Cardiac Transplant Patients Research Articles

Long term follow up after surgery in congenitally corrected transposition of the great arteries with a right ventricle in the systemic circulation

Aim of the studyTo investigate the long-term outcome of surgical treatment for congenitally corrected transposition of the great arteries (CCTGA), in patients with biventricular repair with the right ventricle as systemic ventricle.MethodsA total of 32 patients with CCTGA were operated between January 1972 and October 2008. These operations comprised 18 patients with a repair with a normal left ventricular outflow tract, 11 patients with a Rastelli repair of the left ventricle to the pulmonary artery and 3 patients with a cardiac transplantation.ResultsExcluding the cardiac transplantation patients, mean age at operation was 16 years (sd 15 years, range 1 week - 49 years). Median follow-up was 12 years (sd 10 years, range 7 days - 32 years). Survival obtained from Kaplan-Meier analysis at 20 years after surgery was 63% (CI 53-73%). For the non-Rastelli group these data at 20 years were 62% (CI 48-76%) and for the Rastelli group 67% (CI 51-83%). Freedom of reoperation at 20 years was 32% (CI 19-45%) in the overall group. In the non-Rastelli group the data at 20 years were 47% (CI 11-83%) and for the Rastelli group 21% (CI 0-54%) after almost 19 years.ConclusionsLong term follow up confirms that surgery in CCTGA with the right ventricle as systemic ventricle has a suboptimal survival and limited freedom of reoperation. Death occurred mostly as a result of cardiac failure.

Behcet's disease and heart transplantation: A word of caution

Behcet's disease is a rare autoimmune disease characterized by oral and genital ulcers, and by multisystem disease, including arthritis, neurologic complications and vasculitis. Large-vessel and coronary artery aneurysms are often an indication for surgery, but the return of aneurysms, thrombosis, and the tendency to exhibit an exaggerated inflammatory response at puncture sites (pathergy) complicate surgical recovery. As such, cardiac transplantation, which requires atrial and large-vessel anastomoses, has not been reported in patients with Behcet's disease. We report the first orthotopic heart transplant with >1-year survival in a patient with Behcet's disease despite major complications. The investigators remain pessimistic about cardiac transplantation in patients with Behcet's disease until advances in preventing recurrent vascular pathology ensue.

The Utility of a Video Game System in Rehabilitation of Burn and Nonburn Patients: A Survey Among Occupational Therapy and Physiotherapy Practitioners

The objective of this study was to investigate perceptions of occupational therapists and physiotherapists on the use of Nintendo Wii™ (Nintendo of America Inc., Redmond, WA) in rehabilitation. Occupational therapists and physiotherapists in a rehabilitation hospital trialed four Wii games that addressed physical movement, balance, coordination, and cognitive performance. Then, they completed an opinion survey on the utility of Wii in rehabilitation. The results were compared between burn care therapists (BTs) and nonburn care therapists, using chi(2) with a P < .05 considered significant. The participation rate was 79% (63/80), and they agreed that Wii was easy to set up (71%), operate (68%), and safe to use (76%). Participants agreed that Wii would be beneficial in outpatient (76%) and inpatient (65%) settings and that it could improve treatment compliance (73%). Participants recommended 15 to 30-minute Wii intervention (59%) daily (81%) and twice per week (43%). Participants believed that neurologic (71%), trauma (68%), burn (59%), and musculoskeletal (49%) patients would benefit from Wii intervention but not cardiac (43%) or organ transplant patients (18%). Participants believed that outcomes using Wii could be measured reliably (49%), and skills learned while playing could be transferable to daily function (60%). The significant differences between BTs and nonburn care therapists' perceptions are that BT-treated younger patients (21-40 years vs >60 years, P < .05) and BT favored the therapeutic benefit of Wii in rehabilitation (93% vs 58%, P = .02), specifically in burn rehabilitation (85% vs 39%, P = .001). Occupational therapists and physiotherapists favored the use of Wii in rehabilitation as an adjunct to traditional therapy because it is therapeutic, engaging, and may increase patient participation in rehabilitation.

