Cardiac Transplant Patients Research Articles

The Utility of Pyscho-Social Assessment Tools in Predicting Cardiovascular Outcomes in Post Cardiac Transplant Patients

Purpose Donor selection in Heart Transplantation generally focuses on objective evidence to assess patient suitability on physiologic parameters; however less emphasized but equally as important is the psychosocial or social background of the recipient. The role of personality is one such aspect. Its significance remains largely unknown but it is generally accepted that individuals with Type D personality generally do poorly in the setting of cardiovascular disease. Type D personality is a combination of features that include social inhibition and negative affectivity. Methods and Materials A retrospective review of patient psychosocial assessments and consultation with the team social worker was used to identify patients within the last 2 years who would have been diagnosed with Type D personality based on the DS 14 scale. A total of 67 patents were transplanted within the last two years. After excluding those under the age of 18 at the time of transplant and those who were followed by other programs post transplant we were left with 31 patients. End points of the this study included: >2R rejection, rejection free days and mortality. Results were compared using unpaired, student. Results The average age between those with and without type D personality was 51.6 and 43.4. (p Conclusions Type D personality, is an independent predictor of mortality and early allograft rejection.

Correlation of circulating donor-specific anti-HLA antibodies and presence of C4d in endomyocardial biopsy with heart allograft outcomes: A single-center, retrospective study

Donor-specific antibodies (DSA) are associated with increased cardiac graft loss and cardiac vasculopathy (CAV). Detection of antibody-mediated rejection (AMR) relies on graft dysfunction, C4d immunofluorescence (IF) and DSA. We retrospectively studied the relationship of DSA, endomyocardial biopsy (EMB) and C4d IF to cardiac transplant outcomes. DSA were evaluated against HLA class I and II specificities, both pre- and post-transplant, using microbead-based assays. Of 626 cardiac transplant patients, 109 with concurrent EMBs and C4d IF and DSA measurement were included in this study. In patients with and without DSA, CAV occurred in 31% and 13% and acute cellular rejection (ACR) in 100% and 84%, respectively. One hundred ten of 170 EMBs procured during episodes of graft dysfunction had concurrent DSA. In these patients, C4d IF correlated better with DSA to class I or both class I and II and less so in patients with DSA to class II. Graft failure (GF) rates of 40%, 29% and 58% with average times to GF of 33, 77 and 48 months were seen in patients with DSA to class I, II or both, respectively. Patients with DSA to class I or to both class I and II showed a correlation with C4d IF and had higher GF rates compared to patients with DSA to only class II or no DSA; patients with DSA to class II remained at risk for CAV. Episodes of ACR and CAV, but not AMR, appeared to be more frequently associated with graft dysfunction in patients with circulating DSA.

Which patients undergoing colonoscopy should have spontaneous bacterial endocarditis (SBE) prophylaxis?

Evidence-Based Answer Routine administration of prophylactic antibiotics to prevent infective endocarditis (IE) from colonoscopy is not recommended. It is reasonable to give prophylactic treatment to patients with a known gastrointestinal (GI) tract infection as well as a prosthetic heart valve, valve repair with prosthetic material, or previous IE, cardiac transplant patients with subsequent valvulopathy, and some patients with congenital heart disease (SOR: C, consensus guidelines).

Late Gadolinium Enhancement in Cardiac Transplant Patients Is Associated With Adverse Ventricular Functional Parameters and Clinical Outcomes

BackgroundHeart transplant recipients (HTRs) experience multiple cardiac complications, many of which might produce myocardial fibrosis. Cardiovascular magnetic resonance imaging (CMR) can image myocardial fibrosis using late gadolinium enhancement (LGE) imaging. We hypothesized that the presence and volume of LGE in heart transplant recipients correlates with left ventricular (LV) functional parameters and clinical outcomes. MethodsThirty-eight stable HTRs underwent a CMR study and clinical follow-up. ResultsIn 38 stable HTRs, LGE was seen in 19 patients (50%), of which 15 (79%) had a nonischemic pattern and 4 (21%) had an ischemic pattern. LGE volume was associated with reduced LV ejection fraction (EF) (R2 = 0.57; P = 0.001) and increased LV end-diastolic volume (R2 = 0.59; P = 0.001). The presence of LGE was associated with cardiovascular death or hospitalization within the next year (P = 0.04), and patients who died or were hospitalized had more LGE than those that were not hospitalized (15 g vs 7 g; P = 0.03). ConclusionsLGE is common in HTR and is associated with adverse ventricular remodelling and adverse clinical outcomes. LGE might be a useful noninvasive approach to monitor graft disease in asymptomatic patients after heart transplant.

