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Cardiac Transplantation (cardiac + transplantation)
Selected AbstractsBridging Patients to Cardiac TransplantationCONGESTIVE HEART FAILURE, Issue 5 2000Michael B. Higginbotham MD Potential recipients of heart transplants have the most advanced form of congestive heart failure, in which standard therapy fails to maintain clinical stability. In the absence of guidelines derived from evidence obtained in clinical trials, caring for these patients becomes a challenge. A successful approach requires the proper coordination of surgical and nonsurgical strategies, including revascularization and valvular surgery as well as mechanical ventricular support and medical strategies. Intensive medical therapy is the most commonly used approach for prolonged bridging to transplantation. Although carefully individualized regimens are necessary to achieve desired goals, most centers adopt a fairly standardized approach involving vasodilators, diuretics, and inotropic support. Bridging patients with cardiac decompensation to transplantation presents a major therapeutic challenge. Appropriate strategies will maximize patients' chances that the bridge from decompensation to transplantation remains intact. [source] Twenty-Four Hours Postoperative Results After Orthotopic Cardiac Transplantation in SwineJOURNAL OF CARDIAC SURGERY, Issue 4 2007Matthias Siepe M.D. However, there is no functional data available for a longer time period after transplantation. We have established a pig model to investigate myocardial function 24 hours after orthotopic transplantation.Materials and Methods: Orthotopic cardiac transplantations (HTx) in pigs were performed with a postoperative observation period of 24 hours (n = 6). To analyze myocardial function after transplantation, hemodynamical parameters (Swan-Ganz- and impedance-catheter data) as well as tissue and blood samples were obtained. Regional myocardial blood flow (RMBF) was assessed using fluorescent microspheres. Results: The impedance-catheter parameters demonstrated a preserved contractility in both ventricles 24 hours post-transplantation. In contrast, cardiac output 24 hours after HTx was diminished by 50% as compared to the preoperative value. Conversely, pulmonary vascular resistance increased significantly. The RMBF was increased in both ventricles. Metabolic and histological analyses indicate myocardial recovery 24 hours after HTx with no irreversible damage. Conclusions: For the first time, we were able to establish a porcine model to investigate myocardial function 24 hours after heart transplantation. While the contractility of the transplanted hearts was well-preserved, impaired cardiac output was going along with an increase in pulmonary vascular resistance. Using this clinical relevant model, improvements of human cardiac transplantation and post-transplant contractile dysfunction, especially, could be investigated. [source] Pretransplant Diabetes, Not Donor Age, Predicts Long-Term Outcomes in Cardiac TransplantationJOURNAL OF CARDIAC SURGERY, Issue 2 2006Steven R. Meyer M.D. Objectives were to review the outcomes of using cardiac donors 50 years of age and older and to identify predictors of outcome at a single institution. Methods: A retrospective analysis of all adult cardiac transplants (n = 338) performed at our institution between 1988 and 2002 was conducted. Results: Of these, 284 patients received hearts from donors <50 years old and 54 received hearts from donors ,50 years old. Recipients of hearts from older donors had a greater frequency of pretransplant diabetes (19% vs 33%), renal failure (16% vs 30%), and dialysis (3% vs 9%). There were no differences in ICU or postoperative length of stay, days ventilated, or early rejection episodes. Recipients of older donor hearts, however, had increased perioperative mortality (7% vs 17%; p = 0.03). Multivariate analysis identified older donors (OR 2.599; p = 0.03) and donor ischemia time (OR 1.006; p = 0.002) as significant predictors of perioperative mortality. Actuarial survival at 1 (87% vs 74%), 5 (76% vs 69%), and 10 (59% vs 58%) years was similar (p = 0.08) for the two groups. Separate multivariate analyses identified pretransplant diabetes as the sole predictor of long-term survival (HR 1.659; p = 0.02) and transplant coronary disease (HR 2.486; p = 0.003). Conclusions: Despite increased perioperative mortality, donors ,50 years old may be used with long-term outcomes similar to those of younger donor hearts. This has potential to expand the donor pool. Pretransplant diabetes has a significant impact on long-term outcomes in cardiac transplantation and requires further investigation. [source] Effect of Donor Age on Long-Term Survival Following Cardiac TransplantationJOURNAL OF CARDIAC SURGERY, Issue 2 2006Veli K. Topkara M.D. Our objective was to analyze the effect of donor age on outcomes after cardiac transplantation. Methods: We retrospectively studied 864 patients who underwent cardiac transplantation at New York Presbyterian Hospital , Columbia University between 1992 and 2002. Patients were divided into two groups; donor age <40 years (Group A, n = 600) and donor age ,40 years (Group B, n = 264). Results: Characteristics including gender, body mass index, and cytomegalovirus (CMV) status were significantly different between the two donor age groups. Race, CMV status, toxoplasmosis status, left ventricular assist device prior to transplant, diabetes mellitus, and retransplantation were similar in both the recipient groups, while age, gender, and BMI were different. Early mortality was lower in Group A, 5%, versus 9.5% in Group B. Multivariate analysis revealed recipient female gender (odd ratio (OR) = 1.71), retransplantation (OR = 1.63), and increased donor age (OR = 1.02) as significant predictors of poor survival in the recipient population. Actuarial survival at 1 year (86.7% vs 81%), 5 years (75% vs 65%), and 10 years (56% vs 42%) was significantly different as well with a log rank p = 0.002. Conclusions: These findings suggest that increased donor age is an independent predictor of long-term survival. However, the shortage of organs makes it difficult to follow strict guidelines when placing