RESUMO
BACKGROUND: Despite optimized medical therapy, severe idiopathic pulmonary arterial hypertension (IPAH) is a devastating disease with a poor outcome. Autoantibodies have been detected in IPAH that can contribute to worsening of the disease. OBJECTIVES: The objective of this prospective, open-label, single-arm, multicenter trial was to evaluate the safety and efficacy of immunoadsorption (IA) as an add-on to optimized medical treatment for patients with IPAH. METHODS: A total of 10 IPAH patients received IA over 5 days. Their clinical parameters, including hemodynamics measured by right heart catheter, were assessed at baseline and after 3 and 6 months. The primary endpoint was the change in pulmonary vascular resistance (PVR). Secondary endpoints included the change in 6-min walking distance, quality of life, safety, and plasma levels of IgG and autoantibodies. RESULTS: The evaluation of the 10 IPAH patients (75% female; 51 ± 12 years; 166 ± 10 cm; WHO functional class III; 53% on combination therapy) revealed that IA was a safe procedure that efficiently removed IgG and autoantibodies from the circulation. After 3 months, the mean PVR improved significantly by 13.2% (p = 0.03) and the cardiac index improved by 13.1%, but no significant changes were found in 6-min walking distance. The quality of life physical functioning subscale score significantly improved after 6 months. The serious adverse events in 3 patients were possibly related to IA and included pneumonia, temporary disturbance in attention, and thrombocytopenia. CONCLUSIONS: IA as an add-on to targeted medical treatment for IPAH is a safe procedure with beneficial effects on hemodynamics, especially in patients with high levels of autoantibodies. Larger-scale controlled studies are needed to assess its efficacy in IPAH and to identify responders.
Assuntos
Autoanticorpos/isolamento & purificação , Remoção de Componentes Sanguíneos/métodos , Hipertensão Pulmonar Primária Familiar/terapia , Imunoglobulina G/isolamento & purificação , Adulto , Idoso , Teste de Esforço , Feminino , Humanos , Técnicas de Imunoadsorção , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Qualidade de Vida , Resistência VascularRESUMO
Anticoagulation in mechanical circulatory support (MCS) patients dictated by local practice, and therefore uniform standards for management are lacking. To characterize the worldwide variance in anticoagulation and antiplatelet therapy in patients with MCS devices, a 42 item survey was created and distributed electronically in August 2014. The survey assessed the center-perceived thromboembolic risk (minimal, low, moderate, or high) and characterized the antiplatelet and anticoagulant strategies for the Thoratec HeartMate II (HMII) and HeartWare HVAD (HVAD). A total of 83/214 centers (39%) responded: North America (60/152), Europe (18/50), Australia (2/4), and Asia (3/8). Although the most common target international normalized ratio (INR) was 2-3 for both devices, significant variability exists. Anticoagulation intensity tended to be lower with the HMII, with more centers targeting INR values of less than 2.5. Aspirin monotherapy was the most common antiplatelet regimen; however, the HVAD patients were more likely to be on daily aspirin doses over 100 mg. In addition, parenteral bridging was more frequent with the HVAD device. While 43.8% of respondents indicated an increase in the perceived risk of HMII device thrombosis in 2014, intensification of anticoagulation (22%) or antiplatelet (11%) therapy was infrequent. Our findings verify the wide variety of anticoagulation practice patterns between MCS centers.
Assuntos
Anticoagulantes/uso terapêutico , Coração Auxiliar/efeitos adversos , Inibidores da Agregação Plaquetária/uso terapêutico , Tromboembolia/prevenção & controle , Pesquisas sobre Atenção à Saúde , Humanos , Padrões de Prática Médica , Tromboembolia/etiologiaRESUMO
AIMS: Calcineurin inhibitors (CNIs) taken after heart transplantation lead to excellent short-term outcomes, but long-term use may cause chronic nephrotoxicity. Our aim was to identify, appraise, select and analyse all high-quality research evidence relevant to the question of the clinical impact of CNI-sparing strategies in heart transplant patients. METHODS: We carried out a systematic review and meta-analysis of randomized controlled trials on CNI reduction in heart transplant recipients. Primary outcomes were kidney function and acute rejection after 1 year. Secondary outcomes included graft loss, all-cause mortality and adverse events. RESULTS: Eight open-label studies were included, with 723 patients (four tested de novoâ CNI reduction and four maintenance CNI reduction). Calcineurin inhibitor reduction did not improve creatinine clearance at 12 months 5.46 [-1.17, 12.03] P = 0.32 I(2) = 65.4%. Acute rejection at 12 months (55/360 vs. 52/332), mortality (18/301 vs. 15/270) and adverse event rates (55/294 vs. 52/281) did not differ between the low-CNI and standard-CNI groups. There was significant benefit on creatinine clearance in patients with impaired renal function at 6 months [+12.23 (+5.26, +18.82) ml min(-1) , P = 0.0003] and at 12 months 4.63 [-4.55, 13.82] P = 0.32 I(2) = 75%. CONCLUSIONS: This meta-analysis did not demonstrate a favourable effect of CNI reduction on kidney function, but there was no increase in acute rejection. To provide a better analysis of the influence of CNI reduction patterns and associated treatments, a meta-analysis of individual patient data should be performed.