Revisiting the effects of CMV on long-term transplant outcome

Indirect effects of cytomegalovirus (CMV) in transplantation are of three types: increase in systemic immunosuppression, increased risk of malignancy (especially Epstein-Barr virus-related B-cell lymphoproliferative disease), and the possible contribution to allograft injury. Despite modern and potent antiviral drugs, the real impact of CMV in transplantation, especially kidney transplantation, remains a challenge because many confounding factors arise when analyzing this question.This review will fuel the discussion and review some of the recent data. A recent study on cardiac allograft in mice has shown that CMV in latently infected recipients could break graft acceptance. Although the exact nature of response was not addressed, this study suggested that CMV reactivation inside the graft played an important part in graft losses. Other recent results suggest that the quality of immune response against CMV influences graft outcome in both cardiac and kidney transplant patients. Other evidence suggests the link between CMV infection, immune senescence and vascular disease in the whole population. Studies have opened the perspective for new strategies to prevent indirect effects of CMV. Although a causal relationship between CMV reactivation and graft injury is supported by a large body of experimental and clinical data, definitive proof in clinical transplantation is still lacking to exclude an associative relationship. Large randomized clinical trials analyzing long-term graft survival and comparing prophylaxis with preemptive, especially D/R, is probably an efficient way to establish a causal relationship. Research on new antiviral strategies applicable over the long term is important.

Viral Endomyocardial Infection Is an Independent Predictor and Potentially Treatable Risk Factor for Graft Loss and Coronary Vasculopathy in Pediatric Cardiac Transplant Recipients

This study sought to evaluate the outcome and prevalence of viral endomyocardial infection after cardiac transplantation. Viral myocardial infection causes heart failure, but its role after cardiac transplantation is unclear. We hypothesized that viral infection of the cardiac allograft reduces graft survival. Between June 1999 and November 2004, 94 pediatric cardiac transplant patients were screened for the presence of viral genome in serial endomyocardial biopsies (EMBs) using polymerase chain reaction (PCR) assays. Graft loss, advanced transplant coronary artery disease (TCAD), and acute rejection (AR) were compared in the PCR-positive (n = 37) and PCR-negative (n = 57) groups, using time-dependent Kaplan-Meier and Cox regression analyses. From November 2002 to November 2004, intravenous immunoglobulin therapy (IVIG) was administered to patients with PCR-positive EMBs. The outcomes of the IVIG-treated, PCR-positive patients (n = 20) were compared with IVIG-untreated, PCR-positive patients (n = 17). Viral genomes were detected in EMBs from 37 (39%) patients; parvovirus B19, adenovirus, and Epstein-Barr virus (EBV) were the most common. The PCR-positive group (n = 37, 25% graft loss at 2.4 years) had decreased graft survival (p < 0.001) compared with the PCR-negative group (n = 57, 25% graft loss at 8.7 years) and developed advanced TCAD prematurely (p = 0.001). The number of AR episodes was similar in both groups. On multivariate analysis, presence of viral genome was an independent risk factor for graft loss (relative risk: 4.2, p = 0.015). The time to advanced TCAD after becoming PCR-positive was longer in the IVIG-treated patients (p = 0.03) with a trend toward improved graft survival (p = 0.06). Viral endomyocardial infection is an independent predictor of graft loss in pediatric cardiac transplant recipients. This effect appears to be mediated through premature development of advanced TCAD. IVIG therapy in this subgroup may improve survival and merits further investigation.

Infección por Nocardia en pacientes trasplantados cardiacos

Introduction The incidence of Nocardia infection in transplant patients ranges between 0.7 and 3% with a high mortality (26–63%). This fact, together with a median time to diagnosis in about two weeks ago that the state of alertness is of vital clinical importance. Methods From a cohort of 570 cardiac transplant patients, we reviewed the medical records of those who underwent the diagnosis of Nocardia infection during follow-up. Results We identified four cases (incidence 0.73%), two scattered. In all, had pulmonary involvement. Mortality was high (2 of 4 patients). Conclusion In cardiac transplant patients Nocardia infection is rare but has a high mortality, being necessary an early diagnosis to establish an appropriate treatment.

