Mortality In Ambulatory Patients Research Articles

Malnutrition in heart failure with preserved ejection fraction.

Malnutrition may be an important geriatric condition in adults with heart failure with preserved ejection fraction (HFpEF), but studies on its prevalence and associated clinical outcomes are limited. The aim of this study was to determine if malnutrition is associated with short-term morbidity and mortality in ambulatory patients with HFpEF. We examined 231 patients with a clinical diagnosis of HFpEF seen at two dedicated academic HFpEF programs (Weill Cornell Medicine and Michigan Medicine) from June 2018 to April 2022. Malnutrition was defined by Mini-Nutritional Assessment Short Form (MNA-SF) scores ≤11. The primary endpoint was a 6-month composite of all-cause mortality and all-cause hospitalization. A Cox proportional-hazard models was used to examine the association between malnutrition and the primary endpoint, adjusting for race, prior hospitalization history, and the validated Meta-Analysis Global Group in Chronic (MAGGIC) heart failure prognostic risk score. The median age of the cohort was 73 years (interquartile range 64-81). The most common comorbid conditions included hypertension (prevalence 81%), atrial fibrillation (43%), and obesity (63%). The prevalence of malnutrition was 42% (n = 97), and MNA-SF scores did not significantly correlate with body mass index (R = -0.02, p = 0.71). At the 6-month follow-up, 62 patients (26.8%) were hospitalized and four patients died (1.7%). In a fully-adjusted analysis, malnutrition was independently associated with the composite outcome of all-cause mortality and all-cause hospitalization (HR 1.94 [95% CI: 1.17-3.20], p = 0.01). Despite a high prevalence of obesity, two out of five ambulatory adults with HFpEF are malnourished. Malnutrition was independently associated with adverse outcomes at 6 months. Future work is necessary to develop interventions that can address malnutrition.

Which frailty tool best predicts morbidity and mortality in ambulatory patients with heart failure? A prospective study.

Frailty is common in patients with heart failure (HF) and is associated with adverse outcome, but it is uncertain how frailty should best be measured. To compare the prognostic value of commonly-used frailty tools in ambulatory patients with HF. We assessed, simultaneously, three screening tools [clinical frailty scale (CFS); Derby frailty index (DFI); acute frailty network (AFN) frailty criteria), three assessment tools (Fried criteria; Edmonton frailty score (EFS); deficit index (DI)) and three physical tests (handgrip strength, timed get-up-and-go test (TUGT), 5-metre walk test (5MWT)] in consecutive patients with HF attending a routine follow-up visit. 467 patients (67% male, median age=76 years, median NT-proBNP = 1156ng/L) were enrolled. During a median follow-up of 554 days, 82 (18%) patients died and 201 (43%) patients were either hospitalised or died. In models corrected for age, Charlson score, haemoglobin, renal function, sodium, NYHA, atrial fibrillation (AF), and body mass index, only log[NT-proBNP] and frailty were independently associated with all-cause death. A base model for predicting mortality at 1 year including NYHA, log[NT-proBNP], sodium and AF, had a C-statistic=0.75. Amongst screening tools: CFS (C-statistic=0.84); amongst assessment tools: DI (C-statistic=0.83) and amongst physical test: 5MWT (C-statistic=0.80), increased model performance most compared with base model (P<0.05 for all). Frailty is strongly associated with adverse outcomes in ambulatory patients with HF. When added to a base model for predicting mortality at 1 year including NYHA, NT-proBNP, sodium, and AF, CFS provides comparable prognostic information with assessment tools taking longer to perform.

PREDICTING 1-YEAR MORTALITY IN AMBULATORY HEART FAILURE PATIENTS: EMPIRIC MODELS OUTPERFORM PHYSICIAN INTUITIVE ESTIMATES

Accurate prognosis assessment is key in heart failure (HF) care. This multicenter Canadian prospective cohort study compared the accuracy of physician predictions versus model predictions to estimate 1-year mortality in ambulatory patients with HF.

Frailty phenotype as a predictor of bleeding and mortality in ambulatory patients receiving direct oral anticoagulants.

