Rituximab in recurrent idiopathic giant cell myocarditis after heart transplantation: a potential therapeutic approach

Giant cell myocarditis (GCM) is a very aggressive form of myocardial inflammation. While immunosuppressive therapy is usually able to keep under control the disease and prolong the average transplant‐free survival in many patients, effective therapeutic strategies to prevent or treat the recurrence of GCM in transplanted organs are still to be defined. We report the case of a young woman with idiopathic GCM who, despite immediate aggressive immunosuppressive therapy, rapidly progressed to irreversible heart failure and required urgent heart transplantation. Yet, 2 months later, the disease recurred in the transplanted heart, despite an intensive four‐drug antirejection regimen. The introduction of rituximab, an anti‐CD20 monoclonal antibody, 375 mg/m²/week i.v. for four consecutive weeks and then every 4 months as maintenance therapy, determined a complete and steady clinical remission of the disease. After nineteen months since rituximab administration, the patient is doing well and repeated follow‐up endo‐myocardial biopsies confirmed the complete resolution of myocardial inflammation. Our experience seems to suggest that rituximab can be a reasonably effective and safe therapeutic option in GCM recurring in transplanted organs.     

Heart Transplantation for Giant Cell Myocarditis: A Case Series

BackgroundGiant cell myocarditis (GCM) has a poor prognosis without heart transplant, but post-transplant survival is unknown.PurposeTo describe the post-transplant survival of patients with GCM at a large transplant center.MethodsSeven patients underwent heart transplant for histologically confirmed GCM of the explanted heart. The median age was 59 years, and 43% (3 of 7) were female. All patients had cardiogenic shock, multiorgan failure, elevated troponin, and recurrent ventricular tachycardia, and some required mechanical circulatory support. All patients received rabbit antithymocyte globulin (rATG) in the perioperative period at a dose of 1.5 mg/kg daily for 1 to 5 days and 4 received intravenous immunoglobulin 1 g/kg daily for 2 days after rATG. All patients had early initiation of tacrolimus by first to third postoperative day depending on renal function, early mycophenolate, and high dose steroid. All were maintained using tacrolimus, mycophenolate, and prednisone.ResultsOne patient had asymptomatic recurrence of GCM at 3 months, managed by up-titration of tacrolimus, and had asymptomatic 2R cellular rejection at 4 months, managed with steroid bolus. No patient had high-grade rejection. One patient died at 267 days, possibly of GCM. Six of 7 (86%) remain alive at a median of 842 days (2.3 years) post transplant.ConclusionsPatients with GCM have excellent post-transplant survival with use of rATG and triple drug immunosuppressive therapy; however, some patients remain at risk for GCM recurrence after transplant, which may respond to augmented immunosuppression.     

Acute myocarditis supported by extracorporeal membrane oxygenation successfully bridged to transplantation: a giant cell myocarditis

Giant cell myocarditis is a rare and fatal heart disease in previously healthy young patients. We report the case of a 43-year-old patient presenting unstable acute congestive heart failure as a consequence of myocarditis who was supported for four days by an extracorporeal membrane oxygenation. While no cardiac recovery was observed and no viral and autoimmune causes of myocarditis were found, he underwent successful orthotopic heart transplantation in emergency. Giant cell myocarditis was diagnosed on the explanted heart. The patient has been on a triple-immunosuppression therapy with no signs of recurrence of the disease or rejection 16 months after surgery. This experience is compared with published cases and implication of diagnosis and treatment are discussed.     

Long-term follow-up of Thoratec ventricular assist device bridge-to-recovery patients successfully removed from support after recovery of ventricular function.

