Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 142
Filtrar
1.
Eur J Heart Fail ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31407860

RESUMO

Current pharmacological therapies for heart failure with reduced ejection fraction are largely either repurposed anti-hypertensives that blunt overactivation of the neurohormonal system or diuretics that decrease congestion. However, they do not address the symptoms of heart failure that result from reductions in cardiac output and reserve. Over the last few decades, numerous attempts have been made to develop and test positive cardiac inotropes that improve cardiac haemodynamics. However, definitive clinical trials have failed to show a survival benefit. As a result, no positive inotrope is currently approved for long-term use in heart failure. The focus of this state-of-the-art review is to revisit prior clinical trials and to understand the causes for their findings. Using the learnings from those experiences, we propose a framework for future trials of such agents that maximizes their potential for success. This includes enriching the trials with patients who are most likely to derive benefit, using biomarkers and imaging in trial design and execution, evaluating efficacy based on a wider range of intermediate phenotypes, and collecting detailed data on functional status and quality of life. With a rapidly growing population of patients with advanced heart failure, the epidemiologic insignificance of heart transplantation as a therapeutic intervention, and both the cost and morbidity associated with ventricular assist devices, there is an enormous potential for positive inotropic therapies to impact the outcomes that matter most to patients.

3.
JACC Heart Fail ; 7(6): 505-515, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31146874

RESUMO

OBJECTIVES: This study assessed sex-related differences in a large cohort of unselected patients with heart failure (HF) across the ejection fraction (EF) spectrum. BACKGROUND: Females are under-represented in randomized clinical trials. Potential sex-related differences in HF may question the generalizability of trials. METHODS: In the Swedish Heart Failure Registry population multivariate Cox and logistic regression models were fitted to investigate differences in prognosis, prognostic predictors, and treatments across males and females. RESULTS: Of 42,987 patients, 37% were females (55% with HF with preserved EF [HFpEF], 39% with HF with mid-range EF [HFmrEF], and 29% with HF with reduced EF [HFrEF]). Females were older and more symptomatic and more likely to have hypertension and kidney disease but less likely to have diabetes and ischemic heart disease. After adjustments, females were more likely to use beta-blockers and digoxin but less likely to receive HF device therapy. Crude mortality/HF hospitalization rates for HFpEF (hazard ratio [HR]: 1.16) and HFmrEF (HR: 1.14) were significantly higher in females but lower in females with HFrEF (HR: 0.95). After adjustments, the risk was significantly lower in females regardless of EF (HR: 0.80 in HFrEF, HR: 0.91 in HFmrEF, and HR: 0.93 in HFpEF). The main sex-related differences in prognostic predictors concerned diabetes in HFrEF and anemia in HFmrEF. CONCLUSIONS: Males and females with HF showed different characteristics across the EF spectrum. Males reported a lower crude risk of mortality/morbidity in HFpEF and HFmrEF but higher risk of HFrEF, although after adjustments, prognosis was better in females regardless of EF. The observed sex-related differences highlight the need for an adequate representation of females in HF randomized controlled trials to improve generalizability.

4.
Int J Cardiol ; 293: 39-44, 2019 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-31178223

RESUMO

Abnormalities of myocardial energy metabolism appear as a common background of the two major cardiac disorders: ischemic heart disease (IHD) and heart failure (HF). Myocardial ischemia has been recently conceived as a multifaceted syndrome that can be precipitated by a number of mechanisms including metabolic abnormalities. HF is a progressive disorder characterised by a complex interaction of haemodynamic, neurohormonal and metabolic disturbances. HF may further promote metabolic changes, generating a vicious cycle. Thus, targeting cardiac metabolism in IHD patients may prevent the deterioration of left ventricular function, stopping the progression to HF. For these reasons, several studies have explored the potential benefits of trimetazidine (TMZ), an inhibitor of free fatty acids oxidation that shifts cardiac and muscle metabolism to glucose utilization. Because of its mechanism of action, TMZ has been found to provide a cardioprotective effect in patients with angina, diabetes mellitus, and left ventricular (LV) dysfunction, and those undergoing revascularization procedures, without relevant side effects. In addition, the lack of interference with heart rate, arterial pressure, and most of frequent comorbidities, makes TMZ an attractive option for patients and clinicians as well. The impact of TMZ on long term mortality and morbidity in ischemic syndromes and in heart failure need to be conclusively confirmed in properly designed RCT.