Limited prospective data exist about the clinical relevance of frailty in patients with atrial fibrillation (AF) or venous thromboembolism (VTE) receiving direct oral anticoagulants (DOACs). The aim of this study was to evaluate whether frailty phenotype identifies DOAC-treated patients at higher risk of adverse clinical outcomes. Consecutive, adult outpatients treated with DOACs for AF or VTE were prospectively enrolled. Patients were classified as frail, pre-frail, or non-frail according to frailty phenotype. Study outcomes were clinically relevant bleeding, including major and clinically relevant non-major bleeding, arterial and venous thromboembolism, and all-cause mortality. 236 patients (median age 78 years, 44% females) were included, of whom 156 (66%) had AF and 80 (34%) VTE. Ninety-eight (41%) patients were frail, 115 (49%) pre-frail, and 23 (10%) non-frail. Inappropriately high or low dose DOAC was used in 33% of frail and in 20% of non-frail or pre-frail patients. Over a median follow-up of 304 days, the incidence of clinically relevant bleeding, thromboembolism, and mortality were 20%, 4%, 9% in frail, and 10%, 3%, and 2% in pre-frail, respectively, while no study outcome occurred among non-frail patients. Risk ratios (95% confidence intervals) for these outcomes in frail versus pre-frail and non-frail patients were respectively 2.5 (1.8, 3.7), 1.9 (0.9, 4.0), and 6.3 (2.9, 13.6). In a prospective cohort of ambulatory patients receiving DOAC treatment for AF or VTE, frailty phenotype identified patients at higher risk of bleeding and all-cause mortality. Frailty assessment could be valuable to guide targeted interventions potentially improving patient prognosis.

Patient- and Process-Related Contributors to the Underuse of Aortic Valve Replacement and Subsequent Mortality in Ambulatory Patients With Severe Aortic Stenosis.

BackgroundMany patients with severe aortic stenosis (AS) and an indication for aortic valve replacement (AVR) do not undergo treatment. The reasons for this have not been well studied in the transcatheter AVR era. We sought to determine how patient‐ and process‐specific factors affected AVR use in patients with severe AS.Methods and ResultsWe identified ambulatory patients from 2016 to 2018 demonstrating severe AS, defined by aortic valve area ≤1.0 cm2. Propensity scoring analysis with inverse probability of treatment weighting was used to evaluate associations between predictors and the odds of undergoing AVR at 365 days and subsequent mortality at 730 days. Of 324 patients with an indication for AVR (79.3±9.7 years, 57.4% men), 140 patients (43.2%) did not undergo AVR. The odds of AVR were reduced in patients aged >90 years (odds ratio [OR], 0.24 [95% CI, 0.08–0.69]; P=0.01), greater comorbid conditions (OR, 0.88 per 1‐point increase in Combined Comorbidity Index [95% CI, 0.79–0.97]; P=0.01), low‐flow, low‐gradient AS with preserved left ventricular ejection fraction (OR, 0.11 [95% CI, 0.06–0.21]), and low‐gradient AS with reduced left ventricular ejection fraction (OR, 0.18 [95% CI, 0.08–0.40]) and were increased if the transthoracic echocardiogram ordering provider was a cardiologist (OR, 2.46 [95% CI, 1.38–4.38]). Patients who underwent AVR gained an average of 85.8 days of life (95% CI, 40.9–130.6) at 730 days.ConclusionsThe proportion of ambulatory patients with severe AS and an indication for AVR who do not receive AVR remains significant. Efforts are needed to maximize the recognition of severe AS, especially low‐gradient subtypes, and to encourage patient referral to multidisciplinary heart valve teams.

Bamlanivimab and Etesevimab Improve Symptoms and Associated Outcomes in Ambulatory Patients at Increased Risk for Severe Coronavirus Disease 2019: Results From the Placebo-Controlled Double-Blind Phase 3 BLAZE-1 Trial.

BackgroundIn the phase 2/3 BLAZE-1 trial, bamlanivimab and etesevimab together reduced coronavirus disease 2019 (COVID-19)–related hospitalizations and any-cause mortality in ambulatory patients. Herein, we assess the impact of bamlanivimab and etesevimab treatment on the severity and length of symptoms and health outcomes among patients at increased risk for severe COVID-19.MethodsIn the phase 3 portion of BLAZE-1 (NCT04427501), symptomatic patients with increased risk for severe COVID-19 were randomized (2:1) to a single infusion of 700 mg bamlanivimab and 1400 mg etesevimab or placebo. Hospitalization events, vital signs, and symptomatology were monitored throughout the trial.ResultsOverall, 769 patients were randomized to bamlanivimab and etesevimab together (n = 511) or placebo (n = 258). The time to sustained symptom resolution was significantly shorter among patients who received bamlanivimab and etesevimab compared with placebo (8 vs 10 days; P < .01). The median time to first sustained symptom resolution of body aches and pain, chills, fatigue, feeling feverish, headache, and shortness of breath was significantly different in patients receiving bamlanivimab and etesevimab compared to placebo (P < .05). The proportion of patients who experienced COVID-19–related hospitalization by day 29 was significantly reduced among the bamlanivimab and etesevimab group compared with placebo (0.8% vs 5.4%; P < .01). The mean duration of hospital stay was numerically shorter among patients who received bamlanivimab and etesevimab (7.3 vs 13.5 days; P = .16), with fewer intensive care admissions.ConclusionsPatients receiving bamlanivimab and etesevimab together resolved their symptoms more rapidly than those receiving placebo. Bamlanivimab and etesevimab treatment was associated with reduced rates of hospitalizations and shorter hospital stays.Clinical Trials RegistrationNCT04427501.

