Mortality In Cardiac Transplant Recipients Research Articles

Ten-year outcomes post percutaneous coronary intervention in cardiac transplant recipients

BackgroundCardiac allograft vasculopathy (CAV) is one of the major late causes of mortality in cardiac transplant recipients beyond the first year. Given the lack of longer term data for PCI in cardiac transplant recipients, we report ten year follow up of such cardiac transplant recipients who underwent PCI at Mayo Clinic. MethodsA retrospective observational study was conducted that included cardiac transplant recipients who underwent PCI at the Mayo Clinic. Continuous variables were presented as mean (SD) or median (IQR) and discrete variables were presented as frequency (percentage). ResultsThirty-eight consecutive cardiac transplant recipients underwent PCI from January 1, 1995, to June 30, 2023, at the Mayo Clinic. The median age of the cohort was 61.00 years (IQR:51.00–70.00) comprised predominantly of men (65.80%), and 47.40% of the cohort presented with an acute coronary syndrome. The antirejection therapy prior to the PCI included steroids (47.30%), cyclosporine (26.30%), tacrolimus (15.80%), mycophenolate (42.10%), azathioprine (13.10%), & sirolimus (31.57%). Intravascular ultrasound during PCI was utilized in 10.50% of the cases. The median time duration between heart transplant and PCI was 9.00 years (IQR:6.00–13.00 years). Two individuals needed repeat heart transplant for severe CAV. In hospital mortality was 5.20% and the long-term median survival was 7.20 years with a 10-year mortality rate of 65.70%. ConclusionsThis is the first publication reporting ten-year outcomes for PCI in cardiac transplant patients. The salient features for our cohort were a 65.70% mortality rate at 10 years and a median survival of 7.20 years.

Predictors and Clinical Outcomes of Lymphoproliferative Disorders in Heart Transplant Recipients

Post-transplant lymphoproliferative disorder (PTLD) is an important cause of morbidity and mortality in cardiac transplant recipients. However, the incidence and predictors of PTLD in the real world has not been well studied. We analyzed the temporal trends, clinical characteristics, predictors, and clinical outcomes of PTLD using 28,136 recipients of deceased donor, heart alone transplants between 2000 and June 2015 from the International Society for Heart and Lung Transplantation Thoracic Organ Transplant Registry. Ten-year incidence of PTLD after successful discharge for transplants during 2000-2007 was 3.8%. The adjusted overall risk of mortality was significantly higher in patients who had PTLD within 3 years after heart transplantation compared to those with no PTLD (HR 2.22, 95% CI 1.86-2.65, p<0.001). The adjusted risk of PTLD was lower for transplants in 2008-2015 vs. 2000-2007 period (HR 0.75, 95% CI 0.57-0.98, p=0.038). Risk mortality was also lower for transplants in 2008-2015 vs. 2000-2007 period (HR 0.86, 95% CI 0.81-0.91, p<0.001). Age at transplant, male gender, Epstein-Barr virus (EBV) mismatch (donor EBV (+), recipient EBV (-)), and use of discharge cyclosporin were independent risk factors for PTLD. Treated acute rejection within 1-year was significantly related with increased rate of PTLD within 3 years (1.4% vs. 0.9%, p<0.001) (Figure 1). The incidence as well as mortality of PTLD has decreased in recent years. Close observation and balanced immunosuppression according to the patient's characteristics such as age, gender, EBV status and rejection history is the key to decrease the burden of PTLD which can be detrimental in the course of heart transplantation.

Conduction Abnormalities Associated with Tricuspid Annuloplasty in Cardiac Transplantation.

Prophylactic DeVega tricuspid annuloplasty (DVA) of the donor heart has been reported to improve tricuspid regurgitation (TR), renal dysfunction, and mortality in cardiac transplant recipients. This is the first study to investigate the electrical, as well as, hemodynamic effects of DVA during orthotopic heart transplantation (OHT). Electrocardiographic, echocardiographic, and hemodynamic data of 76 patients with DVA and 104 patients without DVA who underwent OHT between 2013 and 2017 at Columbia University Medical Center (New York, NY) were studied. Patients with DVA were older (56.5 ± 1.2 vs. 52.4 ± 1.0 years of age; p = 0.017) and predominantly men (78% vs. 68%; p = 0.02). There were no significant differences in right ventricular function and TR. Patients with DVA had increased incidence of right bundle branch block compared with without DVA (37% ± 5.9% vs. 9% ± 2.9%; p < 0.001). Three patients with DVA developed complete heart block (CHB), whereas no patients without DVA developed CHB (p = 0.04). Four patients with DVA received a pacemaker (PPM), whereas only one patient in the without DVA group received a PPM. Complete heart block was significantly increased in patients who received prophylactic DVA. Possible risk of conduction abnormalities should be considered with performance of DVA annuloplasty in cardiac transplant recipients.

