Showing papers in "Journal of Heart and Lung Transplantation in 2003"

The registry of the International Society for Heart and Lung Transplantation: twentieth official adult heart transplant report--2003.

Abstract: Although only a small number of lung and heart– lung transplantation procedures were performed between 1963 and 1973, the current eras of heart–lung and lung transplantation, which began in 1981 and 1983, respectively, are now entering their third decades. The optimism of the considerable success of these modalities has been tempered by limitations, such as the shortage of donor organs, and by problems, such as chronic allograft dysfunction. This portion of the Twentieth Official Report summarizes the current status of adult heart–lung and lung transplantation from data submitted to the Registry from centers around the world. The Registry now contains information on more than 2000 adult heart–lung recipients and almost 14,000 adult lung recipients, and provides a robust database for analysis.

Humoral rejection in cardiac transplantation: risk factors, hemodynamic consequences and relationship to transplant coronary artery disease.

Abstract: Background Acute cellular rejection is the mechanism of most immune-related injury in cardiac transplant recipients. However, antibody-mediated humoral rejection (HR) has also been implicated as an important clinical entity following orthotopic heart transplantation. Humoral rejection has been reported to play a role in graft dysfunction in the early post-transplant period, and to be a risk factor for the development of transplant coronary artery disease. Some involved in transplantation pathology doubt the existence of clinically significant humoral rejection in cardiac allografts. Those who recognize its existence disagree on its possible role in graft dysfunction or graft coronary artery disease. In this study, we report clinical features of patients with the pathologic diagnosis of HR at our institution since July 1997, when we began systematic surveillance for humoral rejection. Methods We reviewed medical records of patients with the pathologic diagnosis of HR without concurrent cellular rejection between July 1997 and January 2001. Diagnosis was based on routine histology (“swollen cells” distending capillaries, interstitial edema and hemorrhage) and immunofluorescence (capillary deposition of immunoglobulin and complement with HLA-DR positivity), or immunoperoxidase staining of paraffin-embedded tissue (numerous CD68-positive macrophages and fewer swollen endothelial cells distending capillaries). Results A total of 44 patients (4 to 74 years old) showed evidence of HR without concurrent cellular rejection at autopsy or on one or more biopsies. Although females comprised only 26% of our transplant population, 23 patients (52%) with HR were female. A positive peri-operative flow cytometry T-cell crossmatch was observed in 32% of HR patients compared with 12% of controls ( p = 0.02). Hemodynamic compromise consisting of shock, hypotension, decreased cardiac output/index and/or a rise in capillary wedge or pulmonary artery pressure was observed in 47% of patients at the time of diagnosis of HR. Six patients (5 females) died (14% mortality) with evidence of HR at or just before autopsy, 6 days to 16 months after transplantation. The incidence of transplant coronary artery disease was 10% greater at 1 year, and 36% greater at 5 years, in patients with HR when compared with non-HR patients. Conclusion Humoral rejection was associated with acute hemodynamic compromise in 47% of patients, and was the direct cause of death in 6 patients (13%). Humoral rejection is a clinicopathologic entity with a high incidence in women and is associated with acute hemodynamic compromise, accelerated transplant coronary artery disease and death.

Mechanical Circulatory Support device database of the International Society for Heart and Lung Transplantation: first annual report--2003.

Abstract: Over the last 2 decades, mechanical circulatory support devices have been developed with the goal of supporting patients with advanced heart failure as a bridge to cardiac transplantation, a bridge to recovery, and an alternative to transplantation (also called chronic or destination therapy). The current generation of devices provides a differentiated spectrum of circulatory support. The major limitations of mechanical circulatory support devices are infection, coagulopathies and device dysfunction. The Scientific Council on Mechanical Circulatory Support of the International Society for Heart and Lung Transplantation has established an international database to generate critical data to advance knowledge about the effectiveness of mechanical circulatory support device therapy for one of the most difficult and costly contemporary medical problems, the malignant syndrome of advanced heart failure.

A review of lung transplant donor acceptability criteria.

Abstract: (A consensus report from The Pulmonary Council of the International Society for Heart and Lung Transplantation)

Aspergillus infections after lung transplantation: clinical differences in type of transplant and implications for management

Abstract: Background: Invasive aspergillosis is a serious opportunistic infection in lung transplant recipients. It has not been fully discerned whether there are differences in the characteristics, risk factors and outcome of Aspergillus infection in single as compared with bilateral lung transplant recipients. Methods: English-language articles identified by a Medline search through December 2000 and bibliographies were used as data sources to identify cases of Aspergillus infections in lung transplant recipients. The studies selected had to have provided a definition of invasive aspergillosis to distinguish colonization from infection. Results: The median incidence of Aspergillus infections in lung transplant recipients was 6.2%. In total, 58% (45 of 78) of the Aspergillus infections were tracheobronchitis or bronchial anastomotic infections, 32% (25 of 78) were invasive pulmonary, and 22% (25 of 78) were disseminated infections. Single lung transplant recipients with Aspergillus infections were significantly older ( p = 0.006), more likely to have had chronic obstructive pulmonary disease as an underlying illness ( p = 0.05), more likely to have developed Aspergillus infections later after transplantation ( p = 0.019), and tended to have a higher incidence of invasive aspergillosis ( p = 0.11) than all other lung transplant recipients. Overall mortality in lung transplant recipients with Aspergillus infections was 52%. Single lung transplant recipients ( p = 0.03), and patients with late-onset infections (occurring at least 3 months after transplantation ([ p = 0.045]) infections had significantly higher mortality. Conclusions: Single lung transplant recipients with Aspergillus infections had an overall greater morbidity and poorer outcome than other types of lung transplant recipients. Recognition of the unique characteristics of Aspergillus infections in single lung (vs bilateral or heart–lung) transplant recipients has implications relevant for the management of lung transplant recipients with aspergillosis.