Use of the model for end-stage liver disease score for guiding clinical decision-making in the selection of patients for emergency cardiac transplantation

The outcomes of emergency cardiac transplantation remain controversial, but recipient selection is essential for success. With a shortage of organs, it is essential to determine an objective method, such as a risk score, for choosing patients who are at too great a risk to undergo cardiac transplantation. In this study, we analysed the model for end-stage liver disease in terms of predicting operative mortality after emergency cardiac transplantation. We analysed the Nancy University database of heart transplantation and selected all patients who underwent emergency heart transplantation between January 2005 and January 2012. The calibration and discriminatory power were evaluated to determine the model for end-stage liver disease (MELD) score. Preoperative and peri-operative variables regarding the prediction of operative mortality were analysed by univariate and multivariate logistic regression models. Forty-three patients underwent emergency cardiac transplantation. The operative mortality was 20.9% (n = 9). The Hosmer-Lemeshow test demonstrated a calibrated model for predicting operative mortality (P = 0.15), and the MELD score presented an excellent discrimination between survivors and non-survivors (AUC: 0.89 ± 0.05; 95% CI: 0.79-0.99). In the univariate analysis, an MELD score of ≥ 16 and bilirubin concentration were predictive markers of operative mortality. Multivariate logistic regression tested the contribution of the univariate risk predictors (P < 0.15) and confirmed that an MELD score of ≥ 16 was predictive of operative mortality. The MELD score appears to be adequate for predicting operative mortality among patients who undergo heart transplantation. The MELD score could therefore be used to guide clinical decision-making for emergency transplantation.

Management of Calcineurin Inhibitors-Related Chronic Kidney Disease in Cardiac Transplantation

Background: The use of calcineurin inhibitors revolutionized transplantation by prolonging patients’ survival. However, their utility is limited by the development of significant chronic kidney disease. Methods: We reviewed the English literature looking for recent publications regarding the management of chronic kidney disease in cardiac transplant patients. We chose relevant papers based on design, number of patients and clinical utility. Results: Most publications on the subject involve small populations with few prospective, randomized studies. Early use of tacrolimus appears to be associated with better kidney function after one year compared to cyclosporine. Once chronic kidney disease is established, successful strategies include reduction or elimination of calcineurin inhibitors while relying on mycophenolate mofetil, proliferation signal inhibitors or anti-CD 25 antibodies to prevent rejection. There is no follow up longer than two years with these approaches. Kidney transplantation might offer improved long-term survival compared to dialysis in end-stage disease. Conclusions: Prospective studies with long-term follow-up are needed to decide about the timing and to confirm the utility of replacing calcineurin inhibitors with other agents in cardiac transplant patients with chronic kidney disease.

Does Cyclosporine Down Regulate IL-17 in Cardiac Allograft Vasculopathy?

Background: Cardiac Allograft Vasculopathy (CAV) is characterized by vascular inflammation and intimal proliferation which results in luminal stenosis and myocardial infarction. During vascular inflammation elaboration of several cytokines and differential expression of growth factors have been noted. CAV remains the major threat to long-term graft survival. CD4 and CD8 T-cell subsets play a significant role in the development of transplant rejection. Chronic transplant rejection often leads to development of CAV. A new CD4 effector cell subset that produces IL-17 (Th17) has been shown to be up-regulated in the murine system in the setting of CAV. This study assesses the level of IL-17 in cardiac transplant patients with and without CAV as compared to nontransplanted controls. Methods: Levels of IL-17, IL-6, MCP-1 were measured by ELISA in plasma of four nontransplanted controls, nine cardiac allograft recipients with CAV (HT-GVD) and eight post transplant subjects without a diagnosis of CAV (HT-No GVD). All post transplant patients were immune suppressed with cyclosporine. HT-GVD patients were 1-15 years post transplant while HT-No GVD subjects were 1 - 10 years post transplant. Results: IL-17, MCP-1 and IL-6 were significantly down regulated in HT-GVD subjects compared to the HT-No GVD subjects (p 0.001) but not significant between controls and HT-No GVD (p = ns). Conclusions: A decrease in IL-17 in HT-GVD subjects as compared to HT-No GVD in the presence of cyclosporine treatment could be a consequence of down regulation of IL-6. It is likely that cyclosporine differentially regulates pro inflammatory molecules in the setting of graft vascular disease.

