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Background: Animal studies suggest that gut microbiome metabolites such as trimethylamine N-oxide (TMAO) may influence cognitive function and dementia risk. However potential health effects of TMAO and related metabolites remain unclear.Objective: We examined prospective associations of TMAO, γ-butyrobetaine, crotonobetaine, carnitine, choline, and betaine with risk of cognitive impairment and dementia among older adults aged 65 years and older in the Cardiovascular Health Study (CHS).Methods: TMAO and metabolites were measured in stored plasma specimens collected at baseline. Incident cognitive impairment was assessed using the 100-point Modified Mini-Mental State Examination administered serially up to 7 times. Clinical dementia was identified using neuropsychological tests adjudicated by CHS Cognition Study investigators, and by ICD-9 codes from linked Medicare data. Associations of each metabolite with cognitive outcomes were assessed using Cox proportional hazards models.Results: Over a median of 13 years of follow-up, 529 cases of cognitive impairment, and 522 of dementia were identified. After multivariable adjustment for relevant risk factors, no associations were seen with TMAO, carnitine, choline, or betaine. In contrast, higher crotonobetaine was associated with 20-32% higher risk of cognitive impairment and dementia per interquintile range (IQR), while γ-butyrobetaine was associated with ∼25% lower risk of the same cognitive outcomes per IQR.∥Conclusion:These findings suggest that γ-butyrobetaine, crotonobetaine, two gut microbe and host metabolites, are associated with risk of cognitive impairment and dementia. Our results indicate a need for mechanistic studies evaluating potential effects of these metabolites, and their interconversion on brain health, especially later in life. [ABSTRACT FROM AUTHOR]

Aims: Prior cohorts demonstrating the importance of serum chloride levels in heart failure either excluded or had partial representation of patients with heart failure with preserved ejection fraction (HFpEF). We aimed to examine the relationship between serum chloride concentration and outcomes in HFpEF.Methods and Results: We included participants from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist Trial (TOPCAT) who met the following criteria: met inclusion by the natriuretic peptide stratum, had recorded serum chloride levels, and were from the Americas (n = 942). Multivariable Cox proportional hazards models tested the association of serum chloride with clinical outcomes, and mixed effects modelling tested the association of spironolactone or loop diuretic on serial serum chloride levels. The median serum chloride level was 102 [25th-75th percentile 100-105 mmol/L (range 84-114 mmol/L)]. After multivariable adjustment, every standard deviation decrease in serum chloride (4.05 mmol/L) was associated with ∼50% increased risk for cardiovascular death [hazard ratio (HR) 1.51, 95% confidence interval (CI) 1.11-2.06, P = 0.008] and ∼30% increased risk for all-cause death (HR 1.29, 95% CI 1.02-1.62, P = 0.04), but not with the primary composite endpoint or heart failure hospitalization (P > 0.3 for both). There were no significant interactions between spironolactone use and the serum chloride-risk relationship (P > 0.1) for each endpoint. Spironolactone was not (P = 0.33) but loop diuretic use was associated with lower serial serum chloride levels (P < 0.001).Conclusion: Lower serum chloride was independently associated with increased risk of cardiovascular and all-cause death in HFpEF. Loop diuretic use, but not spironolactone, lead to a decrease in serum chloride levels over time. [ABSTRACT FROM AUTHOR]

Disparities in cancer screening and outcomes based on factors such as sex, socioeconomic status, and race and ethnicity in the United States are well documented. A blood-based multi-cancer early detection (MCED) test that detects a shared cancer signal across multiple cancer types and also predicts the cancer signal origin was developed and validated in the Circulating Cell-free Genome Atlas study (CCGA; NCT02889978). CCGA is a prospective, multicenter, case-control, observational study with longitudinal follow-up (overall N = 15,254). In this pre-specified, exploratory, descriptive analysis, test performance was evaluated among racial and ethnic groups. Overall, 4077 participants comprised the independent validation set with confirmed cancer status (cancer: n = 2823; non-cancer: n = 1254). Participants were stratified into the following racial/ethnic groups: Black (non-Hispanic), Hispanic (all races), Other (non-Hispanic), Other/unknown and White (non-Hispanic). Cancer and non-cancer participants were predominantly White (n = 2316, 82.0% and n = 996, 79.4%, respectively). Across groups, specificity for cancer signal detection ranged from 98.1% [ n = 103; 95% CI: 93.2–99.5%] to 100% [ n = 85; 95% CI: 95.7–100.0%]. The sensitivity for cancer signal detection across groups ranged from 43.9% [ n = 57; 95% CI: 31.8–56.7%] to 63.0% [ n = 192; 95% CI: 56.0–69.5%] and generally increased with clinical stage. The MCED test had consistently high specificity and similar sensitivity across racial and ethnic groups, though results are limited by sample size for some groups. Results support the broad applicability of this MCED test and clinical implementation on a population scale as a complement to standard screening. • Performance of a blood-based multi-cancer test was assessed by race and ethnicity. • The test specificity was consistently high regardless of race and ethnicity. • Sensitivity of cancer signal detection was similar across racial and ethnic groups. • Sensitivity was comparable among groups for 12 high-mortality cancers. • Results support the potential population-wide use of this blood-based cancer test. [ABSTRACT FROM AUTHOR]