Living with heart failure: depression and quality of life in patients and spouses

Abstract: Background: Although spouses are a key support for patients with heart failure, and help them remain in the community, no one has studied patient-spouse pairs to determine the nature of their experience. Therefore, we conducted a study of patients and spouses to compare their levels of depression and health-related quality of life (HRQOL), and to identify factors that contribute to depression and HRQOL in patient-spouse pairs. Methods: Forty-eight couples, in which all patients were men with heart failure, were recruited from a university-affiliated, outpatient heart failure clinic. Data were collected using the Beck Depression Inventory, the 12-item Short Form (that measures physical and mental components of QOL), and the 6-minute walk test. Results: Patients with heart failure were significantly more depressed and had poorer physical quality of life compared with spouses. Patients' depression was correlated with their own functional status and mental quality of life, with the combination of 6-minute walk distance and mental QOL contributing 51% of the variance in patient depression. Spouse depression and HRQOL did not significantly influence patient depression. In contrast, spouses' depression was related to their husbands' functional status and employment, as well as their own mental QOL. The mental component of spouse QOL and the age of the patient accounted for 33% of the adjusted variance in spousal depression. Conclusions: Patients with heart failure and their spouses experience significantly different levels of depression and physical QOL. In developing interventions, it may be important to take these differences into account and focus on their unique needs as well as those issues that affect the couple together. Interventions that improve patient functional status may result in decreased depression and improved HRQOL on the part of both patients and spouses.

Post-transplantation lymphoproliferative disease in heart and heart-lung transplant recipients: 30-year experience at Stanford University.

Abstract: Background: Post-transplantation lymphoproliferative disease (PTLD) is an important source of morbidity and mortality in transplant recipients, with a reported incidence of 0.8% to 20%. Risk factors are thought to include immunosuppressive agents and viral infection. This study attempts to evaluate the impact of different immunosuppressive regimens, ganciclovir prophylaxis and other potential risk factors in the development of PTLD. Methods: We reviewed the records of 1,026 (874 heart, 152 heart–lung) patients who underwent transplantation at Stanford between 1968 and 1997. Of these, 57 heart and 8 heart–lung recipients developed PTLD. During this interval, 4 different immunosuppressive regimens were utilized sequentially. In January 1987, ganciclovir prophylaxis for cytomegalovirus serologic-positive patients was introduced. Other potential risk factors evaluated included age, gender, prior cardiac diagnoses, HLA match, rejection frequency and calcium-channel blockade. Results: No correlation of development of PTLD was found with different immunosuppression regimens consisting of azathioprine, prednisone, cyclosporine, OKT3 induction, tacrolimus and mycophenolate mofetil. A trend suggesting an influence of ganciclovir on the prevention of PTLD was not statistically significant ( p = 0.12). Recipient age and rejection frequency, as well as high-dose cyclosporine immunosuppression, were significantly ( p Conclusions: The overall incidence of PTLD was 6.3%. It was not altered by sequential modifications in treatment regimens. Younger recipient age and higher rejection frequency were associated with increased PTLD occurrence. The 15% prevalence of PTLD in 58 long-term survivors was unexpectedly high.

Late rejection episodes more than 1 year after pediatric heart transplantation: risk factors and outcomes.

Abstract: Background Little is known about late rejection episodes after pediatric heart transplantation. We determined the frequency of late rejection episodes (>1 year) after pediatric heart transplantation, defined risk factors for its occurrence, and evaluated outcome after late rejection. Methods We analyzed data from 685 pediatric recipients ( Results We followed 431 patients for >1 year (median follow-up, 32.9 months) of whom 106 (24.6%) experienced 1 or more late rejection episodes (total of 178 episodes, 27 with severe hemodynamic compromise). Probability of freedom from first late rejection was 73% at 3 years and 66% at 4 years after transplantation. Risk factors (multivariate analysis) for first late rejection were >1 episode of rejection in the first year ( p = 0.009), recipient black race ( p = 0.0002), and older age at transplantation ( p = 0.0003). Only 4 of 325 (1.2%) children who survived beyond 1 year without late rejection died compared with 26 of 106 (24.6%) with late rejection ( p Conclusions Approximately 25% of pediatric recipients in the PHTS who survived beyond 1 year experienced late rejection episodes. Late rejection is associated with poor survival, especially when associated with hemodynamic compromise. Absence of late rejection episodes is associated with very low risk of death during medium-term follow-up after pediatric heart transplantation. Determining the risk factors for late rejection will help to identify a cohort of patients who may benefit from enhanced rejection surveillance and treatment.

Perceived control reduces emotional stress in patients with heart failure.

Abstract: We studied patients with heart failure (HF) to determine if perceived control reduces emotional distress (ie, anxiety, depression and hostility) in chronic, debilitating cardiac illness and whether the demographic, clinical and psychologic characteristics of patients with high and low perceived control differed Psychological assessment of 222 patients with heart failure included an evaluation of perceived control using the Control Attitudes Scale, as well as anxiety, depression and hostility using the Multiple Affect Adjective Checklist Using multivariate analysis to control for differences in demographic and clinical characteristics, we found that patients with high perceived control had significantly greater 6-minute walk distances and less emotional distress than patients with low perceived control Interventions designed to increase perceived control may be an important aspect of HF care, but require testing in randomized trials

Retransplantation in 7,290 primary transplant patients: a 10-year multi-institutional study.

Abstract: Background Cardiac retransplantation is a controversial procedure due to the disparity between donor heart demand and supply. Methods Of 7,290 patients undergoing primary cardiac transplantation between January 1990 and December 1999 at 42 institutions contributing to the Cardiac Transplant Research Database (CTRD), 106 patients later underwent a second and 1 patient a third cardiac transplant procedure. Results The actuarial freedom from retransplantation was 99.2% and 96.8% at 1 and 10 years, respectively. Reasons for retransplantation included early graft failure ( n = 34), acute cardiac rejection ( n = 15), coronary allograft vasculopathy (CAV, n = 39), non-specific graft failure ( n = 7), and miscellaneous ( n = 10). The only risk factor associated with retransplantation was younger age, reflecting the policy of preferential retransplantation of younger patients. Survival after retransplantation was inferior to that after primary transplantation (56% and 38% at 1 and 5 years, respectively). Risk factors associated with death after retransplantation included retransplantation for acute rejection ( p = 0.0005), retransplantation for early graft failure ( p = 0.03), and use of a female donor ( p = 0.005). Survival after retransplantation for acute rejection was poorest (32% and 8% at 1 and 5 years, respectively) followed by retransplantation for early graft failure (50% and 39% at 1 and 5 years, respectively). Survival after retransplantation for CAV has steadily improved with successive eras. Conclusions The results of retransplantation for acute rejection and early graft failure are poor enough to suggest that this option is not advisable. However, retransplantation for CAV is currently associated with satisfactory survival and should continue to be offered to selected patients.

Heart transplantation in children after mechanical circulatory support with pulsatile pneumatic assist device

Abstract: Background Mechanical support with a pulsatile pneumatic ventricular assist device (VAD) is a complex rescue procedure performed in children with untreatable cardiogenic shock. Its impact on early and long-term survival after subsequent heart transplantation (HTx) remains to be determined. Methods We reviewed retrospectively the course of 95 children (median age, 8 years; range, 8 days–17 years; body weight, 24 kg; range, 3–110 kg) who underwent HTx. Group A, the elective-HTx group, consists of 33 children who were treated as outpatients before transplantation. Group B, the emergency-HTx group, has 44 children who were critically ill and hospitalized before transplantation but without ventricular assist devices, whereas Group C, the VAD-HTx group, consists of 18 children resuscitated and supported with pulsatile pneumatic VADs for a median time of 20 days. Results Overall actuarial survival after cardiac transplantation was 86% at 1 month, 82% at 1 year, and 78% at 5 years, without significant differences among the 3 sub-groups. Group A had the best long-term survival rate, 88% at 1 month, 88% at 1 year, and 80% at 5 years. Group B had a survival rate of 88% at 1 month, 82% at 1 year, and 79% at 5 years. Group C had a survival rate of 72% at 1 month, 72% at 1 year, and 72% at 5 years. We found no differences in neurologic outcome, acute cardiac rejection, or transplant failure. The survival rate was significantly better in the children with cardiomyopathy compared with those with congenital heart defects (p = 0.014). Conclusions Bridging to HTx with a pulsatile pneumatic VAD is a safe procedure in pediatric patients. After HTx, overall survival of these children is similar to that of patients who were bridged with inotropes or who were awaiting heart transplantation electively.

Use of extracorporeal life support as a bridge to pediatric cardiac transplantation

Abstract: Background Extracorporeal life support (ECLS) has been used for post-cardiotomy rescue, but its use as a bridge to heart transplantation (OHT) in patients with post-surgical or end-stage ventricular failure remains controversial. Methods Records were reviewed for patients receiving ECLS for ventricular failure from January 1991 to August 2001. Patients listed for OHT were analyzed separately. Listing for OHT requirements were improbable myocardial recovery, absence of contraindications (central nervous system damage, high pulmonary resistance, ongoing infection, etc.), and parental consent. Outcome variables included patient demographics, diagnosis, days from ECLS initiation to United Network for Organ Sharing (UNOS) listing (latency), list time, renal function, and survival to discharge. Results Of 145 patients with ventricular failure who received ECLS, 21 pediatric patients were UNOS listed. Of 124 non-listed patients, 57 (46%) survived to discharge. All but 3 survivors were separated from ECLS in ≤7 days. Twelve underwent OHT and 10 survived to discharge (list time, 6 days; median ECLS time, 14 days). Five had ECLS discontinued without undergoing OHT (1 later underwent OHT, 2 survived to discharge). Five experienced complications while receiving ECLS and died without undergoing OHT. Six of 9 patients who required dialysis for renal failure died. Of 11 infants listed, 4 were weaned from ECLS without undergoing OHT (2 survived to discharge), 5 had OHT (ECLS support, 4 days; 4 survived to discharge) and 2 died (ECLS support, 16 and 47 days). Conclusions (1) Extracorporeal life support can be used as a bridge to OHT (even among the infant population) for at least 2 weeks with acceptable survival and hospital discharge rates, and (2) renal insufficiency with the concomitant requirement for dialysis decreases the likelihood of survival before and after OHT.

Dobutamine stress echocardiography predicts myocardial improvement in patients supported by left ventricular assist devices (LVADs): hemodynamic and histologic evidence of improvement before LVAD explantation.