BACKGROUND: In certain forms of severe heart failure there is sufficient improvement in cardiac function during ventricular assist device (VAD) support to allow removal of the device. However, it is critical to know whether there is sustained recovery of the heart and long-term patient survival if VAD bridging to recovery is to be considered over the option of transplantation. METHODS: To determine long-term outcome of survivors of VAD bridge-to-recovery procedures, we retrospectively evaluated 22 patients with non-ischemic heart failure successfully weaned from the Thoratec left ventricular assist device (LVAD) or biventricular assist device (BVAD) after recovery of ventricular function at 14 medical centers. All patients were in imminent risk of dying and were selected for VAD support using standard bridge-to-transplant requirements. There were 12 females and 10 males with an average age of 32 (range, 12-49). The etiologies were 12 with myocarditis, 7 with cardiomyopathies (4 post-partum [PPCM], 1 viral [VCM], and 2 idiopathic [IDCM]), and 3 with a combination of myocarditis and cardiomyopathy. BVADs were used in 13 patients and isolated LVADs in 9 patients, for an average duration of 57 days (range, 11-190 days), before return of ventricular function and successful weaning from the device. Post-VAD survival was compared with 43 VAD bridge-to-transplant patients with the same etiologies who underwent cardiac transplantation instead of device weaning. RESULTS: Nineteen of the 22 patients are currently alive. Three patients required heart transplantation, 1 within 1 day, 2 at 12 and 13 months post-weaning, and 2 died at 2.5 and 6 months. The remaining 17 patients are alive with their native hearts after an average of 3.2 years (range, 1.2-10 years). The actuarial survival of native hearts (transplant-free survival) post-VAD support is 86% at 1 year and 77% at 5 years, which was not significantly different (p = 0.94) from that of post-VAD transplanted patients, also at 86% and 77%, respectively. CONCLUSIONS: Long-term survival for bridge-to-recovery with VADs for acute cardiomyopathies and myocarditis is equivalent to that for cardiac transplantation. Recovery of the native heart, which can take weeks to months of VAD support, is the most desirable clinical outcome and should be actively sought, with transplantation used only after recovery of ventricular function has been ruled out.     

Case Series: Recurrence of Cardiac Sarcoidosis After Orthotopic Heart Transplantation

Orthotopic heart transplantation for cardiac sarcoidosis (CS) is becoming increasingly common. Historically, there have been concerns regarding disease recurrence within the allograft. Although rarely reported in the literature, cases of recurrent CS tend to be observed in patients after dose reduction of immunosuppressive therapy and cessation of corticosteroids. Here, we present 2 cases of recurrent CS after orthotopic heart transplantation, confirmed on endomyocardial biopsy. Case 1 reports a 50-year-old man with a fulminant course of giant cell myocarditis who developed allograft recurrence with granulomas 5 years after transplantation despite maintenance corticosteroid therapy. Case 2 reports a 47-year-old man with CS who developed recurrence with the presence of giant cells 2 years after transplantation, with a benign clinical course. With these cases, we demonstrate the clinical overlap between CS and giant cell myocarditis and highlight the spectrum of the disease process. We also demonstrate that CS can recur despite corticosteroid maintenance therapy.     

Giant cell myocarditis: clinical presentation, bridge to transplantation with mechanical circulatory support, and long-term outcome.

BACKGROUND: The multicenter Giant Cell Myocarditis Registry recorded 64 cases from 36 centers before 1996. The median transplant-free survival of 30 patients without immunosuppression was 3 months. Of 34 patients who received heart transplantations, 9 experienced recurrence of giant cell myocarditis in their transplanted hearts and 1 patient died. METHODS: We reviewed our experience in 340 heart transplantations since 1984. Unexpected giant cell myocarditis was found in the explanted hearts of 7 patients (6 men and 1 female, aged 18-65 years). RESULTS: The duration from the onset of symptoms to assist-device implant or transplantation ranged from 11 days to 9 years, whereas the time interval from referral or deterioration ranged from 2 days to 4 months. Four patients required mechanical circulatory support before surgery (total artificial hearts in 2 and left ventricular assist devices in 2), and 3 patients required inotropic drugs. Six patients are alive with no sign of recurrent giant cell myocarditis at 12 to 113 months after surgery. One patient died suddenly 75 months after surgery, and autopsy showed severe graft vascular disease with no recurrence of giant cell myocarditis. Surveillance, right ventricular endomyocardial biopsy specimens showed recurrent asymptomatic giant cell myocarditis in 3 patients at 5 to 13 months after surgery, and found recurrence in 1 patient 30 months after surgery. This patient received augmented immunosuppression. CONCLUSIONS: Giant cell myocarditis often is not diagnosed before transplantation. It can present as dilated cardiomyopathy with late deterioration, or it can present with rapid hemodynamic deterioration. In our experience, these patients can be bridged successfully to transplant with mechanical circulatory assist. Giant cell myocarditis may recur after transplantation but may respond to augmented immunosuppression.     

