Twenty-year follow-up of promising clinical studies reported in highly circulated newspapers: a meta-epidemiological study.

OBJECTIVES: Researchers have identified cases in which newspaper stories have exaggerated the results of medical studies reported in original articles. Moreover, the exaggeration sometimes begins with journal articles. We examined what proportion of the studies quoted in newspaper stories were confirmed. METHODS: We identified newspaper stories from 2000 that mentioned the effectiveness of certain treatments or preventions based on original studies from 40 main medical journals. We searched for subsequent studies until June 2022 with the same topic and stronger research design than each original study. The results of the original studies were verified by comparison with those of subsequent studies. RESULTS: We identified 164 original articles from 1298 newspaper stories and randomly selected 100 of them. Four studies were not found to be effective in terms of the primary outcome, and 18 had no subsequent studies. Of the remaining studies, the proportion of confirmed studies was 68.6% (95% CI 58.1% to 77.5%). Among the 59 confirmed studies, 13 of 16 studies were considered to have been replicated in terms of effect size. However, the results of the remaining 43 studies were not comparable. DISCUSSION: In the dichotomous judgement of effectiveness, about two-thirds of the results were nominally confirmed by subsequent studies. However, for most confirmed results, it was impossible to determine whether the effect sizes were stable. CONCLUSIONS: Newspaper readers should be aware that some claims made by high-quality newspapers based on high-profile journal articles may be overturned by subsequent studies within the next 20 years.

Prevalence, Determinants, and Prognostic Significance of Hospital Acquired Pneumonia in Patients with Acute Heart Failure.

The prognostic impact of hospital-acquired pneumonia (HAP) in acute heart failure (AHF) patients have not been fully elucidated. We evaluated 776 consecutive hospitalized AHF patients. The primary in-hospital outcomes were all-cause death and worsening heart failure (WHF), while the outcome following discharge was all-cause death. The clinical diagnosis of HAP was based on clinical practice guidelines by the Infectious Diseases Society of America and the American Thoracic Society. Patients with HAP had a significantly higher incidence of in-hospital death (12% vs. 1%, p < 0.001), WHF during the hospitalization (28% vs. 7%, p < 0.001), and longer length of hospital stay (p = 0.003) than those without. Among patients who survived at discharge, during a median follow-up period of 741 (interquartile range 422-1000) days, the incidence of all-cause death was significantly higher in patients with HAP than in those without (p < 0.001). In the multivariable Cox regression, HAP development was independently associated with all-cause death after discharge (HR [hazard ratio] 1.86, 95%CI [confidence interval] 1.08-3.19). Furthermore, older age (OR [odds ratio] 1.04, 95%CI 1.01-1.08), male sex (OR 2.21, 95%CI 1.14-4.28), and higher serum white blood cell count (OR 1.18, 95%CI 1.09-1.29) and serum C-reactive protein (OR 1.08, 95%CI 1.01-1.06) were independently associated with HAP development. In hospitalized patients with AHF, HAP development was associated with worse clinical outcomes, suggesting the importance of prevention and early screening for HAP.

Optimal sampling in derivation studies was associated with improved discrimination in external validation for heart failure prognostic models.

OBJECTIVES: The objective of the study was to identify determinants of external validity of prognostic models. STUDY DESIGN AND SETTING: We systematically searched for studies reporting prognostic models of heart failure (HF) and examined their performance for predicting 30-day death in a cohort of consecutive 3,452 acute HF patients. We applied published critical appraisal tools and examined whether bias or other characteristics of original derivation studies determined model performance. RESULTS: We identified 224 models from 6,354 eligible studies. The mean c-statistic in the cohort was 0.64 (standard deviation, 0.07). In univariable analyses, only optimal sampling assessed by an adequate and valid description of the sampling frame and recruitment details to collect the population of interest (total score range: 0-2, higher scores indicating lower risk of bias) was associated with high performance (standardized ß = 0.25, 95% CI: 0.12 to 0.38, P < 0.001). It was still significant after adjustment for relevant study characteristics, such as data source, scale of study, stage of illness, and study year (standardized ß = 0.24, 95% CI: 0.07 to 0.40, P = 0.01). CONCLUSION: Optimal sampling representing the gap between the population of interest and the studied population in derivation studies was a key determinant of external validity of HF prognostic models.

Prognostic value of base excess as indicator of acid-base balance in acute heart failure.

