Cost-Utility Analysis of Vericiguat in Heart Failure with Reduced Ejection Fraction After Worsening Heart Failure Events in China.

OBJECTIVE: Vericiguat is a new medication to demonstrate clinical efficacy in heart failure with reduced ejection fraction (HFrEF) after worsening heart failure (WHF) events, but its cost-utility was unknown. We aimed to assess the cost-utility of combining the application of vericiguat with standard treatment in HFrEF patients who had WHF events. METHODS: A multistate Markov model was implemented to mimic the economic results of HFrEF patients who had WHF events in China after receiving vericiguat or placebo. An analysis of cost-utility was conducted; most parameters were set according to the published studies and related databases. All the utilities and costs were decreased at a rate of 5% annually. The incremental cost-effectiveness ratios (ICERs) were the primary outcome measure. We also conducted sensitivity analyses. RESULTS: Over a 20 year lifetime horizon, additional use of vericiguat led to an elevated cost from US$9725.03 to US$20,660.76 at the current vericiguat costs. This was related to increased quality-adjusted life years (QALYs) from 2.50 to 2.66, along with an ICER of US$65,057.24 per QALY, which was over the willingness-to-pay (WTP) threshold of US$36,096.30 per QALY. If the vericiguat costs were discounted at 80%, it contributed to an ICER of US$12,226.77 per QALY. Additional use of vericiguat for patients with plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) of ≤ 5314 pg per ml produced an ICER of US$23,688.46 per QALY. The outcomes of the one-way sensitivity analysis showed the risk of death from cardiovascular disease in both groups was variable with the highest sensitivity. The probabilistic sensitivity analysis showed that 41.6% of the mimicked population receiving vericiguat combined with standard therapy was cost-effective at the WTP threshold of US$36,096.30 per QALY. CONCLUSIONS: From the perspective of Chinese public healthcare system, the combined use of vericiguat and standard treatment in patients with HFrEF following WHF events did not generate advantages in cost-utility in China but was a cost-effective therapeutic strategy for those who with plasma NT-proBNP of ≤ 5314 pg per ml.

The Value of Echocardiography Combined with NT-pro BNP Level in Assessment and Prognosis of Diastolic Heart Failure.

BACKGROUND: To investigate the significance of echocardiography combined with N-terminal pro-B-type natriuretic peptide (NT-pro BNP) levels in the evaluation and prognosis of diastolic heart failure (DHF). METHODS: Clinical data were collected from 168 patients with DHF. Serum levels of NT-pro BNP were first measured by ELISA. Meanwhile, the echocardiography was used to examine left ventricular end-diastolic diameter (LVEDD), left ventricular diameter (LVD), and other parameters. Multivariate logistic regression analysis was performed for variables in heart failure assessment grade or poor prognosis. Finally, the predictive ability for New York Heart Association (NYHA) class as well as prognosis was assessed by ROC curves. RESULTS: NT-pro BNP was the overexpression in the serum of patients with DHF. And the degree of elevation was related to NYHA class, while NT-pro BNP levels were significantly higher in the P-MACE group than in the N-MACE group. According to the multivariate logistic regression analysis, the ratio of peak velocity of left atrial early diastolic blood flow to early diastolic peak velocity of mitral annulus (E/Ea) and serum NT-pro BNP level was risk factors for NYHA class and prognosis. However, LVEF, LVEDD, and flow propagation velocity (Vp) can be a benefit condition. In addition, ROC curve showed that echocardiography combined with NT-pro BNP content had higher accuracy in NYHA class and prognostic assessment of DHF than applied separately. CONCLUSIONS: The diagnosis of echocardiography combined with NT-pro BNP levels has the potential to distinguish the NYHA class in heart function of patients with DHF and determine the prognosis of patients.

Potential Value of Presepsin Guidance in Shortening Antibiotic Therapy in Septic Patients: a Multicenter, Prospective Cohort Trial.

