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1.
Long-term clinical outcomes with use of an angiotensin-converting enzyme inhibitor early after heart transplantation.
Arashi, H, Sato, T, Kobashigawa, J, Luikart, H, Kobayashi, Y, Okada, K, Sinha, S, Honda, Y, Yeung, AC, Khush, K, et al
American heart journal. 2020;:30-37
Abstract
BACKGROUND The safety and efficacy of angiotensin converting enzyme inhibition (ACEI) after heart transplantation (HT) is unknown. This study examined long-term clinical outcomes after ACEI in HT recipients. METHODS The ACEI after HT study was a prospective, randomized trial that tested the efficacy of ACEI with ramipril after HT. In this study, long-term clinical outcomes were assessed in 91 patients randomized to either ramipril or placebo (median, 5.8 years). The primary endpoint was a composite of death, retransplantation, hospitalization for rejection or heart failure, and coronary revascularization. RESULTS The primary endpoint occurred in 10 of 45 patients (22.2%) in the ramipril group and in 14 of 46 patients (30.4%) in the placebo group (Hazard ratio (HR), 0.68; 95% CI, 0.29-1.51; P = .34). When the analysis was restricted to comparing patients who remained on a renin-angiotensin system inhibitor beyond 1 year with those who did not, there was a trend to improved outcomes (HR, 0.54; 95% CI, 0.22-1.28, P = .16). There was no significant difference in creatinine, blood urea nitrogen, and potassium at 3 years after randomization. The cumulative incidence of the primary endpoint was significantly higher in patients in whom the index of microcirculatory resistance increased from baseline to 1 year compared with those in whom it did not (39.1 vs 17.4%, HR: 3.36; 95% CI, 1.07-12.7; P = .037). CONCLUSION The use of ramipril after HT safely lowers blood pressure and is associated with favorable long-term clinical outcomes. Clinical Trial Registration-URL: https://www.clinicaltrials.gov. Unique identifier: NCT01078363.
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2.
The pharmaceutical management of cardiac allograft vasculopathy after heart transplantation.
Spitaleri, G, Farrero Torres, M, Sabatino, M, Potena, L
Expert opinion on pharmacotherapy. 2020;(11):1367-1376
Abstract
INTRODUCTION Cardiac allograft vasculopathy (CAV) is a major limitation to long-term survival after heart transplantation. Its peculiar pathophysiology involves multifactorial pathways including immune-mediated and metabolic risk factors, which are associated with the development of specific pathological lesions. The often diffuse and chronic nature of the disease reduces the effectiveness of revascularization procedures, and pharmacological prevention of the disease is the sole therapeutic approach with some proven efficacy. AREAS COVERED In this article, after briefly outlining the risk factors for CAV, the authors revise the potential pharmacological approaches that may reduce the burden of CAV. While several therapies have shown convincing efficacy in terms of CAV prevention diagnosed by coronary imaging, very few have been reported to improve prognosis with any meaningful level of evidence. EXPERT OPINION The authors believe that a customizable approach is necessary for clinical practice given the currently available evidence. Furthermore, it is important, in the future, to address the glaring therapeutic gap of an effective treatment against donor-specific antibodies, whose effect on endothelial injury is currently one of the major mechanisms of CAV development and for which no pharmacological treatment is currently available.
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3.
Hypertension in cardiac transplant recipients: tackling a new face of an old foe.
Campbell, PT, Krim, SR
Current opinion in cardiology. 2020;(4):368-375
Abstract
PURPOSE OF REVIEW Systemic hypertension (HTN) is a common complication arising in the heart transplant recipient. This article aims to review the most current literature and update readers on the epidemiology, pathophysiology and management of HTN in heart transplant patients. RECENT FINDINGS In contrast to the general nontransplant hypertensive patient population, traditional risk factors, including family history of HTN, obesity and diabetes, play a minor role in the genesis of posttransplant HTN. Dysregulation in sodium and water balance, vascular stiffness, endothelial dysfunction, abnormal cardiorenal neural reflexes resulting from immunosuppression and cardiac denervation seem to be the predominant factors leading to postheart transplant HTN. Calcineurin inhibitors induced nephrotoxicity and steroid use further contributes to posttransplant HTN. SUMMARY Owing to the paucity of data, particularly randomized controlled trials to guide the evaluation and management of HTN in the cardiac transplant patients, much of the available data come from the renal transplant population. The choice of antihypertensive should be based on timing related to transplantation and patient's comorbidities. Although calcium channel blockers and loop diuretics are the preferred agents in the early postheart transplant period, angiotensin-converting-enzyme inhibitors and angiotensin receptor blockers may be beneficial in the late postheart transplant period especially in the setting of diabetes and in the presence of proteinuria.
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4.