Background: There are currently limited accurate national estimates for pediatric heart failure (HF).Objectives: This study aims to describe the current burden of primary and comorbid pediatric HF in the United States.Methods: International Classification of Diseases, Clinical Modification codes were used to identify HF cases and comorbidities from the Kids' Inpatient Database, National Inpatient Sample, National Emergency Department (ED) Sample, and National Vital Statistics System for 2012 and 2016. To describe HF events, all visits/events among pediatric and adult subjects were included in the analysis. HF events were classified into 1 of 3 groups: 1) no HF; 2) primary HF; or 3) comorbid HF. We compared patients with and without HF and calculated unique event rates with age and sex standardization.Results: Congenital heart disease, conduction disorders/arrhythmias, and cardiomyopathy were responsible for the majority of pediatric HF-related ED visits and hospitalizations. Compared to 2012, in 2016, there was an increase in comorbid HF ED visits (rate ratio: 1.93; P < 0.001) and primary HF hospitalizations (rate ratio: 1.14; P = 0.002). Pediatric HF burden was lower compared to adult HF; however, deaths in the ED and in-hospital were significantly more likely in children presenting with HF than adults.Conclusions: The burden of pediatric HF continues to increase. Compared to adults with HF presenting to the ED and in-hospital, outcomes are inferior and per patient resource use is higher for children hospitalized with HF. National initiatives to understand risk factors for morbidity and mortality in pediatric HF and continued surveillance and mitigation of preventable risk factors may attenuate this uptrend. [ABSTRACT FROM AUTHOR]

Cardiorenal syndrome encompasses a spectrum of disorders involving both the heart and kidneys in which acute or chronic dysfunction in 1 organ may induce acute or chronic dysfunction in the other organ. It represents the confluence of heart-kidney interactions across several interfaces. These include the hemodynamic cross-talk between the failing heart and the response of the kidneys and vice versa, as well as alterations in neurohormonal markers and inflammatory molecular signatures characteristic of its clinical phenotypes. The mission of this scientific statement is to describe the epidemiology and pathogenesis of cardiorenal syndrome in the context of the continuously evolving nature of its clinicopathological description over the past decade. It also describes diagnostic and therapeutic strategies applicable to cardiorenal syndrome, summarizes cardiac-kidney interactions in special populations such as patients with diabetes mellitus and kidney transplant recipients, and emphasizes the role of palliative care in patients with cardiorenal syndrome. Finally, it outlines the need for a cardiorenal education track that will guide future cardiorenal trials and integrate the clinical and research needs of this important field in the future. [ABSTRACT FROM AUTHOR]

Background: Worsening renal function (WRF) in the setting of aggressive diuresis for acute heart failure treatment may reflect renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Well-validated tubular injury biomarkers, N-acetyl-β-d-glucosaminidase, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1, are now available that can quantify the degree of renal tubular injury. The ROSE-AHF trial (Renal Optimization Strategies Evaluation-Acute Heart Failure) provides an experimental platform for the study of mechanisms of WRF during aggressive diuresis for acute heart failure because the ROSE-AHF protocol dictated high-dose loop diuretic therapy in all patients. We sought to determine whether tubular injury biomarkers are associated with WRF in the setting of aggressive diuresis and its association with prognosis.Methods: Patients in the multicenter ROSE-AHF trial with baseline and 72-hour urine tubular injury biomarkers were analyzed (n=283). WRF was defined as a ≥20% decrease in glomerular filtration rate estimated with cystatin C.Results: Consistent with protocol-driven aggressive dosing of loop diuretics, participants received a median 560 mg IV furosemide equivalents (interquartile range, 300-815 mg), which induced a urine output of 8425 mL (interquartile range, 6341-10 528 mL) over the 72-hour intervention period. Levels of N-acetyl-β-d-glucosaminidase and kidney injury molecule 1 did not change with aggressive diuresis (both P>0.59), whereas levels of neutrophil gelatinase-associated lipocalin decreased slightly (-8.7 ng/mg; interquartile range, -169 to 35 ng/mg; P<0.001). WRF occurred in 21.2% of the population and was not associated with an increase in any marker of renal tubular injury: neutrophil gelatinase-associated lipocalin (P=0.21), N-acetyl-β-d-glucosaminidase (P=0.46), or kidney injury molecule 1 (P=0.22). Increases in neutrophil gelatinase-associated lipocalin, N-acetyl-β-d-glucosaminidase, and kidney injury molecule 1 were paradoxically associated with improved survival (adjusted hazard ratio, 0.80 per 10 percentile increase; 95% confidence interval, 0.69-0.91; P=0.001).Conclusions: Kidney tubular injury does not appear to have an association with WRF in the context of aggressive diuresis of patients with acute heart failure. These findings reinforce the notion that the small to moderate deteriorations in renal function commonly encountered with aggressive diuresis are dissimilar from traditional causes of acute kidney injury. [ABSTRACT FROM AUTHOR]