INTRODUCTION: Long-term use of antibiotics for septic patients leads to bacterial resistance, increased mortality, and hospital stay. In this study, we investigated an emerging biomarker presepsin-guided strategy, which can be used to evaluate the shortening of antibiotic treatment in patients with sepsis without risking a worse outcome. METHODS: In this multicenter prospective cohort trial, patients were assigned to the presepsin or control groups. In the presepsin group, antibiotics were ceased based on predefined cut-off ranges of presepsin concentrations. The control group stopped antibiotics according to international guidelines. The primary endpoints were the number of days without antibiotics within 28 days and mortality at 28 and 90 days. Secondary endpoints were the percentage of patients with a recurrent infection, length of stay in ICU and hospital, hospitalization costs, days of first episode of antibiotic treatment, percentage of antibiotic administration and multidrug-resistant bacteria, and SOFA score. RESULTS: Overall, 656 out of an initial 708 patients were eligible and assigned to the presepsin group (n = 327) or the control group (n = 329). Patients in the presepsin group had significantly more days without antibiotics than those in the control group (14.54 days [SD 9.01] vs. 11.01 days [SD 7.73]; P < 0.001). Mortality in the presepsin group showed no difference to that in the control group at days 28 (17.7% vs. 18.2%; P = 0.868) and 90 (19.9% vs. 19.5%; P = 0.891). Patients in the presepsin group had a significantly shorter mean length of stay in the hospital and lower hospitalization costs than control subjects. There were no differences in the rate of recurrent infection and multidrug-resistant bacteria and the SOFA score tendency between the two groups. CONCLUSIONS: Presepsin guidance has potential to shorten the duration of antibiotic treatment in patients with sepsis without risking worse outcomes of death, recurrent infection, and aggravation of organ failure. TRIAL REGISTRATION: ChiCTR, ChiCTR1900024391. Registered 9 July 2019-Retrospectively registered, http://www.chictr.org.cn.

Quantitative assessment of AD markers using naked eyes: point-of-care testing with paper-based lateral flow immunoassay.

Aß42 is one of the most extensively studied blood and Cerebrospinal fluid (CSF) biomarkers for the diagnosis of symptomatic and prodromal Alzheimer's disease (AD). Because of the heterogeneity and transient nature of Aß42 oligomers (Aß42Os), the development of technologies for dynamically detecting changes in the blood or CSF levels of Aß42 monomers (Aß42Ms) and Aß42Os is essential for the accurate diagnosis of AD. The currently commonly used Aß42 ELISA test kits usually mis-detected the elevated Aß42Os, leading to incomplete analysis and underestimation of soluble Aß42, resulting in a comprised performance in AD diagnosis. Herein, we developed a dual-target lateral flow immunoassay (dLFI) using anti-Aß42 monoclonal antibodies 1F12 and 2C6 for the rapid and point-of-care detection of Aß42Ms and Aß42Os in blood samples within 30 min for AD diagnosis. By naked eye observation, the visual detection limit of Aß42Ms or/and Aß42Os in dLFI was 154 pg/mL. The test results for dLFI were similar to those observed in the enzyme-linked immunosorbent assay (ELISA). Therefore, this paper-based dLFI provides a practical and rapid method for the on-site detection of two biomarkers in blood or CSF samples without the need for additional expertise or equipment.

Assessment of right ventricle in pulmonary arterial hypertension with three-dimensional echocardiography and cardiovascular magnetic resonance.

AIM: To correlate 3-D Echo and CMR RV parameters and to verify whether they are similarly related to the clinical conditions of patients with pulmonary arterial hypertension (PAH), a disease in which the RV plays a crucial prognostic role. METHODS: We enrolled 34 consecutive PAH patients followed by our PAH clinics. All patients underwent a 3-D Echo and CMR assessment of RV volumes and functions in the same day. The presence or absence of correlation between major findings was investigated; functional RV parameters were also analyzed in relation to 6-min walking test (6MWT) results and BNP/Nt-proBNP plasma levels. Twenty-four subjects served as controls. RESULTS: Good agreement was found between 3-D Echo and CMR measures of RV volumes [RV-end-diastolic volume (r = 0.72, P < 0.0001), RV-end-systolic volume (ESV) (r = 0.80, P < 0.0001)] and function [RV-EF (r = 0.73, P < 0.0001), RV-ESV/SV (r = 0.83, P = 0.001)] for all the subjects of the study. These correlations were stronger in PAH patients than in control subjects. Importantly, 3-D Echo and CMR RV-EF and RV to pulmonary arterial coupling (RV-ESV/SV) similarly correlated with BNP/Nt-proBNP levels and with functional capacity measured at 6MWT in the PAH patients group. CONCLUSIONS: 3-D Echo demonstrated a significant agreement with CMR in the assessment of RV volume and function in PAH patients. Both techniques showed a similar correlation with clinical and prognostic parameters. The use of 3-D Echo should be amply boosted in the real-world clinical evaluation of PAH patients.

