RESUMO
PURPOSE: The Kantrowitz CardioVAD (KCV) is an electrically powered, pneumatically driven circulatory assist device which provides diastolic augmentation and systolic unloading to the failing heart. It consists of a 60cc-pumping chamber, a percutaneous access device (PAD), and an external controller. The pumping chamber, is surgically implanted in the descending thoracic aorta with the patient on cardiopulmonary bypass. Its physiologic function is analogous to that of the intra-aortic balloon pump (IABP). METHODS: Between 1997 and 2000, 5 men (age 59 to 73) with end-stage cardiomyopathy refractory to maximal drug treatment and with documented hemodynamic improvement on an IABP were enrolled in a feasibility study. RESULTS: Mean bypass time was 157 minute (range 120 to 196 minute); mean cross-clamp time was 101 minute (range 69 to 144). Patient 1 died intra-operatively. Compared with preoperative values, at 1 month, cardiac index increased (1.7 to 2.6 L/min/m(2)) and there were significant decreases in creatinine (2.6 to 1.5 mg/dL), pulmonary capillary wedge pressure (PCWP) (32 to 14 mm Hg), and right atrial pressure (RA) (19 to 9 mm Hg). NYHA class improved (IV to II). The mean increase in cardiac index with the KCV OFF to ON was 0.53 L/min/m(2) (36%). Two patients were discharged home. The device was used intermittently without thromboembolic complications. The only device related complications were attributed to PAD design and have been corrected. CONCLUSION Our initial human trial demonstrates successful implantation of the KCV in end-stage patients, the ability of the device to be used intermittently without anticoagulation, and documents hemodynamic and functional improvement in the status of these patients.
Assuntos
Cardiomiopatia Dilatada/cirurgia , Coração Auxiliar , Idoso , Aorta Torácica/cirurgia , Cardiomiopatia Dilatada/fisiopatologia , Estudos de Viabilidade , Hemodinâmica , Humanos , Balão Intra-Aórtico , Cinética , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The use of outpatient intravenous inotropic therapy in heart transplant candidates is contentious. In addition to concerns about morbidity and mortality rates, the current United Network for Organ Sharing (UNOS) heart allocation system presently grants no waiting list priority status benefit to candidates who receive intravenous inotropic therapy in the outpatient setting (UNOS status 2), whereas identical therapy given in an intensive care unit setting does increase priority status (UNOS status 1). The goal of this study was to determine whether an increase in UNOS waiting list priority status is justified in heart transplant candidates receiving outpatient intravenous inotropic therapy by comparing the waiting list mortality of UNOS status 2 candidates on such therapy with that of UNOS status 2 candidates maintained on oral heart failure agents alone. METHODS: This is a retrospective analysis of the pretransplantation outcomes of heart transplant candidates initially listed as UNOS status 2, comparing 29 candidates receiving intravenous outpatient inotropic therapy (group 1) to 109 candidates maintained on oral heart failure agents alone (group 2). RESULTS: The waiting list mortality was not significantly different between the two groups (group 1=7% vs group 2=20%, p=.18); however, group 1 patients had greater morbidity rates while awaiting transplantation than group 2 patients. A greater percentage of group 1 than group 2 patients clinically deteriorated to UNOS status 1 while awaiting transplantation (45% vs 11%), resulting in more group 1 patients undergoing transplantation overall, (59% vs 33%, p=.01) and more group 1 than group 2 patients undergoing transplantation at a higher priority status, UNOS status 1 (76% vs 33%, p=.003). Group 1 patients had more pretransplantation heart failure admissions (1.2 vs 0.6 admissions/total waiting period, p=.02) and longer hospital stays (26+/-39 vs 8.8+/-16 days, p=.03), spent a greater percentage of their total waiting time hospitalized (7% vs 2%, p=.003), and were more likely than group 2 patients to receive intravenous inotropic therapy during hospitalization (70% vs 25%, p=.001). CONCLUSION: This study suggests that heart transplant candidates who require maintenance outpatient intravenous inotropic therapy represent a subgroup of UNOS status 2 candidates with greater waiting list morbidity, but no greater waiting list mortality than candidates who can be maintained on oral heart failure agents alone. However, the current UNOS heart allocation system provides for this increased illness acuity by assigning a higher priority status when necessary. A larger, prospective study is necessary to determine whether a true difference in waiting list mortality rates exists and if an increase in priority status is justified for UNOS status 2 candidates requiring maintenance inotropic therapy.
