Depressive symptoms, cardiac structure and function, and risk of incident heart failure with preserved ejection fraction and heart failure with reduced ejection fraction in late life

BACKGROUND: Depressive symptoms are associated with heightened risk of heart failure (HF), but their association with cardiac function and with HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF) in late life is un-clear. We aimed to determine the prevalence of depression in HFpEF and in HFrEF in late life, and the association of depressive symptoms with cardiac function and incident HFpEF and HFrEF. METHODS AND RESULTS: We studied 6025 participants (age, 75.3±5.1 years; 59% women; 20% Black race) in the ARIC (Atherosclerosis Risk in Communities) study at visit 5 who underwent echocardiography and completed the Center for Epidemiologic Studies Depression Scale questionnaire. Among HF-free participants (n=5086), associations of Center for Epidemiologic Studies Depression Scale score with echocardiography and incident adjudicated HFpEF and HFrEF were assessed using multivariable linear and Cox proportional hazards regression. Prevalent HFpEF, but not HFrEF, was associated with a higher prevalence of depression compared with HF-free participants (P0.05). Over 5.5-year follow-up, higher Center for Epidemiologic Studies Depression Scale score was associated with heightened risk of incident HFpEF (hazard ratio [HR] [95% CI], 1.06 [1.04–1.12]; P=0.02), but not HFrEF (HR [95% CI], 1.02 [0.96–1.08]; P=0.54), independent of echocardiographic measures, NT-proBNP (N-terminal pro-B-type natriuretic peptide), troponin, and hs-CRP (high-sensitivity C-reactive protein) (HR [95% CI], 1.06 [1.00–1.12]; P=0.04). CONCLUSIONS: Worse depressive symptoms predict incident HFpEF in late life, independent of common comorbidities, cardiac structure and function, and prognostic biomarkers. Further studies are necessary to understand the mechanisms linking depression to risk of HFpEF

Predicting Risk in Patients Hospitalized for Acute Decompensated Heart Failure and Preserved Ejection Fraction: The Atherosclerosis Risk in Communities Study Heart Failure Community Surveillance

Background Risk-prediction models specifically for hospitalized heart failure with preserved ejection fraction are lacking. Methods and Results We analyzed data from the ARIC (Atherosclerosis Risk in Communities) Study Heart Failure Community Surveillance to create and validate a risk score predicting mortality in patients ≥55 years of age admitted with acute decompensated heart failure with preserved ejection fraction (ejection fraction ≥50%). A modified version of the risk-prediction model for acute heart failure developed from patients in the EFFECT (Enhanced Feedback for Effective Cardiac Treatment) study was used as a composite predictor of 28-day and 1-year mortalities and evaluated together with other potential predictors in a stepwise logistic regression. The derivation sample consisted of 1852 hospitalizations from 2005 to 2011 (mean age, 77 years; 65% women; 74% white). Risk scores were created from the identified predictors and validated in hospitalizations from 2012 to 2013 (n=821). Mortality in the derivation and validation sample was 11% and 8% at 28 days and 34% and 31% at 1 year. The modified EFFECT score, including age, systolic blood pressure, blood urea nitrogen, sodium, cerebrovascular disease, chronic obstructive pulmonary disease, and hemoglobin, was a powerful predictor of mortality. Another important predictor for both 28-day and 1-year mortalities was hypoxia. The risk scores were well calibrated and had good discrimination in the derivation sample (area under the curve: 0.76 for 28-day and 0.72 for 1-year mortalities) and validation sample (area under the curve: 0.73 and 0.71, respectively). Conclusions Mortality after acute decompensation in patients with heart failure with preserved ejection fraction is high, with one third of patients dying within a year. A prediction tool may allow for greater discrimination of the highest risk patients. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT00005131

A Single Visualization Technique for Displaying Multiple Metabolite-Phenotype Associations

To assist with management and interpretation of human metabolomics data, which are rapidly increasing in quantity and complexity, we need better visualization tools. Using a dataset of several hundred metabolite measures profiled in a cohort of similar to 1500 individuals sampled from a population-based community study, we performed association analyses with eight demographic and clinical traits and outcomes. We compared frequently used existing graphical approaches with a novel ` rain plot' approach to display the results of these analyses. The ` rain plot' combines features of a raindrop plot and a conventional heatmap to convey results of multiple association analyses. A rain plot can simultaneously indicate e ff ect size, directionality, and statistical significance of associations between metabolites and several traits. This approach enables visual comparison features of all metabolites examined with a given trait. The rain plot extends prior approaches and o ff ers complementary information for data interpretation. Additional work is needed in data visualizations for metabolomics to assist investigators in the process of understanding and convey large-scale analysis results e ff ectively, feasibly, and practically