Incidence of cytomegalovirus in cardiac transplant recipients receiving induction immunosuppression with antithymocyte globulin.

Cytomegalovirus (CMV) is a major cause of morbidity and mortality in cardiac transplant recipients. Use of induction immunosuppression in cardiac transplantation may have an impact on the incidence of CMV, but literature is limited. Single-center, retrospective cohort study comparing the risk of CMV infection and disease in cardiac transplant patients receiving antithymocyte globulin (ATG) induction therapy to those receiving no antibody induction. A total of 75 patients were included in our analysis, 50 who received ATG induction and 25 who did not. CMV infection occurred in 10 (20%) and 5 (20%) patients in the ATG and No ATG groups, respectively (P > 0.99). CMV disease occurred in 10 (20%) and 4 (16%) patients in the ATG and No ATG groups, respectively (P = 0.763). The median time from transplant to CMV infection was 200.0 [142.5, 364.5] days in the ATG group vs 221.0 [192.0, 299.0] days in the No ATG group (P = 0.723). The median time from end of CMV prophylaxis to CMV infection was 94.5 [66.5, 151.0] days in the ATG group vs 53.0 [41.0,149.5] days in the No ATG group (P = 0.202). Freedom from CMV infection was highest in the D+/R+ group and lowest in the D+/R- group. In cardiac transplant recipients, ATG induction was not associated with an increased incidence of CMV infection or disease in the setting of valganciclovir prophylaxis and an initial maintenance immunosuppression regimen of primarily steroids, mycophenolate mofetil, and tacrolimus.

Clinical Outcomes After Tricuspid Annuloplasty Prior to Cardiac Transplantation: A Single Center Experience

Allograft tricuspid regurgitation (TR) occurs after orthotopic heart transplantation (OHT) and is associated with significant morbidity. Prophylactic tricuspid repair with DeVega annuloplasty (DVA) of the donor heart has been reported to improve TR, renal dysfunction and mortality in cardiac transplant recipients. This is the first study to investigate the electrical and hemodynamic effects of DVA during OHT.

345 - Analysis of Hospitalizations and In-Hospital Mortality after Cardiac Transplantation in the United States

Background: Roughly around two thousand cardiac transplantations are being performed every year in US. Cardiac transplant recipients (CTR) have a better survival with three year survival approaching 75%. There is limited data on the most common causes of hospitalizations and in-hospital mortality in these cardiac transplant recipients. Objective: We sought to find out the most common reasons for hospitalization and in-hospital mortality in CTR in the United States using National Inpatient Sample (NIS) from 2008 to 2014. Methods: With NIS data, we identified CTR who were hospitalized from 2008 to 2014 using International Classification of Diseases—9th edition (ICD-9) code V42.1. We then identified the most common reasons of hospitalizations and in-hospital mortality using appropriate ICD-9 codes for primary admission diagnoses. Results: Our study shows that there were 110,894 hospitalizations of CTR from 2008 to 2014. The ten most common reason for hospitalization among these patients were pneumonia (6.5%), septicemia (5%), acute renal failure (4.9%), complication of graft, implant or device (4.4%), intestinal infection (3%), complications of surgical or medical care (2.8%), fluid and electrolyte imbalance (2.5%), skin and subcutaneous tissue infection (2.4%), congestive heart failure (2.4%) and viral infections including herpes simplex, zoster, influenza etc (2.3%). A total of 2395 CTR died during hospitalization. We found that the ten most common reasons for in-hospital mortality in these patients were sepsis (26.2%), respiratory failure (7.5%), complication of graft, implant or device (5.8%), pneumonia (4.3%), acute renal failure (4.1%), acute cerebrovascular accident (3.9%), congestive heart failure (2.9%), lung cancer (2.5%), acute myocardial infarction (2.3%) and intestinal infections (2.1%). Conclusion: Infectious causes are among the most common reasons for hospitalization and in-hospital mortality in cardiac transplant recipients.Tabled 1Most common reasons for hospitalization in cardiac transplant recipients in the United StatesReason for hospitalizationPercentage of total hospitalizations of cardiac transplant recipientsPneumonia6.5%Sepsis5.0%Acute renal failure4.9%Complication of graft, implant or device4.4%Intestinal infection3.0%Complication of surgical or medical care2.8%Fluid and electrolyte imbalance2.5%Skin and subcutaneous tissue infection2.4%Congestive heart failure2.4%Viral infections2.1%Most common reasons for in-hospital mortality in cardiac transplant recipientsReasons for in-hospital mortalityPercentage of total hospitalizations of cardiac transplant recipientsSepsis26.2%Respiratory failure7.5%Complication of graft, implant or device5.8%Pneumonia4.3%Acute renal failure4.1%Acute cerebrovascular accident3.9%Congestive heart failure2.9%Lung cancer2.5%Acute myocardial infarction2.3%Intestinal infections2.1% Open table in a new tab

