Browsing by keyword "Heart failure"
Now showing items 1-8 of 8
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Chronic kidney disease and outcomes in heart failure with preserved versus reduced ejection fraction: the Cardiovascular Research Network PRESERVE StudyBACKGROUND: There is scant evidence on the effect that chronic kidney disease (CKD) confers on clinically meaningful outcomes among patients with heart failure with preserved left ventricular ejection fraction (HF-PEF). METHODS AND RESULTS: We identified a community-based cohort of patients with HF. Electronic medical record data were used to divide into HF-PEF and reduced left ventricular EF on the basis of quantitative and qualitative estimates. Level of CKD was assessed by estimated glomerular filtration rate (eGFR) and by dipstick proteinuria. We followed patients for a median of 22.1 months for outcomes of death and hospitalization (HF-specific and all-cause). Multivariable Cox regression estimated the adjusted relative-risk of outcomes by level of CKD, separately for HF-PEF and HF with reduced left ventricular EF. We identified 14 579 patients with HF-PEF and 9762 with HF with reduced left ventricular EF. When compared with patients with eGFR between 60 and 89 mL/min per 1.73 m(2), lower eGFR was associated with an independent graded increased risk of death and hospitalization. For example, among patients with HF-PEF, the risk of death was nearly double for eGFR 15 to 29 mL/min per 1.73 m(2) and 7x higher for eGFR/min per 1.73 m(2), with similar findings in those with HF with reduced left ventricular EF. CONCLUSIONS: CKD is common and an important independent predictor of death and hospitalization in adults with HF across the spectrum of left ventricular systolic function. Our study highlights the need to develop new and effective interventions for the growing number of patients with HF complicated by CKD.
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Circulating extracellular RNAs, myocardial remodeling, and heart failure in patients with acute coronary syndromeBackground: Given high on-treatment mortality in heart failure (HF), identifying molecular pathways that underlie adverse cardiac remodeling may offer novel biomarkers and therapeutic avenues. Circulating extracellular RNAs (ex-RNAs) regulate important biological processes and are emerging as biomarkers of disease, but less is known about their role in the acute setting, particularly in the setting of HF. Methods: We examined the ex-RNA profiles of 296 acute coronary syndrome (ACS) survivors enrolled in the Transitions, Risks, and Actions in Coronary Events Center for Outcomes Research and Education Cohort. We measured 374 ex-RNAs selected a priori, based on previous findings from a large population study. We employed a two-step, mechanism-driven approach to identify ex-RNAs associated with echocardiographic phenotypes (left ventricular [LV] ejection fraction, LV mass, LV end-diastolic volume, left atrial [LA] dimension, and LA volume index) then tested relations of these ex-RNAs with prevalent HF (N=31, 10.5%). We performed further bioinformatics analysis of microRNA (miRNAs) predicted targets' genes ontology categories and molecular pathways. Results: We identified 44 ex-RNAs associated with at least one echocardiographic phenotype associated with HF. Of these 44 exRNAs, miR-29-3p, miR-584-5p, and miR-1247-5p were also associated with prevalent HF. The three microRNAs were implicated in the regulation p53 and transforming growth factor-beta signaling pathways and predicted to be involved in cardiac fibrosis and cell death; miRNA predicted targets were enriched in gene ontology categories including several involving the extracellular matrix and cellular differentiation. Conclusions: Among ACS survivors, we observed that miR-29-3p, miR-584-5p, and miR-1247-5p were associated with both echocardiographic markers of cardiac remodeling and prevalent HF. Relevance for Patients: miR-29c-3p, miR-584-5p, and miR-1247-5p were associated with echocardiographic phenotypes and prevalent HF and are potential biomarkers for adverse cardiac remodeling in HF.