Predicting 1-Year Mortality in Ambulatory Heart Failure Patients: Empiric Models Outperform Physician Intuitive Estimates

<h3>Purpose</h3> This multicenter Canadian prospective cohort study evaluated the accuracy of physician predictions in comparison to model predictions in estimating 1-year mortality in ambulatory patients with heart failure (HF). <h3>Methods</h3> We included consented consecutive ambulatory HF patients (left ventricular ejection fraction (LVEF) <40%) followed at 11 HF clinics in 5 provinces in Canada (2018-2020). In a closed-question survey, HF cardiologists and family doctors, using their clinical judgment, estimated patient 1-year mortality in absolute terms. We collected clinical information to describe the population and calculate predicted mortality using three predictive models: the Seattle HF Model (SHFM), the MAGGIC score and the HF Meta-score. We documented patients' mortality over one year. Physicians were unaware of model predictions. We calculated mortality using Cox proportional hazards and assessed model and physician predictive accuracy using discrimination and calibration. <h3>Results</h3> We included 1,563 ambulatory HF patients, mean age of 63±14 years, 24% female, 70% NTHA class I-II, mean LVEF of 28±7%, and median brain natriuretic peptide of 350 pg/ml (25^th-75^th percentile 130-700). The population 1-year mortality was 7% (95%CI 6%-8%). Models' discrimination (c-statistic 0.80 for MAGGIC and HF meta-score, 0.84 for SHFM) proved superior to physicians (0.77 for family doctors and 0.78 for HF cardiologists). Models' calibration was adequate for patients at lower risk, but overestimated risk in those whose 1-year mortality was > 20%. In contrast, family doctors and HF cardiologists overestimated risk throughout the risk spectrum. In low-risk patients (1-year mortality ∼1%), physicians predicted a risk 7%-10%; in medium-risk patients (1-year mortality ∼5%), physicians predicted 15%-20%; and in high-risk patients (mortality >15%), physicians predicted >25%. <h3>Conclusion</h3> Predictive models showed higher accuracy in predicting 1-year mortality in ambulatory HF population than family doctors and HF cardiologists, both of whom consistently overestimated risk, potentially exposing patients early to more aggressive care. Incorporating predictive models in family and HF cardiology practices may improve patient management and resource use.

Predictors of 1‑year mortality in ambulatory patients with advanced heart failure awaiting heart transplant.

Heart failure (HF) is a complex syndrome involving diverse pathways and pathological processes that can manifest themselves in circulation as abnormal levels of various biomarkers. The aim of the study was to assess the factors associated with a worse prognosis in patients with advanced HF awaiting heart transplant during a 1‑year follow‑up. We prospectively assessed the data of 203 adult patients with advanced HF, who were hospitalized at our institution between 2016 and 2018. The study end point was all‑cause death during a 1‑year follow‑up. The median age of patients was 57 years (range, 52-60); 87.7% of patients were male. During follow‑up, 62 patients (30.5%) died. Serum levels of procalcitonin (hazard ratio [HR], 1.027; 95% CI, 1.020-1.034; P <0.001; per 10‑unit increase), high‑sensitivity C‑reactive protein (hs‑CRP; HR, 1.099; 95% CI, 1.016-1.883; P = 0.02; per 1‑unit increase), sodium (HR, 1.171; 95% CI, 1.076-1.272; P <0.001; per 1 ‑unit increase), and N ‑terminal pro-B ‑type natriuretic peptide (NT ‑proBNP; HR, 1.068; 95% CI, 1.033-1.105; P <0.001; per 1000‑unit increase) were independent risk factors for mortality. Procalcitonin generated the largest area under the curve (0.780; 95% CI, 0.712-0.848). Our study showed that higher serum hs ‑CRP, NT‑proBNP, and procalcitonin levels and lower serum sodium levels were independent risk factors for death during a 1‑year follow‑up in patients with advanced HF. Procalcitonin showed the strongest predictive power, sensitivity, and specificity, allowing for an effective identification of 1‑year survivors and nonsurvivors awaiting heart transplant.