Assuntos
Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/efeitos adversos , Rejeição de Enxerto/induzido quimicamente , Transplante de Coração , Nefropatias/induzido quimicamente , Nefropatias/fisiopatologia , Complicações Pós-Operatórias/induzido quimicamente , Inibidores de Calcineurina/uso terapêutico , Causas de Morte , Creatinina/metabolismo , Relação Dose-Resposta a Droga , Rejeição de Enxerto/epidemiologia , Transplante de Coração/efeitos adversos , Transplante de Coração/mortalidade , Humanos , Nefropatias/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
OBJECTIVES: This study was designed to delineate the role of implantable cardioverter defibrillator (ICD) therapy for the primary and secondary prevention of sudden cardiac death in patients listed for heart transplantation. SETTING: Retrospective observational multicentre study. PATIENTS: 1089 consecutive patients listed for heart transplantation in two tertiary heart transplant centres were enrolled. Of 550 patients (51%) on the transplant list with an ICD, 216 had received their ICD for the primary prevention of sudden cardiac death and 334 for secondary prevention. 539 patients did not receive an ICD. INTERVENTION: Treatment with or without an ICD was left to the discretion of the heart failure specialist. MAIN OUTCOME MEASURE: All-cause mortality. RESULTS: ICDs appear to be associated with a reduction in all-cause mortality in patients implanted with the device for primary and secondary prevention compared to those without an ICD despite a median time on the waiting list of only 8 months (estimated 1-year: 88±3% vs. 77±3% vs. 67±3%; p=0.0001). A Cox regressional hazard model (corrected for age, sex, underlying heart disease, atrial fibrillation, cardiac resynchronisation therapy, New York Heart Association (NYHA) class, ejection fraction, co-medication and year of listing) suggested an independent beneficial effect of ICDs that was most pronounced in patients who had received an ICD for primary prevention (HR 0.4, 95% CI 0.19 to 0.85; p=0.016). CONCLUSIONS: ICD implantation appears to be associated with an immediate and sustained survival benefit for patients awaiting heart transplantation.
Assuntos
Arritmias Cardíacas/prevenção & controle , Morte Súbita Cardíaca/prevenção & controle , Desfibriladores Implantáveis , Cardioversão Elétrica/instrumentação , Insuficiência Cardíaca/terapia , Transplante de Coração , Prevenção Primária/instrumentação , Prevenção Secundária/instrumentação , Listas de Espera , Adulto , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/mortalidade , Morte Súbita Cardíaca/etiologia , Cardioversão Elétrica/efeitos adversos , Cardioversão Elétrica/mortalidade , Feminino , Alemanha , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/mortalidade , Insuficiência Cardíaca/cirurgia , Humanos , Estimativa de Kaplan-Meier , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevenção Primária/métodos , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Prevenção Secundária/métodos , Suíça , Centros de Atenção Terciária , Fatores de Tempo , Resultado do Tratamento , Listas de Espera/mortalidadeRESUMO
The efficacy of everolimus with reduced cyclosporine in de novo heart transplant patients has been demonstrated convincingly in randomized studies. Moreover, everolimus-based immunosuppression in de novo heart transplant recipients has been shown in two randomized trials to reduce the increase in maximal intimal thickness based on intravascular ultrasound, indicating attenuation of cardiac allograft vasculopathy (CAV). Randomized trials of everolimus in de novo heart transplantation have also consistently shown reduced cytomegalovirus infection versus antimetabolite therapy. In maintenance heart transplantation, conversion from calcineurin inhibitors to everolimus has demonstrated a sustained improvement in renal function. In de novo patients, a renal benefit may only be achieved if there is an adequate reduction in exposure to calcineurin inhibitor therapy. Delayed introduction of everolimus may be appropriate in patients at high risk of wound healing complications, e.g. diabetic patients or patients with ventricular assist device. The current evidence base suggests that the most convincing reasons for use of everolimus from the time of heart transplantation are to slow the progression of CAV and to lower the risk of cytomegalovirus infection. A regimen of everolimus with reduced-exposure calcineurin inhibitor and steroids in de novo heart transplant patients represents a welcome addition to the therapeutic armamentarium.
Assuntos
Medicina Baseada em Evidências , Rejeição de Enxerto/tratamento farmacológico , Transplante de Coração , Imunossupressores/uso terapêutico , Sirolimo/análogos & derivados , Everolimo , Rejeição de Enxerto/epidemiologia , Humanos , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco , Sirolimo/uso terapêuticoRESUMO
This retrospective analysis of patients from eight countries included in the European Cubicin(®) Outcomes Registry and Experience (EU-CORE(SM)) captures the first post-approval years of clinical experience with daptomycin in its licensed indications. Of the total 1127 patients enrolled in EU-CORE between 2006 and 2008, 373 had a primary complicated skin and soft-tissue infection (cSSTI), most commonly surgical-site infection (48%), and 244 had bacteraemia, 55% of which were catheter-related. The most common pathogens were Staphylococcus aureus in cSSTIs (43%) and coagulase-negative staphylococci in bacteraemia (36%). The most frequently prescribed daptomycin doses were 4 mg/kg and 6 mg/kg for cSSTIs, and 6 mg/kg for bacteraemia. The median duration of inpatient and outpatient treatment, respectively, was 13 days and 8 days for cSSTIs and 8 days and 10 days for bacteraemia. Clinical success was reported for 81% of patients with cSSTIs and 77% with bacteraemia, with 82% success overall for infections caused by S. aureus. A trend towards higher clinical success was noted with higher daptomycin doses in bacteraemia (78% for 6 mg/kg vs. 90% for doses >6 mg/kg). Daptomycin demonstrated a favourable safety profile. Adverse events regardless of relationship to study drug were reported for 11% of patients with cSSTIs and 24% with bacteraemia, most commonly septic shock [7 patients (2%) with cSSTIs and 5 patients (2%) with bacteraemia]. These results demonstrate that daptomycin is effective and well tolerated in the treatment of cSSTIs and bacteraemia caused by Gram-positive bacteria in clinical practice.
