Early aspirin use and the development of cardiac allograft vasculopathy

Kim, Min Ji; Bergmark, Brian A; Zelniker, Thomas A; Mehra, Mandeep R.; Stewart, Garrick C.; Page, Deborah; Woodcome, E.L.; Smallwood, Jennifer A.; Gabardi, Steven; Givertz, Michael M.

doi:10.1016/j.healun.2017.06.015

Cited by 43 publications

(45 citation statements)

References 25 publications

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“…Similarly, CAV and graft dysfunction have been independently associated with increased risk of SCD . Treatments for CAV that have improved outcomes include proliferation signal inhibitors (eg, everolimus or sirolimus), aspirin,, and statins . Patients with CAV amenable to percutaneous interventions may have better survival than non‐revascularized patients .…”

Section: Discussionmentioning

confidence: 99%

The evolving risk of sudden cardiac death after heart transplant. An analysis of the ISHLT Thoracic Transplant Registry

Alba

Fan

Manlhiot

et al. 2019

Clinical Transplantation

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Sudden cardiac death (SCD) is responsible for ~10% of post-heart transplant deaths.We conducted a retrospective analysis of the ISHLT registry evaluating the risk of post-transplant SCD. Adult heart transplant recipients (2004)(2005)(2006)(2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014) surviving the first year were included. We used multivariable multistate competing risk survival analysis to evaluate the impact of history of treated rejection and cardiac allograft vasculopathy (CAV) on SCD risk. We used a probabilistic analytical model and MonteCarlo simulation to estimate the impact of CAV severity and graft dysfunction on SCD. We included 25 242 recipients. During a median follow-up of 4.7 (2.3-7.0) years, 582 patients died suddenly. Treated rejection (HR 1.76, 95% CI 1.36-2.31) and CAV (HR 3.32, 95% CI 2.73-4.03) were important risk factors for SCD. The estimated SCD risk in patients with severe CAV without and with graft dysfunction was 3.2% (95% CI 2.0-4.6) and 5.4% (95% CI 3.8-7.0), respectively, at 2 years from the CAV diagnosis, and 4.9% (95% CI 3.4-6.5) and 8.0% (95% CI 6.1-10.0), respectively, in those who also had treated rejection. These results provide evidence that recipients with severe CAV and graft dysfunction or treated rejection are at clinically significant increased SCD risk. The benefit of ICD post-transplant remains uncertain. K E Y W O R D Scardiac allograft vasculopathy, heart transplant, rejection, risk, sudden cardiac death

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Section: Discussionmentioning

confidence: 99%

The evolving risk of sudden cardiac death after heart transplant. An analysis of the ISHLT Thoracic Transplant Registry

Alba

Fan

Manlhiot

et al. 2019

Clinical Transplantation

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“…We also observed platelet and coagulation activation in patients with CAV suggesting a potential role for antithrombotic therapy. Two recent observational clinical studies showed reduction in CAV and improved survival in patients treated with aspirin early post‐transplant …”

Section: Discussionmentioning

confidence: 99%

Biomarker discovery in cardiac allograft vasculopathy using targeted aptamer proteomics

Almufleh

Zhang

Mielniczuk

et al. 2019

Clinical Transplantation

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Cardiac allograft vasculopathy (CAV) limits long-term survival after heart transplantation. Non-invasive evaluation is challenging, and currently, there is no validated biomarker for CAV diagnosis or prognostication. To identify potential candidate CAV biomarkers, we utilized the Slow Off-rate Modified Aptamer (SOMAscan) assay, which evaluates over 1000 serum proteins, including many relevant to biological pathways in CAV. We evaluated three heart transplant patient groups according to angiographic ISHLT CAV grade: CAV 1-2 (mild-moderate CAV), CAV 3 (severe CAV), and CAV 0 (normal control). SOMAscan assays were performed and proteins quantitated.Comparisons of proteins between study groups were performed using one-way ANOVA (false discovery rate q-value < 0.10). Thirty-one patients (12 mild-moderate CAV, 9 severe CAV, 10 controls) were included: 81% male, median age 57 years and median 1.1 years post-transplant. Compared to controls, patients with mild-moderate CAV had similar characteristics, while patients with severe CAV had longer time from transplant and increased allosensitization. Statistical/bioinformatics analysis identified 14 novel biomarkers for CAV, including 4 specific for mild-moderate CAV.These proteins demonstrated important actions including apoptosis, inflammation, and platelet/coagulation activation. Upon preliminary receiver operating characteristics curve analysis, our protein biomarkers showed moderate-to-high discriminative ability for CAV (area under curve: 0.72 to 0.94). These candidate biomarkers are being validated in prospective studies. K E Y W O R D Saptamer proteomic profiling, cardiac allograft vasculopathy, serum biomarkers

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“…A recent multicenter, double‐blind, randomized study found that ramipril does not slow development of epicardial plaque volume 1 year after transplant, but does stabilize levels of endothelial progenitor cells and improve microvascular function, two surrogate measures associated with long‐term survival . Early administration of aspirin, on the other hand, appears to provide a meaningful benefit on long‐term CAV development and CAV‐related clinical events, although by the weaker evidence of a retrospective propensity score‐based analysis .…”

Section: Discussionmentioning

confidence: 99%

“…Most of studies (58%) investigated the effect of mTOR inhibitors (sirolimus or everolimus) in comparison with calcineurin inhibitors (CNIs, cyclosporin or tacrolimus) or to mycophenolate derivatives (MMF) [74,[76][77][78][79][80][82][83][84][85][86]. The other agents investigated for CAV prevention included induction therapies, tacrolimus versus cyclosporine, Ace inhibitors, aspirin, statins and granulocyte-colony-stimulating factor [73,75,81, [87][88][89][90][91][92][93].…”

Section: Prevention Of Cavmentioning

confidence: 99%

Coronary artery disease in heart transplantation: new concepts for an old disease

et al. 2018

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Cardiac allograft vasculopathy (CAV) remains one of the main long-term complications after heart transplantation. We performed a systematic review focused on articles published in the previous 6 years to reappraise the novel evidences supporting risk factors, pathology, prevention, and treatment of CAV. We identified a search string for a literature search on PubMed. We excluded articles specifically focused on diagnosis/biomarkers/imaging only or complications of other diseases. We included 98 studies out of our search. Forty-eight articles describe risk factors for CAV, 13 pathology, 24 prevention, and 13 treatment for CAV. While confirming known concepts, we found supportive evidence that CAV pathophysiology may vary according to the time post-transplant and the prevalence of metabolic versus immune-mediated risk factors. Selective revascularization of focal lesions in patients with CAV may result in some clinical benefit, but CAV prevention, rather than treatment, by controlling risk factors and by using targeted immunosuppressive therapies is the most evidence-based approach to reduce disease progression.

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Early aspirin use and the development of cardiac allograft vasculopathy

Cited by 43 publications

References 25 publications

The evolving risk of sudden cardiac death after heart transplant. An analysis of the ISHLT Thoracic Transplant Registry

The evolving risk of sudden cardiac death after heart transplant. An analysis of the ISHLT Thoracic Transplant Registry

Biomarker discovery in cardiac allograft vasculopathy using targeted aptamer proteomics

Coronary artery disease in heart transplantation: new concepts for an old disease

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