Age Differences in Effects of Sacubitril/Valsartan on Cardiac Remodeling, Biomarkers, and Health Status.

BACKGROUND: Sacubitril/valsartan (Sac/Val) improves outcomes in patients with heart failure with reduced ejection fraction (HFrEF). OBJECTIVES: In this study, the authors sought to explore age differences in effects of Sac/Val on biomarkers, Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 scores and cardiac remodeling. METHODS: After initiation and titration of Sac/Val, concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-cTnT), and soluble suppressor of tumorigenicity 2 (sST2) were measured and KCCQ-23 scores obtained from baseline to 12 months. Left ventricular ejection fraction (LVEF), and indexed left ventricular end-systolic (LVESVi) and indexed left ventricular end-diastolic (LVEDVi) and left atrial volume index (LAVi) volumes were measured with the use of echocardiography. Safety end points were assessed. Age-stratified analysis was performed for groups aged <65, 65-74, and ≥75 years. RESULTS: Among 794 participants with HFrEF (mean age 65.1 years, 28.5% women), compared with patients aged <65 years (n = 369), 65-74 years (n = 237), and those aged ≥75 years (n = 188), had similar reductions in hs-cTnT and sST2, but less NT-proBNP reduction (-45.6% vs -40.2% vs -30.5%, respectively; P = 0.02). Gains in KCCQ-23 were smaller (+11.8 vs +11.4 vs +6.0 points; P = 0.03) in patients aged ≥75 years, although similar proportions of each age group achieved ≥10-point and ≥20-point increases in KCCQ-23 by month 12. Improvements in LVEF, LVEDVi, LVESVi, and LAVi were similar among age groups. Incidence of safety end points was also similar. CONCLUSIONS: Sac/Val resulted in significant improvements in prognostic biomarkers and measures of cardiac remodeling and health status from baseline to month 12 across age categories. Older study participants showed somewhat blunted reduction in NT-proBNP and less improvement in KCCQ-23 overall summary scores. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling, and Outcomes [PROVE-HF]; NCT02887183).

Comparative Effect of Angiotensin Receptor Neprilysin Inhibition on B-type Natriuretic Peptide Levels Measured by Three Different Assays: The PROVE-HF Study.

BACKGROUND: Several different B-type natriuretic peptide (BNP) assays are used clinically for diagnostic and prognostic evaluation of heart failure (HF). BNP binds weakly to neprilysin and is cleaved in multiple areas adjacent to the binding sites for the antibodies used in these immunoassays. We assessed the changes in BNP following neprilysin inhibition as measured by 3 immunoassays that recognize different epitopes. METHODS: Among 130 participants with HF with reduced ejection fraction, blood was collected prior to treatment with sacubitril/valsartan (sac/val) and then repeatedly measured through 52 weeks of treatment. BNP concentrations were measured with 3 widely used BNP assays (Siemens, Abbott, and Quidel). RESULTS: Study participants had a mean age of 65 ± 13 years and 76% were men. The median BNP concentration at baseline was 133 ng/L by the Siemens assay, 127 ng/L by the Abbott assay, and 141 ng/L by the Quidel assay. Following initiation of sac/val, there were significantly greater declines in BNP measured by Quidel and Abbott (P = 0.009 and P < 0.001), respectively (both with N-terminal capture antibodies), compared to Siemens (with C-terminal capture antibodies). The difference from baseline was not statistically significant until after week 12 (mean -10.1% for Quidel and -14.3% for Abbott) compared to non-significant differences before 12 weeks (mean -4.5% for Quidel and -6.0% for Abbott). CONCLUSIONS: Following initiation of sac/val, BNP measurements may modestly differ depending on the assay method used, particularly after a few months of treatment. Whether these differences relate to neprilysin-mediated degradation of antibody binding sites deserves further study. STUDY REGISTRATION: PROVE-HF ClinicalTrials.gov Identifier: NCT02887183.

Finding acute coronary syndrome with serial troponin testing for rapid assessment of cardiac ischemic symptoms (FAST-TRAC): a study protocol.