Lung Ultrasound in Acute Heart Failure: Association Between Quality of Life, Symptoms and B-Lines

Background: Impaired health-related quality of life (HRQL) and pulmonary congestion are common and important findings among patients hospitalized for acute heart failure (AHF). There are few data describing the association between HQRL, symptoms and pulmonary congestion in AHF. Purpose: This study investigates whether worse HRQL and symptoms is associated with more pulmonary congestion. Pulmonary congestion measured by lung ultrasound (LUS) in patients with AHF is a marker of worse prognosis at baseline and pre-discharge. Methods: In this 2-site, prospective, observational study, four-zone LUS was performed at baseline (LUS1) and within 72h of hospital discharge (LUS2) in patients hospitalized for AHF. B-lines were quantified off-line, blinded to clinical findings and outcomes, by a core laboratory. Clinicians managing the patients were blinded to LUS findings. HRQL was assessed at baseline using the patient-reported Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ-TSS). Physician assessment of functional limitation at baseline was reported using the NYHA classification. In a subset of participants, patient-reported dyspnea at rest was also examined, at baseline and pre-discharge, using a numeric ranking scale (range 0–10; 10 worst). Dyspnea on exertion was also examined at baseline. Results: Among 322 patients (mean age 72, 60% men, mean LVEF 39%) the median [interquartile range] KCCQ-TSS score was 33 [18–48]. Those with worse KCCQ-TSS scores, analyzed in tertiles, were younger, more likely to be obese and have diabetes mellitus and asthma/COPD, more likely to be on diuretics and report worse dyspnea at rest. At baseline, worse KCCQ-TSS was associated with worse NYHA class (Spearman's rho = −0.33, p<0.0001), dyspnea at rest (Spearman's rho = −0.41, p<0.0001) and dyspnea on exertion (Spearman's rho = −0.44, p<0.0001). A higher number of B-lines on LUS1 was weakly associated with worse NYHA class (Spearman's rho = 0.15, p=0.007) (Figure 1) but was not significantly associated with KCCQ-TSS (p=0.91), dyspnea at rest (p=0.74) or dyspnea on exertion (p=0.96). Among 118 patients with LUS2 performed within 72h of hospital discharge, pre-discharge dyspnea at rest was not significantly associated with B-lines (p=0.98). Conclusion: Among patients hospitalized for AHF, at baseline, worse KCCQ-TSS was associated with worse NYHA class, dyspnea at rest and dyspnea on exertion but was not significantly associated with pulmonary congestion assessed by LUS. A higher number of B-lines at baseline was associated with worse NYHA class. Patient-reported breathlessness and HQRL measures, although important, may not consistently reflect the degree of pulmonary congestion in patients with AHF

Rationale, design, and baseline characteristics in Evaluation of LIXisenatide in Acute Coronary Syndrome, a long-term cardiovascular end point trial of lixisenatide versus placebo

Background: Cardiovascular (CV) disease is the leading cause of morbidity and mortality in patients with type 2 diabetes mellitus (T2DM). Furthermore, patients with T2DM and acute coronary syndrome (ACS) have a particularly high risk of CV events. The glucagonlike peptide 1 receptor agonist, lixisenatide, improves glycemia, but its effects on CV events have not been thoroughly evaluated. Methods: ELIXA (www.clinicaltrials.gov no. NCT01147250) is a randomized, double-blind, placebo-controlled, parallelgroup, multicenter study of lixisenatide in patients with T2DM and a recent ACS event. The primary aim is to evaluate the effects of lixisenatide on CV morbidity and mortality in a population at high CV risk. The primary efficacy end point is a composite of time to CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for unstable angina. Data are systematically collected for safety outcomes, including hypoglycemia, pancreatitis, and malignancy. Results: Enrollment began in July 2010 and ended in August 2013; 6,068 patients from 49 countries were randomized. Of these, 69% are men and 75% are white; at baseline, the mean ± SD age was 60.3 ± 9.7 years, body mass index was 30.2 ± 5.7 kg/m2, and duration of T2DM was 9.3±8.2 years. The qualifying ACS wasamyocardial infarctionin83% and unstableangina in 17%. The study will continue until the positive adjudication of the protocol-specified number of primary CV events. Conclusion: ELIXA will be the first trial to report the safety and efficacy of a glucagon-like peptide 1 receptor agonist in people with T2DM and high CV event risk. © 2015 Elsevier Inc. All rights reserved