Assuntos
Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Daptomicina/efeitos adversos , Daptomicina/uso terapêutico , Dermatopatias Bacterianas/tratamento farmacológico , Infecções dos Tecidos Moles/tratamento farmacológico , Adulto , Bacteriemia/microbiologia , Europa (Continente) , Feminino , Cocos Gram-Positivos/efeitos dos fármacos , Humanos , Masculino , Padrões de Prática Médica , Sistema de Registros , Estudos Retrospectivos , Dermatopatias Bacterianas/microbiologia , Infecções dos Tecidos Moles/microbiologia , Infecção da Ferida Cirúrgica/tratamento farmacológico , Infecção da Ferida Cirúrgica/microbiologia , Resultado do TratamentoRESUMO
BACKGROUND: Viral infection and anti-cardiac immunity are involved in the pathogenesis of dilated cardiomyopathy (DCM). Immunity targeting particular antigens may evoke expansion of reactive T-cell clones. MATERIAL AND METHODS: Myocardial tissues from explanted hearts were investigated for clonal T-cell-receptor- (TCR-) ß rearrangements by an established semi-nested polymerase chain reaction (PCR), followed by high-resolution GeneScan analysis and direct sequencing. From 17 explanted DCM hearts, 3 myocardial samples each were obtained from the right ventricle, the septum, and the left ventricle (total: 9 myocardial samples per case). Six explanted hearts with non-DCM cardiomyopathy entities served as controls. RESULTS: GeneScan analysis revealed polyclonal TCR-ß rearrangements in all controls. In contrast, at least 1 myocardial sample in 9 out of 17 DCM hearts (total: 20 of the 81 DCM specimens) displayed single dominant TCR-ß PCR products consistent with the presence of clonal T-cell populations. Direct sequencing of the clonal TCR-ß PCR-products disclosed an involvement of Vß 19.01 segments in 14 of the dominant amplificates (70%). Further TCR-Vß segments involved in clonal TCR-ß rearrangements of DCM hearts were Vß 6-1.01 (n=1), Vß 6-3.01 (n=2), Vß 6-5.01 (n=1), Vß 10-3.02 (n=1), and Vß 19.03 (n=1). CONCLUSIONS: The detectability of clonal TCR-ß rearrangements indicates a pathogenic relevance of this finding in DCM. The predominance of Vß 19.01 segments suggests that the immune response in DCM patients targets particular epitopes. However, the partly heterogenic TCR-ß populations in various myocardial samples from the respective cases support the notion that T-cell immunity may target multiple epitopes in human DCM.
Assuntos
Cardiomiopatia Dilatada/imunologia , Cardiomiopatia Dilatada/patologia , Rearranjo Gênico da Cadeia beta dos Receptores de Antígenos dos Linfócitos T/genética , Reação em Cadeia da Polimerase/métodos , Análise de Sequência de DNA/métodos , Adulto , Antígenos/química , Cardiomiopatia Dilatada/genética , Epitopos/química , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Miocardite/genética , Miocardite/imunologia , Miocardite/patologia , Miocárdio/patologiaRESUMO
The evidence base relating to the use of everolimus in heart transplantation has expanded considerably in recent years, providing clinically relevant information regarding its use in clinical practice. Unless there are special considerations to take into account, all de novo heart transplant patients can be regarded as potential candidates for immunosuppression with everolimus and reduced-exposure calcineurin inhibitor therapy. Caution about the use of everolimus immediately after transplantation should be exercised in certain patients with the risk of severe proteinuria, with poor wound healing, or with uncontrolled severe hyperlipidemia. Initiation of everolimus in the early phase aftertransplant is not advisable in patients with severe pretransplant end-organ dysfunction or in patients on a left ventricular assist device beforetransplant who are at high risk of infection or of wound healing complications. The most frequent reason for introducing everolimus in maintenance heart transplant patients is to support minimization or withdrawal of calcineurin inhibitor therapy, for example, due to impaired renal function or malignancy. Due to its potential to inhibit the progression of cardiac allograft vasculopathy and to reduce cytomegalovirus infection, everolimus should be initiated as soon as possible after heart transplantation. Immediate and adequate reduction of CNI exposure is mandatory from the start of everolimus therapy.
