Primary results from post hoc analysis of the apollo-b brazilian subpopulation, a phase 3 study of patisiran in patients with transthyretin amyloidosis with cardiomyopathy

BACKGROUND: Transthyretin amyloidosis (ATTR) is a progressive, fatal disease caused by toxic misfolded transthyretin (TTR) amyloid deposits. Patisiran, an RNA interference therapeutic, inhibits synthesis of wild-type and variant TTR and is approved for the treatment of hereditary ATTR with polyneuropathy. OBJECTIVE: Describe efficacy and safety of patisiran in patients from Brazil with ATTR cardiomyopathy (ATTR-CM) via a post hoc subgroup analysis of the global APOLLO-B study (NCT03997383). METHODS: Patients 18­85 years of age with ATTR-CM and heart failure were randomized 1:1 to patisiran 0.3 mg/kg or placebo every 3 weeks for 12 months. Primary endpoint was change from baseline (CFB) in functional capacity (6-minute walk test) at Month 12 for patisiran vs placebo. Secondary endpoints included CFB to Month 12 in health status and quality of life (Kansas City Cardiomyopathy QuestionnaireOverall Summary [KCCQ-OS]). Exploratory endpoints included CFB in cardiac biomarkers and Perugini grade by Tc-99m scintigraphy, the latter assessed in a subset of patients in an imaging study within APOLLO-B. RESULTS: Of 360 patients in APOLLO-B, 42 were from Brazil (patisiran, n=20; placebo, n=22): median (range) age at screening, 73 (51, 85) years; male, 81%; wild-type ATTR, 54.8%. No patients were receiving tafamidis at baseline. Patisiran showed benefit vs placebo in 6-minute walk test (median [95% CI] CFB [meters]: −2.02 [−58.5, 42.9] vs −30.1 [−72.2, 3.5]; HodgesLehmann estimate of median difference [95% CI]: 31.4 [−16.6, 79.4]; Figure 1A) and in KCCQ-OS (least squares mean [SEM] CFB: 9.4 [3.8] vs 2.6 [3.7]; least squares mean difference [SEM]: 6.8 [5.3]; Figure 1B). Death was reported in 0 patisiran patients vs 3 (13.6%) placebo. The ratio of adjusted geometric mean fold-change (patisiran:placebo [95% CI]) was 0.77 (0.57, 1.03) for NT-proBNP and 0.87 (0.68, 1.12) for troponin I. In the imaging subset (n=35), 11/18 (61.1%) patisiran patients improved Perugini grade vs 0/10 placebo at Month 12 (Figure 2). Few patisiran patients experienced serious (8 [40%]) or severe (4 [20%]) adverse events; none were drug related. CONCLUSION: In Brazilian patients with ATTR-CM, potential benefit was observed with patisiran on functional capacity, health status and quality of life, cardiac biomarkers, and Perugini grade, consistent with data from the global APOLLO-B population. The results are descriptive; the study was not powered to detect treatment effects specific to this subgroup.

Physical training improves myocardial perfusion but not left ventricular function response to exercise in patients with microvascular angina.

BACKGROUND: Patients with primary microvascular angina (PMA) commonly exhibit abnormal left ventricular function (LVF) during exercise, potentially owing to myocardial ischemia. Herein, we investigated in PMA patients the effect of the reduction of myocardial perfusion disorders, by using aerobic physical training, upon LVF response to exercise. METHODS: Overall, 15 patients (mean age, 53.7±8.9 years) with PMA and 15 healthy controls (mean age, 51.0±9.4 years) were studied. All subjects were subjected to baseline resting and exercise ventriculography, myocardial perfusion scintigraphy (MPS), and cardiopulmonary testing. PMA group members then participated in a 4-month physical training program and were reevaluated via the same methods applied at baseline. RESULTS: Baseline left ventricular ejection fraction (LVEF) determinations by ventriculography were similar for both groups (PMA, 67.7±10.2%; controls, 66.5±5.4%; P=0.67). However, a significant rise in LVEF seen in control subjects during exercise (75.3±6.2%; P=0.0001) did not materialize during peak exercise in patients with PMA (67.7±10.2%; P=0.47). Of the 12 patients in the PMA group who completed the training program, 10 showed a significant reduction in reversible perfusion defects during MPS. Nevertheless, LVEF at rest (63.5±8.7%) and at peak exercise (67.3±15.9%) did not differ significantly (P=0.30) in this subset. CONCLUSIONS: In patients with PMA, reduced left ventricular inotropic reserve observed during exercise did not normalize after improving myocardial perfusion through aerobic physical training.

