Impact of Hyperuricemia on Long-term Outcomes of Kidney Transplantation: Analysis of the FAVORIT Study.

BACKGROUND: Elevated uric acid concentration is associated with higher rates of cardiovascular (CV) morbidity and mortality in the general population. It is not known whether hyperuricemia increases the risk for CV death or transplant failure in kidney transplant recipients. STUDY DESIGN: Post hoc cohort analysis of the FAVORIT Study, a randomized controlled trial that examined the effect of homocysteine-lowering vitamins on CV disease in kidney transplantation. SETTING & PARTICIPANTS: Adult recipients of kidney transplants in the United States, Canada, or Brazil participating in the FAVORIT Study, with hyperhomocysteinemia, stable kidney function, and no known history of CV disease. PREDICTOR: Uric acid concentration. OUTCOMES: The primary end point was a composite of CV events. Secondary end points were all-cause mortality and transplant failure. Risk factors included in statistical models were age, sex, race, country, treatment assignment, smoking history, body mass index, presence of diabetes mellitus, history of CV disease, blood pressure, estimated glomerular filtration rate (eGFR), donor type, transplant vintage, lipid concentrations, albumin-creatinine ratio, and uric acid concentration. Cox proportional hazards models were fit to examine the association of uric acid concentration with study end points after risk adjustment. RESULTS: 3,512 of 4,110 FAVORIT participants with baseline uric acid concentrations were studied. Median follow-up was 3.9 (IQR, 3.0-5.3) years. 503 patients had a primary CV event, 401 died, and 287 had transplant failure. In unadjusted analyses, uric acid concentration was significantly related to each outcome. Uric acid concentration was also strongly associated with eGFR. The relationship between uric acid concentration and study end points was no longer significant in fully adjusted multivariable models (P=0.5 for CV events; P=0.09 for death, and P=0.1 for transplant failure). LIMITATIONS: Unknown use of uric acid-lowering agents among study participants. CONCLUSIONS: Following kidney transplantation, uric acid concentrations are not independently associated with CV events, mortality, or transplant failure. The strong association between uric acid concentrations with traditional risk factors and eGFR is a possible explanation.

Destaques do VII international symposium of thrombosis and anticoagulation (ISTA) / Highlights of VII international symposium of thrombosis and anticoagulation (ISTA)

O VII Simpósio Internacional de Trombose e Anticoagulação (ISTA) foi realizado em São Paulo, SP, Brasil, nos dias 24 e 25 de outubro de 2014, tendo como principais propósitos a discussão e o compartilhamento de conhecimentos sobre os avanços recentes na abordagem diagnóstica e terapêutica de pacientes com distúrbios trombóticos, nas suas diversas formas de apresentação clínica. O programa científico deste simpósio foi cuidadosamente desenvolvido por líderes de três importantes institutos de pesquisa clínica: o Instituto Brasileiro de Pesquisa Clínica(BCRI), o Duke Clinical Research Institute (DCRI), e Instituto de Pesquisa do Hospital do Coração. Composto por dois dias de apresentações acadêmicas e discussão aberta, o simpósio teve como principal objetivo educar, motivar e inspirar os clínicos, cardiologistas, hematologistas, e outros médicos através de apresentações e discussões de aspectos práticos de condutas que envolvem síndromes relacionadas à trombose e suas respectivas terapias antitrombóticas. Estas atividades possibilitaram uma interação direta entre a plateia e o corpo de palestrantes, composto por médicos de grande experiência clínica e pelos médicos pesquisadores que desenvolveram os principais estudos publicados que guiam nossas condutas em situações relacionadas ao tema "trombose e anticoagulação". Este artigo resume os anais deste simpósio.

