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1.
Lancet Diabetes Endocrinol ; 7(8): 618-628, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31272931

RESUMO

BACKGROUND: After acute coronary syndrome, diabetes conveys an excess risk of ischaemic cardiovascular events. A reduction in mean LDL cholesterol to 1·4-1·8 mmol/L with ezetimibe or statins reduces cardiovascular events in patients with an acute coronary syndrome and diabetes. However, the efficacy and safety of further reduction in LDL cholesterol with an inhibitor of proprotein convertase subtilisin/kexin type 9 (PCSK9) after acute coronary syndrome is unknown. We aimed to explore this issue in a prespecified analysis of the ODYSSEY OUTCOMES trial of the PCSK9 inhibitor alirocumab, assessing its effects on cardiovascular outcomes by baseline glycaemic status, while also assessing its effects on glycaemic measures including risk of new-onset diabetes. METHODS: ODYSSEY OUTCOMES was a randomised, double-blind, placebo-controlled trial, done at 1315 sites in 57 countries, that compared alirocumab with placebo in patients who had been admitted to hospital with an acute coronary syndrome (myocardial infarction or unstable angina) 1-12 months before randomisation and who had raised concentrations of atherogenic lipoproteins despite use of high-intensity statins. Patients were randomly assigned (1:1) to receive alirocumab or placebo every 2 weeks; randomisation was stratified by country and was done centrally with an interactive voice-response or web-response system. Alirocumab was titrated to target LDL cholesterol concentrations of 0·65-1·30 mmol/L. In this prespecified analysis, we investigated the effect of alirocumab on cardiovascular events by glycaemic status at baseline (diabetes, prediabetes, or normoglycaemia)-defined on the basis of patient history, review of medical records, or baseline HbA1c or fasting serum glucose-and risk of new-onset diabetes among those without diabetes at baseline. The primary endpoint was a composite of death from coronary heart disease, non-fatal myocardial infarction, fatal or non-fatal ischaemic stroke, or unstable angina requiring hospital admission. ODYSSEY OUTCOMES is registered with ClinicalTrials.gov, number NCT01663402. FINDINGS: At study baseline, 5444 patients (28·8%) had diabetes, 8246 (43·6%) had prediabetes, and 5234 (27·7%) had normoglycaemia. There were no significant differences across glycaemic categories in median LDL cholesterol at baseline (2·20-2·28 mmol/L), after 4 months' treatment with alirocumab (0·80 mmol/L), or after 4 months' treatment with placebo (2·25-2·28 mmol/L). In the placebo group, the incidence of the primary endpoint over a median of 2·8 years was greater in patients with diabetes (16·4%) than in those with prediabetes (9·2%) or normoglycaemia (8·5%); hazard ratio (HR) for diabetes versus normoglycaemia 2·09 (95% CI 1·78-2·46, p<0·0001) and for diabetes versus prediabetes 1·90 (1·65-2·17, p<0·0001). Alirocumab resulted in similar relative reductions in the incidence of the primary endpoint in each glycaemic category, but a greater absolute reduction in the incidence of the primary endpoint in patients with diabetes (2·3%, 95% CI 0·4 to 4·2) than in those with prediabetes (1·2%, 0·0 to 2·4) or normoglycaemia (1·2%, -0·3 to 2·7; absolute risk reduction pinteraction=0·0019). Among patients without diabetes at baseline, 676 (10·1%) developed diabetes in the placebo group, compared with 648 (9·6%) in the alirocumab group; alirocumab did not increase the risk of new-onset diabetes (HR 1·00, 95% CI 0·89-1·11). HRs were 0·97 (95% CI 0·87-1·09) for patients with prediabetes and 1·30 (95% CI 0·93-1·81) for those with normoglycaemia (pinteraction=0·11). INTERPRETATION: After a recent acute coronary syndrome, alirocumab treatment targeting an LDL cholesterol concentration of 0·65-1·30 mmol/L produced about twice the absolute reduction in cardiovascular events among patients with diabetes as in those without diabetes. Alirocumab treatment did not increase the risk of new-onset diabetes. FUNDING: Sanofi and Regeneron Pharmaceuticals.

