RESUMO
Cardiovascular diseases have become a significant cause of morbidity in patients with human immunodeficiency virus (HIV) infection. Heart transplantation (HT) is a well-established treatment of end-stage heart failure (ESHF) and is performed in selected HIV-infected patients in developed countries. Few data are available on the prognosis of HIV-infected patients undergoing HT in the era of combined antiretroviral therapy (cART) because current evidence is limited to small retrospective cohorts, case series, and case reports. Many HT centers consider HIV infection to be a contraindication for HT; however, in the era of cART, HT recipients with HIV infection seem to achieve satisfactory outcomes without developing HIV-related events. Consequently, selected HIV-infected patients with ESHF who are taking effective cART should be considered candidates for HT. The present review provides epidemiological data on ESHF in HIV-infected patients from all published experience on HT in HIV-infected patients since the beginning of the epidemic. The practical management of these patients is discussed, with emphasis on the challenging issues that must be addressed in the pretransplant (including HIV criteria) and posttransplant periods. Finally, proposals are made for future management and research priorities.
Assuntos
Terapia Antirretroviral de Alta Atividade/efeitos adversos , Infecções por HIV/complicações , Insuficiência Cardíaca/cirurgia , Transplante de Coração , Infecções por HIV/tratamento farmacológico , Insuficiência Cardíaca/induzido quimicamente , Humanos , PrognósticoRESUMO
BACKGROUND: A number of changes in the management of heart transplantation (HT) patients have each tended to reduce the risk of post-HT hematologic cancer, but little information is available concerning the overall effect on incidence in the HT population. METHODS: Comparison of data from the Spanish Post-Heart-Transplantation Tumour Registry for the periods 1991-2000 and 2001-2010. RESULTS: The incidence among patients who underwent HT in the latter period was about half that observed in the former, with a particularly marked improvement in regard to incidence more than five yr post-HT. CONCLUSIONS: Changes in HT patient management have jointly reduced the risk of hematologic cancer in the Spanish HT population. Long-term risk appears to have benefited more than short-term risk.
Assuntos
Transplante de Coração/estatística & dados numéricos , Neoplasias Hematológicas/epidemiologia , Idoso , Feminino , Seguimentos , Insuficiência Cardíaca/cirurgia , Neoplasias Hematológicas/prevenção & controle , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Sistema de Registros , Fatores de Risco , Espanha/epidemiologiaRESUMO
Toxoplasma gondii is an opportunistic pathogen that causes neurologic and extraneurologic manifestations in immunosuppressed patients. Encephalitis and intracranial mass lesions are easily recognized as typical manifestations of toxoplasmosis. However, meningitis caused by T. gondii is a rare condition with very few cases described in the literature. We present the case of a heart transplant recipient who developed toxoplasmic encephalitis associated with meningitis. After an extensive review of the medical literature, we found only 1 case of meningitis in solid organ transplant recipients and <25 cases in immunosuppressed patients, such as patients infected with human immunodeficiency virus or those with Hodgkin's disease. In this report, we consider toxoplasmosis in the differential diagnosis of meningitis in immunocompromised individuals.
Assuntos
Encefalite/parasitologia , Transplante de Coração/efeitos adversos , Meningite/parasitologia , Toxoplasmose Cerebral/etiologia , Antiprotozoários/administração & dosagem , Antiprotozoários/uso terapêutico , Clindamicina/administração & dosagem , Clindamicina/uso terapêutico , Quimioterapia Combinada , Humanos , Masculino , Meningite/complicações , Pessoa de Meia-Idade , Inibidores da Síntese de Proteínas/administração & dosagem , Inibidores da Síntese de Proteínas/uso terapêutico , Pirimetamina/administração & dosagem , Pirimetamina/uso terapêutico , Toxoplasmose Cerebral/parasitologiaRESUMO
Anti-Pneumocystis prophylaxis is recommended for at least 6-12 months after solid organ transplantation, as most cases of Pneumocystis jirovecii pneumonia (PCP) occur during the first year post transplantation. Herein, we report 4 cases of late-onset PCP (>1 year post transplant). PCP appeared in a range of 50-68 months post transplant. Two cases had history of humoral rejection episodes treated with rituximab, and the other 2 had low CD4+ T-cell count (<200 cells/mm(3) ) at the time of diagnosis. All 4 patients survived. In conclusion, although the number of cases is low, we must be aware of the possibility of late-onset PCP in solid organ transplant patients. The role of previous use of rituximab or persistent CD4+ T-cell lymphopenia should be addressed in future studies.