OBJECTIVE: To determine the utility of a highly sensitive troponin assay when utilized in the emergency department. METHODS: The FAST-TRAC study prospectively enrolled >1,500 emergency department patients with suspected acute coronary syndrome within 6 hours of symptom onset and 2 hours of emergency department presentation. It has several unique features that are not found in the majority of studies evaluating troponin. These include a very early presenting population in whom prospective data collection of risk score parameters and the physician's clinical impression of the probability of acute coronary syndrome before any troponin data were available. Furthermore, two gold standard diagnostic definitions were determined by a pair of cardiologists reviewing two separate data sets; one that included all local troponin testing results and a second that excluded troponin testing so that diagnosis was based solely on clinical grounds. By this method, a statistically valid head-to-head comparison of contemporary and high sensitivity troponin testing is obtainable. Finally, because of a significant delay in sample processing, a unique ability to define the molecular stability of various troponin assays is possible. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00880802.

Natriuretic Peptide-guided Therapy for Heart Failure.

Heart failure (HF) is a complex syndrome with high mortality and hospitalization rates. Conventional care in patients with HF is usually based on clinical history and physical examination. Natriuretic peptides (NPs), B-type NP (BNP) and N-terminal proBNP, are the gold-standard biomarkers in HF. They are recommended for diagnosing HF, when the physician is uncertain of the diagnosis, and for estimating the prognosis. NPs also guide therapy in HF, as serial NP measurements inform medication adjustments to achieve targets independently of symptoms. In this regard, the data are conflicting. In patients with HF and reduced left ventricular ejection fraction (HFrEF) there is a suggestion that NP-guided therapy is helpful. The studies STARS-BNP and PROTECT demonstrated a reduction in cardiac events with NP-guided therapy. Additionally, mortality in patients aged <75 years reduced in the BATTLESCARRED and TIME-CHF studies, and in a meta-analysis. On the contrary, no differences were observed in the studies PRIMA and GUIDE-IT. In HF with preserved ejection fraction (HFpEF) and in the acute setting, no differences were detected with NP-guided therapy compared with conventional care. In patients at risk of developing HF, NP can be useful to guide therapy and prevent HF. In summary, NP-guided therapy seems to be useful in patients with HFrEF, especially in those aged <75 years, but has no use in HFpEF or in acute HF.

Machine learning with D-dimer in the risk stratification for pulmonary embolism: a derivation and internal validation study.

AIM: To develop a machine learning model to predict the diagnosis of pulmonary embolism (PE). METHODS AND RESULTS: We undertook a derivation and internal validation study to develop a risk prediction model for use in patients being investigated for possible PE. The machine learning technique, generalized logistic regression using elastic net, was chosen following an assessment of seven machine learning techniques and on the basis that it optimized the area under the receiver operator characteristic curve (AUC) and Brier score. Models were developed both with and without the addition of D-dimer. A total of 3347 patients were included in the study of whom, 219 (6.5%) had PE. Four clinical variables (O2 saturation, previous deep venous thrombosis or PE, immobilization or surgery, and alternative diagnosis equal or more likely than PE) plus D-dimer contributed to the machine learning models. The addition of D-dimer improved the AUC by 0.16 (95% confidence interval 0.13-0.19), from 0.73 to 0.89 (0.87-0.91) and decreased the Brier score by 14% (10-18%). More could be ruled out with a higher positive likelihood ratio than by the Wells score combined with D-dimer, revised Geneva score combined with D-dimer, or the Pulmonary Embolism Rule-out Criteria score. Machine learning with D-dimer maintained a low-false-negative rate at a true-negative rate of nearly 53%, which was better performance than any of the other alternatives. CONCLUSION: A machine learning model outperformed traditional risk scores for the risk stratification of PE in the emergency department. However, external validation is needed.

Associations of cardiac injury biomarkers with risk of peripheral artery disease: The Multi-Ethnic Study of Atherosclerosis.

