FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W1517060477> ?p ?o ?g. }

• W1517060477 endingPage "2572" @default.
• W1517060477 startingPage "2571" @default.
• W1517060477 abstract "The author reviews the article by Arora and colleagues (page 2700) and puts into context the observations made regarding the use of everolimus in patients several years out from transplant with established cardiac allograft vasculopathy, as well as the utility of the novel imaging technique, virtual histology, used in the study. The author reviews the article by Arora and colleagues (page 2700) and puts into context the observations made regarding the use of everolimus in patients several years out from transplant with established cardiac allograft vasculopathy, as well as the utility of the novel imaging technique, virtual histology, used in the study. Cardiac allograft vasculopathy (CAV) remains a major cause of death in cardiac transplant recipients beyond the first year posttransplant (1Stehlik J Edwards LB Kucheryavaya AY et al.The Registry of the International Society for Heart and Lung Transplantation: Twenty-eighth Adult Heart Transplant Report–2011..J Heart Lung Transpl. 2011; 30: 1078-1094Abstract Full Text Full Text PDF PubMed Scopus (449) Google Scholar). Although dramatic improvements have occurred in posttransplant survival, these have occurred mainly in the first year after transplant as a result of improved management of acute cellular rejection and infection. In contrast, the prevention of CAV in de novo transplant recipients and the treatment of CAV in established transplant patients remain challenging. The proliferation signal inhibitors (PSI) sirolimus and everolimus have been studied in randomized clinical trials in conjunction with calcineurin inhibitors (CNI) and corticosteroids and in comparison to antiproliferative agents. Everolimus was shown to reduce the incidence and severity of CAV as defined by intravascular ultrasound (IVUS) when compared to azathioprine and more recently, Mycophenolate mofetil (MMF; Ref. 2Eisen HJ Tuzcu EM Dorent R et al.Everolimus for the prevention of allograft rejection and vasculopathy in cardiac-transplant recipients.N Engl J Med. 2003; 349: 847-858Crossref PubMed Scopus (1025) Google Scholar). The use of PSIs was associated with adverse clinical events including renal insufficiency, pericardial effusions and hypertriglyceridemia and adoption as routine immunosuppressive therapy has not been uniform; everolimus and sirolimus have been approved by the FDA for renal but not cardiac transplantation. Another challenge is the management of patients who develop CAV after cardiac transplantation which occurs in over 40% of patients 8 years after transplant and is the cause of death in more than 30% of patients beyond the first year posttransplant (1Stehlik J Edwards LB Kucheryavaya AY et al.The Registry of the International Society for Heart and Lung Transplantation: Twenty-eighth Adult Heart Transplant Report–2011..J Heart Lung Transpl. 2011; 30: 1078-1094Abstract Full Text Full Text PDF PubMed Scopus (449) Google Scholar). PSIs have been studied in randomized clinical trials of cardiac transplant patients with established CAV with conflicting results (3Mancini D Pinney S Burkhoff D et al.Use of rapamycin slows progression of cardiac transplantation vasculopathy..Circulation. 2003; 108: 48-53Crossref PubMed Scopus (376) Google Scholar,4Arora S Ueland T Wennerblom B et al.Effect ofeverolimus introduction on cardiac allograft vasculopathy—Results of a randomized, multicenter trial.Transplantation. 2011; 92: 235-243Crossref PubMed Scopus (61) Google Scholar). Mancini randomized patients with established CAV to either add sirolimus to their immunosuppressive regimen or to continue standard immunosuppression. Patients receiving sirolimus had slower progression of CAV using a combined endpoint of cardiac events and cardiac catheterization scores (3Mancini D Pinney S Burkhoff D et al.Use of rapamycin slows progression of cardiac transplantation vasculopathy..Circulation. 2003; 108: 48-53Crossref PubMed Scopus (376) Google Scholar). Arora et al. in the NOCTET trial randomized patients (who were on average 5.8 ± 4.3 years posttransplant at the time of enrollment) with established CAV to receive everolimus (with a reduction in CNI dose) or continue standard dose CNI immunosuppression (4Arora S Ueland T Wennerblom B et al.Effect ofeverolimus introduction on cardiac allograft vasculopathy—Results of a randomized, multicenter trial.Transplantation. 2011; 92: 235-243Crossref PubMed Scopus (61) Google Scholar). Progression of CAV in these patients, defined by IVUS, was not affected by the addition of everolimus. IVUS has been a critical diagnostic tool for detecting CAV and also as a surrogate marker for future adverse cardiac events and for prognosis. Although not routinely used clinically, IVUS has been incorporated into most major clinical trials of immunosuppression in cardiac transplantation to assess efficacy in ameliorating and preventing CAV. IVUS parameters such as change in maximal intimal thickness from the baseline, early posttransplant IVUS study to the study obtained 1 year later have been particularly robust as prognosticators. What traditional IVUS parameters do not provide is tissue characterization of the morphologic changes of CAV. Arora reports the use of a novel IVUS technique, virtual histology (VH), which employs radiofrequency backscatter to define plaque and vascular intimal wall tissue composition in a subset of cardiac transplant recipients from the NOCTET study (5Arora S Erikstad I Ueland T et al.Virtual Histology assessment of cardiac allograft vasculopathy following introduction of everolimus—Results of a multicenter trial.Am J Transplant. 