5.
Eur Heart J Cardiovasc Pharmacother ; 5(3): 171-180, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31119266

RESUMO

Oral anticoagulation in patients presenting with non-valvular atrial fibrillation and a CHA2DS2-VASc score of 1 (CHA2DS2-VASc of 2 in women) remains a challenging approach in clinical practice. Therapeutic decisions need to balance the individual benefit of reducing thromboembolic risk against the potential harm due to an increase in bleeding risk in this intermediate risk patient population. Within the current opinion statement of the European Society of Cardiology working group of cardiovascular pharmacotherapy and the European Society of Cardiology council on stroke the currently available evidence on the anti-thrombotic management in patients presenting with a CHA2DS2-VASc of 1 is summarized. Easily applicable tools for a personalized refinement of the individual thromboembolic risk in patients with atrial fibrillation and a CHA2DS2-VASc score of 1 that guide clinicians through the question whether to anticoagulate or not are provided.

7.
J Am Coll Cardiol ; 73(18): 2345-2353, 2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31072579

RESUMO

The term "inotrope" is familiar and intimately connected with pharmaceuticals clinically used for treatment of low cardiac output with cardiogenic shock. Traditional inotropic agents exert their effect by modulating calcium signaling in the myocardium. Their use is associated with poor long-term outcomes. Newer molecules in development intend to break from calcium mediation and the associated detrimental long-term effects by targeting distinct mechanisms of action to improve cardiac performance. Thus, "inotropy" does not sufficiently describe the range of potential novel pharmaceutical products. To enhance communication around and evaluation of current, emerging, and potential therapies, this review proposes a novel nuanced and holistic framework to categorize pharmacological agents that improve myocardial performance based on 3 myocardial mechanisms: calcitropes, which alter intracellular calcium concentrations; myotropes, which affect the molecular motor and scaffolding; and mitotropes, which influence energetics. Novel chemical entities can easily be incorporated into this structure, distinguishing themselves based on their mechanisms and clinical outcomes.

8.
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.

9.
J Cardiovasc Med (Hagerstown) ; 20(8): 500-503, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31033777

RESUMO

: Economic evaluations have a widespread application in many areas of clinical research and play a key role in the clinical decision-making process. However, economic analyses have been sometimes used to produce new 'evidence' that is not adequately tested in the target population. This is the case of data arising from a systematic review of clinical trials evaluating the use of direct acting oral anticoagulants for the prevention of stroke in patients with atrial fibrillation. Taking into account this example, here we discuss the concerns raised by the improper interpretation of the results. Our conclusions are three-fold. Data from economic analyses should not be shifted to a clinical recommendation. Simulation models should not be used to generate new 'evidence' that is not supported by experimental data and is misleading. Clinical judgment is therefore pivotal to interpret results emerging from economic analyses.

10.
J Cachexia Sarcopenia Muscle ; 10(1): 3-5, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30920780
12.
Int J Cardiol ; 283: 55-63, 2019 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-30538056