Pre-cardiac transplant amiodarone use is not associated with postoperative mortality: An updated meta-analysis

BackgroundAmiodarone remains the preferred agent for the treatment and prevention of life-threatening ventricular arrhythmias in patients with end-stage heart failure. While several reports suggest that pre-operative amiodarone exposure worsens outcomes in heart transplant recipients, other studies have failed to validate this relationship. We sought to clarify this issue by performing a meta-analysis of the available literature surrounding this topic. MethodsWe searched Medline, SCOPUS and the Cochrane Central Register of Controlled Trials through December 15th 2016, as well as proceedings from related conferences over the prior 3years. Included studies evaluated patients undergoing cardiac transplantation who had received pre-transplant amiodarone and reported postoperative mortality. Outcomes were pooled using a Hartung-Knapp random-effects model producing odds ratios (OR) and 95% confidence intervals (CI). Statistical heterogeneity was evaluated using the Cochrane Q statistic p-value and I2 value. Publication bias was assessed by visual inspection of funnel plots and using Egger's weighted regression statistic. ResultsNine studies including 16,509 participants were included in the overall analysis. Use of pre-transplant amiodarone was not associated with an increase in postoperative mortality versus control (OR 1.38, 95% 0.8 to 2.36). Moderate statistical heterogeneity was present (I2=45.8%, p=0.06); visual inspection of funnel plot analysis did not suggest publication bias. No association was noted between a longer duration of follow-up and higher odds of mortality with amiodarone use (p=0.91). ConclusionMeta-analysis of the available evidence suggests that pre-operative amiodarone exposure does not increase mortality in cardiac transplant recipients.

(1179) - Pre-Transplant Amiodarone Exposure Increases Mortality in Cardiac Transplant Recipients: A Meta-Analysis

(1179) - Pre-Transplant Amiodarone Exposure Increases Mortality in Cardiac Transplant Recipients: A Meta-Analysis

Abstract 540: Correlation of Improved Cholesterol Efflux Capacity of High Density Lipoprotein With Survival and Allograft Vasculopathy in Cardiac Transplant Recipients

Background: Coronary allograft vasculopathy (CAV) is an important cause of mortality after cardiac transplantation. High density lipoprotein (HDL) cholesterol efflux capacity has been inversely associated with coronary artery disease and is impaired in cardiac transplant recipients. We performed a single center case-cohort study to test the hypothesis that reduced efflux capacity is a risk factor for mortality and a second, multi-center retrospective study to test if efflux capacity is associated with CAV progression. Methods: We designed a single center case-cohort study in which we identified cardiac transplant patients who died between 2009-2012 (cases, n=34) and controls as cardiac transplant patients who were alive as of the fourth quarter of 2013 (n=57). Efflux capacity was measured by incubating apolipoprotein B-depleted serum with macrophages in a validated ex vivo system. In a second study, we utilized pre-transplant samples from the Clinical Trials in Organ Transplantation 5 (CTOT5) study to determine the association between ATP-binding-cassette (ABC) A1-dependent cholesterol efflux and CAV progression at 1 year. Results: In our single center study, the average time from transplant to study entry was well-matched between cases and controls (7.6±1.0 vs 7.7±0.8 years, respectively, p=0.48). Multivariable Cox proportional hazard ratios demonstrated that higher levels of HDL cholesterol efflux capacity were associated with survival (HR 0.61, 95% CI 0.43-0.85), even after adjustment for HDL cholesterol mass. To determine whether excess mortality observed in subjects with reduced efflux could be attributable to CAV progression, we tested the relationship between intravascular ultrasound (IVUS) progression of CAV and cholesterol efflux capacity using linear regression. ABCA1-dependent efflux and IVUS progression were significantly associated (β = -0.90, 95% CI [-1.73 - -0.07], p = 0.037, R2 = 0.37). Conclusion: Reduced efflux capacity is an important mediator of CAV progression and mortality in cardiac transplant recipients. This finding suggests that interventions to increase HDL cholesterol efflux capacity may provide clinical benefit in cardiac transplant recipients.