hearts; therefore, decisions need to be made on a relative basis. [source] Orthotopic Cardiac Transplantation: Comparison of Outcome Using Biatrial, Bicaval, and Total TechniquesJOURNAL OF CARDIAC SURGERY, Issue 1 2005Jeffrey A. Morgan M.D. More recently, however, bicaval and total techniques have been devised in an attempt to improve cardiac anatomy, physiology, and postoperative outcome. A bicaval approach preserves the donor atria and combines the standard left atrial anastomosis with a separate bicaval anastomosis. Total orthotopic heart transplantation involves complete excision of the recipient atria with separate bicaval end-to-end anastomoses, as well as pulmonary venous anastomoses. The aim of this study was to conduct a literature review of studies that compared the three surgical techniques (biatrial, bicaval, and total) for performing orthotopic cardiac transplantation. Numerous outcome variables were evaluated, and included post-transplant survival, atrial dimensions, atrioventricular valvular insufficiency, arrhythmias, pacing requirements, vasopressor requirements, and hospital stay. Methods: We conducted a Medline (Pubmed) search using the terms "biatrial and cardiac transplantation,""bicaval and cardiac transplantation," and "total technique and cardiac transplantation," which yielded 192 entries: 39 of these were studies that compared surgical techniques and were included in the review. Results: There was overwhelming evidence that the bicaval technique provided anatomic and functional advantages, with improvements in post-transplant survival, atrial geometry, and hemodynamics, as well as decreased valvular insufficiency, arrhythmias, pacing requirements, vasopressor requirements, and hospital stay. Conclusions: The bicaval technique was superior to both biatrial and total techniques for numerous outcome variables. To further elucidate this issue, a prospective randomized trial comparing the three techniques, with long-term follow-up, is warranted. [source] Long-Term Results of Cardiac TransplantationJOURNAL OF CARDIAC SURGERY, Issue 3 2003Alberto Juffe M.D. From April 1991 to December 2000, 345 patients underwent heart transplantation at the Juan Canalejo Hospital. The mean age of recipients was54.5 ± 11.4 years; 286 (83%) were male patients. Idiopathic (52.2%) and ischemic (34.9%) end-stage cardiomyopathy were the main causes leading to transplantation. Ninety-four patients had undergone a previous heart operation. The mean left ventricular ejection fraction was22.8 ± 11.4. Forty patients (11.5%) were transplanted in urgent (status I) condition. The mean time spent on the waiting list was 35.9 days. In-hospital mortality was 10.6% and 24% for transplantations performed on an elective and urgent basis, respectively. Operative (30-day), one-year and six-year survival was 87.2%, 81.3% and 64%, respectively. In terms of actuarial survival, there were no significant differences with regard to the recipient's age, sex, previous cardiac surgery, and the etiology of the end-stage cardiomyopathy. The six-year actuarial survival for recipients receiving hearts from female donors was 59% compared with 72% for male donors(p = 0.05). There has been a low incidence of rejection, as well as cardiac graft vasculopathy. Actuarial survival at six years was 66% for patients transplantated on an elective basis compared with 57% for patients transplanted on an urgent basis(p = 0.04). The aim of the study was to evaluate long-term results for patients who underwent orthotopic heart transplantation. In our experience, status I is associated with a higher mortality.(J Card Surg 2003;18:183-189) [source] Genetically Manipulated Human Skeletal Myoblast Cells for Cardiac TransplantationJOURNAL OF CARDIAC SURGERY, Issue 6 2002Kh H Haider Aim: Considering the promise of skeletal myoblast cell transplantation to improve cardiac function in myocardial myopathies, we aim in the present study to investigate the potential of human skeletal myoblast cells (HSMC) as a carrier for therapeutic genes for the heart muscle. Methods: Skeletal muscle sample is obtained from rectus femoris of the donor and is processed in the tissue culture to generate HSMC by a patented process of Cell Therapy Inc. The HSMC are grown in large 225 mm2 tissue culture flasks coated with collagen for enhanced cell adherence, using patented Super Medium (Cell Therapy Inc., Singapore) containing 10% fetal calf serum, to 80% confluence. The HSMC are passaged at regular time intervals of 48-72 hours to prevent in vitro differentiation. The HSMC thus obtained are transduced three times with retroviral vector carrying Lac-Z reporter gene before transplantation. The Lac-Z transduced HSMC are harvested by trypsinization, washed and re-suspended in serum free Super Medium. Ischemic Porcine model is created by clamping ameroid ring around left circumflex coronary artery in Yorkshire swine, four weeks prior to cell transplantation. For cell transplantation, the animal is anaesthetized, ventilated and heart is exposed by left thoracotomy. Fifteen injections (0.25 ml each) containing 300 million cells are injected in to the left ventricle endocardially under direct vision. For control animal, only culture medium without cells is injected. The animal is euthanized at pre-determined time, heart is explanted and processed for histological examination. The cryosectioning of the tissue and subsequent staining for Lac-Z expression and Hematoxylin-Eosin staining is carried out by standard methods. Results: The skeletal muscle samples processed by the patented method of Cell Therapy yield 85-90% pure HSMC. The preliminary data shows that repeated transductions of myoblast cells with retrovirus carrying Lac-Z yield highly efficient 70-75% Lac-Z positive HSMC population (Figure 1). Dye exclusion test using Trypan blue reveals >95% cell viability at the time of injection. Gross sections of the cardiac tissue stained positive for Lac-Z expression (Figure 2). Histological examination showed the presence of grafted myoblast cells expressing Lac-Z gene in the cardiac tissue (Figure 3). Conclusion: In the light of our preliminary results, we conclude that HSMC may prove to be excellent carriers of transgene for cardiac muscle