Nucleocapsid and Spike Protein-Based Anti-SARS-CoV-2 Assay Performance in the Minority and Rural Coronavirus Insights Study: Characteristics of Socioeconomically Disadvantaged Populations with Health Disparities.

BACKGROUND: COVID-19 has had a devastating impact on Black, Hispanic, and other underserved, disadvantaged populations. Here anti-SARS-CoV-2 tests are characterized in disadvantaged patients to examine equivalence in US populations. METHODS: Underserved participant adults (age > 18 years) were enrolled before the availability of SARS-CoV-2 vaccines in Federal Qualified Health Centers in California, Florida, Louisiana, Illinois, and Ohio and contributed samples to the Minority and Rural Coronavirus Insights Study (MRCIS). A subset coined the MRCIS SARS-CoV-2 Antibody Cohort of 2365 participants was tested with the Roche Anti-SARS-CoV-2 assay (Cobas e601). Five hundred ninety-five of these were also tested with the Ortho Clinical Diagnostics VITROS Anti-SARS-CoV-2 IgG assay (VITROS-5600); 1770 were also tested with the Abbott ARCHITECT SARS-CoV-2 IgG assay (ARCHITECT-2000). Assay-specific cutoffs classified negative/positive results. RESULTS: Eight point four percent (199/2365) of the MRCIS SARS-CoV-2 Antibody Cohort was SARS-CoV-2 RNA positive at enrollment. Agreement between the Ortho/Roche and the Abbott/Roche antibody testing did not vary by enrollment RNA status. The Ortho (anti-spike protein) vs Roche (anti-nucleocapsid protein) comparison agreed substantially: kappa = 0.63 (95% CI: 0.57-0.69); overall agreement, 83%. However, agreement was even better for the Abbott vs Roche assays (both anti-nucleocapsid protein tests): kappa = 0.85 (95% CI: 0.81-0.87); overall agreement, 95%. Anti-SARS-CoV-2 comparisons stratified by demographic criteria demonstrated no significant variability in agreement by sex, race/ethnicity, or age. CONCLUSIONS: Analytical agreement is 96.4% for anti-spike-protein vs anti-nucleocapsid-protein comparisons. Physiologically, seroreversion of anti-nucleocapsid reactivity after infection occurred in the disadvantaged population similarly to general populations. No anti-SARS-CoV-2 assays included demonstrated a clinically significant difference due to the demographics of the disadvantaged MRCIS SARS-CoV-2 Antibody Cohort.

Race differences in cardiac testing rates for patients with chest pain in a multisite cohort.

BACKGROUND: Identifying and eliminating racial health care disparities is a public health priority. However, data evaluating race differences in emergency department (ED) chest pain care are limited. METHODS: We conducted a secondary analysis of the High-Sensitivity Cardiac Troponin T to Optimize Chest Pain Risk Stratification (STOP-CP) cohort, which prospectively enrolled adults with symptoms suggestive of acute coronary syndrome without ST-elevation from eight EDs in the United States from 2017 to 2018. Race was self-reported by patients and abstracted from health records. Rates of 30-day noninvasive testing (NIT), cardiac catheterization, revascularization, and adjudicated cardiac death or myocardial infarction (MI) were determined. Logistic regression was used to evaluate the association between race and 30-day outcomes with and without adjustment for potential confounders. RESULTS: Among 1454 participants, 42.3% (615/1454) were non-White. At 30 days NIT occurred in 31.4% (457/1454), cardiac catheterization in 13.5% (197/1454), revascularization in 6.0% (87/1454), and cardiac death or MI in 13.1% (190/1454). Among Whites versus non-Whites, NIT occurred in 33.8% (284/839) versus 28.1% (173/615; odds ratio [OR] 0.76, 95% confidence interval [CI] 0.61-0.96) and catheterization in 15.9% (133/839) versus 10.4% (64/615; OR 0.62, 95% CI 0.45-0.84). After covariates were adjusted for, non-White race remained associated with decreased 30-day NIT (adjusted OR [aOR] 0.71, 95% CI 0.56-0.90) and cardiac catheterization (aOR 0.62, 95% CI 0.43-0.88). Revascularization occurred in 6.9% (58/839) of Whites versus 4.7% (29/615) of non-Whites (OR 0.67, 95% CI 0.42-1.04). Cardiac death or MI at 30 days occurred in 14.2% of Whites (119/839) versus 11.5% (71/615) of non-Whites (OR 0.79 95% CI 0.57-1.08). After adjustment there was still no association between race and 30-day revascularization (aOR 0.74, 95% CI 0.45-1.20) or cardiac death or MI (aOR 0.74, 95% CI 0.50-1.09). CONCLUSIONS: In this U.S. cohort, non-White patients were less likely to receive NIT and cardiac catheterization compared to Whites but had similar rates of revascularization and cardiac death or MI.