Robot-assisted laparoscopic radical prostatectomy after heart transplantation

Prostate cancer (CaP) is the leading visceral malignancy in males. Patients who undergo cardiac transplantation are immune compromised, thus presenting a therapeutic challenge. Immunosuppresion could accelerate tumor growth, while medical intervention may be associated with increased treatment mortality or morbidity. Due to paucity of such cases, there are no randomized trials that address the treatment algorithm for cardiac transplant patients with CaP, with only a few scattered reports in the literature. Treatment options range from hormonal manipulation to radiation therapy to radical prostatectomy. To our knowledge, we report the first successful robot-assisted laparoscopic radical prostatectomy in a heart transplant patient with CaP.

Predicting acute cardiac rejection from donor heart and pre-transplant recipient blood gene expression

Acute rejection in cardiac transplant patients remains a contributory factor to limited survival of implanted hearts. Currently, there are no biomarkers in clinical use that can predict, at the time of transplantation, the likelihood of post-transplant acute cellular rejection. Such a development would be of great value in personalizing immunosuppressive treatment. Recipient age, donor age, cold ischemic time, warm ischemic time, panel-reactive antibody, gender mismatch, blood type mismatch and human leukocyte antigens (HLA-A, -B and -DR) mismatch between recipients and donors were tested in 53 heart transplant patients for their power to predict post-transplant acute cellular rejection. Donor transplant biopsy and recipient pre-transplant blood were also examined for the presence of genomic biomarkers in 7 rejection and 11 non-rejection patients, using non-targeted data mining techniques. The biomarker based on the 8 clinical variables had an area under the receiver operating characteristic curve (AUC) of 0.53. The pre-transplant recipient blood gene-based panel did not yield better performance, but the donor heart tissue gene-based panel had an AUC = 0.78. A combination of 25 probe sets from the transplant donor biopsy and 18 probe sets from the pre-transplant recipient whole blood had an AUC = 0.90. Biologic pathways implicated include VEGF- and EGFR-signaling, and MAPK. Based on this study, the best predictive biomarker panel contains genes from recipient whole blood and donor myocardial tissue. This panel provides clinically relevant prediction power and, if validated, may personalize immunosuppressive treatment and rejection monitoring.

Evaluación de psicopatología, afrontamiento y apoyo familiar en el cumplimiento de pautas médicas en los 12 meses posteriores a un trasplante cardiaco

Introduction and objectivesFailure of compliance with the medical regimen is one of the major risk factors associated with morbidity and mortality in heart transplantation patients. The aim of this study is to evaluate the influence of some psychosocial factors, such as the presence of pre-transplant psychiatric disorders, and coping strategies and family support measured after 12months, in the compliance with the medical regimen in cardiac transplantation patients. MethodsA prospective observational study was conducted over a period of 16months to evaluate 22subjects included in a heart transplantation program. Patients were assessed in the pre-transplant period and one year after transplantation. The evaluation collected medical history and sociodemographic data, clinical measurement of depression and anxiety, a structured psychiatric interview, coping strategies, family function questionnaire, and a tool designed to measure the compliance with the medical regimen. ResultsMore than one-quarter (27%) of patients had a psychiatric disorder in the pre-transplant evaluation. The most frequently used coping strategies were acceptance and positive re-interpretation. Correlation analysis showed that there is a greater non-compliance with less family support and greater use of interpersonal coping strategies. No correlation was found between psychiatric conditions and compliance with guidelines. The overall percentage of non-compliance was 36.6%. ConclusionsIt has been shown that family support is an important factor associated with compliance with the medical regimen in patients with cardiac transplantation and, despite receiving adequate support, there is a high rate of non-compliance.

Could contrast-enhanced cardiovascular MRI potentially be used to screen pediatric cardiac transplant patients for transplant coronary artery disease?

“…recent studies suggest that contrast-enhanced cardiovascular MRI techniques can provide a noninvasive means to image and quantify the effects of increased angiogenesis and inflammation in coronar...