Assuntos
Anti-Infecciosos/uso terapêutico , Transplante de Órgãos/efeitos adversos , Pneumocystis carinii , Pneumonia por Pneumocystis/tratamento farmacológico , Combinação Trimetoprima e Sulfametoxazol/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pneumonia por Pneumocystis/diagnóstico , Pneumonia por Pneumocystis/microbiologia , Fatores de TempoRESUMO
BACKGROUND: Information concerning the risk factors and outcome of late infection (LI) after solid organ transplantation (SOT) still remains scarce. METHODS: We prospectively analyzed all patients undergoing SOT from July 2003 to March 2008, who survived the first 6 months after surgery and with a minimum 1-year follow-up. Risk factors associated with the development of bacterial and cytomegalovirus (CMV) LI and survival were identified. RESULTS: Overall, 942 SOT recipients (491 kidney, 280 liver, 65 heart, and 106 double transplants) were included. During the study period 147 patients (15.6%) developed 276 episodes of LI (incidence rate, 0.43 per 1000 transplantation-days). Bacteria were the most prevalent etiology (88.0%). Primary sources of infection included urinary tract (36.9%), intra-abdominal (16.7%), and sepsis without source (13.4%). Independent risk factors for late bacterial infection were: age (hazard ratio [HR] [per year] 1.0; 95% confidence interval [CI]: 1.0-1,0), female gender (HR 1.7; 95%CI: 1.1-2.6), anti-hepatitis C virus (HCV) positive serostatus (HR 1.8; 95%CI: 1.1-3.0), chronic allograft dysfunction (HR 3.2; 95%CI: 1.7-6.1), early CMV disease (HR 2.2; 95%CI 1.2-4.1), and early bacterial infection (HR 2.5; 95%CI 1.6-3.8). The occurrence of chronic allograft dysfunction was an independent risk factor for late CMV disease (HR 6.5; 95%CI: 1.7-24.6), whereas immunosuppression based on mammalian target of rapamycin inhibitors protected against the development of late CMV disease (HR 0.3; 95%CI: 0.1-1.0). Cox model selected anti-HCV positive serostatus (adjusted HR [aHR] 2.67; 95%CI: 1.27-5.59), age (aHR [per year] 1.06; 95%CI: 1.02-1.10), and the occurrence of LI (aHR 9.12; 95%CI: 3.90-21.33) as independent factors for mortality. CONCLUSIONS: LI did not constitute an uncommon complication in our cohort, and patients at risk may benefit from close clinical monitoring.
Assuntos
Imunossupressores/efeitos adversos , Infecções Oportunistas/complicações , Infecções Oportunistas/epidemiologia , Transplante de Órgãos , Complicações Pós-Operatórias , Adulto , Infecções Bacterianas/complicações , Infecções Bacterianas/epidemiologia , Estudos de Coortes , Citomegalovirus , Infecções por Citomegalovirus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Micoses/complicações , Micoses/epidemiologia , Doenças Parasitárias/complicações , Doenças Parasitárias/epidemiologia , Estudos Prospectivos , Fatores de Risco , Espanha/epidemiologia , Viroses/complicações , Viroses/epidemiologiaRESUMO
BACKGROUND: Pulmonary function tests (PFTs) are often impaired in patients with advanced heart failure. There is limited data about their impact on survival after heart transplantation (HT). We sought to assess the prevalence and type of PFT abnormalities in patients on HT waiting list and their impact on outcomes. METHODS: We performed a retrospective analysis of a prospective registry of consecutive patients undergoing HT between 2012 and 2018. Patients were classified into 4 groups according to pre-HT PFT results: 1. normal pattern: forced vital capacity (FVC) ≥ 80% and forced expiratory volume in 1 second (FEV1) to FVC ratio (FEV1/FVC) ≥ 0.7; 2. obstructive: FEV1/FVC < 0.7; 3. nonobstructive: FEV1/FVC ≥ 0.7 and FVC < 80% when total lung capacity value was not available; and 4. restrictive: FEV1/FVC ≥ 0.7 and total lung capacity < 80%. The prevalence of impaired carbon monoxide diffusing capacity corrected for hemoglobin < 80% and FEV1 < 70% was also analyzed. High-urgency HT patients and those referred from other centers without quantitative pulmonary evaluation were excluded. RESULTS: Among 123 patients who underwent HT, 83 patients with complete PFT were included. Median follow-up was 2.7 ± 1.9 years. Of these, 29 (34.9%) had an obstructive pattern, 20 (24.1%) a nonobstructive, 18 (21.7%) a restrictive, and 16 (19.3%) a normal pattern. Fifty-one (61.4%) patients had FEV1 < 70% and 58 (69.9%) a carbon monoxide diffusing capacity corrected for hemoglobin < 80%. There was a tendency to lower survival in all altered PFT groups compared with normal (P = .054) but not within the other groups. Patients with an impaired FEV1 had significantly higher mortality than patients with normal values (P = .008). Area under receiver operating characteristic curve for FEV1 was 0.73 (95% confidence interval [0.60-0.86]). A cutoff value of FEV1 (60.5) predicts mortality with 66% sensitivity and 64% specificity. CONCLUSIONS: PFT alterations have a very high prevalence on HT waiting list patients. Patients with impaired FEV1 had worse outcomes after heart transplantation.