RESUMO

BACKGROUND: The cornerstone of the treatment of patients affected by stable angina is based on drugs administration classified as first (beta-blockers, calcium channel blockers, short acting nitrates) or second line treatment (long-acting nitrates, ivabradine, nicorandil, ranolazine and trimetazidine). However, few data on comparison between different classes of drugs justify that one class of drugs is superior to another. METHODS: We performed a systematic review of the literature following PRISMA guidelines. INCLUSION CRITERIA: i) paper published in English; ii) diagnosis of stable coronary disease; iii) randomized clinical trial; iv) comparison of two anti-angina drugs; v) a sample size >100 patients; vi) a follow-up lasting at least 2 weeks; vii) paper published after 1999, when a meta-analysis of trials comparing beta-blockers, calcium antagonists, and nitrates for stable angina of Heidenreich et al. was published. OUTCOME: to establish whether the categorization in first and second line antianginal treatment is scientifically supported. RESULTS: Eleven trials fulfilled inclusion criteria. The results show that there is a paucity of data comparing the efficacy of antianginal agents. The little data available show that there are not compounds superior to others in terms of improvement in exercise test duration, frequency of anginal attacks, need for sub-lingual nitroglycerin. CONCLUSION: The categorization of antianginal drug in first and second line is not confirmed.

13.
Eur J Heart Fail ; 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30411833

RESUMO

Myriad advances in all fields of cardiac imaging have stimulated and reflected new understanding of cardiac performance, myocardial damage and the mechanisms of heart failure. In this paper, the Heart Failure Association assesses the potential usefulness of innovative imaging modalities in enabling more precise diagnostic and prognostic evaluation, as well as in guiding treatment strategies. Many new methods have gradually penetrated clinical practice and are on their way to becoming a part of routine evaluation. This paper focuses on myocardial deformation and three-dimensional ultrasound imaging; stress tests for the evaluation of contractile and filling function; the progress of magnetic resonance techniques; molecular imaging and other sound innovations. The Heart Failure Association aims to highlight the ways in which paradigms have shifted in several areas of cardiac assessment. These include reassessing of the simplified concept of ejection fraction and implementation of the new parameters of cardiac performance applicable to all heart failure phenotypes; switching from two-dimensional to more accurate and reproducible three-dimensional ultrasound volumetric evaluation; greater tissue characterization via recently developed magnetic resonance modalities; moving from assessing cardiac function and congestion at rest to assessing it during stress; from invasive to novel non-invasive hybrid techniques depicting coronary anatomy and myocardial perfusion; as well as from morphometry to the imaging of pathophysiologic processes such as inflammation and apoptosis. This position paper examines the specific benefits of imaging innovations for practitioners dealing with heart failure aetiology, risk stratification and monitoring, and, in addition, for scientists involved in the development of future research.

14.
Eur Heart J ; 2018 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-30165445

RESUMO

Chronic stable angina is the most prevalent symptom of ischaemic heart disease and its management is a priority. Current guidelines recommend pharmacological therapy with drugs classified as being first line (beta blockers, calcium channel blockers, short acting nitrates) or second line (long-acting nitrates, ivabradine, nicorandil, ranolazine, and trimetazidine). Second line drugs are indicated for patients who have contraindications to first line agents, do not tolerate them or remain symptomatic. Evidence that one drug is superior to another has been questioned. Between January and March 2018, we performed a systematic review of articles written in English over the past 50 years English-written articles in Medline and Embase following preferred reporting items and the Cochrane collaboration approach. We included double blind randomized studies comparing parallel groups on treatment of angina in patients with stable coronary artery disease, with a sample size of, at least, 100 patients (50 patients per group), with a minimum follow-up of 1 week and an outcome measured on exercise testing, duration of exercise being the preferred outcome. Thirteen studies fulfilled our criteria. Nine studies involved between 100 and 300 patients, (2818 in total) and a further four enrolled greater than 300 patients. Evidence of equivalence was demonstrated for the use of beta-blockers (atenolol), calcium antagonists (amlodipine, nifedipine), and channel inhibitor (ivabradine) in three of these studies. Taken all together, in none of the studies was there evidence that one drug was superior to another in the treatment of angina or to prolong total exercise duration. There is a paucity of data comparing the efficacy of anti-anginal agents. The little available evidence shows that no anti-anginal drug is superior to another and equivalence has been shown only for three classes of drugs. Guidelines draw conclusions not from evidence but from clinical beliefs.