Abstract 18729: Serum Heat Shock Protein-70 is Associated With Decreased Frequency and Severity of Cellular Rejection in Cardiac Transplant Patients

Background: Heat Shock Protein-70 (HSP70) is a highly conserved intracellular protein that is up-regulated in cells undergoing stressful stimuli. A recent study demonstrated an inverse relationship between HSP70 expression and cellular rejection grade in endomyocardial biopsies (EBx)from cardiac transplant patients. Peripheral blood based HSP70 levels have not been studied in such individuals. We hypothesized that serum HSP70 levels will be associated with severity of cellular rejection in cardiac transplant patients. Methods: 177 cardiac transplant patients (56 ± 13 years; 8.5 ± 5 years mean time from transplant) were recruited from the Emory Cardiovascular Biobank from 2004-2012. Cellular rejection was defined based on revised International Society of Heart and Lung Transplant (ISHLT) grade of 1R or higher seen on EBx. Frequency of rejection was collected from time of transplant to enrollment date. Serum HSP70 was measured using ELISA and analyzed as detectable vs non-detectable. Nonparametric correlations and ANOVA were used to study univariate relationships while linear and ordinal logistic regression (adjusted for age, gender, race, length of time since transplant, and immunosuppressant medications) were performed to analyze the relationship between HSP70 levels and frequency and severity of cellular rejection respectively. Results: HSP70 was detectable in 35% of patients with grade 0R ISHLT class, 33% for grade 1R, 16% for Grade 2R, 0% for Grade 3R (p for group=0.005). There was an inverse correlation between HSP70 and frequency of rejection (r= -0.2, p= 0.03) with 34% of those with detectable HSP70 in the lowest quintile based on frequency of rejection whereas 9% was detected in the highest quintile (p=0.019). In adjusted regression models, HSP70 remained a significant independent predictor of a) ISHLT class with an OR of 0.43 (p=0.02) and b) frequency of rejection (β=-1.5, p=0.05). Conclusion: Detectable serum HSP70 is associated with decreased frequency and severity of cellular rejection in post cardiac transplant patients. The utility of HSP70 as a marker of graft function needs further study.

Hypothermia Prevents Inflammation but Leads to Cellular Stress in a Co-Culture Model of Endothelial Cells and Macrophages: Possible Role of Vitamin C Application During Transplantation

Background: During cardiac transplantation patients are often cooled to a temperature of 14-18°C for organ protection during ischemia. Reperfusion injury and prolonged inflammation are common complications following organ transplantation. We hypothesized that hypothermia and rewarming time have an important influence on tissue and organ function after heart transplantation. The aim of our studies was therefore to investigate the effects of deep hypothermia and rewarming on the inflammatory response of human endothelial cells and macrophages. Methods: We established an in vitro co-culture model consisting of human umbilical vein endothelial cells (HUVEC) and macrophages (THP-1 cells). The co-culture cells were exposed to dynamic temperature changes: deep hypothermia (20°C for 20 min), slow rewarming (30 min up to 37°C) and normothermia (24h at 37°C). To imitate inflammatory reaction, endothelial cells and macrophages were stimulated with 500 U/mL TNF-a throughout the cooling and rewarming period. Vitamin C (50 uM) was administrated at the beginning of the experiment and remained on the cells during the whole experiment. We investigated cell morphology (fluorescence microscopy), cell viability (MTT assay, LDH assay), cell differentiation (FACS analysis), cytokine secretion (ELISA), intracellular reactive oxygen species concentration (ROS), Adenosin- Triphsophat (ATP) content as well as pErk and IkappaB-a protein expression (Western Blot Analysis). Results: Hypothermia decreased the inflammatory reaction of the co-culture cells as proven in significant diminished extracellular IL-8, IL-6 and MCP-1 content after hypothermia and rewarming. On the other hand hypothermia led to a significant increase of extracellular ROS concentration after 24 hours which is in line with a significantly decreased intracellular ATP content in the hypothermia treated cells compared to normothermic control cells. Moreover, we could demonstrate that hypothermia and rewarming diminished the IkappaB-a protein levels, led to a significant up-regulation of pErk during the rewarming period. Vitamin C treatment during the whole experiment inhibited this hypothermia induced ROS production and restored the intracellular ATP content despites the hypothermic treatment of the cells. Conclusion: In a co-culture model consisting of endothelial cells and macrophages, hypothermia led to diminished inflammation. However, there is evidence for hypothermia induced cellular stress with diminished intracellular ATP concentration. Treating the co-culture cells with Vitamin C abolished this adverse effect of hypothermic treatment. We could demonstrate that Vitamin C acts as an antioxydizing defence. Hereby further understanding of the effects of hypothermia on the regulation of intracellular signalling and the counter-regulatory mechanisms that limit this process will improve our ability to predict the effects of hypothermia on inflammation and reperfusion injury after heart transplantation.