Socioeconomic position is associated with N-terminal pro-brain natriuretic peptide (NT-proBNP)-Results of the population-based Heinz Nixdorf Recall study.

OBJECTIVES: N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) is a diagnostic marker for heart failure and a prognostic factor for cardiovascular disease (CVD). The aim of this study was to examine the association of socioeconomic position (SEP) with NT-proBNP while assessing sex-differences and the impact of CVD risk factors and prevalent CVD on the association. METHODS: Baseline data of 4598 participants aged 45-75 years of the Heinz Nixdorf Recall Study were used. Income and education were used as SEP indicators. Age- and sex-adjusted linear regression models were fitted to calculate effect size estimates and 95% confidence intervals (95%-CIs) for the total effect of SEP indicators on NT-proBNP, while potential mediation was assessed by additionally accounting for traditional CVD risk factors (i.e., systolic blood pressure, HDL cholesterol, LDL cholesterol, diabetes, anti-hypertensive medication, lipid-lowering medication, BMI, current smoking). Education and income were included separately in the models. RESULTS: With an age- and sex-adjusted average change in NT-proBNP of -6.47% (95%-CI: -9.91; -2.91) per 1000€, the association between income and NT-proBNP was more pronounced compared to using education as a SEP indicator (-0.80% [95%-CI: -1.92; 0.32] per year of education). Sex-stratified results indicated stronger associations in men (-8.43% [95%-CI: -13.21; -3.38] per 1000€; -1.63% [95%-CI: -3.23; -0.001] per year of education) compared to women (-5.10% [95%-CI: -9.82; -0.01] per 1000€; -1.04% [95%-CI: -2.59; 0.50] per year of education). After adjusting for CVD risk factors some of the observed effect size estimates were attenuated, while the overall association between SEP indicators and NT-proBNP was still indicated. The exclusion of participants with prevalent coronary heart disease or stroke did not lead to a substantial change in the observed associations. CONCLUSIONS: In the present study associations of education and income with NT-proBNP were observed in a population-based study sample. Only parts of the association were explained by traditional CVD risk factors, while there were substantial sex-differences in the strength of the observed association. Overt coronary heart disease or stroke did not seem to trigger the associations.

Economic Evaluation of an N-terminal Pro B-type Natriuretic Peptide-Supported Diagnostic Strategy Among Dyspneic Patients Suspected of Acute Heart Failure in the Emergency Department.

Our objective was to perform an economic evaluation of an N-terminal pro B-type natriuretic peptide (NT-proBNP)-supported diagnostic strategy in dyspneic patients suspected of acute heart failure in the emergency department (ED). A decision-tree model was developed to evaluate clinical outcomes and costs for NT-proBNP-supported assessment compared with clinical assessment alone over 6 months from the United States (US) Medicare perspective. The model considered rule-in/rule-out cutoffs identified in the ICON and ICON-RELOADED studies. Acute heart failure prevalence, diagnostic accuracies, and medical resource use conditional on disease status and test results were derived from ICON-RELOADED. Several assumptions based on previous studies of NT-proBNP acute dyspnea and verified with clinicians were applied to medical resource use and assessed in sensitivity analyses. Compared with clinical assessment alone, NT-proBNP-supported assessment improved overall probability of correct diagnosis by a relative 7% (18% for true-positive and 5% for true-negative). This led to relative reductions in medical resource use in ED and hospital, including fewer initial hospitalizations (-14%), required echocardiograms (-31%), cardiology admissions (-16%), intensive care unit admissions (-12%), ED readmissions (-3%), and hospital readmissions (-22%). NT-proBNP use decreased average inpatient management costs by a relative 10%, yielding cost savings of US$2,337 per patient ED visit. These findings were robust in sensitivity analyses. In conclusion, based on a contemporary trial of patients with acute dyspnea, this analysis reaffirmed that using NT-proBNP as a diagnostic tool may improve the management of patients with dyspnea presenting to EDs and is likely to be cost-saving from the US Medicare perspective.