Abstract: Background: Cardiac function may improve in patients with end-stage heart failure who receive long-term support (>30 days) with left ventricular assist devices (LVADs). Dobutamine stress echocardiography (DSE) has been used to quantitate myocardial recovery in patients with heart failure supported with LVADs. By recording the hemodynamic response with the use of DSE, we evaluated and applied the resulting data to patients receiving LVAD support. Methods and results: The study population included 16 patients who underwent LVAD implantation, regained functional capacity on full LVAD support, and tolerated decreased mechanical support with no worsening of dyspnea or fatigue. All 16 patients underwent dobutamine stress with increasing doses of dobutamine (from 5 to 40 mcg/kg/min). Hemodynamics and 2-dimensional (2-D) echocardiography was performed at each dose level. In addition, paired myocardial samples were obtained and analyzed histologically to determine myocyte size and collagen content. Dobutamine stress separated the study population into 2 groups: those who had favorable responses to dobutamine (9/16) and those who had unfavorable responses (i.e., experienced hemodynamic deterioration; 7/16). Favorable dobutamine responses were characterized by improved cardiac index, improved force-frequency relationship in the left ventricle (dP/dt), improved left ventricular ejection fraction, and decreased left ventricular end-diastolic dimension. All 9 favorable responders underwent LVAD explantation, and 6 survived for more than 12 months. In all patients studied, LVAD support resulted in decreased myocyte size ( n = 14, 33.9 ± 0.9 μm before vs 16.6 ± 0.8 μm after support, p = 0.0001; normal, 5–15 μm) but resulted in no consistent changes in collagen content. Conclusions: Dobutamine stress echocardiography with hemodynamic assessment may be a useful tool in assessing physiologic improvement in myocardial function of patients with end-stage heart failure who receive LVAD support. It may help predict which patients can tolerate LVAD removal. Prospective analysis of cardiac function is now warranted to better define myocardial recovery in patients supported with LVADs.

Clinical features and outcomes of paramyxoviral infection in lung transplant recipients treated with ribavirin.

Abstract: Background: Paramyxoviral infections are reported in 6% to 21% of lung transplant recipients. Aerosolized ribavirin is used to treat paramyoxviral infections, but data on outcomes of this treatment in lung transplant patients are limited. Methods: Lung recipients treated with aerosolized ribavirin from 1992 through 2000 for pulmonary respiratory syncytial virus (RSV) or parainfluenza virus (PIV) infection were assessed for the following variables: age; gender; underlying diagnosis; time from transplantation; duration of illness; clinical symptoms; and change from baseline FEV 1 (forced expiratory volume in 1 second). Outcomes included FEV 1 values at 30 and 90 days, need for intubation, development of acute rejection or obliterative bronchiolitis (OB) in the year after treatment; and 90-day and overall mortality. Results: Fifteen patients received ribavirin for a median of 5 days (range 3 to 7) for 17 episodes of RSV ( n = 12) or PIV ( n = 5) infection. The clinical presentations of RSV and PIV infection were similar. Infection occurred a median of 520 days (range 7 to 1,700) after transplantation. Three episodes required intubation; 2 episodes were fatal accounting for a 90-day mortality per episode of 12%. The FEV 1 at presentation declined by 25% (range 4% to 44%) from baseline. In 3 patients the FEV 1 did not return to baseline by 90 days or thereafter. All 3 patients had underlying pulmonary fibrosis (IPF) vs no IPF in 0 of 9 evaluable patients who recovered ( p = 0.009). There was no correlation between response to ribavirin and subsequent development of OB. Conclusions: About 33% of lung transplant patients with lower respiratory tract paramyxoviral infections who were treated with inhaled ribavirin died or did not return to baseline FEV 1 . This effect was acute and not associated with later complications, including OB. Underlying IPF may be a risk factor for failure to return to baseline. Larger, prospective, multicenter studies are required to confirm these findings.

Pediatric arteriovenous extracorporeal membrane oxygenation (ECMO) as a bridge to cardiac transplantation.

Abstract: Background: Since 1990, extracorporeal membrane oxygenation (ECMO) has been used as a bridge to cardiac transplantation in 47 patients. Methods: A review of the ECMO database, approved by the Arkansas Children's Hospital institutional review board, forms the basis of this report. We made statistical comparison using Fisher's exact probability testing. The ECMO circuitry was a roller occlusion pump with computer-assisted perfusion system technology. Results: Thirty-two (68%) patients underwent transcatheter septostomy for cardiac decompression. Diagnosis at presentation was either congenital heart disease (CHD, n = 15) or cardiomyopathy ( n = 32). Ages ranged from 1 day to 22 years old (median, 18 months old), and weight ranged from 2.9 to 100 kg (median, 10 kg). The average duration of support was 242 hours (range, 22–1,078 hours). Overall long-term survival was 47%, with 16 (34%) patients successfully bridged to cardiac transplantation (of which 9 [56%] survived) and 13 (28%) successfully weaned from ECMO. Patients undergoing ECMO after cardiotomy had 31% survival. Survival was improved significantly ( p p Conclusions: Patients with cardiomyopathy has a better prognosis than did those with CHD when using ECMO as a bridge to transplantation or survival. Complications are significant and increase with the duration of support. Extracorporeal membrane oxygenation for salvage and subsequent transplantation in this high-risk group of patients requires critical review. Alternative support options must be developed in the pediatric population that will allow improved outcomes, comparable with outcomes achieved in the adult population.