Rehabilitation practice patterns for patients with heart failure: the South American perspective.

Heart failure (HF) is an important public health issue in South America. Economic impacts are substantial. Chagas heart disease is a prevalent HF etiology; it is caused by the protozoan Trypanosoma cruzi. Cardiac rehabilitation (CR) is an integral component of HF care. The benefits of CR in HF patients need to be assessed. The effectiveness and safety of CR delivery, such as home-based interventions, should be explored. Strategies to improve adherence in CR are imperative. We describe past and current CR trends for HF patients and discuss the future of this important intervention.

Avaliação do paciente com artrite / Assessment of patients with arthritis

Artrites são manifestações clínicas de uma série de doenças. Sua classificação etiológica é muitas vezes difícil e depende de história clínica e exame físico cuidadosos. Artrite séptica e gota se apresentam mais comumente como monoartrite aguda e quadros reacionais são geralmente poliarticulares. A internação hospitalar é fator de risco para o desenvolvimento tanto de artrites reacionais quanto para crises de gota e artrite séptica. O diagnóstico precoce é muito importante a fim de iniciar o tratamento precocemente, alívio dos sintomas e preservação da funcionalidade articular. A punção do líquido sinoviale sua análise são de fundamental importância diagnóstica nos quadros de monoartrite aguda.

Arthritis are clinical manifestations of plenty of diseases. Its etiological classification is many timesdifficult and depends on careful clinical history and physical examination. Gout and skeptical arthritispresents commonly as acute monoarthritis and reactional arthritis are often polyarticular. Hospitalaradmission is a risk factor to the development of reactional arthritis, crisis of gout and septical arthritis.Early diagnosis is imperative to start early treatment, symptom relief and articular function preservation.Synovial fluid aspiration and its analysis are of critical diagnostic importance in cases of acute monoarthritis.

Pneumonia comunitária e pneumonia hospitalar em adultos / Community-acquired pneumonia and nosocomial pneumonia in adults

Pneumonia bacteriana comunitária e hospitalar em adultos são problemas de saúde pública crescentes, com inúmeras internações anualmente e causas frequentes de morbimortalidade. A rápida caracterização do quadro clínico deve ser acompanhada de decisão quanto à necessidade de internação do paciente e o tratamento deve ser baseado na gravidade da apresentação e aspectos epidemiológicos. O acompanhamento clínico é imprescindível, tanto ambulatorialmente quanto na internação, atento aos critérios de falha terapêutica e necessidade de revisão da terapêutica inicialmente instituída. Particularmente na pneumonia hospitalar (nosocomial), o diagnóstico é um desafio e a análise do tempo do início do quadro é fundamental para o direcionamento empírico do tratamento. Ênfase na prevenção é uma tentativa de redução na frequência dos casos.

Community and hospital acquired bacterial pneumonia in adults are increasing public health problems, with numerous hospitalizations annually and frequent causes of morbidity and mortality. Rapid characterization of the clinical picture must be accompanied by a decision regarding the need for patient hospitalization and treatment should be based on severity of presentation and epidemiological aspects. The follow up is essential, both outpatient and in hospital, in keeping with the criteria of treatment failure and need for review of initial treatment. Particularly in hospital-acquired pneumonia (nosocomial), the diagnosisis a challenge and analysis of time of onset is crucial for directing empirical treatment. Emphasison prevention is an attempt to reduce the frequency of cases.

Anticoagulação em pacientes hospitalizados / Anticoagulation in hospitalized patients

Os eventos tromboembólicos, principalmente o tromboembolismo venoso, acrescem importante morbidade e mortalidade e representam a segunda causa mais comum de complicações em pacientes hospitalizados. A anticoagulação é o tratamento padrão nestes casos, porém frequentemente seu manejo é complexo e requer conhecimento adequado tanto da farmacologia das drogas quanto da fisiologia da coagulação. Este artigo revê alguns pontos essenciais para quem lida com esses eventos e fornece noções práticas do manejo dos antagonistas da vitamina K e dos anticoagulantes parenterais.

Thromboembolic events, particularly venous thromboembolism, add significant morbidity and mortality and represent the second most common cause of complications in hospitalized patients. Anticoagulation is the standard treatment in these cases, but often their management is complex and requires adequate knowledge of both the pharmacology of drugs and the physiology of coagulation. This article reviews some key points to those who deal with these events and provides practical notions of management of vitamin K antagonists and parenteral anticoagulants.