Association of angiotensin‐converting enzyme inhibitor‐associated angioedema with transplant and immunosuppressant use

Immunosuppressants decrease circulating dipeptidyl peptidase IV (DPPIV) activity in transplant patients, and decreased DPPIV activity has been associated with angiotensin-converting enzyme (ACE) inhibitor-associated angioedema. One study has reported an increased incidence of ACE inhibitor-associated angioedema among transplant patients compared to published rates, while several case series report angioedema in patients taking specific immunosuppressant agents. To test the hypothesis that transplant patients are at increased risk of ACE inhibitor-associated angioedema. We assessed the proportion of transplant patients in 145 cases with ACE inhibitor-associated angioedema and 280 ACE inhibitor-exposed controls. We measured the relationship between case-control status, transplant status, and immunosuppressant use and circulating DPPIV activity. We also assessed the incidence of angioedema among consecutive patients who underwent renal or cardiac transplant and were treated with an ACE inhibitor. Transplant patients were significantly overrepresented among ACE inhibitor-associated angioedema cases compared to controls (odds ratio 18.5, 95% CI 2.3-147.2, P = 0.0004). Immunosuppressant use, chronic renal failure, seasonal allergies and smoking were also associated with ACE inhibitor-associated angioedema in univariate analysis. The association of transplant status with ACE inhibitor-associated angioedema was no longer significant after inclusion of immunosuppressant therapy in a multivariate analysis. Dipeptidyl peptidase IV activity was significantly decreased in sera from cases compared to ACE inhibitor-exposed controls, as well as in individuals taking immunosuppressants. Two of 47 ACE inhibitor-treated renal transplant patients and one of 36 ACE inhibitor-treated cardiac transplant patients developed angioedema. Transplant patients are at increased risk of ACE inhibitor-associated angioedema possibly because of the effects of immunosuppressants on the activity of DPPIV.

Ochroconis gallopava peritonitis in a cardiac transplant patient on continuous ambulatory peritoneal dialysis

Ochroconis gallopava has rarely been isolated in immunosuppressed patients. We report the first case to our knowledge of O. gallopava peritonitis in a cardiac transplant patient on continuous ambulatory peritoneal dialysis. A 58-year-old man who had undergone cardiac transplant 8 years earlier alerted his dialysis nurses to the presence of black material in his catheter lumen. Fungal hyphae were seen on direct microscopy of the black material and from the dialysate effluent, and O. gallopava was cultured from both after 1 day. He was treated successfully with a single dose of intravenous voriconazole, followed by 2 weeks of oral voriconazole.

Thyroid nodule and thyroid cancer management pre- and post-cardiac transplantation

Thyroid nodules are common in the adult population. Widespread use of sensitive imaging studies often leads to their incidental discovery. Recent guidelines recommend thyroid-stimulating hormone determination and ultrasonography during initial nodule evaluation. Fine-needle aspiration is often performed to detect malignancy. However, the management of thyroid nodules in cardiac transplantation patients has not been directly addressed by recent guidelines. Confounding medications such as amiodarone and anti-coagulants present a management dilemma. The timing of fine-needle aspiration is crucial because (1) malignancy diagnosed pre-operatively usually precludes organ transplantation, and (2) patients undergoing solid-organ transplantation are at increased risk of developing de novo malignancies, including thyroid. With the rising incidence of thyroid cancer, donor-related malignancy will likely become a more prominent issue. This review addresses thyroid nodule management in the cardiac transplant population and provides recommendations for organ donation and transplantation in donors and recipients with thyroid cancer.