Temporal changes in left ventricular systolic function in heart donors: results of serial echocardiography.

Abstract: Background: Heart donor availability continues to limit cardiac transplantation rates and many donor hearts are not transplanted because of left ventricular dysfunction. The aim of this study was to determine whether intensive donor management results in improved left ventricular systolic function as measured by serial echocardiography. Methods: Using the California Transplant Donor Network Database, all donors who underwent serial echocardiography during donor management (from 1996 to 2000) were identified. The study includes those donors with ejection fractions Results: In 13 of 16 subjects, initial ejection fractions were Conclusions: This pilot study indicates that in some cases, intensive donor management is associated with improved donor left ventricular function. Prospective studies are indicated to determine the predictors of improved donor left ventricular dysfunction and of recipient survival when sub-optimal hearts are transplanted.

Tricuspid Regurgitation After Cardiac Transplantation: How Many Biopsies Are Too Many?

Abstract: Background Tricuspid regurgitation (TR) is common in patients after orthotopic cardiac transplantation (OHT). Endomyocardial biopsy (EMB) used to monitor for rejection may be a cause of TR. The purpose of this study was to identify a correlation between the severity of TR and the number of EMBs. Methods We studied 101 patients with OHT at our institution between May 1987 and August 2001. The number of EMBs performed in each patient was determined. Data on technique of anastomosis, liver and renal function, ejection fraction, and pulmonary artery pressure were also extracted. Echocardiography reports were reviewed to determine the presence and severity of TR. Symptoms of right heart failure were assessed by the amount of diuretic intake. Results Twenty-five (25%) of 101 patients had evidence of severe TR, whereas 76 (75%) had non-severe TR. Multivariate analysis identified EMB as the only independent predictor of the severity of TR ( p Conclusions The development of TR after OHT is in large part due to EMBs used to monitor for rejection. There is a direct correlation between the number of EMBs and the severity of TR. We suggest a cutoff of less than 31 EMBs to reduce the risk of severe TR.

Resistance exercise training and alendronate reverse Glucocorticoid-Induced osteoporosis in heart transplant recipients

Abstract: Background: Immunosuppression therapy with bolus glucocorticoids causes regional osteoporosis in the axial skeleton of heart transplant recipients (HTR). No preventive strategy is generally accepted for steroid-induced bone loss. Methods: To determine the efficacy of an anti-osteoporosis regimen that combined a bisphosphonate agent (alendronate sodium) with the osteogenic stimulus of mechanical loading, 25 HTRs were randomly assigned either to a group that received alendronate (10 mg/day) for 6 months (ALEN; n = 8), a group that received alendronate (10 mg/day) and performed specific resistance exercises for 6 months (ALEN + TRN; n = 8) or to a non-intervention control group (CONTR; n = 9). Alendronate was initiated at 2 months after transplantation. Bone mineral density (BMD) of the total body, femur neck and lumbar spine (L-2 and L-3) was measured by dual-energy X-ray absorptiometry before and 2, 5 and 8 months after transplantation. Resistance training consisted of lumbar extension exercise (MedX) performed 1 day/week and 8 variable resistance exercises (MedX) performed 2 days/week. Results: Pre-transplantation BMD values did not differ among the 3 groups. BMD of the total body, femur neck and lumbar vertebra were significantly decreased below baseline at 2 months after transplantation in CONTR (−2.6 ± 0.9%, −5.1 ± 1.8%, −12.5 ± 4.2%, respectively), ALEN (−2.8 ± 0.8%, −5.3 ± 1.6%, −12.0 ± 3.9%) and ALEN + TRN groups (−2.7 ± 1.0%, −5.6 ± 2.1%, −11.2 ± 3.7%). CONTR had further significant losses of BMD after 3 and 6 months. ALEN had no further regional BMD losses after initiation of alendronate therapy. ALEN + TRN restored BMD of the whole body, femur neck and lumbar vertebra to within 0.9%, 2.1%, and 3.4% of pre-transplantation levels, respectively. Conclusions: Resistance exercise plus alendronate was more efficacious than alendronate alone in restoring BMD in HTRs. Our results indicate that anti-osteoporosis therapy in this population should include both an anti-resorptive agent as well as an osteogenic stimulus, such as mechanical loading.

The registry of the International Society for Heart and Lung Transplantation: introduction to the Twentieth Annual Reports--2003.

Abstract: We are pleased to present the Twentieth Annual Reports of the Scientific Registry of the International Society for Heart and Lung Transplantation (the Registry). The mission of the Registry is to advance the state of knowledge and patient care regarding therapies for the failing heart and lung by: analyzing outcomes and treatment modalities for advanced heart and lung failure and transplantation; serving as a resource for health-care providers, governmental agencies, patient-related organizations and pharmaceutical companies seeking information regarding patient care and outcomes; and providing benchmark aggregate data for use by individual centers to assess their center-specific practices and outcomes. For the first time, all of the Registry reports are being published in a single issue of this journal; these include reports on the Adult Heart, Adult Lung and Heart–Lung, Pediatric Heart and Lung, and Mechanical Circulatory Support Device (MCSD) Database. The Registry remains the world’s most comprehensive record of heart and lung transplant activity, practices and outcomes. At present, the Registry contains data regarding 62,851 heart transplants, 2,955 heart–lung transplants and 15,199 lung transplants. More than 220 centers from 24 countries submit data to the Registry (Appendix), and participation in the Registry is open to any center in the world performing heart or lung transplantation. We wish to extend our sincere thanks to the many thoracic transplant surgeons, physicians and data coordinators in transplant programs throughout the world, whose timely and accurate submission of data has made these analyses possible. In what follows, we relate information regarding progress made toward reaching our 2002–2003 goals: (1) increasing worldwide heart and lung transplant reporting; (2) initiation of the MCSD Database; and (3) facilitation of access to data for clinical inquiries and research projects.