BACKGROUND: Acid-base balance can change as a result of pulmonary oedema and low tissue perfusion in acute heart failure patients. However, its long-term prognostic significance remains to be clarified. METHODS: We prospectively examined a cohort of 472 consecutive acute heart failure patients who underwent arterial blood gas analysis on admission between January 2013 and May 2016. Acidaemia, alkalaemia and normal range of base excess were defined as pH <7.38, >7.42 and -2 to 2 mEq/L, respectively. The primary outcome was all-cause death. RESULTS: During a median follow-up period of 714 days, 101 patients died. Although there was no difference in mortality among patients with acidaemia, normal pH and alkalaemia (p = 0.92), patients with high base excess had the highest mortality compared with others. Multivariable Cox proportional hazard models revealed that high base excess was an independent determinant of mortality (hazard ratio 1.83, 95% confidence interval 1.08-3.13 (high versus normal base excess), hazard ratio 0.81, 95% confidence interval 0.47-1.41 (low versus normal base excess)), even after adjustment for significant prognostic covariates. Furthermore, regarding mortality stratified by base excess and carbon dioxide partial pressure (pCO2), patients with high base excess (>2.1 mEq/L) and high pCO2 (>40 mmHg) had the highest mortality compared with others. CONCLUSIONS: High base excess, but not low base excess, on admission was associated with long-term mortality in acute heart failure patients, indicating the importance of evaluating acid-base balance on admission by base excess for stratifying the risk of mortality in patients with acute heart failure.

Elevated admission urinary N-acetyl-ß-D-glucosamidase level is associated with worse long-term clinical outcomes in patients with acute heart failure.

BACKGROUND: The prognostic significance of urinary N-acetyl-ß-D-glucosamidase in acute heart failure has not been fully elucidated. Accordingly, this study investigated whether urinary N-acetyl-ß-D-glucosamidase could be associated with subsequent adverse events in acute heart failure patients. METHODS: We studied 708 consecutive acute heart failure patients who had accessible N-acetyl-ß-D-glucosamidase data on admission from the National Cerebral and Cardiovascular Center Acute Decompensated Heart Failure registry. We assessed the relationship between the admission N-acetyl-ß-D-glucosamidase level and the combined endpoint of all-cause death and worsening heart failure. Worsening heart failure was defined as worsening symptoms and signs of heart failure requiring intensification of intravenous therapy such as diuretics, vasodilators and inotropes or initiation of mechanical support after stabilisation with initial treatment during hospitalisation, or readmission due to heart failure after discharge. RESULTS: During a median follow-up period of 763 (interquartile range 431-1028) days, higher urinary N-acetyl-ß-D-glucosamidase was significantly related to increased events of all-cause death and worsening heart failure. In addition, patients with higher urinary N-acetyl-ß-D-glucosamidase and lower estimated glomerular filtration rate on admission had the worst clinical outcomes. In multivariable Cox regression, urinary N-acetyl-ß-D-glucosamidase on admission was independently associated with adverse events (hazard ratio 1.19, 95% confidence interval 1.04-1.35) even after adjustment by covariates including the baseline estimated glomerular filtration rate. CONCLUSIONS: Higher urinary N-acetyl-ß-D-glucosamidase level on admission was independently associated with worse clinical outcomes. Our findings indicate the potential value of assessing urinary N-acetyl-ß-D-glucosamidase on admission for further risk stratification in patients with acute heart failure.

Identification of malignant early repolarization pattern by late QRS activity in high-resolution magnetocardiography.

