Early aspirin initiation following heart transplantation is associated with reduced risk of allograft vasculopathy during long‐term follow‐up

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

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

“…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

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

“…Peled et al studied 206 patients over a median follow‐up of 10.5 years. Early post‐transplant treatment with aspirin 75 or 100mg daily was associated with a significant 84% reduction in CAV risk, and 68% reduction in the risk of the combined end‐point of CAV or death . In another retrospective cohort study of 120 patients with a mean follow‐up of 7 years, aspirin use was associated with a significantly reduced risk of developing moderate to severe angiographic CAV (adjusted hazard ratio 0.13), 92% lower than patients not on aspirin .…”

Section: Managementmentioning

confidence: 93%

“…47 Two recent retrospective observational studies showed that aspirin use was associated with reduced CAV risk and or 100mg daily was associated with a significant 84% reduction in CAV risk, and 68% reduction in the risk of the combined end-point of CAV or death. 48 In another retrospective cohort study of 120 patients with a mean follow-up of 7 years, aspirin use was associated with a significantly reduced risk of developing moderate to severe angiographic CAV (adjusted hazard ratio 0.13), 92% lower TA B L E 2 Summary of imaging modalities utilized for cardiac allograft vasculopathy surveillance [23][24][25][26][27][28][29][30]…”

Section: Aspirinmentioning

confidence: 99%

Cardiac allograft vasculopathy: Insights on pathogenesis and therapy

Lee

Nair

Chih

2020

Cardiac allograft vasculopathy (CAV) is a unique accelerated form of coronary vascular disease affecting heart transplant recipients. This complication is a significant contributor to medium‐ to long‐term post‐transplant morbidity and mortality. There is a high prevalence of CAV with approximately one in three patients developing CAV by 5 years post‐transplant. Morphologically, CAV is characterized by concentric coronary intimal hyperplasia in both the epicardial arteries and intramural microvasculature. Although several immune and non‐immune factors have been identified, their precise pathogenic mechanisms, interactions, and relative importance in the development of CAV are not well defined. The advent of improved imaging surveillance modalities has resulted in earlier detection during the disease process. However, overall management of CAV remains challenging due to paucity of treatment. This review aims to discuss key concepts on the pathogenesis of CAV and current management strategies, focusing on the use of mammalian target of rapamycin inhibitors.