Assuntos
Insuficiência Cardíaca/complicações , Transplante de Coração , Pneumopatias/complicações , Adulto , Feminino , Transplante de Coração/mortalidade , Humanos , Pulmão/fisiopatologia , Pneumopatias/epidemiologia , Pneumopatias/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prevalência , Curva ROC , Testes de Função Respiratória , Estudos RetrospectivosRESUMO
UNLABELLED: Matrix metalloproteinases (MMPs) are proteolytic enzymes responsible for extracellular matrix protein degradation. They have an important role in tissue remodeling processes. Their activity is regulated at the transcriptional, translational, and posttranslational level and by tissue inhibitors (TIMPs). Our aim was to analyze whether expression changes in MMPs that degrade collagens and their inhibitors in the myocardium have an impact on ventricular remodeling and the fibrogenesis in congestive heart failure. METHODS: We analyzed left ventricle biopsies from 18 patients with idiopathic dilated cardiomyopathy (iCDM) and severe congestive heart failure (HF) and 13 biopsies from organ donors. mRNA expression was quantified by real-time PCR, and fibrosis levels measured with picrosirius red staining. RESULTS: The patients mean age was 53 +/- 3 years. Expression levels of MMP-1, MMP-2, MMP-3, and TIMP1 did not show differences in pathological hearts compared to control hearts. Expression levels of MMP-1 and MMP-3 were low. MMP-9 expression levels were down-regulated in the cardiomyopathic hearts (49.77 +/- 7.6 ng equivalents of cDNA [ng-eq]) compared to controls (91.24 +/- 10.8 ng-eq, P < .005). MMP-2 expression levels correlated with the fibrosis levels (P < .05, R2 = 0.33, n = 18). CONCLUSION: MMP-9 mRNA expression down-regulation suggested that the protein levels were regulated at the posttranscriptional level. The correlation between MMP-2 expression levels and the collagen fraction in the pathological hearts indicated a putative role of MMP-2 in the fibrosis that takes place in congestive heart failure.
Assuntos
Cardiomiopatia Dilatada/enzimologia , Regulação Enzimológica da Expressão Gênica , Insuficiência Cardíaca/enzimologia , Transplante de Coração/fisiologia , Ventrículos do Coração/enzimologia , Metaloproteinase 9 da Matriz/genética , Cardiomiopatia Dilatada/genética , Colágeno/metabolismo , DNA Complementar/genética , Regulação para Baixo , Insuficiência Cardíaca/genética , Humanos , Metaloproteinases da Matriz/genética , Biossíntese de Proteínas , Transcrição GênicaRESUMO
BACKGROUND: With the introduction of prolonged prophylaxis with valganciclovir in cytomegalovirus (CMV) donor/recipient serodiscordance (D+/R-) patients, concerns about a high incidence of late and invasive CMV disease associated with mortality have emerged. We compared the characteristics of CMV disease in D+/R- patients receiving prolonged valganciclovir prophylaxis with R+ patients. METHODS: We prospectively followed all solid organ transplant recipients from January 2004 to December 2005. CMV prophylaxis with valganciclovir or ganciclovir was administered as follows: donor- recipient serodiscordance (D+/R-), 12 weeks; induction with antithymocyte globulin or acute rejection episodes requiring steroid pulses, 15 to 30 days; and CMV R+ double kidney-pancreas, 15 days. Transplant characteristics and the development of CMV disease variables were collected for all patients. We defined 2 groups according to the risk of CMV disease: CMV donor/recipient mismatch (D+/R-) and recipient CMV-positive (R+) groups. RESULTS: During the study period we performed 481 solid organ transplantations: 237 kidney, 34 kidney-pancreas, 157 liver, 38 heart, 13 liver-kidney, and 2 heart-kidney. Overall, 36 patients developed CMV disease (7.5%). CMV donor-recipient mismatch (D+/R-) was associated with a greater risk of CMV disease compared with CMV-positive recipients (16% vs 7%; P = .036). Prophylaxis against CMV was longer in the D+/R- group (mean days 73 vs 15; P < .001). CMV disease appeared later in the D+/R- than in R+ group (mean days 123 vs 59; P < .001). We observed a trend toward a lower incidence of tissue-invasive CMV disease among the D+/R- group compared with the R+ group without significance (14% vs 41%; P = .382). Three patients died in the first 30 days after the onset of CMV disease, all of them in the R+ group. CONCLUSIONS: In our setting, high-risk patients (D+/R-) receiving prolonged prophylaxis with valganciclovir developed later CMV disease, but this was neither more tissue-invasive nor more life-threatening than in the R+ group.