BACKGROUND: The early repolarization pattern (ERP) in electrocardiography (ECG) has been considered as a risk for ventricular fibrillation (VF), but effective methods for identification of malignant ERP are still required. We investigated whether high spatiotemporal resolution 64-channel magnetocardiography (MCG) would enable distinction between benign and malignant ERPs. METHODS: Among all 2,636 subjects who received MCG in our facility, we identified 116 subjects (43 ± 18 years old, 54% male) with inferior and/or lateral ERP in ECG and without structural heart disease, including 13 survivors of VF (ERP-VF(+)) and 103 with no history of VF (ERP-VF(-)). We measured the following MCG parameters in a time-domain waveform of relative current magnitude: (a) QRS duration (MCG-QRSD), (b) root-mean-square of the last 40 ms (MCG-RMS40), and (c) low amplitude (<10% of maximal) signal duration (MCG-LAS). RESULTS: Compared to ERP-VF(-), ERP-VF(+) subjects presented a significantly longer MCG-QRS (108 ± 24 vs. 91 ± 23 ms, p = .02) and lower MCG-RMS40 (0.10 ± 0.08 vs. 0.25 ± 0.20, p = .01) but no difference in MCG-LAS (38 ± 22 vs. 29 ± 23 ms, p = .17). MCG-QRSD and MCG-RMS40 showed significantly larger area under the ROC curve compared to J-peak amplitude in ECG (0.72 and 0.71 vs. 0.50; p = .04 and 0.03). The sensitivity, specificity, and odds ratio for identifying VF(+) based on MCG-QRSD ≥ 100 ms and MCG-RMS40 ≤ 0.24 were 69%, 74%, and 6.33 (95% CI, 1.80-22.3), and 92%, 48%, and 10.9 (95% CI, 1.37-86.8), respectively. CONCLUSION: Magnetocardiography is an effective tool to distinguish malignant and benign ERPs.

A comprehensive validation of very early rule-out strategies for non-ST-segment elevation myocardial infarction in emergency departments: protocol for a multicentre prospective cohort study.

INTRODUCTION: Recent advances in troponin sensitivity enabled early and accurate judgement of ruling-out myocardial infarction, especially non-ST elevation myocardial infarction (NSTEMI) in emergency departments (EDs) with development of various prediction-rules and high-sensitive-troponin-based strategies (hs-troponin). Reliance on clinical impression, however, is still common, and it remains unknown which of these strategies is superior. Therefore, our objective in this prospective cohort study is to comprehensively validate the diagnostic accuracy of clinical impression-based strategies, prediction-rules and hs-troponin-based strategies for ruling-out NSTEMIs. METHODS AND ANALYSIS: In total, 1500 consecutive adult patients with symptoms suggestive of acute coronary syndrome will be prospectively recruited from five EDs in two tertiary-level, two secondary-level community hospitals and one university hospital in Japan. The study has begun in July 2018, and recruitment period will be about 1 year. A board-certified emergency physician will complete standardised case report forms, and independently perform a clinical impression-based risk estimation of NSTEMI. Index strategies to be compared will include the clinical impression-based strategy; prediction rules and hs-troponin-based strategies for the following types of troponin (Roche Elecsys hs-troponin T; Abbott ARCHITECT hs-troponin I; Siemens ADVIA Centaur hs-troponin I; Siemens ADVIA Centaur sensitive-troponin I). The reference standard will be the composite of type 1 MI and cardiac death within 30 days after admission to the ED. Outcome measures will be negative predictive value, sensitivity and effectiveness, defined as the proportion of patients categorised as low risk for NSTEMI. We will also evaluate inter-rater reliability of the clinical impression-based risk estimation. ETHICS AND DISSEMINATION: The study is approved by the Ethics Committees of the Kyoto University Graduate School and Faculty of Medicine and of the five hospitals where we will recruit patients. We will disseminate the study results through conference presentations and peer-reviewed journals.

Comparison of Mortality Prediction Models on Long-Term Mortality in Hospitalized Patients With Acute Heart Failure　- The Importance of Accounting for Nutritional Status.

BACKGROUND: The ideal mortality prediction model (MPM) for acute heart failure (AHF) patients would have sufficient and stable predictive ability for long-term as well as short-term mortality. However, published MPMs for AHF predominantly predict short-term mortality up to 90 days, and their prognostic performance for long-term mortality remains unclear. Methods and Results: We analyzed 609 AHF patients in a prospective registry from January 2013 to May 2016. We compared the prognostic performance for long-term mortality among 8 systematically identified MPMs for AHF that predict short-term mortality up to 90 days from admission. The PROTECT 7-day model showed the highest c-index for long-term as well as short-term mortality among the studied MPMs. Sensitivity analyses revealed serum albumin and total cholesterol to be the most important variables, as dropping these variables resulted in a significant decline in c-index, when compared with other variables specific to the PROTECT 7-day model. Furthermore, significant improvements in c-index and net reclassification were observed when serum albumin or serum albumin plus total cholesterol was added to the studied MPMs, other than the PROTECT 7-day model. CONCLUSIONS: The PROTECT 7-day model demonstrated the highest predictive performance for long-term as well as short-term mortality in AHF patients among the published MPMs. Our findings indicate the importance of accounting for nutritional status such as serum albumin and total cholesterol in AHF patients when developing a MPM.

