Adrenomedullin (ADM) is a peptide hormone first discovered in 1993 in pheochromocytoma. It is synthesized by endothelial and vascular smooth muscle cells and diffuses freely between blood and ...interstitium. Excretion of ADM is stimulated by volume overload to maintain endothelial barrier function. Disruption of the ADM system therefore results in vascular leakage and systemic and pulmonary oedema. In addition, ADM inhibits the renin–angiotensin–aldosterone system. ADM is strongly elevated in patients with sepsis and in patients with acute heart failure. Since hallmarks of both conditions are vascular leakage and tissue oedema, we hypothesize that ADM plays a compensatory role and may exert protective properties against fluid overload and tissue congestion. Recently, a new immunoassay that specifically measures the biologically active ADM (bio‐ADM) has been developed, and might become a biomarker for tissue congestion. As a consequence, measurement of bio‐ADM might potentially be used to guide diuretic therapy in patients with heart failure. In addition, ADM might be used to guide treatment of (pulmonary) oedema or even become a target for therapy. Adrecizumab is a humanized, monoclonal, non‐neutralizing ADM‐binding antibody with a half‐life of 15 days. Adrecizumab binds at the N‐terminal epitope of ADM, leaving the C‐terminal side intact to bind to its receptor. Due to its high molecular weight, the antibody adrecizumab cannot cross the endothelial barrier and consequently remains in the circulation. The observation that adrecizumab increases plasma concentrations of ADM indicates that ADM‐binding by adrecizumab is able to drain ADM from the interstitium into the circulation. We therefore hypothesize that administration of adrecizumab improves vascular integrity, leading to improvement of tissue congestion and thereby may improve clinical outcomes in patients with acute decompensated heart failure. A phase II study with adrecizumab in patients with sepsis is ongoing and a phase II study on the effects of adrecizumab in patients with acute decompensated heart failure with elevated ADM is currently in preparation.
Abstract Patients with heart failure continue to suffer adverse health consequences despite advances in therapies over the past 2 decades. Identification of novel therapeutic targets that may ...attenuate disease progression is therefore needed. The inflammasome may play a central role in modulating chronic inflammation and in turn affecting heart failure progression. The inflammasome is a complex of intracellular interaction proteins that trigger maturation of proinflammatory cytokines interleukin-1β and interleukin-18 to initiate the inflammatory response. This response is amplified through production of tumor necrosis factor α and activation of inducible nitric oxide synthase. The purpose of this review is to discuss recent evidence implicating this inflammatory pathway in the pathophysiology of heart failure.
•The first characterization of patients admitted for heart failure in China is presented.•Differences in patient characteristics and treatments were identified in China compared with other ...registries.•A high prevalence of patients discharged from the hospital for heart failure did not receive target drug dosing.•Low systolic blood pressure, acute myocardial infarction, infection, right bundle branch block, and elevated total bilirubin and blood urea nitrogen were predictors of in-hospital mortality in Chinese patients with heart failure.
Contemporary data on the epidemiology of heart failure (HF) in China are scarce. The China-HF Registry was designed to investigate clinical characteristics, management, and outcomes of patients hospitalized for HF in China.
Data were collected prospectively on 13,687 patients with a primary discharge diagnosis of HF who were enrolled from 132 participating hospitals from January 2012 to September 2015. Data from the China-HF Registry was compared with previously published literature. The mean age was 65 ± 15 years, 59.1% were male, and 36.0% had preserved ejection fraction. Age, body mass index, and systolic blood pressure were lower than in high-income countries. Common comorbidities included hypertension (50.9%), coronary heart disease (49.6%), and atrial fibrillation (24.4%). The overall use of diuretics, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEI/ARB), and β-blockers at admission was 30.1%, 27.0%, and 25.6%, respectively, which was lower than in other registries. For patients discharged alive, ACEI/ARB, β-blocker, and mineralocorticoid receptor antagonist use in patients with reduced ejection fraction was 67.5%, 70.0%, and 74.1%, respectively; device use was much lower. The median length of hospital stay was 10 (range 7–15) days, and in-hospital mortality was 4.1 ± 0.3%. Predictors of mortality included low systolic blood pressure, acute myocardial infarction, infection, right bundle branch block, and elevated total bilirubin and blood urea nitrogen level.
Several important findings in patient profile and treatment patterns among Chinese patients with HF were noted compared with published literature. These data underscore the need for regional characterization of HF for global clinical trials and for the identification of several quality improvement opportunities.
ABSTRACT
Aims
The primary objective of this systematic review was to estimate the prevalence and temporal changes in chronic comorbid conditions reported in heart failure (HF) clinical trials.
...Methods and results
We searched MEDLINE for HF trials enrolling more than 400 patients published between 2001 and 2016.Trials were divided into HF with reduced ejection fraction (HFrEF), HF with preserved ejection fraction (HFpEF), or trials enrolling regardless of ejection fraction. The prevalence of baseline chronic comorbid conditions was categorized according to the algorithm proposed by the Chronic Conditions Data Warehouse, which is used to analyse Medicare data. To test for a trend in the prevalence of comorbid conditions, linear regression models were used to evaluate temporal trends in prevalence of comorbidities. Overall, 118 clinical trials enrolling a cumulative total of 215 508 patients were included. Across all comorbidities examined, data were reported in a mean of 35% of trials, without significant improvement during the study period. Reporting of comorbidities was more common in HFrEF trials (51%) compared with HFpEF trials (27%). Among trials reporting data, hypertension (63%), ischaemic heart disease (44%), hyperlipidaemia (48%), diabetes (33%), chronic kidney disease (25%) and atrial fibrillation (25%) were the major comorbidities. The prevalence of comorbidities including hypertension, atrial fibrillation and chronic kidney disease increased over time while the prevalence of smoking decreased in HFrEF trials.
