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1.
Dis Markers ; 2019: 6984845, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275451

RESUMO

Disturbed redox balance in heart failure (HF) might contribute to impairment of cardiac function, by oxidative damage, or by regulation of cell signaling. The role of polymorphism in glutathione transferases (GSTs), involved both in antioxidant defense and in regulation of apoptotic signaling pathways in HF, has been proposed. We aimed to determine whether GST genotypes exhibit differential risk effects between coronary artery disease (CAD) and idiopathic dilated cardiomyopathy (IDC) in HF patients. GSTA1, GSTM1, GSTP1, and GSTT1 genotypes were determined in 194 HF patients (109 CAD, 85 IDC) and 274 age- and gender-matched controls. No significant association was found for GSTA1, GSTM1, and GSTT1 genotypes with HF occurrence due to either CAD or IDC. However, carriers of at least one variant GSTP1∗Val (rs1695) allele were at 1.7-fold increased HF risk than GSTP1∗Ile/Ile carriers (p = 0.031), which was higher when combined with the variant GSTA1∗B allele (OR = 2.2, p = 0.034). In HF patients stratified based on the underlying cause of disease, an even stronger association was observed in HF patients due to CAD, who were carriers of a combined GSTP1(rs1695)/GSTA1 "risk-associated" genotype (OR = 2.8, p = 0.033) or a combined GSTP1∗Ile/Val+Val/Val (rs1695)/GSTP1∗AlaVal+∗ValVal (rs1138272) genotype (OR = 2.1, p = 0.056). Moreover, these patients exhibited significantly decreased left ventricular end-systolic diameter compared to GSTA1∗AA/GSTP1∗IleIle carriers (p = 0.021). Higher values of ICAM-1 were found in carriers of the GSTP1∗IleVal+∗ValVal (rs1695) (p = 0.041) genotype, whereas higher TNFα was determined in carriers of the GSTP1∗AlaVal+∗ValVal genotype (rs1138272) (p = 0.041). In conclusion, GSTP1 polymorphic variants may determine individual susceptibility to oxidative stress, inflammation, and endothelial dysfunction in HF.

2.
Eur J Prev Cardiol ; 26(13): 1396-1398, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31161936
3.
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.

5.
Eur J Prev Cardiol ; : 2047487318807767, 2018 Oct 18.
Artigo em Inglês | MEDLINE | ID: mdl-30335505

RESUMO

Background We assessed the prevalence of newly diagnosed prediabetes and type-2 diabetes mellitus (T2DM), and their impact on long-term mortality in patients hospitalized for worsening heart failure with reduced ejection fraction (HFrEF). Methods We included patients hospitalized with HFrEF and New York Heart Association (NYHA) functional class II-III. Baseline two-hour oral glucose tolerance test was used to classify patients as normoglycaemic or having newly diagnosed prediabetes or T2DM. Outcomes included post-discharge all-cause and cardiovascular mortality during the median follow-up of 2.1 years. Results At baseline, out of 150 patients (mean-age 57 ± 12 years; 88% male), prediabetes was diagnosed in 65 (43%) patients, and T2DM in 29 (19%) patients. These patients were older and more often with NYHA class III symptoms, but distribution of comorbidities was similar to normoglycaemic patients. Taking normoglycaemic patients as a reference, adjusted risk of all-cause mortality was significantly increased both in patients with prediabetes (hazard ratio, 2.6; 95% confidence interval (CI), 1.1-6.3; p = 0.040) and in patients with T2DM (hazard ratio, 5.3; 95% CI, 1.7-15.3; p = 0.023). Likewise, both prediabetes (hazard ratio, 2.9; 95% CI, 1.1-7.9; p = 0.041) and T2DM (hazard ratio, 9.7; 95% CI 2.9-36.7; p = 0.018) independently increased the risk of cardiovascular mortality compared with normoglycaemic individuals. There was no interaction between either prediabetes or T2DM and heart failure aetiology or gender on study outcomes (all interaction p-values > 0.05). Conclusions Newly diagnosed prediabetes and T2DM are highly prevalent in patients hospitalized for worsening HFrEF and NYHA functional class II-III. Importantly, they impose independently increased long-term risk of higher all-cause and cardiovascular mortality.