INTRODUCTION: We investigated the associations of high-sensitivity cardiac Troponin T (hs-cTnT) and N-terminal pro B-type natriuretic peptide (NT-proBNP) levels with risk of developing clinical peripheral artery disease (PAD) or a low ankle-brachial index (ABI). METHODS: Hs-cTnT and NT-proBNP were measured in 6692 and 5458 participants respectively without baseline PAD between 2000 and 2002 in the Multi-ethnic Study of Atherosclerosis. A significant number also had repeat biomarker measurement between 2004 and 2005. Incident clinical PAD was ascertained through 2017. Incident low ABI, defined as ABI <0.9 and decline of ≥0.15 from baseline, was assessed among 5920 eligible individuals who had an ABI >0.9 at baseline and at least one follow-up ABI measurement 3-10 years later. Multivariable Cox proportional hazards and logistic regression modeling were used to determine the association of these biomarkers with clinical PAD and low ABI, respectively. RESULTS: Overall, 121 clinical PAD and 118 low ABI events occurred. Adjusting for demographic and clinical characteristics, each log unit increment in hs-cTnT and NT-proBNP was associated with a 30% (adjusted hazard ratio (HR) 1.3, 95% confidence interval (CI): 1.1, 1.6) and 50% (HR) 1.5, 95% CI: 1.2, 1.8) higher risk of clinical PAD respectively. No significant associations were observed for incident low ABI. Change in these biomarkers was not associated with either of the PAD outcomes. CONCLUSIONS: NT-proBNP and hs-cTnT are independently associated with the development of clinical PAD. Further study should determine whether these biomarkers can help to better identify those at higher risk for PAD.

Circulating heart failure biomarkers beyond natriuretic peptides: review from the Biomarker Study Group of the Heart Failure Association (HFA), European Society of Cardiology (ESC).

New biomarkers are being evaluated for their ability to advance the management of patients with heart failure. Despite a large pool of interesting candidate biomarkers, besides natriuretic peptides virtually none have succeeded in being applied into the clinical setting. In this review, we examine the most promising emerging candidates for clinical assessment and management of patients with heart failure. We discuss high-sensitivity cardiac troponins (Tn), procalcitonin, novel kidney markers, soluble suppression of tumorigenicity 2 (sST2), galectin-3, growth differentiation factor-15 (GDF-15), cluster of differentiation 146 (CD146), neprilysin, adrenomedullin (ADM), and also discuss proteomics and genetic-based risk scores. We focused on guidance and assistance with daily clinical care decision-making. For each biomarker, analytical considerations are discussed, as well as performance regarding diagnosis and prognosis. Furthermore, we discuss potential implementation in clinical algorithms and in ongoing clinical trials.

Stethoscope hygiene: A legal consideration for cardiologists practicing in a new era of infection control (COVID-19).

The stethoscope is a tool cherished by the field of cardiology and ubiquitous throughout medicine. However, little consideration has been given to its safe usage regarding its potential for pathogenic contamination despite thorough evidence that stethoscopes can harbor pathogens that can be transmitted to patients upon contact. The COVID-19 (SARS-COV-2) pandemic has led to increased infection control vigilance, including toward the stethoscope, as evidenced by a recent increase in literature highlighting stethoscope hygiene/contamination. A consequence of this increase in awareness is that stethoscopes may be implicated in medical malpractice lawsuits as a potential cause of healthcare-associated infections (HAIs). While there is limited evidence demonstrating a direct connection between stethoscope contamination and HAIs, malpractice lawsuits often do not require direct causative evidence. Regardless, efforts should be made to bolster stethoscope hygiene to not only mitigate patient harm, but also prevent providers from potential medical-legal conflicts. The continued relevance and utility of the stethoscope as a rapid, cost-effective diagnostic tool needs to be appropriately balanced with increased hygiene performance. Providers should anticipate increased scientific evidence and patient awareness regarding stethoscope contamination in the post-COVID-19 era.

Artificial intelligence MacHIne learning for the detection and treatment of atrial fibrillation guidelines in the emergency department setting (AIM HIGHER): Assessing a machine learning clinical decision support tool to detect and treat non-valvular atrial fibrillation in the emergency department.

OBJECTIVE: Advanced machine learning technology provides an opportunity to improve clinical electrocardiogram (ECG) interpretation, allowing non-cardiology clinicians to initiate care for atrial fibrillation (AF). The Lucia Atrial Fibrillation Application (Lucia App) photographs the ECG to determine rhythm detection, calculates CHA2DS2-VASc and HAS-BLED scores, and then provides guideline-recommended anticoagulation. Our purpose was to determine the rate of accurate AF identification and appropriate anticoagulation recommendations in emergency department (ED) patients ultimately diagnosed with AF. METHODS: We performed a single-center, observational retrospective chart review in an urban California ED, with an annual census of 70,000 patients. A convenience sample of hospitalized patients with AF as a primary or secondary discharge diagnosis were evaluated for accurate ED AF diagnosis and ED anticoagulation rates. This was done by comparing the Lucia App against a gold standard board-certified cardiologist diagnosis and using the American College of Emergency Physicians AF anticoagulation guidelines. RESULTS: Two hundred and ninety seven patients were enrolled from January 2016 until December 2019. The median age was 79 years and 44.1% were female. Compared to the gold standard diagnosis, the Lucia App detected AF in 98.3% of the cases. Physicians recommended guideline-consistent anticoagulation therapy in 78.5% versus 98.3% for the Lucia App. Of the patients with indications for anticoagulation and discharged from the ED, only 25.0% were started at discharge. CONCLUSION: Use of a cloud-based ECG identification tool can allow non-cardiologists to achieve similar rates of AF identification as board-certified cardiologists and achieve higher rates of guideline-recommended anticoagulation therapy in the ED.