Assuntos
Cardiotônicos/uso terapêutico , Cardiopatias/tratamento farmacológico , Transplante de Coração , Pacientes Ambulatoriais , Listas de Espera , Administração Oral , Adulto , Cardiotônicos/administração & dosagem , Feminino , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida , Resultado do TratamentoRESUMO
BACKGROUND: In heart transplant recipients methotrexate has been shown to reverse recurrent/persistent acute rejection refractory to intensified conventional immunosuppression. This study sought to determine whether methotrexate produces a sustained decline of heart allograft rejection rates and renders rejection rates of patients with a history of recurrent/persistent rejection similar to those of heart transplant recipients without such history. METHODS: Rejection, infection, and cardiac allograft vasculopathy were compared in 35 patients treated with methotrexate (12 +/- 9 mg/week for 34 +/- 54 weeks) and 236 patients never given methotrexate. Because the mean time from transplantation to initiation of methotrexate was 9.4 months, patients treated without methotrexate were analyzed for events < or = 9.4 versus > 9.4 months after heart transplantation. RESULTS: Demographics, perioperative and maintenance immunosuppression, and postoperative follow-up time (58 +/- 32 vs 57 +/- 33 months) were similar in the two groups. Rejection rates decreased in both groups but remained significantly higher in the patients treated with methotrexate after initiation of therapy than in the patients treated without methotrexate more than 9.4 months after transplantation (0.15 +/- 0.16 vs 0.06 +/- 0.12 episodes/patient/month; p = 0.0014). Infection rates were higher in patients after methotrexate initiation than in patients treated without methotrexate more than 9.4 months after heart transplantation (0.17 +/- 0.24 vs 0.06 +/- 0.13 episodes/patient/month; p = 0.015). At the end of the follow-up period methotrexate- and non-methotrexate-treated groups did not differ in the percentage of patients with angiographically detectable cardiac allograft vasculopathy (17.1% and 21.2%, respectively) and survival (71.4% and 64.0%, respectively). CONCLUSIONS: Even after reversal of rejection by methotrexate, patients requiring methotrexate for the treatment of persistent/recurrent rejection continued to have higher rejection rates than patients not requiring methotrexate. In spite of persistently higher rejection rates, patients treated with methotrexate did not have higher rates of cardiac allograft vasculopathy. This finding raises the question whether methotrexate provides a protective influence on the development of cardiac allograft vasculopathy in this high-risk group.
Assuntos
Doença das Coronárias/tratamento farmacológico , Rejeição de Enxerto/tratamento farmacológico , Transplante de Coração/imunologia , Imunossupressores/uso terapêutico , Metotrexato/uso terapêutico , Doença Aguda , Adolescente , Adulto , Idoso , Criança , Angiografia Coronária/efeitos dos fármacos , Doença das Coronárias/imunologia , Doença das Coronárias/mortalidade , Feminino , Seguimentos , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/mortalidade , Transplante de Coração/mortalidade , Humanos , Imunossupressores/efeitos adversos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Taxa de SobrevidaAssuntos
Ciclosporina/administração & dosagem , Ciclosporina/uso terapêutico , Transplante de Coração/imunologia , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Azatioprina/uso terapêutico , Biópsia por Agulha , Creatinina/sangue , Ciclosporina/farmacocinética , Quimioterapia Combinada , Emulsões , Feminino , Seguimentos , Rejeição de Enxerto/epidemiologia , Transplante de Coração/patologia , Humanos , Imunossupressores/farmacocinética , Masculino , Pessoa de Meia-Idade , Prednisona/uso terapêutico , Fatores de TempoRESUMO
OBJECTIVES: This study compared the survival of patients with heart failure who have waited > 6 months for heart transplantation with that patients who undergo heart transplantation after a similarly prolonged waiting period. BACKGROUND: There are little data describing outcome in patients with severe heart failure who have waited for extended periods of time on the heart transplant waiting list. METHODS: Sixty-three consecutive patients who spent > 6 months on the heart transplant waiting list were examined. Mean (+/- SD) age was 53 +/- 9 years, mean left ventricular ejection fraction was 19 +/- 6%, and all were taking digoxin and diuretic and vasodilator agents. Patients who underwent transplantation during the follow-up period were censored from the pretransplantation analysis, and their survival was examined as part of the posttransplantation phase of the study. RESULTS: Of the 63 original patients examined, 25 underwent transplantation, 10 during inotropic or mechanical circulatory support. The pretransplantation mortality rate was 6% at 6 months after the 6-month milestone on the waiting list, 12% at 12 months and 22% at 18 months. The posttransplantation mortality rate was 5% at 6 months, 10% at 12 months and 24% at 18 months. There were no differences in survival at any time between the two phases of the study. CONCLUSIONS: Survival of patients who have survived > 6 months on the heart transplant waiting list is generally good. Although heart transplantation did not appear to confer additional survival advantage over medical therapy, a large proportion of the patients who underwent transplantation were critically ill at the time of transplantation and would undoubtedly have died of progressive heart failure had they not undergone transplantation. We conclude that heart transplantation should still be considered a therapeutic alternative in patients with heart failure even after a prolonged waiting period on the heart transplant waiting list.