17.
J Am Coll Cardiol ; 72(1): 96-118, 2018 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-29957236

RESUMO

Statins are the most common drugs administered for patients with cardiovascular disease. However, due to statin-associated muscle symptoms, adherence to statin therapy is challenging in clinical practice. Certain nutraceuticals, such as red yeast rice, bergamot, berberine, artichoke, soluble fiber, and plant sterols and stanols alone or in combination with each other, as well as with ezetimibe, might be considered as an alternative or add-on therapy to statins, although there is still insufficient evidence available with respect to long-term safety and effectiveness on cardiovascular disease prevention and treatment. These nutraceuticals could exert significant lipid-lowering activity and might present multiple non-lipid-lowering actions, including improvement of endothelial dysfunction and arterial stiffness, as well as anti-inflammatory and antioxidative properties. The aim of this expert opinion paper is to provide the first attempt at recommendation on the management of statin intolerance through the use of nutraceuticals with particular attention on those with effective low-density lipoprotein cholesterol reduction.

18.
Eur Heart J Cardiovasc Pharmacother ; 4(3): 180-188, 2018 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-29726985

RESUMO

Renin angiotensin aldosterone system inhibitors/antagonists/blockers (RAASi) are a cornerstone in treatment of patients with cardiovascular diseases especially in those with heart failure (HF) due to their proven effect on surrogate and hard endpoints. Renin angiotensin aldosterone system inhibitors are also the basis in treatment of arterial hypertension, and they are furthermore indicated to reduce events and target organ damage in patients with diabetes and chronic kidney disease, where they have specific indication because of the evidence of benefit. Renin angiotensin aldosterone system inhibitor therapy, however, is associated with an increased risk of hyperkalaemia. Patients with chronic kidney disease and HF are at increased risk of hyperkalaemia and ∼50% of these patients experience two or more yearly recurrences. A substantial proportion of patients receiving RAASi therapy have their therapy down-titrated or more often discontinued even after a single episode of elevated potassium (K+) level. Since RAASi therapy reduces mortality and morbidity in patients with cardiovascular disease steps should, when hyperkalaemia develops, be considered to lower K+ level and enable patients to continue their RAASi therapy. The use of such measures are especially important in those patients with the most to gain from RAASi therapy.

20.
J Card Fail ; 24(6): 365-374, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29597053

RESUMO

BACKGROUND: The aim of this study was to characterize N-terminal pro-B-type natriuretic peptide (NT-proBNP) in terms of determinants of levels and of its prognostic and discriminatory role in heart failure with mid-range (HFmrEF) versus preserved (HFpEF) and reduced (HFrEF) ejection fraction. METHODS AND RESULTS: In 9847 outpatients with HFpEF (n = 1811; 18%), HFmrEF (n = 2122; 22%) and HFrEF (n = 5914; 60%) enrolled in the Swedish Heart Failure Registry, median NT-proBNP levels were 1428, 1540, and 2288 pg/mL, respectively. Many determinants of NT-proBNP differed by ejection fraction, with atrial fibrillation (AF) more important in HFmrEF and HFpEF, diabetes and hypertension in HFmrEF, and age and body mass index in HFrEF and HFmrEF, whereas renal function, New York Heart Association functional class, heart rate, and anemia were similar. Hazard ratios for death and death/HF hospitalization for NT-proBNP above the median ranged from 1.48 to 2.00 and were greatest for HFmrEF and HFpEF. Areas under the receiver operating characteristic curve for death and death/HF hospitalization were greater in HFmrEF than in HFpEF and HFrEF and were reduced by AF in HFpEF and HFmrEF but not in HFrEF. CONCLUSIONS: In HFpEF and especially HFmrEF, NT-proBNP was more prognostic and discriminatory, but also more affected by confounders such as AF. These data support the use of NT-proBNP for eligibility, enrichment, and surrogate end points in HFpEF and HFmrEF trials, and suggest that cutoff levels for eligibility should be carefully tailored to comorbidity.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA