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Background: Myocardial blood flow (MBF) quantification by Rubidium-82 positron emission tomography (PET) has shown promise for cardiac allograft vasculopathy (CAV) surveillance and risk stratification post heart transplantation. The objective was to determine the prognostic value of serial PET performed early post transplantation., Methods and Result: Heart transplant (HT) recipients at the University of Ottawa Heart Institute with 2 PET examinations (PET1 = baseline, PET2 = follow-up) within 6 years of transplant were included in the study. Evaluation of PET flow quantification included stress MBF, coronary vascular resistance (CVR), and myocardial flow reserve (MFR). The primary composite outcome was all-cause death, re-transplant, myocardial infarction, revascularization, allograft dysfunction, cardiac allograft vasculopathy (CAV), or heart failure hospitalization. A total of 121 patients were evaluated (79% male, mean age 56 ± 11 years) with consecutive scans performed at mean 1.4 ± 0.7 and 2.6 ± 1.0 years post HT for PET1 and PET2, respectively. Over a mean follow-up of 3.0 (IQR 1.8, 4.6) years, 26 (22%) patients developed the primary outcome: 1 death, 11 new or progressive angiographic CAV, 2 percutaneous coronary interventions, 12 allograft dysfunction. Unadjusted Cox analysis showed a significant reduction in event-free survival in patients with PET1 stress MBF < 2.1 (HR: 2.43, 95% CI 1.11-5.29 P = 0.047) and persistent abnormal PET1 to PET2 CVR > 76 (HR: 2.19, 95% CI 0.87-5.51 P = 0.045). There was no association between MFR and outcomes., Conclusion: Low-stress MBF and persistent increased CVR on serial PET imaging early post HT are associated with adverse cardiovascular outcomes. Early post-transplant and longitudinal assessment by PET may identify at-risk patients for increased surveillance post HT., (© 2020. American Society of Nuclear Cardiology.)

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., (© 2019 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging has prognostic utility in populations with cardiac disease, including heart transplant (HT) recipients. The etiology of specific LGE patterns and their correlation with outcomes after HT are unclear. Antibody-mediated rejection and cardiac allograft vasculopathy are major causes of death, and their evaluation remains challenging. We report identical diffuse subepicardial LGE in 2 highly allosensitized HT recipients who developed allograft failure. We postulate this LGE pattern may be related to antibody-mediated rejection and cardiac allograft vasculopathy, and portends poor outcomes. These cases illustrate a potential role of cardiac magnetic resonance for antibody-mediated rejection evaluation and risk stratification., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Vasoplegia occurs in up to 16% of patients who undergo heart transplantation (HT) and is associated with significant morbidity and mortality. We present a case of a 61-year-old man with ischemic cardiomyopathy receiving sacubitril/valsartan (Entresto; Novartis, Cambridge, MA) who developed profound hypotension after HT. He was treated with intravenous methylene blue and high-dose vasopressors, but developed acute kidney injury requiring dialysis and a prolonged stay in the intensive care unit. This case supports a potent vasodilatory effect of sacubitril/valsartan, and if confirmed by other studies, might warrant consideration for withholding treatment while awaiting HT, particularly in patients with risk factors for vasoplegia., (Copyright © 2017 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

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