Assuntos
Insuficiência Cardíaca/cirurgia , Transplante de Coração , Análise Atuarial , Fatores de Confusão Epidemiológicos , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/mortalidade , Humanos , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento , Listas de EsperaAssuntos
Ciclosporina/uso terapêutico , Taxa de Filtração Glomerular/efeitos dos fármacos , Transplante de Coração/imunologia , Adulto , Idoso , Análise de Variância , Azatioprina/uso terapêutico , Pressão Sanguínea/efeitos dos fármacos , Ciclosporina/efeitos adversos , Quimioterapia Combinada , Feminino , Seguimentos , Humanos , Terapia de Imunossupressão/efeitos adversos , Terapia de Imunossupressão/métodos , Testes de Função Renal , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prednisona/uso terapêutico , Estudos Retrospectivos , Fatores de TempoRESUMO
The purpose of this study was to determine factors associated with the development of a persistently depressed cardiac output during the first year after cardiac transplantation. With this aim in mind, the records of 133 consecutive patients undergoing orthotopic cardiac transplantation and surviving for > or = 1 year after transplantation were reviewed. For each patient, the mean cardiac index for each of the 3-month periods, 0-3, 4-6, 7-9, and 10-12 months after transplantation was calculated. Of the 133 patients, 19 (14%) had a mean cardiac index < 2.4 l/min/m2 during > or = 3 of these 3-month periods. The pre- and post-transplantation clinical, immunologic, and hemodynamic data of these 19 patients (study group) were compared with the remaining 114 patients (control group). Compared with the control group, the patients in the study group were older (56 +/- 5 vs. 46 +/- 15 years; p = 0.0001), more frequently had ischemic heart disease as the original diagnosis (58 vs. 37%; p < 0.05), had a lower preoperative cardiac index (1.91 +/- 0.53 vs. 2.71 +/- 1.0 l/min/m2; p = 0.0001), more frequently did not receive perioperative anti-T cell therapy (47 vs. 25%; p = 0.046), and had a greater median number of infections during the first year after transplantation (5 vs. 3; p = 0.027). However, only one factor--a low preoperative cardiac index--emerged as an independent predictor of the development of a persistently depressed cardiac index during the first year after transplantation.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Baixo Débito Cardíaco/etiologia , Transplante de Coração/efeitos adversos , Análise de Variância , Baixo Débito Cardíaco/fisiopatologia , Feminino , Seguimentos , Transplante de Coração/fisiologia , Hemodinâmica/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/fisiopatologia , Prognóstico , Estudos Retrospectivos , SobreviventesRESUMO
To evaluate the risk/benefit ratio of perioperative OKT3 in cardiac transplant patients receiving triple-drug immunosuppression, patients who underwent cardiac transplantation between July 1, 1988 and December 31, 1989 (n = 33) and who received perioperative OKT3 were retrospectively compared with patients who underwent transplantation between January 1, 1990 and June 30, 1991 (n = 46), and who received no perioperative anti-T cell therapy. To allow similar follow-up, data were analyzed through June 30, 1990 for the OKT3 group and through December 31, 1991 for the no anti-T cell therapy group. Patients in the no anti-T cell therapy group waited longer for a donor organ; other pretransplant characteristics did not differ. The azathioprine dose 1 month after transplant was higher in the no anti-T cell therapy group (144 +/- 63 mg vs 109 +/- 55 mg, p = 0.016); other post-transplant immunosuppression was similar. The incidence of total and treated rejection and the time to the first rejection did not differ between the groups. The OKT3 group had a higher number of infections (0.8 +/- 0.9 vs 0.3 +/- 0.3, p = 0.006) and intravenously treated infections (0.5 +/- 0.6 vs 0.1 +/- 0.2, p = 0.004) per patient per month. Cytomegalovirus infection developed in 46% of the OKT3 group versus 22% of the no anti-T cell therapy group (p = 0.025). Patient survival did not differ between the groups. Thus, an immunosuppressive regimen that includes perioperative OKT3 increases infections, especially cytomegalovirus infections, without decreasing or delaying rejection or increasing survival.