6.
Eur Heart J ; 39(45): 4030-4039, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30101326

RESUMO

Aims: Evidence suggests an excess risk of non-thromboembolic major adverse cardiac events (MACE) associated with atrial fibrillation (AF), particularly in individuals free of overt coronary artery disease (CAD). Metabolic syndrome (MetS) increases cardiovascular risk in the general population, but less is known how it influences outcomes in AF patients. We aimed to assess whether MetS affects the risk of MACE in AF patients without overt CAD. Methods and results: This prospective, observational study enrolled 843 AF patients (mean-age, 62.5 ± 12.1 years, 38.6% female) without overt CAD. Metabolic syndrome was defined according to the National Cholesterol Education Program. The 5-year composite MACE included myocardial infarction (MI), coronary revascularization, and cardiac death. Metabolic syndrome was present in 302 (35.8%) patients. At 5-year follow-up, 118 (14.0%) patients experienced MACE (2.80%/year). Metabolic syndrome conferred a multivariable adjusted hazard ratio (aHR) of 1.98 for MACE [95% confidence interval (CI), 1.23-3.16; P = 0.004], and for individual outcomes: MI (aHR, 2.00; 95% CI, 1.69-5.11; P < 0.001), revascularization (aHR, 2.33; 95% CI, 1.40-3.87; P = 0.001), and cardiac death (aHR, 2.59; 95% CI, 1.25-5.33; P = 0.011). Following the propensity score (PS)-adjustment for MetS, the association between MetS and MACE (PS-aHR, 1.87; 95% CI, 1.21-3.01; P = 0.012), MI (PS-aHR, 1.72; 95% CI, 1.54-5.00; P = 0.008), revascularization (PS-aHR, 2.18; 95% CI, 1.69-3.11; P = 0.015), and cardiac death (PS-aHR, 2.27; 95% CI, 1.14-5.11; P = 0.023) remained significant. Conclusion: Metabolic syndrome is common in AF patients without overt CAD, and confers an independent, increased risk of MACE, including MI, coronary revascularization, and cardiac death. Given its prognostic implications, prevention and treatment of MetS may reduce the burden of non-thromboembolic complications in AF.

9.
Eur J Heart Fail ; 20(5): 853-872, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29520964

RESUMO

The coexistence of type 2 diabetes mellitus (T2DM) and heart failure (HF), either with reduced (HFrEF) or preserved ejection fraction (HFpEF), is frequent (30-40% of patients) and associated with a higher risk of HF hospitalization, all-cause and cardiovascular (CV) mortality. The most important causes of HF in T2DM are coronary artery disease, arterial hypertension and a direct detrimental effect of T2DM on the myocardium. T2DM is often unrecognized in HF patients, and vice versa, which emphasizes the importance of an active search for both disorders in the clinical practice. There are no specific limitations to HF treatment in T2DM. Subanalyses of trials addressing HF treatment in the general population have shown that all HF therapies are similarly effective regardless of T2DM. Concerning T2DM treatment in HF patients, most guidelines currently recommend metformin as the first-line choice. Sulphonylureas and insulin have been the traditional second- and third-line therapies although their safety in HF is equivocal. Neither glucagon-like preptide-1 (GLP-1) receptor agonists, nor dipeptidyl peptidase-4 (DPP4) inhibitors reduce the risk for HF hospitalization. Indeed, a DPP4 inhibitor, saxagliptin, has been associated with a higher risk of HF hospitalization. Thiazolidinediones (pioglitazone and rosiglitazone) are contraindicated in patients with (or at risk of) HF. In recent trials, sodium-glucose co-transporter-2 (SGLT2) inhibitors, empagliflozin and canagliflozin, have both shown a significant reduction in HF hospitalization in patients with established CV disease or at risk of CV disease. Several ongoing trials should provide an insight into the effectiveness of SGLT2 inhibitors in patients with HFrEF and HFpEF in the absence of T2DM.