Sex Difference in the Association between Physical Activity and All-Cause Mortality in Ambulatory Patients with Chronic Kidney Disease.

(1) Background: The purpose of this article was to investigate the association between self-reported physical activity (PA) and all-cause mortality in ambulatory patients with chronic kidney disease (CKD), stage 4–5 including maintenance dialysis. (2) Methods: Ambulatory patients with CKD (eGFR < 30 mL/min/1.73 m2) with conservative treatment or chronic dialysis were included. PA was assessed using the Saltin–Grimby Physical Activity Level Scale. A Cox proportional hazards regression model––adjusted for age, sex, plasma–albumin, body mass index, socioeconomic status, and treatment––was applied. (3) Results: Participants (n = 374) were followed 39 ± 15 months from entry to death or censoring. Throughout the study period of 39 months, 156 deaths (42%) were registered. Regarding physical activity, 128 (34%) of the participants were inactive, 212 (57%) were moderately active, and 34 (9%) were highly or vigorously active. Moderate PA was associated with a decreased mortality risk in women (n = 150) compared to inactivity (HR 0.27 (0.15; 0.51), p < 0.001), whereas a high/vigorous level of PA was not significantly associated with mortality risk compared to inactivity. In men (n = 224), the associations between PA levels and mortality risk were not significant. (4) Conclusions: Moderate PA was associated with reduced all-cause mortality in ambulatory women with stage 4–5 CKD with or without maintenance dialysis treatment. Physical activity was not significantly associated with mortality in men.

ROLE OF SACUBITRIL/VALSARTAN IN THE TREATMENT OF CHRONIC HEART FAILURE WITH REDUCED EJECTION FRACTION IN ELDERLY HYPERTENSIVES WITH COMORBIDITY: FROM CLINICAL TRIALS TO REAL WORLD

Objective: Sacubitril/Valsartan (SV) has been shown to reduce cardiovascular mortality in ambulatory patients with chronic heart failure (CHF) and reduced left ventricular ejection fraction (HFrEF). However there are few real-word evidences about its efficacy in elderly hypertensives with HFrEF and comorbidities. Design and method: In this prospective open-label study, 54 subjects (mean age 78.6 ± 8.2 years, 75.0% men), with HFrEF (29.8 ± 4.3%), in New York Heart Association (NYHA) class II-III were assigned to receive SV twice daily at different dosage of 24/26, 49/51, 97/103 mg. These patients were gender and age-matched with a control group of patients with HFrEF receiving optimal standard therapy for CHF. The office blood pressure (BP), the NT-pro-BNP, eGFR, blood glucose and glycated haemoglobin (HbA1c), uric acid (UA), left ventricular ejection fraction (LVEF) and NYHA class were evaluated at a mean follow-up of 14-months. Mortality and re-hospitalisation for HF were collected. Categorical variables were compared with the Pearson's test and difference of continuous variables, were evaluated by the analysis of variance for repeated measures. Results: NYHA class significantly improved in the SV than control group (24.9 vs. 6.4% moved from III-- &gt; II and 55.4 vs. 25.2% from II-- &gt; I classes, p &lt; 0.05). A significant improvement of LVEF and eGFR levels was found in the ARNIs than controls (42.4 vs. 34.2%, 73.8 vs. 61.2 ml/min for all p &lt; 0.001, respectively). The NT-pro-BNP, systolic BP, diastolic BP, blood glucose, HbA1c and UA values were lower in SV than controls (3107 vs 4552 pg/ml, 112.2 vs. 120.4 and 68.8 vs 75.6 mmHg, 108.4 vs 122.6 mg/dl, 5.4 vs. 5.9% and 5.9 vs 6.4 mg/dl, p &lt; 0.05). Mortality and re-hospitalisation for CHF was lower in the SV than controls (20.1 vs. 33.6 and vs. 27.7 vs. 46.3%, p &lt; 0.05). Conclusions: In elderly hypertensives with HFrEF and comorbidities SV treatment seems effective and safe. The improvement of LVEF, BP, eGFR, serum glucose, UA and HbA1c could be the mechanisms by which SV plays a beneficial role on clinical outcomes

The impact of malnutrition on short-term morbidity and mortality in ambulatory patients with heart failure