Assuntos
Transplante de Coração , Imunossupressores/uso terapêutico , Muromonab-CD3/uso terapêutico , Adulto , Azatioprina/administração & dosagem , Ciclosporina/administração & dosagem , Infecções por Citomegalovirus/diagnóstico , Quimioterapia Combinada , Feminino , Rejeição de Enxerto , Humanos , Masculino , Metilprednisolona/administração & dosagem , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: The diffuse nature of cardiac allograft vasculopathy makes early detection of the disease by traditional noninvasive methods or coronary angiography difficult. The aim of this study was to determine if there is a relation between abnormalities in vessel wall morphology, as assessed by intracoronary ultrasound, and a decreased vasodilatory response to the endothelium-dependent vasodilator papaverine hydrochloride and if cardiac allograft vasculopathy detected by coronary angiography is associated with specific intracoronary ultrasound findings. METHODS AND RESULTS: Twenty-three heart transplant recipients underwent 25 intracoronary ultrasound studies and 24 studies of coronary vasomotor tone 10 days to 8.3 years after surgery using a 20-mHz intracoronary ultrasound catheter. The studies were divided in two groups according to the presence (n = 7, group 1) or absence (n = 18, group 2) of angiographically evident cardiac allograft vasculopathy. Qualitative assessment of vessel wall morphology and quantitative analysis of the vasodilator response to the injection of papaverine hydrochloride into the coronary artery distal to the imaging site were performed off-line, and results for the two study groups were compared. A significantly higher percentage of patients with than without angiographic evidence of cardiac allograft vasculopathy had a three-interface vessel wall morphology by intracoronary ultrasound (100% versus 11%, P < .001). In two recipients who underwent two serial studies, the appearance of three interfaces in the vessel wall or a progressive thickening of the inner interface of the vessel wall occurred in conjunction with the appearance of angiographic cardiac allograft vasculopathy. The vasodilator response to papaverine was less in patients with than in those without angiographically evident cardiac allograft vasculopathy both in terms of absolute and relative increases in lumen diameter (+0.1 +/- 0.12 mm versus +0.3 +/- 0.17 mm, P < .05, and +5.1 +/- 5.3% versus +8.2 +/- 5.3%, P = NS) and lumen cross-sectional area (+0.5 +/- 0.6 mm2 versus +1.7 +/- 1.1 mm2, P < .02, and +7.1 +/- 8.8% versus 16.6 +/- 11.0%, P = .055), respectively. CONCLUSIONS: Intracoronary ultrasound assessment of vessel wall morphology and evaluation of vascular response to endothelium-dependent vasodilators are useful techniques for detecting cardiac allograft vasculopathy.