cells which otherwise are refractory to ordinary gene transfection methods. The use of HSMC mediated gene delivery to cardiac muscle is safer as compared to direct injection of viral vectors in to the heart muscle. Furthermore, the grafted myoblast cells will additionally serve to strengthen the weakened heart muscle. Figure 1.Human Skeletal myoblasts transduced with Lac-Z carrying retrovirus and stained with x-gal. Figure 2.Gross sections of heart muscle stained for Lac-Z expression. Figure 3.X-gal stained porcine heart muscle counter-stained with Eosin. The heart was explanted 6 weeks after transplantation of Lac-Z stained human myoblasts. The arrow shows Lac-Z expressing myoblast cells. [source] Genome-Wide Transcription Profile of Endothelial Cells After Cardiac Transplantation in the RatAMERICAN JOURNAL OF TRANSPLANTATION, Issue 7 2010B. Mikalsen Transcriptome analyses of organ transplants have until now usually focused on whole tissue samples containing activation profiles from different cell populations. Here, we enriched endothelial cells from rat cardiac allografts and isografts, establishing their activation profile at baseline and on days 2, 3 and 4 after transplantation. Modulated transcripts were assigned to three categories based on their regulation profile in allografts and isografts. Categories A and B contained the majority of transcripts and showed similar regulation in both graft types, appearing to represent responses to surgical trauma. By contrast, category C contained transcripts that were partly allograft-specific and to a large extent associated with interferon-,-responsiveness. Several transcripts were verified by immunohistochemical analysis of graft lesions, among them the matricellular protein periostin, which was one of the most highly upregulated transcripts but has not been associated with transplantation previously. In conclusion, the majority of the differentially expressed genes in graft endothelial cells are affected by the transplantation procedure whereas relatively few are associated with allograft rejection. [source] Alemtuzumab Induction Prior to Cardiac Transplantation with Lower Intensity Maintenance Immunosuppression: One-Year OutcomesAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010J. J. Teuteberg Induction therapy with alemtuzumab (C-1H) prior to cardiac transplantation (CTX) may allow for lower intensity maintenance immunosuppression. This is a retrospective study of patients who underwent CTX at a single institution from January 2001 until April 2009 and received no induction versus induction with C-1H on a background of tacrolimus and mycophenolate. Those with C-1H received dose-reduced calcineurin inhibitor and no steroids. A total of 220 patients were included, 110 received C-1H and 110 received no induction. Recipient baseline characteristics, donor age and gender were not different between the two groups. Mean tacrolimus levels (ng/mL) for C-1H versus no induction: months 1,3 (8.5 vs. 12.9), month 4,6 (10.2 vs. 13.0), month 7,9 (10.2 vs. 11.9) and month 10,12 (9.9 vs. 11.3) were all significantly lower for the C-1H group, p < 0.001. There were no differences between the C-1H and no induction groups at 12 months for overall survival 85.1% versus 93.6% p = 0.09, but freedom from significant rejection was significantly higher for the C-1H group, 84.5% versus 51.6%, p < 0.0001. In conclusion, induction therapy after CTX with C-1H results in a similar 12 month survival, but a greater freedom from rejection despite lower calcineurin levels and without the use of steroids. [source] Role of Alloantibodies in the Pathogenesis of Graft Arteriosclerosis in Cardiac TransplantationAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2006B. Soleimani Graft arteriosclerosis (GA) remains the leading obstacle to long-term survival of cardiac allografts. The pathogenesis of this chronic disease, though perceived to be multifactorial, is most likely immune-driven. Based on clinical and experimental observations, the humoral arm of the immune system has long been suspected to play a pivotal role in the disease process. In this article, we shall review the evidence generated from key clinical and experimental studies on the role of alloantibodies in GA. We will argue that although the strong correlation between the presence of anti-donor antibodies in clinical and experimental GA is highly suggestive of a pathogenic role for alloantibodies, a direct causal link between GA and the humoral arm of the alloresponse cannot yet be established based on the currently available evidence, and may in fact be one of a number of pathogenic processes that potentiate this vasculopathy. Finally, in this article, we shall discuss some of the potential mechanisms by which alloantibodies may exert their pathogenic effect in GA. [source] Immunosuppression in Cardiac Transplantation: Science, Common Sense and the Heart of the MatterAMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2006M. R. Mehra No abstract is available for this article. [source] Bridge to Transplant with the HeartMate DeviceJOURNAL OF CARDIAC SURGERY, Issue 4 2001William Piccione Jr. The incidence and prevalence of chronic heart failure continues to increase, with an estimated 400,000 new cases per year in the United States. Cardiac transplantation is an effective therapy but is severely limited to approximately 2300 patients per year due to the donor shortage. With ever increasing waiting times, a significant number of patients become severely debilitated or expire prior to transplantation. A mechanical circulatory support device was first used as a "bridge to transplantation" in 1969. Since then, mechanical devices have increased tremendously in reliability and efficaciousness. The HeartMate left ventricular assist device (LVAD) has been utilized extensively in a bridge to transplant application with excellent results. Patients refractory to aggressive medical management can be sustained reliably until transplantation. In addition, bridging allows for the correction of physiologic and metabolic dearrangements often seen in these severely ill patients prior to transplantation. Nutritional, economic, and quality-of-life issues also favor earlier LVAD