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Cognitive change in heart failure: a systematic reviewBACKGROUND: Cognitive impairment, highly prevalent in patients with heart failure (HF), increases risk for hospitalization and mortality. However, the course of cognitive change in HF is not well characterized. The purpose of this systematic review was to examine the available evidence longitudinal changes in cognitive function in patients with HF. METHODS AND RESULTS: A literature search of several electronic databases was performed. Studies published from January 1, 1980, to September 30, 2012, that used validated measures to diagnose HF and assess cognitive function >/=2x in adults with HF were eligible for inclusion. Change in cognitive function was examined in the context of HF treatments applied (eg, medication initiation, left ventricular assist device implantation), length of follow-up, and comparison group. Fifteen studies met eligibility criteria. Significant decline in cognitive function was noted among patients with HF followed up for >1 year. Improvements in cognition were observed among patients with HF undergoing interventions to improve cardiac function (eg, heart transplantation) and among patients examined over short time periods (year). Studies comparing patients' cognition over time with their own baseline tended to report improvements, whereas studies using a comparison group without HF tended to report declines or stability in cognition over time among patients with HF. CONCLUSIONS: Patients with HF are at increased risk for cognitive decline, but this risk seems to be modifiable with cardiac treatment. Further research is needed to identify the mechanisms that cause cognitive changes in HF.
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Duchenne Muscular Dystrophy: the Heart of the MatterPURPOSE OF REVIEW: Duchenne muscular dystrophy is one of many neuromuscular disorders, but it frequently causes severe disability early in life and early death. Cardiac involvement is an important cause of morbidity and mortality. RECENT FINDINGS: Heart disease in Duchenne muscular dystrophy can include a cardiomyopathy leading to end-stage heart failure along with associated supraventricular and ventricular arrhythmias. This article reviews the diagnosis and treatment of heart disease in Duchenne muscular dystrophy as well as emerging therapies.
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Heart failure among US nursing home residents with diabetes mellitusBACKGROUND: Type 2 diabetes mellitus is associated with an increased risk of developing heart failure. However, few recent studies have examined the characteristics of older adults living in US nursing homes with heart failure and diabetes mellitus. This study is important for clinical practice and public health action plans for heart failure. OBJECTIVE: To estimate the prevalence of, and factors associated with, heart failure in long-stay nursing home residents with diabetes mellitus. METHODS: We conducted a cross-sectional study using the US 2016 Minimum Data Set data consisting of all residents with diabetes aged > /=65 years in Medicare/Medicaid certified nursing homes (n = 297,570). Diabetes mellitus and heart failure were operationalized using the resident's transfer notes at admission and the progress notes during admission through physical examination findings and current treatment orders. RESULTS: Among all residents with diabetes, 26.4% had heart failure. Increasing age of residents, and comorbidities including coronary artery disease (aOR: 1.34; 95% CI: 1.31-1.37), end stage renal disease (aOR: 1.30; 95% CI: 1.26-1.35), and chronic obstructive pulmonary disease (aOR: 1.60; 95% CI: 1.57-1.63) were associated with a higher odds of heart failure. CONCLUSIONS: This is one of the first U.S studies to examine the prevalence and factors associated with heart failure in nursing home residents with diabetes mellitus. It highlights a clinically complex population with multiple comorbid conditions. Future research is needed to understand the pharmacological management of these residents and the extent to which appropriate management can improve quality of life for a medically vulnerable population.
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Incident frailty and cognitive impairment by heart failure status in older patients with atrial fibrillation: the SAGE-AF studyBackground: Atrial fibrillation (AF) and heart failure (HF) frequently co-occur in older individuals. Among patients with AF, HF increases risks for stroke and death, but the associations between HF and incident cognition and physical impairment remain unknown. We aimed to examine the cross-sectional and prospective associations between HF, cognition, and frailty among older patients with AF. Methods: The SAGE-AF (Systematic Assessment of Geriatric Elements in AF) study enrolled 1244 patients with AF (mean age 76 years, 48% women) from five practices in Massachusetts and Georgia. HF at baseline was identified from electronic health records using ICD-9/10 codes. At baseline and 1-year, frailty was assessed by Cardiovascular Health Survey score and cognition was assessed by the Montreal Cognitive Assessment. Results: Patients with prevalent HF (n = 463, 37.2%) were older, less likely to be non-Hispanic white, had less education, and had greater cardiovascular comorbidity burden and higher CHA2DS2VASC and HAS-BLED scores than patients without HF (all P's < 0.01). In multivariable adjusted regression models, HF (present vs. absent) was associated with both prevalent frailty (adjusted odds ratio [aOR]: 2.38, 95% confidence interval [CI]: 1.64-3.46) and incident frailty at 1 year (aOR: 2.48, 95% CI: 1.37-4.51). HF was also independently associated with baseline cognitive impairment (aOR: 1.60, 95% CI: 1.22-2.11), but not with developing cognitive impairment at 1 year (aOR 1.04, 95%CI: 0.64-1.70). Conclusions: Among ambulatory older patients with AF, the co-existence of HF identifies individuals with physical and cognitive impairments who are at higher short-term risk for becoming frail. Preventive strategies to this vulnerable subgroup merit consideration.