The VII International Symposium on Thrombosis and Anticoagulation (ISTA) was held in São Paulo, Brazil, on 24 and 25 October 2014, with the main objectives to discuss and share knowledge on recent advances in the diagnosis and management of patients with thrombotic disorders. The scientific program of this symposium was carefully developed by leaders of three major clinical research institutes: the Brazilian Institute of Clinical Research (BCRI), the Duke Clinical Research Institute from Duke University, and the Research Institute from Hospital do Coração. Comprising two days of academic presentations and open discussion, the symposium aimed to educate, motivate and inspire clinicians, cardiologists, hematologists, and other doctors through presentations and discussions of practical aspects in themes related to thrombosis and anticoagulation. These activities were presented by physicians of great clinical experience and who participated in the main publications that guide our approach on situations related to the theme "thrombosis and anticoagulation". This article summarizes the proceedings of this symposium.

Effects of cardiac resynchronization therapy on muscle sympathetic nerve activity.

INTRODUCTION: Muscle sympathetic nerve activity (MSNA) is an independent prognostic marker in patients with heart failure (HF). Therefore, its relevance to the treatment of HF patients is unquestionable. OBJECTIVES: In this study, we investigated the effects of cardiac resynchronization therapy (CRT) on MSNA response at rest and during exercise in patients with advanced HF. METHODS: We assessed 11 HF patients (51 ± 3.4 years; New York Heart Association class III-IV; left ventricular ejection fraction 27.8 ± 2.2%; optimal medical therapy) submitted to CRT. Evaluations were made prior to and 3 months after CRT. MSNA was performed at rest and during moderate static exercise (handgrip). Peak oxygen consumption (VO2 ) was evaluated by means of cardiopulmonary exercise test. HF patients with advanced NYHA class without CRT and healthy individuals were also studied. RESULTS: CRT reduced MSNA at rest (48.9 ± 11.1 bursts/min vs 33.7 ± 15.3 bursts/min, P < 0.05) and during handgrip exercise (MSNA 62.3 ± 13.1 bursts/min vs 46.9 ± 14.3 bursts/min, P < 0.05). Among HF patients submitted to CRT, the peak VO2 increased (12.9 ± 2.8 mL/kg/min vs 16.5 ± 3.9 mL/kg/min, P < 0.05) and an inverse correlation between peak VO2 and resting MSNA (r = -0.74, P = 0.01) was observed. CONCLUSIONS: In patients with advanced HF and severe systolic dysfunction: (1) a significant reduction of MSNA (at rest and during handgrip) occurred after CRT, and this behavior was significantly superior to HF patients receiving only medical therapy; (2) MSNA reduction after CRT had an inverse correlation with O2 consumption outcomes.

CHronic use of Amiodarone aGAinSt Implantable cardioverter-defibrillator therapy for primary prevention of death in patients with Chagas cardiomyopathy Study: rationale and design of a randomized clinical trial.

BACKGROUND: The implantable cardioverter defibrillator (ICD) is better than antiarrhythmic drug therapy for the primary and secondary prevention of all-cause mortality and sudden cardiac death in patients with either coronary artery disease or idiopathic dilated cardiomyopathy. This study aims to assess whether the ICD also has this effect for primary prevention in chronic Chagas cardiomyopathy (CCC). METHODS: In this randomized (concealed allocation) open-label trial, we aim to enroll up to 1,100 patients with CCC, a Rassi risk score for death prediction of ≥10 points, and at least 1 episode of nonsustained ventricular tachycardia on a 24-hour Holter monitoring. Patients from 28 centers in Brazil will be randomly assigned in a 1:1 ratio to receive an ICD or amiodarone (600 mg/d for 10 days, then 200-400 mg/d until the end of the study). The randomization sequence will be generated by computer, and the members of the committees responsible for end point validation and data analysis will be blinded to study assignment. The primary end point is all-cause death, and enrolment will continue until 256 patients have reached this end point. Key secondary end points include cardiovascular death, sudden cardiac death, hospitalization for heart failure, and quality of life. We expect follow-up to last 3 to 6 years, and data analysis will be done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov number NCT01722942. CONCLUSION: CHAGASICS is the first large-scale trial to assess the benefit of ICD therapy for the primary prevention of death in patients with CCC and nonsustained ventricular tachycardia, who have a moderate to high risk of death.