Mechanical bridge with extracorporeal membrane oxygenation and ventricular assist device to heart transplantation

The aim of this study was to evaluate the effect of double bridges with extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VADs) in clinical heart transplantation. Between May 1994 and October 2000, 134 patients underwent heart transplantation at the National Taiwan University Hospital. Ten patients received ECMO or VAD support as bridges to transplantation. The ages ranged from 3 to 63 years. The indications included cardiac arrest under cardiopulmonary resuscitation in 2 and profound cardiogenic shock refractory to conventional therapy in 8 patients. Usually ECMO was first set up as rescue therapy. If ECMO could not be weaned off after short-term (usually 1 week) support, suitable VADs (HeartMate or Thoratec VAD) were implanted for medium-term or long-term support. Five patients received ECMO support as emergency rescue for 2 to 9 days, and then moved to Thoratec VAD for 8, 49, and 55 days, respectively, or centrifugal VAD for 31 days, or HeartMate VAD for 224 days. They all survived. The survival rate of double bridges with ECMO and VAD was 100%. In postcardiotomy cardiogenic shock, circulatory collapse from acute myocardial infarction or myocarditis, ECMO is the device of choice for short-term support. If heart transplantation is indicated, VADs should replace ECMO for their superiority as a bridge to heart transplantation. Our preliminary data of double bridges with ECMO and VAD revealed good results and were reliable and effective bridges to transplantation.     

Cardiac transplantation using extended-donor criteria organs for systemic amyloidosis complicated by heart failure

BACKGROUND: Systemic amyloidosis complicated by heart failure is associated with high cardiovascular morbidity and mortality. Heart transplantation for patients with systemic amyloidosis is controversial due to recurrence of disease in the transplanted organ or progression of disease in other organs. METHODS: All patients with systemic amyloidosis and heart failure referred for heart transplant evaluation from 1997 to 2004 were included in this retrospective cohort analysis. An interdisciplinary protocol for cardiac transplantation using extended-donor criteria organs, followed in 6 months by either high-dose chemotherapy and stem cell transplantation for patients with primary (AL) or by orthotopic liver transplantation for familial (ATTR) amyloidosis, was developed. Survival of the transplanted amyloid cohort was compared to survival of those amyloid patients not transplanted and to patients transplanted for other indications. RESULTS: A total of 25 patients with systemic amyloidosis and heart failure were included in the study; 12 patients received heart transplants. Amyloid heart transplant recipients were more likely female (58% vs. 8%, P=0.02) and had lower serum creatinine (1.3+/-0.5 vs. 2.0+/-0.7 mg/dL, P=0.01) than nontransplanted amyloid patients. Survival at 1-year after heart transplant evaluation was higher among transplanted patients (75% vs. 23%) compared to patients not transplanted (P=0.001). Short-term survival posttransplant did not differ between transplanted amyloid patients and contemporaneous standard and extended-donor criteria heart transplant patients (P=0.65). CONCLUSIONS: Cardiac transplantation for amyloid patients with extended-donor criteria organs followed by either stem cell or liver transplantation is associated with improved survival compared to patients not transplanted. Short- to intermediate-term survival is similar to patients receiving heart transplantation for other indications. This clinical management strategy provides cardiac amyloid patients a novel therapeutic option.     