RESUMO
OBJECTIVES: Even though left ventricular assist devices (LVADs) may fit into the bodies of small adult patients, their prognosis is worse than that of larger patients. We investigated the relationship between lethal complications and the body surface area (BSA) in patients who received an LVAD. METHODS: Our study included 167 patients who received a BerlinHeart INCOR LVAD in our centre. The median BSA was 2.00 m(2) (range: 1.56-2.47 m²). From the line graph showing the relationship between the BSA for the cut-off point and the P-value of the log-rank test for the Kaplan-Meier probability of freedom from events, the definitive cut-off point was determined on the basis that, with a decrease in the BSA below this value, the P-value gradually increases. RESULTS: For freedom from death due to stroke or systemic bleeding, a definitive cut-off point existed and this was a BSA of 1.867 m(2). For freedom from death due to sepsis, no definitive cut-off point was found. The multivariate Cox analysis revealed that a BSA of <1.867 m(2) was an independent risk factor for death due to stroke or systemic bleeding (hazard ratio: 2.665, 95% confidence interval: 1.349-5.265, P = 0.0048). One-year freedom from death due to stroke or systemic bleeding during the VAD support was 49.1% in patients with a BSA of <1.867 m(2) (n = 42) and 82.7% in those with a BSA of ≥ 1.867 m(2) (n = 125; P = 0.0033). CONCLUSIONS: The lower BSA is an independent risk factor for mortality due to stroke or systemic bleeding during the VAD support.
Assuntos
Superfície Corporal , Procedimentos Cirúrgicos Cardíacos/instrumentação , Coração Auxiliar , Implantação de Prótese/instrumentação , Acidente Vascular Cerebral/etiologia , Idoso , Feminino , Insuficiência Cardíaca/cirurgia , Hemorragia/etiologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Prognóstico , Análise de Regressão , Fatores de RiscoRESUMO
BACKGROUND: There has been no large evaluation of the ISHLT 2004 acute cellular rejection grading scheme for heart graft endomyocardial biopsy specimens (EMBs). METHODS: We evaluated agreement within the CARGO II pathology panel and between the panel (acting by majority) and the collaborating centers (treated as a single entity), regarding the ISHLT grades of 937 EMBs (with all grades ≥2R merged because of small numbers). RESULTS: Overall all-grade agreement was almost 71% both within the panel and between the panel and the collaborating centers but, in both cases, was largely because of agreement on grade 0: for the average pair of pathologists, fewer than a third of the EMBs assigned grade ≥2R by at least one were assigned this grade by both. CONCLUSION: The 2004 revision has done little to improve agreement on the higher ISHLT grades. An EMB grade ≥2R is not by itself sufficient as a basis for clinical decisions or as a research criterion. Steps should be taken toward greater uniformity in EMB grading, and efforts should be made to replace the ISHLT classification with diagnostic criteria--EMB based or otherwise--that correspond better with the pathophysiology of the transplanted heart.
Assuntos
Rejeição de Enxerto/genética , Rejeição de Enxerto/patologia , Transplante de Coração/efeitos adversos , Patologia Clínica/normas , Biópsia/normas , Corantes , Amarelo de Eosina-(YS) , Europa (Continente) , Regulação da Expressão Gênica , Rejeição de Enxerto/imunologia , Hematoxilina , Humanos , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Coloração e Rotulagem/normas , Estados UnidosRESUMO
BACKGROUND: The main cause of early death after heart transplantation (HTx) is so-called early primary or secondary graft failure (GF). The risk of profound GF has not declined in the past decade, as the consequence of the liberalisation of donor acceptance criteria because of the scarcity of donors. It is therefore important to try to diagnose graft failure and recognise the mechanisms of early graft dysfunction. AIM: To establish haemodynamic and echocardiographic criteria of early GF to define patients who should be considered for assist device support or re-transplantation. METHODS: Between January 2000 and March 2009, 116 HTx patients were studied. On the basis of echocardiography and continuous invasive monitoring, three groups were identified: (1) The true graft failure group (GF) consisted of 46 patients; (2) The latent right ventricular (RV) dysfunction group (RV-D) consisted of 25 patients with small left ventricular (LV) chamber (ã 39 mm) and RV ejection fraction (RVEF) ã 50%; (3) The control group consisted of 45 consecutive HTx patients without any haemodynamic complications. RESULTS: Postoperatively, only the GF group required large doses of norepinephrine (ã 0.3 µmg/kg/min) and inhalative NO (40 ppm). Nevertheless, right and left filling pressures were significantly higher than in the controls (right 12 ± 3.6 vs. 9.0 ± 2 and left atrial pressure 13.0 ± 3.2 vs. 9.6 ± 2 mm Hg, both p ã 0.001). Cardiac index was significantly smaller (2.9 ± 0.7 vs. 3.7 ± 0.9, p ã 0.001) but neither pulmonary artery pressure (29.5 ± 6 vs. 29.7 ± 7 mm Hg) nor transpulmonary gradient (6 ± 5 vs. 5.1 ± 5 mm Hg) nor pulmonary vascular resistance (273 ± 97 vs. 287 ± 144 dyn × s × cm-5) differed significantly from those of the control group. In the GF group, LV end diastolic dimension (LVEDD) was significantly smaller and function poorer than in controls (39.8 ± 5 vs. 44.4 ± 5 mm, respectively, p = 0.001). RV function was also significantly worse (RVEF 42.2 ± 14% vs. 56.0 ± 9%), respectively, p = 0.001), whereas RV dimension did not differ significantly. Mechanical support after failure of the initial medical treatment was necessary in 37% of patients; 29 (63.0%) patients from the GF group died, the cause of death being sepsis with multi-organ failure. In the RV-D group, remodelling was quite similar but LVEF was excellent and maximal systolic velocity from the posterior wall was significantly higher than in GF. No death occurred. CONCLUSIONS: True early GF represents a grave haemodynamic situation with high mortality. Bedside echocardiography helps to distinguish between latent RV dysfunction and true GF.