Assuntos
Antivirais/uso terapêutico , Infecções por Citomegalovirus/prevenção & controle , Ganciclovir/análogos & derivados , Transplante de Órgãos/efeitos adversos , Adulto , Infecções por Citomegalovirus/epidemiologia , Feminino , Seguimentos , Ganciclovir/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Incidência , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/virologia , Estudos Prospectivos , Imunologia de Transplantes , ValganciclovirRESUMO
BACKGROUND: Cytomegalovirus (CMV) disease is associated with an increased net immunosuppressive state in solid organ transplant recipients, leading to more bacterial and fungal infections. The release of pro- and anti-inflammatory cytokines could be one of the responsible factors. METHODS: We prospectively included all patients undergoing solid organ transplantation between April and November 2004. During follow-up, plasma samples were collected in the immediate postsurgical period, at the first and second months, at the time of maximum antigenemia during CMV disease, and at 6 months posttransplantation. We determine the levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, and IL-10. Log-transformed data were compared by a nonparametric Wilcoxon test for related variables. RESULTS: During the study period, we monitored 146 recipients of solid organ transplantation: 77 kidneys, 8 kidney-pancreas, 46 liver, 11 heart, 2 liver-kidney, and 2 heart-kidney. No differences were observed between the TNF-alpha and IL-10 levels in the immediate postsurgical period or during CMV disease. TNF-alpha and IL-10 levels during CMV disease were higher than levels during the first month (mean TNF-alpha first month = 12.71 pg/mL vs CMV disease = 22.71 pg/mL, P = .028; mean IL-10 first month = 3.47 pg/mL vs CMV disease = 19.2 pg/mL, P = .018). Th1/Th2 ratio (measured as TNF-alpha/IL-10) was 1.75 in the immediate postsurgical period, 7.5 during the first month, 1.86 at the time of CMV disease, and 4.61 at the sixth month. The difference in Th1/Th2 ratio during CMV disease and in the first month was statistically significant (P = .043). CONCLUSION: During CMV disease, we observed an increase in TNF-alpha and IL-10 release, which was similar to that during the postsurgical period. An imbalance toward an anti-inflammatory pattern was noted in these two periods. This could reflect a cooperative factor increasing the net state of immunosuppression during CMV disease.
Assuntos
Citocinas/metabolismo , Infecções por Citomegalovirus/imunologia , Transplante de Órgãos/estatística & dados numéricos , Células Th1/imunologia , Células Th2/imunologia , Imunologia de Transplantes , Citocinas/sangue , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/epidemiologia , Seguimentos , Humanos , Interleucina-10/sangue , Interleucina-6/sangue , Estudos Prospectivos , Fator de Necrose Tumoral alfa/sangueRESUMO
UNLABELLED: Besides the well-established role of mast cells in allergic reactions as an important source of vasoactive and proinflammatory products, they have been related to tissue fibrosis and remodelling processes. In a heart failure (HF) animal model, mast cells were shown to synthesize transforming growth factor beta1 and basic fibroblast growth factor in myocardial tissue and were localized to an area with fibrosis. Our objective was to quantify mast cell density in left ventricles from patients with congestive heart failure who were candidates for transplantation and to analyze whether they showed a correlation with the fibrosis level of the same area. METHODS: We obtained myocardial biopsies from 20 patients with end-stage HF secondary to idiopathic dilated cardiomyopathy (iDCM) undergoing heart transplantation and 15 controls (donors without cardiopathy). Mast cells were detected by immunohistochemistry with a human mast cell chymase antibody and fibrosis levels measured with picrosirius red staining of collagen fibrils with later quantification by morphometry. RESULTS: The patients mean age was 51 +/- 3 years. Fibrosis levels in the myocardial sections from patients with congestive HF was three-fold higher than those in control myocardium (12.41 +/- 1.7% vs 3.98 +/- 0.63%, P < .001). Mast cell density correlated with the collagen fraction and could be fitted to a linear regression curve: collagen fraction = 0.78 + 0.05 mast cell density (n = 33, P < .005, R2 = 0.28). CONCLUSION: The elevated collagen fraction present in failing hearts may be the cause of increased stiffness and loss of elasticity that is detected in patients with end-stage HF. Due to the mast cells capacity to synthesize vasoactive and fibrogenic products and the correlation between their density and fibrosis levels, they probably play a role in the ventricular remodelling in HF.