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Mdm2 regulates cardiac contractility by inhibiting GRK2-mediated desensitization of beta-adrenergic receptor signalingThe oncoprotein Mdm2 is a RING domain-containing E3 ubiquitin ligase that ubiquitinates G protein-coupled receptor kinase 2 (GRK2) and beta-arrestin2, thereby regulating beta-adrenergic receptor (betaAR) signaling and endocytosis. Previous studies showed that cardiac Mdm2 expression is critical for controlling p53-dependent apoptosis during early embryonic development, but the role of Mdm2 in the developed adult heart is unknown. We aimed to identify if Mdm2 affects betaAR signaling and cardiac function in adult mice. Using Mdm2/p53-KO mice, which survive for 9-12 months, we identified a critical and potentially novel role for Mdm2 in the adult mouse heart through its regulation of cardiac beta1AR signaling. While baseline cardiac function was mostly similar in both Mdm2/p53-KO and wild-type (WT) mice, isoproterenol-induced cardiac contractility in Mdm2/p53-KO was significantly blunted compared with WT mice. Isoproterenol increased cAMP in left ventricles of WT but not of Mdm2/p53-KO mice. Additionally, while basal and forskolin-induced calcium handling in isolated Mdm2/p53-KO and WT cardiomyocytes were equivalent, isoproterenol-induced calcium handling in Mdm2/p53-KO was impaired. Mdm2/p53-KO hearts expressed 2-fold more GRK2 than WT. GRK2 polyubiquitination via lysine-48 linkages was significantly reduced in Mdm2/p53-KO hearts. Tamoxifen-inducible cardiomyocyte-specific deletion of Mdm2 in adult mice also led to a significant increase in GRK2, and resulted in severely impaired cardiac function, high mortality, and no detectable betaAR responsiveness. Gene delivery of either Mdm2 or GRK2-CT in vivo using adeno-associated virus 9 (AAV9) effectively rescued beta1AR-induced cardiac contractility in Mdm2/p53-KO. These findings reveal a critical p53-independent physiological role of Mdm2 in adult hearts, namely, regulation of GRK2-mediated desensitization of betaAR signaling.
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MLK3 mediates impact of PKG1alpha on cardiac function and controls blood pressure through separate mechanismscGMP-dependent protein kinase 1alpha (PKG1alpha) promotes left ventricle (LV) compensation after pressure overload. PKG1-activating drugs improve heart failure (HF) outcomes but are limited by vasodilation-induced hypotension. Signaling molecules that mediate PKG1alpha cardiac therapeutic effects but do not promote PKG1alpha-induced hypotension could therefore represent improved therapeutic targets. We investigated roles of mixed lineage kinase 3 (MLK3) in mediating PKG1alpha effects on LV function after pressure overload and in regulating BP. In a transaortic constriction HF model, PKG activation with sildenafil preserved LV function in MLK3+/+ but not MLK3-/- littermates. MLK3 coimmunoprecipitated with PKG1alpha. MLK3-PKG1alpha cointeraction decreased in failing LVs. PKG1alpha phosphorylated MLK3 on Thr277/Ser281 sites required for kinase activation. MLK3-/- mice displayed hypertension and increased arterial stiffness, though PKG stimulation with sildenafil or the soluble guanylate cyclase (sGC) stimulator BAY41-2272 still reduced BP in MLK3-/- mice. MLK3 kinase inhibition with URMC-099 did not affect BP but induced LV dysfunction in mice. These data reveal MLK3 as a PKG1alpha substrate mediating PKG1alpha preservation of LV function but not acute PKG1alpha BP effects. Mechanistically, MLK3 kinase-dependent effects preserved LV function, whereas MLK3 kinase-independent signaling regulated BP. These findings suggest augmenting MLK3 kinase activity could preserve LV function in HF but avoid hypotension from PKG1alpha activation.