placement in refractory patients. This report summarizes the overall bridging experience with the HeartMate LVAD and focuses on our experience with this device at Rush-Presbyterian-St. Luke's Medical Center. [source] Connective Tissue Growth Factor Promotes Fibrosis Downstream of TGF, and IL-6 in Chronic Cardiac Allograft RejectionAMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2010A. J. Booth Cardiac transplantation is an effective treatment for multiple types of heart failure refractive to therapy. Although immunosuppressive therapeutics have increased survival rates within the first year posttransplant, chronic rejection (CR) remains a significant barrier to long-term graft survival. Indicators of CR include patchy interstitial fibrosis, vascular occlusion and progressive loss of graft function. Multiple factors have been implicated in the onset and progression of CR, including TGF,, IL-6 and connective tissue growth factor (CTGF). While associated with CR, the role of CTGF in CR and the factors necessary for CTGF induction in vivo are not understood. To this end, we utilized forced expression and neutralizing antibody approaches. Transduction of allografts with CTGF significantly increased fibrotic tissue development, though not to levels observed with TGF, transduction. Further, intragraft CTGF expression was inhibited by IL-6 neutralization whereas TGF, expression remained unchanged, indicating that IL-6 effects may potentiate TGF,-mediated induction of CTGF. Finally, neutralizing CTGF significantly reduced graft fibrosis without reducing TGF, and IL-6 expression levels. These findings indicate that CTGF functions as a downstream mediator of fibrosis in CR, and that CTGF neutralization may ameliorate fibrosis and hypertrophy associated with CR. [source] The Role of Intraoperative Transesophageal Echocardiography in Heart TransplantationECHOCARDIOGRAPHY, Issue 7 2002Paval Romano M.D. The number of centers that perform heart transplants has increased rapidly in recent years. Although transthoracic and transesophageal echocardiography (TTE and TEE) are utilized frequently to diagnose and manage cardiac complications commonly found in this population postoperatively, little has been written about the routine use of intraoperative TEE. Intraoperative echo is ideally suited to identify acute complications during cardiac transplantation. This can include immediate signs of rejection, valvular abnormalities, and mechanical complications related to the surgical procedure. Many of these patients might require ventricular assist devices (VAD) to provide circulatory support, and intraoperative TEE can be used to verify correct positioning of the VAD hardware. In addition, many of the chronic complications that patients with heart transplants are at risk for may be serious yet asymptomatic. Therefore, a high quality, complete intraoperative echocardiographic study might serve as an important baseline to compare postoperative changes. [source] Cytomegalovirus hyperimmunoglobulin: mechanisms in allo-immune response in vitroEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 12 2007K. Hoetzenecker Abstract Background Cytomegalovirus hyperimmunoglobulin (CMVIg) containing drugs are routinely administered in cardiac transplantation for prophylaxis against CMV disease. Yet little is known about their influence on transplant relevant immune functions. The aim of this study was to evaluate the effect of CMVIg on cellular immunity in in vitro experiments and to define their role in tolerance inducing mechanisms. Materials and methods/results CMVIg reduces proliferation in mixed lymphocyte reactions and anti-CD3 blastogenesis assays and is related to decreased production of immune modulating cytokines interleukin (IL)-2, interferonr (IFN,), IL-10. This antiproliferative effect is associated with a cell-cycle arrest in the G0/G1 phase and induction of apoptosis in CD8+ and natural killer cells. Co-incubation with CMVIg causes down-regulation of cell bound immunoglobulin and Fc,RIII surface expression on natural killer cells and leads to attenuation of antibody dependent cellular cytotoxicity effector functions. Conclusions We conclude that CMVIg induces immunological features on leukocytes in vitro that are known to be related to tolerance induction. Our observations extend the current concept of CMVIg as passive CMV prophylaxis to a therapeutic drug compound capable of reducing allogeneic immune response. [source] Prognostic significance of soluble interleukin-2 receptor levels in patients with dilated cardiomyopathyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 6 2003C. J. Limas Abstract Background Activation of T lymphocytes is thought to mediate myocardial dysfunction in dilated cardiomyopathy (CMP), probably through cytotoxic cytokines, but its value as a prognostic factor has not been evaluated. Methods For 2 years we prospectively followed 76 patients (65 males, 11 females, age 49 ± 7 years) with CMP and New York Heart Association(NYHA) Class II,III heart failure; left ventricular (LV) function was assessed echocardiographically. Thirty-three patients (28 males, five females, age 52 ± 6 years) with ischaemic heart disease (IHD) and similar NYHA and LV function characteristics were used as controls. Serum sIL-2R levels, peripheral blood lymphocyte proliferation (basal, + concanavalin A) and HLA-DQB1 genotyping was carried out in all patients. Results The CMP patients had increased sIL-2R levels (1259 ± 130 pg mL,1) compared with the IHD patients (703 ± 80 pg mL,1, P < 0·01, only 3 > 800 pg mL,1). In the CMP patients, there was a significant (r = +0·45, P= 0·04) correlation between sIL-2R and the LV end-diastolic diameter but not with the LV ejection fraction or NYHA Class. During the 24-month follow up, 17 of the CMP patients had an adverse clinical course (death, need for cardiac transplantation, or worsening heart failure). Of these, 14 (75%) had elevated (, 800 pg mL,1) sIL-2R levels (Group I) compared with only five (6%) with a stable clinical course (Group II). Neither [3H] thymidine incorporation into the peripheral blood lymphocytes nor the excess of HLA-DQB1-30 histidine homozygotes in the Group I patients (38% vs. 17%, P < 0·05) could predict