Assuntos
Doença das Coronárias/diagnóstico por imagem , Doença das Coronárias/etiologia , Vasos Coronários/diagnóstico por imagem , Transplante de Coração/efeitos adversos , Cateterismo Cardíaco , Angiografia Coronária , Doença das Coronárias/diagnóstico , Vasos Coronários/efeitos dos fármacos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico/fisiologia , Papaverina , Ultrassonografia de Intervenção , Vasodilatação/fisiologiaRESUMO
The morbidity and mortality from heart transplantation has been reduced dramatically over the last several years. However, the long-term survival in heart transplant recipients is limited by arteriopathy in the allograft coronary arteries, the pathophysiology of which is poorly understood. The diagnosis of this arteriopathy is at present limited to cardiac catheterization. Noninvasive studies have proven to be of limited benefit in diagnosing this arteriopathy. The authors performed cardiac vest studies in nine heart transplant recipient patients. Six of the vest studies were abnormal; five of the patients had documented transplant coronary artery disease by cardiac catheterization. They found that the sensitivity and negative predictive value of the cardiac vest in identifying arteriopathy in transplant recipients was 100%. The authors propose that cardiac vest could be a sensitive, noninvasive screening test for identifying arteriopathy in heart transplant recipients.
Assuntos
Assistência Ambulatorial , Doença das Coronárias/patologia , Transplante de Coração/fisiologia , Volume Sistólico/fisiologia , Doença das Coronárias/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , CintilografiaRESUMO
UNLABELLED: To further elucidate the significance of endocardial infiltrates in heart transplant patients, the presence, frequency, and type of endocardial infiltrates were evaluated in 5026 endomyocardial biopsy specimens obtained from 200 heart transplant patients 0 to 75 months after heart transplantation. The relationship of endocardial infiltrates to immunologic, clinical, and demographic variables was then explored. Endocardial infiltrates were detected in 557 endomyocardial biopsy specimens (11%) from 117 heart transplant patients (58%) at 6.3 +/- 9.4 months (mean +/- SD; range, 0 to 49 months) after heart transplantation. Heart transplant patients with endocardial infiltrates were younger (p = 0.03), had a greater incidence of idiopathic dilated cardiomyopathy before heart transplantation (p = 0.05), and included a greater percentage of females (p < 0.05). Both total and treated rejection rates were significantly higher in patients with endocardial infiltrates versus those without endocardial infiltrates (p = 0.0001). Rejection on the subsequent endomyocardial biopsies was more often present in endocardial biopsy specimens with endocardial infiltrates than in those without endocardial infiltrates, both in the presence (37% versus 24%; p < 0.001) and absence (33% versus 19%; p < 0.0001) of concomitant findings of rejection. No association was identified between endocardial infiltrates and posttransplantation lymphoproliferative disorder, cytomegalovirus infection, Epstein-Barr virus infection, or cardiac allograft vasculopathy. Multivariate regression analysis confirmed that the occurrence of endocardial infiltrates is associated with rejection when adjustment is made for patient's age, gender, heart disease before transplantation, follow-up time, and number of endomyocardial biopsies after heart transplantation (p = 0.0001). CONCLUSIONS: (1) Endocardial infiltrates may occur with or without associated endomyocardial biopsy findings of rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Endocárdio/patologia , Transplante de Coração/patologia , Leucócitos Mononucleares/patologia , Miocárdio/patologia , Biópsia , Chicago/epidemiologia , Doença das Coronárias/epidemiologia , Doença das Coronárias/patologia , Infecções por Citomegalovirus/epidemiologia , Infecções por Citomegalovirus/patologia , Feminino , Previsões , Oclusão de Enxerto Vascular/epidemiologia , Oclusão de Enxerto Vascular/patologia , Rejeição de Enxerto/epidemiologia , Rejeição de Enxerto/patologia , Infecções por Herpesviridae/epidemiologia , Infecções por Herpesviridae/patologia , Herpesvirus Humano 4 , Humanos , Incidência , Transtornos Linfoproliferativos/epidemiologia , Transtornos Linfoproliferativos/patologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Transplante Homólogo , Infecções Tumorais por Vírus/epidemiologia , Infecções Tumorais por Vírus/patologiaRESUMO