Intermediate and long-term results after pediatric heart transplantation: incidence and role of pretransplant diagnosis

Abstract From November 1985 to 31 July 1997, 65 pediatric patients underwent heart transplantation at Bambino Gesù Hospital in Rome. Two of them underwent retransplantation, both 6 years after the first transplant. The 67 transplant patients had a mean age of 59 months; 11 were under 1 year of age. Their indications for transplantation were cardiomyopathies (38), lymphocytic myocarditis (8), and congenital heart diseases (19). Two patients of the first group successfully received a combined heart and kidney transplant. The 1-, 5-, and 11-year actuarial survival rates for the 65 patients who underwent heart transplantation were 68%, 62%, and 42%, respectively. In the 1st postoperative year in patients who had had cardiomyopathy, a total of 50 episodes of acute rejection (AR), with one death, occurred (mean 1.7 AR/patient per year ± 1.5) and, in patients who had had congenital heart diseases, 19 ARs (one death) occurred with a mean of 1.58 AR/patient per year ± 1.4. The incidence of AR was significantly higher in patients who had had myocarditis with a total of 26 episodes (mean 3.7 AR/patient per year ± 2) and one death. Rehabilitation of heart transplanted children and infants was complete (NYHA class 1) in 52 % of patients of this series. We conclude that heart transplantation may give a good intermediate and long-term survival in selected patients; the extension of indications to desperately ill patients, or patients with systemic diseases or complex congenital heart diseases may bring less encouraging results, but should not be definitely excluded. Scarcity of donors remains the main limit, being still the first cause of death for patients on our waiting list. Our limited experience seems to suggest that, as described in adults, the cellular amplification of the immune response might affect the post-heart transplant follow up of pediatric patients with myocarditis resulting in a poor outcome for this population.     

Heart Transplantation for End-Stage Heart Failure Due to Cardiac Sarcoidosis

Background

Cardiac sarcoidosis with end-stage heart failure has a poor prognosis without transplantation. The rates of sarcoid recurrence and rejection are not well established after heart transplantation.

Methods

A total of 19 heart transplant recipients with sarcoid of the explanted heart were compared with a contemporaneous control group of 1,050 heart transplant recipients without cardiac sarcoidosis. Assessed outcomes included 1st-year freedom from any treated rejection, 5-year actuarial survival, 5-year freedom from cardiac allograft vasculopathy (CAV), 5-year freedom from nonfatal major adverse cardiac events (NF-MACE), and recurrence of sarcoid in the allograft or other organs. Patients with sarcoidosis were maintained on low-dose corticosteroids after transplantation.

Results

There were no significant differences between the sarcoid and control groups in 1st-year freedom from any treated rejection (79% and 90%), 5-year posttransplantation survival (79% and 83%), 5-year freedom from CAV (68% and 78%), and 5-year freedom from NF-MACE (90% and 88%). Causes of death (n = 5) in the sarcoid group were coccidioidomycosis, pneumonia, rejection, hemorrhage, and CAV. No patient had recurrence of sarcoidosis in the cardiac allograft. Three of 19 patients (16%) experienced recurrence of extracardiac sarcoid, with no mortality.

Conclusions

Patients with cardiac sarcoidosis undergoing heart transplantation have acceptable long-term outcomes without evidence of recurrence of sarcoidosis in the allograft when maintained on low-dose corticosteroids. Progression of extracardiac sarcoid was uncommon, possibly related to immunosuppression. In patients with cardiac sarcoidosis, heart transplantation is a viable treatment modality.     

Cardiac arrest in the organ donor does not negatively influence recipient survival after heart transplantation.

OBJECTIVE: Cardiac arrest in the organ donor raises concerns about the possibility of ischemic cardiac damage. We evaluated the outcome of heart transplantation in patients receiving an organ from donors who had suffered a period of cardiac arrest. METHODS: Demographics, operative details and outcome data were obtained retrospectively. Actuarial survival was reported using Kaplan-Meier analysis and compared with the log rank test. Cox proportional hazards regression was used to model risk adjusted survival. RESULTS: Between 1 January 1991 and 1 November 2004 38 patients were transplanted with hearts from multiorgan donors who were resuscitated after a cardiac arrest. The mean (standard deviation) duration of cardiac arrest was 15 (8)min. The interval between donor cardiac arrest and organ excision was 69 (5)h. The 30-day mortality was 2.6% (1/38). In the same interim 566 patients underwent cardiac transplantation with hearts from organ donors without a cardiac arrest. Median time to follow up was 61 months (IQR 15-166). One and 5-year survival comparing the arrest and non-arrest groups was 94.2% versus 83.6% and 79.8% versus 74.5%, respectively, p=0.35. Donor cardiac arrest was not an adverse predictor of mortality on multivariate analysis, the adjusted odds ratio was 0.86 (95% CI 0.60-1.25, p=0.42). CONCLUSIONS: With careful case selection, there was no evidence that survival after cardiac transplantation was worse following a period of cardiac arrest in the organ donor. A history of cardiac arrest in the organ donor should not exclude an organ from being considered for transplantation.     

