1,721,587 research outputs found

    Combination decongestion therapy in hospitalized heart failure: loop diuretics, mineralocorticoid receptor antagonists and vasopressin antagonists

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    Congestion is the most common reason for admissions and readmissions for heart failure (HF). The vast majority of hospitalized HF patients appear to respond readily to loop diuretics, but available data suggest that a significant proportion are being discharged with persistent evidence of congestion. Although novel therapies targeting congestion should continue to be developed, currently available agents may be utilized more optimally to facilitate complete decongestion. The combination of loop diuretics, natriuretic doses of mineralocorticoid receptor antagonists and vasopressin antagonists represents a regimen of currently available therapies that affects early and persistent decongestion, while limiting the associated risks of electrolyte disturbances, hemodynamic fluctuations, renal dysfunction and mortality

    Thromboembolism in Heart Failure Patients in Sinus Rhythm: Epidemiology, Pathophysiology, Clinical Trials, and Future Direction

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    Despite advances in medical and device therapy, patients with heart failure remain at high risk for morbidity and mortality. Experimental and clinical studies have shown an association between heart failure and a hypercoagulable state, and that patients with heart failure experience an increased incidence of stroke and other thromboembolic events, regardless of whether they are in atrial fibrillation. Although oral anticoagulation is recommended when atrial fibrillation is present, the benefits of this therapy in patients with heart failure in sinus rhythm are uncertain. Older randomized controlled trials comparing warfarin with antiplatelet therapy were, for the most part, underpowered and failed to show convincing benefits of warfarin therapy in this population. Several recent studies that assessed the effects of low-dose direct-acting oral anticoagulant therapy in patients with coronary artery disease in sinus rhythm either included or specifically targeted patients with heart failure. Post hoc analysis of their results showed that this treatment strategy wasDespite advances in medical and device therapy, patients with heart failure remain at high risk for morbidity and mortality. Experimental and clinical studies have shown an association between heart failure and a hypercoagulable state, and that patients with heart failure experience an increased incidence of stroke and other thromboembolic events, regardless of whether they are in atrial fibrillation. Although oral anticoagulation is recommended when atrial fibrillation is present, the benefits of this therapy in patients with heart failure in sinus rhythm are uncertain. Older randomized controlled trials comparing warfarin with antiplatelet therapy were, for the most part, underpowered and failed to show convincing benefits of warfarin therapy in this population. Several recent studies that assessed the effects of low-dose direct-acting oral anticoagulant therapy in patients with coronary artery disease in sinus rhythm either included or specifically targeted patients with heart failure. Post hoc analysis of their results showed that this treatment strategy was associated with improved outcomes in patients with acute coronary syndrome or stable coronary artery disease and also a significant reduction in thromboembolic events, including ischemic stroke. This review presents the rationale for anticoagulant therapy in patients with heart failure in sinus rhythm, discusses gaps in our knowledge base, offers suggestions for when anticoagulation might be considered, and identifies potential directions for future research.(J Am Coll Cardiol HF 2021;9:243-53) (c) 2021 by the American College of Cardiology Foundation

    Tricuspid Regurgitation in Patients With Heart Failure and Preserved Ejection Fraction: JACC State-of-the-Art Review

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    Heart failure with preserved ejection fraction (HFpEF) is associated with high morbidity and mortality. Important risk factors for the development of HFpEF are similar to risk factors for the progression of tricuspid regurgitation (TR), and both conditions frequently coexist and thus is a distinct phenotype or a marker for advanced HF. Many patients with severe, symptomatic atrial secondary TR have been enrolled in current transcatheter device trials, and may represent patients at an advanced stage of HFpEF. Management of HFpEF thus may affect the pathophysiology of TR, and the physiologic changes that occur following transcatheter treatment of TR, may also impact symptoms and outcomes in patients with HFpEF. This review discusses these issues and suggests possible management strategies for these patients. (J Am Coll Cardiol 2024;84:195 -212) (c) 2024 by the American College of Cardiology Foundation

    Cachexia and Wasting in Chronic Illness: Regulatory and Clinical Trial Update

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    ABSTRACT Cachexia, a syndrome marked by nonintentional weight loss, muscle wasting, functional decline and poor prognosis, affects 50%–80% of cancer patients, severely impacting quality of life, treatment tolerance and survival. A ‘Regulatory and Trial Update Workshop’ was organized by the Society on Cachexia and Wasting Disorders (SCWD) in December 2024 in Washington, DC, focused on clinical trial endpoints, standards of care and recent advancements. This article provides a summary of the discussions that were held during the first day of the workshop. Despite ongoing research, effective therapies for cachexia remain limited. Existing treatments, such as nutritional supplements, progestins, anti‐inflammatories and anabolic agents, have shown mixed results, often improving appetite or lean mass without consistent functional benefits. Common muscle mass measurements, like CT scans of the L3 vertebra, are inadequate as primary endpoints because of biological variability and small effect sizes and because they do not necessarily translate into clinical benefit. Trials continue to face challenges in meeting regulatory requirements, which mandate improvements in both body composition and functional outcomes. Regulatory consensus emphasizes demonstrating clinically meaningful benefits in patient‐reported outcomes/physical function and/or morbidity–mortality using validated instruments, adequate safety exposure, recognition that handgrip and weight alone are insufficient, feasibility in advanced disease, consideration of general activity measures, optional but informative body composition data and, for a pan‐cancer label, benefits across at least three distinct cancers. Patient‐centred endpoints, emphasizing real‐life functioning and social participation, are essential as patients prioritize daily activity and independence over isolated physical measures. Clinical trials presented during the meeting included the MENAC trial, which tested a multimodal intervention combining nutrition, exercise, anti‐inflammatory drugs and cancer therapy, achieved modest weight stabilization but no significant improvements in muscle mass or activity. In contrast, TCMCB07, an MC‐4 receptor antagonist, demonstrated promising results in preclinical and early‐phase human studies, showing weight stabilization and improved caloric intake with good tolerability. ART27.13, a dual CB1/CB2 receptor agonist, also demonstrated positive effects in appetite stimulation and weight stabilization. For S‐pindolol, which targets appetite and metabolism, Phase IIb/III trials are to be initiated, following an earlier Phase II trial that showed improved muscle mass and muscle strength (hand grip strength). Future treatments must focus on integrating patient‐centred goals, therapeutic mechanisms and meaningful clinical outcomes