Malnutrition is common in patients with chronic heart failure (CHF) and is associated with adverse outcomes, but it is uncertain how malnutrition should best be evaluated. This prospective cohort study aims to compare the short-term prognostic value of 9 commonly used malnutrition tools in patients with CHF. We assessed, simultaneously, 3 simple tools [Controlling Nutritional Status (CONUT) score, Geriatric Nutritional Risk Index, and Prognostic Nutritional Index], 3 multidimensional tools [Malnutrition Universal Screening Tool, Mini Nutritional Assessment-Short Form (MNA-SF), Subjective Global Assessment], and 3 laboratory tests (serum cholesterol, albumin, and total lymphocyte count) in consecutive patients with CHF attending a routine follow-up. The primary end point was all-cause mortality; the secondary end point was the combination of all-cause hospitalization and all-cause mortality. In total, 467 patients [67% male, median age 76 y (range: 21-98 y), median N-terminal pro-B-type natriuretic peptide (NT-proBNP) 1156 ng/L] were enrolled. During a median follow-up of 554 d, 82 (18%) patients died and 201 (43%) patients either had a nonelective hospitalization or died. In models corrected for age, hemoglobin (Hb), renal function, New York Heart Association (NYHA) class, NTproBNP, BMI, and comorbidities, all malnutrition tools, except total lymphocyte count and serum cholesterol, were independently associated with worse morbidity and mortality. A base model for predicting mortality, including age, NYHA class, log [NT-proBNP], Hb, renal function, and comorbidities, had a C-statistic of 0.757. CONUT (C-statistic=0.777), among simple tools; MNA-SF (C-statistic=0.776), among multidimensional tools; and albumin (C-statistic=0.773), among biochemical tests, increased model performance most compared with the base model. Patients with serum albumin<30 g/L had a 6-fold increase in mortality compared with patients with albumin ≥35 g/L. Malnutrition is strongly associated with adverse outcomes in patients with CHF. Measuring serum albumin provides comparable prognostic information to simple or multidimensional malnutrition tools.

Abstract 15520: Prognostic Value of Soluble ST2 Measurements for Morbidity and Mortality in Ambulatory Patients With HFpEF

Background: Soluble ST2 (sST2) has emerged as a powerful prognostic marker in chronic systolic heart failure with reduced ejection fraction (HFrEF). Elevated levels of sST2 are associated with adverse cardiac remodeling and fibrosis. However, few studies have investigated the relative prognostic value of sST2 collected from ambulatory patients with chronic heart failure with preserved ejection fraction (HFpEF) for long term outcomes. Hypothesis: We sought to determine the prognostic utility of a baseline sST2 partition value in the ambulatory setting as it related to risk for heart failure hospitalization and all-cause mortality. Methods: Single-center, retrospective observational study of subjects presenting to an ambulatory heart failure (HF) clinic from July 2014 to December 2016. Baseline sST2 levels were available for 156 subjects with stage C heart failure.. For purposes of this analysis in HFpEF, we excluded patients with EF ≤ 40% resulting in a study cohort of 73 subjects. The mean follow-up was 3.09 years ± 1.46 years. Analysis was performed with IBM SPSS Statistics 26. Discrete variables were expressed as counts (percentage) and were compared using the Chi-squared test. Mean differences of continuous variables were expressed as a mean ± standard deviation and compared using the unpaired Student’s t- test. The log-rank test (Mantel-Cox) was used to compare survival times on Kaplan-Meier curves. Results: Patients who had baseline sST2 ≥ 35 ng/ml were at increased risk for heart failure hospitalization (p=0.189) and all-cause mortality (p=0.073) compared to patients who had sST2 &lt; 35 ng/ml. Patients with sST2 ≥ 35 ng/ml had a mean of 1.03 HF hospitalizations, 24.1% of this group had ≥ 2 HF hospitalizations and 17.2% all-cause mortality. Patients with sST2 &lt; 35 ng/ml had a mean of 0.57 HF hospitalizations, 14.0% had ≥ 2 HF hospitalizations and 4.55% all-cause mortality. Conclusion: Subjects with sST2 levels ≥ 35 ng/ml were at increased risk of recurrent hospitalization and all-cause mortality. The results of this study highlight the value of sST2 concentrations as a prognostic biomarker for identifying patients with HFpEF that are at increased risk for morbidity and mortality in the ambulatory setting.

Prognostic Value of Soluble ST2 Measurements for Morbidity and Mortality in Ambulatory Patients with HFrEF