Assessment of therapeutic effects of statin on cardiac sympathetic nerve activity after reperfusion therapy in patients with first ST-segment elevation myocardial infarction and normal low-density lipoprotein cholesterol.

BACKGROUND: Statin treatment reduces enhanced cardiac sympathetic nerve activity (CSNA) in patients with heart disease, and reduces adverse cardiac events in patients with coronary artery disease. METHODS: We retrospectively evaluated the first ST-segment elevation myocardial infarction (STEMI) patients and low-density lipoprotein cholesterol < 120 mg/dL in our database who underwent 123I-metaiodobenzylguanidine (MIBG) scintigraphy 3 weeks after admission. Sixty STEMI patients after primary coronary angioplasty were selected, and used propensity score matching to compare patients treated with strong statin (n = 30), and those who did not (n = 30). Moreover, echocardiographic left ventricular (LV) parameters were determined, and plasma procollagen type III amino terminal peptide (PIIINP) was also measured before and 3 weeks after treatment. RESULTS: Following primary angioplasty, age, gender, risk factors, culprit coronary artery, peak serum creatine phosphokinase concentration, and recanalization time were similar in the two groups. However, the statin group showed significantly lower delayed total defect score and washout rate evaluated by 123I-MIBG scintigraphy (22.4 ± 8.1 vs. 29.6 ± 10.5; P < 0.01, and 30.4 ± 8.9% vs. 40.1 ± 11.4%; P < 0.005, respectively) and higher delayed heart/mediastinum count ratio (2.17 ± 0.38 vs. 1.96 ± 0.30, P < 0.05) compared with the non-statin group. Moreover, the degree of change in LV parameters and PIIINP was more favorable in the statin group than in the non-statin group. CONCLUSIONS: Administration of statin improves CSNA after reperfusion therapy in patients with first STEMI.

Assessment of ventricular dysfunction in Egyptian children with Beta-thalassemia major.

OBJECTIVE/BACKGROUND: The purpose of this study was to evaluate serum cardiac troponin I and serum N-terminal (NT) pro-brain natriuretic peptide (pro-BNP) levels and the utility of tissue Doppler imaging in assessing cardiovascular changes following left ventricular (LV) dysfunction in children with beta-thalassemia major (ß-TM). In children with ß-TM who depend on regular blood transfusion, cardiac iron toxicity is a common serious complication. The most common cause of death among these patients is congestive heart failure. METHODS: This is a cross-sectional study which included 50 patients with ß-TM and 50 healthy controls. Tissue Doppler imaging was performed and levels of serum ferritin, cardiac troponin I, and NT pro-BNP were estimated for all included patients. RESULTS: Serum NT pro-BNP and cardiac troponin (cTnI) showed a significant increase in patients with ß-TM (p < .001). In patients with ß-TM, LV dimensions (LV end systolic diameter) and (LV end diastolic diameter) were large (p < .01); LV mass (p < .01), E wave, and E/A ratio (p < .01) were high (p < .05); and deceleration time was short (p < .05). Besides, transmitral ratio (E/Em) (p < .05) and tricuspid valve velocity were higher (p < .05), and early diastolic velocity (Em) (p < .05) and systolic wave velocity (Sm) were lower in patients with ß-TM (p < .05). A significant positive correlation was detected between the pro-BNP and E wave (r = 0.558, p < .001), E/A ratio (r = 0.403, p < .001), E/Em ratio (r = 0.576, p < .001), and ferritin (r = 0.545, p < .001). CONCLUSION: Pulsed wave tissue Doppler imaging and NT pro-BNP had a significant role in the estimation of ventricular dysfunction in children with ß-TM.

