Cardiovascular Disease In Transplant Recipients Research Articles

SUN-573 Use of PCSK9 Inhibitors Post-Transplant

Background:Dyslipidemia is common in patients after transplant. While statins are the mainstay of therapy, interactions with immunosuppressants such as calcineurin inhibitors (CNIs) can limit dose titration or lead to intolerance of this important drug class. Withdrawal of statin therapy can precipitate hyperlipidemia and potentially accelerate cardiovascular disease in transplant recipients, including coronary allograft vasculopathy (CAV) in heart transplant (HT) patients. Proprotein convertase subtilisin-kexin type 9 inhibitors (PCSK9i) may provide a safe, effective option for such patients. PCSK9i profoundly reduce low-density lipoprotein (LDL) and subsequently the risk of cardiovascular events in nontransplant patients. Further, these novel agents have no known interactions with CNIs. There is a paucity of data describing PSCK9i use post-transplant, with only a few small case series reported in HT recipients. Here, we summarize our experience along with available literature on this topic.Methods:In this retrospective case series we investigated adult recipients of heart transplant who were treated with PCSK9 inhibitors from July 2015 to 2019 because of statin intolerance or refractory hyperlipidemia. We compared the data of patients at baseline and after various durations of therapy with the PSCK9i evolocumab and alirocumab using the median and interquartile range (IQR). Specifically, we evaluated PCSK9i efficacy, effect on immunosuppressant levels, cardiac function and adverse events.Results:Five patients (4 men; median age 54, IQR 52-60) underwent heart transplant an average of 7.4 years ago. Median treatment duration of evolocumab or alirocumab was 12 months (IQR 7-17). This led to a reduction of total cholesterol by 94 mg/dl (p=0.04) (47% decrease) and LDL cholesterol by 83 mg/dl (p=0.04) (69% decrease). No statistically significant difference in HDL cholesterol, triglycerides or liver function tests (LFTs) were observed. There were no episodes of rejection. Immunosuppressant levels remained at goal. One patient noted a few days of fatigue after alirocumab injections but otherwise no side effects were reported.Conclusion:The PCSK9 inhibitors evolocumab and alirocumab are promising alternatives to statin therapy in transplant recipients with statin intolerance or refractory hyperlipidemia. Our study showed their potential to significantly reduce LDL cholesterol in heart transplant patients without altering IST levels. No episodes of transplant rejection were noted. Further long-term studies to establish the safety and efficacy of PSCK9 inhibitors post-transplant are needed.

Anaesthetic Management of Renal Transplant Surgery in Patients of Dilated Cardiomyopathy with Ejection Fraction Less Than 40%

Cardiovascular disease (CVD) is an important comorbidity of chronic kidney disease, and reducing cardiovascular events in this population is an important goal for the clinicians who care for chronic kidney disease patients. The high risk for CVD in transplant recipients is in part explained by the high prevalence of conventional CVD risk factors (e.g., diabetes, hypertension, and dyslipidemia) in this patient population. Current transplant success allows recipients with previous contraindications to transplant to have access to this procedure with more frequency and safety. Herein we provide a series of eight patients with dilated cardiomyopathy with poor ejection fraction posted for live donor renal transplantation which was successfully performed under regional anesthesia with sedation.

Cytomegalovirus Exposure and Cardiovascular Disease in Kidney Transplant Recipients

Some data suggest that cytomegalovirus (CMV) may be involved in atherogenesis. However, there are few data suggesting that CMV may contribute to posttransplantation atherosclerosis. We studied a cohort of 570 consecutive renal transplant recipients. The impact of CMV on atherosclerotic events was analyzed with respect to other known main cardiovascular risk factors. The mean follow-up duration (± SD) was 87 ± 31 months. A total of 357 patients were considered to be CMV exposed, and 213 were considered to be CMV naive. Cox regression analysis revealed that CMV exposure (hazard ratio [HR], 1.80 [95% confidence interval {CI}, 1.06-3.05]; P = .030) was an independent risk factor for atherosclerotic events. A total of 213 patients remained CMV negative during follow-up, 225 CMV-positive patients had no replication after transplantation, and 132 CMV-positive patients experienced CMV replication after transplantation. Atherosclerotic event rates were 8.5%, 13.3%, and 18.2%, respectively (P = .034). Cox regression analysis revealed that patients with posttransplantation CMV replication had an increased risk of atherosclerotic events (HR, 2.06 [95% CI, 1.03-4.15]; P = .042) and death (HR, 1.76 [95% CI, 1.08-2.89]; P = .024). There was also a trend toward an increased risk of atherosclerotic events in CMV-positive patients without posttransplantation replication (HR, 1.62 [95% CI, .91-3.05]; P = .098). Both pretransplantation CMV exposure and posttransplantation CMV replication contribute to the increased risk of cardiovascular disease in transplant recipients.