Assuntos
Colágeno/metabolismo , Insuficiência Cardíaca/patologia , Insuficiência Cardíaca/cirurgia , Transplante de Coração/patologia , Mastócitos/patologia , Miocárdio/patologia , Fibrose , Humanos , Pessoa de Meia-Idade , Doadores de Tecidos , Disfunção Ventricular Esquerda/fisiopatologiaRESUMO
BACKGROUND: Tricuspid regurgitation is frequently observed after orthotopic heart transplantation (OHT), in association with severe pulmonary hypertension. However, the incidence of left-sided valvular disease has not been addressed. AIM: We analyzed the incidence and prognostic implications of left-sided valve disease in 141 patients after OHT. METHODS: Echocardiography was performed with every endomyocardial biopsy during the first year after OHT and every 6 months thereafter. Mitral regurgitation (MR) grade II or III was considered significant. Graft vasculopathy was assessed using coronary angiography. RESULTS: Eight patients (6%) developed significant left-sided valvular disease, namely, MR in 6 (4%) and aortic regurgitation (AR) in 2 (1.4%). The 2 cases with AR were diagnosed the first week after OHT, whereas significant MR was diagnosed at mean follow- up of 34 +/- 6 months. Mean regurgitant orifice and volume were 34 +/- 14 mm2 and 41 +/- 15 mL/beat, respectively. Patients with significant MR had experienced a greater number of acute rejection episodes >or=3A, (1.8 +/- 1.7 vs 0.8 +/- 1.05; P = .02) and were associated with allograft vasculopathy in 83% vs 6% among unaffected patients (P = .0001). Four of 6 patients with significant MR died during follow-up (67%) and 1 of the living patients underwent reparative mitral valve surgery. The probability of survival using Kaplan-Meier curves was significantly lower when patients developed late significant MR (54% vs 76%; P = .0001). CONCLUSIONS: The incidence of significant left-sided valvular disease after OHT was low. MR was associated with a higher degree of previous acute rejection, of graft vasculopathy, and mortality. The presence of moderate or severe MR of late appearance identified a group of OHT patients with poor outcomes.
Assuntos
Transplante de Coração/efeitos adversos , Insuficiência da Valva Mitral/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Angiografia Coronária , Ecocardiografia , Feminino , Seguimentos , Doenças das Valvas Cardíacas/classificação , Doenças das Valvas Cardíacas/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Insuficiência da Valva Mitral/diagnóstico por imagem , Estudos Retrospectivos , Fatores de TempoRESUMO
UNLABELLED: Endomyocardial biopsy is the gold-standard procedure to diagnose acute cellular rejection after heart transplantation. This study assessed whether the blood levels of cytokines involved in inflammation and immune activation are useful to detect the presence of acute cellular rejection. METHODS: Blood specimens collected before 275 endomyocardial biopsies in 66 patients were assayed for levels of TNFalpha, IL6, IL1beta, and IL2 receptor. The biopsies were grouped according to the presence (n = 41) or absence (n = 234) of acute cellular rejection grade > or = 3A of the International Society for Heart and Lung Transplantation. We compared the levels of cytokines in the two groups. RESULTS: Circulating IL6 levels were significantly higher when there was a low grade (0-2) cellular rejection in the biopsy versus the group of biopsies grade > or = 3A (19.8 +/- 27 versus 12.9 +/- 10 pg/mL; P = .001). An IL6 level higher than 30 pg/mL showed a negative predictive value of 95% for the presence of acute rejection grade > or = 3A. CONCLUSION: In heart transplant patients, high levels of serum IL6 were associated with low grade cellular rejection. Determination of IL6 levels may be useful to reduce the number of endomyocardial biopsies during follow-up in these patients.
Assuntos
Rejeição de Enxerto/imunologia , Transplante de Coração/imunologia , Interleucina-6/sangue , Adulto , Biomarcadores/sangue , Biópsia , Citocinas/sangue , Rejeição de Enxerto/sangue , Transplante de Coração/patologia , Humanos , Estudos RetrospectivosRESUMO
BACKGROUND: Failure of compliance with medical regimen is one of the major risk factors associated with morbidity and mortality in heart transplant (HT) recipients. Nevertheless, to date, there is no specific, gold-standard, comprehensive set of tools for assessing compliance in these patients. OBJECTIVE: The objective of the present study was to develop a specific instrument for the assessment of noncompliance with medical recommendations in HT recipients. METHODS: This prospective observational study used a nonprobability sampling method, which was performed from January 2006 to December 2012. All of the patients met clinical criteria for being included on the waiting list for a HT. We designed a scale for measuring the compliance degree at 12 months after heart transplantation. This scale included the most important aspects of the medical regimen, using nine discrete quantitative variables. The total score was described as the patient's Noncompliance Factor (NCF). The results were analysed by mean, ranks, and percentages. RESULTS: The sample was constituted of 61 participants who underwent surgical HT intervention and completed the 12-month follow-up assessment. The overall incidence of noncompliance was around 30% and only 43.1% of the recipients had an acceptable degree of compliance. CONCLUSIONS: The overall incidence of noncompliance in HT recipients is high and this can generate worse clinical outcomes. Evaluation by specific screening instruments like the one proposed in the present study can be useful for a systematic detection of this phenomenon.