Diagnosis, prevention and treatment of cardiac allograft vasculopathy

The major limitation of long-term survival after cardiac transplantation is allograft vasculopathy, which consists of concentric and diffuse intimal hyperplasia. The disease still has a significant incidence, estimated at 30% five years after cardiac transplantation. It is a clinically silent disease and so diagnosis is a challenge. Coronary angiography supplemented by intravascular ultrasound is the most sensitive diagnostic method. However, new non-invasive diagnostic techniques are likely to be clinically relevant in the future. The earliest possible diagnosis is essential to prevent progression of the disease and to improve its prognosis. A new nomenclature for allograft vasculopathy has been published in July 2010, developed by the International Society for Heart and Lung Transplantation (ISHLT), establishing a standardized definition. Simultaneously, the ISHLT published new guidelines standardizing the diagnosis and management of cardiac transplant patients. This paper reviews contemporary concepts in the pathophysiology, diagnosis, prevention and treatment of allograft vasculopathy, highlighting areas that are the subject of ongoing research.

Continuous flow left ventricular assist devices: a valid option for heart failure patients

Recent outstanding clinical advances with new mechanical circulatory systems (MCS) have led to additional strategies in the treatment of end stage heart failure (HF). Heart transplantation (HTx) can be postponed and for certain patients even replaced by smaller implantable left ventricular assist devices (LVAD). Mechanical support of the failing left ventricle enables appropriate hemodynamic stabilisation and recovery of secondary organ failure, often seen in these severely ill patients. These new devices may be of great help to bridge patients until a suitable cardiac allograft is available but are also discussed as definitive treatment for patients who do not qualify for transplantation. Main indications for LVAD implantation are bridge to recovery, bridge to transplantation or destination therapy. LVAD may be an important tool for patients with an expected prolonged period on the waiting list, for instance those with blood group 0 or B, with a body weight over 90 kg and those with potentially reversible secondary organ failure and pulmonary artery hypertension. However, LVAD implantation means an additional heart operation with inherent peri-operative risks and complications during the waiting period. Finally, cardiac transplantation in patients with prior implantation of a LVAD represents a surgical challenge. This review summarises the current knowledge about LVAD and continuous flow devices especially since the latter have been increasingly used worldwide in the most recent years. The review is also based on the institutional experience at Berne University Hospital between 2000 and 2012. Apart from short-term devices (Impella, Cardiac Assist, Deltastream and ECMO) which were used in approximately 150 cases, 85 pulsatile long-term LVAD, RVAD or bi-VAD and 44 non-pulsatile LVAD (mainly HeartMateII and HeartWare) were implanted. After an initial learning curve, one-year mortality dropped to 10.4% in the last 58 patients.

Drug-Related Problems and Hospital Admissions in Cardiac Transplant Recipients

Drug-related problems (DRPs) in the general population account for 15% of all hospital admissions, of which approximately 30% are preventable. Cardiac transplant patients may be at increased risk for DRPs because of their complicated medication regimens that include drugs with a narrow therapeutic index. To determine the incidence and preventability of DRPs causing hospital admission in cardiac transplant patients at a single institution. Between November 2009 and January 2010, a prospective longitudinal study investigated the incidence and preventability of DRPs in a single cardiac transplant center. Three independent reviewers used validated scoring systems to determine the incidence and preventability of drug-related hospital admissions. DRPs were classified by type, pharmacologic class, and impact on length of stay. During the 3-month study period, 48 cardiac transplant patients were hospitalized. DRPs accounted for 40% (19/48) of these admissions and 58% (11/19) were adjudicated to be preventable. Common DRPs included supratherapeutic (32%) and subtherapeutic (16%) dosage, adverse drug reaction (32%), drug interaction (5%), and nonadherence (5%). Pharmacologic classes implicated included immunosuppressant (63%), antimicrobial (11%), electrolyte/fluid (11%), and anticoagulant (5%). Average length of stay in drug-related compared to non-drug-related admissions was 11.4 versus 8.5 days (p = 0.458). When annualized, 44 hospitalizations or 500 hospital days may have been prevented. Hospital admissions following cardiac transplantation are often drug related (40%) and preventable (58%). Incorporating this insight into the multidisciplinary transplant team may improve outcomes, assist in meeting national quality mandates by the United Network for Organ Sharing and Centers for Medicare Services, and lead to new benchmarks for transplant centers.