Because of the critical donor organ shortage for heart transplantation, selection of recipients should be based on the potential for maximum benefit. To evaluate the effects of advancing age on outcome after heart transplantation, we compared the clinical variables of 12 recipients aged 65 years or older (66.1 +/- 0.9 years [x +/- standard deviation]; range, 65 to 67 years) with those of 57 patients aged 55 to 64 years (59.3 +/- 2.7 years) at the time of the procedure. The two study groups were similar in sex, race, pretransplantation heart disease, immunocompatibility, maintenance immunosuppression, and length of first hospitalization at the time of the procedure. Groups were also similar regarding the incidence of malignancies, fractures, diabetes, neurologic complications, and renal dysfunction occurring over the follow-up period. Patients 65 years of age or older had a significantly higher number of hospital days (36 +/- 29 versus 15 +/- 18 days; p < 0.02) and increased frequency of infections/month (0.7 +/- 0.3 versus 0.3 +/- 0.4 infections/month; p < 0.03) during the first postoperative year. Older patients had a higher incidence of cytomegalovirus infections (50% versus 19%; p < 0.06), lower rates of rejection at 1 and 6 months after operation (p < 0.03), and more severe functional limitation (p < 0.002) than patients aged 55 to 64 years. One-year actuarial survival was not significantly different in the two groups. The results of our study suggest that, because of lower rejection and higher infection rates, heart transplantation recipients older than 65 years of age should receive less intense immunosuppression.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Cardiomiopatia Dilatada/cirurgia , Transplante de Coração , Isquemia Miocárdica/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Cardiomiopatia Dilatada/epidemiologia , Comorbidade , Infecções por Citomegalovirus/epidemiologia , Feminino , Rejeição de Enxerto/epidemiologia , Humanos , Terapia de Imunossupressão , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/epidemiologia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
To determine if high-risk heart operation with circulatory support standby is an acceptable alternative to direct heart transplantation, we reviewed 21 patients who were accepted as heart transplant candidates but offered a heart operation because of the availability of circulatory support. Preoperative left ventricular ejection fraction was 0.25 +/- 0.08 (mean +/- standard deviation), and New York Heart Association functional class was 3.4 +/- 0.7. The patients underwent 16 bypass graft operations, 4 mitral and 2 aortic valve replacements, and 4 defibrillator implantations (combined procedures in 5 patients). An intraaortic balloon pump was placed in 12 patients. One patient required biventricular assist device support but was weaned in 11 days. Twenty patients were discharged 14.8 +/- 11.5 days postoperatively. One patient died 15 days postoperatively of amiodarone-induced respiratory failure, and 1 died suddenly 2 months postoperatively. At 10.5 +/- 6 months postoperatively, 19 patients (90%) are alive. Mean functional class is 1.9 +/- 0.9. None of the patients has undergone transplantation, but 2 are awaiting donor organs. We conclude that in selected heart transplant candidates high-risk heart operation is a viable alternative to direct heart transplantation.
Assuntos
Doenças das Valvas Cardíacas/cirurgia , Isquemia Miocárdica/cirurgia , Análise Atuarial , Adulto , Angina Pectoris/cirurgia , Valva Aórtica/cirurgia , Ponte de Artéria Coronária , Desfibriladores Implantáveis , Feminino , Seguimentos , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Humanos , Balão Intra-Aórtico , Masculino , Pessoa de Meia-Idade , Valva Mitral/cirurgia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
To elucidate the pathogenic mechanisms of acute allograft dysfunction that is not caused by acute cellular rejection, we have studied the clinical and immunopathologic characteristics of 11 heart transplant recipients who had acute allograft dysfunction in the absence of interstitial mononuclear cell infiltrates on endomyocardial biopsy samples. Six of eleven patients (54%) had a striking increase in levels of anti-HLA antibodies in close temporal proximity with the episode of acute allograft dysfunction. Cardiac allograft function improved in all patients with intensification of immunosuppression.
Assuntos
Formação de Anticorpos , Transplante de Coração , Coração/fisiopatologia , Imunologia de Transplantes , Adulto , Idoso , Feminino , Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/terapia , Histocompatibilidade , Humanos , Imunossupressores/administração & dosagem , Masculino , Pessoa de Meia-IdadeRESUMO
This study shows that perioperative OKT3 provides no benefit in terms of the time of onset or frequency of rejection or patient survival. However, it does result in an increased incidence of infection, particularly CMV infection. Thus, the risk/benefit ratio of perioperative OKT3 does not appear favorable. However, a multicenter, randomized trial including a larger number of patients and longer patient follow-up will be required to definitively answer the question.
