Long-term Survival Following Heart Transplantation for Chagas Versus Non-Chagas Cardiomyopathy: A Single-center Experience in Northeastern Brazil Over 2 Decades.

Data on post-heart transplant (HT) survival of patients with Chagas cardiomyopathy (CC) are scarce. We sought to evaluate post-HT survival in patients with CC as compared with other causes of heart failure across different eras of HT. Methods: We conducted a retrospective, cohort study of 376 adult HT recipients between October 1997 and November 2019. Participants were classified according to the etiology of heart failure as CC (N = 66), nonischemic cardiomyopathy (N = 214), and ischemic cardiomyopathy (N = 96), and according to the era of HT as early (1997-2009), recent (2010-2014), and current era (2015-2019). Results: After a mean follow-up of 5.0 y (0-20.5 y), post-HT survival rates at 1, 5, and 10 y were comparable between groups. One-y survival improved from 70% in the early eras to 80% in the current era (hazard ratio [HR], 0.63; 95% confidence interval [CI], 0.41-0.97; P = 0.034). After adjustment for sex, age, and mechanical circulatory support, time-related improvement in survival was observed only in patients without CC (HR, 0.54; 95% CI, 0.32-0.91; P = 0.019) but not in those with CC (HR, 0.99; 95% CI, 0.36-2.73; P = 0.98). Causes of death were similar between patients with CC and the other etiological subgroups. Conclusions: Posttransplant survival is comparable between patients with CC, nonischemic cardiomyopathy, and ischemic cardiomyopathy. Although survival has improved significantly over years for most HT recipients, it has remained unchanged for those with Chagas disease. These trends underscore the importance of scientific research, policy discussions and a collaborative registry of heart transplantation in Chagas cardiomyopathy.

A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: Rationale and design of the RIVER trial.

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. DESIGN: RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

Rivaroxaban in Patients with Atrial Fibrillation and a Bioprosthetic Mitral Valve.

BACKGROUND: The effects of rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve remain uncertain. METHODS: In this randomized trial, we compared rivaroxaban (20 mg once daily) with dose-adjusted warfarin (target international normalized ratio, 2.0 to 3.0) in patients with atrial fibrillation and a bioprosthetic mitral valve. The primary outcome was a composite of death, major cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months. RESULTS: A total of 1005 patients were enrolled at 49 sites in Brazil. A primary-outcome event occurred at a mean of 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (difference calculated as restricted mean survival time, 7.4 days; 95% confidence interval [CI], -1.4 to 16.3; P<0.001 for noninferiority). Death from cardiovascular causes or thromboembolic events occurred in 17 patients (3.4%) in the rivaroxaban group and in 26 (5.1%) in the warfarin group (hazard ratio, 0.65; 95% CI, 0.35 to 1.20). The incidence of stroke was 0.6% in the rivaroxaban group and 2.4% in the warfarin group (hazard ratio, 0.25; 95% CI, 0.07 to 0.88). Major bleeding occurred in 7 patients (1.4%) in the rivaroxaban group and in 13 (2.6%) in the warfarin group (hazard ratio, 0.54; 95% CI, 0.21 to 1.35). The frequency of other serious adverse events was similar in the two groups. CONCLUSIONS: In patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months. (Funded by PROADI-SUS and Bayer; RIVER ClinicalTrials.gov number, NCT02303795.).

Prescribility of generic microemulsion Cyclosporine A in heart transplant patients

OBJETIVO: Determinar a prescritibilidade (eficácia terapêutica e biosegurança) da Ciclosporina microemulsäo genérica. MÉTODO: Casuística: 20 transplantados cardíacos, sendo 13 homens e sete mulheres, com idade média de 49,62 anos, iniciaram o tratamento tríplice imunossupressor, com Ciclosporina microemulsäo genérica ou Sigmasporin Microral«. A condiçäo para inclusäo era ter um seguimento mínimo de três meses. Procedimentos: avaliaçäo clínica, biópsias endomiocárdicas, dosagem de ciclosporina, exames de rotina de bioquímica e hematologia. RESULTADOS: O período de observaçäo médio foi de 10 meses e máximo de 16 meses. Foram avaliadas 151 biópsias, sendo 31,7 por cento - grau 0, 43,7 por cento - Ia e 23,1 por cento - Ib. Obtivemos uma rejeiçäo clínica confirmada com biópsia III a e uma mediastinite, ambas com boa evoluçäo. A ciclosporinemia média foi de 303 ng/ml. A evoluçäo destes pacientes transcorreu sem outros problemas. CONCLUSAO: A Ciclosporina microemulsäo genérica demonstrou excelente eficácia terapêutica e biosegurança, sendo portanto considerada prescritível.

Comparaçäo farmacocinética entre apresentaçöes de ciclosporina A microemulsäo em transplantados cardíacos / Pharmacokinetic comparacion between cyclosporine A microemulsion formulations in heart transplant patients

O presente trabalho tem como finalidade analisar os princípios da equivalência terapêutica e da conversibilidade de dois preparados farmacêuticos com ciclosporina emulsäo: o produto referência e a ciclosporina microemulsäo genérica. Estudo multicêntrico, randomizado, com 25 transplantados cardíacos com evoluçäo maior de um ano e com terapia imunossupressora estável. O protocolo escolhido foi o X latino. Segundo este protocolo, cada paciente é seu próprio controle, e, durante a execuçäo da pesquisa, realiza-se o cruzamento da medicaçäo testada. Após assinatura de consentimento informado e avaliaçäo clínico-laboratorial inicial, os pacientes säo randomizados para iniciar com ciclosporina padräo ou com ciclosporina genérica. A cada 15 dias, os pacientes realizam novos contrtoles clínico e laboratorial e trocam de medicamentos. No total, säo dois períodos de observaçäo com duas rodadas de troca em cada. Os parâmetros farmacocinéticos dos dois produtos, a ciclosporinemia e a área sob a curva näo mostraram diferenças estatísticamente significativas. O efeito clínico e os efeitos colaterais foram semelhantes no período de observaçäo. Os resultados confirmam a total conversibilidade entre a ciclosporina microemulsäo padräo e a genérica.(au)