Use of Idarucizumab to reverse the anticoagulant effect of dabigatran in cardiac transplant surgery. A multicentric experience in Spain.
Crespo-Leiro, MG, López-Vilella, R, López Granados, A, Mirabet-Pérez, S, Díez-López, C, Barge-Caballero, E, Segovia-Cubero, J, González-Vilchez, F, Rangel-Sousa, D, Blasco-Peiró, T, et al
Clinical transplantation. 2019;(12):e13748
Abstract
BACKGROUND Anticoagulation in heart transplant (HT) recipients increases the risk of hemorrhagic complications, so correct reversal of anticoagulation is needed. Dabigatran, a direct thrombin inhibitor, is increasingly used for anticoagulation in patients with non-valvular atrial fibrillation (NVAF) whose effect can be reversed by idarucizumab. AIM: To present a nationwide experience using idarucizumab for the urgent reversal of dabigatran before HT. METHODS Multicenter observational study in 12 Spanish centers to analyze the clinical outcomes after using idarucizumab before HT surgery. RESULTS Fifty-three patients were included (81.1% male). 7.5% required re-operation in the immediate postoperative period to control bleeding and 66% transfusion of blood products. Median length of stay in the intensive care unit was 6 days and total hospital stay 24 days. 30-day survival was 92.4%. There were four deaths in the first month, all in the first 5 days post-HT. Only in one patient (transplanted due to a congenital heart disease, after sternotomy) who had surgical problems and right ventricular failure post-HT death was associated with bleeding. CONCLUSIONS These results may support the use of dabigatran as an alternative to vitamin K antagonists in patients listed for HT requiring anticoagulation due to NVAF. More studies are needed to reaffirm these observations.
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5.
The Role of GDF-15 in Heart Failure Patients With Chronic Kidney Disease.
Benes, J, Kotrc, M, Wohlfahrt, P, Conrad, MJ, Franekova, J, Jabor, A, Lupinek, P, Kautzner, J, Melenovsky, V, Jarolim, P
The Canadian journal of cardiology. 2019;(4):462-470
Abstract
BACKGROUND Growth differentiation factor-15 (GDF-15) is a stress-inducible cytokine and member of the transforming growth factor-β cytokine superfamily that refines prognostic assessment in subgroups of patients with heart failure (HF). We evaluated its role in HF patients with chronic kidney disease (CKD, estimated glomerular filtration rate <60 mL/min/1.73 m2). METHODS A total of 358 patients with stable systolic HF were followed for a median of 1121 (interquartile range, 379-2600) days. Comprehensive evaluation including B-type natriuretic peptide (BNP) and GDF-15 testing was performed at study entry; the analysis was stratified according to kidney function. RESULTS Patients with CKD (33.8%) were older, had more often diabetes, and were less often treated with angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB). GDF-15 was associated with estimated glomerular filtration rate, whereas BNP was associated with left ventricular-end diastolic diameter and ejection fraction (P < 0.01). During follow-up, 244 patients (68.2%) experienced an adverse outcome (death, urgent transplantation, implantation of mechanical circulatory support). In patients with HF and CKD, the Cox proportional hazard model identified BNP, GDF-15, sex, systolic blood pressure, sodium, total cholesterol, and ACEi/ARB treatment as significant variables associated with an adverse outcome (P < 0.05). In multivariable analysis, BNP was replaced by GDF-15. Net reclassification improvement confirmed prognostic superiority of the model encompassing GDF-15 (GDF-15, sodium, total cholesterol, ACEi/ARB treatment) compared with the model without GDF-15 (BNP, sex, sodium, ACEi/ARB treatment), net reclassification improvement 0.62, P = 0.005. In contrast, in patients with HF and normal kidney function, BNP remained superior to GDF-15 in a multivariable model. CONCLUSIONS In patients with systolic HF and CKD, GDF-15 is more strongly associated with adverse outcomes than the conventionally used BNP.
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6.
Safety and tolerability of high-intensity statin therapy in heart transplant patients receiving immunosuppression with tacrolimus.
Heeney, SA, Tjugum, SL, Corkish, ME, Hollis, IB
Clinical transplantation. 2019;(1):e13454
Abstract
BACKGROUND Following heart transplantation (HT), HMG CoA reductase inhibitors (statins) have been shown to reduce total and low-density lipoprotein (LDL) cholesterol, development of cardiac allograft vasculopathy (CAV), and mortality. Studies in HT patients have demonstrated the safety of low/moderate intensity statins; however, little data exist using high-intensity (HI) statins. The study aim was to evaluate the safety and efficacy of HI statins in HT recipients receiving tacrolimus. METHODS This single-center, retrospective analysis included adult HT recipients from January 1, 2005, to December 31, 2015, who received HI statin therapy during posttransplant follow-up. The primary outcome, tolerability, was defined as the absence of myalgias, hepatotoxicity, rhabdomyolysis, or HI statin dose reduction/discontinuation. The secondary end point was the mean reduction in total and LDL cholesterol. RESULTS Among the 24 patients included, one experienced myalgias and therapy discontinuation (4%; P > 0.99). No other HI statin dose reduction/discontinuation occurred, and no instances of rhabdomyolysis or hepatotoxicity were observed. The average reduction in total and LDL cholesterol after conversion to HI statin was 35 mg/dL (P = 0.02) and 19 mg/dL (P = 0.10), respectively. CONCLUSIONS High-intensity statin therapy appears safe and efficacious in HT recipients receiving tacrolimus and is a reasonable option for the treatment of refractory hyperlipidemia.