Assuntos
Transplante de Coração/imunologia , Muromonab-CD3/uso terapêutico , Azatioprina/uso terapêutico , Ciclosporina/uso terapêutico , Feminino , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/patologia , Transplante de Coração/patologia , Transplante de Coração/fisiologia , Humanos , Terapia de Imunossupressão/métodos , Período Intraoperatório , Masculino , Metilprednisolona/uso terapêutico , Pessoa de Meia-Idade , Muromonab-CD3/administração & dosagem , Muromonab-CD3/efeitos adversos , Prednisona/uso terapêutico , Estudos Retrospectivos , Linfócitos T/imunologia , Resultado do TratamentoRESUMO
BACKGROUND: Photopheresis is a technique in which reinfusion of mononuclear cells exposed to UV-A light ex vivo after in vivo treatment with 8-methoxypsoralen initiates host-immunosuppressive responses. METHODS AND RESULTS: To determine if photopheresis safely reverses International Society for Heart and Lung Transplantation (ISHLT) rejection grades 2, 3A, and 3B without hemodynamic compromise, 16 heart transplant patients with ISHLT rejection grades 2, 3A, and 3B were randomized to photopheresis or corticosteroid therapy. The average number of mononuclear cells treated with each photopheresis procedure was 9.8 +/- 9.1 x 10(9) (mean +/- SD). Photopheresis and corticosteroids reversed eight of nine and seven of seven episodes of rejection, respectively. The median time from initiation of treatment to rejection reversal was 25 days (range, 6-67 days) in the photopheresis group and 17 days (range, 8-33 days) in the corticosteroid group. Hemodynamics were normal before either treatment and did not change after reversal of rejection. No adverse reactions occurred with photopheresis, and all patients in either treatment group are alive. CONCLUSIONS: These preliminary, short-term results in prospectively randomized patients indicate that photopheresis may be as effective as corticosteroids for treating ISHLT rejection grades 2, 3A, and 3B. The apparently low toxicity and potential efficacy of photopheresis warrant further analysis of its role in the prevention and treatment of heart transplant rejection.
Assuntos
Rejeição de Enxerto/tratamento farmacológico , Transplante de Coração/imunologia , Leucaférese , Metilprednisolona/uso terapêutico , Fotoquimioterapia/métodos , Prednisona/uso terapêutico , Adulto , Endocárdio/patologia , Feminino , Transplante de Coração/patologia , Humanos , Masculino , Metoxaleno/uso terapêutico , Miocárdio/patologia , Fatores de TempoRESUMO
To determine the relationship of cytomegalovirus infections (CMVI) to immunosuppression in heart transplants, we retrospectively compared demographic and clinical variables in 154 consecutive heart transplant patients. Forty-one CMVI were compared; of these, 30 (73%) were identified in tissue, and nine (22%) were identified by blood or urine culture. Twenty (49%) of the CMVI were self-limited, and 21 (51%) were progressive, requiring treatment. When comparing patients with and without CMVI, demographic variables, mean preexisting heart disease, cyclosporine level, cumulative corticosteroid dose, and the use of anti-T-cell antibodies were examined. Only the use of OKT3 was significantly associated with the subsequent development of CMVI. Although CMVI subsequently developed in 30 of 79 (38%) patients who had received OKT3, CMVI developed in only 11 of 75 (15%) patients who had not received OKT3 (p = 0.01). Furthermore, the incidence of CMVI increased with increasing total OKT3 dose (none, 11 of 64 [17%]; < or = 75 mg, 23 of 66 [35%]; > 75 mg, 6 of 14 [43%]; p = 0.01). Logistic regression showed that the only two variables predictive of CMVI were the use of OKT3 (p = 0.0023) and ischemic rather than idiopathic heart disease before transplantation (p = 0.0098). Rejection rates, incidence of allograft vasculopathy, and 1-year actuarial survival were not influenced by previous CMVI. Pneumocystis carinii pneumonia occurred more frequently in patients with CMVI than in those without (13 of 41 [32%] patients versus 3/113 [3%] patients; p < 0.001). No correlation existed between CMVI and lymphoproliferative disorder (p = 0.84).(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Infecções por Citomegalovirus/etiologia , Transplante de Coração , Imunossupressores/efeitos adversos , Adolescente , Adulto , Idoso , Criança , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/imunologia , Feminino , Humanos , Terapia de Imunossupressão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Muromonab-CD3/administração & dosagem , Muromonab-CD3/efeitos adversos , Complicações Pós-Operatórias , Estudos Retrospectivos , Fatores de RiscoRESUMO