Multi-organ transplantation: Is there a protective effect against acute and chronic rejection?

Abstract: Background Heart–lung transplantation (Tx) is known to offer a protective effect against acute cardiac rejection. This study was undertaken to evaluate acute and chronic heart and/or lung rejection in the setting of multiple-transplanted organs from the same donor compared with single-organ transplantation. Methods Acute (treated rejection episodes of heart or lungs) and chronic (allograft vasculopathy in hearts and bronchiolitis obliterans syndrome [BOS] in lungs) rejection events were analyzed in 348 heart transplant (H) recipients, 24 heart–lung (HL) recipients, 82 double-lung (L) recipients and 8 heart–kidney (HK) recipients >18 years of age, who were transplanted between 1990 and 2002. Results Survival at 3 years differed among groups as follows: HK, 100%; H, 82%; HL, 74%; and L, 70%. The probability of acute rejection within the first 3 months was higher in H recipients than in HL (81% vs 22%; p p = 0.00009) recipients. Acute cardiac rejection occurred more frequently during the first 2 years in isolated H recipients compared with HL (2.8 vs 0.27 episodes; p p p = 0.02) recipients. Chronic cardiac rejection (allograft vasculopathy) was more likely within 3 years after H compared with HL (32% vs 16%; p = 0.04) or HK (32% vs 0%; p = 0.14). The onset of chronic lung rejection (BOS) within 3 years was similar in HL and L recipients (39% vs 40%; p = 0.9). Conclusions Recipients of multiple organs from a single donor undergo less acute rejection of the heart or lungs compared with isolated heart or lung transplant recipients. Cardiac allograft vasculopathy is decreased significantly when cardiac transplantation is combined with a lung allograft. A lower incidence of cardiac allograft vasculopathy is observed when cardiac transplantation is combined with a renal allograft, and may prove statistically significant when more cases have been accumulated. These phenomena may result from immune modulation of the recipient by simultaneous transplant of disparate tissues or introduction of immune-modulating hematopoietic elements.

Acute and chronic pleural complications in lung transplantation.

Abstract: Background Lung transplant recipients may have pleural complications. However, the influence of these complications on the prognosis is not well known. Methods We analyzed pleural complications and clinical and radiologic data from 100 patients who underwent lung transplantation in a general hospital in a 9-year period. Pre-operative evaluation, surgical protocol, immunosuppressive regimen, and follow-up were carried out systematically. Chest computerized tomography (CT) was performed at 3 and 12 months after transplantation. Results All patients had early post-operative pleural effusion ipsilateral to the graft, which required drainage for a mean of 19.3 days (range, 5–52 days). Thirty-four patients had 43 acute pleural complications: 15 hemothoraxes, 10 persistent air leaks, 8 pneumothoraxes, 7 transient air leaks, and 3 empyemas. Multivariate analysis showed hemothorax and persistent air leak were associated with increased post-operative mortality (p = 0.024, p = 0.011, respectively). Post-operative mortality was not associated with any pre-transplant variable. Chest CT findings at 3 months revealed ≥1 pleural alteration in 58 of 70 patients (83%): 34 post-operative residual ipsilateral pleural effusions; 36 pleural thickenings; and 3 residual pneumothoraxes, 1 with a coexisting bronchial dehiscence. Chest CT at 12 months showed pleural alterations in 50 of 58 patients (86%): pleural thickening in 48, calcification in 4, and residual pleural effusion in 4. Conclusions Pleural complications are common in lung transplant recipients. Hemothorax and persistent air leak are associated with increased post-operative mortality. Chest CT showed pleural alterations in most patients 12 months after transplantation.

Timing of cardiac transplantation in patients with heart failure receiving β-adrenergic blockers ☆

Abstract: Background: Previous work shows that patients with heart failure patients who have peak oxygen consumption (Vo2 peak) >14 ml/kg/min do not derive a survival benefit from cardiac transplantation. However, this was shown before β-blocker therapy for patients with systolic heart failure became common, and β-blockers improve survival in patients with heart failure without changing Vo 2 peak. Our purpose was to re-evaluate the utility of Vo 2 peak >14 ml/kg/min as an indicator of the need for cardiac transplantation in patients with heart failure who are taking β-blockers. Methods: Actuarial, hemodynamic, and exercise ventilatory data were collected from 540 patients with heart failure, 256 of whom were taking β-blockers. We tracked death and cardiac transplantation. We stratified the percentage of patients event-free 1 and 3 years after Vo 2 peak study by their Vo 2 peak and β-blocker status, and compared 1- and 3-year post-transplant survival (United Network of Organ Sharing [UNOS] data). We also compared total mortality for the patients with heart failure as stratified by β-blocker stats and Vo 2 peak (excluding the 42 who underwent transplantation) with UNOS post-transplant survival. Results: Patients with heart failure who were receiving β-blockers and whose Vo 2 peak was ≥12 ml/kg/min had greater 1- and 3-year event-free survival rates (95% confidence intervals, 92.6%–96.6% and 85.8%–96.0%) than did post-transplant patients (83.9%–86.3% and 75.4%–76.6%). However, in patients with heart failure not taking β-blockers, Vo 2 peak Conclusions: Patients with heart failure who are receiving β-blockers do not derive a survival advantage at 1 and 3 years after cardiac transplantation if Vo 2 peak is ≥12 ml/kg/min. Patients not taking β-blockers whose Vo 2 peak is

Total artificial heart bridge to transplantation: a 9-year experience with 62 patients.