Assuntos
Transplante de Coração/psicologia , Programas de Rastreamento/métodos , Cooperação do Paciente/estatística & dados numéricos , Feminino , Seguimentos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Estudos Prospectivos , Fatores de Risco , Estudos de Amostragem , Listas de EsperaRESUMO
In this article, the full description of a heart failure with reduced ejection fraction (HF_REF) cohort of 192 patients is provided. Tables with the baseline demographic, prior history, ECG parameters, echocardiographic parameters, laboratory values and pharmacological treatment of these patients are included. Also, the quartile values of the analyzed circulating biomarkers: high sensitivity Troponin T (hs-TnT), galectin-3 (Gal-3), C-terminal propeptide of type I procollagen (CICP), soluble AXL (sAXL) and Brain Natriuretic Peptide (BNP) are given. The main demographic and clinical features of the patients' subgroups that have hs-TnT, Gal-3, CICP or BNP above the third quartile are described. Tables with Pearson correlation analysis of the HF_REF patients' biomarker levels are included. And Pearson correlation analysis of the HF_REF patients' hs-TnT, Gal-3, CICP levels with patients' biochemical parameters, blood count and inflammation parameters are also described. These data are related to the research articles (AXL receptor tyrosine kinase is increased in patients with heart failure (M. Batlle, P. Recarte-Pelz, E. Roig, M.A. Castel, M. Cardona, M. Farrero, et al., 2014) [1] and Use of serum levels of high sensitivity troponin T, galectin-3 and C-terminal propeptide of type I procollagen at long term follow-up in Heart Failure patients with reduced ejection fraction: comparison with soluble AXL and BNP (M. Batlle, B. Campos, M. Farrero, M. Cardona, B. González, M.A. Castel, et al., 2016) [2].
RESUMO
BACKGROUND: Prognostic biomarkers are needed to improve the management of the heart failure (HF) epidemic, being the brain natriuretic peptides the most valuable. Here we evaluate 3 biomarkers, high sensitivity troponin T (hs-TnT), galectin-3 (Gal-3) and C-terminal propeptide of type I procollagen (CICP), compare them with a recently described new candidate (sAXL), and analyze their relationship with BNP. METHODS: HF patients with reduced ejection fraction (n=192) were included in this prospective observational study, with measurements of candidate biomarkers, functional, clinical and echocardiographic variables. A Cox regression model was used to determine predictors for clinical events, i.e. all-cause mortality and heart transplantation. RESULTS: Hs-TnT circulating values were correlated to clinical characteristics indicative of more advanced HF. When analyzing the event-free survival at a mean follow-up of 3.6years, patients in the higher quartile of either BNP, hs-TnT, CICP and sAXL had increased risk of suffering a clinical event, but not Gal-3. Combination of high sAXL and BNP values had greater predictive value (HR 6.8) than high BNP alone (HR 4.9). In a multivariate Cox regression analysis, BNP, sAXL and NYHA class were independent risk factors for clinical events. CONCLUSIONS: In this HF cohort, hs-TnT is a good HF marker and has a very significant prognostic value. The prognostic value of CICP and sAXL was of less significance. However, hs-TnT did not add predictive value to BNP, while sAXL did. This suggests that elevated troponin has a common origin with BNP, while sAXL could represent an independent pathological mechanism.