Relapse of giant cell myocarditis supported with veno-arterial extracorporeal membrane oxygenation

Giant cell myocarditis (GCM) is a fatal form of myocarditis that often presents with acute heart failure. An inflammatory infiltrate with giant cells and myocardial necrosis is characteristic. During the acute presentation, mechanical circulatory support may be necessary for hemodynamic support while immunosuppression is initiated. We report a case of GCM relapse which was supported with veno-arterial membrane oxygenation until recovery. The patient is doing well one year after explantation.     

Outcome after invasive recurrence in patients with ductal carcinoma in situ of the breast

BACKGROUND: Local recurrence is used as a marker of treatment failure for patients with ductal carcinoma in situ (DCIS). As follow-up lengthens, distant recurrence, breast cancer-specific survival (BCSS), and overall survival must be monitored. METHODS: A prospective database was used to analyze 1031 patients with DCIS. Patients having invasive recurrence after DCIS treatment were compared with patients having infiltrating ductal carcinoma (IDC). End points included distant recurrence, BCSS, and overall survival. RESULTS: Overall, patients with DCIS had a BCSS of 99%. BCSS was 85% for patients with invasive recurrences. DDFS in this group was 80%. Stage I IDC patients had a BCSS of 91%, whereas it was 38% in those with stage I IDC and invasive recurrences. CONCLUSIONS: Most patients with DCIS that recur can be salvaged. For the small subgroup of patients who recur with invasive breast cancer, survival is similar to that of patients with stage IIA IDC.     

Short- and long-term mechanical ventricular assistance towards myocardial recovery

Long-term LVADs are primarily used as a bridge to transplantation because cardiac transplantation currently offers a better long-term outlook for most patients. Some patients will not get the opportunity for transplantation due to organ shortages and long waiting lists, however, and alternate care strategies must be considered. LVAD weaning and explantation may be an appropriate course of action for patients who have IDC and in whom transplantation is not the optimal therapy. The data demonstrate that LVAD weaning may be performed successfully in selected patients with IDC, and that transplantation may be delayed or avoided altogether; however, VAD weaning is not without its risks. Many of the patients have demonstrated recurrence of heart failure at various times after undergoing device removal. Through proper monitoring, most of these patients can be identified early enough to be relisted for transplantation, although some will require reinsertion of an LVAD while waiting. The critical steps in establishing a successful VAD weaning program are proper patient selection, ventricular unloading in the early stages, the institution of heart failure medications, frequent monitoring for ventricular recovery, and a period of ventricular retraining before explantation. In addition, the surgeons must be able to perform the explantation procedure with a low operative mortality. As experience with LVAD weaning and explantation grows, we may be able to better predict which patients may be successfully treated without resorting to transplantation. Explantation may eliminate, or safely delay, the need for cardiac transplantation. Although it is unlikely that these patients will be studied in a randomized fashion, the collection of accurate and complete data may allow us to establish a database that can answer many of today's questions.     

Recurrence of giant cell myocarditis in cardiac allograft.