Effect of intravenous carperitide versus nitrates as first-line vasodilators on in-hospital outcomes in hospitalized patients with acute heart failure: Insight from a nationwide claim-based database.

BACKGROUNDS: Carperitide is a recombinantly produced intravenous formulation of human atrial natriuretic peptide. Despite of negative impacts of nesiritide on clinical outcomes for acute heart failure (AHF), carperitide has been used for around a half of Japanese AHF patients as a vasodilator based on limited evidences. We sought to determine the effect of carperitide compared to nitrates in the early care for AHF patients treated with vasodilators. METHODS AND RESULTS: We conducted a cohort study of patients admitted with AHF to 808 hospitals from April 2012 to March 2014. Patients were extracted from 1,422,703 hospitalizations according to ICD-10 heart failure codes. Patients who had sepsis or mechanical supports during hospitalization were excluded. Outcomes were in-hospital death, length of hospitalization and cost of hospitalization. Among 76,924 patients, 45,595 were in patients treated with either carperitide or nitrates during the first 2 days (carperitide; 33,386, nitrates; 12,209). After application of inverse probability of treatment weighting with variables including demographics, comorbidities and treatments, there was perfect balance in both groups. Patients who were treated with carperitide had substantially higher covariate adjusted in-hospital mortality (HR 1.49 95%CI 1.35-1.64), longer length of hospitalization (Coefficients 0.062 95%CI 0.048 to 0.076) and greater cost of hospitalization (Coefficients 0.024 95%CI 0.010 to 0.037) compared to those treated with nitrates. CONCLUSIONS: In Japanese AHF patients during their early inpatient care, carperitide use was significantly associated with worse outcomes when compared to nitrates use, suggesting the routine use of carperitide might not be recommended as a first-line vasodilator for AHF.

Evidence-Based Utilization of Prognostic Prediction Models in Cardiovascular Medicine.

Prediction models are combinations of predictors to assess the risks of specific endpoints such as the presence or prognosis of a disease. Many novel predictors have been developed, modelling techniques have been evolving, and prediction models are currently abundant in the medical literature, especially in cardiovascular medicine, but evidence is still lacking regarding how to use them. Recent methodological advances in systematic reviews and meta-analysis have enabled systematic evaluation of prediction model studies and quantitative analysis to identify determinants of model performance. Knowing what is critical to model performance, under what circumstances model performance remains adequate, and when a model might require further adjustment and improvement will facilitate effective utilization of prediction models and will enhance diagnostic and prognostic accuracy in clinical practice. In this review article, we provide a current methodological overview of the attempts to implement evidence-based utilization of prognostic prediction models for all potential model users, including patients and their families, health-care providers, administrators, researchers, guideline developers and policy makers.

Elevated Plasma D-Dimer Level Is Associated With Short-Term Risk of Ischemic Stroke in Patients With Acute Heart Failure.

BACKGROUND AND PURPOSE: The incidence of heart failure increases the subsequent risk of ischemic stroke, and its risk could be higher in the short-term period after an acute heart failure (AHF) event. However, its determinants remain to be clarified. Plasma D-dimer level reflects fibrin turnover and exhibits unique properties as a biomarker of thrombosis. The aim of this study is to investigate whether D-dimer level is a determinant of short-term incidence of ischemic stroke in patients with AHF. METHODS: We examined 721 consecutive hospitalized AHF patients with plasma D-dimer level on admission from our prospective registry between January 2013 and May 2016. The study end points were incidence of ischemic stroke during hospitalization and at 30 days after admission. RESULTS: Of the total participants (mean age, 76 years; male, 60%; atrial fibrillation, 54%; mean left ventricular ejection fraction, 38%), in-hospital ischemic stroke occurred in 18 patients (2.5%) during a median hospitalization period of 21 days, and 30-day ischemic stroke occurred in 16 patients (2.2%). Higher D-dimer level on admission was an independent determinant of subsequent risk of in-hospital ischemic stroke even after adjustment by CHA2DS2-VASc score (odds ratio, 2.29; 95% confidence interval, 1.46-3.60; P<0.001) or major confounders, including age, atrial fibrillation, and antithrombotic therapy (odds ratio, 2.31; 95% confidence interval, 1.43-3.74; P<0.001). Subgroup analyses showed consistent findings in patients without atrial fibrillation (odds ratio, 2.46; 95% confidence interval, 1.39-4.54; P=0.002) and those without antithrombotic therapy (odds ratio, 2.79; 95% confidence interval, 1.53-5.57; P<0.001). Similar results were obtained for 30-day ischemic stroke as an alternative outcome. CONCLUSIONS: Elevated plasma D-dimer level on admission was significantly associated with increased incidence of ischemic stroke shortly after admission for AHF, suggesting a predictive role of D-dimer for short-term ischemic stroke events in patients with AHF. CLINICAL TRIAL REGISTRATION: URL: https://www.umin.ac.jp/ctr/index.htm. Unique identifier: UMIN000017024.