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7.
Bone mineral density and osteoporosis in heart transplanted patients: A single-center retrospective study at Skåne University Hospital in Lund 1988-2016.
Löfdahl, E, Söderlund, C, Rådegran, G
Clinical transplantation. 2019;(3):e13477
Abstract
Bone mineral density (BMD) in the lumbar spine and femoral neck, the incidence of osteoporosis, and survival up to 10 years after heart transplantation (HT) were investigated in 169 patients who underwent HT at Skåne University Hospital in Lund, Sweden, 1988-2016. Within the first year post-transplantation, mean (SD) BMD decreased by 3.9% (10.1) (P < 0.001) and 9.0% (10.5) (P < 0.001) in the lumbar spine and femoral neck, respectively. The cumulative incidence of osteoporosis in the lumbar spine and femoral neck increased rapidly within the first year after HT and was detected in 17% and 13% of the patients, respectively. A higher T score before HT was a negative predictor of osteoporosis up to 10 years post-HT in the lumbar spine (HR 0.13; 95% CI 0.063-0.26; P < 0.001) and femoral neck (HR 0.54; 95% CI 0.34-0.85; P < 0.001). Moreover, only 13%, 14%, and 6% of the HT patients received calcium, vitamin D, and/or bisphosphonates before HT. In conclusion, BMD drops significantly during the first postoperative year. Optimization of BMD early among HT candidates, potentially through usage of osteoporosis preventive treatment, may be a future means to prevent osteoporosis late postoperatively.
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8.
A peripheral T-cell lymphoma (PTCL) arising as a post-transplant lymphoproliferative disorder: efficacy of pralatrexate in primary refractory disease and review of the literature.
Ma, H, Bhagat, G, O'Connor, OA
Leukemia & lymphoma. 2019;(13):3300-3303
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9.
Assessment of Arterial Stiffness in Stable Heart Transplant Recipients.
Krucińska, B, Kurowski, A, Czyżewski, Ł
Transplantation proceedings. 2018;(7):2085-2089
Abstract
INTRODUCTION Arterial stiffness depends on both genetic and environmental factors. The aim of this study was to assess arterial stiffness in patients after heart transplant. METHODS The study was conducted between May and June 2017. Fifty patients from the Transplantology Clinic of the Institute of Cardiology in Anin, Warsaw, Poland, were enrolled in the study. Pulse wave velocity (PWV), central systolic blood pressure (CSBP), and central diastolic blood pressure (CDBP) were measured and patients' medical records were also analyzed. RESULTS In the study, 50 patients aged 57.9 years on average were evaluated, of whom 88% were male patients, with average PWV of 8.94 m/s and an average time after transplant of 9.7 years. The study has shown that age (R = 0.77), total cholesterol concentration (R = 0.22, P = .017) and creatinine concentration (R = 0.34; P = .15) show positive correlation with PWV. CONCLUSIONS Our data indicates that age has significant impact on arterial stiffness and the type of immunosuppressive drugs and transplant rejection episodes do not impact an increase in arterial stiffness.
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10.
The fat mass and obesity related gene polymorphism influences the risk of rejection in heart transplant patients.
Hubacek, JA, Vymetalova, J, Lanska, V, Dlouha, D
Clinical transplantation. 2018;(12):e13443
Abstract
Heart transplantation is a relatively common treatment for end-stage heart failure. The major complication of heart transplantation is organ rejection. Epigenetic could play a role in the pathogenesis of organ rejection, and the FTO gene is a mediator of DNA methylation. We analyzed a tagging FTO SNP rs17817449 in both donor and recipient DNA obtained through 370 heart transplantations. Recipient FTO genotypes were not associated with either type of rejection or with the general increase in the risk of rejection. When compared with patients without a history of rejection, carriers of transplanted hearts with the FTO TT genotype exhibited a significantly increased risk (P = 0.02) of suffering from both types of rejection in comparison to carriers of hearts with at least one G allele (OR; 95% CI = 2.56; 1.15-5.69). Our results suggest that the donor, but not the recipient, FTO genotype could be a significant predictor of acute rejection in heart transplant patients.