Background Soluble ST2 (sST2) has emerged as a powerful prognostic marker in chronic systolic heart failure with reduced ejection fraction (HFrEF). Elevated levels of sST2 are associated with adverse cardiac remodeling and fibrosis. However, few studies have demonstrated the relative prognostic value of sST2 collected from stable patients in the ambulatory setting and correlated it with long term clinical outcomes. Hypothesis In our study, we sought to determine the prognostic utility of a baseline sST2 partition value in the ambulatory setting as it related to subsequent risk for heart failure hospitalization and all-cause mortality. Methods Single-center, retrospective observational study of subjects presenting to an ambulatory heart failure (HF) clinic from July 2014 to December 2016. There were 156 subjects with stage C heart failure and a baseline sST2 level. For purposes of this analysis in HFrEF, we excluded patients with EF > 40% resulting in a study cohort of 103 subjects. The mean follow-up was 2.20 years ± 1.53 years. Analysis was performed with IBM SPSS Statistics 26 software package. Discrete variables were expressed as counts (percentage) and were compared using the Chi-squared test. Mean differences of continuous variables were expressed as a mean ± standard deviation and compared using the unpaired Student's t-test. The log-rank test (Mantel-Cox) was used to compare survival times on Kaplan-Meier curves. To determine the diagnostic and prognostic accuracies of sST2 and BNP, receiver operating characteristic (ROC) plots were analyzed, and areas under the curve (AUC) were calculated. Results Patients who had baseline sST2 ≥ 35 ng/ml were at increased risk for heart failure hospitalization and all-cause mortality compared to patients who had sST2 Conclusion Subjects with sST2 levels ≥ 35 ng/ml were at increased risk of recurrent hospitalization and all-cause mortality. Additionally, we saw that elevated sST2 was associated with increased atrial arrhythmia, hypotension, and anemia. The results of this study highlight the value of sST2 concentrations as a prognostic biomarker for identifying patients with HFrEF that are at increased risk for morbidity and mortality in the ambulatory setting. Key words: Soluble ST2, cardiac remodeling, biomarkers, heart failure

Relation between plasma ceramides and cardiovascular death in chronic heart failure: A subset analysis of the GISSI-HF trial.

AimsCeramides exert several biological activities that may contribute to the pathophysiology of cardiovascular disease and heart failure (HF). The association between plasma levels of distinct ceramides (that have been previously associated with increased cardiovascular risk) and cardiovascular mortality in patients with chronic HF has received little attention.Methods and resultsIn a post hoc ancillary analysis of the Gruppo Italiano per lo Studio della Sopravvivenza nella Insufficienza Cardiaca‐Heart Failure (GISSI‐HF; NCT00336336) trial, we randomly selected a sample of 200 ambulatory patients with chronic HF who died due to cardiovascular causes and 200 patients who were alive at the end of the trial (after a median follow‐up period of 3.9 years). We measured baseline plasma concentrations of six previously identified high‐risk ceramide species [Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0), and Cer(d18:1/24:1) and their individual plasma ratios with Cer(d18:1/24:0)]. Patients who died due to cardiovascular causes had significantly (P < 0.05 or less) higher levels of plasma Cer(d18:1/16:0) and Cer(d18:1/24:1), but lower levels of plasma Cer(d18:1/22:0) and Cer(d18:1/24:0) than had those who did not. All plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly higher in patients who died due to cardiovascular causes. In Cox regression analyses, all five plasma ratios of each ceramide with Cer(d18:1/24:0) were significantly associated with a greater risk of cardiovascular mortality (with unadjusted hazard ratios ranging from 1.23 to 1.59; P < 0.001 or less). These significant associations were attenuated after adjustment for multiple established risk factors, New York Heart Association functional class, left ventricular ejection fraction, use of medications, plasma pentraxin‐3 levels, and, especially, plasma N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) levels. When we applied a Bonferroni correction for multiple comparisons (using a P‐threshold 0.05/5 ceramide ratios = 0.01), none of the five plasma ratios of each ceramide with Cer(d18:1/24:0) remained statistically associated with the risk of cardiovascular mortality (with adjusted hazard ratios ranging from 1.10 to 1.23).ConclusionsHigher levels of specific plasma ceramides [especially when used in ratios with Cer(d18:1/24:0)] are associated with increased cardiovascular mortality in ambulatory patients with chronic HF. However, these associations are weakened after adjustment for established cardiovascular risk factors, medication use, and plasma NT‐proBNP concentrations.

The use of the CALL Risk Score for predicting mortality in Brazilian heart failure patients.