Impact of iron deficiency on long-term clinical outcomes of hospitalized patients with heart failure.

BACKGROUND: Iron deficiency (ID) is commonly observed in chronic heart failure (HF) patients and is associated with worse clinical outcomes. While ID is frequent finding in hospitalized heart failure (HHF), its impact on long-term outcome in HHF patients remains unclear. METHODS: We evaluated iron status at discharge in 578 HHF patients. Absolute ID was defined as serum ferritin <100 µg/L, and functional ID (FID) was defined as serum ferritin of 100-299 µg/L with transferrin saturation <20%. The primary outcome of interest was the composite of all-cause mortality and HF admission at one year. RESULTS: Among the study population, 185 had absolute ID, 88 had FID and 305 had no evidence of ID. At one-year post-discharge, 64 patients had died and 112 had been readmitted with HF. Patients with absolute ID had more adverse events than those with FID or no ID (p = 0.021). In multivariate Cox regression analyses, absolute ID was significantly associated with increased risk of adverse events at one year (HR 1.50, 95% CI 1.02-2.21, p = 0.040) compared with the remaining patients. Sensitivity analysis revealed that its prognostic effect did not differ across anemic status, or between HF with reduced and preserved ejection fraction (p for interaction = 0.17, 0.68, respectively). CONCLUSION: Absolute ID, but not FID, at discharge was associated with increased risk of one-year mortality or HF admission in patients with HHF. Further studies are required to evaluate the role of repleting iron stores and its impact on clinical outcomes in patients with HHF.

Long-term prognostic significance of urinary sodium concentration in patients with acute heart failure.

BACKGROUND: Lower urinary sodium concentration (UNa) may reflect impaired renal perfusion, higher neurohormonal activity and diuretic resistance. However, the prognostic impact of UNa in patients with acute heart failure (AHF) has not been fully elucidated. METHODS: We investigate the association between UNa and clinical outcomes in 669 patients admitted with AHF in our prospective registry. Patients were stratified into tertiles based on UNa in a spot urine sample on admission. RESULTS: Patients with lower UNa were more likely to have a history of prior heart failure admission, ß-blockers and diuretics use, and had lower blood pressure and serum sodium level, and higher blood urea nitrogen, estimated glomerular filtration rate, blood glucose and troponin T levels on admission than those with higher UNa. Plasma renin activity, aldosterone, cortisol and dopamine levels were also significantly higher in patients with lower UNa (all p<0.001). Furthermore, patients with lower UNa had significantly less weight loss, lower net fluid loss/furosemide equivalent dose and higher incidence of worsening renal function during hospitalization than those with higher UNa (all p<0.01). During a median follow-up period of 560days, lower UNa was significantly associated with the composite of all-cause death and worsening heart failure (p<0.001). In multivariable Cox-proportional hazards model, UNa remained an independent determinant of long-term adverse events (HR, 1.24, 95% CI, 1.06-1.45, p=0.006). CONCLUSIONS: Lower UNa was associated with worse long-term clinical outcomes along with increased neurohormonal activities, impaired response to diuretics and higher incidence of worsening renal function in patients with AHF.

Rationale and Design of Low-dose Administration of Carperitide for Acute Heart Failure (LASCAR-AHF).

