J. Kobashigawa

Mitral regurgitation after cardiac transplantation.

The contribution of the left atrium to mitral valve competence was assessed using the model of altered atrial size and geometry created by atrial anastomosis during cardiac transplantation. Sixteen patients underwent Doppler and 2-dimensional echocardiography after orthotopic transplantation. Mitral regurgitation was present in 14 of 16 patients. Left atrial geometry was uniformly abnormal, in a snowman configuration. Compared with 16 normal control subjects, the transplanted left atria were dilated (23 +/- 6 vs 13 +/- 3 cm2 during ventricular systole, p less than 0.001). Mitral valve anular diameter indexes, anular systolic reduction and ventricular function were normal in both groups. Ventricular volumes were small in the transplanted heart relative to donor body size (15 +/- 5 vs 20 +/- 8 cm3/m2 in systole, p less than 0.05). The ratio between ventricular length and anular diameter was smaller in the transplant patients (0.87 +/- 0.1 vs 1.0 +/- 0.2, p less than 0.05). In the presence of abnormal left atria, mitral regurgitation may occur without other structural abnormalities of the mitral apparatus. This study suggests that the left atrium plays an important role in mitral valve competence for primary cardiac disease associated with left atrial enlargement, even in the absence of intrinsic mitral valve disease or left ventricular dysfunction.

First-year intravascular ultrasound results as a surrogate marker for outcomes after heart transplantation.

Heart transplantation is the therapy of choice for selected patients with end-stage heart disease. The half-life of heart transplant recipients is now slightly more than 9 years with one of the major causes of late death being cardiac allograft vasculopathy (CAV). The mechanisms of this complication appear to be due to immune-mediated factors although non-immune factors also play a role. It appears that the processes of this long-term complication begin in the donor even before transplantation. Peri-operative and early post-operative events continue to play a pivotal role in the upregulation of the immune system, which causes chronic vascular insults. It appears that the events of the first year after transplant may determine the recipient’s immune response to the donor heart and the subsequent development of CAV. As of yet, there is no clear surrogate marker for the development of CAV. However, recent work has suggested that the first-year intravascular ultrasound (IVUS) data might provide this information. Pre-transplant and peri-operative events may dictate the recipient’s immune response to the donor heart. It has been demonstrated that coronary artery endothelial cells in the donor may express major histocompatability complex Class I and II antigens in response to brain death. In addition, within hours of brain death, upregulation of the immune system can be seen with, for example, intercellular adhesion molecule (ICAM) being identified on cell surfaces. Clinically, it has been reported that the mode of death in the donor, such as explosive brain death (bleed, closed head trauma, gunshot wounds), has been associated with greater development of subsequent CAV. In a consecutive cohort of 61 heart transplant recipients, Mehra et al found that recipients whose donor died from explosive brain death were more likely to develop severe intimal thickness (0.59 mm vs 0.32 mm, p 0.02). Cardiac events (sudden death, myocardial infarction, re-vascularization) were also more frequent in the explosive brain-death group in a 5-year follow-up than those patients whose donors died from gradual brain death (37% vs 12%, p 0.01). It is likely that explosive brain death, which is accompanied by sudden elevations in intracranial pressure and surges of sympathetic outflow, may cause greater donor heart endothelial cell injury and thereby enhance the recipient’s immune response to the transplanted organ. Early post-operative events may also influence outcome. A multicenter study has demonstrated that increased cellular rejection in the first 3 months, as represented by high average biopsy score, correlates with greater intimal thickness by IVUS at 1 year post-transplant. The study suggested that recurrent lower grades of rejections or a smoldering rejection process was more influential in causing vascular damage. Donor-specific antibody found on immunoflourescence staining on endoFrom the Department of Cardiology, UCLA Medical Center, Los Angeles, California. Submitted and accepted May 8, 2003. Reprint requests: Jon A. Kobashigawa, MD, UCLA Medical Center, 100 UCLA Medical Plaza Building, Suite 630, Los Angeles, California 90095-6988. Telephone: 310-794-1200; Fax: 310-794-1211. E-mail: jonKmednet.ucla.edu J Heart Lung Transplant 2003;22:711–714. Copyright

Psychiatric disorders and outcome following cardiac transplantation

BACKGROUNDnPsychosocial factors are frequently included in determining candidacy for cardiac transplantation. Although there are some data demonstrating a link between preoperative psychosocial status and postoperative outcome, a definitive answer has yet to be reached.nnnMETHODSnWe studied 107 consecutive patients, transplanted from January 1990 to September 1991, with a retrospective review of pretransplant psychiatric evaluations to define a DSM III-R Axis I diagnosis. The medical outcome data included 1-year survival, rehospitalizations, infections, and rejection episodes, gathered from the transplant database.nnnRESULTSnThere were no discernable differences between the groups with (n = 25) and without (n = 82) a DSM III-R Axis I psychiatric disorder prior to transplant in the evaluation of demographic data and medical outcome variables.nnnCONCLUSIONnThese data demonstrate that individuals with a history of psychiatric disorder who are carefully selected for compliance with medical care display no inherent difference from individuals without psychiatric disorder in medical outcome and survival at 1 year after cardiac transplantation.

Mycobacterium haemophilum Infections in Heart Transplant Recipients: Case Report and Review of the Literature

Non‐tuberculous mycobacteria are becoming increasingly important pathogens among transplant recipients. We report a case of disseminated Mycobacterium haemophilum infection in a heart transplant recipient, manifesting as cellulitis, subcutaneous nodules, septic arthritis, and pneumonitis. Our case illustrates diverse challenges in the identification and treatment of this pathogen, such as its unique culture requirements and variable antimicrobial susceptibilities. Heightened clinical suspicion is necessary to establish a timely diagnosis so that optimal treatment can be administered.

Giant cell myocarditis in a young man responsive to T-lymphocyte cytolytic therapy

We describe a case of a 40-year-old man who presented with recent-onset, rapidly decompensating heart failure, and who was found to have giant cell myocarditis (GCM) on biopsy. The patient responded to myocardial rest on a biventricular assist device, as well as immunosuppression that included eradication of T cells using OKT3 therapy, coupled with high-dose steroids. The patient was successfully weaned off mechanical support, and ultimately discharged home, where he continues to do well. Based on a review of the clinical and experimental literature, we believe treatment with T-lymphocytic cytolytic therapy may be beneficial. Further studies using this therapy in the treatment of GCM are warranted.

Potential immunosuppressive effects of statins

The paper by Chin et al. in this publication is the first to report on a significant outcome benefit of early statin use in pediatric heart transplant patients. Atorvastatin administered within nine wk after transplant compared with those patients given atorvastatin late (mean of 95 wk post-transplant) resulted in a significantly lower first year incidence for rejection and lower five yr incidence for angiographic graft coronary artery disease (GCAD). These results are similar to what has been reported in the adult literature (1). Graft coronary artery disease in heart transplantation is one of the leading factors that limit long term survival. It is characterized by concentric intimal proliferation and diffuse narrowing along the entire length of the vessel and is believed to be mostly immune mediated. This can lead to obliteration of the graft vessels and ultimately to the graft failure. Both immune and non-immune risk factors have been associated with the development of this disease process. Among non-immune risk factors, cholesterol and triglycerides have been the most reported (2, 3). GCAD in pediatric heart transplant patients is reported to be less than in adult patients; however, it may be under reported (4). Lipid levels have also been shown to be widely elevated following cardiac transplantation (5). A number of factors are thought to contribute to post-transplant hyperlipidemia in pediatric heart transplant recipients. Steroids contribute to increased apolipoprotein B production and also contribute to post-transplant obesity. Cyclosporine may enhance this effect and also independently increase hepatic lipase activity and decrease lipoprotein lipase activity (6). The effect would be impaired very low-density lipoprotein and low-density lipoprotein (LDL) clearance. Hyperlipidemia is a well-established risk factor for non-transplant atherosclerosis. Both clinical and experimental observations suggest that it may be important in the development of GCAD (7–9). In a small retrospective study, elevated lipid values six months following transplantation had a strong predictive value for the development of GCAD at three yr (8). In a more recent study, post-transplant elevation of LDL at one yr was the only predictor for the development or progression of GCAD by intravascular ultrasound (IVUS) (10). The allogeneic state of the transplanted heart, which also leads to endothelial activation, may further augment the vascular response to hyperlipidemia. In this respect, greater intimal thickening, more intimal angiogenesis and a greater accumulation of T-cells is seen in transplanted vasculature compared with native vessels in animals exposed to the same level of hyperlipidemia (11, 12). Clinical trials using 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statins in non-transplant patients with coronary heart disease have demonstrated outcomes benefit in the most recent clinical trials in both primary and secondary prevention (13–15). These effects have been reported in the literature and include anti-atherothrombotic and pleiotrophic effects. The anti-atherothrombotic effects appear to be mediated through cholesterol lowering. They include stabilization of atherosclerotic plaque to prevent rupture, decrease in myocardial necrosis, and an improvement in ventricular function. The pleiotrophic effects are believed to be cholesterol independent and include an anti-inflammatory effect, anti-hypertrophic effect, antioxidant effect, decrease in neurohormonal activation, maintenance of endothelial cell function, and increase in endothelial progenitor cells (16). It is likely that some or all *Editorial to accompany the paper ‘‘Prevention of pediatric graft coronary artery disease: Atorvastatin’’ (Chin et al. 2008). Pediatr Transplantation 2008: 12: 381–384 Copyright 2008 Blackwell Munksgaard

