Showing papers in "Journal of Heart and Lung Transplantation in 2006"

International guidelines for the selection of lung transplant candidates: 2006 update--a consensus report from the Pulmonary Scientific Council of the International Society for Heart and Lung Transplantation.

Abstract: Since the writing of the 1998 guidelines for the selection of candidates for lung transplantation, there has been an increased understanding of the natural history of various lung diseases as well as new treatment strategies developed that may forestall the need for transplantation for certain disorders. This has resulted in several changes to the current strategy for selecting patients for this procedure. The primary goal of this document is to provide up-to-date guidelines to help physicians in the referral and selection process of candidates for lung transplantation. With limited prospective randomized studies to support the recommendations outlined in this document, this update to the international guidelines is based primarily on a consensus of opinion rendered by experts in the field. The bulleted guidelines should therefore not be considered to be hard and fast rules. Because of the potential for long waiting times to transplantation, physicians should err on the side of early referral of their patients to a lung transplant center. © 2006 International Society for Heart and Lung Transplantation.

Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates--2006.

Abstract: wo of the previous International Society for Heart and ung Transplantation (ISHLT) consensus conferences ave addressed listing criteria for patients awaiting eart transplantation. Guidelines from these two onferences were completed before the acceptance of -blocker and device therapies in the clinical treatment f late-stage heart failure. Guidelines addressing the mangement of heart failure are now available from the uropean Society of Cardiology (ESC) as well as the merican College of Cardiology (ACC), American Heart ssociation (AHA) and Heart Failure Society of America HFSA) in the USA; however, these statements are not omprehensive regarding the criteria for listing patients or heart transplantation. Thus, the ISHLT has reponded to this urgent need to re-evaluate the listing riteria to provide succinct and clear guidance to ransplant centers. These recommendations can be sed to update listing and management policies for otential heart transplant recipients.

Right Heart Failure After Left Ventricular Assist Device Implantation in Patients With Chronic Congestive Heart Failure

Abstract: Background Right heart failure (RHF) is not an infrequent complication of left ventricular assist device (LVAD) implantation. Few studies have examined outcomes for LVAD patients who subsequently develop RHF. This study details one center's experience with RHF in chronic congestive heart failure (CHF) patients. Methods One hundred eight patients with chronic CHF (≥6 months) who underwent HeartMate LVAD implantation were identified during June 1996 to July 2004. Acute heart failure patients requiring LVADs were excluded to eliminate the impact of confounding non-cardiac factors. RHF was defined as the need for a subsequent right ventricular assist device (RVAD), ≥14 days of intravenous inotropes/pulmonary vasodilators, or both. Forty-two (38.9%) RHF patients were identified. Fourteen of these required RVAD insertion. Outcome parameters included early (≤30-day) mortality, intensive care unit (ICU) length of stay (LOS), incidence of re-operation for bleeding and acute renal failure, and stroke, bridge-to-transplantation rate and post-transplantation survival rate. Results More female patients developed RHF than not (73.3% vs 26.7%, p = 0.003). RHF patients had a higher early mortality rate, greater ICU LOS, higher rates of re-operation for bleeding and renal failure, and lower bridge-to-transplantation rate than non-RHF patients (19.0% vs 6.2%, p = 0.039; 23.8 ± 23.7 vs 9.6 ± 7.1 days, p p = 0.026; 61.0% vs 22.6%, p p = 0.003; respectively). Fourteen (33.3%) RHF patients required RVAD insertion. Elevated intra-operative central venous pressure (CVP) was found to be an independent predictor of post-LVAD RHF. Overall bridge-to-transplantation rate for the entire study cohort was 73.1%. Conclusions The development of RHF after LVAD insertion confers significant morbidity and mortality. Judicious application of inotropes and pulmonary vasodilators and timely RVAD insertion, if necessary, should be maintained. Further investigations evaluating pre- and intra-operative risk factors for the development of RHF are warranted.

Registry of the International Society for Heart and Lung Transplantation: Twelfth Official Pediatric Heart Transplantation Report-2009.

