Search PubMed⌕ Search

Biomedical subjects

B Radovancevic

Publications and source records attributed to B Radovancevic.

At least 19 recordsLinked to original sources
PubMed1999

Decreased expression of tumor necrosis factor-alpha in failing human myocardium after mechanical circulatory support : A potential mechanism for cardiac recovery.

BACKGROUND: An increasing number of observations in patients with end-stage heart failure suggest that chronic ventricular unloading by mechanical circulatory support may lead to recovery of cardiac function. Tumor necrosis factor-alpha (TNF-alpha) is a proinflammatory cytokine capable of producing pulmonary edema, dilated cardiomyopathy, and death. TNF-alpha is produced in the myocardium in response to volume overload; however, the effects of normalizing ventricular loading conditions on myocardial TNF-alpha expression are not known. We hypothesize that chronic ventricular unloading by the placement of a left ventricular assist device (LVAD) may eliminate the stress responsible for persistent TNF-alpha expression in human failing myocardium. METHODS AND RESULTS: Myocardial tissue was obtained from normal hearts and from paired samples of 8 patients with nonischemic end-stage cardiomyopathy at the time of LVAD implantation and removal. Tissue sections were stained for TNF-alpha, and quantitative analysis of the stained area was performed. We found that TNF-alpha content decreased significantly after LVAD support. Furthermore, the magnitude of the changes did not correlate with the length of LVAD support, although greater reductions in myocardial TNF-alpha content were found in patients who were successfully weaned off the LVAD who did not require transplantation. CONCLUSIONS: These data show for the first time that chronic mechanical circulatory assistance decreases TNF-alpha content in failing myocardium; furthermore, we suggest that the magnitude of the change may predict which patients will recover cardiac function.

Adult↗
PubMed1999

The role of flow cytometry-detected IgG and IgM anti-donor antibodies in cardiac allograft recipients.

BACKGROUND: At our transplant center, cardiac allograft recipients undergo transplantation following a negative IgG anti-human globulin (AHG) crossmatch (XM). Flow cytometry crossmatching (FCXM) is a more sensitive XM procedure than the AHG XM procedure, yet there is limited information regarding the clinical relevance of FCXM to cardiac allograft outcome. METHODS: FCXM was performed retrospectively using the pretransplant sera from 140 recipients of primary cardiac allografts who underwent transplantation after AHG-IgG-NEG XM. The FCXM results were correlated to posttransplant rejection and patient survival. RESULTS: All of the patients were auto-XM-NEG. Twenty-two of 140 patients (16%) displayed IgG(+) FCXM and had a significantly poorer 1-year survival rate than did 57 of the FCXM-NEG recipients (68% vs. 86%, P<0.02). Moreover, 50% of the IgG(+) FCXM recipients experienced early rejections (< or =14 days postoperatively) compared with only 16% for the FCXM-NEG recipients (P<0.01). The survival rate of 92% for IgM(+) FCXM recipients (n=37) was significantly improved compared with the 86% survival rate for FCXM-NEG control recipients (P<0.05), suggesting a protective role for IgM. Consistent with this interpretation is that the 1-year survival rate of 79% for the IgG, IgM FCXM(+) recipients (n=24) was significantly better than the 68% survival rate for the IgG(+) FCXM recipients (P<0.02). CONCLUSIONS: These data suggest that IgG(+) FCXM identifies a subset of AHG-IgG-NEG XM cardiac allograft recipients who are at risk for early rejections and poor survival. In contrast, the presence of IgM may be beneficial to survival.

Aged↗
PubMed1999

A randomized, multicenter comparison of tacrolimus and cyclosporine immunosuppressive regimens in cardiac transplantation: decreased hyperlipidemia and hypertension with tacrolimus.