Evaluation of the myocardial performance index and tissue doppler imaging by comparison to near-simultaneous catheter measurements in pediatric cardiac transplant patients

Parameters derived from Doppler echocardiography, such as the myocardial performance index (MPI) and the ratio of peak velocity of early diastolic prograde flow (E) across the atrioventricular valve (AVV) divided by the peak velocity of early diastolic tissue motion at the AVV annulus (E') (E:E' ratio), are routinely used to assess ventricular function. However, they have not been compared with measurements obtained by cardiac catheterization (CC) in children. We prospectively studied post-cardiac transplant children undergoing CC with near-simultaneous echocardiographic imaging for MPI and E:E'. CC data included right atrial pressure (RAp), pulmonary artery wedge pressure (PAWp) and cardiac index (CI). One investigator, who was blinded to the CC data, measured right ventricular (RV) and left ventricular (LV) MPI and E:E' offline. Correlations between echocardiographic and catheter measurements were calculated. Receiver-operating-characteristics (ROC) curves were created to evaluate the utility of echocardiographic measurements that exhibited statistically significant correlations with CC measurements. Twenty-four patients (age range 0.8 to 21 years) underwent 142 CCs during the study period. Of the 12 correlations studied, 3 met statistical significance (p < 0.05) (RV E:E' vs RAp, RV E:E' vs PAWp and LV MPI vs CI). The ROC areas for these correlations were 0.38, 0.42 and 0.68, respectively. There were no cut-off points where both the sensitivity and specificity for any measurement were >0.80. Our data suggest that MPI and E:E' are poor predictors of simultaneously obtained, catheter-derived hemodynamic parameters in post-transplant children. These limitations should be carefully considered before ascribing diagnostic value to these measurements.

Cecal volvulus in a cardiac transplant patient: Report of a case and critical review

Cecal volvulus in a cardiac transplant patient: Report of a case and critical review

Increase of B-type Natriuretic Peptide from Baseline Increases the Risk of Death or Retransplant in Pediatric Cardiac Transplant Patients, Midterm Results

BACKGROUND; Several studies have demonstrated the utility of B-type natriuretic peptide (BNP) in the months following cardiac transplant. The purpose of this study was to analyze longitudinal BNP data in pediatric cardiac transplant patients and determine the efficacy of BNP in routine follow-up of transplant to help predict the adverse event of death or re-transplant. From October 2002 to July 2007, 53 pediatric cardiac transplant patients were treated in an unmatched case-control study. Along with routine studies, BNP values were obtained at regular intervals. Six patients were excluded due to recent transplant, and three patients were excluded due to poor compliance. A baseline BNP was established for each subject utilizing the mean of all BNP values during year 2 post-transplant, or the first year of measured BNP in those patients whose transplant preceded the study by more than 1 year (time from transplant to first BNP 7.0 +/- 3.5 years). The median BNP of all data points since transplant was utilized as an additional surrogate baseline. Univariate logistic regression was used to evaluate BNP versus other covariates on cardiac death. Forty-four patients provided 1254 BNP data points spanning 173 patient years. Nine (20.5%) had an adverse event. Patients who experienced an adverse event had a higher baseline BNP (mean 365 +/- 290; median 375 +/- 352)) when compared to patients without an event (mean 128 +/- 78; median 121 +/- 62; p = 0.04 and p = 0.06)). All subjects with adverse events had a BNP value >or= 250 during the 90 days preceding the event compared to 32.4% of those who did not (odds ratio: 23.13, p < 0.01). A log fold increase in the BNP value compared to the baseline median BNP is a risk for cardiac death in the subsequent 90-day period (OR: 6.82, 95% confidence interval: 1.25-37.11, p = 0.03). Routine BNP monitoring in the post-cardiac transplant pediatric patient allows for the determination of a median BNP, which can be used as a baseline. A log fold increase from the median BNP, or a BNP value >or= 250, increases the risk of death or re-transplant and suggests a 90-day period of heightened clinical surveillance, perhaps necessitating increased medication or re-listing for repeat transplant.