2.
Eur J Heart Fail ; 21(5): 553-576, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30989768

RESUMO

Cardiomyopathies are a heterogeneous group of heart muscle diseases and an important cause of heart failure (HF). Current knowledge on incidence, pathophysiology and natural history of HF in cardiomyopathies is limited, and distinct features of their therapeutic responses have not been systematically addressed. Therefore, this position paper focuses on epidemiology, pathophysiology, natural history and latest developments in treatment of HF in patients with dilated (DCM), hypertrophic (HCM) and restrictive (RCM) cardiomyopathies. In DCM, HF with reduced ejection fraction (HFrEF) has high incidence and prevalence and represents the most frequent cause of death, despite improvements in treatment. In addition, advanced HF in DCM is one of the leading indications for heart transplantation. In HCM, HF with preserved ejection (HFpEF) affects most patients with obstructive, and ∼10% of patients with non-obstructive HCM. A timely treatment is important, since development of advanced HF, although rare in HCM, portends a poor prognosis. In RCM, HFpEF is common, while HFrEF occurs later and more frequently in amyloidosis or iron overload/haemochromatosis. Irrespective of RCM aetiology, HF is a harbinger of a poor outcome. Recent advances in our understanding of the mechanisms underlying the development of HF in cardiomyopathies have significant implications for therapeutic decision-making. In addition, new aetiology-specific treatment options (e.g. enzyme replacement therapy, transthyretin stabilizers, immunoadsorption, immunotherapy, etc.) have shown a potential to improve outcomes. Still, causative therapies of many cardiomyopathies are lacking, highlighting the need for the development of effective strategies to prevent and treat HF in cardiomyopathies.

3.
Eur J Heart Fail ; 20(11): 1505-1535, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29806100

RESUMO

This article updates the Heart Failure Association of the European Society of Cardiology (ESC) 2007 classification of advanced heart failure and describes new diagnostic and treatment options for these patients. Recognizing the patient with advanced heart failure is critical to facilitate timely referral to advanced heart failure centres. Unplanned visits for heart failure decompensation, malignant arrhythmias, co-morbidities, and the 2016 ESC guidelines criteria for the diagnosis of heart failure with preserved ejection fraction are included in this updated definition. Standard treatment is, by definition, insufficient in these patients. Inotropic therapy may be used as a bridge strategy, but it is only a palliative measure when used on its own, because of the lack of outcomes data. Major progress has occurred with short-term mechanical circulatory support devices for immediate management of cardiogenic shock and long-term mechanical circulatory support for either a bridge to transplantation or as destination therapy. Heart transplantation remains the treatment of choice for patients without contraindications. Some patients will not be candidates for advanced heart failure therapies. For these patients, who are often elderly with multiple co-morbidities, management of advanced heart failure to reduce symptoms and improve quality of life should be emphasized. Robust evidence from prospective studies is lacking for most therapies for advanced heart failure. There is an urgent need to develop evidence-based treatment algorithms to prolong life when possible and in accordance with patient preferences, increase life quality, and reduce the burden of hospitalization in this vulnerable patient population.

5.
Cardiol Clin ; 35(4): 567-588, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29025548

RESUMO

Interventional procedures for pericardial diseases include pericardiocentesis, drainage of pericardial effusion, intrapericardial therapy, and percutaneous balloon pericardiotomy or percutaneous pericardiostomy. Echocardiographic and fluoroscopic guidance have greatly increased safety and feasibility. Several devices for pericardiocentesis have been tested (PerDucer, PeriAttacher, visual puncture systems, Grasper, Scissors, and Reverse slitter), mainly to facilitate access to the pericardium in the absence of effusion for epicardial ablations or left atrial appendage ligation. In selected patients with pericardial effusions that cannot be managed medically or with prolonged drainage, various medications can be applied intrapericardially to prevent further recurrences or induce sclerosis of the pericardial space.