BACKGROUNDS: Despite current therapies, acute heart failure (AHF) remains a major public health burden with high rates of in-hospital and post-discharge morbidity and mortality. Carperitide is a recombinantly produced intravenous formulation of human atrial natriuretic peptide that promotes vasodilation with increased salt and water excretion, which leads to reduction of cardiac filling pressures. A previous open-label randomized controlled study showed that carperitide improved long-term cardiovascular mortality and heart failure (HF) hospitalization for patients with AHF, when adding to standard therapy. However, the study was underpowered to detect a difference in mortality because of the small sample size. METHODS: Low-dose Administration of Carperitide for Acute Heart Failure (LASCAR-AHF) is a multicenter, randomized, open-label, controlled study designed to evaluate the efficacy of intravenous carperitide in hospitalized patients with AHF. Patients hospitalized for AHF will be randomly assigned to receive either intravenous carperitide (0.02 µg/kg/min) in addition to standard treatment or matching standard treatment for 72 h. The primary end point is death or rehospitalization for HF within 2 years. A total of 260 patients will be enrolled between 2013 and 2018. CONCLUSION: The design of LASCAR-AHF will provide data of whether carperitide reduces the risk of mortality and rehospitalization for HF in selected patients with AHF.

Usefulness of the Direct and/or Total Bilirubin to Predict Adverse Outcomes in Patients With Acute Decompensated Heart Failure.

Abnormal liver function test results are often observed in acute decompensated heart failure (ADHF). However, the prognostic value of bilirubin fractionation has not been elucidated. The prognostic value of direct bilirubin (DB), in comparison with total bilirubin (TB), was examined in 556 consecutive patients with ADHF. Patients with elevated DB showed mostly similar patient characteristics including signs of elevated right-sided pressure (frequent hepatomegaly, jugular venous distention, dilated inferior vena cava, and elevated gamma-glutamyltransferase) and decreased cardiac output (cold extremities, decreased pulse pressure, and lower blood pressure) and other parameters of heart failure (HF) severity (increased plasma renin activity, decreased sodium, total cholesterol, and ejection fraction) to elevated TB; however, only patients with elevated DB showed a significant difference in the frequency of HF history and alkaline phosphatase value. Kaplan-Meier analysis showed that patients with elevated DB had a significantly higher rate of the composite end point of all-cause mortality or HF readmission (p = 0.021) compared with those with normal DB, whereas patients with elevated TB did not show a statistically significant difference compared with those with normal TB (NS). A multivariate Cox hazards model showed that DB was an independent predictor of adverse events (adjusted hazard ratio 1.052, 95% confidence interval 1.001 to 1.099, p = 0.034), whereas TB was not (adjusted hazard ratio 1.017, 95% confidence interval 0.985 to 1.046, p = 0.27). Adding DB to existing prognostic variables resulted in higher C-statistics than adding TB (C-statistics: 0.670 to 0.675, 0.670 to 0.674, respectively). In conclusion, elevated DB in ADHF was an independent prognostic predictor that was superior to TB. DB may be useful for further risk stratification in ADHF.

Prognostic value of malnutrition assessed by Controlling Nutritional Status score for long-term mortality in patients with acute heart failure.

BACKGROUND: The prognostic value of nutritional status is poorly understood and evidence-based nutritional assessment indices are required in acute heart failure (AHF). We investigated the prognostic value of malnutrition assessed by the Controlling Nutritional Status (CONUT) score (range 0-12, higher=worse, consisting of serum albumin, cholesterol and lymphocytes) in AHF patients. METHODS: The CONUT score was measured on admission in 635 consecutive AHF patients. The primary outcome was all-cause death. RESULTS: Median CONUT score was 3 (interquartile range 2 to 5). During the median follow-up of 324days, CONUT score was independently associated with death (HR 1.26, 95% CI 1.11-1.42, P<0.001) after adjustment for confounders in a multivariate Cox model. The CONUT score demonstrated the best C-statistic for predicting death (0.71) among other common nutritional markers in HF. Furthermore, addition of the CONUT score to an established risk prediction model from the Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure study significantly increased the C-statistic from 0.75 to 0.77 (P=0.02). The net reclassification improvement afforded by CONUT score was 21% for all-cause death, 27% for survival and 49% overall (P<0.001). CONCLUSION: Malnutrition assessed by the CONUT score on admission was an independent determinant of long-term death in AHF, and its prognostic value outweighed that of other nutritional indices. Moreover, addition of the score to the existing risk prediction model significantly increased the predictive ability for death, indicating beneficial clinical application of the CONUT score in AHF patients.

Circulating Omega-6, But Not Omega-3 Polyunsaturated Fatty Acids, Are Associated with Clinical Outcomes in Patients with Acute Decompensated Heart Failure.