Abstract: Pediatric heart transplantation celebrates its twentyfifth birthday in 2007, and the first recipients are now entering adulthood. This, the Tenth Official Pediatric Report of the Registry of the International Society for Heart and Lung Transplantation (ISHLT), is dedicated to the courageous recipients and their families, and to the generous donor families who have made this possible. This report documents decades-long survival enjoyed by many pediatric heart transplant recipients. We can now look back over the past 25 years and evaluate indications, survival and morbidity by age of the recipient and era of transplantation. Because much has changed over one-quarter century, we can only be reasonably certain that the late outcomes of the earliest pediatric transplants will be reflected accurately in current recipients. However, these data form a standard and a point of reference to predict future outcomes and perhaps compare actual outcomes in the years to come, as new therapies and management protocols are developed and tested. The data stream for the Registry of the ISHLT is global, and geographic differences have emerged. Geographic comparisons for age at transplant and indication for transplantation are presented for the first time in this tenth report. Previous publications have reported on a steadily improving early survival. 1 We now have a more complete knowledge base for late survival and we report, for the first time, morbidity as late as 10 years after transplantation. Re-transplantation as an indication for transplant has been slowly increasing in North America, but is almost non-existent elsewhere in the world. This report documents the recent rise in the number of re-transplant procedures and further evaluates the late outcomes after re-transplantation. Questions remain about the role of re-transplantation for pediatric recipients who become adults. Will adult transplant programs worldwide accept the burden of re-transplantation for pediatric recipients who are now in need of a second heart transplant, or perhaps a kidney transplant, due to calcineurin inhibitor‐induced renal failure? Certainly this challenge will grow and the pediatric transplant community must evaluate potential changes at the point of care in childhood that could reduce the demand for re-transplantation and perhaps increase the likelihood of multi-decade survival with less morbidity. The two main post-transplant morbidities that have steadily increased are coronary artery vasculopathy and renal failure. Malignancy has remained an important but low-frequency event. In this report, we continue to evaluate late outcomes as a function of early events

Acute antibody-mediated rejection of cardiac transplants.

Abstract: Under the direction of the International Society for Heart and Lung Transplantation, a multidisciplinary review of the cardiac biopsy grading system was undertaken in 2004, with task forces examining the areas of histopathology of rejection, clinical issues, and research. An important new area addressed by the Immunopathology Task Force sub-committee was the clinical and diagnostic criteria for antibody-mediated rejection. This article is a companion paper to the revised working formulation for the standardization of nomenclature in the diagnosis of heart rejection and reviews the published literature documenting the serologic and morphologic evidence that antibody-mediated rejection is clinically significant and associated with graft loss, accelerated transplant-associated coronary artery disease, and death. This article also provides a more in-depth analysis of antibody-mediated rejection developed by the Immunopathology Task Force for revision of the 1990 working formulation for the standardization of nomenclature in the diagnosis of heart rejection.

Registry of the International Society for Heart and Lung Transplantation: Tenth Official Pediatric Lung and Heart/Lung Transplantation Report—2007

Abstract: This tenth official pediatric report of the International Society for Heart and Lung Transplantation (ISHLT) covers the international pediatric lung and heart-lung transplantation experience from 1982 to 2006. As of last year's report, pediatric lung and heart-lung transplant data are now reported separately from pediatric heart transplant data and adult lung transplant data. For the first time this year, Registry data are analyzed by geographic region in addition to the usual aggregate analyses. All figures and tables included in this report and additional supplementary slides are available from the ISHLT website (www.ishlt.org/registries).

Clinical performance with the Levitronix Centrimag short-term ventricular assist device.

Abstract: Background The Levitronix ventricular assist device (VAD) is a centrifugal pump designed for extracorporeal support and that operates without mechanical bearings or seals. The rotor is magnetically levitated so that rotation is achieved without friction or wear, which seems to minimize blood trauma and mechanical failure. The aim of this study is to report our early results with the Levitronix Centrimag device. Methods Between June 2003 and April 2005, 18 patients (pts) were supported using the Levitronix at our institution. Fourteen were male. Mean age was 40.3 ± 18.3 (range 8 to 64) years. Indications for support at implantation were: post-cardiotomy cardiogenic shock in 12 cases (Group A), and bridge to decision regarding long-term ventricular support in 6 cases (Group B). Results Mean support time was 14.2 ± 15.2 days for all patients (range 1 to 64 days). Operative (30-day) mortality was 50% (9 pts). Six pts were in Group A and 3 pts were in Group B. Overall, 6 pts (33%) were discharged home and are presently alive and well (mean follow-up 13 months, range 5 to 17 months). Bleeding requiring re-operation occurred in 8 cases (44%), cerebral thromboembolism in 1 and pulmonary embolism in 1. There were no device failures. Conclusions The Levitronix functioned well and proved to be useful in patients with extremely poor prognosis previously considered non-suitable for a long-term assist device. The device was technically easy to implant and manage. There was no device dysfunction and complications were acceptable or consistent with other devices. Survival to explant or a definitive procedure (VAD or transplantation) was encouraging.

Mycophenolate mofetil and risk of developing malignancy after orthotopic heart transplantation: analysis of the transplant registry of the International Society for Heart and Lung Transplantation.