Assuntos
Tamponamento Cardíaco/cirurgia , Derrame Pericárdico/cirurgia , Pericardiectomia/métodos , Pericardiocentese/métodos , Pericardite/cirurgia , Apêndice Atrial/cirurgia , Ecocardiografia , Fluoroscopia , Humanos , Complicações Pós-Operatórias/epidemiologia , Cirurgia Assistida por Computador
6.
Clin Res Cardiol ; 106(8): 645-655, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28361371

RESUMO

AIM: Patient-reported outcomes such as health-related quality of life (HRQoL) are main treatment goals for heart failure (HF) and therefore endpoints in multinational therapy trials. However, little is known about country-specific differences in HRQoL and in treatment-associated HRQoL improvement. The present work sought to examine those questions. METHODS AND RESULTS: We analysed data from the Cardiac Insufficiency Bisoprolol Study in Elderly (CIBIS-ELD) trial, in which patients from central and south-eastern Europe completed the HRQoL questionnaire SF-36 at baseline and the end of a 12-week beta-blocker up-titration (follow-up). 416 patients from Serbia (mean age 72.21 years, 69% NYHA-class I-II, 27.4% women) and 114 from Germany (mean age 73.64 years, 78.9% NYHA-class I-II, 47.4% women) were included. Controlling for clinical variables, the change in mental HRQoL from baseline to follow-up was modulated by Country: Serbian patients, M baseline = 37.85 vs. M follow-up = 40.99, t(526) = 5.34, p < .001, reported a stronger increase than Germans, M baseline = 37.66 vs. M follow-up = 38.23, t(526) = 0.68, ns. For physical HRQoL, we observed a main effect of Country, M Serbia = 39.28 vs. M Germany = 35.29, t(526) = 4.24, p < .001. CONCLUSION: We observed significant differences in HF patients from Germany and Serbia and country-specific differences between Serbian and German patients in mean physical HRQoL. Changes in mental HRQoL were modulated by country. Those results may reflect psychological, sociocultural, aetiological differences or regional differences in phenotype prevalence. More importantly, they suggest that future multinational trials should consider such aspects when designing a trial in order to avoid uncertainties aligned to data interpretation and to improve subsequent treatment optimisation.


Assuntos
Bisoprolol/administração & dosagem , Carbazóis/administração & dosagem , Nível de Saúde , Insuficiência Cardíaca/psicologia , Medidas de Resultados Relatados pelo Paciente , Propanolaminas/administração & dosagem , Qualidade de Vida , Antagonistas de Receptores Adrenérgicos alfa 1/administração & dosagem , Antagonistas de Receptores Adrenérgicos beta 1/administração & dosagem , Idoso , Carvedilol , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/fisiopatologia , Humanos , Masculino , Volume Sistólico/efeitos dos fármacos , Inquéritos e Questionários
7.
Curr Pharm Des ; 22(31): 4752-4762, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27306092

RESUMO

Advances in pharmacotherapy as well as device therapy in common cardiovascular diseases, especially implementation of rapid coronary reperfusion as a key management strategy in acute ischemic disease, improved overall survival. Yet, this success contributes to increased number of patients susceptible to heart failure development due to damaged myocardium. Although survival after heart failure diagnosis has improved over time, the death rate remains high: ≈50% of people diagnosed with this disease will die within 5 years. Thus, not only there is a space for novel concepts and strategies in the treatment of symptomatic heart failure, but also they are urgently needed. The mechanisms underlying the development of heart failure are multiple, complex, and not well understood. However, regardless of the cause of heart failure, or whether its presentation is acute or chronic, altered mitochondrial function/bioenergetics appears to play a substantial role in its pathophysiology. As such, the mitochondria are potentially promising, but still underused, target for new HF therapies. This review will focus on changes that occur in the mitochondria of failing myocardium, as well as on targets and approaches that suggest potential therapeutic effect in this ominous disease.