Background: Patients with moderate-to-severe chronic kidney disease (CKD) are poorly represented in clinical trials of cardiac resynchronization therapy (CRT).Objectives: This study sought to assess the real-world comparative effectiveness of CRT with defibrillator (CRT-D) versus implantable cardioverter-defibrillator (ICD) alone in CRT-eligible patients with moderate-to-severe CKD.Methods: We conducted an inverse probability-weighted analysis of 10,946 CRT-eligible patients (ejection fraction <35%, QRS >120 ms, New York Heart Association functional class III/IV) with stage 3 to 5 CKD in the National Cardiovascular Data Registry (NCDR) ICD Registry, comparing outcomes between patients who received CRT-D (n = 9,525) versus ICD only (n = 1,421). Outcomes were obtained via Medicare claims and censored at 3 years. The primary endpoint of heart failure (HF) hospitalization or death and the secondary endpoint of death were assessed with Cox proportional hazards models. HF hospitalization, device explant, and progression to end-stage renal disease were assessed using Fine-Gray models.Results: After risk adjustment, CRT-D use was associated with a reduction in HF hospitalization or death (hazard ratio [HR]: 0.84; 95% confidence interval [CI]: 0.78 to 0.91; p < 0.0001), death (HR: 0.85; 95% CI: 0.77 to 0.93; p < 0.0004), and HF hospitalization alone (subdistribution HR: 0.84; 95% CI: 0.76 to 0.93; p < 0.009). Subgroup analyses suggested that CRT was associated with a reduced risk of HF hospitalization and death across CKD classes. The incidence of in-hospital, short-term, and mid-term device-related complications did not vary across CKD stages.Conclusions: In a nationally representative population of HF and CRT-eligible patients, use of CRT-D was associated with a significantly lower risk of the composite endpoint of HF hospitalization or death among patients with moderate-to-severe CKD in the setting of acceptable complication rates. [ABSTRACT FROM AUTHOR]

Introduction: The lifetime risk of heart failure (HF) is 20% (in whites), and the prevalence of symptomatic HF is >5 million in the United States. HF prevention by reducing risk factors and increasing heart healthy life style is an important public health goal. Twitter, averaged three hundred million monthly active users, is rapidly becoming the basic instrument in daily life. Twitter may potentially offer tremendous opportunities for advancing the prevention of HF. Methods: We performed data mining of Twitter to assess patients' perceptions regarding HF. Twitter postings containing the terms "heart failure" and "cardiac failure", or "cardiomyopathy" were obtained between July 23, 2009 and June 15, 2017. Each tweet was reviewed by 2 investigators. We resolved disagreements by discussion or by involving the co-authors to adjudicate and establish consensus. All analyses performed in this study relied on public, anonymized data and adhere to the terms and conditions, terms of use and privacy policies of Twitter. No specific tweets with identifying personal information are included in this report. Data mining was performed with R version 3.2.3 and Python version 3.4.2. Results: We analyzed a total of 729,828 Twitter messages. HF Tweets could be characterized by tone, emotion, attitude, style, and perspective. Most of the hand-coded Tweets in our sample (92%) included health-related information. The most commonly represented theme was research article in HF. Tweets associated with HF were categorized as self-reported HF (8%), self-awareness (7%), reported HF awareness in close person (i.e. family, friends, cousin) (3%), reported HF awareness in public person (i.e. politicians, famous athletes or celebrities) (2%), academic purpose or scientific research related to HF (8%), perception about HF in terms of diagnosis and management (7%), emotional language with positive or negative sentiments (23%), advertisements or updated news (21%), metaphor (17%), discussed the treatment and management of HF, particularly diet and exercise (3%), and mentioned death from HF (1%). Conclusions: The use of Twitter for HF research is still in early stage but the result appears promising. Because of the magnitude of the morbidity, mortality, and cost caused by HF, more effort should be emphasized on its primary prevention on public awareness. [ABSTRACT FROM AUTHOR]