AimsThis study aimed to develop and validate a simple method for predicting long‐term all‐cause mortality in ambulatory patients with chronic heart failure (CHF) residing in an area where Chagas disease is endemic, which will be important not only for patients living in Latin America but also to those living in developed non‐endemic countries.Methods and resultsA total of 677 patients with a wide spectrum of aetiologies for left ventricular systolic dysfunction and receiving optimized evidence‐based treatment for CHF were prospectively followed for approximately 11 years. We established a risk score using Cox proportional hazard regression models. After multivariable analysis, four variables were independently associated with mortality and included in the CALL Risk Score: Chagas cardiomyopathy aetiology alone [hazard ratio, 3.36; 95% confidence interval (CI), 2.61–4.33; P < 0.001], age ≥60 years (hazard ratio, 1.36; 95% CI, 1.06–1.74; P = 0.016), left anterior fascicular block (hazard ratio, 1.64; 95% CI, 1.27–2.11; P < 0.001), and left ventricular ejection fraction <40% (hazard ratio, 1.73; 95% CI, 1.30–2.28; P < 0.001). The internal validation considered the bootstrapping, a resampling technique recommended for prediction model development. Hence, we established a scoring system attributing weights according to each risk factor: 3 points for Chagas cardiomyopathy alone, 1 point for age ≥60 years, and 2 points each for left anterior fascicular block and left ventricular ejection fraction <40%. Three risk groups were identified: low risk (score ≤2 points), intermediate risk (score of 3 to 5 points), and high risk (score ≥6 points). High‐risk patients had more than two‐fold increase in mortality (26.9 events/100 patient‐years) compared with intermediate‐risk patients (10.1 events/100 patient‐years) and almost seven‐fold increase compared with low‐risk patients (4.3 events/100 patient‐years). The CALL Risk Score data sets from the development and internal validation cohorts both displayed suitable discrimination c‐index of 0.689 (95% CI, 0.688–0.690; P < 0.001) and 0.687 (95% CI, 0.686–0.688; P < 0.001), respectively, and satisfactory calibration [Greenwood–Nam–D'Agostino test (8) = 7.867; P = 0.447] and [Greenwood–Nam–D'Agostino test (8) = 10.08; P = 0.273], respectively.ConclusionsThe CALL Risk Score represents a simple and validated method with a limited number of non‐invasive variables that successfully predicts long‐term all‐cause mortality in a real‐world cohort of patients with CHF. Patients with CHF stratified as high risk according to the CALL Risk Score should be monitored and aggressively managed, including those with CHF secondary to Chagas disease.

Sacubitril/Valsartan in Asian Patients with Heart Failure with Reduced Ejection Fraction.

The Prospective comparison of Angiotensin Receptor-neprilysin inhibitor (ARNI) with Angiotensin converting enzyme inhibitor (ACEI) to Determine Impact on Global Mortality and morbidity in Heart Failure (HF) trial (PARADIGM-HF) showed that adding a neprilysin inhibitor (sacubitril) to a renin-angiotensin system blocker (and other standard therapy) reduced morbidity and mortality in ambulatory patients with chronic HF with reduced ejection fraction (HFrEF). In PARADIGM-HF, valsartan combined with sacubitril (a so-called ARNI) was superior to the current gold standard of an ACEI, specifically enalapril, reducing the risk of the primary composite outcome of cardiovascular (CV) death or first HF hospitalization by 20% and all-cause death by 16%. Following the results of PARADIGM-HF, sacubitril/valsartan was approved by American and European regulatory authorities for the treatment of HFrEF. The burden of HF in Asia is substantial, both due to the huge population of the region and as a result of increasing CV risk factors and disease. Both the prevalence and mortality associated with HF are high in Asia. In the following review, we discuss the development of sacubitril/valsartan, the prototype ARNI, and the available evidence for its efficacy and safety in Asian patients with HFrEF.

Sex differences in outcomes of heart failure in an ambulatory, population-based cohort from 2009 to 2013.

Heart failure remains a substantial cause of morbidity and mortality in women. We examined the sex differences in heart failure incidence, mortality and hospital admission in a population-based cohort. All Ontario residents who were diagnosed with heart failure in an ambulatory setting between Apr. 1, 2009, and Mar. 31, 2014, were included in this study. Incident cases of heart failure were captured through physician billing using a validated algorithm. Outcomes were mortality and hospital admission for heart failure within 1 year of the diagnosis. Probability of death and hospital admission were calculated using the Kaplan-Meier method. The hazard of death was assessed using a multivariable Cox proportional hazard model. A total of 90 707 diagnoses of heart failure were made in an ambulatory setting during the study period (47% women). Women were more likely to be older and more frail, and had different comorbidities than men. The incidence of heart failure decreased during the study period in both sexes. The mortality rate decreased in both sexes, but remained higher in women than men. The female age-standardized mortality rate was 89 (95% confidence interval [CI] 80-100) per 1000 in 2009 and 85 (95% CI 75-95) in 2013, versus male age-standardized mortality rates of 88 (95% CI 80-97) in 2009 and 83 (95% CI 75-91) in 2013. Conversely, the rates of incident heart failure hospital admissions after heart failure diagnosis decreased in men and increased in women. Despite decreases in overall heart failure incidence and mortality in ambulatory patients, mortality rates remain higher in women than in men, and rates of hospital admission for heart failure increased in women and declined in men. Further studies should focus on sex differences in health-seeking behaviour, medical therapy and response to therapy to provide guidance for personalized care.