Assuntos
Galectina 3/sangue , Insuficiência Cardíaca/sangue , Peptídeo Natriurético Encefálico/sangue , Fragmentos de Peptídeos/sangue , Pró-Colágeno/sangue , Proteínas Proto-Oncogênicas/sangue , Receptores Proteína Tirosina Quinases/sangue , Troponina T/sangue , Biomarcadores/sangue , Estudos de Coortes , Feminino , Seguimentos , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/epidemiologia , Humanos , Masculino , Estudos Prospectivos , Volume Sistólico/fisiologia , Receptor Tirosina Quinase AxlRESUMO
INTRODUCTION: Daclizumab is a monoclonal antibody that binds to the interleukin-2 receptor. It has been used as induction therapy in heart transplantation with two to five repeated administrations over several weeks. The objective of our study was to estimate the efficacy and safety of induction therapy with only one dose of daclizumab in a consecutive series of patients undergoing heart transplantation. METHODS: Thirty-two consecutive heart transplants performed since July 2002, who received single-dose daclizumab as induction therapy, were compared with the 30 patients transplanted previously, who received OKT3. In both groups, maintenance immunosuppression included cyclosporine or tacrolimus, mycophenolate mofetil, and corticosteroids. Follow-up time was 1 year. RESULTS: There were no baseline differences between the two groups regarding age, gender, or etiology. In the group treated with daclizumab there were more diabetics (43% versus 10%, P = .01) and the ischemia time was longer (192 versus 156 minutes, P = .03). During the first posttransplant year, 76% of patients treated with OKT3 and 55% of those treated with daclizumab presented acute rejection > or =3A; 20% and 25%, respectively, presented infections; and 5 (17%) patients in the OKT3 group and 2 (6%) in the group treated with daclizumab died. None of these differences was statistically significant. CONCLUSIONS: Our experience suggests that induction therapy with a single-dose regimen of daclizumab seems to have an efficacy and safety profile similar to OKT3, and it is easier to administer and has a lower cost than other induction regimens.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Rejeição de Enxerto/prevenção & controle , Transplante de Coração/imunologia , Imunoglobulina G/uso terapêutico , Muromonab-CD3/uso terapêutico , Doença Aguda , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Daclizumabe , Esquema de Medicação , Feminino , Rejeição de Enxerto/epidemiologia , Humanos , Imunoglobulina G/administração & dosagem , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Infecções/epidemiologia , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/prevenção & controle , Estudos RetrospectivosRESUMO
BACKGROUND: The N-terminal pro-brain natriuretic peptide (NT-proBNP) has been useful in the diagnosis and follow-up of heart failure. Whether it can be useful in the detection of acute rejection (AR) after heart transplantation (HT) has not been addressed. Our aim was to assess the prognostic value of NT-proBNP determinations after HT. METHODS: We analyzed 137 endomyocardial biopsies (EMB) performed in 51 patients as assessment of AR and correlated them with NT-proBNP determinations. The value of NT-proBNP in the early follow-up of the novo HT was also assessed. RESULTS: AR grade > or =3A was diagnosed in 10 of the 137 performed biopsies. There were no significant differences in NT-proBNP values between patients with or without AR (1047 +/- 629 versus 1886 +/- 3026 pg/mL, P = NS). There were 24 de novo HT, in these patients increased NT-proBNP levels showed an inverse significant correlation with time since HT (r = -0.40, P = .0001). During follow-up, 15 of the novo HT had a descending NT-proBNP curve over time, and in the remaining 9 (37%) a late increase of NT-proBNP values were observed. Those 9 patients had the following complications: AR > or =3A in 5 cases, 1 death, 2 required a permanent pacemaker, and in the last patient a significant EMB could not be obtained. CONCLUSIONS: NT-proBNP values follow a descending curve early after HT. During the first months, a late increase of NT-proBNP value was associated with HT complications, with AR being the most frequent. Isolated increased NT-proBNP levels were not useful for the detection of AR. More studies are needed to establish the prognostic value of NT-proBNP after HT.
Assuntos
Transplante de Coração/fisiologia , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Adulto , Idoso , Biomarcadores/metabolismo , Biópsia , Seguimentos , Rejeição de Enxerto/epidemiologia , Transplante de Coração/patologia , Humanos , Pessoa de Meia-Idade , Precursores de Proteínas/metabolismo , Análise de Regressão , Fatores de TempoRESUMO
BACKGROUND: Invasive pulmonary aspergillosis (IPA) remains a major cause of mortality in transplant recipients. New strategies in therapy are needed. METHODS: We prospectively followed all solid organ and bone marrow transplant recipients from January 1998 to January 2003 who showed pulmonary infiltrates. We retrospectively analyzed all of the patients diagnosed as having IPA. Clinical and epidemiological data were collected. Influence of new treatment strategies on survival was also analyzed. RESULTS: Thirty-one cases of API were found: 8 definite, 18 probable, 5 possible among recipients of liver (11), bone marrow (9), kidney (7), kidney-pancreas (3), and heart (1) transplants. Five patients (16%) were previously receiving antifungal prophylaxis. The most common symptoms were fever (74%) and dyspnea and dry cough (48%). Six cases (19%) showed dissemination to extrapulmonary sites: central nervous system (CNS) in five and bone in one. The most common radiographic patterns were alveolar infiltrates (58%); the lesions were usually diffuse and bilateral (58%). The most common Aspergillus species identified was A. fumigatus (74%). The test to detect Aspergillus antigen (galactomannan) in serum performed in 13 cases, was positive in eight (61%). The crude mortality rate was 61% (19 of 31), but in patients on mechanical ventilation, it was 94% (OR 88, IC 95%: 7.1-1094), and in patients with CNS involvement, it was 100%. The influence of the different treatment regimens on survival was analyzed in definite and probable cases: Group 1 (12) included patients who received conventional monotherapy and group 2 (12) patients received combination antifungal therapy or liposomal amphotericin B (1-AMB) at high doses. The mortality in group 1 was 83% (10 of 12), and in group 2 it was 42% (5 of 12) (P < 0.05). CONCLUSIONS: The mortality rate of IPA remains high, especially among patients with CNS involvement or those under mechanical ventilation. Combined antifungal therapy or monotherapy with 1-AMB at high doses significantly reduced mortality compared with conventional monotherapy.