Association Between Angiotensin Receptor-Neprilysin Inhibition, Cardiovascular Biomarkers, and Cardiac Remodeling in Heart Failure With Reduced Ejection Fraction.

BACKGROUND: Sacubitril/valsartan (S/V) treatment is associated with reverse cardiac remodeling and reductions in biomarkers reflecting ventricular wall stress and myocardial injury, such as NT-proBNP (N-terminal pro-B-type natriuretic peptide), hs-cTnT (high-sensitivity cardiac troponin T), and soluble suppressor of tumorigenicity 2 (sST2). How longitudinal changes in these biomarkers analyzed collectively are associated with cardiac remodeling in patients with heart failure with reduced ejection fraction treated with S/V is uncertain. METHODS: In a prospective study of S/V in patients with heart failure with reduced ejection fraction, this prespecified exploratory analysis included patients with serially collected biomarkers and echocardiographic measures of cardiac remodeling through 12 months of treatment. A multivariate latent growth curve model assessed associations between simultaneous changes in biomarkers and left ventricular ejection fraction and left atrial volume index. RESULTS: Seven hundred fifteen out of 794 total study participants were included (mean age 65 years, 73% male). Mean baseline left ventricular ejection fraction and left atrial volume index were 29% and 40 mL/m2, respectively. Adjusted geometric mean baseline concentrations for biomarkers included NT-proBNP of 649 pg/mL, hs-cTnT of 15.9 ng/L, and sST2 of 24.7 ng/mL. Following initiation of S/V, circulating concentrations of NT-proBNP, hs-cTnT, and sST2 significantly decreased within 30 days and remained significantly different than baseline at all subsequent timepoints. From baseline to month 12, decreases in adjusted biomarker concentrations averaged -27.9% (95% CI, -35.1% to -20.7%; P<0.001) for NT-proBNP; -6.7% (95% CI, -8.8% to -4.7%; P<0.001) for hs-cTnT; and -1.6% (95% CI, -2.9% to -0.4%; P<0.001) for sST2. NT-proBNP concentrations were predictive of later changes in hs-cTnT. The magnitude of reductions in NT-proBNP and hs-cTnT concentrations associated with improvements in left ventricular ejection fraction and left atrial volume index. There was no association between changes in sST2 and changes in other measures. CONCLUSIONS: Following initiation of S/V, NT-proBNP, hs-cTnT, and sST2 concentrations decreased significantly. Longitudinal changes in NT-proBNP and hs-cTnT together associated with left atrial and left ventricular reverse remodeling. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02887183.

Improvement of Health Status Following Initiation of Sacubitril/Valsartan in Heart Failure and Reduced Ejection Fraction.

BACKGROUND: Treatment of heart failure with reduced ejection fraction (EF) may improve patient-reported health outcomes. OBJECTIVES: The purpose of this study was to determine timing and magnitude of change in Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 scores following initiation of sacubitril/valsartan and interaction with change in amino-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations. METHODS: From a single-arm, open-label study of patients initiated on sacubitril/valsartan, KCCQ-23 scores and NT-proBNP were obtained at baseline and follow-up through 12 months. Cross-sectional and longitudinal analyses evaluated magnitude and rate of change in KCCQ-23 scores and associations with NT-proBNP. Patient-level data from the randomized EVALUATE-HF study were used as historic controls. RESULTS: The analysis cohort (n = 678, age 64.7 years, 71.5% men, EF 28.9%) had a baseline KCCQ-23 overall score (OS) of 65.6. Following sacubitril/valsartan initiation, the majority (n = 412; 60.8%) of participants experienced a rise in KCCQ-23 OS ≥10 points; 26.0% increased by ≥20 points. Comparable improvement in KCCQ-23 scores was seen in various subgroups. Change in KCCQ-23 OS was inversely associated with change in circulating NT-proBNP concentrations. Among a control group of patients in EVALUATE-HF, linear rate of change in KCCQ-12 OS/14-day interval in the enalapril arm was 0.37 points (p = 0.06), whereas in the sacubitril/valsartan arm, scores increased at a rate of 1.19 points (p < 0.001), nearly identical to this dataset (1.08 points; p < 0.001). CONCLUSIONS: Treatment of heart failure with reduced EF with sacubitril/valsartan is associated with rapid and significant improvement in KCCQ-23 scores which was significantly related to change in NT-proBNP. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).