The cardiovascular determinants of physical function in patients with end-stage kidney disease on haemodialysis.

Patients with end-stage kidney disease (ESKD) are often sedentary and decreased functional capacity associates with mortality. The relationship between cardiovascular disease (CVD) and physical function has not been fully explored. Understanding the relationships between prognostically relevant measures of CVD and physical function may offer insight into how exercise interventions might target specific elements of CVD. 130 patients on haemodialysis (mean age 57 ± 15 years, 73% male, dialysis vintage 1.3 years (0.5, 3.4), recruited to the CYCLE-HD trial (ISRCTN11299707), underwent cardiovascular phenotyping with cardiac MRI (left ventricular (LV) structure and function, pulse wave velocity (PWV) and native T1 mapping) and cardiac biomarker assessment. Participants completed the incremental shuttle walk test (ISWT) and sit-to-stand 60 (STS60) as field-tests of physical function. Linear regression models identified CV determinants of physical function measures, adjusted for age, gender, BMI, diabetes, ethnicity and systolic blood pressure. Troponin I, PWV and global native T1 were univariate determinants of ISWT and STS60 performance. NT pro-BNP was a univariate determinant of ISWT performance. In multivariate models, NT pro-BNP and global native T1 were independent determinants of ISWT and STS60 performance. LV ejection fraction was an independent determinant of ISWT distance. However, age and diabetes had the strongest relationships with physical function. In conclusion, NT pro-BNP, global native T1 and LV ejection fraction were independent CV determinants of physical function. However, age and diabetes had the greatest independent influence. Targeting diabetic care may ameliorate deconditioning in these patients and a multimorbidity approach should be considered when developing exercise interventions.

Revisiting heart failure assessment based on objective measures in NYHA functional classes I and II.

OBJECTIVE: New York Heart Association (NYHA) functional class plays a central role in heart failure (HF) assessment but might be unreliable in mild presentations. We compared objective measures of HF functional evaluation between patients classified as NYHA I and II in the Rede Brasileira de Estudos em Insuficiência Cardíaca (ReBIC)-1 Trial. METHODS: The ReBIC-1 Trial included outpatients with stable HF with reduced ejection fraction. All patients had simultaneous protocol-defined assessment of NYHA class, 6 min walk test (6MWT), N-terminal pro-brain natriuretic peptide (NT-proBNP) levels and patient's self-perception of dyspnoea using a Visual Analogue Scale (VAS, range 0-100). RESULTS: Of 188 included patients with HF, 122 (65%) were classified as NYHA I and 66 (35%) as NYHA II at baseline. Although NYHA class I patients had lower dyspnoea VAS Scores (median 16 (IQR, 4-30) for class I vs 27.5 (11-49) for class II, p=0.001), overlap between classes was substantial (density overlap=60%). A similar profile was observed for NT-proBNP levels (620 pg/mL (248-1333) vs 778 (421-1737), p=0.015; overlap=78%) and for 6MWT distance (400 m (330-466) vs 351 m (286-408), p=0.028; overlap=64%). Among NYHA class I patients, 19%-34% had one marker of HF severity (VAS Score >30 points, 6MWT <300 m or NT-proBNP levels >1000 pg/mL) and 6%-10% had two of them. Temporal change in functional class was not accompanied by variation on dyspnoea VAS (p=0.14). CONCLUSIONS: Most patients classified as NYHA classes I and II had similar self-perception of their limitation, objective physical capabilities and levels of natriuretic peptides. These results suggest the NYHA classification poorly discriminates patients with mild HF.

Assessment of Plasma Amyloid-ß42/40 and Cognitive Decline Among Community-Dwelling Older Adults.