Assuntos
Rejeição de Enxerto/diagnóstico , Rejeição de Enxerto/fisiopatologia , Transplante de Coração/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Direita/fisiopatologia , Causalidade , Comorbidade , Diagnóstico Precoce , Ecocardiografia , Feminino , Rejeição de Enxerto/epidemiologia , Transplante de Coração/fisiologia , Hemodinâmica , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Insuficiência de Múltiplos Órgãos/mortalidade , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/epidemiologia , Disfunção Ventricular Direita/diagnóstico por imagem , Disfunção Ventricular Direita/epidemiologiaRESUMO
BACKGROUND: Detection of cardiac recovery that allows long-term cardiac stability after ventricular assist device (VAD) explantation is a major goal. After normalization of ventricular diameters during unloading, the pre-explant left ventricular ejection fraction (LVEF) allows the detection of patients with the potential to remain stable after VAD explantation. However, some patients with LVEF >45 before VAD explantation show early recurrence of heart failure (HF). We aimed to find out if unstable improvement can be recognized before VAD explantation. METHODS AND RESULTS: Among 96 patients weaned from VADs since 1995, a relatively homogenous group of 53 patients with nonischemic chronic cardiomyopathy (CCM) was selected for the study. The pre-explant stability of major parameters of LV function, size, and geometry that were measured by echocardiography during serial "off-pump" trials was tested for relationship with cardiac stability after VAD explantation. LVEF, systolic peak wall motion velocity (Sm), end-diastolic diameter (LVEDD), end-diastolic relative wall thickness (RWT(ED)) and end-diastolic short/long-axis ratio (S/L(ED)) were selected for evaluation. In postweaning unstable patients, the selected parameters showed relevant instability already before VAD explantation during the time period between best cardiac improvement and VAD explantation and also during the final off-pump trial just before VAD explantation. For all parameters, there were significant differences (P<0.05) in pre-explant changes between patients with and without postweaning cardiac stability. Using the optimal cutoff values obtained from receiver-operating characteristic analysis, we found for our selected parameters predictive values for postexplant cardiac stability of ≥1 year, ≥3 years, and ≥5 years, ranging between 94 and 100, 92, and 100, and 78 and 100, respectively. Using for all parameter changes the cutoff value of 10, we found similar predictive values for cardiac stability of ≥1 year, ≥3 years, and ≥5 years, ranging between 93 and 97, 90 and 96, and 83 and 92, respectively. CONCLUSIONS: Our results strongly suggest the possibility to improve the prediction of postexplant transplant/VAD-free outcome in CCM patients with cardiac improvement during VAD support by analyzing the pre-explant stability of several LV off-pump echocardiographic parameters during serial off-pump trials.
Assuntos
Insuficiência Cardíaca/cirurgia , Coração Auxiliar , Função Ventricular Esquerda , Adolescente , Adulto , Idoso , Fármacos Cardiovasculares/uso terapêutico , Terapia Combinada , Remoção de Dispositivo , Feminino , Insuficiência Cardíaca/diagnóstico por imagem , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos , Hipertrofia Ventricular Esquerda/diagnóstico por imagem , Hipertrofia Ventricular Esquerda/fisiopatologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Tamanho do Órgão , Prognóstico , Modelos de Riscos Proporcionais , Recuperação de Função Fisiológica , Recidiva , Estudos Retrospectivos , Volume Sistólico , Resultado do Tratamento , Ultrassonografia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Continuous-flow (CF) ventricular assist devices (VAD) are an established option for treatment of end-stage heart failure. However, the effect of long-term CF with lack of peripheral arterial wall motions on blood pressure regulation and end-organ arterial wall sclerosis, especially in the case of long-term support (> 3 years), remains unclear. METHODS: Tissue samples obtained at autopsy from liver, kidney, coronary arteries, and brain from 27 VAD recipients supported for > 180 days between 2000 and 2010 were histologically examined to assess vascular alterations, including perivascular infiltrate, intravascular infiltrate, wall thickness, thrombosis, endothelial cell swelling, vessel wall necrosis, and peri-vascular fibrosis. Pulsatile-flow (PF) devices had been inserted in 9 patients and CF devices had been inserted in 16. The pathologist was blinded to the group distribution. Demographic, pharmacologic, and clinical data were retrospectively analyzed before surgery and during the follow-up period of up to 24 months. RESULTS: Median duration of support was 467 days (range, 235-1,588 days) in the PF group and 263 days (range, 182-942 days) in the CF group. Demographic and clinical data before and after surgery were similar. Amiodarone was more often used during follow-up in CF group than in the PF group (61% vs 10%, p = 0.009). Throughout the follow-up period, mean arterial pressure did not differ between recipients of the 2 pump types, nor did systolic and diastolic pressure, except at 2 weeks after VAD implantation, when systolic blood pressure was higher (p = 0.05) and diastolic lower (p = 0.03) in the PF group. Histologic studies did not identify any relevant differences in arterial wall characteristics between the 2 groups. CONCLUSION: Long-term mechanical circulatory support with CF devices does not adversely influence arterial wall properties of the end-organ vasculature.
