasodilator, and tailored immunosuppressive regimen that maximally decrease Allograft rejection and CAV progression while causing minimal side effects. Patients that are less responsive to pharmacotherapy should be considered for invasive management with percutaneous coronary intervention. Although surgical revascularization is a poor option, repeat OHT is the only definitive treatment option but given its morbidity should be reserved for a highly selected patient population.

  • role of percutaneous coronary intervention in the treatment of Cardiac Allograft Vasculopathy
    American Journal of Cardiology, 2018
    Co-Authors: Michael S Lee, Will Finch, Gentian Lluri, Kyung Woo Park
    Abstract:

    We evaluated our quarter-century experience with percutaneous coronary intervention (PCI) in patients with Cardiac Allograft Vasculopathy (CAV). CAV is a progressive form of atherosclerosis that is characterized by diffuse intimal thickening. It is a major cause of morbidity and mortality after orthotopic heart transplantation (OHT). Effective treatment options are limited. PCI has been used as a palliative treatment in selected patients. We retrospectively analyzed 140 patients with CAV who underwent PCI from 1992 to 2017 at the University of California, Los Angeles (UCLA) Medical Center. The primary end point was freedom from death, myocardial infarction (MI), target vessel revascularization (TVR), and repeat OHT, at a follow-up of 10 years. PCI was unsuccessful in 3 patients (2%). Balloon angioplasty (n = 7), bare metal stents (n = 50), or drug-eluting stents (DES, n = 80) were used for PCI. Freedom from the primary end point was 17 ± 8%. The use of DES did not provide significant benefit for the primary end point (23 ± 14% vs 10 ± 9%, p = 0.16). Freedom from the individual end points was low: death was 43 ± 10%, MI was 74 ± 12%, TVR was 54 ± 12%, and repeat OHT was 42 ± 15%. Freedom from TVR was not significantly different from DES and bare metal stent (67 ± 14% vs 52 ± 20%, p = 0.46). In conclusion, among patients who underwent PCI for CAV, freedom from the composite of death, MI, TVR, and repeat OHT was low.

  • Cardiac Allograft Vasculopathy
    Reviews in Cardiovascular Medicine, 2011
    Co-Authors: Michael S Lee, Will Finch, Giora Weisz, Ajay J Kirtane
    Abstract:

    Cardiac Allograft Vasculopathy (CAV) is the most important cause of morbidity and mortality following Cardiac transplantation. CAV is largely mediated by immunologic damage and infiltration of the endothelium, resulting in proliferation of vascular smooth muscle cells and subsequent luminal narrowing. There are various risk factors for the development and progression of CAV. Coronary angiography is the gold standard for the diagnosis of CAV; intravascular ultrasound also plays an important role. The management of CAV includes immunosuppression, drugs that modify conventional coronary artery disease risk factors, and percutaneous coronary intervention (PCI) or surgical revascularization for severe obstructive lesions. Although revascularization with PCI has a high immediate success rate, rates of in-stent restenosis are higher as compared with PCI of native coronary arteries, although the advent of drug-eluting stents has somewhat improved in-stent restenosis rates. Thus, the only definitive treatment of CAV is repeat transplantation. Randomized trials are needed to determine the optimal immunosuppressive and conventional risk factor-modifying agents and revascularization strategies for patients who develop CAV.

  • comparison of percutaneous coronary intervention with bare metal and drug eluting stents for Cardiac Allograft Vasculopathy
    Jacc-cardiovascular Interventions, 2008
    Co-Authors: Michael S Lee, J A Kobashigawa, Jonathan M Tobis
    Abstract:

    Objectives We sought to compare percutaneous coronary intervention (PCI) with bare-metal stents (BMS) and drug-eluting stents (DES) for Cardiac Allograft Vasculopathy (CAV). Background Cardiac Allograft Vasculopathy is a rapidly progressive form of atherosclerosis and is one of the main limitations to long-term survival after orthotopic heart transplantation. Percutaneous coronary intervention has been used as a palliative treatment option for CAV but is associated with worse clinical outcomes and greater rate of restenosis compared with PCI of native coronary arteries. Methods Between 1995 and 2007, data on 82 consecutive heart transplant patients who underwent PCI with BMS and DES at the University of California at Los Angeles Medical Center were retrospectively analyzed. Results A total of 82 lesions were treated with 98 BMS and 76 lesions were treated with 80 DES. Follow-up angiography was performed on 57 of 82 lesions (70%) treated with BMS and 58 of 76 (76%) treated with DES (p = 0.7) at a mean follow-up of 9.5 ± 5.5 months for BMS and 12.6 ± 8.2 months for DES (p = 0.02). Compared with BMS, DES was associated with a lower binary restenosis rate (12% vs. 30%, p = 0.02), lower percent diameter stenosis (24 ± 20 vs. 34 ± 36, p = 0.06), and less late lumen loss (0.24 ± 0.75 mm vs. 0.82 ± 1.03 mm, p = 0.01). No angiographic stent thrombosis was observed with DES. Conclusions When compared with BMS, PCI with DES was safe and reduced the rate of angiographic restenosis in patients with CAV. A randomized clinical trial comparing BMS versus DES with longer follow-up is needed to identify the optimal long-term revascularization strategy in patients with CAV.

Alan C Yeung - One of the best experts on this subject based on the ideXlab platform.

  • impact of endothelin 1 on Cardiac Allograft Vasculopathy late mortality and re transplantation following heart transplantation
    Journal of the American College of Cardiology, 2018
    Co-Authors: Rushi V Parikh, Alan C Yeung, Hannah A Valantine, Kiran K Khush, Helen Luikart, David Grimm, William F Fearon
    Abstract:

    Cardiac Allograft Vasculopathy (CAV) is a leading cause of mortality and re-transplantation late after heart transplantation (HT). Endothelin-1 (ET-1) has been implicated in the development of CAV, but has not been well-studied after HT. In 90 HT patients, plasma ET-1 was assayed within 8 weeks of

  • coronary endothelial dysfunction and the index of microcirculatory resistance as a marker of subsequent development of Cardiac Allograft Vasculopathy
    Circulation, 2017
    Co-Authors: Jang Hoon Lee, Alan C Yeung, Hannah A Valantine, Kiran K Khush, Helen Luikart, Kozo Okada, Yuhei Kobayashi, Seema Sinha, Yasuhiro Honda, William F Fearon
    Abstract:

    Cardiac Allograft Vasculopathy (CAV) is a leading cause of long-term morbidity and mortality after heart transplantation.1 Conventional methods for monitoring for CAV detect CAV after it has developed, which may be too late to modify its course. Endothelial dysfunction and the index of microcirculatory resistance (IMR) assessed soon after transplantation have both been shown in separate studies to predict development of CAV and long-term adverse outcome.2,3 The purpose of this study (URL: http://clinicaltrials.gov. Unique identifier: NCT01078363) is to quantify the combined impact of early endothelial dysfunction and elevated microvascular resistance as a marker of subsequent development of CAV at 1 year after Cardiac transplantation. Forty-four heart transplant recipients underwent intracoronary acetylcholine injection (50–100 µg over 30 seconds), coronary physiology assessment, and volumetric intravascular ultrasound analysis performed in the left anterior descending coronary artery within 8 weeks after transplantation (baseline) and at 1 year. Endothelial dysfunction was defined as ≥20% change in diameter of the left anterior descending coronary artery as measured by quantitative angiography after acetylcholine and in comparison with baseline angiography.2 Elevated microvascular resistance was defined as an IMR≥20.3 IMR was assessed with a coronary pressure/thermistor-tipped wire …

  • association of periarterial neovascularization with progression of Cardiac Allograft Vasculopathy and long term clinical outcomes in heart transplant recipients
    Journal of Heart and Lung Transplantation, 2016
    Co-Authors: Hideki Kitahara, Helen Luikart, Kozo Okada, Shigemitsu Tanaka, Hyoungmo Yang, Kojiro Miki, Yuhei Kobayashi, Takumi Kimura, Paul G Yock, Alan C Yeung
    Abstract:

    Background This study investigated the relationship between periarterial neovascularization, development of Cardiac Allograft Vasculopathy (CAV), and long-term clinical outcomes after heart transplantation. Proliferation of the vasa vasorum is associated with arterial inflammation. The contribution of angiogenesis to the development of CAV has been suggested. Methods Serial (baseline and 1-year post-transplant) intravascular ultrasound was performed in 102 heart transplant recipients. Periarterial small vessels (PSV) were defined as echolucent luminal structures Results During the first year post-transplant, the proliferative group showed a greater increase in maximum intimal thickness (0.33 ± 0.36 mm vs 0.10 ± 0.28 mm, p p = 0.025) than the non-proliferative group. On Kaplan-Meier analysis, Cardiac death-free survival rate over a median of 4.7 years was significantly lower in the proliferative group than in the non-proliferative group (hazard ratio, 3.10; p = 0.036). Conclusions The increase in PSV, potentially representing an angioproliferative response around the coronary arteries, was associated with early CAV progression and reduced survival after heart transplantation.

  • abstract 11831 geographic distribution of Cardiac Allograft Vasculopathy associated with acute cellular rejection a serial three dimensional ivus study of heart transplant recipients
    Circulation, 2014
    Co-Authors: Kozo Okada, Alan C Yeung, Hideki Kitahara, Shigemitsu Tanaka, Hyoungmo Yang, Yuhei Kobayashi, Paul G Yock, Hongseok Lim, Kyuhachi Otagiri, Peter J Fitzgerald
    Abstract:

    Background: Cardiac Allograft Vasculopathy (CAV) results from cumulative arterial injury induced by a combination of alloimmune responses and non-specific insults in the context of impaired repair mechanisms. This study aimed to characterize early arterial responses and geographic distribution of CAV associated with acute cellular rejection in heart transplant recipients. Methods: We studied 92 heart transplant recipients who underwent baseline (4-6 weeks post-transplant) and 1-year intravascular ultrasound (IVUS) in the first 50 mm of the left anterior descending (LAD) coronary artery. Average intimal thickness and volumetric IVUS indices for vessel and intima were obtained in 3 equally divided subsegments (proximal, middle, and distal), respectively. Paradoxical arterial remodeling over time was defined as [[Unable to Display Character: ∆]]vessel volume / [[Unable to Display Character: ∆]]intimal volume <0. Acute cellular rejection was defined by endomyocardial biopsy as ISHLT Grade ≥2R. Res...

  • comparison of drug eluting versus bare metal stents in Cardiac Allograft Vasculopathy
    American Journal of Cardiology, 2011
    Co-Authors: Jennifer A Tremmel, Fumiaki Ikeno, Sharon A Hunt, David P Lee, Alan C Yeung, William F Fearon
    Abstract:

    Although not a definitive treatment, percutaneous coronary intervention offers a palliative benefit to patients with Cardiac Allograft Vasculopathy. Given the superior outcomes with drug-eluting stents (DESs) over bare metal stents (BMSs) in native coronary artery disease, similar improvements might be expected in transplant patients; however, the results have been mixed. Consecutive Cardiac transplantation recipients at a single center receiving a stent for de novo Cardiac Allograft Vasculopathy from 1997 to 2009 were retrospectively analyzed according to receipt of a DES versus a BMS. The angiographic and clinical outcomes were subsequently evaluated at 1 year. The baseline clinical and procedural characteristics were similar among those receiving DESs (n = 18) and BMSs (n = 16). Quantitative coronary angiography revealed no difference in the reference diameter, lesion length, or pre-/postprocedural minimal luminal diameter. At the 12-month angiographic follow-up visit, the mean lumen loss was significantly lower in the DES group than in the BMS group (0.19 ± 0.73 mm vs 0.76 ± 0.97 mm, p = 0.02). The DES group also had a lower rate of in-stent restenosis (12.5% vs 33%, p = 0.18), as well as a significantly lower rate of target lesion revascularization (0% vs 19%, p = 0.03). At 1 year, DESs were associated with a lower composite rate of Cardiac death and nonfatal myocardial infarction (12% vs 38%, p = 0.04). In conclusion, DESs are safe and effective in the suppression of neointimal hyperplasia after percutaneous coronary intervention for Cardiac Allograft Vasculopathy, resulting in significantly lower rates of late lumen loss and target lesion revascularization, as well as a reduced combined rate of Cardiac death and nonfatal myocardial infarction.