Abstract: Background Malignancy after organ transplantation has been described as the "price of immunotherapy." Evolving strategies aimed at effective immunosuppression could have differing effects on the likelihood of developing malignancy. We analyzed data from the transplant registry of the International Society for Heart and Lung Transplantation (ISHLT) to ascertain which factors are associated with the development of malignancy after orthotopic heart transplantation (OHT). Methods Multivariate modeling was performed to determine factors predictive of first post-transplant malignancy in patients taking standard immunosuppressive regimens, defined as cyclosporine or tacrolimus and azathioprine or mycophenolate mofetil (MMF), who underwent OHT between January 1, 1995 and December 31, 1997. Results Of the 3,895 transplants described in the cohort, 703 (18%) developed post-transplant malignancy at any time during the follow-up period, and 549 (14%) developed malignancy within the first 5 years post-transplant. The breakdown of malignancy was as follows: skin: 47%; post-transplant lymphoproliferative disease: 10%; other malignancies: 24%; combination of types: 10%; and unreported: 10%. Multivariate modeling revealed that independent predictors of increased risk were prior malignancy and increased age, whereas the use of MMF as part of a standard immunosuppressive regimen was associated with an adjusted relative risk (RR) = 0.73 (95% confidence interval 0.56 to 0.95). Relative to a recipient age of 55 years, the risk of malignancy for 30, 45 and 60 years of age was 0.32, 0.46 and 1.37, respectively. Although the use of tacrolimus appeared protective in the univariate analysis, it was not significant according to multivariate analysis. Female gender appeared to be protective. Neither OKT3 nor anti-thymocyte globulin (ATG) use was associated with a significantly increased risk of malignancy. Conclusions The choice of immunosuppressive regimen may affect the likelihood of developing malignancy after OHT. Induction immunosuppression does not appear to increase the risk of subsequent malignancy. The use of MMF in standard immunosuppressive regimens is associated with a significantly lower risk of developing malignancy.

Validation of the proposed International Society for Heart and Lung Transplantation grading system for primary graft dysfunction after lung transplantation.

Abstract: Background A scoring system was recently proposed to grade the severity of primary graft dysfunction (PGD), a frequent early complication of lung transplantation. The purposes of this study are to: (1) validate the PGD grading system with respect to patient outcomes; and (2) compare the performance of criteria employing the arterial oxygenation to fraction of inspired oxygen (P/F) ratio to an alternative grading system employing the oxygenation index (OI). Methods We retrospectively reviewed the medical records of 402 patients having undergone lung transplantation at our institution from 1992 through 2004. The ISHLT PGD grading system was modified and grades were assigned up to 48 hours post-transplantation as follows: Grade 1 PGD, P/F >300; Grade 2, P/F 200 to 300; and Grade 3, P/F Results The prevalence of severe PGD (P/F Grade 3) declined after transplant, from 25% at T0 to 15% at T48. Grouping patients by P/F grade at T48 demonstrated the clearest differentiation of 90-day death rates (Grade 1, 7%; Grade 2, 12%; Grade 3, 33%) ( p = 0.0001). T48 OI grade also differentiates 90-day death rates. There was no difference in longer-term survival between patients with PGD Grades 1 and 2. OI grade at T0 qualitatively improved differential mortality between Grades 1 and 2; however, the differences did not reach statistical significance. Patients with a worst score T(0–48) of Grade 3 PGD did have significantly decreased long-term survival, as well as longer ICU and hospital stay, when compared with Grades 1 and 2 PGD. Significant risk factors for short- and long-term mortality in our multivariate model were P/F Grade 3 [worst score T(0–48) as well as T0 grade], single-lung transplant, use of cardiopulmonary bypass and high pre-operative mean pulmonary artery pressure. Conclusions There is an increased risk of short- and long-term mortality and length of hospital stay associated with severe (Grade 3) PGD. The proposed ISHLT grading system can rapidly identify patients with poor outcomes who may benefit from early, aggressive treatment. Refinement of the scoring system may further improve patient risk stratification.

Reverse remodeling of the myocardial extracellular matrix after prolonged left ventricular assist device support follows a biphasic pattern.

Abstract: Background Collagens are important components of the extracellular matrix (ECM). Alterations in collagen structure and composition can lead to end-stage heart failure. Left ventricular assist devices (LVADs) are frequently used as a bridge to heart transplantation (HTx). In this study, we analyzed changes in composition of the collagens as well as the synthesis or degradation of these collagens after prolonged LVAD support. Methods The ECM volume was quantified after Picro-Sirius red staining. With immunohistochemistry (IHC), Type I and Type III collagen proteins were analyzed and, using quantitative polymerase chain reaction (PCR), collagen mRNA expression was analyzed. Collagen synthesis and degradation was studied by measuring N-terminal pro-peptide for Type I collagen (PINP), N-terminal pro-peptide for Type III collagen (PIIINP) and carboxyterminal telopeptide for Type I collagen (ICTP) in plasma. Collagen composition was measured using the hydroxyproline/Sircol assay. Results The ECM volume increased in the first 200 days after LVAD implantation. At between 200 and 400 days the ECM volume decreased, but remained higher than pre-LVAD. After 400 days the ECM volume was smaller than the pre-LVAD volume. IHC did not show a significant difference pre- and post-LVAD for collagen composition. Collagen mRNA expression did not change but an augmented synthesis of collagen during the first month after LVAD support was detected upon measurement of plasma PINP and PIIINP levels. In addition, the quality of the collagen network improved. Conclusions Reverse remodeling during LVAD support follows a biphasic pattern. Initially, an increase in Type I and Type III collagen turnover occurs, which is paralleled by a volume increase of the ECM. Subsequently, this turnover decreases as ECM volume decreases, which results in a restoration of the collagen network.