The Contribution of Cytomegalovirus to Atherosclerotic Events after Kidney Transplantation

With improvements in management of acute rejection and allograft function over the past decades, short-term survival after solid-organ transplantation is excellent, and death with a functioning graft has become the outcome for the majority of solid-organ transplant recipients. Thus, there is a necessity to focus not only on interventions to maintain graft function, but also to address other posttransplantation complications contributing to death among transplant recipients. Chief among these concerns is posttransplantation atherosclerosis. Atherosclerosis resulting in cardiovascular events is now the major cause of death in long-term survivors of renal, cardiac, and hematopoietic stem cell transplantations [1–3]. In a cohort of 2202 adult kidney transplant recipients with >10year graft survival, cardiovascular disease (CVD) was the major cause of mortality, followed by malignancy and infection [4]. The cause of posttransplantation atherosclerosis is multifactorial. Risk factors resembling those for atherosclerosis in the general population include pretransplantation CVD, diabetes, hypertension, hyperlipidemia, tobacco use, obesity, and renal disease [1]. For transplant recipients, additional contributors include transplant-related medications such as steroids, transplant nephropathy, posttransplantation diabetes, and posttransplantation dyslipidemia. Thus, identifying comorbidities that influence the progression of CVD in transplant recipients might provide interventions to prolong survival and quality of life.

CARDIOVASCULAR DISEASE IN RENAL TRANSPLANT RECIPIENTS

Renal transplant recipients have a markedly increased risk of premature cardiovascular disease (CVD) compared with the general population, although considerably lower than that of patients receiving maintenance haemodialysis. CVD in transplant recipients is poorly characterised and differs from the nonrenal population, with a much higher proportion of fatal to nonfatal cardiac events. In addition to traditional ischaemic heart disease risk factors such as age, gender, diabetes and smoking, there are additional factors to consider in this population such as the importance of hypertension, left ventricular hypertrophy and uraemic cardiomyopathy. There are factors specific to transplantation such immunosuppressive therapies and graft dysfunction which contribute to this altered risk profile. However, understanding and treatment is limited by the absence of large randomised intervention trials addressing risk factor modification, with the exception of the ALERT study. The approach to managing these patients should begin early and be multifactorial in nature.

Cardiovascular disease in transplant recipients: current and future treatment strategies.

A cardiovascular disease event in a transplant recipient may be the result of a pretransplantation disease process, a direct effect of immunosuppressant medications, or the result of exposure to a variety of traditional and nontraditional risk factors after transplantation. Although the understanding of posttransplantation cardiovascular disease remains incomplete, there is evidence that the impact of posttransplantation cardiovascular disease has been decreased, through increased attention to this problem. In the absence of controlled studies to guide therapy, this review summarizes treatment of cardiovascular disease risk factors for which there is strong evidence of benefit in the nontransplantation setting, observational evidence of a similar risk in transplant recipients, and evidence that treatment can be safely administered to transplant recipients. Putative risk factors for posttransplantation cardiovascular disease for which the current level of evidence is insufficient to support specific treatment recommendations are also discussed. Potential new strategies to decrease the risk for cardiovascular disease events after transplantation in the future, including aggressive pretransplantation risk reduction, individualized treatments to prevent different types of cardiovascular disease, dedicated efforts to reduce cardiovascular disease events during transitions between dialysis and transplantation, and manipulation of immunosuppressant protocols, are also introduced.

Random blood glucose measurements and survival in nondiabetic renal transplant recipients

New-onset diabetes after renal transplantation (PTDM), a common consequence of immunosuppression, is associated with reduced patient survival. However, we know little about the impact of less marked changes in glucose homeostasis. To investigate this problem, we used data on average random blood glucose values during the first, second, and third months posttransplantation, derived from a cohort of 1186 patients who received their first cadaveric or living-donor transplant between 1984 and 2002. We analyzed both patient and death-censored graft survivals, subgrouping recipients into those with end-stage renal failure due to diabetic nephropathy versus those with PTDM versus patients without diabetes. We confirmed that PTDM patients display reduced survival following transplantation, but a long-term survival similar to that of patients with diabetic nephropathy and end-stage renal disease. However, among patients without diabetes, random blood glucose was also a strong determinant of outcome, even when in the low normal range. In contrast, neither the presence of diabetes nor random glucose levels showed a significant impact on graft survival. PTDM is recognized to be an important, potentially modifiable, risk factor for cardiovascular disease in transplant recipients. Our data suggest that there is a gradation of increased risk associated with impaired glycemic control that affects patients who do not have diabetes. These data support the need for improved understanding of glycemic control in transplant recipients and for more detailed screening for impaired glucose tolerance in this population.