Atrial Natriuretic Peptide and Treatment With Sacubitril/Valsartan in Heart Failure With Reduced Ejection Fraction.

OBJECTIVES: This study sought to assess associations between longitudinal change in atrial natriuretic peptide (ANP) and reverse cardiac remodeling following initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF). BACKGROUND: Neprilysin inhibition results in an increase of several vasoactive peptides that may mediate the beneficial effects of sacubitril/valsartan, including ANP. METHODS: In a prospective study of initiation and titration of sacubitril/valsartan in patients with HFrEF, blood was collected at scheduled time points into tubes containing protease inhibitors. This pre-specified exploratory analysis included patients in whom ANP was measured at baseline and serially through 12 months of treatment. RESULTS: Among 144 participants (mean age: 64.5 years; left ventricular ejection fraction: 30.8%), following initiation of sacubitril/valsartan, there was an early and significant increase in ANP, with the majority of rise from 99 pg/ml at baseline to 156 pg/ml at day 14 (p < 0.001). There was a further trend toward a second increase from day 30 to day 45 (p = 0.07). At maximal rise, ANP had doubled. In longitudinal analyses, early rise in ANP was followed by a subsequent increase in urinary cycle guanosine monophosphate. Larger early increase in ANP was associated with larger later improvements in left ventricular ejection fraction and left atrial volume index (p < 0.001 for both). CONCLUSIONS: Concentrations of ANP doubled after initiation of sacubitril/valsartan in patients with HFrEF. Larger early increases in ANP were associated with a greater magnitude of subsequent reverse cardiac remodeling. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).

Reverse Cardiac Remodeling Following Initiation of Sacubitril/Valsartan in Patients With Heart Failure With and Without Diabetes.

OBJECTIVE: This study sought to determine whether patients with heart failure and reduced ejection fraction (HFrEF) with type 2 diabetes mellitus (T2DM) have similar reverse cardiac remodeling with sacubitril/valsartan as patients without T2DM. BACKGROUND: Sacubitril/valsartan promotes reverse cardiac remodeling and improves outcomes in patients with HFrEF. Patients with HFrEF with T2DM have worse prognosis than those without T2DM. METHODS: In this post hoc analysis of PROVE-HF (Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure), we examined changes in N-terminal pro-b-type natriuretic peptide (NT-proBNP), measures of cardiac remodeling, and Kansas City Cardiomyopathy Questionnaire Overall Summary (KCCQ-OS) scores from baseline to 12 months following initiation of sacubitril/valsartan between patients with HFrEF with and without T2DM. Using latent growth curve modeling, we evaluated the longitudinal association between changes in NT-proBNP, left ventricular ejection fraction, and KCCQ-OS. RESULTS: Among 794 patients enrolled, 361 (45.5%) had T2DM. NT-proBNP concentrations were modestly higher at baseline among patients with T2DM but were reduced after initiation of sacubitril/valsartan. Cross-sectional improvement was observed in left ventricular ejection fraction (T2DM: 28.3% at baseline and 37% at 12 months vs. non-T2DM: 28.1% at baseline and 38.3% at 12 months) and KCCQ-OS (T2DM: 71 at baseline and 83 at 12 months vs. non-T2DM: 76 at baseline and 88 at 12 months). Similar changes were also observed for other echocardiographic measures. In longitudinal analyses, the average NT-proBNP change was similar in patients with T2DM (-5.6% vs. -7.1% per 90-day interval; p = 0.64), whereas improvements in KCCQ-OS scores were slightly smaller (2.1 vs. 3.46 per 90-day interval; p = 0.07). CONCLUSIONS: Sacubitril/valsartan favorably affects natriuretic peptide levels, reverse cardiac remodeling, and health status in patients with HFrEF with and without T2DM. (Effects of Sacubitril/Valsartan Therapy on Biomarkers, Myocardial Remodeling and Outcomes [PROVE-HF]; NCT02887183).