BACKGROUND: Circulating polyunsaturated fatty acid (PUFA) levels are associated with clinical outcomes in cardiovascular diseases including coronary artery disease and chronic heart failure (HF). However, their clinical implications in acute decompensated HF (ADHF) remain unclear. The aim of this study was to investigate the clinical roles of circulating PUFAs in patients with ADHF. METHODS: Circulating levels of PUFAs, eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), arachidonic acid (AA) and dihomo-gamma linoleic acid (DGLA), were measured on admission in 685 consecutive ADHF patients. Adverse events were defined as all-cause death and worsening HF. RESULTS: During a median follow-up period of 560 days, 262 (38.2%) patients had adverse events. Although patients with adverse events had lower n-6 PUFA (AA + DGLA) level than those without, n-3 PUFA (EPA + DHA) level was comparable between the groups. Kaplan-Meier analyses showed that lower n-6 PUFA level on admission was significantly associated with the composite of all-cause death and worsening HF, all-cause death, cardiovascular death and worsening HF (p < 0.001, p = 0.005, p = 0.021, p = 0.019, respectively). In a multivariate Cox model, lower n-6 PUFA level was independently associated with increased risk of adverse events (HR 0.996, 95% CI: 0.993-0.999, p = 0.027). CONCLUSIONS: Lower n-6 but not n-3 PUFA level on admission was significantly related to worse clinical outcomes in ADHF patients. Measurement of circulating n-6 PUFA levels on admission might provide information for identifying high risk ADHF patients.

Usefulness of Geriatric Nutritional Risk Index for Assessing Nutritional Status and Its Prognostic Impact in Patients Aged ≥65 Years With Acute Heart Failure.

Malnutrition is becoming one of the most important determinants of worse clinical outcomes in patients with acute heart failure (AHF). However, appropriate tools for evaluating the nutritional status in patients aged ≥65 years with AHF remain unclear. We examined 490 consecutive patients aged ≥65 years with AHF. They were divided into 2 groups according to Geriatric Nutritional Risk Index (GNRI; cut-off value = 92). During a median period of 189 days, the mortality rate was significantly higher in the lower GNRI group than the higher GNRI group (p <0.001). In multivariate analyses, lower GNRI was an independent determinant of adverse events (HR 0.92, 95% CI 0.88 to 0.95, p <0.001). The GNRI showed the best prognostic value (C-statistic: 0.70) among other nutritional indexes. Adding GNRI to an existing outcome prediction model for mortality in AHF significantly increased the C-statistic from 0.68 to 0.74 (p = 0.017). The net reclassification improvement afforded by GNRI was 60% overall, 27% for events, and 33% for nonevents (p <0.001). In conclusion, lower GNRI on admission was independently associated with worse clinical outcomes in patients aged ≥65 years with AHF, and it was superior to other nutritional parameters. Furthermore, the assessment of nutritional status using GNRI is very helpful for risk stratification.

Prognostic significance of endogenous erythropoietin in long-term outcome of patients with acute decompensated heart failure.

AIMS: Although previous reports suggest that an elevated endogenous erythropoietin (EPO) level is associated with worse clinical outcomes in chronic heart failure (HF) patients, the prognostic implication of EPO in patients with acute decompensated HF (ADHF) and underlying mechanisms of the high EPO level in severe HF patients who have a poor prognosis remain unclear. METHODS AND RESULTS: We examined 539 consecutive ADHF patients with EPO measurement on admission from our registry. During a median follow-up period of 329 days, a higher EPO level on admission was independently associated with worse clinical outcomes [hazard ratio (HR) 1.25, 95% confidence interval (CI) 1.06-1.48, P = 0.008], and haemoglobin level was the strongest determinant of EPO level (P < 0.001), whereas estimated glomerular filtration rate (eGFR) was not significant in multivariate regression analysis. In the anaemic subgroup of 318 patients, a higher EPO level than expected on the basis of their haemoglobin level was related to increased adverse events (HR 1.63, 95% CI 1.05-2.49, P = 0.028). Moreover, estimated plasma volume excess rate was positively associated with EPO level (P = 0.003), and anaemic patients with a higher than expected EPO level tended to have a higher estimated plasma volume excess rate and plasma lactate level, and lower systemic oxygen saturation level with the preservation of the reticulocyte production index than those with a lower than expected EPO level. CONCLUSION: A high EPO level predicts long-term worse clinical outcomes in ADHF patients, independent of anaemia and impaired renal function. Anaemia and hypoxia due to severe congestion may synergistically contribute to a high EPO level in high-risk HF patients.