BACKGROUND: Giant cell myocarditis causes essentially irreversible fulminant left ventricular dysfunction with associated conduction abnormalities and congestive failure. Response to immunosuppressive therapy is poor and cardiac transplantation is the only viable treatment option. The histologic hallmarks of giant cell myocarditis include a polymorphous inflammatory response with numerous multinucleated giant cells and extensive myocyte necrosis in a geographic pattern. There were 38 patients who received a cardiac transplant for giant cell myocarditis in the Giant Cell Myocarditis Registry. Among these patients, there were 9 recurrences of disease in the allograft. Concern has been expressed that recurrence of giant cell myocarditis in the allograft might be a contraindication for cardiac transplantation in the future. METHODS: In our single-center analysis we describe the clinical and histologic findings of 5 patients transplanted for giant cell myocarditis at the Cleveland Clinic. RESULTS: All but 1 of the patients were New York Heart Association (NYHA) class 4 with an average cardiac index (CI) of 1.52 liters/min x m(2). Of the 5 patients transplanted, 1 developed recurrent giant cell myocarditis. Routine right ventricular endomyocardial biopsy at 1 week exhibited severe multifocal myocardial fibrosis in addition to mild acute vascular rejection and mild grade 1A cellular rejection. Follow-up biopsy in this patient indicated grade IIIA moderate acute rejection in addition to multinucleated giant cells. Two distinct inflammatory processes were noted consisting of foci of T-cell inflammation identified by immunohistochemistry to be consistent with rejection, and a second inflammatory process with few mononuclear cells staining for macrophage or T-cell markers with eosinophils and myocyte necrosis consistent with giant cell myocarditis. Follow-up right ventricular endomyocardial biopsies (RVBXs) in this patient have subsequently demonstrated improvement in the degree of inflammatory infiltrate without vascular or significant cellular rejection. Vascular rejection was noted in 1 of the remaining 4 patients and was treated successfully with muramab-CD3 and plasmapheresis. CONCLUSIONS: Giant cell myocarditis should be expected to recur in the allograft and often does so concurrently with rejection. However, the disease in the allograft responds to therapy in a favorable manner, which differs dramatically from that in the native heart. This might be the result of detection of the disease at an earlier stage than in the native heart, or the immunosuppression milieu in the allograft. The favorable response to therapy suggests that the likelihood of recurrence of giant cell myocarditis should not be considered a barrier to transplantation.     

Differences in clinical profile and survival after heart transplantation according to prior heart disease

OBJECTIVE: The objective of this study was to compare baseline characteristics and long-term survival among patients undergoing heart transplantation (HT) according to the 3 main types of prior heart disease: ischemic, idiopathic dilated cardiomyopathy (IDC), and valvular. MATERIALS AND METHODS: Four hundred twenty-three HTs performed between 1989 and 2005 were included. We excluded pediatric transplantation, retransplantations, combined transplantations (lung and kidney), and transplantations due to heart diseases other than ischemic, IDC, and valvular. Baseline characteristics of the recipients were analyzed, as well as short-term and long- term survival by groups. Analysis of variance (ANOVA) was used for continuous variables and chi-square was used for categorical variables. Survival analysis was computed using Kaplan-Meier curves and the log-rank test, as well as multivariate analysis using logistic regression. RESULTS: The ischemic and valvular heart disease groups were older and had a more frequent history of prior heart surgery and circulatory support at the time of transplantation compared with the IDC group. The incidence of arterial hypertension and dyslipidemia was higher among ischemic heart disease recipients. Survival rates at 30 days did not show significant differences (ischemic, 88%; IDC, 93%; and valvular; 84%; P = .21). Long-term survival rates were greater in the IDC than in the valvular or ischemic heart disease groups (75% vs 65% and 62%, respectively; P = .021). The multivariate analysis showed an association between the IDC group and long-term survival (odds ratio [OR], 0.55; 95% confidence interval [CI] 0.35-0.89; P = .015). CONCLUSIONS: (1) Patients showed a different clinical profiles depending on their pretransplantation heart disease. (2) There were no differences in early mortality between the groups. (3) Long-term survival was significantly greater among IDC transplant recipients and similar in ischemic and valvular heart disease transplant recipients.     

Survival benefits of heart and lung transplantation.