2012; 12: 2700-2709Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar). Patients in this study had established CAV and were randomly assigned to receive everolimus in addition to CNI and antiproliferative agents or to continue their immunosuppression unchanged. Markers of inflammation, VCAM-1, von Willenbrand Factor (vWF) and CRP, were also assayed. Patients receiving everolimus had a significant increase in calcified and necrotic vascular wall components compared to controls but only those more than 5.1 years posttransplant; in these patients, VCAM-1 and vWF levels were also increased. These findings at least raise the concern that initiation of PSIs in some patients with established CAV may not slow progression but may potentiate inflammation and the development of necrosis and calcification in the CAV tissue with uncertain consequences. The use of everolimus to slow progression of CAV is very different from initiation of therapy in de novo patients early posttransplant in whom CAV has not begun but where the pathophysiologic groundwork has been set and one cannot extrapolate from Arora’s findings to these patients. The observation that there is a time-dependent effect of everolimus on the development of necrosis and calcification, with patients less than 5.1 years posttransplant not developing these changes or increases in inflammatory mediators, is intriguing but was not explained. This may indicate that certain patients may not have the enhanced inflammation or vascular changes seen later. Arora’s protocol involved continuation of azathioprine or MMF with everolimus and it is not clear if discontinuing these when everolimus was started would have yielded different results. Perhaps the most intriguing aspect of this study is VH, which provides greater tissue characterization and definition of the vascular wall. VH characterization of atherosclerotic lesions has identified morphologies associated with adverse cardiac events in nontransplant patients with coronary artery disease but CAV is very different. Nonetheless, VH tissue characterization should be further investigated in cardiac transplant patients to determine if it can provide additional prognostic information and perhaps identify patients with established CAV who might benefit from PSIs. In addition, future clinical trials of immunosuppression should include VH to provide more detailed information of the impact of new therapies on CAV. The author of this manuscript has a conflict of interest to disclose as described by the American Journal of Transplantation. H.J.E received research grant support from Novartis for a clinical trial of everolimus and from Pfizer for a study of sirolimus in cardiac transplant recipients. Both studies have been completed." @default.
• W1517060477 created "2016-06-24" @default.
• W1517060477 creator A5076902671 @default.
• W1517060477 date "2012-10-01" @default.
• W1517060477 modified "2023-09-23" @default.
• W1517060477 title "A Novel Definition of Cardiac Allograft Vasculopathy" @default.
• W1517060477 cites W1811302155 @default.
• W1517060477 cites W2060869747 @default.
• W1517060477 cites W2069514855 @default.
• W1517060477 cites W2122783053 @default.
• W1517060477 cites W2172064850 @default.
• W1517060477 doi "https://doi.org/10.1111/j.1600-6143.2012.04240.x" @default.
• W1517060477 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23009137" @default.
• W1517060477 hasPublicationYear "2012" @default.
• W1517060477 type Work @default.
• W1517060477 sameAs 1517060477 @default.
• W1517060477 citedByCount "0" @default.
• W1517060477 crossrefType "journal-article" @default.
• W1517060477 hasAuthorship W1517060477A5076902671 @default.
• W1517060477 hasBestOaLocation W15170604771 @default.
• W1517060477 hasConcept C126322002 @default.
• W1517060477 hasConcept C164705383 @default.
• W1517060477 hasConcept C177713679 @default.
• W1517060477 hasConcept C2778849806 @default.
• W1517060477 hasConcept C2909963992 @default.
• W1517060477 hasConcept C2911091166 @default.
• W1517060477 hasConcept C71924100 @default.
• W1517060477 hasConceptScore W1517060477C126322002 @default.
• W1517060477 hasConceptScore W1517060477C164705383 @default.
• W1517060477 hasConceptScore W1517060477C177713679 @default.
• W1517060477 hasConceptScore W1517060477C2778849806 @default.
• W1517060477 hasConceptScore W1517060477C2909963992 @default.
• W1517060477 hasConceptScore W1517060477C2911091166 @default.
• W1517060477 hasConceptScore W1517060477C71924100 @default.
• W1517060477 hasFunder F4320307765 @default.
• W1517060477 hasFunder F4320310388 @default.
• W1517060477 hasIssue "10" @default.
• W1517060477 hasLocation W15170604771 @default.
• W1517060477 hasLocation W15170604772 @default.
• W1517060477 hasOpenAccess W1517060477 @default.
• W1517060477 hasPrimaryLocation W15170604771 @default.
• W1517060477 hasRelatedWork W2008851126 @default.
• W1517060477 hasRelatedWork W2011347913 @default.
• W1517060477 hasRelatedWork W2044741466 @default.
• W1517060477 hasRelatedWork W2049397185 @default.
• W1517060477 hasRelatedWork W2073151595 @default.
• W1517060477 hasRelatedWork W2074833529 @default.
• W1517060477 hasRelatedWork W2159512267 @default.
• W1517060477 hasRelatedWork W2304633692 @default.
• W1517060477 hasRelatedWork W2399063111 @default.
• W1517060477 hasRelatedWork W3011906917 @default.
• W1517060477 hasVolume "12" @default.
• W1517060477 isParatext "false" @default.
• W1517060477 isRetracted "false" @default.
• W1517060477 magId "1517060477" @default.
• W1517060477 workType "article" @default.