Prognostic Implications of Serial Assessments of Pulmonary Hypertension in Severe Chronic Heart Failure

Abstract: Background It is unknown whether time-related changes of pulmonary hypertension (PH) have prognostic relevance in severe chronic heart failure (CHF). Methods All CHF patients referred for follow-up from 1996 through 2003 were screened for this study. Eligibility depended on availability of a concomitant clinical, laboratory, electrocardiographic (ECG), echocardiographic and right-heart catheterization (RHC) assessment at index evaluation, as well as absence of pre-capillary PH. Results One hundred ninety-six patients (age 54 ± 9 years; 27% women, 73% men; 50% in New York Heart Association [NYHA] Class III or IV) were included. PH at index evaluation was an independent predictor of acute heart failure or cardiovascular death (AHF/CD), with adjusted risk ratio (RR) = 2.30, 95% confidence interval (CI) 1.42 to 3.73 and p p = 0.001), and from time-related changes in the other hemodynamic parameters ( p ≤ 0.033). Conclusions PH retains independent prognostic significance even after adjusting for a large set of clinical/laboratory/instrumental parameters. Furthermore, serial measurements of mPAP seem to provide additional prognostic information as compared with a single assessment. These findings indicate that serial evaluations of PAP may help identify a sub-set of high-risk CHF patients deserving a particularly close follow-up to facilitate timely indications for non-pharmacologic strategies, including (when appropriate) heart transplantation.

Disseminated Scedosporium apiospermum Infection in a Cystic Fibrosis Patient After Double-lung Transplantation

Abstract: Scedosporium apiospermum is a saprophytic ubiquitous filamentous fungus It can cause a wide spectrum of diseases, from localized to invasive infections S apiospermum has been described as one of the major fungal agents of chronic colonization of airways in cystic fibrosis (CF) patients Invasive infections due to S apiospermum are only rarely reported in CF after lung transplantation A 26-year-old woman with CF and chronic bronchial colonization by S apiospermum developed bilateral chorioretinitis and subcutaneous nodules 4 weeks after double-lung transplantation (LTx) Isolates of S apiospermum from sputum samples before and after LTx and from vitreal fluid were typed by random amplification of polymorphic DNA (RAPD) The patient was treated with voriconazole (VRC) The patient improved with VRC given orally for 6 months Two days after VRC discontinuation, she developed sub-acute meningitis (isolation of S apiospermum from the cerebrospinal fluid) She was again given VRC, but died 23 days later from uncontrolled fungal infection Molecular typing of clinical isolates of S apiospermum performed by RAPD demonstrated that all isolates belonged to the same genotype S apiospermum is a frequent, but late colonizing fungal agent in CF patients In the case of LTx, these patients can develop invasive infection due to the colonizing strain, as confirmed by molecular typing

Fish Oils Produce Anti-inflammatory Effects and Improve Body Weight in Severe Heart Failure

Abstract: Background Fish oils have been shown to reduce production of tumor necrosis factor-alpha (TNF-α) in healthy subjects. We sought to evaluate the effects of fish oils on pro-inflammatory cytokines and body weight in patients with advanced heart failure. Methods Fourteen patients (New York Heart Association [NYHA] Class III to IV heart failure) were randomized in a double-blinded trial to active therapy with 8 g of n-3 fatty acids (Group A, n = 7) or placebo (Group B, n = 7) for 18 weeks. TNF-α and interleukin-1 (IL-1) production were measured by radioimmunoassay after endotoxin stimulation of peripheral blood mononuclear cells. Results Placebo-treated patients had a 44% increase in TNF-α (from 1.28 to 1.84 pg/ml; p = 0.07) but no significant change in IL-1 (from 0.68 to 0.78 pg/ml) production. n-3 fatty acids resulted in a 59% reduction in TNF-α (from 1.64 to 0.68 pg/ml; p = 0.02) and 39% decrease in IL-1 (from 1.98 to 1.21 pg/ml; p = 0.09) production. There was an inverse correlation between change in TNF-α production and change in percent body fat ( r = −0.6; p = 0.02). Conclusions Fish oils decrease TNF-α production in heart failure and improve body weight. Fish oil therapy may represent a novel therapeutic approach in late-stage heart failure characterized by cardiac cachexia.

Mechanical unloading leads to echocardiographic, electrocardiographic, neurohormonal, and histologic recovery.

Abstract: Background Mechanical unloading during left ventricular assist device (LVAD) support may lead to cardiac recovery. Predictors of recovery, however, have not been identified. We aimed to evaluate the time course and durability of echocardiographic, electrocardiographic (ECG), histologic, and neurohormonal changes that occur with LVAD support and to screen for non-invasive markers of cardiac recovery. Methods LVAD patients underwent monthly testing, including echocardiographic, ECG, and serum B-type natriuretic peptide (BNP) measurement. Paired myocardial tissue samples from implant and explant were also analyzed. Results Thirty-six LVAD patients were prospectively followed for an average of 101 ± 99 days. Left ventricular ejection fraction (LVEF) and end-diastolic diameter (LVEDD) significantly improved at 30 days compared with pre-LVAD (19% ± 6.6% vs 33% ± 8.1%, 7.1 ± 1.2 cm vs 4.9 ± 1.0 cm, respectively; both p Conclusions We demonstrate echocardiographic, ECG, histologic, and neurohormonal improvement during LVAD support. Cardiac recovery peaked by 60 days, and there was a trend toward progressive improvement in QRS duration with ongoing support. We report the association of ECG changes with echocardiographic and histologic improvements. Future prospective studies may yield important markers of recovery.

Mycobacterium abscessus infections in lung transplant recipients: the international experience.

Abstract: Background The clinical significance of Mycobacterium abscessus infection in the lung transplant population is not well understood. Methods An international survey was performed to determine the incidence and clinical outcomes of M abscessus infections before and after lung transplantation. Results Thirty-one (50%) of the 62 transplant centers affiliated with the International Society of Heart and Lung Transplantation responded to the survey. Of 5,200 transplants performed, 17 patients (0.33%) (M/F, 12:5) were identified with M abscessus after transplantation. Two patients had respiratory colonization before lung transplantation. Post-transplantation M abscessus infections occurred in the pulmonary allograft in 12, in skin/soft tissue in 3, or both in 2. Median time to diagnosis after transplantation was 18.5 months (range, 1–111 months). Therapies included multiple antibiotics in 16, surgical debridement in 2, interferon-γ in 1, or no therapy owing to presumed colonization in 1. Eleven (73%) of 16 treated patients had a radiologic or microbiologic response to treatment. Concurrent infections were common, with Aspergillus ( n = 8) and Pseudomonas aeruginosa ( n = 5) most frequently seen. Death in 2 patients was attributed to M abscessus . Ten of 17 patients are alive and considered cured. Conclusions M abscessus infection in the lung transplant recipient is uncommon and challenging; however, successful treatment can occur. Prolonged combination anti-microbial therapy is required for pulmonary involvement, and surgical debridement is recommended for cutaneous lesions. Concurrent infections are common and may contribute to mortality in this immunosuppressed population.

Peripheral vascular reactivity in patients with pulsatile vs axial flow left ventricular assist device support.

Abstract: Background Left ventricular assist devices (LVADs) are either pulsatile or axial flow devices. The latter can be operated at a low-speed setting to allow pulsatility or at a high-speed setting to create continuous flow. The purpose of this study was to compare the effect of continuous flow and pulsatile flow on peripheral vascular reactivity. Methods Twenty consecutive patients were divided into two groups based on the type of LVAD they received. Ten patients had a pulsatile flow LVAD, and 10 had an axial flow LVAD. For the purpose of the study protocol, the axial flow devices were operated at a high speed to ensure continuous flow. The patients’ peripheral artery vasoreactivity was assessed with an ultrasound vascular transducer that measured flow-mediated dilation (FMD). Results The FMD of the patients supported with pulsatile flow (15.6 ± 5%) was higher than the FMD of the patients supported with temporary continuous flow (1.8 ± 3%). The difference was statistically significant (p Conclusions Pulsatile flow is associated with a better peripheral vascular reactivity than continuous flow. Patients supported by axial flow devices should be kept on the lowest speed setting to allow maximum pulsatility.

Limiting factors of exercise performance 1 year after lung transplantation.