Growth differentiation factor-15, a novel systemic biomarker of oxidative stress, inflammation, and cellular aging: Potential role in cardiovascular diseases.

Growth differentiation factor-15 (GDF-15) is a cytokine upregulated in multiple pathological conditions where oxidative stress, endothelial dysfunction, tissue aging, and chronic inflammation are the hallmarks. GDF-15 has many sources of production, including cardiac and vascular myocytes, endothelial cells, adipocytes and macrophages in response to metabolic stress, oncogenic transformation and the burden of proinflammatory cytokines or reactive oxygen species. Although the main sources of GDF-15 are extracardiac tissues, it has been shown to be elevated in many cardiac disorders. In experimental models of heart disease, GDF-15 release is induced after an ischemic insult and in pressure overload scenarios. Likewise, in recent years, an increasing body of evidence has emerged linking GDF-15 to the risk of mortality in acute coronary syndromes, atrial fibrillation and heart failure. Additionally, GDF-15 has been shown to add prognostic information beyond other conventional biomarkers such as natriuretic peptides and cardiac troponins. Further studies are needed to assess whether the incorporation of GDF-15 into clinical practice can improve cardiovascular outcomes.

Risk stratification scores for patients with acute heart failure in the Emergency Department: A systematic review.

AIMS: This study aimed to systematically identify and summarise all risk scores evaluated in the emergency department setting to stratify acute heart failure patients. METHODS AND RESULTS: A systematic review of PubMed and Web of Science was conducted including all multicentre studies reporting the use of risk predictive models in emergency department acute heart failure patients. Exclusion criteria were: (a) non-original articles; (b) prognostic models without predictive purposes; and (c) risk models without consecutive patient inclusion or exclusively tested in patients admitted to a hospital ward. We identified 28 studies reporting findings on 19 scores: 13 were originally derived in the emergency department (eight exclusively using acute heart failure patients), and six in emergency department and hospitalised patients. The outcome most frequently predicted was 30-day mortality. The performance of the scores tended to be higher for outcomes occurring closer to the index acute heart failure event. The eight scores developed using acute heart failure patients only in the emergency department contained between 4-13 predictors (age, oxygen saturation and creatinine/urea included in six scores). Five scores (Emergency Heart Failure Mortality Risk Grade, Emergency Heart Failure Mortality Risk Grade 30 Day mortality ST depression, Epidemiology of Acute Heart Failure in Emergency department 3 Day, Acute Heart Failure Risk Score, and Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure) have been externally validated in the same country, and two (Emergency Heart Failure Mortality Risk Grade and Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure) further internationally validated. The c-statistic for Emergency Heart Failure Mortality Risk Grade to predict seven-day mortality was between 0.74-0.81 and for Multiple Estimation of risk based on Emergency department Spanish Score In patients with Acute Heart Failure to predict 30-day mortality was 0.80-0.84. CONCLUSIONS: There are several scales for risk stratification of emergency department acute heart failure patients. Two of them are accurate, have been adequately validated and may be useful in clinical decision-making in the emergency department i.e. about whether to admit or discharge.

Racial and Ethnic Differences in Biomarkers, Health Status, and Cardiac Remodeling in Patients With Heart Failure With Reduced Ejection Fraction Treated With Sacubitril/Valsartan.