Conclusion
Many HF trials do not report baseline comorbidities. A more rigorous, systematic, and standardized framework needs to be adopted for future clinical trials to ensure adequate comorbidity reporting and improve recruitment of multi‐morbid HF patients.
Global left atrial failure in heart failure Triposkiadis, Filippos; Pieske, Burkert; Butler, Javed ...
European journal of heart failure,
11/2016, Letnik:
18, Številka:
11
Journal Article
Recenzirano
Odprti dostop
The left atrium plays an important role in the maintenance of cardiovascular and neurohumoral homeostasis in heart failure. However, with progressive left ventricular dysfunction, left atrial (LA) ...dilation and mechanical failure develop, which frequently culminate in atrial fibrillation. Moreover, LA mechanical failure is accompanied by LA endocrine failure deficient atrial natriuretic peptide (ANP) processing‐synthesis/development of ANP resistance) and LA regulatory failure (dominance of sympathetic nervous system excitatory mechanisms, excessive vasopressin release) contributing to neurohumoral overactivity, vasoconstriction, and volume overload (global LA failure). The purpose of the present review is to describe the characteristics and emphasize the clinical significance of global LA failure in patients with heart failure.
Objective The aim of this study was to assess the association between frailty and risk for heart failure (HF) in older adults. Background Frailty is common in the elderly and is associated with ...adverse health outcomes. Impact of frailty on HF risk is not known. Methods We assessed the association between frailty, using the Health ABC Short Physical Performance Battery (HABC Battery) and the Gill index, and incident HF in 2825 participants aged 70 to 79 years. Results Mean age of participants was 74 ± 3 years; 48% were men and 59% were white. During a median follow up of 11.4 (7.1-11.7) years, 466 participants developed HF. Compared to non-frail participants, moderate (HR 1.36, 95% CI 1.08-1.71) and severe frailty (HR 1.88, 95% CI 1.02-3.47) by Gill index was associated with a higher risk for HF. HABC Battery score was linearly associated with HF risk after adjusting for the Health ABC HF Model (HR 1.24, 95% CI 1.13-1.36 per SD decrease in score) and remained significant when controlled for death as a competing risk (HR 1.30; 95% CI 1.00-1.55). Results were comparable across age, sex, and race, and in sub-groups based on diabetes mellitus or cardiovascular disease at baseline. Addition of HABC Battery scores to the Health ABC HF Risk Model improved discrimination (change in C-index, 0.014; 95% CI 0.018-0.010) and appropriately reclassified 13.4% (net-reclassification-improvement 0.073, 95% CI 0.021-0.125; P = .006) of participants (8.3% who developed HF and 5.1% who did not). Conclusions Frailty is independently associated with risk of HF in older adults.
Patients with worsening heart failure with reduced ejection fraction (HFrEF) spend a large proportion of time in the hospital and other health care facilities. The benefits of guideline-directed ...medical therapy (GDMT) in the outpatient setting have been shown in large randomized controlled trials. However, the decision to initiate, continue, switch, or withdraw HFrEF medications in the inpatient setting is often based on multiple factors and subject to significant variability across providers. Based on available data, in well-selected, treatment-naïve patients who are hemodynamically stable and clinically euvolemic after stabilization during hospitalization for HF, elements of GDMT can be safely initiated. Inpatient continuation of GDMT for HFrEF appears safe and well-tolerated in most hemodynamically stable patients. Hospitalization is also a potential time for switching from an angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker to sacubitril/valsartan therapy in eligible patients, and is the subject of ongoing study. Therapy withdrawal or need for dose reduction is rarely required, but if needed identifies a particularly at-risk group of patients with progressive HF. If recurrent intolerance to neurohormonal blockers is observed, these patients should be evaluated for advanced HF therapies. There is an enduring need for using the teachable moment of HFrEF hospitalization for optimal initiation, continuation, and switching of GDMT to improve post-discharge patient outcomes and the quality of chronic HFrEF care.
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Empagliflozin was shown to reduce risk of cardiovascular death among high-risk patients with type 2 diabetes mellitus (1), which led to the U.S. Food and Drug Administration (FDA) expanding its ...labeling in December 2016 for reducing cardiovascular risk. ...we sought to determine specialty-specific prescriber trends of SGLT2i in a large U.S. tertiary care system over the last 5 years. ...these data from an integrated tertiary care system may not be generalizable to all settings.
Patients with acute myocardial infarction (MI) are at risk for developing heart failure (HF) and subsequently are at an increased risk of mortality. Sodium-glucose cotransporter-2 inhibitors have ...been proven to improve outcomes in patients with HF with reduced ejection fraction, and, in the case of empagliflozin, in HF with preserved ejection fraction even without diabetes, but their efficacy and safety in the post-MI population has not yet been evaluated.
The EMPACT-MI trial will evaluate the safety and efficacy of empagliflozin compared with placebo in patients hospitalized for MI with or at high risk of new onset HF, in addition to standard care. EMPACT-MI is a streamlined, multinational, randomized, double-blind, placebo-controlled trial randomizing 5,000 participants at approximately 480 centers in 22 countries. Eligible patients presenting with spontaneous MI must have new signs or symptoms of pulmonary congestion requiring treatment or new left ventricular dysfunction (LVEF<45%), and at least 1 additional risk factor for development of future HF. Eligible and consenting patients are randomized to empagliflozin 10mg or placebo daily in addition to standard of care within 14 days of hospital admission for MI. The primary composite end point is time to first hospitalization for HF or all-cause mortality.
EMPACT-MI will inform clinical practice regarding the role of empagliflozin in patients after an MI with high-risk for the development of future HF and mortality.
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