Abstract: Background After lung transplantation (LTx) exercise capacity frequently remains limited, despite significantly improved pulmonary function. The aim of this study was to evaluate maximal exercise capacity and peripheral muscle force before and 1 year after LTx, and to determine whether peripheral muscle force and lactate threshold (LT) limit exercise capacity 1 year after LTx. Methods Twenty-five subjects (mean age 43 years, 8 women and 17 men, 4 single-lung transplantations) were included in the study. Measurements included maximal exercise capacity, lactate threshold (symptom-limited bicycle ergometer test) and muscle force test (hand-held dynamometer) were performed before and 1 year after LTx. Results Before LTx, all patients showed severe exercise intolerance (mean ± SD): work capacity (W peak ), 11.6 ± 18 W; peak oxygen uptake (Vo 2 ), 8.6 ± 3.6 ml/min/kg. After LTx, exercise capacity improved significantly: W peak , 69 ± 27 W ( p 2 , 15.7 ± 4.3 ml/min/kg ( p p r = 0.76, p r = 0.41, p r = 0.53, p Conclusions The occurrence of an early and pathologic LT and peripheral muscle weakness contributes to the limitation of exercise capacity and reflects a peripheral deficit post-LTx.

Five-year results of a randomized, single-center study of tacrolimus vs microemulsion cyclosporine in heart transplant patients.

Abstract: Background Previous multicenter, randomized trials, lacking standardized post-transplant protocols, have compared tacrolimus (Tac) and cyclosporine (CyA, Sandimmune) and demonstrated similar outcomes with some different adverse effects. The microemulsion form of CyA (mCyA, Neoral) has replaced Sandimmune CyA as the more widely utilized CyA formulation. This is the first 5-year follow-up study of a large, single-center trial ( n = 67) under a standardized post-transplant protocol comparing Tac and mCyA. Methods Sixty-seven heart transplant patients were randomized to Tac ( n = 33) or mCyA ( n = 34), both in combination with corticosteroids and azathioprine without cytolytic induction. Five-year end-points included survival, Grade ≥3A or treated rejection, angiographic cardiac allograft vasculopathy (CAV; any lesion ≥30% stenosis), renal dysfunction (creatinine ≥2.0 mg/dl), use of two or more anti-hypertensive medications, percent diabetic and lipid levels. Results Five-year survival, freedom from Grade ≥3A or any treated rejection and angiographic CAV, mean cholesterol level and percent diabetic were similar between the two groups. The Tac group had a significantly lower 5-year mean triglyceride level (Tac 97 ± 34 vs mCyA 175 ± 103 mg/dl, p = 0.011) and average serum creatinine level (Tac 1.2 ± 0.5 mg/dl vs mCyA 1.5 ± 0.4 mg/dl, p = 0.044). There was a trend toward fewer patients requiring two or more anti-hypertensive drugs in the Tac group (Tac 33% vs mCyA 59%, p = 0.065). Conclusions Tac and mCyA appear to be comparable with regard to 5-year survival, freedom from rejection and CAV. However, compared with mCyA, Tac appears to reduce the adverse effect profile for hypertriglyceridemia and renal dysfunction and the need for hypertensive medications.

High frequency of bronchogenic carcinoma after single-lung transplantation.

Abstract: Background Lung transplantation is a commonly employed therapy in the treatment of patients with advanced lung diseases related to tobacco use. Little is known about the long-term incidence or risk factors for primary lung cancer after lung transplantation. To determine the frequency, clinical features and risk factors for primary bronchogenic malignancy after lung transplantation, we designed a matched cohort study of single and bilateral lung transplant recipients with extended follow-up. Methods We retrospectively reviewed the records of 262 lung transplant recipients who survived ≥90 days post-transplant and assessed for the development of primary lung cancer. One hundred thirty-one consecutive single-lung transplant (SLTx) recipients were matched to 131 consecutive bilateral lung transplant (BLTx) recipients by native disease. Risk factors for lung cancer development were derived using univariate and multivariate proportional hazards models. Results Of the SLTx recipients, 6.9% developed primary lung cancer after transplantation as compared with 0% of the BLTx recipients (p = 0.002), after a mean of 52 months. Histologically, non–small-cell cancers were present in the native lung, which led to death in 67% (6 of 9) of the patients despite treatment. Significant risk factors for the development of primary lung cancer were increasing age (p = 0.004), >60-pack-year smoking history (p = 0.03), and SLTx as compared with BLTx (p Conclusions Single-lung transplant confers a significantly elevated risk of developing primary post-transplant lung cancer as compared with BLTx in patients with comparable native disease, age and tobacco history.

Determining the best ventilatory efficiency measure to predict mortality in patients with heart failure.