BACKGROUND: Tacrolimus-based immunosuppression seems safe and effective in liver and kidney transplantation. To assess the safety and efficacy of tacrolimus (TAC)-based immunosuppression after cardiac transplantation as well as the relative impact of tacrolimus on immunosuppression-related side effects such as hypertension and hyperlipidemia, we conducted a prospective, randomized, open-label, multicenter study of otherwise identical tacrolimus- and cyclosporine-based immunosuppressive regimens in adult patients undergoing cardiac transplantation. METHODS: Eighty-five adult patients (pts) at six United States cardiac transplant centers, undergoing their first cardiac transplant procedure, were prospectively randomized to receive either TAC-based (n = 39) or cyclosporine (CYA)-based (n = 46) immunosuppression. All pts received a triple-drug protocol with 15 pts (18%) receiving peri-operative OKT3 to delay TAC/CYA due to pre-transplant renal dysfunction. Endomyocardial biopsies were performed at Weeks 1, 2, 3, 4, 6, 8, 10, 12, 24, and 52. The study duration was 12 months. RESULTS: Patients were mostly male (87%) Caucasian (90%) with a mean age of 54 years and primary diagnoses of coronary artery disease (55%) and idiopathic dilated cardiomyopathy (41%). There were no significant demographic differences between groups. Patient and allograft survival were not different in the two groups. The probability and overall incidence of each grade of rejection, whether treated or not, and the types of treatment required did not differ between the groups. At baseline and through 12 months of follow-up, chemistry and hematology values were similar between the groups except serum cholesterol was higher in the CYA group at 3, 6, and 12 months (239 vs 205 mg/dL, 246 vs 191 mg/dL, 212 vs 186 mg/dL, respectively, p < 0.001). Likewise, LDL-cholesterol, HDL-cholesterol and triglycerides were significantly higher in the CYA group. More CYA patients received therapy for hypercholesterolemia (71% vs 41% at 12 months, p = 0.01). There were no significant differences in renal function, hyperglycemia, hypomagnesemia, or hyperkalemia during the first 12 months. More CYA patients developed new-onset hypertension requiring pharmacologic treatment (71% vs 48%, p = 0.05). The incidence of infection was the same for the two groups (2.6 episodes/pt/12 month follow-up). CONCLUSION: Tacrolimus-based immunosuppression seems effective for rejection prophylaxis during the first year after cardiac transplantation and is associated with less hypertension and hyperlipidemia and no difference in renal function, hyperglycemia or infection incidence when compared to cyclosporine-based immunosuppression.

Adult↗
PubMed1999

Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome.

BACKGROUND: There is controversy regarding the application of transfusion triggers in cardiac surgery. The goal of this study was to determine if lowering the hemoglobin threshold for red cell (RBC) transfusion to 8 g per dL after coronary artery bypass graft surgery would reduce blood use without adversely affecting patient outcome. STUDY DESIGN AND METHODS: Consecutive patients (n = 428) undergoing elective primary coronary artery bypass graft surgery were randomly assigned to two groups: study patients (n = 212) received RBC transfusions in the postoperative period if the Hb level was < 8 g per dL or if predetermined clinical conditions required RBC support, and control patients (n = 216) were treated according to individual physician's orders (hemoglobin levels < 9 g/dL as the institutional guideline). Multiple demographic, procedure-related, transfusion, laboratory, and outcome data were analyzed. Questionnaires were administered for patient self-assessment of fatigue and anemia. RESULTS: Preoperative and operative clinical characteristics, as well as the intraoperative transfusion rate, were similar for both groups. There was a significant difference between the postoperative RBC transfusion rates in study (0.9 +/- 1.5 RBC units) and control (1.4 +/- 1.8 RBC units) groups (p = 0.005). There was no difference in clinical outcome, including morbidity and mortality rates, in the two groups; group scores for self-assessment of fatigue and anemia were also similar. CONCLUSIONS: A lower Hb threshold of 8 g per dL does not adversely affect patient outcome. Moreover, RBC resources can be saved without increased risk to the patient.

Aged↗
PubMed1998

Long-term results of triple-drug-based immunosuppression in nonneonatal pediatric heart transplant recipients.