969-93 Long Term Outcome of Mono-Immunosuppression in Cardiac Transplant Recipients

Steroid-free immunosuppression has been reported to be successful in select cardiac transplant recipients. Further reduction of immuno-suppression meditation (using cyclosporine alone) has been reported; however, there is concern regarding long term outcome. In our institution, since 1989, 16 cardiac transplant patients on double-immunosuppression (cyclosporine and azathioprine) whose WBC decreased to less than 4,000 were also taken off azathioprine and maintained on mono-immunosuppression (cyclosporine alone). Five year actuarial survival for this group is 92%, and there has been no evidence for transplant coronary artery disease (defined as any luminal irregularity) in any of the annual coronary angiograms. Comparison of actuarial survival curves between mono-immunosuppression patients and tripleimmunosuppression patients is as follows: Download : Download high-res image (69KB) Download : Download full-size image Conclusion Mono-immunosuppression (cyclosporine alone) appears successful in select cardiac transplant recipients. The low risk for transplant coronary artery disease may be due to a lowering of associated risk factors and the selection of an “immuno-privileged” patient population.

733-6 Outcome of Patients Transplanted with Bypassed Donor Hearts

As the waiting list for donor hearts increases, innovative ways to expand the donor pool are being utilized. For urgent status I and older age recipients (ages 60–70 years), we have been using donor hearts with normal left ventricular function but with pre-existing coronary artery disease and performing saphenous vein bypass grafts (SVG) at the time of transplantation. We now report our short term results. Between March 1992 and June 1994, 10 patients (5 urgent status I with mean age 50.4 years and 5 older age patients with mean age 65.4 years) underwent cardiac transplantation in our institution having either 1, 2 or 3 SVGs performed at the time of transplant surgery. The mean donor age was 54.2 years. Six of 10 patients have survived to 1 year with 3 early deaths and 1 late death due to infection (2 patients), rejection and early graft failure. Autopsies revealed all SVGs to be patent in all 4 patients. At the first year coronary angiogram, 9 of 10 SVGs (in 6 patients) were found to be patent without significant stenoses present. Cardiac function at 1 year after transplant was as follows: Average Cardiac Function at 1 year post OHT RA (mmHg) PA (mmHg) PCW (mmHg) CO (L/min) LVEF (%) SVG patients 4xa0±xa02 17xa0±xa06 9xa0±xa04 6.4xa0±xa01.6 60xa0±xa04 Conclusion Patients transplanted with bypassed donor hearts appear to have normal cardiac function and acceptable short term survival considering their preop high risk status. A majority of SVGs remain patent at 1 year with coronary ischemia not appearing to be responsible for early mortality.