Effect of Peripheral Vascular Disease on Mortality in Cardiac Transplant Recipients (from the United Network of Organ Sharing Database)

Peripheral vascular disease (PVD) portends increased morbidity and mortality in patients with heart failure. In those with advanced heart failure, heart transplantation (HT) is the only causative therapy to increase survival. However, little is known about the impact of symptomatic PVD on survival of HT recipients in large multicenter cohorts. The aim of this study was to investigate an association between recipient symptomatic PVD and survival after HT. We analyzed 20,297 patients from the United Network of Organ Sharing data set. Survival analysis using a control cohort established by propensity matching was performed. There was an increased prevalence of traditional cardiovascular risk factors in 711 patients with symptomatic PVD compared with 19,586 patients without PVD. Patients with pretransplant symptomatic PVD had increased post-transplant mortality compared with those without PVD (1-, 5- and 10-year survival rate 91.5% vs 94.9%, 74.8% vs 82.6%, 48.6% vs 54.7%, respectively, log-rank p<0.001). On multivariate analysis based on the propensity matching, factors associated with a lower survival rate were presence of PVD (hazard ratio 1.20, 95% confidential interval 1.02 to 1.42, p=0.030), and female gender (hazard ratio 1.22, 95% confidence interval 1.02 to 1.47, p=0.034). In conclusion, patients with symptomatic PVD have a lower survival rate after HT. Symptomatic PVD should be considered an independent risk factor for poor prognosis in patients undergoing HT evaluation.

61-P

Antibody mediated rejection (AMR) is a significant source of morbidity and mortality in cardiac transplant recipients. Because antibody mediated rejection is known to use the complement pathway, assessment of antibodies that fix complement, such as C1q may show promise here as a quantitative marker of the degree of severity of disease, as well as response to treatment. This was a retrospective case study of 5 patients with biopsy proven AMR. Charts were analyzed for rejection episodes, echocardiographic data, and treatment for AMR. AMR was determined from C4d and CD68 stained sections. Final clinical diagnosis included evidence of allograft dysfunction, HLA donor specific antibody (DSA) and C1q DSA. The 5 cases are graphically presented with time points for biopsy evaluation, echocardiogram, HLA and C1q antibody testing, and treatment. The results of this study indicate that measuring donor specific C1q antibodies may be useful in assessing the severity of AMR as well as the response to treatment. Evaluation of these cases indicate pursuing a larger study is a worthwhile endeavor to further investigate the role of C1q testing as an independent and quantifiable marker for AMR. C1q antibody evaluation may help reduce the frequency of routine surveillance biopsy in cardiac transplant patients, leading to a less invasive method of assessing for rejection. In addition, it can be used to appropriately guide treatment. Studies with longer-term follow-up may help to determine how long after treatment the antibodies will take to completely clear, as more information is needed on how to properly interpret elevated levels of C1q antibodies post-treatment. Correlation of post-treatment levels of C1q with the clinical status of the patient, as well as biopsy data, will help to determine if measurement of C1q can help determine if a particular treatment was a success or a failure. Overall, this study is a good starting point for the assessment of C1q HLA DSA as a marker for AMR.

Single photon emission computed tomography myocardial perfusion imaging to detect cardiac allograft vasculopathy