BACKGROUND: Few reports document long-term results of pediatric cardiac transplantation in which triple therapy (cyclosporine, azathioprine, and corticosteroids) was the mainstay of immunosuppression. This report details a single center's pediatric transplant experience and analyzes the relative contributions of selected pre/posttransplant risk factors on long-term morbidity and mortality. METHODS: Retrospective data were collected for all non-neonatal pediatric transplant recipients including: presenting diagnosis, cardiac hemodynamics (particularly pulmonary vascular resistance index), donor ischemic time, occurrence of postoperative infections, episodes of allograft rejection, incidence of posttransplant lymphoproliferative disease or coronary artery disease (CAD), and overall survival. Analysis of single variables and a Cox-proportional hazards model were utilized to determine the impact of pre/posttransplant risk factors on long-term survival. RESULTS: From 1984 to 1995, 64 patients (mean age, 8.3 years), 46 of whom had cardiomyopathy and 18 who had inoperable complex congenital heart disease, underwent cardiac transplantation and received triple-drug immunosuppression. Orthotopic transplantation was performed unless the pulmonary vascular resistance index remained >6 um2 (despite use of pulmonary vasodilator). One patient required heterotopic transplantation. Average donor ischemic time was 217 min. An average of 1.2 rejection episodes/patient occurred (average follow-up period: 50 months). No patient developed posttransplant lymphoproliferative disease, but 22 patients (34%) developed CAD. Overall survival was 80%, 60%, and 57% at 1, 5, and 10 years, respectively. Of outcome variables analyzed, rejection frequency was significantly increased in patients who subsequently developed CAD, but the presence of CAD was not significantly correlated with mortality. CONCLUSION: Triple-drug-based immunosuppressive maintenance therapy in pediatric heart transplant recipients results in good long-term graft survival.

Adolescent↗
PubMed1998

Transmyocardial laser revascularization in allograft coronary artery disease.

We used transmyocardial laser revascularization to treat accelerated cardiac allograft atherosclerosis in 2 patients. One patient received transmyocardial laser revascularization as sole therapy, the other as an adjunct to coronary artery bypass grafting. The systolic function improved in both patients, although the patient who had adjunctive transmyocardial laser revascularization died of systemic infection and renal failure on postoperative day 55. The second patient is alive and well 1 1/2 years after the laser procedure. We discuss 4 other patients who received transmyocardial laser revascularization treatment elsewhere in the United States. Transmyocardial laser revascularization has the potential to become important in the treatment of transplant atherosclerosis. Randomized clinical trials are warranted to assess the efficacy of transmyocardial laser revascularization in this setting.

Coronary Artery Bypass↗
PubMed1998

Usefulness of the QTc interval in predicting acute allograft rejection.

BACKGROUND: Endomyocardial biopsy (EMB) is the gold standard for detecting cardiac allograft rejection. However, EMB is invasive, costly, and unsuitable for frequent monitoring. Recent studies have shown that acute allograft rejection causes ventricular conduction disturbances. Therefore we tested the hypothesis that the electrocardiographic QTc interval correlates with the histopathologic degree of allograft rejection. METHODS: Between January 1994 and April 1997, 65 adult cardiac allograft recipients (mean age 52.1 +/- 1.7 years) were studied from transplantation until hospital discharge. During EMB, a 12-lead electrocardiogram was obtained. In grading acute allograft rejection, we used both the Texas Heart Institute (THI) scale and the International Society for Heart and Lung Transplantation (ISHLT) scale. 212 paired biopsy specimens and QTc intervals (mean 3.3 per patient) were obtained. We considered an increase of more than 10% of the QTc interval a rejection. RESULTS: Of the biopsy specimens 177 showed no or mild rejection (THI grade 0-5; ISHLT grade O-IIIA), and 35 showed moderate to severe rejection (THI grade 6-10; ISHLT IIIA-IV). The mean QTc interval was 449 +/- 2 msec for the first group and 517 +/- 11 msec for the second group (p = 0.0001). The correlation between the biopsy grades and the percentage of the changes in the QTc interval was r = 0.73 (p = 0.001). The QTc interval had a sensitivity of 86% (30/ 35) in predicting rejection and a specificity of 88% (1551177) in predicting the absence of rejection. CONCLUSIONS: Determination of the QTc interval is an accurate, noninvasive means of detecting acute cardiac rejection. Adoption of QTc testing may allow EMB to be used less frequently and more selectively.

Electrocardiography↗
PubMed1998

Noninvasive rejection monitoring of cardiac transplants using high resolution intramyocardial electrograms: initial US multicenter experience.