BACKGROUND: Among patients with heart failure and reduced ejection fraction (left ventricular (LV) ejection fraction ≤40%), sacubitril/valsartan (S/V) treatment is associated with improved health status and reverse cardiac remodeling. Data regarding racial and ethnic differences in response to S/V are lacking. METHODS: This was an analysis from the PROVE-HF study (Prospective Study of Biomarkers, Symptom Improvement and Ventricular Remodeling During Entresto Therapy for Heart Failure). Longitudinal changes in NT-proBNP (N-terminal pro-B-type natriuretic peptide), cardiac reverse remodeling, and health status scores were compared between groups using multivariate latent growth curve modeling. RESULTS: Among the 782 patients included in this study, 22.7% were non-Hispanic Black (from here referred to as Black), 14.9% were Hispanic, and 62.4% were non-Hispanic White (from here referred to as White). At baseline, compared with White patients, Black and Hispanic patients had lower NT-proBNP (g=0.34) and differences between groups in baseline values for LV end-diastolic volume index and LV end-systolic volume index were negligible (g<0.10). Following S/V initiation, NT-proBNP decreased in all 3 groups (P<0.0001) associated with improvements in LV ejection fraction, LV end-diastolic volume index, and LV end-systolic volume index. Although total improvement in LV measures was similar between groups, Black patients averaged larger gains in the first half of the trial while White patients averaged larger gains in the second half. Improvements in Kansas City Cardiomyopathy Questionnaire-23 Total Symptom scores were seen in all 3 groups. Treatment with S/V was well-tolerated. CONCLUSIONS: Among Black, Hispanic, and White patients with heart failure and reduced ejection fraction, treatment with S/V was associated with similar reduction in NT-proBNP, improvement in health status, and reverse remodeling. More data regarding racial and ethnic responses to heart failure and reduced ejection fraction treatment are needed. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT02887183.

Prognostic value of brain natriuretic peptide vs history of heart failure hospitalization in a large real-world population.

BACKGROUND: In heart failure (HF) patients, both natriuretic peptides (NP) and previous HF hospitalization (pHFH) have been used to predict prognosis. HYPOTHESIS: In a large real-world population, both NP levels and pHFH have independent and interdependent predictive value for clinical outcomes of HFH and all-cause mortality. METHODS: Linked electronic health records and insurance claims data from Decision Resource Group were used to identify HF patients that had a BNP or NT-proBNP result between January 2012 and December 2016. NT-proBNP was converted into BNP equivalents by dividing by 4. Index event was defined as most recent NP on or after 1 January 2012. Patients with incomplete records or age < 18 years were excluded. During one-year follow up, HFH and mortality rates stratified by index BNP levels and pHFH are reported. RESULTS: Of 64 355 patients (74 ± 12 years old, 49% female) with available values, median BNP was 259 [IQR 101-642] pg/ml. The risk of both HFH and mortality was higher with increasing BNP levels. At each level of BNP, mortality was only slightly higher in patients with pHFH vs those without pHFH (RR 1.2 [95%CI 1.2,1.3], P < .001); however, at each BNP, HFH was markedly increased in patients with pHFH vs those without pHFH (RR 2.0 [95%CI 1.9,2.1], P < .001). CONCLUSION: In this large real-world heart failure population, higher BNP levels were associated with increased risk for both HFH and mortality. At any given level of BNP, pHFH added greater prognostic value for prediction of future HFH than for mortality.

Sex-based differences in biomarkers, health status, and reverse cardiac remodelling in patients with heart failure with reduced ejection fraction treated with sacubitril/valsartan.

AIMS: We sought to determine sex-based differences in biomarkers, self-reported health status, and magnitude of longitudinal changes in measures of reverse cardiac remodelling among patients with heart failure with reduced ejection fraction (HFrEF, left ventricular ejection fraction ≤40%) treated with sacubitril/valsartan (S/V). METHODS AND RESULTS: This was a subgroup analysis of patients initiated on S/V in the Prospective Study of Biomarkers, Symptom Improvement and Ventricular Remodeling During Entresto Therapy for Heart Failure (PROVE-HF) study. There were 226 (28.5%) women in the study. Though women had lower baseline N-terminal pro B-type natriuretic peptide (NT-proBNP), they had more rapid early reduction in the biomarker after initiation of S/V. Compared to men, women had lower average baseline Kansas City Cardiomyopathy Questionnaire (KCCQ)-23 Total Symptom score (67.6 vs. 71.9; P = 0.003) but showed greater linear improvement (7.4 vs. 5.5 points; P < 0.001) and faster pace of KCCQ change (P < 0.001) over the course of the trial. Women and men demonstrated similar degrees of reverse left ventricular remodelling following S/V initiation; however, women did so earlier than men with more consistent changes. These results remained unchanged with adjustment for relevant covariates. Reduction in NT-proBNP was associated with reverse cardiac remodelling in both women and men. Treatment with S/V was well tolerated in all. CONCLUSIONS: In women with HFrEF, treatment with S/V was associated with significant NT-proBNP reduction, health status improvement and reverse cardiac remodelling.