In patients with acute myocardial infarction, the impact of hyperglycemia as a risk factor for mortality is not homogeneous across age-groups.

OBJECTIVE: To assess the impact of hyperglycemia in different age-groups of patients with acute myocardial infarction (AMI). RESEARCH DESIGN AND METHODS: A total of 2,027 patients with AMI were categorized into one of five age-groups: <50 years (n = 301), ≥50 and <60 (n = 477), ≥60 and <70 (n = 545), ≥70 and <80 (n = 495), and ≥80 years (n = 209). Hyperglycemia was defined as initial glucose ≥115 mg/dL. RESULTS: The adjusted odds ratios for hyperglycemia predicting hospital mortality in groups 1-5 were, respectively, 7.57 (P = 0.004), 3.21 (P = 0.046), 3.50 (P = 0.003), 3.20 (P < 0.001), and 2.16 (P = 0.021). The adjusted P values for correlation between glucose level (as a continuous variable) and mortality were 0.007, <0.001, 0.043, <0.001, and 0.064. The areas under the ROC curves (AUCs) were 0.785, 0.709, 0.657, 0.648, and 0.613. The AUC in group 1 was significantly higher than those in groups 3-5. CONCLUSIONS: The impact of hyperglycemia as a risk factor for hospital mortality in AMI is more pronounced in younger patients.

The role of invasive therapies in elderly patients with acute myocardial infarction.

INTRODUCTION: In elderly patients with acute myocardial infarction, very little is known about the role of surgical myocardial revascularization and percutaneous coronary intervention (invasive therapies--IT), especially in the context of long-term outcomes after hospital discharge. METHODS: We analyzed 1588 patients with MI who had been included prospectively in a databank and followed for up to 7.5 years. In this population, 548 patients were >70 years old (elderly group--EG), and 1040 were <70 years of age (younger group--YG); 1088 underwent IT during hospitalization, and the remaining 500 were treated medically (conservative therapy--CT). Patients were monitored either by visit or by phone at least once a year. A standard questionnaire was administered to all patients. The impact of IT was analyzed with both non-adjusted and adjusted models. RESULTS: By the end of the follow-up period, the survival rates for the IT and CT groups were, respectively, 71.9% versus 47.2% in the global population (hazard ratio=0.55, P<0.001), 81.5% versus 66.6% in the YG (hazard ratio=0.68, P=0.018) and 48.8% versus 20.3% in the EG (hazard ratio=0.58, P<0.001). In the adjusted models, the hazard ratios were 0.62 (P<0.001) in the global population, 0.74 in the YG (P=0.073) and 0.64 (P=0.001) in the EG. CONCLUSION: Long-term follow-up of patients with myocardial infarction revealed that IT during the in-hospital phase was at least as effective in elderly patients as in younger patients.

The role of invasive therapies in elderly patients with acute myocardial infarction

INTRODUCTION: In elderly patients with acute myocardial infarction, very little is known about the role of surgical myocardial revascularization and percutaneous coronary intervention (invasive therapies - IT), especially in the context of long-term outcomes after hospital discharge. METHODS: We analyzed 1588 patients with MI who had been included prospectively in a databank and followed for up to 7.5 years. In this population, 548 patients were ¡Ý70 years old (elderly group - EG), and 1040 were <70 years of age (younger group - YG); 1088 underwent IT during hospitalization, and the remaining 500 were treated medically (conservative therapy - CT). Patients were monitored either by visit or by phone at least once a year. A standard questionnaire was administered to all patients. The impact of IT was analyzed with both non-adjusted and adjusted models. RESULTS: By the end of the follow-up period, the survival rates for the IT and CT groups were, respectively, 71.9% versus 47.2% in the global population (hazard ratio=0.55, P<0.001), 81.5% versus 66.6% in the YG (hazard ratio=0.68, P=0.018) and 48.8% versus 20.3% in the EG (hazard ratio=0.58, P<0.001). In the adjusted models, the hazard ratios were 0.62 (P<0.001) in the global population, 0.74 in the YG (P=0.073) and 0.64 (P=0.001) in the EG. CONCLUSION: Long-term follow-up of patients with myocardial infarction revealed that IT during the in-hospital phase was at least as effective in elderly patients as in younger patients.