Abstract: Background The SynCardia CardioWest total artificial heart (CardioWest TAH) is a biventricular, orthotopic, pneumatic, pulsatile blood pump driven by an external console. For each ventricle, the length of the blood-flow path is shorter and the inflow and outflow valves are larger than in any other bridge-to-transplant device, resulting in greater blood flow at smaller pre-load. Such a device should be optimal for bridging transplant candidates who have biventricular failure and for whom all other therapies have failed. Methods From January 1, 1993, to April 1, 2002, we prospectively studied 62 consecutive CardioWest TAH implant recipients to document safety and efficacy in bridge to transplantation. We used multisystem monitoring and multidrug therapy for anti-coagulation in 58 patients starting September 1, 1994. Results Before implantation, patients were critically ill with biventricular heart failure. Mortality in this group from the time of implantation until transplantation was 23%. Causes of death during device support included multi-organ failure (6), sepsis (3), and valve entrapment (2). Forty-eight patients underwent transplantation (77%). Forty-two survived to hospital discharge (68% of the total, 88% of those undergoing transplantation). Adverse events included bleeding (20%), device malfunction (5%), fit complications (3%), mediastinal infections (5%), visceral embolus (1.6%), and stroke during support (1.6%). The linearized stroke rate was 0.068 events per patient-year. Conclusions Sixty-eight percent of critically ill transplant candidates for whom medical therapy failed were bridged to transplantation with the CardioWest TAH and survived long-term. Most deaths that occurred during device support were related to pre-implant problems. Infection and stroke were rare events. Therefore, we recommend the CardioWest TAH as the biventricular bridge-to-transplant device of choice.

Bridge to transplantation with the Jarvik-7 (CardioWest) total artificial heart: a single-center 15-year experience.

Abstract: Background At our institution, the total artificial heart (TAH) Jarvik-7 (CardioWest) has been used since 1986 as a bridge to transplantation for the most severely ill patients with terminal congestive heart failure. Methods: Between 1986 and 2001, 127 patients (108 males, mean age 38 ± 13) were bridged to transplantation with the Jarvik-7 TAH. All were in terminal biventricular failure despite high-dose inotropic support. Nine patients had a body surface area (BSA) of 2 . In Group I patients (78%), the etiology of cardiac failure was dilated cardiomyopathy, either idiopathic ( n = 60) or ischemic ( n = 38). The other 29 patients (Group II) had disease of miscellaneous origin. We analyzed our experience with regard to 3 time periods: 1986 to 1992 ( n = 63); 1993 to 1997 ( n = 36); and 1998 to 2001 ( n = 33). Results Although Group II patients represented 30% of indications before 1992, they comprised only 15% during the 2 subsequent periods. Duration of support for transplant patients increased dramatically after 1997, reaching 2 months for the most recent period (5 to 271 days). In Group I, the percentage of transplanted patients increased from 43% before 1993 to 55% between 1993 and 1997, and reached 74% thereafter. The major cause of death was multiorgan failure (67%). The clinical thromboembolic event rate was particularly low with no instance of cerebrovascular accident and 2 transient ischemic attacks. Total bleeding complication rate was 26%, including 2 deaths related to intractable hemorrhage and 2 others related to atrial tamponade. The cumulative experience was 3,606 total implant days with only 1 instance of mechanical dysfunction. Conclusions TAH is a safe and efficient bridge for patients with terminal congestive heart failure awaiting cardiac transplantation.

LVAD bloodstream infections: therapeutic rationale for transplantation after LVAD infection

Abstract: Introduction Patients who have ventricular assist devices (VADs) and experience bloodstream infection (BSI) have high mortality. We addressed 2 questions raised by the United Network for Organ Sharing (UNOS) priority policy for this problem: 1) Are organs wasted on this ultra-high-risk group? 2) Can device-related BSI be differentiated from transient BSI? Methods Patients with VADs who underwent heart transplantation from 1987 to 2001, who had BSI during VAD support, and who had positive cultures at VAD explant (device-related BSI, n = 10) were compared with those with negative cultures at explant (non–device-related BSI, n = 11). Results Patients with device-related BSI had an 80% (8/10) rate of persistent bacteremia; 30 days and 1 year after transplantation, mortality was 14% and 26%, respectively. Non–device-related BSI ( n = 11) persisted in 18% (2/11); peri-operative and 1-year mortalities were 9% and 13%. Duration of VAD support predicted infection (132 vs 48 days, p p Conclusions These data suggest that urgent (Status 1A) cardiac transplantation is effective in stable patients with device-related BSI, and these data support the current UNOS policy. However, an extra-device source of BSI should be excluded by considering the isolated organism, the baseline nutritional status, and other risk factors.