Assuntos
Artérias Cerebrais/patologia , Vasos Coronários/patologia , Insuficiência Cardíaca/terapia , Coração Auxiliar/classificação , Artéria Hepática/patologia , Artéria Renal/patologia , Adulto , Idoso , Fenômenos Biomecânicos/fisiologia , Pressão Sanguínea/fisiologia , Artérias Cerebrais/fisiopatologia , Vasos Coronários/fisiopatologia , Feminino , Fibrose , Seguimentos , Insuficiência Cardíaca/fisiopatologia , Artéria Hepática/fisiopatologia , Humanos , Hiperplasia , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Necrose , Artéria Renal/fisiopatologia , Estudos Retrospectivos , Fatores de TempoRESUMO
AIMS: Prolongation of waiting times for heart transplantation (HTx) increases the need for new therapies. In short-term follow-up studies, immunoadsorption (IA) appeared beneficial in dilated cardiomyopathy (DCM) associated with ß(1)-adrenoreceptor-autoantibodies (ß(1)-AABs). This study aimed to investigate the long-term benefits of IA in HTx candidates with DCM, patients' responsiveness to IA, and the impact of ß(1)-AAB removal on IA results. METHODS AND RESULTS: In a single-centre retrospective study of prospectively gathered information we evaluated all ß(1)-AAB-positive and -negative HTx candidates with end-stage DCM [left ventricular ejection fraction (LVEF) <30%] who underwent IA between 1995 and 2005 (follow-up thereafter: 5.3-14.7 years). As controls we used all ß(1)-AAB-positive DCM patients referred for HTx during the same time period who received no IA therapy. We also looked for differences in efficacy between unspecific IA (unselective antibody removal) and specific IA (selective ß(1)-AAB removal). The main outcome measures were cardiac function and HTx/ventricular assist device (VAD)-free patient survival. The probability for 5-year HTx/VAD-free survival for the108 ß(1)-AAB-positive DCM patients who underwent unspecific IA reached 69.4 ± 4.4% and was significantly higher (P < 0.05) than for both ß(1)-AAB-positive DCM patients without IA (25.4 ± 11.4%) and ß(1)-AAB-negative DCM patients who also underwent IA (47.4 ± 11.5). In patients with high ß(1)-AAB levels, unspecific and specific IA showed the same high efficiency in ß(1)-AAB removal. LVEF and New York Heart Assocation class improved (P < 0.01) after both, but without differences in improvement after specific or unspecific IA. The prevalence of responders to specific and unspecific IA was similar (78.3% vs. 79.6%). In 76% of the patients with ß(1)-AAB reappearance, redetection of AABs coincided with worsening of cardiac function. CONCLUSIONS: Removal of ß(1)-AABs by specific or unspecific IA can improve cardiac function allowing long-term stability in end-stage DCM, which can spare many patients from HTx or will delay HTx listing for years. In ß(1)-AAB-positive DCM patients the benefits of IA appeared to be associated with the removal of these antibodies.
Assuntos
Cardiomiopatia Dilatada/imunologia , Cardiomiopatia Dilatada/terapia , Técnicas de Imunoadsorção , Receptores Adrenérgicos beta 1/imunologia , Adolescente , Antagonistas Adrenérgicos beta/uso terapêutico , Adulto , Idoso , Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Autoanticorpos/imunologia , Cardiomiopatia Dilatada/cirurgia , Cardiotônicos/uso terapêutico , Estudos de Casos e Controles , Digoxina/uso terapêutico , Diuréticos/uso terapêutico , Feminino , Transplante de Coração , Humanos , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores de Risco , Taxa de Sobrevida , Resultado do Tratamento , Listas de EsperaRESUMO
We describe the case of a 37-year-old man with a rare giant thymic neuroendocrine tumor. The patient presented with a swelling of the neck associated with superior vena cava syndrome and underwent stent implantation in the right innominate vein (brachiocephalic vein). Computed tomography imaging revealed a large tumor of the mediastinum, measuring 15 × 10 × 12 cm. CT-guided core-needle biopsy for histology revealed a thymic carcinoid. Surgical resection of the tumor and repair with interposition of a 14-mm Gore-Tex prosthesis between the left innominate vein and the right atrial appendage were performed. Histopathological analysis classified the tumor as an atypical thymic carcinoid. Postoperative course was uneventful. Since complete resection could not be achieved, the patient received two cycles of peptide-receptor radionuclide therapy followed by conventional radiotherapy, and remains symptom-free at 12 months after surgery.