Assuntos
Aspergilose Broncopulmonar Alérgica/patologia , Transplante de Medula Óssea/efeitos adversos , Complicações Pós-Operatórias/microbiologia , Imunologia de Transplantes , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Aspergilose Broncopulmonar Alérgica/tratamento farmacológico , Aspergilose Broncopulmonar Alérgica/epidemiologia , Aspergilose Broncopulmonar Alérgica/mortalidade , Quimioterapia Combinada , Humanos , Complicações Pós-Operatórias/tratamento farmacológico , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/patologia , Estudos Retrospectivos , Análise de SobrevidaRESUMO
BACKGROUND: Bacteremia and septic shock remain important causes of morbidity and mortality after solid-organ transplantation. The aim of this study was to assess the characteristics and risk factors for mortality among patients with bloodstream infections and shock. METHODS: From January 1991 to December 2000, all episodes of bloodstream infection were prospectively examined, considering bacteremia or fungemia as significant according to the CDC criteria. Septic shock was diagnosed in a patient with systemic inflammatory response syndrome and persistent dysfunction of at least one organ caused by hypoperfusion despite hemodynamic support. RESULTS: There were 466 episodes of bacteremia in 382 patients, with 66 of them developing septic shock. Risk factors for developing shock were age >50 (P = .006), liver transplant (P = .029), nosocomial infection (P = .034), pulmonary focus (P = .0001), P. aeruginosa infection (P = .001), and polymicrobial etiology (P = .039). On multivariate analysis, only age, nosocomial infection, and pulmonary source were significant. Among 66 shock patients, bacteremia was due to gram-negative bacteria in 53%, gram-positive bacteria in 24%, fungal in 7.5%, and polymicrobial in 12% of patients. The most frequent source was the lung (26%). Empiric antimicrobial therapy was correctly chosen in 79%; however, 36 patients died (54%), including 27 despite correct therapy. Urinary tract infections had less mortality than other foci. CONCLUSIONS: Risk factors for developing septic shock in bacteremia were age more than 50 years, nosocomial acquisition, and pulmonary focus. Despite adequate empiric antibiotic therapy, the mortality remained high.
Assuntos
Bacteriemia/epidemiologia , Transplante de Órgãos/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Choque Séptico/epidemiologia , Bacteriemia/classificação , Bacteriemia/mortalidade , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/mortalidade , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco , Choque Séptico/mortalidadeRESUMO
OBJECTIVE: The aim was to analyse the relationship between magnetic resonance (MR) imaging parameters and myocardial water content early after coronary occlusion with or without reperfusion. METHODS: 21 pigs were used. After 78 min of coronary occlusion (n = 7) or 48 min of coronary occlusion and 30 min of reperfusion (n = 14) the heart was excised. In seven animals in the reperfusion protocol the area at risk was perfused for 5 min with an anoxic buffer, starting 5 min after coronary occlusion. Serial T2 weighted and density weighted images of the heart were obtained from apex to base, by using a 1.5 tesla magnetic resonance imager. Water content was measured in samples from control and at-risk myocardium and relaxation parameters were measured in corresponding areas of the magnetic resonance images. RESULTS: Water content was 399(SEM 2) ml x 100 g-1 dry tissue in control myocardium, 427(8) in ischaemic myocardium, and 511(8) in reperfused myocardium (p < 0.001). Reperfused myocardium that had received intracoronary infusion contained less water than myocardium that did not: 498(9) v 534(4) ml x 100 g-1 (p = 0.003). T2 relaxation time and T2 weighted signal intensity in the different sampling sites of magnetic resonance images correlated well with water content in the corresponding myocardial samples (r = 0.76 and r = 0.83) and with the relative volume of extracellular space, as calculated by quantitative histology (r = 0.58 and r = 0.59, p < 0.001). The increase in T2 weighted signal intensity in the area at risk with respect to control myocardium allowed differentiation between ischaemic and reperfused myocardium [9(8)% v 63(3)% respectively]. The area at risk measured by MR imaging correlated very well with that determined at pathology by the fluorescein method (r = 0.92). CONCLUSIONS: Magnetic resonance imaging allows evaluation of myocardial oedema associated with acute coronary occlusion and reperfusion, and analysis of its spatial distribution. Changes in myocardial water content occurring early during acute myocardial infarction allow quantification of the area at risk and detection of reperfusion by magnetic resonance imaging.