Cardiac allograft vasculopathy (CAV) is a major cause of morbidity and mortality in cardiac transplant recipients. This study evaluates the usefulness of single photon emission computed tomography (SPECT) and various SPECT-derived diastolic variables to detect CAV in heart transplant patients. A retrospective review of 141 SPECT studies with corresponding coronary angiograms within 12 months was performed on 99 transplant recipients. Diastolic function was assessed using computer-derived measures of peak filling rate (PFR), time to peak filling rate (TPFR), and mean first one-third filling rate (MFR/3). Angiography identified CAV in 53 of the 141 studies (38%). Of the 53, SPECT identified 7 with reversible myocardial defects (sensitivity 13%) and stress-induced electrocardiographic evidence of ischaemia was seen in one patient (sensitivity 2%). SPECT imaging was negative in 86 of the 88 negative coronary angiograms (specificity 98%). The positive predictive value and negative predictive value were 78 and 65%, respectively. If a more stringent definition of CAV was used (≥70% stenosis), the sensitivity and specificity were unchanged (14 and 98%, respectively). There was no statistical difference in diastolic variables between patients with or without angiographic evidence of CAV in regard to PFR (3.57 ± 1.14 vs. 3.18 ± 1.21 EDV/s, P = 0.90), TPFR (149 ± 32 vs. 153 ± 43 ms, P = 0.33), or MFR/3 (1.37 ± 0.43 vs. 1.27 ± 0.42 EDV/s, P = 0.94). Adenosine stress/rest technetium-99m tetrofosmin-gated SPECT is not a sensitive test for detection of CAV in heart transplant recipients. Diastolic dysfunction, as assessed by SPECT, was not shown to be associated with development of CAV.

Prolonged time between donor brain death and organ retrieval results in an increased risk of mortality in cardiac transplant recipients

In cardiac transplantation longer ischemic times relate to poorer outcomes. However, brain death also promotes donor organ injury. The aim of this study was to ascertain if there was an association between longer time periods between donor brain death and organ retrieval with recipient mortality. This retrospective single centre study included 157 cardiac transplants performed between February 1999 and 2009. The time between the second brain stem death test and the cross-clamp time at organ retrieval was noted in hours. This was compared with survival time in years. Cox regression analysis was performed. The following variables were included: donor and recipient sex, age and cytomegalovirus status; donor smoking history; ischemic time and number of rejection episodes. Of the 157 transplants, 37 recipients have died. The mean follow-up was 4.1 years. The mean time between brain stem death test and cross-clamp time was 13.2±3.96 hours. Considering the above variables, the most significant finding is: increased time between brain stem death test and organ retrieval cross-clamp time, predicted a greater recipient mortality [hazard ratio (HR)=1.15; 95% confidence interval (CI)=1.06-1.24; P<0.001]. Longer delays between donor brain death and cross-clamp time are associated with a higher-risk of mortality in cardiac transplant recipients.

Cardiac Allograft Vasculopathy

Cardiac allograft vasculopathy (CAV), characterized by diffuse intimal thickening and luminal narrowing in the arteries of the allograft, is the leading cause of morbidity and mortality in cardiac transplant recipients. Many transplant centers perform routine annual surveillance coronary angiography. However, angiography can underdiagnose or miss CAV due to its diffuse nature. Intravascular ultrasound (IVUS) is more sensitive than angiography. IVUS provides not only accurate information on lumen size, but also quantification of intimal thickening, vessel wall morphology, and composition. IVUS has evolved as a valuable adjunct to angiography and the optimal diagnostic tool for early detection. Noninvasive testing such as dobutamine stress echocardiography and nuclear stress test have shown considerable accuracy in diagnosing significant CAV. Computed tomographic imaging and cardiac magnetic resonance imaging are promising new modalities but require further study. This article reviews the diagnostic methods that are currently available.

481: Use of Peripheral Gene Expression Testing in the Detection of Coronary Allograft Vasculopathy with Intravascular Ultrasound

Coronary allograft vasculopathy (CAV) is one of the major causes of late morbidity and mortality in cardiac transplant recipients. Intravascular ultrasound (IVUS) allows for direct visualization of the coronary lumen thus allowing for accurate determination of disease severity. Peripheral gene expression testing with Allomap has been shown to correlate with the presence of CAV using standard coronary angiography. It is unknown if Allomap testing in primary cardiac transplant recipients allows for early detection of CAV using IVUS testing.

328: Increased LV Mass and Concentricity as Assessed by Cardiac MRI Are Associated with Increased Mortality in Cardiac Transplant Recipients

328: Increased LV Mass and Concentricity as Assessed by Cardiac MRI Are Associated with Increased Mortality in Cardiac Transplant Recipients

Treat the bones and get less rejection!