Photopheresis is a potential therapy for rejection in which reinfusion of mononuclear cells exposed to ultraviolet-A light ex vivo, after treatment with 8-methoxypsoralen in vivo, initiates host immune responses that specifically inhibit the cytotoxicity of the photomodulated mononuclear cells. Between May 1990 and January 1991, 7 heart transplant (HT) patients (age 42.2 +/- 16.7 [mean +/- SD] years) on triple immunosuppression (cyclosporine, corticosteroids, and azathioprine) had 9 episodes of non-hemodynamically compromising moderate rejection that were treated with photopheresis. These episodes of rejection occurred at an average of 114.4 +/- 180.5 (range 8-575) days after HT. After oral administration the mean serum level of 8-methoxypsoralen achieved was 129.0 +/- 72.4 ng/ml. An average of 10.4 +/- 9.6 x 10(9) mononuclear cells were treated with each photopheresis procedure. Photopheresis was performed twice when less than 5 x 10(9) mononuclear cells had been treated with the first procedure. Of 9 rejection episodes treated with photopheresis, 5 required 1 procedure and 4 required 2 procedures. Photopheresis was used to treat a single episode of rejection in 5 pts. and 2 separate rejection episodes in 2 additional pts. Eight of 9 episodes of rejection were successfully reversed by photopheresis as assessed by endomyocardial biopsy (EMB) performed 7 days after treatment. Immunohistochemical analysis of EMB samples revealed that postphotopheresis cell counts for T cells, B cells, and macrophages were reduced compared to pretreatment values and correlated with the histopathologic resolution of rejection. Hemodynamics were normal prephotopheresis and remained unchanged at the time when the postphotopheresis EMB showed no evidence rejection No adverse effects have been observed with photopheresis. Over a follow-up period of 5.3 +/- 4.0 months, rejection and infection rates/pt./follow-up months were 0.3 +/- 0.4 and 0.04 +/- 0.07, respectively. The preliminary, short term results of this pilot study indicate that photopheresis may be efficacious in the treatment of moderate rejection in hemodynamically stable HT patients and thus may be an alternative to corticosteroid pulses.
Assuntos
Remoção de Componentes Sanguíneos/métodos , Rejeição de Enxerto , Transplante de Coração/efeitos adversos , Linfócitos/imunologia , Terapia PUVA , Adulto , Transfusão de Sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Muromonab-CD3/uso terapêutico , Receptores de Antígenos de Linfócitos T/fisiologiaRESUMO
BACKGROUND: A sudden increase in the incidence of post-transplantation lymphoproliferative disorder among the patients in our cardiac-transplantation program was temporally related to introduction of the immunosuppressive drug OKT3. This monoclonal antibody has come to be widely used in recent years both to prevent and to treat rejection after cardiac transplantation. METHODS: In order to identify variables that predict the development of post-transplantation lymphoproliferative disorder, we analyzed retrospectively a series of 154 consecutive cardiac-transplant recipients at a single institution. Univariate analyses and multivariate analysis by logistic regression were performed. RESULTS: Among 75 patients who did not receive OKT3, post-transplantation lymphoproliferative disorder developed in 1 (1.3 percent), as compared with 9 of 79 patients who received the drug (11.4 percent); the incidence among the OKT3-treated patients was ninefold higher (odds ratio, 9.5; 95 percent confidence interval, 1.6 to 54.7). According to multivariate analysis, the only factor significantly associated with the development of post-transplantation lymphoproliferative disorder was the use of OKT3 (P = 0.001). A significant increase in risk with increasing doses was also apparent: 4 of 65 patients who received a cumulative dose of 75 mg of OKT3 or less (6.2 percent) had post-transplantation lymphoproliferative disorder, whereas 5 of 14 patients who received more than 75 mg had the disorder (35.7 percent; P less than 0.001). CONCLUSION: The addition of OKT3 to the immunosuppressive regimen increases the incidence of post-transplantation lymphoproliferative disorder after cardiac transplantation, and the risk increases sharply after cumulative doses greater than 75 mg. We suggest that the risks and benefits of prophylactic OKT3 administration be reassessed in the light of these findings, particularly since the value of prophylactic immunotherapy in cardiac-transplant recipients remains to be clearly established.