Endomyocardial biopsy (EMB) remains the mainstay for the diagnosis of acute cellular rejection in cardiac transplant patients. A noninvasive alternative that would supplant or reduce the number of EMBs would be a highly desirable and cost-effective tool. To evaluate one potential alternative, a pacemaker with high resolution telemetry capabilities and two fractally coated epimyocardial leads were implanted in 30 patients at five transplant centers during the heart transplant procedure. Ventricular electrograms were recorded during intrinsic and paced activity and digitized to a laptop-based data acquisition device. Electrograms were recorded at frequent intervals and systematically on days when EMBs were performed. The electrogram data were then transferred via the Internet to a central data processing site. Clinical patient management was blinded to the electrogram results and varied considerably among the five centers. Using EMB together with clinical assessment of the transplant revealed 18 cases of clinically significant rejection beyond postoperative day 27 that required antirejection therapy. The normalized parameter values extracted from the electrogram recordings during pacing (the ventricular evoked response) that were associated with significant rejection were statistically lower (86% +/- 16% versus 96% +/- 22%, P < 0.005). The application of a single-threshold diagnosis model to the parameter values allowed detection of significant rejection with a negative predictive value of 98%. This analysis also showed that as many as 55% of the routine surveillance EMBs could have been eliminated had the pacemaker monitoring technique been used as a screening tool prior to EMB. A prospective study should further define the role of this technique in the detection and management of cardiac transplant patients.

Electrocardiography↗
PubMed1998

Low serum cholesterol levels predict high perioperative mortality in patients supported by a left-ventricular assist system.

BACKGROUND: Although the use of a left-ventricular assist system (LVAS) provides circulatory support for end-stage heart failure patients awaiting heart transplantation, this procedure is accompanied by a relatively high perioperative mortality. The aim of this retrospective study was to identify those patients preoperatively which have the highest perioperative mortality. METHODS AND RESULTS: Forty-five consecutive patients undergoing LVAS implantation were evaluated for preoperative risk factors, including body mass index, hemodynamic data, and blood chemistry studies by multivariate analysis. They were divided into (1) patients who were successfully transplanted (n = 25) and (2) patients who died before transplantation (n = 20). The nonsurvivors were subclassified into patients who died within 14 days after surgery (n = 11) and patients who died after 2 weeks of device implantation (n = 9). Hemodynamic parameters were the same in both groups, but total cholesterol was significantly lower in the nonsurvivors than in the survivors (90 +/- 7 vs. 144 +/- 8 mg/dl, respectively, p < 0.0001). The sensitivity of predicting perioperative death with a serum cholesterol below 100 mg/dl was 100%, the specificity of predicting survival with a serum cholesterol above 120 mg/dl was 87%. CONCLUSION: In this small retrospective study, there was a correlation between total cholesterol levels and survival of patients with advanced heart failure on mechanical support. A cholesterol level below 100 mg/dl was accompanied by a high perioperative mortality. In contrast, a cholesterol level above 120 mg/dl was accompanied by a 87% chance of survival. The results suggest a predictive value of cholesterol which is independent of the hemodynamic status.

Biomarkers↗
PubMed1998

Comparison of PRA-STAT, sHLA-EIA, and anti-human globulin-panel reactive antibody to identify alloreactivity in pretransplantation sera of heart transplant recipients: correlation to rejection and posttransplantation coronary artery disease.

BACKGROUND: Screening pretransplantation recipient sera for percent panel reactive antibodies (%PRA) by an anti-human globulin (AHG) assay may identify recipients who are at risk for graft rejection or development of posttransplantation coronary artery disease. However, the pretransplantation AHG-%PRA does not always correlate with the occurrence of graft rejection or coronary artery disease. METHODS: We compared the predictive capacity of the AHG-%PRA with that of an enzyme-linked immunoassay (EIA)-based PRA assay that identifies immunoglobulin G bound to soluble human leukocyte antigen (sHLA) class I molecules from pooled platelets of 240 random donors (sHLA-EIA), and that of an EIA-based assay that detects immunoglobulin G anti-HLA class I antibodies bound to sHLA derived from individual HLA-typed cell cultures (PRA-STAT). The pretransplantation sera from 130 cardiac allograft recipients were comparatively tested and results evaluated. RESULTS: Although AHG-%PRA- and sHLA-EIA-determined PRA results were comparable, neither assay discriminated potential recipients at risk for rejection or coronary artery disease. However, cardiac allograft recipients with pretransplantation PRA-STAT sera > 10% were at risk for (1) graft rejection (77% vs 56%, p < .05); (2) more rejections/recipient (1.9 vs 1.0, p < .02); (3) graft rejection within 30 days (92% vs 38%, p < .001); or (4) development of coronary artery disease (48% vs 23%, p < .05) than recipients with pretransplantation PRA-STAT sera < 10%. CONCLUSIONS: PRA-STAT analysis of pretransplantation sera from potential cardiac allograft recipients may be more clinically informative about HLA alloimmunity and a better predictor of adverse clinical events than either AHG-%PRA- or sHLA-EIA-determined PRA.

Antibody Specificity↗
PubMed1997

Major histocompatibility complex class II antigen expression in rejecting cardiac allografts: detection using in vivo imaging with radiolabeled monoclonal antibody.

BACKGROUND: Increased expression of major histocompatibility complex class II (MHC-II) antigen occurs during cardiac allograft rejection. We tested the hypotheses that (1) radiolabeled antibody to MHC-II antigen allows detection of cardiac allograft rejection using nuclear imaging techniques and (2) uptake of radiolabeled antibody to MHC-II antigen correlates with severity of rejection. METHODS AND RESULTS: Thirteen beagles with cervical cardiac allografts were studied for 64+/-23 days by use of myocardial biopsy and in vivo imaging. Uptake of radiolabeled (131I [n=2], 123I [n=1], or 111In [n=10]) antibody to MHC-II increased over baseline in 7 animals that developed histological evidence of progressively worsening allograft rejection (group A), from 72.2+/-46.1 to 176.8+/-102.0 counts/pixel/mCi (P<.009). In 4 beagles without progressively worsening allograft rejection (group B), uptake was unchanged during follow-up (74.4+/-43.8 and 60.2+/-37.4 counts/pixel/mCi; P=NS). In animals studied with 111In-labeled antibody, uptake increased from 102.9+/-23.1 at baseline to 233.2+/-82.7 counts/pixel/mCi at follow-up in group A animals (P=.036), with no significant change in group B (91.1+/-34.9 and 75.9+/-24.9 counts/pixel/mCi; P=NS). Uptake of 111In-labeled antibody was 107.5+/-35.7, 135.9+/-70.8, and 307.8+/-90.1 counts/pixel/mCi in biopsy samples showing evidence of mild, moderate, and severe rejection, respectively (P=.001). Biopsy samples showing mild, moderate, and intense MHC-II expression antibody uptake had uptakes of 92.6+/-36.3, 158.5+/-54.7, and 307.8+/-90.1 counts/pixel/mCi, respectively (P=.00004). CONCLUSIONS: Radiolabeled monoclonal antibodies to MHC-II antigen can detect cardiac allograft rejection in this large mammal model of cardiac allograft transplantation, and this technique may have a potential role in the detection of rejection in patients after cardiac transplantation.

Animals↗
PubMed1997

Revascularization procedures in patients with transplant coronary artery disease.

OBJECTIVE: To assess the efficacy of revascularization in cardiac transplant patients who developed de novo coronary artery disease. METHODS: Eighteen patients underwent one or more of four methods of revascularization: percutaneous transluminal coronary angioplasty (PTCA), percutaneous transluminal coronary rotational atherectomy (PTCRA), coronary artery bypass grafting (CABG), and transmyocardial laser revacularization (TMLR). Eleven PTCA procedures were performed in 10 patients 55.3 +/- 6.6 months after transplantation. Six patients underwent PTCRA 83.3 +/- 11.2 months after transplantation. Five patients underwent CABG 54.0 +/- 12.6 months after transplantation; the mean left ventricular ejection fraction was 49.6 +/- 16.9 (20-65%); hypertrophy was present in two of these patients. One patient with distal coronary artery disease and New York Heart Association class IV symptoms underwent TMLR only. One patient underwent both CABG and TMLR because of triple vessel proximal disease, diffuse distal disease, and New York Heart Association class IV symptoms. RESULTS: PTCA was successful in 10 procedures with decrease in mean stenosis from 87.7 +/- 2.7 to 24.3 +/- 6.0%. Follow-up, at 16.9 +/- 4.0 months, showed restenosis in two patients. PTCRA was successful in all patients with a decrease in mean stenosis from 83.4 +/- 4.4 to 11.7 +/- 1.9%. Short-term follow-up did not reveal reocclusion. Two CABG patients who had hypertrophy died of heart failure 2 and 9 days after their operations. One CABG patient with excellent cardiac function died after 15 days because of pulmonary failure. In one patient, left ventricular ejection fraction improved from 35 to 50%, and he is alive 64 months later. Six months after TMLR, the New York Heart Association class in one patient improved from IV to II, and his left ventricular ejection fraction improved from 29 to 42%. The ejection fraction in the patient who underwent both CABG and TMLR improved from 20 to 56% but the patient expired 7 weeks later. CONCLUSIONS: It appears that revascularization procedures can be effective in patients with coronary artery disease after cardiac transplantation and that coronary angioplasty or atherectomy would be a therapy of choice for single proximal lesions. CABG should be used cautiously and only reserved for patients with multi-vessel disease without hypertrophy. Laser revascularization with or without bypass grafting has potential to become the therapy of choice for transplant coronary artery disease.

Angioplasty, Balloon, Coronary↗
PubMed1996

Sudden cardiac death in cardiac transplant recipients.

BACKGROUND: Sudden cardiac death (SCD) remains a significant cause of mortality in the general population. Its role in cardiac transplant patients-including its incidence, mechanism, potential risk factors, or influence on survival in this patient population-has not been well described. METHODS AND RESULTS: We undertook a retrospective analysis of the clinical and autopsy records of 257 patient deaths. SCD was analyzed in relation to severity and frequency of rejection episodes, clinical history of arrhythmias, coronary artery disease (CAD), hypertension, diabetes, left ventricular dysfunction, and clinical history of premorbid symptoms. A total of 25 patients were identified as having died of SCD, an incidence of 9.7%: 20% died < or = 12 months after transplantation, 80% died after > 12 months, and 20% died after > or = 60 months. Patient survival ranged from 2.5 to 138 months (mean, 45.7 months). The mean number of rejection episodes per patient was 2.6, most occurring within 12 months after transplantation. Echocardiography or multigated acquisition scan revealed an ejection fraction (EF) > or = 50% in 68% of patients; however, the presence of arrhythmias, primarily atrial, was evident in 68% of patients and was equally distributed between patients with EFs > or = 50% and EFs < 50%. CAD was present in 53% of patients (10 of 19) whose angiograms were available, and the appearance of CAD after transplantation was between 29 and 85 months (mean, 51.4 months). Of the 9 patients with normal cardiac catheterization studies, 6 with available autopsy reports had documented CAD. Autopsy data in 13 of 25 patients revealed CAD in 92% and rejection in 15% (International Society for Heart and Lung Transplantation grade > 3A). Of the deaths, 64% occurred within 3 months of the last endomyocardial biopsy, 96% had normal biopsies, and the only rejection was without hemodynamic compromise. CONCLUSIONS: SCD occurs relatively frequently in the cardiac transplant population, and CAD is present in most of the patients. Because the frequency of arrhythmias is relatively high in this group, more aggressive antiarrhythmic therapy may be beneficial for patients with allograft CAD in the prevention of SCD.

Adult↗
PubMed1996

Treatment of hyperlipidemia after heart transplantation and rationale for the Heart Transplant Lipid Registry.

Hyperlipidemia occurs frequently after heart transplantation, and accelerated coronary artery disease remains the major cause of morbidity and mortality in patients who survive more than 1 year after heart transplantation. However, the risks and benefits of lipid-lowering therapy after heart transplantation remain poorly defined, and national guidelines for lipid-lowering drug therapy do not specifically address treatment of dyslipidemia in transplant recipients. Since the initial reports in the 1980s of rhabdomyolysis in heart transplant patients receiving high-dosage lovastatin, results of 11 post-transplantation series that used lovastatin, simvastatin, or pravastatin at lower dosages as drug monotherapy have been published. These studies have shown an overall 1% incidence of rhabdomyolysis, defined as creatine kinase > 10 times the upper limit of normal plus muscle symptoms. One randomized, controlled prospective trial has investigated the effects of lipid-lowering pharmacotherapy on patient outcome in cardiac transplant recipients. At 1-year follow-up in this nonblinded, single-center trial, patients treated with pravastatin (20 or 40 mg/day) initiated within 2 weeks of transplantation had a significant reduction in mortality rate and a significantly lower incidence of transplant arteriopathy. A number of important issues remain unanswered regarding treatment guidelines in patients with hyperlipidemia after heart transplantation. In January 1995 we began the Heart Transplant Lipid Registry, with 12 participant centers, to gather data prospectively on the efficacy and safety of lipid-lowering drugs in the treatment of dyslipidemia after heart transplantation.

Anticholesteremic Agents↗
PubMed1996

Improved left ventricular function after chronic left ventricular unloading.

BACKGROUND: This study assessed the effect of prolonged left ventricular unloading on native ventricular function. METHODS: We reviewed data from 31 patients (30 men, 1 woman) supported more than 30 days (mean, 137 days; range, 31 to 505 days) with the HeartMate left ventricular assist system. The patients' mean age was 46 years (range, 22 to 64 years); 17 had idiopathic and 14 had ischemic cardiomyopathy. Data (anatomic, physiologic, hemodynamic, histologic, and biochemical) were collected at the time of HeartMate implantation, during support with the device temporarily off, and at the time of device explantation. RESULTS: Routine chest roentgenogram showed improvement in cardiothoracic ratio (0.62 +/- 0.04 to 0.55 +/- 0.03; p < 0.0001). Echocardiography performed with the pump off showed a significant decrease in left ventricular end-diastolic dimension (6.81 +/- 0.87 cm to 5.39 +/- 1.08 cm; p < 0.0005) and a significant improvement in ejection fraction (0.11 +/- 0.05 to 0.22 +/- 0.17; p < 0.02). Cardiac index increased (1.96 +/- 0.52 L.min-1.m-2 to 2.93 +/- 0.73 L.min-1.m-2; p < 0.0001), mean aortic pressure increased (71.40 +/- 10.63 mm Hg to 76.33 +/- 16.84 mm Hg; p = 0.48), pulmonary capillary wedge pressure decreased (24.18 +/- 6.27 mm Hg to 14.48 +/- 3.01 mm Hg; p < 0.0001), and pulmonary vascular resistance decreased (3.34 +/- 2.00 Wood units to 2.51 +/- 0.88 Wood units; p < 0.05). Comparisons of tissue samples taken at the time of implantation and at the time of transplantation showed a marked reduction in myocytolysis. Calcium uptake, calcium-binding rates, and lipid levels normalized in patients studied. Plasma norepinephrine levels decreased to near normal levels. CONCLUSION: Prospective studies are now indicated to determine whether device removal without transplantation may be beneficial in selected patients.

Adult↗
PubMed1996

Diagnosis, surveillance, and epidemiologic evaluation of viral infections in pediatric cardiac transplant recipients with the use of the polymerase chain reaction.

BACKGROUND: Viral infections, particularly those caused by cytomegalovirus, are a major cause of postoperative morbidity and mortality in heart transplant recipients. These infections have classically been diagnosed by history, physical examination, peripheral viral cultures, and serologic studies. These methods are often time-consuming and lack sensitivity. Positive viral cultures from the heart are rarely obtained, and viral myocarditis and acute cellular rejection are unable to be differentiated histologically. We have therefore used the polymerse chain reaction to diagnose possible viral infection in pediatric heart transplant recipients with findings consistent with acute unexplained rejection. METHODS: Polymerase chain reaction was used as an aid to diagnose cytomegalovirus infection of cardiac tissue obtained by right ventricular endomyocardial biopsy and follow its long-term course. In addition, polymerase chain reaction was used to diagnose infection of the heart by other viruses in patients with clinical and histologic evidence of rejection, especially those with unexplained late rejection or chronic rejection. Polymerase chain reaction primers were designed to amplify nucleic acid sequences from cytomegalovirus, parvovirus, adenovirus, herpes simplex virus, Epstein-Barr virus, and the RNA viruses of the Enterovirus family. RESULTS: Forty patients underwent serial right ventricular endomyocardial biopsy (129 samples) for rejection surveillance with positive results obtained in 41 samples (32%) from 21 patients. Viral genome amplified included cytomegalovirus in 16 samples, adenovirus in 14, enterovirus in 6, parvovirus in 3, and herpes simplex virus in 2. In 13 of the 21 patients positive for viral genome (62%), endomyocardial biopsy histologic scores were consistent with multifocal moderate to severe rejection (Internal Society for Heart and Lung Transplantation scores of 3A or greater). CONCLUSIONS: Polymerase chain reactions may be used as a rapid and sensitive method to evaluate postoperative viral infections in heart transplant recipients, especially in those with late-onset rejection or chronic rejection. Polymerase chain reaction may also be useful in the serial analysis of cytomegalovirus status in transplant recipients. The use of multiple viral primers improves the diagnostic evaluation of these patients and may lead to a better understanding of the epidemiologic characteristics of posttransplantation viral infections and the cause of late or chronic rejection.

Adenoviruses, Human↗