prognosis. Systematic description of metabolite patterns in large numbers of HF patients has not been described. Methods: We analyzed plasma samples from 400 patients with chronic HF. All participants met Framingham criteria for HF and had a previous echocardiogram. Data on demographics, comorbid conditions, functional status (6 minute walk distance [6MWD]), and quality of life (Kansas City Cardiomyopathy Questionnaire [KCCQ]) were collected. A blood sample was obtained and aliquoted plasma stored at -70 OC. Eighty-six amino acids (AA), organic acids (OA) and acylcarnitines (AC) were quantified using targeted metabolomic profiling. Analytes with coefficient of variation!0.05 were considered non-variable and not analyzed further. Data was log transformed to maintain a symmetric distribution. Metabolite levels were tested for association with gender, race, HF type (HFrEF vs HFpEF), diabetes status, NYHA class, and 6MWD using linear regression. Multiple comparisons were accounted for by False Discovery Rate (FDR), with FDR!0.05 being considered significant. Results: The cohort was 50% African American, 50% female, 67% HFrEF, and had an average age of 70. There were significant differences in metabolite abundance by each characteristic examined, including race and gender. A strong pattern emerged for citric acid cycle intermediates and HF phenotype; one or more of these intermediates showed significant association with HF type, NYHA class, and 6MWD. Also of note was an increased abundance of short branched-chain AC among diabetics, which was not accompanied by the expected increase in corresponding branched-chain AA. Each of these associations persisted after adjustment for renal function. Conclusion: There are significant differences in plasma metabolomic profiles among HF patients. Metabolites vary by demographics and diabetes status, and citric acid cycle intermediates may be associated with disease severity/prognosis. Analysis in larger data sets is warranted.Introduction: Acute decompensated heart failure (ADHF) can be complicated by electrolyte abnormalities. While there is an abundance of knowledge regarding the clinical significance of serum sodium levels, to our knowledge, there are limited data regarding the prognostic significance of serum chloride levels in ADHF. Hypothesis: We hypothesize that lower serum chloride levels will be associated with long-term mortality after admission for ADHF. Methods: We reviewed 1,318 consecutive patients with established chronic heart failure, with implantable cardioverter defibrillators, admitted for ADHF to the Cleveland Clinic between 7/2008 and 12/2013 and also validated our findings in an independent ADHF cohort from the University of Pennslvania (N5876). All patients were followed for all-cause mortality. Cox-proportional hazards models were adjusted for admission sodium, blood urea nitrogen, length of stay, age, ischemic cardiomyopathy, beta-blocker use, renin-angiotensin system inhibitor use, and mineralocorticoid antagonist use. Results: In our cohort (median age...

Intrinsic renal sodium avidity (IRSA) is a hallmark feature of acute heart failure (AHF) and can be measured by evaluating the urinary sodium (UNa) concentration. The aim of this study is to assess the role of measuring IRSA through a random Una-sample and its association with decongestive response.

AimsDiuretic response in heart failure is blunted when compared to healthy individuals, but the pathophysiology underlying this phenomenon is unclear. We aimed to investigate whether the diuretic resistance mechanism is related to insufficient furosemide tubular delivery or low tubular responsiveness.Methods and resultsWe conducted a prospective, observational study of 50 patients with acute heart failure patients divided into two groups based on previous furosemide use (furosemide naïve: n = 28 [56%] and chronic furosemide users: n = 22 [44%]). Each patient received a protocol‐derived, standardized furosemide dose based on body weight. We measured diuretic response and urine furosemide concentrations. The furosemide naïve group had significantly higher urine volumes and natriuresis when compared to chronic users at all timepoints (all p < 0.05). Urine furosemide delivery was similar in furosemide naïve versus chronic users after accounting for differences in estimated glomerular filtration rate (28.02 [21.03–35.89] vs. 29.70 [18.19–34.71] mg, p = 0.87). However, the tubular response to delivered diuretic was dramatically higher in naïve versus chronic users, that is the urine volume per 1 μg/ml of urine furosemide at 2 h was 148.6 ± 136.1 versus 50.6 ± 56.1 ml (p = 0.005).ConclusionsPatients naïve to furosemide have significantly better diuresis and natriuresis when compared to chronic furosemide users. The blunted diuretic response in patients with chronic loop diuretic exposure is driven by decreased tubular responsiveness rather than insufficient furosemide tubular delivery.

Objectives: Continuous hemodynamic monitoring offers the opportunity to individualize management in severe preeclampsia (PEC). We compared cardiac output (CO) and systemic vascular resistance (SVR) measured by bioreactance (NICOM), ClearsiteTM Fingercuff [CS), and 3D echocardiography (3DE). Study Design: This prospective observational study included 12 pregnant patients with early PEC. CO and SVR were measured simultaneously by NICOM, CS, and 3DE antepartum and 1 to 2 days postpartum. Using 3DE as the standard, CS and NICOM interchangeability, precision, accuracy, and correlation were assessed. Results: Compared to 3DE CO, CS CO was highly correlated (R2=0.70, p=<0.0001) with low percentage error (PE 29%) which met criteria for interchangeablity. CS-SVR had strong correlation (R2=0.81, p=<0.0001) and low PE (29%). While CS tended to slightly overestimate CO (bias +2.05 +/– 1.18 L/min, limit of agreement (LOA) –0.20 – 4.31) and underestimate SVR (bias –279 +/ –156 dyes/sec/cm5; LOA –580 –18.4) these differences were unlikely to be clinically significant. Thus CS could be interchangeable with 3DE for CO and SVR. NICOM-CO had only moderate correlation with 3DE-CO (R2=0.29, p=0.01) with high PE (52%) above threshold for interchangeability. NICOM CO had low mean bias (–1.2 +/–1.68 L/min) but wide 95% LOA (–4.41 – 2.14) suggesting adequate accuracy but low precision in relation to 3DE CO. NICOM SVR had poor correlation with 3DE SVR (R2=0.32, p=0.001) with high PE (67%), relatively low mean bias (238 +/–256), and wide 95% LOA (– 655–1131). NICOM did not meet the criteria for interchangeable with 3DE for CO and SVR. Conclusions: Clearsite Fingercuff, but not NICOM, has potential to be clinically useful for CO and SVR monitoring in severe preeclampsia.

No abstract