Assuntos
Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Animais , Insuficiência Cardíaca/diagnóstico , Insuficiência Cardíaca/metabolismo , Humanos , Mitocôndrias/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia
8.
BMJ Open ; 6(1): e007842, 2016 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-26733562

RESUMO

INTRODUCTION: Intrapericardial fibrinolysis has been proposed as a means of preventing complications of pericardial effusion such as cardiac tamponade, persistent and recurrent pericardial effusion, and pericardial constriction. There is a need to understand the efficacy and safety of this procedure because it shows promise. METHODS AND ANALYSIS: We aim to assess the effects of intrapericardial fibrinolysis in the treatment of pericardial effusion. We will search PubMed, the Cochrane Library, African Journals online, Cumulative Index to Nursing and Allied Health Literature, Trip database, Clinical trials.gov and the WHO International Clinical Trials Registry Platform for studies that evaluate the efficacy and/or safety of complete pericardial fluid drainage by intrapericardial fibrinolysis irrespective of study design, geographical location, language, age of participants, aetiology of pericarditis or types of fibrinolytics. Two authors will do the search independently, screen the search outputs for potentially eligible studies and assess whether the studies meet the inclusion criteria. Discrepancies between the two authors will be resolved through discussion and arbitration by a third author. Data from the selected studies shall be extracted using a standardised data collection form which will be piloted before use. The methodological quality of studies will be assessed using the Cochrane Collaboration's tools for assessing risk of bias for experimental studies and non-randomised studies, respectively. The primary meta-analysis will use random effects models due to expected interstudy heterogeneity. Dichotomous data will be analysed using relative risk and continuous with data mean differences, both with 95% CIs. ETHICS AND DISSEMINATION: Approval by an ethics committee is not required for this study as it is a protocol for a systematic review of published studies. The results will be disseminated through a conference presentation and peer-reviewed publication. REVIEW REGISTRATION NUMBER: PROSPERO, CRD42014015238.


Assuntos
Drenagem/métodos , Fibrinólise , Fibrinolíticos/uso terapêutico , Derrame Pericárdico/terapia , Pericárdio/patologia , Terapia Trombolítica , Humanos , Derrame Pericárdico/complicações , Projetos de Pesquisa , Revisão Sistemática como Assunto
12.
Hellenic J Cardiol ; 56(5): 394-401, 2015 Sep-Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26429367

RESUMO

INTRODUCTION: The aim of this study was to evaluate oxidative stress markers (OSM) and catecholamine levels in patients with dilated cardiomyopathy (DCM) before and after cardiopulmonary exercise testing, and to investigate the association between changes in these markers and the New York Heart Association classification (NYHA) and left ventricular ejection fraction (LVEF) in these patients. METHODS: We evaluated 74 patients with DCM and 80 control subjects without DCM. Patients were grouped according to NYHA stages I/II or III/IV. Eligible participants were considered to be those with LVEF values <45%. The OSM analysed included superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and glutathione peroxidase (GPX). The catecholamines analysed included adrenaline, noradrenaline, and dopamine. Vitamin C was also evaluated. All values were obtained before and after cardiopulmonary exercise testing. RESULTS: There was a significant increase in GR, adrenaline, and noradrenaline after testing in the DCM patients. A significant difference between controls and patients in CAT and evaluated catecholamines was observed after testing. A significant increase in GR, GPX, adrenaline, and noradrenaline for patients in NYHA I/ II, and in CAT, GR, adrenaline, noradrenaline, and dopamine for patients in NYHA III/IV, was found between the different times of observation. LVEF before testing showed a significant positive correlation with GPX, and a negative correlation with noradrenaline and adrenaline. After testing a significant negative correlation was found with SOD and GR. CONCLUSIONS: The results of our study demonstrate the complexity of the neurohumoral mechanisms and physiological alterations in the failing heart in DCM patients. Further studies are needed, including other biomarkers and larger samples of patients, in order to improve our understanding of the aetiopathogenesis of DCM development and progression.