11.
Int J Cardiol ; 249: 191-197, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-28986061

RESUMO

BACKGROUND: In addition to thromboembolism, atrial fibrillation (AF) may also predispose to major adverse cardiovascular events (MACE) attributable to coronary artery disease (CAD), including myocardial infarction (MI). The 2MACE score (2 points - Metabolic syndrome and Age≥75years, 1 point - MI/revascularization, Congestive heart failure/ejection-fraction <40%, and thrombo-Embolism) was recently proposed to help identify AF patients at risk of MACE. We assessed the predictive validity of the 2MACE score for MACE occurrence in AF patients free of CAD at baseline. METHODS: Non-valvular AF patients (n=794) without CAD (mean-age, 62.5±12.1years, metabolic syndrome, 34.0%; heart failure/ejection-fraction <40%, 25.7%; thromboembolism, 9.7%) were prospectively followed for 5years, or until MACE (composite of non-fatal/fatal MI, revascularization and cardiovascular death). At inclusion, CAD was excluded by medical history, exercise-stress testing and/or coronary angiography. Also, the 2MACE score was determined. RESULTS: At follow-up, 112 patients experienced MACE (2.8%/year). The 2MACE score demonstrated adequate discrimination (C-statistic, 0.699; 95% confidence interval [CI], 0.648-0.750; P<0.001) and calibration (Hosmer-Lemeshow P=0.79) for MACE. The score was significantly associated with MACE, with the adjusted Hazard Ratio (aHR) of 1.56 (95%CI, 1.35-1.73; P<0.001). As for individual outcomes, the score predicted MI (n=46; aHR, 1.49; 95%CI 1.23-1.80), revascularization (n=32; aHR, 1.41; 95%CI, 1.11-1.80) and cardiovascular death (n=34; aHR, 1.43; 95%CI, 1.14-1.81), all P<0.001. CONCLUSIONS: The 2MACE score successfully predicts future MACE, including incident MI, coronary revascularization and cardiovascular death in AF patients free of CAD at baseline. It may have a role in risk-stratification and primary prevention of MACE in AF patients.


Assuntos
Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/fisiopatologia , Morte , Eletrocardiografia/normas , Índice de Gravidade de Doença , Idoso , Fibrilação Atrial/mortalidade , Doenças Cardiovasculares/diagnóstico por imagem , Doenças Cardiovasculares/mortalidade , Doenças Cardiovasculares/fisiopatologia , Estudos de Coortes , Eletrocardiografia/mortalidade , Eletrocardiografia/tendências , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento
12.
Card Fail Rev ; 2(2): 123-129, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28785466

RESUMO

The prevalence of heart failure (HF) is increasing, representing a major cause of death and disability, and a growing financial burden on healthcare systems. Despite the use of effective treatments with both drugs and devices, mortality remains high. There is therefore a need for new and effective therapeutic agents. Ivabradine is a specific sinus node inhibiting agent that was approved in 2005 by the European Medicines Agency, alone or in combination with a beta-blocker. Trimetazidine is a cytoprotective, anti-ischaemic agent established in the treatment of angina pectoris. In the 2012 European Society of Cardiology (ESC) guidelines for diagnosis and treatment of HF, ivabradine was recommended in symptomatic HF patients who are in sinus rhythm with left ventricular ejection fraction ≤35 % and heart rate higher than 70 beats per minute, despite optimal medical therapy, including maximally tolerated dose of beta-blocker. The role of trimetazidine in this setting was not mentioned. In the 2016 ESC guidelines, recommendations for ivabradine are unchanged but trimetazidine is included for the treatment of angina pectoris with HF. This article discusses the need for new therapeutic options in HF and reviews clinical evidence in support of these two therapeutic options.

13.
Int J Cardiol ; 200: 3-7, 2015 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-26404746

RESUMO

The renin-angiotensin-aldosterone system can be blocked at specific levels by using different classes of pharmacologic agents, including angiotensin-converting-enzyme inhibitors, angiotensin II receptor blockers and mineralocorticoid receptor antagonists. Broad use of the latter, such as spironolactone, has been limited by significant incidence of gynecomastia and other sex-related adverse effects. These problems can be overcome with use of eplerenone, a selective mineralocorticoid receptor antagonist. Eplerenone has been specifically developed to bind selectively to the mineralocorticoid receptors in order to minimize binding to the progesterone and androgen receptors. In the last decade, multiple scientific evidences have been accumulated showing the efficacy and safety of the drug in multiple clinical conditions, including heart failure and arterial hypertension. Eplerenone is generally well tolerated, with the most frequent adverse event being hyperkalemia, with sexual adverse events (i.e. gynecomastia) being more uncommon, due to the selectivity of eplerenone. This review focuses on the pharmacodynamic and pharmacokinetic properties of eplerenone, thus providing the scientific basis to fully understand drug-to-drug interactions, in particular, and its efficacy and tolerability, in general. Noteworthy, the activity of eplerenone in special conditions and different patient populations is summarized.