[QT interval dispersion analysis in acute myocardial infarction patients: coronary reperfusion effect]. / Análise da dispersão do intervalo QT em pacientes com infarto agudo do miocárdio: efeito da reperfusão coronariana.

OBJECTIVE: To study the effect of early reperfusion of infarct-related artery on QT(DeltaQT) dispersion interval, as well as how valuable it is as a marker for coronary reperfusion and ventricular arrhythmias. METHODS: One hundred and six patients with reperfusion (WR) and 48 without reperfusion (WtR) who have received thrombolytic therapy in the acute phase of infarction were studied. ECG carried out on admission as well as on day 4 of patients course were analyzed. DeltaQT - defined as the difference between maximum and minimum QT interval - was measured by 12-lead ECG. RESULTS: The reperfusion group showed significant DeltaQT reduction - from 89.66+/-20.47ms down to 70.95+/-21.65ms (p<0.001). On the other hand, the group without reperfusion showed DeltaQT significant increase - from 81.27+/-20.52ms up to 91.85+/-24.66ms (p<0.001). Logistic regression analysis showed that reduction magnitude between pre- and post-thrombolysis DeltaQT was the independent factor to most effectively identify coronary reperfusion (OR 1.045, p<0.0001; CI 95%). No significant difference was found in dispersion measures when patients with ventricular arrhythmias were compared with those with no arrhythmias in the course of the first 48 hours. CONCLUSION: The study shows that DeltaQT is significantly reduced in patients with acute myocardial infarction submitted to successful thrombolysis, and is increased in infarcted patients with closed artery. DeltaQT reduction between the pre- and post-thrombolysis condition was a predictor for coronary reperfusion of those patients, and did not show correlation to ventricular arrhythmias.

Análise da dispersão do intervalo QT em pacientes com infarto agudo do miocárdio: efeito da reperfusão coronariana / QT interval dispersion analysis in acute myocardial infarction patients: coronary reperfusion effect

OBJETIVO: Estudar o efeito da reperfusão precoce da artéria relacionada ao infarto sobre a dispersão do intervalo QT(deltaQT), e seu valor como marcador de reperfusão coronária e de arritmias ventriculares. MÉTODOS: Foram avaliados 106 pacientes com reperfusão (CR) e 48 pacientes sem reperfusão (SR) que receberam terapia trombolítica na fase aguda do infarto. Foram analisados os eletrocardiogramas realizados na admissão e no 4° dia de evolução. A deltaQT, definido como a diferença entre o maior e o menor intervalo QT, foram medidos no ECG de 12 derivações. RESULTADOS: Na evolução do grupo com reperfusão, houve redução significativa da deltaQT de 89,66±20,47ms para 70,95±21,65ms (p<0,001). Por outro lado, no grupo sem reperfusão, houve aumento significativo da deltaQT de 81,27±20,52ms para 91,85±24,66ms (p<0,001). Análise de regressão logística demonstrou que a magnitude de redução entre a deltaQT pré e pós-trombólise foi o fator independente que identificou mais efetivamente a reperfusão coronária (OR 1,045, p<0,0001; IC 95 por cento). Não houve diferença significativa das medidas de dispersão quando comparados os pacientes que apresentaram arritmias ventriculares nas primeiras 48 h com aqueles sem arritmias. CONCLUSÃO: Esse estudo mostra que a deltaQT reduz significativamente em pacientes com infarto agudo do miocárdio submetidos à trombólise com sucesso, aumentando nos pacientes que evoluem com a artéria fechada. A redução deltaQT entre a situação pré e pós-trombólise foi fator preditor de reperfusão coronária nesses pacientes, não apresentando correlação com arritmias ventriculares.