the clinical outcome. Conclusion Increased sIL-2R levels in CMP patients are an independent predictor of a more aggressive clinical course. [source] Simultaneous administration of a low-dose mixture of donor bone marrow cells and splenocytes plus adenovirus containing the CTLA4Ig gene result in stable mixed chimerism and long-term survival of cardiac allograft in ratsIMMUNOLOGY, Issue 2 2003Yongzhu Jin Summary T-cell costimulatory blockade combined with donor bone marrow transfusion may induce mixed chimerism, rendering robust tolerance in transplanted organs and cells. However, most protocols entail high doses of donor bone marrow cells (BMCs) or repeated administration of costly agents that block costimulatory pathways, thus delaying clinical development. To circumvent these shortcomings, we developed a strategy in which the dosage of donor BMCs was reduced but compensated by donor splenocytes (SPLCs). Furthermore, repeated administration of costly agents was replaced with a single injection of adenovirus expressing a gene of interest. In rat cardiac transplantation models, cardiac allografts from DA (RT-1a) rats were transplanted heterotopically into the abdomen of LEW (RT-11) recipient rats. Immediately after cardiac transplantation, an adenovirus vector (AdCTLA4Ig; 5 × 109 plaque-forming units) containing the gene for CTLA4Ig was administered to recipients (n = 6) simultaneously with a low dose of donor BMCs (1 × 108/rat) and SPLCs (5 × 107/rat) via the portal vein. The treated LEW recipient rats developed long-lasting mixed chimerism (>10% at >100 days) and exhibited long-term cardiac allografts (mean survival time of > 200 days) compared with control recipients. Moreover, recipients displaying long-lasting mixed chimerism accepted subsequent donor skin allografts while promptly rejecting third-party skin allografts. These results suggest that blockade of the CD28-B7 pathway, using adenovirus-mediated CTLA4Ig gene transfer, in concert with a low dosage of donor BMCs and SPLCs, may represent a feasible strategy to induce stable mixed chimerism and permit long-term survival of cardiac allografts. [source] Twenty-Four Hours Postoperative Results After Orthotopic Cardiac Transplantation in SwineJOURNAL OF CARDIAC SURGERY, Issue 4 2007Matthias Siepe M.D. However, there is no functional data available for a longer time period after transplantation. We have established a pig model to investigate myocardial function 24 hours after orthotopic transplantation.Materials and Methods: Orthotopic cardiac transplantations (HTx) in pigs were performed with a postoperative observation period of 24 hours (n = 6). To analyze myocardial function after transplantation, hemodynamical parameters (Swan-Ganz- and impedance-catheter data) as well as tissue and blood samples were obtained. Regional myocardial blood flow (RMBF) was assessed using fluorescent microspheres. Results: The impedance-catheter parameters demonstrated a preserved contractility in both ventricles 24 hours post-transplantation. In contrast, cardiac output 24 hours after HTx was diminished by 50% as compared to the preoperative value. Conversely, pulmonary vascular resistance increased significantly. The RMBF was increased in both ventricles. Metabolic and histological analyses indicate myocardial recovery 24 hours after HTx with no irreversible damage. Conclusions: For the first time, we were able to establish a porcine model to investigate myocardial function 24 hours after heart transplantation. While the contractility of the transplanted hearts was well-preserved, impaired cardiac output was going along with an increase in pulmonary vascular resistance. Using this clinical relevant model, improvements of human cardiac transplantation and post-transplant contractile dysfunction, especially, could be investigated. [source] Pretransplant Diabetes, Not Donor Age, Predicts Long-Term Outcomes in Cardiac TransplantationJOURNAL OF CARDIAC SURGERY, Issue 2 2006Steven R. Meyer M.D. Objectives were to review the outcomes of using cardiac donors 50 years of age and older and to identify predictors of outcome at a single institution. Methods: A retrospective analysis of all adult cardiac transplants (n = 338) performed at our institution between 1988 and 2002 was conducted. Results: Of these, 284 patients received hearts from donors <50 years old and 54 received hearts from donors ,50 years old. Recipients of hearts from older donors had a greater frequency of pretransplant diabetes (19% vs 33%), renal failure (16% vs 30%), and dialysis (3% vs 9%). There were no differences in ICU or postoperative length of stay, days ventilated, or early rejection episodes. Recipients of older donor hearts, however, had increased perioperative mortality (7% vs 17%; p = 0.03). Multivariate analysis identified older donors (OR 2.599; p = 0.03) and donor ischemia time (OR 1.006; p = 0.002) as significant predictors of perioperative mortality. Actuarial survival at 1 (87% vs 74%), 5 (76% vs 69%), and 10 (59% vs 58%) years was similar (p = 0.08) for the two groups. Separate multivariate analyses identified pretransplant diabetes as the sole predictor of long-term survival (HR 1.659; p = 0.02) and transplant coronary disease (HR 2.486; p = 0.003). Conclusions: Despite increased perioperative mortality, donors ,50 years old may be used with long-term outcomes similar to those of younger donor hearts. This has potential to expand the donor pool. Pretransplant diabetes has a significant impact on long-term outcomes in cardiac transplantation and requires further investigation. [source] Effect of Donor Age on Long-Term Survival Following Cardiac TransplantationJOURNAL OF CARDIAC SURGERY, Issue 2 2006Veli K. Topkara M.D. Our objective was to analyze the effect of donor age on outcomes after cardiac transplantation. Methods: We retrospectively studied 864 patients who underwent cardiac transplantation at New York Presbyterian Hospital , Columbia University between 1992 and 2002. Patients were divided into two groups; donor age <40 years (Group A, n = 600) and donor age ,40 years (Group B, n = 264). Results: Characteristics including gender, body mass index, and cytomegalovirus (CMV) status were significantly different between the two donor age groups. Race, CMV status, toxoplasmosis status, left ventricular assist device prior to transplant, diabetes mellitus, and retransplantation were similar in both the recipient groups, while age, gender, and BMI were different. Early mortality was lower in Group A, 5%, versus 9.5% in Group B. Multivariate analysis revealed recipient female gender (odd ratio (OR) = 1.71), retransplantation (OR = 1.63), and increased donor age (OR = 1.02) as significant predictors of poor survival in the recipient population. Actuarial survival at 1 year (86.7% vs 81%), 5 years (75% vs 65%), and 10 years (56% vs 42%) was significantly different as well with a log rank p = 0.002. Conclusions: These findings suggest that increased donor age is an independent predictor of long-term survival. However, the shortage of organs makes it difficult to follow strict guidelines when placing hearts; therefore, decisions need to be made on a relative basis. [source] Orthotopic Cardiac Transplantation: Comparison of Outcome Using Biatrial, Bicaval, and Total TechniquesJOURNAL OF CARDIAC SURGERY, Issue 1 2005Jeffrey A. Morgan M.D. More recently, however, bicaval and total techniques have been devised in an attempt to improve cardiac anatomy, physiology, and postoperative outcome. A bicaval approach preserves the donor atria and combines the standard left atrial anastomosis with a separate bicaval anastomosis. Total orthotopic heart transplantation involves complete excision of the recipient atria with separate bicaval end-to-end anastomoses, as well as pulmonary venous anastomoses. The aim of this study was to conduct a literature review of studies that compared the three surgical techniques (biatrial, bicaval, and total) for performing orthotopic cardiac transplantation. Numerous outcome variables were evaluated, and included post-transplant survival, atrial dimensions, atrioventricular valvular insufficiency, arrhythmias, pacing requirements, vasopressor requirements, and hospital stay. Methods: We conducted a Medline (Pubmed) search using the terms "biatrial and cardiac transplantation,""bicaval and cardiac transplantation," and "total technique and cardiac transplantation," which yielded 192 entries: 39 of these were studies that compared surgical techniques and were included in the review. Results: There was overwhelming evidence that the bicaval technique provided anatomic and functional advantages, with improvements in post-transplant survival, atrial geometry, and hemodynamics, as well as decreased valvular insufficiency, arrhythmias, pacing requirements, vasopressor requirements, and hospital stay. Conclusions: The bicaval technique was superior to both biatrial and total techniques for numerous outcome variables. To further elucidate this issue, a prospective randomized trial comparing the three techniques, with long-term follow-up, is warranted. [source] Improved Survival of Cardiac Transplantation Candidates with Implantable Cardioverter Defibrillator Therapy:JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2003Role of Beta-Blocker or Amiodarone Treatment Introduction: Survival in patients awaiting cardiac transplantation is poor due to the severity of left ventricular dysfunction and the susceptibility to ventricular arrhythmia. The potential role of implantable cardioverter defibrillators (ICDs) in this group of patients has been the subject of increasing interest. The aims of this study were to ascertain whether ICDs improve the survival rate of patients on the waiting list for cardiac transplantation and whether any improvement is independent of concomitant beta-blocker or amiodarone therapy. Methods and Results: Data comprised findings from 310 consecutive patients at a single center who were evaluated and deemed suitable for cardiac transplantation and placed on the waiting list. Kaplan-Meier actuarial approach was used for survival analysis. Survival analysis censored patients at time of transplantation or death. Of the 310 patients, 111 (35.8%) underwent successful cardiac transplantation and 164 (52.9%) died while waiting; 35 patients remain on the waiting list. Fifty-nine (19%) patients had ICD placement for ventricular arrhythmias prior to or after being listed. Twenty-nine (49.1%) ICD patients survived until cardiac transplantation, 13 (22%) patients died, and 17 (28.8%) remain on the waiting list. Among non-ICD patients, 82 (32.7%) received transplants, 151 (60.2%) died, and 18 (7.2%) remain on the waiting list. Survival rates at 6 months and 1, 2, 3, and 4 years were better for all ICD patients compared to non-ICD patients (log-rankx2, P = 0.0001). By multivariate analysis, ICD therapy and beta-blocker treatment were the strongest predictors of survival. Further, ICD treatment was associated with improved survival independent of concomitant treatment with beta-blocker or amiodarone. Among ICD and non-ICD patients treated with a beta-blocker or amiodarone, survivals at the 1 and 4 years were 93% vs 69% and 57% vs 32%, respectively (log-rankx2, P = 0.003). Conclusion: ICD therapy is associated with improved survival in high-risk cardiac transplant candidates, and ICD benefit appears to be independent of concomitant treatment. (J Cardiovasc Electrophysiol, Vol. 14, pp. 578-583, June 2003) [source] Human Pathologic Validation of Left Ventricular Linear Lesion Formation Guided by Noncontact MappingJOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 1 2002BRADLEY P. KNIGHT M.D. Linear Lesions Guided by Noncontact Mapping. This case report describes the histopathologic findings associated with two left ventricular, linear radiofrequency lesions in a patient who underwent cardiac transplantation shortly after an ablation procedure for ventricular tachycardia. The lesions were created with conventional ablation equipment guided by a noncontact mapping system. The findings provide pathologic validation that continuous, linear lesions are feasible using a noncontact mapping system for guidance. [source] Eruption cyst formation associated with cyclosporin AJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 5 2003A case report Abstract Background: Cyclosporin A (CyA) is a potent immunomodulatory agent with a wide range of applications. Despite its