Abstract: Background Ventilatory efficiency, the relationship between ventilation (VE) and carbon dioxide production (VCO 2 ), predicts mortality in heart failure patients, but its determination has not been standardized. Additionally, it is unclear if the prognostic power of ventilatory efficiency is independent of exercise intensity. Therefore, we investigated the relative prognostic power of different measures of ventilatory efficiency calculated from maximal and sub-maximal exercise in patients with heart failure. Methods and Results Heart failure patients ( n = 355, 72% males, age 51 ± 10 years) had follow-up for at least 5 years from an exercise test. There were 145 events (133 deaths and 12 emergent cardiac transplants). Ventilatory efficiency calculations were not equivalent. Of the different measures of ventilatory efficiency, the VE/VCO 2 slope to peak exercise was the most significant predictor of mortality in a multivariable Cox model, including ejection fraction, systolic blood pressure, peak oxygen consumption (VO 2 ), gender, etiology, and heart rate. A 5 U increment of the VE/VCO 2 slope to peak exercise corresponded to a 9% increase in mortality risk. When tests were grouped by peak exercise intensity, by quartiles of peak respiratory exchange ratio, the VE/VCO 2 slope to peak exercise was always a better predictor than peak VO 2 . Conclusion Peak and sub-maximal measures of ventilatory efficiency were not equivalent, and the VE/VCO 2 slope to peak exercise was the best predictor of mortality in patients with heart failure. Thus, the prognostic power of ventilatory efficiency is enhanced when exercise extends beyond the ventilatory threshold and includes all of the available exercise data.

Peri-operative renal function and outcome after orthotopic heart transplantation.

Abstract: Background Renal insufficiency is an established risk factor in patients undergoing cardiovascular surgery. We sought to evaluate the relationship between renal function and outcomes after orthotopic heart transplantation (OHT). Methods We conducted a retrospective review of 622 adults who underwent 628 consecutive OHTs between 1994 and 2001 at our institution. The recipients were divided into either normal (Group 1) or impaired (Group 2) pre-operative renal function. Impaired renal function was defined as creatinine clearance (CrCl) Results Early mortality was 7% (38/531) in Group 1 and 17% (16/96) in Group 2 ( p = 0.002). Similarly, the death rate per 100 patient-years was 4.8 and 8.1 for the groups, respectively ( p = 0.03). Nine percent of patients in Group 1 required post-operative dialysis (49/531), whereas 32% of recipients in Group 2 required this intervention (31/96) ( p p p = 0.2). Conclusions CrCl

Cardiomyocyte bridging between hearts and bioengineered myocardial tissues with mesenchymal transition of mesothelial cells

Abstract: Background For the reconstruction of 3-dimensional (3D) tissues, we exploited an original method of tissue engineering that layers individual cell sheets harvested from temperature-responsive culture dishes. Stacked cardiomyocyte sheets demonstrated electrical and morphologic communication, resulting in synchronously beating myocardial tissue. When these bioengineered 3D tissue grafts are transplanted onto damaged hearts, gap junction communication between graft and host is likely critical for synchronized beating and functional improvement. In this study, these graft-to-heart morphologic communications were examined. Methods Neonatal rat cardiomyocyte sheets were harvested from temperature-responsive culture dishes and layered to create 3D tissues. These constructs were then transplanted onto infarcted rat hearts. Histologic analyses and transmission electron microscopy (TEM) were performed to examine morphologic communications. The passage of small molecules through functional gap junctions was also detected using a dye-transfer assay. Results Transplanted cardiomyocytes bridged between the grafts and hearts in intact areas. Connexin-43 staining and TEM revealed the existence of gap junctions and intercalated disks between the bridging cardiomyocytes. Furthermore, it was confirmed that a low-molecule fluorescent dye, calcein, was transferred from the grafts to the hearts via the bridging cardiomyocytes. Immunohistochemistry with anti-intercellular adhesion molecule-1 antibodies revealed that mesothelial cells in the epicardium scattered and transdifferentiated into mesenchymal cells between the graft and host. Conclusions The direct attachment of layered cardiomyocyte sheets on the heart surface promotes mesothelial cell transdifferentiation and cardiomyocyte bridging, leading to functional communication via gap junctions. These results indicate that these bioengineered myocardial tissues may improve damaged heart function via synchronized beating.

Utility of Long-term Surveillance Endomyocardial Biopsy: A Multi-institutional Analysis

Abstract: Background The utility of long-term endomyocardial biopsy surveillance in heart transplant recipients has been questioned. This study was undertaken to identify risk factors for late rejection and to examine the impact of different biopsy surveillance protocols on outcomes using the registry of the Cardiac Transplant Research Database. Methods The study group consisted of all adult patients who underwent heart transplantation at the 33 centers participating in this investigation between January 1, 1993 and January 1, 2002, survived past the second post-transplant year, and were followed-up by a defined surveillance biopsy protocol. Results During a follow-up that consisted of 24,137 patient-years, 1,626 late rejections occurred. Shorter time since transplant, history of rejection, younger age and African-American ethnicity of the recipient were strong risk factors for late rejection. The practice of surveillance biopsy varied among institutions. Continued surveillance increased the rate of diagnosis of late rejection (RR = 1.3, p = 0.002). There was no reduction in the incidence of hemodynamically compromising rejection and no increase in survival in patients with long-term vs intermediate-term surveillance. Short-term surveillance was associated with an increased incidence of hemodynamically compromising rejection, particularly among high-risk patients, and increased mortality in African-American patients. Conclusions There are no apparent benefits from surveillance biopsy beyond 5 years post-transplant. Surveillance biopsy between 2 and 5 years post-transplant was found to reduce mortality in African-American recipients. Non–African-American recipients at high risk for late rejection will likely benefit from surveillance up to 5 years post-transplant.