Assuntos
Antagonistas de Receptores de Mineralocorticoides/farmacologia , Espironolactona/análogos & derivados , Interações de Medicamentos , Eplerenona , Humanos , Antagonistas de Receptores de Mineralocorticoides/uso terapêutico , Sistema Renina-Angiotensina/efeitos dos fármacos , Espironolactona/farmacocinética , Espironolactona/farmacologia
14.
Clin Chem Lab Med ; 52(10): 1437-46, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24988247

RESUMO

Acute heart failure (AHF) is one of the most important cardiovascular syndromes associated with high cardiovascular morbidity, and is the major cause of admission in emergency departments worldwide. The clinical complexity of AHF has significantly increased, mostly due to the comorbidities: diabetes, arterial hypertension, dyslipidemia, obesity, peripheral vascular disease, renal insufficiency and anemia. Numerous clinical trials have demonstrated a frequent association of AHF and diabetes. Since AHF is a very heterogeneous condition, it is important to identify clinical and laboratory parameters useful for risk stratification of these populations. Hyperglycemia may be one of the most convenient, since it is widely measured, easily interpreted, and inexpensive. Acute coronary syndrome (ACS), arrhythmias and poor compliance to chronic medications are considered to be the most frequent precipitating factors of AHF in diabetics. Several studies identified diabetes as the most prominent independent predictor of morbidity and mortality in both acute and chronic heart failure (HF) patients. The following parameters were identified as the independent predictors of in-hospital mortality in patients with AHF and diabetes: older age, systolic blood pressure <100 mmHg, ACS, non-compliance, history of hypertension, left ventricular ejection fraction (LVEF) <50%, serum creatinine >1.5 mg/dL, marked elevation of natriuretic peptides, hyponatremia, treatment at admission without ACE inhibitors/ARBs/ß-blockers, and no percutaneous coronary intervention (PCI) as a treatment modality. The most frequent cause of AHF is ACS, both with ST segment elevation (STEMI) or without (NSTEMI). Hyperglycemia is very common in these patients and although frequently unrecognized and untreated, has a large in-hospital and mortality significance.


Assuntos
Glicemia/metabolismo , Insuficiência Cardíaca/sangue , Síndrome Coronariana Aguda/epidemiologia , Doença Aguda/epidemiologia , Comorbidade , Complicações do Diabetes/sangue , Complicações do Diabetes/epidemiologia , Complicações do Diabetes/fisiopatologia , Insuficiência Cardíaca/complicações , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/fisiopatologia , Humanos
15.
Eur J Heart Fail ; 15(9): 947-59, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23787723

RESUMO

AIMS: The aim of this document was to obtain a real-life contemporary analysis of the demographics and heart failure (HF) statistics, as well as the organization and major activities of the Heart Failure National Societies (HFNS) in European Society of Cardiology (ESC) member countries. METHODS AND RESULTS: Data from 33 countries were collected from HFNS presidents/representatives during the first Heart Failure Association HFNS Summit (Belgrade, Serbia, 29 October 2011). Data on incidence and/or prevalence of HF were available for 22 countries, and the prevalence of HF ranged between 1% and 3%. In five European and one non-European ESC country, heart transplantation was reported as not available. Natriuretic peptides and echocardiography are routinely applied in the management of acute HF in the median of 80% and 90% of centres, respectively. Eastern European and Mediterranean countries have lower availability of natriuretic peptide testing for acute HF patients, compared with other European countries. Almost all countries have organizations dealing specifically with HF. HFNS societies for HF patients exist in only 12, while in 16 countries HF patient education programmes are active. Most HFNS reported that no national HF registry exists in their country. Fifteen HFNS produced national HF guidelines, while 19 have translated the ESC HF guidelines. Most HFNS (n = 23) participated in the organization of the European HF Awareness Day. CONCLUSION: This document demonstrated significant heterogeneity in the organization of HF management, and activities of the national HF working groups/associations. High availability of natriuretic peptide and echocardiographic measurements was revealed, with differences between developed countries and countries in transition.