(457) - Slower Gait Speed as a Measure of Frailty Tracks with INTERMACS Profiles, Quality of Life and Predicted Mortality in Ambulatory Patients with Advanced Heart Failure: A Report from the REVIVAL Registry

(457) - Slower Gait Speed as a Measure of Frailty Tracks with INTERMACS Profiles, Quality of Life and Predicted Mortality in Ambulatory Patients with Advanced Heart Failure: A Report from the REVIVAL Registry

Nutritional status and its effects on muscle wasting in patients with chronic heart failure: insights from Studies Investigating Co-morbidities Aggravating Heart Failure.

Inadequate nutritional status has been linked to poor outcomes in patients with heart failure (HF). Skeletal muscle wasting affects about 20% of ambulatory patients with HF. The impact of nutritional intake and appetite on skeletal muscle wasting has not been investigated so far. We sought to investigate the impact of nutritional status on muscle wasting and mortality in ambulatory patients with HF. We studied 130ambulatory patients with HF who were recruited as a part of the Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF) program. Muscle wasting was defined according to criteria of sarcopenia, i.e., appendicular skeletal muscle mass two standard deviations below the mean of a healthy reference group aged 18-40years. Nutritional status was evaluated using the Mini-Nutritional Assessment-Short Form (MNA-SF). Functional capacity was assessed as peak oxygen consumption (peak VO2) by cardiopulmonary exercise testing, 6‑minute walk testing, and the Short Physical Performance Battery (SPPB). At baseline, 19patients (15%) presented with muscle wasting. Patients with muscle wasting had significantly lower values of peak VO2, 6‑minute walk distance, SPPB, and MNA-SF score than patients without (all p< 0.05). In multivariate analysis, MNA-SF remained an independent predictor of muscle wasting after adjustment for age and New York Heart Association class (odds ratio [OR] 0.66; confidence interval [CI] 0.50-0.88; p< 0.01). A total of 16(12%) patients died during a mean follow-up of 21months. In Cox regression analysis, MNA-SF (OR 0.80, CI 0.64-0.99, p= 0.04), left ventricular ejection fraction (OR 0.93, CI 0.86-0.99, p= 0.05), and peak VO2 (OR 0.78, CI 0.65-0.94, p= 0.008) were predictors of death. MNA-SF is an independent predictor of muscle wasting and mortality in ambulatory patients with HF. Nutritional screening should be included as a fundamental part of the overall assessment of these patients.

Aging and Heart Rate in Heart Failure: Clinical Implications for Long-term Mortality

ObjectiveTo assess the relationship between resting heart rate and long-term all-cause mortality in ambulatory patients with heart failure (HF) relative to age, considering that although heart rate has been strongly associated with mortality in HF, the influence of age on target heart rate is incompletely characterized. Patients and MethodsConsecutive patients in sinus rhythm referred to an ambulatory HF clinic of a university hospital between August 1, 2001, and March 31, 2012, were included. Unadjusted and adjusted Cox regression analyses were performed to assess heart rate as a prognostic marker, both as a continuous variable and after categorization into quintiles. Smooth spline estimates and hazard ratios (HRs) were plotted for 2 age strata (<75 years vs ≥75 years) for each individual heart rate. ResultsA total of 1033 patients were included (766 men [74.2%]; mean age, 65.1±12.6 years). During a mean follow-up of 4.6±3.3 years (median, 3.8 years [25th-75th percentile, 1.9-6.9]), 476 patients (46.1%) died. Mortality was associated with a statistically greater heart rate in the total cohort (HR, 1.18; 95% CI, 1.11-1.26; P<.001). From a clinical viewpoint, this means an 18% increased risk for every 10-beats/min elevation in heart rate. The same characteristics were present in the relationship between heart rate assessed after 6 months and long-term mortality (HR, 1.30; 95% CI, 1.20-1.42; P<.001). Overall, the prognostic importance of heart rate in ambulatory patients with HF was largely influenced by patient age. Remarkably, in the elderly population (≥75 years), heart rate below 68 beats/min conferred an increased risk of death, whereas in younger patients, mortality exhibited a declining slope at even the lowest heart rates. ConclusionOur research, if applicable to the prospective management of patients with ambulatory HF, suggests that patients aged 75 years or older have the best outcomes with target heart rates of 68 beats/min; however, younger patients may benefit from lower heart rates, even below 55 beats/min.