Importance: Plasma measurement of amyloid-ß (Aß) peptides has been associated with cognitive function, but evidence of its ability to identify cognitive decline is still scarce. Objective: To investigate the associations between plasma Aß42/40 and cognitive decline over time among community-dwelling older adults with subjective memory concerns. Design, Setting, and Participants: This multicenter cohort study used data from volunteers in the 5-year study Multidomain Alzheimer Preventive Trial (MAPT). Participants were aged 70 years or older and observed for a median (interquartile range) of 3.9 (2.0-4.0) years. Recruitment of participants started in May 2008 and ended in February 2011. Follow-up ended in April 2016. Data analysis was conducted from April to October 2020. Exposure: Plasma Aß42 and Aß40 were measured at 12 months for 448 participants (92.8%) and at 24 months for the rest. The moment of Aß assessment was defined as the baseline for this study. Main Outcomes and Measures: Cognitive function was assessed at 12, 24, 36, 48, and 60 months by a composite cognitive score based on 4 tests; Mini Mental State Examination (MMSE); Clinical Dementia Rating, sum of boxes; and Alzheimer Disease Cooperative Study-Activities of Daily Living. Mixed-effect linear regressions were performed. Results: A total of 483 participants (median [IQR] age, 76.0 [73.0-80.0]; 286 [59.2%] women) were analyzed. Of them, 161 (33.3%) were classified as low plasma Aß42/40 (≤0.107). After adjusting for age, sex, education, body mass index, Geriatric Depression Scale score, apolipoprotein E ε4 genotype, and MAPT intervention groups, low plasma Aß42/40 was associated with more pronounced decline in composite cognitive score (adjusted between-group mean difference: -0.20, 95% CI, -0.34 to -0.07; P = .004) and decline in MMSE score (adjusted between-group mean difference: -0.59; 95% CI, -1.07 to -0.11; P = .02) during the follow-up period compared with the group with an Aß42/40 ratio greater than 0.107. Conclusions and Relevance: In this study, low plasma Aß42/40 was associated with more pronounced decline in cognitive function (measured by multiple outcomes) over time. Findings suggest that plasma Aß42/40 may be used to identify people at risk of cognitive decline, being an alternative to more complex and expensive measures, such as positron emission tomography imaging or cerebrospinal fluid measurement.

A Sensitive and Cost-Effective Chemiluminescence ELISA for Measurement of Amyloid-ß 1-42 Peptide in Human Plasma.

BACKGROUND: Amyloid-ß42 (Aß42) is associated with plaque formation in the brain of patients with Alzheimer's disease (AD). Studies have suggested the potential utility of plasma Aß42 levels in the diagnosis, and in longitudinal study of AD pathology. Conventional ELISAs are used to measure Aß42 levels in plasma but are not sensitive enough to quantitate low levels. Although ultrasensitive assays like single molecule array or immunoprecipitation-mass spectrometry have been developed to quantitate plasma Aß42 levels, the high cost of instruments and reagents limit their use. OBJECTIVE: We hypothesized that a sensitive and cost-effective chemiluminescence (CL) immunoassay could be developed to detect low Aß42 levels in human plasma. METHODS: We developed a sandwich ELISA using high affinity rabbit monoclonal antibody specific to Aß42. The sensitivity of the assay was increased using CL substrate to quantitate low levels of Aß42 in plasma. We examined the levels in plasma from 13 AD, 25 Down syndrome (DS), and 50 elderly controls. RESULTS: The measurement range of the assay was 0.25 to 500 pg/ml. The limit of detection was 1 pg/ml. All AD, DS, and 45 of 50 control plasma showed measurable Aß42 levels. CONCLUSION: This assay detects low levels of Aß42 in plasma and does not need any expensive equipment or reagents. It offers a preferred alternative to ultrasensitive assays. Since the antibodies, peptide, and substrate are commercially available, the assay is well suited for academic or diagnostic laboratories, and has a potential for the diagnosis of AD or in clinical trials.

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.

Red blood cell distribution width in addition to N-terminal prohormone of B-type natriuretic peptide concentration improves assessment of risk of cardiovascular events in adult patients with congenital heart disease.