Assuntos
Cardiologia/organização & administração , Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/terapia , Sociedades Médicas/estatística & dados numéricos , Comportamento Cooperativo , Gerenciamento Clínico , Europa (Continente)/epidemiologia , Inquéritos Epidemiológicos , Insuficiência Cardíaca/diagnóstico , Humanos , Guias de Prática Clínica como Assunto , Prevalência , Sistema de Registros
16.
Heart Fail Rev ; 18(3): 255-66, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22855353

RESUMO

Despite a myriad of causes, pericardial diseases present in few clinical syndromes. Acute pericarditis should be differentiated from aortic dissection, myocardial infarction, pneumonia/pleuritis, pulmonary embolism, pneumothorax, costochondritis, gastroesophageal reflux/neoplasm, and herpes zoster. High-risk features indicating hospitalization are: fever >38 °C, subacute onset, large effusion/tamponade, failure of non-steroidal anti-inflammatory drugs (NSAIDs), previous immunosuppression, trauma, anticoagulation, neoplasm, and myopericarditis. Treatment comprises 10-14-days NSAID plus 3 months colchicine (2 × 0.5 mg; 1 × 0.5 mg in patients <70 kg). Corticosteroids are avoided, except for autoimmunity, as they facilitate the recurrences. Echo-guided pericardiocentesis (±fluoroscopy) is indicated for tamponade and effusions >2 cm. Smaller effusions are drained if neoplastic, purulent or tuberculous etiology is suspected. In recurrent pericarditis, repeated testing for autoimmune and thyroid disease is appropriate. Pericardioscopy and pericardial/epicardial biopsy may clarify the etiology. Familial clustering was recently associated with tumor necrosis factor receptor-associated periodic syndrome (TNFRSF1A gene mutation). Treatment includes 10-14 days NSAIDs with colchicine 0.5 mg bid for up to 6 months. In non-responders, low-dose steroids, intrapericardial steroids, azathioprine, and cyclophosphamide can be tried. Successful management with interleukin-1 receptor antagonist (anakinra) was recently reported. Pericardiectomy remains the last option in >2 years severely symptomatic patients. In constriction, expansion of the heart is impaired by the rigid, chronically inflamed/thickened pericardium (no thickening ~20 %). Chest radiography, echocardiography, computerized tomography, magnetic resonance imaging, hemodynamics, and endomyocardial biopsy indicate the diagnosis. Pericardiectomy is the only treatment for permanent constriction. Predictors of poor survival are prior radiation, renal dysfunction, high pulmonary artery pressures, poor left ventricular function, hyponatremia, age, and simultaneous HIV and tuberculous infection.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Tamponamento Cardíaco , Colchicina/administração & dosagem , Derrame Pericárdico , Pericardite , Pericárdio/patologia , Doença Aguda , Biópsia , Tamponamento Cardíaco/diagnóstico , Tamponamento Cardíaco/etiologia , Tamponamento Cardíaco/terapia , Diagnóstico Diferencial , Humanos , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/etiologia , Derrame Pericárdico/terapia , Pericardiectomia/métodos , Pericardiocentese/métodos , Pericardite/complicações , Pericardite/diagnóstico , Pericardite/fisiopatologia , Pericardite/terapia , Prognóstico , Recidiva , Fatores de Risco , Síndrome , Moduladores de Tubulina
17.
Acta Chir Iugosl ; 58(2): 45-53, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21879650

RESUMO

Hemodynamic instability is the major concern in surgical patients with pericardial diseases, since general anesthesia and positive pressure ventilation may precipitate cardiac tamponade. In advanced constriction diastolic impairment and myocardial fibrosis/atrophy may cause low cardiac output during and after surgery. Elective surgery should be postponed in unstable patients with pericardial comorbidities. Pericardial effusion should be drained percutaneously (in local anesthesia) and pericardiectomy performed for constrictive pericarditis before any major surgical procedure. In emergencies, volume expansion, catecholamines, and anesthetics keeping cardiac output and systemic resistance should be applied. Etiology of pericardial diseases is an important issue is the preoperative management. Patients with neoplastic pericardial involvement have generally poor prognosis and any elective surgical procedure should be avoided. For patients with acute viral or bacterial infection or exacerbated metabolic, uremic, or autoimmune diseases causing significant pericardial effusion, surgery should be postponed until the causative disorder is stabilized and signs of pericarditis have resolved.


Assuntos
Tamponamento Cardíaco/diagnóstico , Tamponamento Cardíaco/terapia , Derrame Pericárdico/diagnóstico , Derrame Pericárdico/terapia , Pericardite/diagnóstico , Pericardite/terapia , Assistência Perioperatória , Cuidados Pré-Operatórios , Humanos , Pericardite Constritiva/diagnóstico , Pericardite Constritiva/terapia
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