Assuntos
Cardiomiopatia Dilatada/metabolismo , Catecolaminas/metabolismo , Teste de Esforço/métodos , Estresse Oxidativo/fisiologia , Adulto , Cardiomiopatia Dilatada/fisiopatologia , Catalase/metabolismo , Glutationa Peroxidase/metabolismo , Glutationa Redutase/metabolismo , Insuficiência Cardíaca/fisiopatologia , Humanos , Pessoa de Meia-Idade , Superóxido Dismutase/metabolismo , Função Ventricular Esquerda/fisiologia
13.
Eur Heart J ; 36(42): 2921-2964, 2015 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-26320112
14.
PLoS One ; 10(8): e0130462, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26247590

RESUMO

BACKGROUND: To evaluate association between von Willebrand factor (vWF) activity, inflammation markers, disease activity, and subclinical atherosclerosis in patients with rheumatoid arthritis (RA) and low cardiovascular risk. METHODS: Above mentioned parameters were determined in blood samples of 74 non-diabetic, normotensive, female subjects, with no dyslipidemia(42 patients, 32 matched healthy controls, age 45.3±10.0 vs. 45.2±9.8 years). Intima-media thickness (IMT) was measured bilaterally, at common carotid, bifurcation, and internal carotid arteries. Subclinical atherosclerosis was defined as IMT>IMTmean+2SD in controlsat each carotid level and atherosclerotic plaque as IMT>1.5 mm. Majority of RA patients were on methotrexate (83.3%), none on steroids >10 mg/day or biologic drugs. All findings were analysed in the entire study population and in RA group separately. RESULTS: RA patients with subclinical atherosclerosis had higher vWF activity than those without (133.5±69.3% vs. 95.3±36.8%, p<0.05). Predictive value of vWF activity for subclinical atherosclerosis was confirmed by logistic regression. vWF activity correlated significantly with erythrocyte sedimentation rate, fibrinogen, modified disease activity scores (mDAS28-ESR, mDAS28-CRP), modified Health Assessment Questionnaire (p<0.01 for all), duration of smoking, number of cigarettes/day, rheumatoid factor concentration (p<0.05 for all), and anti-CCP antibodies (p<0.01). In the entire study population, vWF activity was higher in participants with subclinical atherosclerosis (130±68% vs. 97±38%, p<0.05) or atherosclerotic plaques (123±57% vs. 99±45%, p<0.05) than in those without. Duration of smoking was significantly associated with vWF activity (ß 0.026, p = 0.039). CONCLUSIONS: We demonstrated association of vWF activity and subclinical atherosclerosis in low-risk RA patients as well as its correlation with inflammation markers, all parameters of disease activity, and seropositivity. Therefore, vWF might be a valuable marker of early atherosclerosis in RA patients.


Assuntos
Artrite Reumatoide/complicações , Aterosclerose/complicações , Fator de von Willebrand/imunologia , Adulto , Antirreumáticos/uso terapêutico , Artrite Reumatoide/sangue , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/imunologia , Aterosclerose/sangue , Aterosclerose/diagnóstico , Aterosclerose/imunologia , Doenças Cardiovasculares/etiologia , Diagnóstico Precoce , Feminino , Humanos , Metotrexato/uso terapêutico , Pessoa de Meia-Idade , Fatores de Risco , Fator de von Willebrand/análise
15.
Eur Heart J ; 36(30): 1958-66, 2015 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-25998514
16.
Eur J Heart Fail ; 17(6): 544-58, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25999021

RESUMO

Acute heart failure is a fatal syndrome. Emergency physicians, cardiologists, intensivists, nurses and other health care providers have to cooperate to provide optimal benefit. However, many treatment decisions are opinion-based and few are evidenced-based. This consensus paper provides guidance to practicing physicians and nurses to manage acute heart failure in the pre-hospital and hospital setting. Criteria of hospitalization and of discharge are described. Gaps in knowledge and perspectives in the management of acute heart failure are also detailed. This consensus paper on acute heart failure might help enable contiguous practice.