Assuntos
Tumor Carcinoide/complicações , Doenças Raras/complicações , Síndrome da Veia Cava Superior/etiologia , Neoplasias do Timo/complicações , Adulto , Tumor Carcinoide/patologia , Humanos , Masculino , Doenças Raras/patologia , Stents , Síndrome da Veia Cava Superior/cirurgia , Neoplasias do Timo/patologia , Carga TumoralRESUMO
Although extreme obesity and being underweight are both known as risk factors for mortality in patients with ventricular assist devices (VAD) and in those listed for urgent heart transplantation (HTx), the risk in patients between these extremes is controversial. We investigate the risk of mortality after their progression to critically ill status (i.e., urgency listing or VAD implantation) in patients stratified by body mass index (BMI). Risk of mortality on the waiting list was studied in group N (n = 134), normal weight, BMI: 18.5-24.9 kg/m(2); group OWt (n = 112), overweight, BMI: 25.0-29.9 kg/m(2); and group OB-I (n = 39), obesity class I, BMI: 30.0-34.9 kg/m(2). Patients' 1 year survival rate on the waiting list in group N (62.2%) and group OB-I (50.6%) was significantly lower than in group OWt (74.3%, p = 0.036 and p = 0.022, respectively). After adjustment for age, gender, serum creatinine, and primary use of VAD, group OB-I (hazard ratio [HR] 1.971, 95% confidence interval [CI] 1.062-3.659, p = 0.032) and group N (HR 1.792, 95% CI 1.058-3.036, p = 0.030) were at higher risk of mortality compared with group OWt. Overweight HTx candidates have the best prognosis on the waiting list. Obesity class I patients are encouraged to reduce their body weight to at least overweight.
Assuntos
Transplante de Coração/métodos , Coração Auxiliar , Adulto , Índice de Massa Corporal , Peso Corporal , Procedimentos Cirúrgicos Cardíacos/métodos , Cardiologia/métodos , Estudos de Coortes , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sobrepeso , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
Cytomegalovirus (CMV) -specific immunity is often estimated by the number of in vitro CMV antigen-inducible interferon-γ-positive (IFN-γ(+) ) T cells. However, recent work indicates that simultaneous production of IFN-γ, tumour necrosis factor-α (TNF-α) and interleukin-2 (IL-2) (referred to as 'polyfunctionality') is more relevant for anti-viral protection. Here, we compared polyfunctionality of CMV-specific T cells (pp65 and IE-1 proteins) in 23 solid-organ transplant patients and seven healthy controls by flow cytometry. The proportions of TNF-α(+) /IFN-γ(+) /IL-2 cells among the activated cells were significantly reduced in transplant patients but not the frequencies of IFN-γ(+) CD8(+) T cells. Immunosuppression reduces polyfunctionality, which reflects the increased infection risk in this patient group.
Assuntos
Linfócitos T CD8-Positivos/imunologia , Ciclosporina/farmacologia , Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Imunossupressores/farmacologia , Interferon gama/biossíntese , Tacrolimo/farmacologia , Adolescente , Adulto , Linfócitos T CD8-Positivos/efeitos dos fármacos , Linfócitos T CD8-Positivos/metabolismo , Feminino , Humanos , Interleucina-2/biossíntese , Ativação Linfocitária , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos , Fator de Necrose Tumoral alfa/biossíntese , Adulto JovemRESUMO
BACKGROUND: Burkitt lymphoma post-transplantation lymphoproliferative disorder (Burkitt-PTLD) is a rare form of monomorphic B-cell PTLD for which no standard treatment has been established. Currently, the treatment of Burkitt lymphoma outside the post-transplantation setting involves high doses of alkylating agents, frequent dosing, and intrathecal and/or systemic central nervous system prophylaxis. In PTLD, however, such protocols are associated with considerable toxicity and mortality. METHODS: The authors present a retrospective series of 8 adult patients with Burkitt-PTLD. Six patients were reported to the prospective German PTLD registry or were enrolled in the PTLD-1 trial, and 2 patients had received treatment before 2000, thus allowing for comparison with the pre-rituximab era. RESULTS: Seven of the 8 patients were men. The median age at presentation was 38 years, and the median time since transplantation was 5.7 years. Five of 8 patients had histologically established, Epstein-Barr virus-associated disease, and 7 of 7 patients were positive for a MYC translocation. Five of 8 patients received sequential immunochemotherapy (4 courses of rituximab [R] followed by 4 cycles of cyclophosphamide, doxorubicin, vincristine, and prednisolone [CHOP] or R plus CHOP [R-CHOP]). In this group, 5 of 5 patients reached complete remission (CR), and their overall survival (OS) was significantly longer (P = .008) compared with the OS for 2 of 8 patients who received first-line CHOP and did not respond. One of 8 patients (who had stage IV disease with meningiosis) received combination therapy (cyclophosphamide pretreatment, rituximab, intrathecal chemotherapy, whole-brain irradiation, and radioimmunotherapy) and reached CR. Overall, 6 of 8 patients reached CR; and, after a median follow-up of 4.7 years (range, 1.7-4.8 years), the median OS was 36.7 months. There was no treatment-related mortality under first-line therapy. CONCLUSIONS: In the largest adult case series in Burkitt-PTLD to date, sequential immunochemotherapy with rituximab followed by standard CHOP or R-CHOP was a both safe and effective treatment.