Mycobacterium abscessus Chest Wall and Pulmonary Infection in a Cystic Fibrosis Lung Transplant Recipient

Abstract: Mycobacterial infections are increasingly recognized in cystic fibrosis (CF) patients before transplant; however, knowledge about the clinical significance or spectrum of infections observed with mycobacterial infections in lung transplant recipients is still evolving. Herein, we report a case of infection with Mycobacterium abscessus in a CF lung transplant recipient. Despite aggressive treatment before and peri-operatively with anti-mycobacterial therapy, the patient developed skin and soft tissue infection of the incision and of bilateral breast implants, eventually leading to disseminated pulmonary infection and death. This report highlights the potential for M abscessus to cause post-transplant disease in CF patients undergoing lung transplant, despite peri-operative anti-mycobacterial therapy. Thus, pre-transplant colonization with M abscessus should be viewed as a strong relative, if not absolute, contraindication to lung transplantation. The combination of the virulent pre-transplant pathogen M abscessus and foreign bodies in the chest likely acted synergistically to contribute to the unfortunate outcome in this patient.

Improved survival after acute myocardial infarction complicated by cardiogenic shock with circulatory support and transplantation: comparing aggressive intervention with conservative treatment.

Abstract: Background The prognosis for patients with myocardial infarction has steadily improved, but remains poor for those developing cardiogenic shock. Utilization of re-vascularization, mechanical circulatory support and transplantation in these patients may improve survival. Methods We retrospectively analyzed the clinical outcome of 138 consecutive patients at the Cleveland Clinic from 1992 to 1998 who met the criteria for cardiogenic shock after acute myocardial infarction. All patients received intensive medical therapy and intra-aortic balloon pump support. Forty-three patients received intensive medical therapy (conservative group) and 95 patients were treated aggressively (aggressive group). The aggressive group comprised patients who were treated with percutaneous intervention/coronary artery bypass grafting ( n = 77, re-vascularization group), and patients who received circulatory support/cardiac transplantation ( n = 18). Results The baseline demographics and angiographic and hemodynamic features were comparable for the two groups. The in-hospital mortality rate was significantly reduced in the aggressive group compared with the conservative group (54% vs 81%, p = 0.002). The in-hospital mortality rate of the circulatory support/transplant group was markedly reduced compared with the conservative group (33% vs 81%, p p = 0.03). The aggressive group had a markedly improved 5-year survival compared with the conservative group (30% vs 6.2%, p = 0.003). Conclusions These data suggest that an aggressive strategy, particularly left ventricular assist device support as a bridge to heart transplantation, may improve survival in post-myocardial infarction patients with cardiogenic shock.

Impact of repetitive episodes of antibody-mediated or cellular rejection on cardiovascular mortality in cardiac transplant recipients : Defining rejection patterns

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

Report of the Psychosocial Outcomes Workgroup of the Nursing and Social Sciences Council of the International Society for Heart and Lung Transplantation: present status of research on psychosocial outcomes in cardiothoracic transplantation: review and recommendations for the field.

Abstract: Cardiothoracic transplantation's success at prolonging life--and its economic costs--must be considered relative to its psychosocial benefits and costs. Moreover, psychosocial outcomes themselves influence long-term post-transplant morbidity and mortality rates. Although psychosocial outcomes--encompassing patients' physical, psychologic and social functioning, their management of their medical regimen and global quality of life--are the focus of many recent studies, these investigations have yet to yield many evidence-based interventions that are routinely applied to improve patient outcomes. Our goals were to summarize existing work on psychosocial outcomes, delineate areas requiring attention, offer recommendations for steps to advance the field, and thereby provide an impetus for the conduct of clinical trials of interventions to improve these outcomes. We concluded that research must generally shift away from descriptive studies and toward prospective and clinical trial designs to: (a) examine a full range of risk factors and clinical sequelae of patients' psychosocial status; and (b) evaluate the effectiveness of psychosocial interventions. In addition, these issues must be considered across all cardiothoracic recipients, including not only heart recipients but the less-studied populations of lung and heart-lung recipients, and must include longer-term (5+ years) outcomes than is typical in most work. The importance of adequately sized samples to ensure statistical power, and the need to construct study samples representative of the larger cardiothoracic transplant population, cannot be overestimated. Implementing these changes in research design and substantive focus will ensure that psychosocial outcomes research will have maximum impact on transplant recipients' clinical care.