Assuntos
Insuficiência Cardíaca/terapia , Guias de Prática Clínica como Assunto/normas , Doença Aguda , Institutos de Cardiologia , Cardiologia/organização & administração , Diuréticos/administração & dosagem , Serviços Médicos de Emergência , Medicina de Emergência/organização & administração , Europa (Continente) , Humanos , Oxigenoterapia , Choque Cardiogênico , Sociedades Médicas , Vasodilatadores/administração & dosagem
17.
Expert Rev Cardiovasc Ther ; 13(3): 237-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25683169

RESUMO

Prompt recognition of cardiac tamponade is critical since the underlying hemodynamic disorder can lead to death if not resolved by percutaneous or surgical drainage of the pericardium. Nevertheless, the management of cardiac tamponade can be challenging because of the lack of the validated criteria for the risk stratification that should guide clinicians in the decision-making process. The Working Group on Myocardial and Pericardial Diseases issued this position statement in order to reply to specific questions: Which patients need immediate drainage of the pericardial effusion?; Is echocardiography sufficient for guidance of pericardiocentesis or should patient be taken to the cardiac catheterization laboratory?; Who should be transferred to specialized/tertiary institution or surgical service?; What type of medical support is necessary during transportation? Current European guidelines published in 2004 do not cover these issues and no additional guidelines are available from major medical and cardiology societies.


Assuntos
Tamponamento Cardíaco/terapia , Derrame Pericárdico/terapia , Triagem/métodos , Tamponamento Cardíaco/fisiopatologia , Drenagem/métodos , Ecocardiografia/métodos , Humanos , Derrame Pericárdico/etiologia , Pericardiocentese/métodos , Pericárdio/patologia
20.
Am Heart J ; 166(1): 13-9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23816016

RESUMO

BACKGROUND: The efficacy and safety of colchicine for the primary prevention of the postpericardiotomy syndrome (PPS), postoperative effusions, and postoperative atrial fibrillation (POAF) remain uncertain. Although preliminary data from a single trial of colchicine given for 1 month postoperatively (COPPS trial) were promising, the results have not been confirmed in a large, multicenter trial. Moreover, in the COPPS trial, colchicine was given 3 days postoperatively. METHODS: The COPPS-2 study is a multicenter, double-blind, placebo-controlled randomized trial. Forty-eight to 72 hours before planned cardiac surgery, 360 patients, 180 in each treatment arm, will be randomized to receive placebo or colchicine without a loading dose (0.5 mg twice a day for 1 month in patients weighing ≥70 kg and 0.5 mg once for patients weighing <70 kg or intolerant to the highest dose). The primary efficacy end point is the incidence of PPS, postoperative effusions, and POAF at 3 months after surgery. Secondary end points are the incidence of cardiac tamponade or need for pericardiocentesis or thoracentesis, PPS recurrence, disease-related admissions, stroke, and overall mortality. CONCLUSIONS: The COPPS-2 trial will evaluate the use of colchicine for the primary prevention of PPS, postoperative effusions, and POAF, potentially providing stronger evidence to support the use of preoperative colchicine without a loading dose to prevent several postoperative complications. ClinicalTrials.gov Identifier: NCT01552187.


Assuntos
Fibrilação Atrial/prevenção & controle , Colchicina/uso terapêutico , Estudos Multicêntricos como Assunto/métodos , Derrame Pericárdico/prevenção & controle , Pericardiectomia/efeitos adversos , Prevenção Primária/métodos , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Fibrilação Atrial/etiologia , Humanos , Derrame Pericárdico/etiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Síndrome , Moduladores de Tubulina/uso terapêutico
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