Viral epidemiologic shift in inflammatory heart disease: The increasing involvement of parvovirus B19 in the myocardium of pediatric cardiac transplant patients

Detection of viral genome in rejecting cardiac transplant patients has been reported, with coxsackievirus and adenovirus causing premature graft failure. Recently, parvovirus B19 (PVB19) genome in myocardial samples has been increasingly reported, but its role in cardiac pathology and effect on transplant graft survival are unknown. The objectives of this study were to determine if changes in the viruses identified in the myocardium represent an epidemiologic shift in viral myocardial disease and whether PVB19 adversely affects transplant graft survival. From September 2002 to December 2005, nested polymerase chain reaction was used to evaluate endomyocardial biopsy specimens for 99 children (aged 3 weeks-18 years) with heart transplants for the presence of viral genome. Cellular rejection was assessed by histology of specimens. Transplant coronary artery disease (TCAD) was diagnosed by coronary angiography or histopathology. Specimens from 700 biopsies were evaluated from 99 patients; 121 specimens had viral genome, with 100 (82.6%) positive for PVB19, 24 for Epstein-Barr virus (EBV; 7 positive for PVB19 and EBV), 3 for CMV, and 1 for adenovirus. Presence of PVB19 genome did not correlate with rejection score, nor did a higher viral copy number. Early development of advanced TCAD (p < 0.001) occurred in 20 children with persistent PVB19 infection (> 6 months). PVB19 is currently the predominant virus detected in heart transplant surveillance biopsy specimens, possibly representing an epidemiologic shift. Cellular rejection does not correlate with the presence or quantity of PVB19 genome in the myocardium, but children with chronic PVB19 infection have increased risk for earlier TCAD, supporting the hypothesis that PVB19 negatively affects graft survival.

Echo rejection score: new echocardiographic approach to diagnosis of heart transplant rejection☆

The gold standard test in the diagnosis of heart transplant rejection is right ventricular (RV) myocardial biopsy, which is an invasive, time-consuming, expensive method. In an effort to find a reliable method to minimise the sequential use of myocardial biopsy, we assessed the main echocardiographic indices for the detection of allograft rejection. Fifty myocardial specimens were examined in this prospective study, which assessed the prominent echocardiographic parameters propounded by previous studies as indicators of rejection. Prior to biopsy, all the patients underwent preoperative transthoracic echocardiography. The accuracy of the echocardiographic indices was compared with that of myocardial biopsy indices as the gold standard. At three myocardial segments, namely, RV base, interventricular septal (Sep) base and lateral left ventricular (Lat) base, peak systolic strain (RV-S, Lat-S and Sep-S) was measured. In addition, time to systole (TS) was measured at the same three segments, yielding the three variables of RV-TS, Sep-TS and Lat-TS. Our logistic regression model revealed that the four factors of Lat-S (%), Sep-TS (ms), posterior wall thickness (PWT; mm) and left ventricular mass index (LVMI; g m(-2)) could denote heart transplant rejection. We devised a new index, the echo rejection score, using the following formula: [(PWT+LVMI)-(Lat-S+Sep-TS)]. This new formula has an area under a curve of 0.932 and a cut-off point of 0; it yields a sensitivity of 100.0%, specificity of 71.0%, positive predictive value of 67.9% and a negative predictive value of 100.0%. If the echo rejection score is >0, there is a 67.9% possibility that a cardiac transplant patient is presenting with allograft rejection, while a score < or =0 denotes a 100% improbability of rejection. Our proposed method for screening patients at risk of acute cardiac rejection with echo rejection score showed a good sensitivity in detection of graft rejection. However, further study is required to determine if it can be used as an adjunct to the myocardial biopsy.