Known since antiquity, rickets was a common disease until the beginning of the 20th century. It took many years and the collaborative effort of several laboratories to identify the compound present in cod liver oil responsible for the therapeutic effect against rickets. The vitamin D structure was finally described in 1936 by the German chemist Adolf Windaus (1876–1959). Since then, we have come to understand the synthesis of 1α,25(OH)2-vitamin D3 (calcitriol) and its mechanism of action through a nuclear receptor, VDR, to regulate calcium homeostasis and bone mineralization. VDR is expressed not only in intestinal cells and osteoblasts but also constitutively in monocytes and in activated macrophages, dendritic cells, natural killer cells, T and B cells, which suggests immunomodulatory functions for calcitriol. Calcitriol acts as an inhibitor of the adaptive immune system. It has inhibitory effects on macrophages and dendritic cells. Calcitriol enables dendritic cells with tolerogenic properties (1) and acts directly in Th cells to enhance the development of a Th2 phenotype (2). These features could be of benefit in the transplantation setting. In retrospective studies, the administration of calcitriol to kidney transplant recipients improved graft function, graft survival and decreased episodes of acute rejection (3–5). Similar results have been published for heart transplantation. Low post-operative calcitriol serum concentrations are independently associated with high 1-year mortality in cardiac transplant recipients (6). Patients receiving low-dose calcitriol after cardiac transplantation required substantially lower cumulative doses of cyclosporin for organ rejection without any detectable change in the episodes of rejection (7). What about liver transplantation and calcitriol? We investigated the effect of calcitriol as an immunosuppressive agent in an experimental model for liver transplantation (8). Calcitriol increased the survival of vascularized liver allografts in rats when compared with controls. Vitamin D reduced the concentration of interleukin (IL)-2 and IL-12 in serum and in grafts, and increased IL-4 and IL-10 in the grafts. The rejection activity after transplantation was significantly lower in treated rats compared with vehicle-treated controls. In this issue of Liver International, Bitetto et al. (9) present a highly anticipated clinical study that investigates whether vitamin D has beneficial immune properties after liver transplantation. Based on a collection of 133 liver transplantation recipients, the authors report that a low pretransplant serum 25-OH vitamin D is independently associated with rejection episodes (Banff score ≥6) in the first 2 months following liver transplantation and that the introduction of vitamin D3 supplementation in the first month after liver transplantation is associated with a decreased risk for acute rejection (Banff score ≥3) in the following 3–8 months. These results are not surprising, but are important nonetheless. It is estimated that two-third of patients with cirrhosis and 96% of patients awaiting liver transplantation have low serum vitamin D levels (10) and the present study found optimal vitamin D levels (>30 ng/ml) in only 7.5% of the patients tested. Osteoporosis, which increases the risk of vertebral fractures, occurs in 12–55% of patients with cirrhosis (10). In the months following liver transplantation, further bone loss occurs in most liver recipients and exacerbates pre-existing osteopenia with a high incidence of fracturing (10). Patients listed for a liver transplantation should then receive vitamin D before and after transplantation. This supplementation is safe, well tolerated and appears to have additional non-negligible immune effects. Acute rejection is rarely a serious issue after liver transplantation today. Nevertheless, immunosuppressive drugs have side effects, which limit the long-term benefit of liver transplantation. Calcineurin inhibitors impair renal function and every large liver transplantation centre must provide dialysis for some of their transplant recipients and some even receive kidney transplantation. The hope that mTOR inhibitors could serve as renal protective immunosuppressors is vanishing. A retrospective, controlled study showed that the administration of sirolimus after orthotopic liver transplantation did not protect against renal dysfunction (11). Another case–control retrospective series suggested that the choice of sirolimus for liver transplant patients with chronic renal insufficiency is associated with the stabilization of renal function but conferred no additional benefit over low-dose calcineurin inhibitor regimens and may in fact be disadvantageous in patients with a creatinine clearance of <30 ml/min (12). In this context, vitamin D as a calcineurin inhibitor sparing immunosuppressant in liver transplantation is an attractive option. The retrospective nature of the work of Bitetto is a disadvantage as are the arbitrarily chosen endpoints. It is imperative that prospective randomized studies be designed in the liver transplantation field to establish definitively the immunosuppressive role of vitamin D as it is already the case in the renal transplantation field (13). We should not miss the opportunity to treat the bones and get less rejection!