Psychosocial vulnerability, physical symptoms and physical impairment after lung and heart–lung transplantation

Abstract: Background Many lung and heart–lung transplant recipients experience distressing physical symptoms and elevated physical impairment levels. Although post-transplant complications and secondary illnesses may largely account for these health limitations, patients’ psychosocial well-being may influence them as well. We examined the contribution of psychosocial variables to patients’ experience of physical symptoms and physical impairment. Methods The study consisted of a cross-sectional sample of 50 patients (36 lung, 14 heart–lung) at between 2 and 17 months post-transplant. They were interviewed to assess physical symptoms, current physical impairment and psychosocial well-being in the areas of mental health, sense of mastery and coping. Medical record reviews established the presence of medical complications and secondary illnesses concurrent with the interviews. Descriptive analyses examined the range of symptoms and levels of physical impairment experienced. Bivariate analyses and multivariate linear regression examined relationships between key variables. Results Average number of physical symptoms and level of physical impairment met or exceeded levels reported in other transplant samples. Elevated depressive and anxiety symptoms, a low sense of mastery, and the presence of concurrent medical complications were each associated with increased number of physical symptoms and physical impairment level. When the impact of concurrent medical complications was controlled, recipients with elevated psychologic distress remained significantly more likely to report more physical symptoms and higher physical impairment levels. Conclusions Patients’ physical health status may be influenced by many factors. To the extent that psychologic distress increases the likelihood of perceived physical limitations, timely identification and treatment of distress may help to maximize quality of life after lung and heart–lung transplantation.

Acquired commissural fusion of aortic valves in patients with left ventricular assist devices.

Abstract: Background Left ventricular assist devices (LVADs) currently are used as bridges for patients who deteriorate clinically while awaiting cardiac transplantation. At the time of transplantation or subsequent death, we can assess the effect of long-term device implantation on cardiac structural changes. We have noted, in our years of experience, that aortic valve commissures may fuse in patients supported by LVADs. These observations may be important in the use of these pumps as long-term destination therapy. Methods We examined 33 hearts (both explants and autopsy specimens) from patients supported either with vented-electric (VE) HeartMates ( n = 21) or with implantable pneumatic HeartMates ( n = 12). We noted commissures involved, fusion length (mm), duration of LVAD support, and type of LVAD. As controls, we examined 49 explanted hearts from patients with heart failure who were not supported by LVADs. Results We found commissural fusion in 17 of the 33 hearts. Of those 17 hearts, 4 (23.5%) had 2 commissural fusions, and 13 (76.5%) had only 1 fusion. Fusion length ranged from 5 mm to 17 mm (mean, 9.9 mm). The lesion was more common in patients fitted with VE HeartMates (p ). We found small amounts of commissural fusion in 8 of the 49 control hearts . Conclusions Acquired commissural fusion is common in patients supported by LVADs, particularly the VE HeartMate. The lesion also occurs occasionally in failing hearts of patients not supported by LVADs. The significance of the lesion in patients who require long-term LVAD support either as a bridge to transplantation or as destination therapy is unclear.

Interleukin-17 stimulates release of interleukin-8 by human airway smooth muscle cells in vitro: a potential role for interleukin-17 and airway smooth muscle cells in bronchiolitis obliterans syndrome.

Abstract: Bronchiolitis obliterans syndrome is the major constraint on the long-term survival after lung transplantation. Both neutrophils and interleukin (IL)-8, a potent neutrophil attractant, have been shown to play an important role in the pathophysiology of obliterative bronchiolitis. We investigated the potential role of human airway smooth muscle cells in obliterative bronchiolitis by studying their release of IL-8 after stimulation with IL-17, a novel T-cell-derived chemokine capable of attracting and activating neutrophils. We demonstrated a significant increase in IL-8 release, reaching a concentration of 86.6 ng/ml (SEM 1.9 ng/ml) with 100 ng/ml IL-17 (p < 0.01, n = 4), as compared with non-stimulated cells. This IL-17-mediated IL-8 release could not be inhibited by dexamethasone. We conclude that human airway smooth muscle cells may play an important pro-inflammatory role in neutrophilic inflammatory diseases such as chronic rejection after lung transplantation; furthermore, IL-17 may be the link between lymphocytes and neutrophils.

Increased expression of extracellular matrix regulators TIMP1 and MMP1 in deteriorating heart failure

Abstract: Background: The authors previously identified and compared alterations in gene expression in the myocardia of patients with deteriorating heart failure who underwent left ventricular assist device (LVAD) implantation with those of patients with stable end-stage failure (ESF). We hypothesized that matrix metalloproteinases (MMPs) and their endogenous inhibitors, the tissue inhibitors of MMPs (TIMPs), would be implicated in the mechanisms that underlie deteriorating heart failure. Methods: Gridded macro-array filters were used to provide a broad overview of MMP and TIMP mRNA expression in heart failure. Precise mRNA levels of TIMP1, MMP1, and β-spectrin were determined using quantitative real-time reverse-transcription polymerase chain reaction (RT-PCR) of myocardial samples from 27 patients with deteriorating heart failure who underwent LVAD implantation, from 17 patients with stable ESF who underwent elective heart transplantation, and from 28 donor organs with good hemodynamic function. Results: Gridded macro-arrays analysis of pooled failing heart samples determined that TIMP1 mRNA was the most readily detectable TIMP in failing myocardium. Quantitative RT-PCR showed that expression levels in individual patients were similar in patients with stable ESF (1.00 ± 0.24, n = 17) and in donor organ samples (1.49 ± 0.22, n = 28) but were significantly increased in the deteriorating heart failure group (5.38 ± 0.32, n = 26, p n = 27, p Conclusions: Patients with deteriorating heart failure have increased expression of TIMP1 and MMP1 mRNA. Correlation with pro-inflammatory cytokines suggests common pathways of regulation and potential activation by IL-6 and IL1-β.