    Renin–angiotensin blockade in heart failure with preserved ejection fraction: a systematic review and meta‐analysis

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    Studies with angiotensin-converting enzyme inhibitors (ACE-Is) and angiotensin receptor blockers (ARBs) in patients with heart failure with preserved ejection fraction (HFpEF) have yielded inconsistent results. To conduct a systematic review and meta-analysis of all evidence for ACE-I and ARBs in patients with HFpEF, we searched PubMed, Ovid SP, Embase, and Cochrane database to identify randomized trials and observational studies that compared ACE-I or ARBs against placebo or standard therapy in HFpEF patients. Random-effect models were used to pool the data, and I2 testing was performed to assess the heterogeneity of the included studies. A total of 13 studies (treatment arm = 8676 and control arm = 8608) were analysed. Pooled analysis of randomized trials for ACE-I and ARBs (n = 6) did not show any effect on all-cause mortality [relative risk (RR) = 1.02, 95% confidence interval (CI) = 0.93-1.11, P = 0.68, I2  = 0%], while results from observational studies showed a significant improvement (RR = 0.91, 95% CI = 0.87-0.95, P = 0.005, I2  = 81.5%). In pooled analyses of all studies, ACE-I showed a reduction of all-cause mortality (RR = 0.91, 95% CI = 0.87-0.95, P = 0.01). There was no reduction in cardiovascular mortality seen, but in pooled analysis of randomized trials, there was a trend towards reduced HF hospitalization risk (RR = 0.91, 95% CI = 0.83-1.01, I2  = 0%, P = 0.074). These data suggest that ACE-I and ARBs may have a role in improving outcomes of patients with HFpEF, underscoring the need for future research with careful patient selection, and trial design and conduct

    Haemoconcentration, renal function, and post-discharge outcomes among patients hospitalized for heart failure with reduced ejection fraction: insights from the EVEREST trial

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    Haemoconcentration has been studied as a marker of decongestion in patients with hospitalization for heart failure (HHF). We describe the relationship between haemoconcentration, worsening renal function, post-discharge outcomes, and clinical and laboratory markers of congestion in a large multinational cohort of patients with HHF

    Prognostic Role of Prior Heart Failure Hospitalization among Patients Hospitalized for Worsening Chronic Heart Failure

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    Background: Hospitalization for heart failure (HF) is associated with increased risk of death among patients with chronic HF. The degree to which hospitalization for HF is a distinct biologic entity with independent prognostic value versus a marker of higher risk chronic HF patients is unclear.Methods: After excluding patients with new-onset HF, the ASCEND-HF trial (Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure) included 4205 patients hospitalized for worsening chronic HF with reduced or preserved ejection fraction. The present analysis compared patients by presence or absence of prior HF hospitalization within 12 months and by timing of prior HF hospitalization relative to index hospitalization. Associations with 180-day all-cause mortality were assessed, including adjustment for 27 prespecified clinical factors.Results: Overall, 2241 (53.3%) patients had a HF hospitalization within the prior 12 months and 1964 (46.7%) did not. Mortality rates at 180 days were 15.5% and 11.9%, respectively. In unadjusted analyses, prior HF hospitalization was associated with increased risk of 180-day mortality (HR, 1.35 [95% CI, 1.14-1.59]; P&lt;0.01). After adjustment, the point estimate was attenuated and the association not statistically significant (HR, 1.18 [95% CI, 0.99-1.40]; P=0.064). Similarly, after adjustment, compared with patients without prior hospitalization, prior HF hospitalization was not associated with mortality, irrespective of timing (0-4 months: HR, 1.10 [95% CI, 0.87-1.39], P=0.41; 4-8 months: HR, 0.95 [95% CI, 0.70-1.27]; P=0.72; 8-12 months: HR, 1.06 [95% CI, 0.74-1.51], P=0.77; &gt;12 months: HR, 0.81 [95% CI, 0.63-1.06], P=0.12).Conclusions: In this cohort of patients hospitalized for worsening HF, prior HF hospitalization was not associated with 180-day mortality after comprehensively accounting for patient characteristics measured during the index patient visit. Clinical confounders measured at the point-of-care may explain previously observed associations between prior HF hospitalization and mortality, and these clinical factors may be a more direct means of predicting patient survival. </p

    Going Beyond Counting First Authors in Author Co-citation Analysis

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    The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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