therapeutic value, multiple adverse effects of CyA have been identified. This case report describes eruption cyst formation as a possible adverse effect of CyA administration during tooth eruption in a boy treated with CyA as a consequence of a cardiac transplantation. The clinical diagnosis of eruption cyst was confirmed by histopathological examination. Treatment: The periodontal treatment consisted of supragingival and subgingival scaling, followed by surgical removal of the tissues overlying the crowns of the teeth associated with eruption cysts, and flap surgery in the region of gingival overgrowth. The patient was then placed on quarterly periodontal supportive therapy and his immunosuppressive medication was switched from CyA to tacrolimus. Results: Twenty months after therapy, neither new cyst formation nor recurrence of gingival overgrowth was registered. Conclusion: Formation of an eruption cyst may be an adverse effect of CyA in children with erupting teeth. Zusammenfassung Hintergrund: Cyclosporin A (CyA) ist potentes immunmodulierendes Pharmakon mit einer breiten Applikationsmöglichkeit. Unabhängig von seinem therapeutischen Wert sind multiple Nebeneffekte von CyA beschrieben worden. Dieser Fallbericht beschreibt die Bildung einer Zyste beim Zahndurchbruch als eine mögliche Nebenwirkung von CyA Medikation bei einem Jungen, der mit CyA wegen einer Herztransplantation behandelt wurde. Die klinische Diagnose der Zystenbildung wurde histopathologisch bestätigt. Behandlung: Die parodontale Behandlung bestand in supragingivaler und subgingivaler Zahnreinigung gefolgt von der chirurgischen Entfernung des die Zahnkronen überdeckenden Gewebes, was mit der Zystenbildung verbunden war, und der Lappenchirurgie in der Region der gingivalen Wucherung. Der Patient wurde dann in das vierteljährliche parodontale Recall übernommen, und seine immunsuppressive Medikation wurde von CyA zu Tacrolimus verändert. Ergebnisse: 20 Monate nach der Therapie wurde weder eine neue Zystenbildung noch eine Wiederkehr der gingivalen Wucherung registriert. Schlussfolgerung: Die Bildung einer Durchbruchszyste kann eine Nebenwirkung bei der CyA Medikation bei Kindern während des Zahndurchbruchs sein. Résumé La cyclosporine A (CyA) est un agent immuno-modulateur puissant avec un large éventail d'applications. Malgré sa valeur thérapeutique, de multiples effets secondaires CyA ont été identifiés. Ce rapport de cas décrit une formation de kystes d'éruption qui pourrait être un effet secondaire possible de l'administration de CyA durant l'éruption dentaire chez un garçon traité par CyA à la suite d'une transplantation cardiaque. Le diagnostic clinique du kyste d'éruption a été confirmé par l'histopathologie. Le traitement parodontal a consisté en détartrage et surfaçage suivis par l'enlèvement chirurgical des tissus recouvrant les couronnes des dents associés aux kystes d'éruptions, et une chirurgie par lambeaux dans la région d'accroissement gingivale. L'enfant a bénéficié d'un suivi parodontal trimestriel et sa médication immunosuppressive est passée du CyA au tacrolimus. Vingt mois après le traitement, ni la formation de kystes ni la réapparition d'hypertrophie gingivale n'a été enregistrée. La formation de kystes d'éruption pourrait donc être un effet secondaire de l'utilisation de la CyA chez les enfants au moment de l'éruption des dents. [source] Analysis of an antibody pharmaceutical, tocilizumab, by capillary electrophoresis using a carboxylated capillaryJOURNAL OF SEPARATION SCIENCE, JSS, Issue 5 2008Atsushi Taga Abstract Antibody pharmaceuticals are becoming more and more prevalent due to their excellent effectiveness in clinical medications, and are expected to allow tailor-made medical treatment for rheumatic diseases, immunosuppression in cardiac transplantation, and cancer. Antibody-type pharmaceuticals of immunoglobulin G (IgG) commonly have N -glycosylated carbohydrate chains attached to heavy chains. The carbohydrate chains play important roles in the effectiveness of antibodies. Therefore evaluation of a glycosylated species is important in the first step of quality control of antibody pharmaceuticals. In the present work, we examined capillary electrophoresis with a newly developed, chemically modified capillary, the inner surface of which is modified with carboxyl groups, for evaluation of IgG molecular species which have carbohydrate chains; tocilizumab was used as a model. The analytical system developed in the present study is useful for determining the content of non-glycosylated peptides. In the analysis of tocilizumab, the ratio of non-glycosylated peptide was estimated to be 1.23% with a relative standard deviation of 3.05%. The method affords high reproducibility with simple operation, and analysis can be completed within 6 min. [source] Laser Polishing in Medical EngineeringLASER TECHNIK JOURNAL, Issue 2 2010Laser Polishing of Components for Left Ventricular Assist Devices Cardiac surgery has made significant progress during the last 50 years. nowadays, almost every congenital or contracted dysfunction of the heart can be treated clinically or at least the etiopathology can be alleviated. During these years, implantable Left Ventricular Assist Devices (LVADs) have proven to be an effective and reliable medical product. In particular, the survival rate of patients with cardiac insufficiency has risen due to these devices. This type of heart-assist device is implanted either to bridge the time until cardiac transplantation or recovery has occurred, or for permanent implantation in the patient's body. Berlin Heart GmbH produces the clinically tested axial pump system INCOR® (Figure 1, above). The INCOR heart-as-sisting pump is a powerful implantable LVAD which has been used in more than 500 clinical applications. The main function of the axial pump is to unload the patient's heart by transporting blood from the left ventricle to the aorta. In order to assure high reliability of the pump's operation, the components used for blood transport have to be highly bio- and hemocompatible. [source] Combined Vitamin C and E Supplementation Retards Early Progression of Arteriosclerosis in Heart Transplant PatientsNUTRITION REVIEWS, Issue 11 2002Article first published online: 16 SEP 200 The development of arteriosclerosis is the limiting factor for the long-term survival and the major cause of mortality in patients with heart transplants. Various factors, including oxidative stress, contribute to the progression of the disease. In a recent clinical trial using the intravascular ultrasound technique, which detects the early stages of disease development, supplementation with vitamins C and E retarded the progression of coronary arteriosclerosis during the early stage following cardiac transplantation. [source] Ventricular Dyssynchrony and Risk Markers of Ventricular Arrhythmias in Nonischemic Dilated Cardiomyopathy:PACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 1p2 2003A Study with Phase Analysis of Angioscintigraphy FAUCHIER, L.,et al.: Ventricular Dyssynchrony and Risk Markers of Ventricular Arrhythmias in Nonischemic Dilated Cardiomyopathy: A Study with Phase Analysis of Angioscintigraphy.Biventricular pacing is a new form of treatment for patients with dilated cardiomyopathy and ventricular dyssynchrony. Limited information is available regarding the relationship between ventricular dyssynchrony and risk markers of ventricular arrhythmias in idiopathic dilated cardiomyopathy (IDC). In 103 patients with IDC, Fourier phase analysis of both ventricles was performed from equilibrium radionuclide angiography (ERNA). The difference between the mean phase of the LV and RV was a measure of interventricular dyssynchrony, and the standard deviations of the mean phases in each ventricle measured intraventricular dyssynchrony. There were no significant differences in inter- and intraventricular dyssynchrony between patients with versus without histories of sustained VT or VF, nonsustained VT, abnormal signal-averaged ECG, or induced sustained monomorphic VT. Dyssynchrony was not related to decreased heart rate variability (HRV). LV and interventricular dyssynchrony were weakly related to QT duration and QT dispersion. During a follow-up of27 ± 23 months, 21 patients had major adverse cardiac events (MACE), including 7 cardiac deaths, 11 progression of heart failure leading to cardiac transplantation, and 3 sustained VT/VF. The only independent predictors of MACE were an increased standard deviation of LV mean phase (P = 0.003), a decreased HRV (standard deviation of normal-to-normal intervals, P = 0.004), and histories of previous VT/VF (P = 0.03) or nonsustained VT (P = 0.04). In conclusion, left intraventricular dyssynchrony evaluated with ERNA was an independent predictor of MACE in IDC and was not related to usual risk markers of ventricular arrhythmias. This may have implications for resynchronization therapy and/or the use of implantable cardioverter defibrillators in IDC. (PACE 2003; 26[Pt. II]:352,356) [source] Biventricular Pacing as Alternative Therapy for Dilated Cardiomyopathy Associated with Congenital Heart DiseasePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 2 2001EDWIN RODRÍGUEZ-CRUZ RODRÍGUEZ-CRUZ, E., et al.: Biventricular Pacing as Alternative Therapy for Dilated Cardiomyopathy Associated with Congenital Heart Disease. Biventricular, alternative, and multisite pacing are currently being explored to improve cardiac function among patients with medically refractory, end-stage dilated cardiomyopathies. Although, due to inherent myocardial abnormalities, patients with repaired congenital heart defects may be at a greater risk than others to develop heart failure, often requiring cardiac transplantation. The efficacy of biventricular pacing among these patients is unknown. This report presents a patient with successfully repaired congenital heart disease in infancy who developed a symptomatic dilated cardiomyopathy at 22 years of age. Following biventricular pacing, systemic ventricular function showed a 14% improvement in ventricular dP/dt. One month later, subjective symptoms improved and cardiac ultrasound illustrated a 125% increase in fractional area of change. Exercise stress testing showed a 17% improvement in aerobic work capacity. [source] Diagnosis and Management of Inadvertently Placed Pacing and ICD Leads in the Left Ventricle: A Multicenter Experience and Review of the LiteraturePACING AND CLINICAL ELECTROPHYSIOLOGY, Issue 5 2000BERRY M. VAN GELDER Three patients from different centers with pacemaker or ICD leads endocardially implanted in the left ventricle are described. All leads, two ventricular pacing leads and one ICD lead, were inserted through a patent foramen ovale or an atrial septum defect. The diagnosis was made 9 months. 14 months, and 16 years, respectively, after implantation. All patients had right bundle branch block configuration during ventricular pacing. Chest X ray was suggestive of a left-sided positioned lead except in the ICD patient. Diagnosis was confirmed with echocardiography in all patients. One patient with a ventricular pacing lead presented with a transient ischcmic attack at 1-month postimplantation. During surgical repair of the atrial septum defect 14 months later, the lead was extracted and thrombus was attached to the lead despite therapy with aspirin. The other patients were asymptomatic without anticoagulation (9 months and 16 years after implant). No thrombus was present on the ICD lead at the time of the cardiac transplantation in one patient. We reviewed 27 patients with permanent leads described in the literature. Ten patients experienced thromboembolic complications, including three of ten patients on antiplatelet therapy. The lead was removed in six patients, anticoagulation with warfarin was effective for secondary prevention in the four remaining patients. In the asymptomatic patients, the lead was removed in five patients. In the remaining patients, 1 patient was on warfarin, 2 were on antiplatelet therapy, and in 3 patients the medication was unknown. After malposition was diagnosed, three additional patients were treated with warfarin. In conclusion, if timely removal of a malpositioned lead in the left ventricle is not preformed, lifelong anticoagulation with warfarin can be recommended as the first choice therapy and lead extraction reserved in case of failure or during concomitant surgery. [source] | ||||||||||||||||||||||||||||