Assuntos
Anticorpos Monoclonais Murinos/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Linfoma de Burkitt/tratamento farmacológico , Linfoma de Burkitt/imunologia , Fatores Imunológicos/uso terapêutico , Transplante de Órgãos , Adulto , Idoso , Algoritmos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Biomarcadores Tumorais/análise , Linfoma de Burkitt/química , Linfoma de Burkitt/patologia , Linfoma de Burkitt/virologia , Irradiação Craniana , Ciclofosfamida/administração & dosagem , Doxorrubicina/administração & dosagem , Infecções por Vírus Epstein-Barr/complicações , Feminino , Seguimentos , Alemanha , Humanos , Hibridização in Situ Fluorescente , Injeções Espinhais , Masculino , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Sistema de Registros , Indução de Remissão , Estudos Retrospectivos , Rituximab , Resultado do Tratamento , Vincristina/administração & dosagemRESUMO
BACKGROUND: Plasmablastic posttransplant lymphoma is a rare subtype of monomorphic B-cell posttransplant lymphoproliferative disorder (PTLD). There is little published clinical data to guide treatment. METHODS: The German prospective PTLD registry D2006-2012 records baseline features, treatment, and outcome of rare PTLD subtypes in adults after solid organ transplantation. Treatment is at the discretion of the local physician. Clinical data on the patients in the registry is collected before, during, and at least 4 weeks, 6 months, 12 and 24 months after treatment. RESULTS: Eight cases of plasmablastic posttransplant lymphoma were reported to the registry until 2011. The majority occurred as late PTLD in male heart transplant recipients. Extranodal manifestations were common in stage I and in stage IV disease. Histological Epstein-Barr virus (EBV) association was confirmed in five of eight cases. MYC/IGH rearrangement was present in two of six patients examined. Although five of eight patients died from early disease progression, we observed that long-term survival can be achieved in localized (2/3) and in disseminated disease (1/5) by immunosuppression reduction (IR) followed by immediate systemic chemotherapy. However, all patients with cytogenetic aberrations and patients with non-EBV-associated PTLD were refractory to IR and to chemotherapy. Chemotherapy parallel to IR was associated with a high rate of infectious complications. CONCLUSIONS: In this series, IR and local therapy were not sufficient to treat plasmablastic posttransplant lymphoma even in localized disease whereas IR and systemic chemotherapy (CHOP-21) could achieve lasting complete remissions. Cytogenetic aberrations and lack of EBV association were linked with poor outcome.
Assuntos
Aberrações Cromossômicas , Infecções por Vírus Epstein-Barr/complicações , Linfoma de Células B/etiologia , Transtornos Linfoproliferativos/etiologia , Transplante de Órgãos/efeitos adversos , Adulto , Idoso , Feminino , Rearranjo Gênico , Alemanha , Humanos , Imuno-Histoquímica , Hibridização in Situ Fluorescente , Linfoma de Células B/genética , Linfoma de Células B/mortalidade , Linfoma de Células B/terapia , Linfoma de Células B/virologia , Transtornos Linfoproliferativos/genética , Transtornos Linfoproliferativos/mortalidade , Transtornos Linfoproliferativos/terapia , Transtornos Linfoproliferativos/virologia , Masculino , Pessoa de Meia-Idade , Transplante de Órgãos/mortalidade , Estudos Prospectivos , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Prospective comparative studies to predict the risk of hemodynamic deterioration in patients referred for transplantation were performed on the basis of standard invasive and non-invasive data and new wave intensity (WI) parameters. METHODS AND RESULTS: Study Group 1 consisted of 151 consecutive outpatients (age 48.7 ± 12 years; 110 men) with end-stage dilative cardiomyopathy. Group 2, consisting of 11 consecutive patients (age 50 ± 11 years; 6 men) with sinus rhythm and "true" decompensation, was used to create "critical values" of WI. There were no demographic or somatic (weight and height) differences between the groups. The follow-up period of ambulatory patients was 31 ± 8 months. Non-invasive WI was studied in the common carotid artery. Complete invasive and non-invasive data were also recorded on the day of investigation. During follow-up 44 pts were lost; there were 15 cardiac deaths (10%), life-saving ventricular assist device implantation in 10 (6.6%) and transplantation in 19 (12.7%). For statistical purposes this group was named the "events" Group B (n = 44). A predisposing factor for events (death, "true" decompensation and "urgent" transplantation in ambulatory patients) was low first peak ("cut-off value" assessed in Group 2 < 4100 mmHg*s³) (OR 45.6, CI 14.5-143.3, p < 0.001). Less powerful predictors of the risk of deterioration were pulmonary capillary pressure (PCP), diastolic pulmonary artery pressure (PAP) and E/A mitral wave relation (p = 0.05). CONCLUSIONS: The new ventricular-arterial coupling parameter 1st peak of WI can potentially be used to distinguish patients at high risk for true deterioration and death. This parameter can be used to predict the need for assist device implantation.