BACKGROUND: Red blood cell distribution width (RDW) is a predictor of adverse outcomes in patients with heart disease. AIM: To establish predictors of high RDW values in patients with congenital heart disease (CHD), and their relationship with cardiovascular events. METHODS: Overall, 561 patients with stable CHD who attended a single outpatient clinic and a matched control population of 2128 patients were studied. Exclusion criteria were renal failure, anaemia, receiving iron therapy and cyanosis. Blood tests included glucose, creatinine, iron, apoferritin, liver enzymes and a complete blood count. C-reactive protein and N-terminal prohormone of B-type natriuretic peptide (NT-pro-BNP) concentrations were also measured in patients with CHD. Major adverse cardiac events (MACE) were defined as cardiovascular/total mortality, arterial thrombotic events, arrhythmias, major bleedings, pulmonary embolism or heart failure needing hospital admission. RESULTS: The median age in patients with CHD was 23 (17-36) years and the median follow-up time was 5.8 (3.2-8.7) years; 103 (4.8%) controls and 40 (7.1%) patients with CHD had an RDW>15% (P=0.032). During follow-up, MACE were reported in 48 patients. CHD of great complexity, cardiovascular risk factors, low haemoglobin concentration and high NT-pro-BNP concentration were risk factors for an RDW>15%. Kaplan-Meier analysis showed a significantly worse cardiovascular outcome in patients with CHD with an RDW>15% (P<0.001). The multivariable survival analysis determined that age, CHD of great complexity, high NT-pro-BNP concentration and an RDW>15% were independent predictive factors for MACE. CONCLUSION: RDW and NT-pro-BNP concentration are independent analytical predictors of MACE in patients with CHD.

Combining Biomarkers and Imaging for Short-Term Assessment of Cardiovascular Disease Risk in Apparently Healthy Adults.

Background Current strategies for cardiovascular disease (CVD) risk assessment focus on 10-year or longer timeframes. Shorter-term CVD risk is also clinically relevant, particularly for high-risk occupations, but is under-investigated. Methods and Results We pooled data from participants in the ARIC (Atherosclerosis Risk in Communities study), MESA (Multi-Ethnic Study of Atherosclerosis), and DHS (Dallas Heart Study), free from CVD at baseline (N=16 581). Measurements included N-terminal pro-B-type natriuretic peptide (>100 pg/mL prospectively defined as abnormal); high-sensitivity cardiac troponin T (abnormal >5 ng/L); high-sensitivity C-reactive protein (abnormal >3 mg/L); left ventricular hypertrophy by ECG (abnormal if present); carotid intima-media thickness, and plaque (abnormal >75th percentile for age and sex or presence of plaque); and coronary artery calcium (abnormal >10 Agatston U). Each abnormal test result except left ventricular hypertrophy by ECG was independently associated with increased 3-year risk of global CVD (myocardial infarction, stroke, coronary revascularization, incident heart failure, or atrial fibrillation), even after adjustment for traditional CVD risk factors and the other test results. When a simple integer score counting the number of abnormal tests was used, 3-year multivariable-adjusted global CVD risk was increased among participants with integer scores of 1, 2, 3, and 4, by ≈2-, 3-, 4.5- and 8-fold, respectively, when compared with those with a score of 0. Qualitatively similar results were obtained for atherosclerotic CVD (fatal or non-fatal myocardial infarction or stroke). Conclusions A strategy incorporating multiple biomarkers and atherosclerosis imaging improved assessment of 3-year global and atherosclerotic CVD risk compared with a standard approach using traditional risk factors.

Association of Cardiac Biomarkers With the Kansas City Cardiomyopathy Questionnaire in Patients With Chronic Kidney Disease Without Heart Failure.