OBJECTIVE: Heart and lung transplantation has gained acceptance as therapy for end-stage cardiac and pulmonary failure. The early and intermediate survival benefits of one center's 10-year experience with 177 patients undergoing thoracic transplantation were examined. SUMMARY BACKGROUND DATA: As experience in cardiac and pulmonary transplantation has increased, improvements in patient selection, organ preservation, preoperative support, and perioperative care have significantly reduced the early threats to patient survival. Graft dysfunction due to chronic rejection appears to be the main risk for longer-term survival, and data compiled by the United Network for Organ Sharing (UNOS) indicate a 70% 5-year survival for heart transplants and a 50% 5-year survival for lung transplant recipients. METHODS: The medical records of 120 heart recipients, 52 lung transplant recipients, and 5 heart-lung recipients were reviewed. Cumulative survival estimates were made using Kaplan-Meier analysis. The etiologies of operative and long-term mortality in each transplant population were identified. A comparison of long-term survival after heart transplantation versus coronary revascularization in a group of patients with ischemic cardiomyopathy was performed. RESULTS: Operative mortality in both the cardiac and pulmonary transplant recipients was 8%. From 1990 to 1995, 70 consecutive adult cardiac transplant procedures were performed without an operative mortality. Three of five patients survived heart-lung transplantation. The extended actuarial survival rate at 5 years was 80% for the cardiac transplant recipients. The 2-year actuarial survival rate for the lung transplant recipients was 88%. Graft dysfunction was the most common cause of operative mortality in the heart transplant group whereas infection was responsible for most of the operative mortality after lung transplantation. CONCLUSIONS: Cardiac and pulmonary transplantation can be applied to morbidly ill patients with excellent operative and intermediate-term survival.     

Combined heart and lung transplantation for unresectable primary cardiac sarcoma

OBJECTIVE: The prognosis for patients with primary cardiac sarcoma is poor. Median survival is less than 10 months, especially when complete surgical excision is not feasible. Removal of all cardiopulmonary structures involved by tumor followed by orthotopic allotransplantation has been proposed to improve long-term survival. METHODS: From 1996 through 1999, we performed combined heart and lung resection followed by en bloc heart and bilateral lung transplantation in 4 patients (2 men and 2 women): 2 with inoperable pulmonary arterial sarcoma and 2 with left atrial sarcoma extending into the pulmonary vein. RESULTS: Median age at diagnosis was 39 years (range 37-45 years). All 4 patients were given chemotherapy before transplantation: doxorubicin and ifosfamide in 2 cases, and doxorubicin, ifosfamide, mesna, and dacarbazine in 2 cases. There were no operative deaths. Median survival after transplantation was 31 months (range 5-49 months). All patients had tumor recurrence: local recurrence in the chest (n = 1) and distant metastases in the brain (n = 2) and abdomen (n = 1). One patient remains alive 49 months after disease progression with cerebral metastasis as the only site of recurrence treated with whole-brain irradiation, resection, and stereotactic radiosurgery. CONCLUSIONS: Combined heart and lung transplantation is a technically feasible treatment for highly selected patients with localized advanced primary cardiac sarcomas. The high incidence of metastatic disease, however, limits its utility.     

Timing of cardiac transplantation in patients with heart failure receiving beta-adrenergic blockers.

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 beta-blocker therapy for patients with systolic heart failure became common, and beta-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 beta-blockers. METHODS: Actuarial, hemodynamic, and exercise ventilatory data were collected from 540 patients with heart failure, 256 of whom were taking beta-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 beta-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 beta-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 beta-blockers and whose VO(2) peak was > or =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 beta-blockers, VO(2) peak <14 ml/kg/min was associated with worse 3-year survival (38.9 - 62.1%) than that for post-transplant patients. Excluding the 42 patients with heart failure in our study who underwent transplantation and then evaluating survival of the remaining patients with heart failure (not event-free survival) did not substantially change these results. CONCLUSIONS: Patients with heart failure who are receiving beta-blockers do not derive a survival advantage at 1 and 3 years after cardiac transplantation if VO(2) peak is > or =12 ml/kg/min. Patients not taking beta-blockers whose VO(2) peak is <14 ml/kg/min have superior survival with cardiac transplantation.