Prolonged elevation of plasma argatroban in a cardiac transplant patient with a suspected history of heparin‐induced thrombocytopenia with thrombosis

Direct thrombin inhibitors (DTIs) provide an alternative method of anticoagulation for patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITT) undergoing cardiopulmonary bypass (CPB). In the following report, a 65-year-old critically ill patient with a suspected history of HITT was administered argatroban for anticoagulation on bypass during heart transplantation. The patient required massive transfusion support (55 units of red blood cells, 42 units of fresh-frozen plasma, 40 units of cryoprecipitate, 40 units of platelets, and three doses of recombinant Factor VIIa) for severe intraoperative and postoperative bleeding. Plasma samples from before and after CPB were analyzed postoperatively for argatroban concentration using a modified ecarin clotting time (ECT) assay. Unexpectedly high concentrations of argatroban were measured in these samples (range, 0-32 microg/mL), and a prolonged plasma argatroban half life (t(1/2)) of 514 minutes was observed (published elimination t(1/2) is 39-51 minutes [< or = 181 minutes with hepatic impairment]). Correlation of plasma argatroban concentration versus the patient's coagulation variables and clinical course suggest that prolonged elevated levels of plasma argatroban may have contributed to the patient's extended coagulopathy. Because DTIs do not have reversal agents, surgical teams and transfusion services should remain aware of the possibility of massive transfusion events during anticoagulation with these agents. This is the first report to measure plasma argatroban concentration in the context of CPB and extended coagulopathy.

Recovery of Renal Function in Heart Transplantation Patients After Conversion From a Calcineurin Inhibitor-Based Therapy to Sirolimus

Background Renal failure is the most important comorbidity in patients with heart transplantation, it is associated with increased mortality. The major cause of renal dysfunction is the toxic effects of calcineurin inhibitors (CNI). Sirolimus, a proliferation signal inhibitor, is an imunossupressant recently introduced in cardiac transplantation. Its nonnephrotoxic properties make it an attractive immunosuppressive agent for patients with renal dysfunction. In this study, we evaluated the improvement in renal function after switching the CNI to sirolimus among patients with new-onset kidney dysfunction after heart transplantation. Methods The study included orthotopic cardiac transplant (OHT) patients who required discontinuation of CNI due to worsening renal function (creatinine clearance < 50 mL/min). We excluded subjects who had another indication for initiation of sirolimus, that is, rejection, malignancy, or allograft vasculopathy. The patients were followed for 6 months. The creatinine clearance (CrCl) was estimated according to the Cockcroft-Gault equation using the baseline weight and the serum creatinine at the time of introduction of sirolimus and 6 months there after. Nine patients were included, 7 (78%) were males and the overall mean age was 60.1 ± 12.3 years and time since transplantation 8.7 ± 6.1 years. The allograft was beyond 1 year in all patients. There was a significant improvement in the serum creatinine (2.98 ± 0.9 to 1.69 ± 0.5 mg/dL, P = .01) and CrCl (24.9 ± 6.5 to 45.7 ± 17.2 mL/min, P = .005) at 6 months follow-up. Conclusion The replacement of CNI by sirolimus for imunosuppressive therapy for patients with renal failure after OHT was associated with a significant improvement in renal function after 6 months.

Uric acid: a prognostic marker not only before but also after heart transplantation☆

Early diagnosis of rejection after heart transplantation is mandatory, since even mild rejection can rapidly progress to more severe rejection. However, the identification of patients at high risk of acute cellular rejection and their non-invasive diagnosis remains a challenge. To identify patients with a high risk of acute cellular rejection during the first post-transplantation year. A retrospective study of 114 consecutive patients submitted to first heart transplantation (between November 2003 and January 2008). The International Society for Heart and Lung Transplantation (ISHLT) grading system was used for the classification of endomyocardial biopsies. Patients were divided into two groups: group A (non-rejecting)--90 patients who had no significant rejection episodes (ISHLT grade <2R); and group B (rejecting)--included 24 patients with moderate or severe rejection episodes (grade > or =2R) during a 1-year post-transplantation follow-up. The Kaplan-Meier method was used for cumulative survival analysis with the Breslow test for assessing statistical differences between curves. The group B patients tended to have more ischaemic aetiology (42% vs 26%, p=0.13) and lower baseline triglycerides (99.1+/-34.2 vs 117.9+/-63.6 mg dl(-1), p=0.17), tended to receive less cardiac allografts from donors of the same ABO blood type (83% vs 92%, p=0.25) and to have longer cardiopulmonary bypass times (108+/-64 min vs 94+/-26 min, p=0.12). Significantly, they had more hyperuricaemia (71% vs 43%, p=0.02) and longer mechanical ventilation times (19.2+/-17.9h vs 14.3+/-5.3h, p=0.031). During follow-up, the group B patients tended to have more severe infections (46% vs 31%, p=0.16), to be more frequently Quilty-positive (50% vs 30%, p=0.073) and to have a higher 1-year mortality (8% vs 2%, p=0.18). Uric acid levels higher than 7.2 mg dl(-1) were identified as the optimal cut-off value to predict acute rejection after heart transplantation (with a sensitivity of 71%, a specificity of 62% and an area under the curve of 0.64). Our work suggests that hyperuricaemia may be a marker of acute cellular rejection that could be another tool helping to identify acute rejection during the follow-up of cardiac-transplanted patients.