Background The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a measure of heart failure (HF) health status. Worse KCCQ scores are common in patients with chronic kidney disease (CKD), even without diagnosed heart failure (HF). Elevations in the cardiac biomarkers GDF-15 (growth differentiation factor-15), galectin-3, sST2 (soluble suppression of tumorigenesis-2), hsTnT (high-sensitivity troponin T), and NT-proBNP (N-terminal pro-B-type natriuretic peptide) likely reflect subclinical HF in CKD. Whether cardiac biomarkers are associated with low KCCQ scores is not known. Methods and Results We studied participants with CKD without HF in the multicenter prospective CRIC (Chronic Renal Insufficiency Cohort) Study. Outcomes included (1) low KCCQ score <75 at year 1 and (2) incident decline in KCCQ score to <75. We used multivariable logistic regression and Cox regression models to evaluate the associations between baseline cardiac biomarkers and cross-sectional and longitudinal KCCQ scores. Among 2873 participants, GDF-15 (adjusted odds ratio 1.42 per SD; 99% CI, 1.19-1.68) and galectin-3 (1.28; 1.12-1.48) were significantly associated with KCCQ scores <75, whereas sST2, hsTnT, and NT-proBNP were not significantly associated with KCCQ scores <75 after multivariable adjustment. Of the 2132 participants with KCCQ ≥75 at year 1, GDF-15 (adjusted hazard ratio, 1.36 per SD; 99% CI, 1.12-1.65), hsTnT (1.20; 1.01-1.44), and NT-proBNP (1.30; 1.08-1.56) were associated with incident decline in KCCQ to <75 after multivariable adjustment, whereas galectin-3 and sST2 did not have significant associations with KCCQ decline. Conclusions Among participants with CKD without clinical HF, GDF-15, galectin-3, NT-proBNP, and hsTnT were associated with low KCCQ either at baseline or during follow-up. Our findings show that elevations in cardiac biomarkers reflect early symptomatic changes in HF health status in CKD patients.

Assessment of successful percutaneous mitral commissurotomy by MRproANP and sCD146.

BACKGROUND: We studied the course of plasma concentrations of 4 cardiovascular biomarkers: natriuretic peptides (BNP, NT-proBNP; mid-regional (MR) pro-atrial NP); and soluble endothelial CD146 (sCD146), in patients with severe mitral valve stenosis undergoing percutaneous mitral commissurotomy (PMC) to identify potential markers of procedural success. METHODS: Biomarkers were tested in 40 patients the day before and the day after PMC. Success was defined as mitral valve area ≥ 1.5 cm2; or an increase of ≥0.5 cm2 in mitral valve area associated with echocardiographic mitral regurgitation

Risk Score for Predicting 2-Year Mortality in Patients With Chagas Cardiomyopathy From Endemic Areas: SaMi-Trop Cohort Study.

Background Risk stratification of Chagas disease patients in the limited-resource setting would be helpful in crafting management strategies. We developed a score to predict 2-year mortality in patients with Chagas cardiomyopathy from remote endemic areas. Methods and Results This study enrolled 1551 patients with Chagas cardiomyopathy from Minas Gerais State, Brazil, from the SaMi-Trop cohort (The São Paulo-Minas Gerais Tropical Medicine Research Center). Clinical evaluation, ECG, and NT-proBNP (N-terminal pro-B-type natriuretic peptide) were performed. A Cox proportional hazards model was used to develop a prediction model based on the key predictors. The end point was all-cause mortality. The patients were classified into 3 risk categories at baseline (low, <2%; intermediate, ≥2% to 10%; high, ≥10%). External validation was performed by applying the score to an independent population with Chagas disease. After 2 years of follow-up, 110 patients died, with an overall mortality rate of 3.505 deaths per 100 person-years. Based on the nomogram, the independent predictors of mortality were assigned points: age (10 points per decade), New York Heart Association functional class higher than I (15 points), heart rate ≥80 beats/min (20 points), QRS duration ≥150 ms (15 points), and abnormal NT-proBNP adjusted by age (55 points). The observed mortality rates in the low-, intermediate-, and high-risk groups were 0%, 3.6%, and 32.7%, respectively, in the derivation cohort and 3.2%, 8.7%, and 19.1%, respectively, in the validation cohort. The discrimination of the score was good in the development cohort (C statistic: 0.82), and validation cohort (C statistic: 0.71). Conclusions In a large population of patients with Chagas cardiomyopathy, a combination of risk factors accurately predicted early mortality. This helpful simple score could be used in remote areas with limited technological resources.