Argon Plasma Coagulation and Intravenous Octreotide Infusion as Effective Therapy of Upper Gastrointestinal Angiodysplasias in Patients with Nonpulsatile Ventricular Assist Devices

Background: Ventricular assist devices (VAD) are commonly used as a bridge to cardiac transplantation in patients with extremely poor ventricular function. More recently, destination therapy has been another indication for those who are not eligible for heart transplantation. The insertion of these devices has been associated with problematic and recurrent gastrointestinal (GI) bleeding. Angiodysplasia bleeding of the upper GI tract has been particularly challenging and requires further investigation to identify the most optimal therapy. Objective: To determine the most effective endoscopic and medical therapy of angiodysplasia bleeding in patients with VAD. Retrospective review of all patients with VAD and upper GI bleeding due to angiodysplasias from 2006 to 2010. Data collected included endoscopic and medical therapies, number of blood products given, coagulation parameters, surgical intervention and outcomes. Setting: Tertiary referral center with high volume VAD implantation. A total of 4 of patients were identified (2 males and 2 females). All 4 patients had non-pulsatile VAD (Thoratec Heartmate II). Average length of stay was 75 days. Location of bleeding was duodenal in 1 patient and gastric in 3 patients. Average number of blood transfusions required was 44.5 units. Average number of endoscopies was 4.5. Average INR at time of bleed was 1.41. All four patients were alive at 30 days after VAD implantation and 2 were alive at 6 months. All deaths were not directly related with GI bleeding (sepsis with severe ESRD and sudden cardiac arrest on same day of discharge). All 4 patients required APC in addition to Octreotide to control bleeding (See Table 1). GI bleeding in patients with VAD due to angiodysplasia is problematic and difficult to treat. It is associated with significant morbidity and blood transfusion requirements, particularly gastric angiodysplasia bleeding. Traditional endoscopic therapies seems not be that effective in this type of lesions. Combination therapy with intravenous octreotide and endoscopic argon plasma coagulation appears to be a successful approach but further prospective studies are needed.Table: [1366]

Avaliação da doença vascular do enxerto no transplante cardíaco: experiência de um centro brasileiro

Cardiac transplantation continues to be the treatment of choice for heart failure refractory to optimized treatment. Two methods have high sensitivity for diagnosing allograft rejection episodes and cardiac allograft vasculopathy (CAV), important causes of mortality after transplantation. To assess the relationship between intravascular ultrasound (IVUS) results and endomyocardial biopsy (BX) reports in the follow-up of patients undergoing cardiac transplantation in a Brazilian reference service. A retrospective epidemiological observational study was carried out with patients undergoing orthotopic cardiac transplantation from 2000 to 2009. The study assessed the medical records of those patients and the results of the IVUS and BX routinely performed in the clinical post-transplant follow-up, as well as the therapy used. Of the 77 patients assessed, 63.63% were males, their ages ranging from 22 to 69 years. Regarding the IVUS results, 33.96% of the patients were classified as Stanford class I, and 32.08%, as Stanford class IV. Of the 143 BX reports, 51.08% were 1R, and 0.69%, 3R. The Quilty effect was described in 14.48% of the BX reports. All patients used antiproliferative agents, 80.51% used calcineurin inhibitors, and 19.48% used proliferation signal inhibitors. The assessment of cardiac transplant patients by use of IVUS provides detailed information for the early and sensitive diagnosis of CAV, which is complemented by histological data derived from BX, establishing a possible causal relationship between CAV and humoral rejection episodes.

Diagnóstico, prevenção e tratamento da doença vascular do aloenxerto

The major limitation of long-term survival after cardiac transplantation is allograft vasculopathy, which consists of concentric and diffuse intimal hyperplasia. The disease still has a significant incidence, estimated at 30% five years after cardiac transplantation. It is a clinically silent disease and so diagnosis is a challenge. Coronary angiography supplemented by intravascular ultrasound is the most sensitive diagnostic method. However, new non-invasive diagnostic techniques are likely to be clinically relevant in the future. The earliest possible diagnosis is essential to prevent progression of the disease and to improve its prognosis. A new nomenclature for allograft vasculopathy has been published in July 2010, developed by the International Society for Heart and Lung Transplantation (ISHLT), establishing a standardized definition. Simultaneously, the ISHLT published new guidelines standardizing the diagnosis and management of cardiac transplant patients. This paper reviews contemporary concepts in the pathophysiology, diagnosis, prevention and treatment of allograft vasculopathy, highlighting areas that are the subject of ongoing research.

233 Pharmacokinetics of Cyclosporine and Tacrolimus in Cardiac Transplant Patients With Diabetes

233 Pharmacokinetics of Cyclosporine and Tacrolimus in Cardiac Transplant Patients With Diabetes