Cirurgia de revascularização do miocárdio minimamente invasiva com utilização da videotoracoscopia / Minimally Invasive Myocardial Bypass Surgery Using Video-Assisted Thoracoscopy

PURPOSE: In order to associate the major benefits of the coronary artery bypass graft (CABG) with a less aggressive procedure minimally invasive coronary artery bypass graft (MICABG) has been utilized. The aim of the work is to report our initial experience with this technical approach, using video assisted thoracic surgery (VATS) to facilitate the operation. METHODS: Twenty-six patients, 19 males with ages from 44 to 83 years old, and having isolated lesion of the anterior descending artery were operated upon. Left anterior minithoracotomy of 8-10 cm was performed at the fourth intercostal space. Through this incision the optical device for VATS as well as the surgical instruments were placed in order to provide the complete left internal mammary artery (LIMA) dissection. Bypass circulation was not used and cardiac rate was decreased with the use of intravenous betablockers. For LIMA--anterior descending artery anastomosis, proximal and distal tourniquets were used and 1.5 mg/kg of heparin was intravenously administered. RESULTS: All patients presented satisfactory postoperative evolution, being discharged from the hospital at 72 h after surgery in the majority of the cases. There were delay in two patients healing of incisions and 25 patients have remained asymptomatic, with a mean in postoperative follow-up of four months. One patient died in the second postoperative month due to stroke. CONCLUSION: MICABG makes the surgery possible with better esthetic effect, lower cost and enables faster recovery than the conventional one. The use of VATS through the thoracotomy itself, allows the LIMA dissection without other incisions. It also permitted more ample dissection of the LIMA when compared to minithoracotomy without VATS.

Cirurgia de revascularizaçäo do miocárdio minimamente invasiva com uso de enxerto composto: relato de caso / Myocardial revascularization minimally invasive surgery with use of compounds graft: report of case

Este trabalho relata nossa experiência com a utilizaçao de enxerto composto em cirurgia de revascularizaçao do miocárdio minimamente invasiva (CRMMI). Uma alternativa para a CRMMI é o uso de enxertos compostos, nos casos em que se pretende revascularizar vários ramos coronarianos, quando a artéria torácica interna se apresenta curta ou ramifica-se precocemente. Foi operada paciente do sexo feminino, 54 anos, portadora de lesao de 90 por cento em artéria interventricular anterior em seu terço proximal e que foi submetida à CRMMI por minitoracotomia esquerda. A artéria torácica interna esquerda (ATIE) foi amplamente dissecada utilizando-se bisturi longo, auxílio de ótica de videotoracoscopia e clipe para ligadura dos ramos intercostais. Após a secçao da ATIE houve ausência de fluxo sanguíneo e evidência de hematoma e dissecçao da sua luz no terço distal. Este segmento comprometido foi desprezado e a ATIE foi prolongada por interposiçao de segmento de veia safena autógena, tornando possível a anastomose com o ramo interventricular anterior. A operaçao teve duraçao de 3 horas. A paciente foi extubada após 4 horas de pós-operatório e o dreno pleural esquerdo foi retirado no 3( dia; a paciente evoluiu bem, nao apresentando intercorrências clínicas pós-operatórias, tendo recebido alta hospitalar 5 dias após a operaçao. A cineangiocoronariografia pós-operatória comprovou anastomose patente. O estudo com ecodoppler realizado no 4( mês de pós-operatório mostrou derivaçao pérvia e fluxo de alta resistência. Em conclusao, o uso de enxerto composto para CRMMI mostrou ser uma alternativa eficaz para ampliar a extensao da ATIE, possibilitando a anastomose, quando a mesma é curta ou apresenta problemas de fluxo ou, ainda, se se pretende tratar mais de uma coronária.

Criptococose pulmonar em pacientes com insuficiência renal crônica: relato de um caso / Pulmonary cryptococcosis in patients with chronic renal failure: report of a case

Relato sobre um paciente com insuficiência renal crônica que apresentou quadro inflamatório pulmonar, sem responder aos diferentes esquemas de antibióticos, vindo a falecer e cuja necrópsia demonstrou criptococose pulmonar