Calcitriol Deficiency and 1-Year Mortality in Cardiac Transplant Recipients

Administration of the vitamin D hormone calcitriol improves survival in solid-organ transplanted experimental animals. We investigated whether lower serum calcitriol concentrations are associated with increased 1-year mortality in cardiac transplant recipients. We prospectively recruited 171 patients who underwent cardiac transplantation at out institution between May 2004 and April 2006. We assessed calciotropic hormones, inflammation markers, and renal function preoperatively and on postoperative days 6 (t1) and 21 (t2). Serum creatinine and C-reactive protein increased, whereas calcitriol decreased significantly after transplantation (P<0.001). As determined by multivariable Cox regression analysis, the calcitriol level at t2 was an independent predictor of 1-year mortality. One-year mortality was 3.7 per 100 person-years in the tertile with the highest calcitriol concentrations at t2 (> 18 pg/mL), 13.2 per 100 person-years in the intermediate tertile (11-18 pg/mL), and 32.1 per 100 person-years in the tertile with the lowest calcitriol concentrations at t2 (< 11 pg/mL) (P<0.001). 25-Hydroxyvitamin D deficiency (serum concentrations below 10 ng/mL), renal insufficiency (serum creatinine > or = 1.6 mg/dL), and high serum concentrations of the inflammation markers C-reactive peptide and tumor necrosis factor-alpha were predictors of a serum calcitriol concentration below 11 pg/mL (P=0.037-0.001). Low postoperative calcitriol concentrations are independently associated with high 1-year mortality in cardiac transplant recipients. A causal relationship has yet to be proven by intervention trials using active vitamin D.

Severe Left Ventricular Hypertrophy 1 Year After Transplant Predicts Mortality in Cardiac Transplant Recipients

Left ventricular hypertrophy (LVH) is a known predictor of morbidity and mortality in patients with essential hypertension. The prevalence and significance of LVH in heart transplant recipients is unknown. Transthoracic echocardiograms were performed as part of a routine protocol 1 year after heart transplantation in 141 consecutive patients. Demographic and echocardiographic data were collected using patients' records and center-specific data from the Cardiac Transplant Research Database and analyzed to determine the prevalence and predictors of LVH at 1 year post-transplantation. Patients were divided into three groups based on left ventricular mass (LVM): normal (LVM <150 g); mild-moderate LVH (LVM 150 to 250 g); and severe LVH (LVM >250 g). LVH was common at 1 year after heart transplantation, present in 83% of heart transplant recipients. Univariate predictors of severe LVH were increased body mass index (p < 0.01), pre-transplant diabetes mellitus (p = 0.02) and pre-transplant hypertension (p = 0.01). By multivariate analysis, pre-transplant hypertension was the only independent predictor of severe LVH (hazard ratio [HR] 2.3, 95% confidence interval [CI] 1.1 to 5.4, p = 0.05). Heart transplant recipients with severe LVH had significantly decreased survival, as compared to patients with normal LVM and mild-moderate LVH (p = 0.03). After multivariate analysis adjusting for age, race, gender, pre-transplant hypertension and diabetes, severe LVH remained a strong, independent predictor of mortality (HR 3.6, 95% CI 1.0 to 12.1, p = 0.04). LVH is common at 1 year after heart transplantation and is a strong, independent predictor of increased mortality. Hypertension before transplantation is an independent predictor of the presence of severe LVH at 1 year after heart transplantation.

Impact of Repetitive Episodes of Antibody-mediated or Cellular Rejection on Cardiovascular Mortality in Cardiac Transplant Recipients: Defining Rejection Patterns

In our previously published work dealing with antibody-mediated (vascular) rejection (AMR), we defined patterns of rejection (AMR and cellular rejection [CR]) based on a review of biopsy diagnoses taken in the first 6 to 12 weeks post-transplant. We have shown the significance of these pattern designations in relation to patient and allograft outcome in five outcome analyses. The current retrospective analysis was done to determine whether our previous criteria for pattern designations provided the greatest degree of discrimination between AMR and CR. Six hundred sixty-five patients from the U.T.A.H. Cardiac Transplant Program were included in our study. Patients induced with OKT3 immunosuppression were excluded. We analyzed the relationship of a number of either AMR or CR episodes to cardiovascular mortality. We constructed Kaplan-Meier survival curves to assess the impact of incremental numbers of AMR or CR episodes on cardiovascular mortality. Three or more episodes of AMR resulted in a statistically significant increase in cardiovascular mortality. By contrast, CR episodes did not increase the risk of cardiovascular mortality. Based on our findings, we believe that clinical trials should be designed to test treatments based on predominant rejection patterns and that end-points for trials should be defined by number of biopsies positive for either CR or AMR. This approach may lead to improved patient and allograft survival.