469: Diabetes Mellitus Following Heart Transplantation

Post transplant diabetes mellitus (DM) is common and contributes to cardiac allograft vasculopathy (CAV). Steroid use is an established risk factor, but the relative impact of other immunosuppressives is less well defined in cardiac recipients. Guidelines and insulin-sparing protocols have been developed in abdominal organ transplantation. However, DM management in cardiac transplant patients is often empirical, defered to primary physicians or endocrinologists outside the transplant center. We investigated the effect of the “conventional” approach in cardiac transplant patients.

Dynamic Changes in Lymphocyte GRK2 Levels in Cardiac Transplant Patients: A Biomarker for Left Ventricular Function

G protein-coupled receptor kinase 2 (GRK2), which is upregulated in the failing human myocardium, appears to have a role in heart failure (HF) pathogenesis. In peripheral lymphocytes, GRK2 expression has been shown to reflect myocardial levels. This study represents an attempt to define the role for GRK2 as a potential biomarker of left ventricular function in HF patients. We obtained blood from 24 HF patients before and after heart transplantation and followed them for up to 1 year, also recording hemodynamic data and histological results from endomyocardial biopsies. We determined blood GRK2 protein by Western blotting and enzyme-linked immunosorbent assay. GRK2 levels were obtained before transplant and at first posttransplant biopsy. GRK2 levels significantly declined after transplant and remained low over the course of the study period. After transplantation, we found that blood GRK2 significantly dropped and remained low consistent with improved cardiac function in the transplanted heart. Blood GRK2 has potential as a biomarker for myocardial function in end-stage HF.

Tailored total lymphoid irradiation in heart transplant patients: 10-years experience of one center

BackgroundTo assess safety and efficacy of tailored total lymphoid irradiation (tTLI) in cardiac transplant patients.MethodsA total of seven patients, of which five had recalcitrant cellular cardiac allograft rejection (RCCAR), confirmed by endomyocardial biopsies, and two had side effects of immunosuppressive drug therapy, were all treated with tTLI. tTLI was defined by the adjustment of both the fraction interval and the final irradiation dosage both being dependent on the patients general condition, irradiation-dependent response, and the white blood and platelet counts. A mean dose of 6.4 Gy (range, 1.6 - 8.8 Gy) was given. Median follow-up was 7 years (range, 1.8 - 12.2 years).ResultstTLI was well tolerated. Two patients experienced a severe infection during tTLI (pneumocystis jirovecii pneumonia, urosepsis and generalized herpes zoster) and one patient developed a lymphoproliferative disorder after tTLI. The rate of rejection episodes before tTLI was 0.43 episodes/patient/month and decreased to 0.02 episodes/patient/month after tTLI (P < .001). At the end of the observation time, all patients except one were alive.ConclusionstTLI is a useful treatment strategy for the management of RCCAR and in patients with significant side effects of immunosuppressive drug therapy. In this series tTLI demonstrated significantly decreased rejection rates without causing relevant treatment-related toxicity.