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.

Critical appraisal of the 2020 ESC guideline recommendations on diagnosis and risk assessment in patients with suspected non-ST-segment elevation acute coronary syndrome.

Multiple new recommendations have been introduced in the 2020 ESC guidelines for the management of acute coronary syndromes with a focus on diagnosis, prognosis, and management of patients presenting without persistent ST-segment elevation. Most recommendations are supported by high-quality scientific evidence. The guidelines provide solutions to overcome obstacles presumed to complicate a convenient interpretation of troponin results such as age-, or sex-specific cutoffs, and to give practical advice to overcome delays of laboratory reporting. However, in some areas, scientific support is less well documented or even missing, and other areas are covered rather by expert opinion or subjective recommendations. We aim to provide a critical appraisal on several recommendations, mainly related to the diagnostic and prognostic assessment, highlighting the discrepancies between Guideline recommendations and the existing scientific evidence.

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.

Echocardiographic assessment of insulin-like growth factor binding protein-7 and early identification of acute heart failure.

AIMS: Concentrations of insulin-like growth factor binding protein-7 (IGFBP7) have been linked to abnormal cardiac structure and function in patients with chronic heart failure (HF), but cardiovascular correlates of the biomarker in patients with more acute presentations are lacking. We aimed to determine the relationship between IGFBP7 concentrations and cardiac structure and to evaluate the impact of IGFBP7 on the diagnosis of acute HF among patients with acute dyspnoea. METHODS AND RESULTS: In this pre-specified subgroup analysis of the International Collaborative of N-terminal pro-B-type Natriuretic Peptide Re-evaluation of Acute Diagnostic Cut-Offs in the Emergency Department (ICON-RELOADED) study, we included 271 patients with and without acute HF. All patients presented to an emergency department with acute dyspnoea, had blood samples for IGFBP7 measurement, and detailed echocardiographic evaluation. Higher IGFBP7 concentrations were associated with numerous cardiac abnormalities, including increased left atrial volume index (LAVi; r = 0.49, P < 0.001), lower left ventricular ejection fraction (r = -0.27, P < 0.001), lower right ventricular fractional area change (r = -0.31, P < 0.001), and higher tissue Doppler E/e' ratio (r = 0.44, P < 0.001). In multivariable linear regression analyses, increased LAVi (P = 0.01), lower estimated glomerular filtration rate (P = 0.008), higher body mass index (P = 0.001), diabetes (P = 0.009), and higher concentrations of amino-terminal pro-B-type natriuretic peptide (NT-proBNP, P = 0.02) were independently associated with higher IGFBP7 concentrations regardless of other variables. Furthermore, IGFBP7 (odds ratio = 12.08, 95% confidence interval 2.42-60.15, P = 0.02) was found to be independently associated with the diagnosis of acute HF in the multivariable logistic regression analysis. CONCLUSIONS: Among acute dyspnoeic patients with and without acute HF, increased IGFBP7 concentrations are associated with a range of cardiac structure and function abnormalities. Independent association with increased LAVi suggests elevated left ventricular filling pressure is an important trigger for IGFBP7 expression and release. IGFBP7 may enhance the diagnosis of acute HF.

Necessity of hospitalization and stress testing in low risk chest pain patients.

BACKGROUND: Copeptin is a marker of endogenous stress including early myocardial infarction(MI) and has value in early rule out of MI when used with cardiac troponin I(cTnI). OBJECTIVES: The goal of this study was to demonstrate that patients with a normal electrocardiogram and cTnI<0.040µg/l and copeptin<14pmol/l at presentation and after 2 h may be candidates for early discharge with outpatient follow-up potentially including stress testing. METHODS: This study uses data from the CHOPIN trial which enrolled 2071 patients with acute chest pain. Of those, 475 patients with normal electrocardiogram and normal cTnI(<0.040µg/l) and copeptin<14pmol/l at presentation and after 2 h were considered "low risk" and selected for further analysis. RESULTS: None of the 475 "low risk" patients were diagnosed with MI during the 180day follow-up period (including presentation). The negative predictive value of this strategy was 100% (95% confidence interval(CI):99.2%-100.0%). Furthermore no one died during follow up. 287 (60.4%) patients in the low risk group were hospitalized. In the "low risk" group, the only difference in outcomes (MI, death, revascularization, cardiac rehospitalization) was those hospitalized underwent revascularization more often (6.3%[95%CI:3.8%-9.7%] versus 0.5%[95%CI:0.0%-2.9%], p=.002). The hospitalized patients were tested significantly more via stress testing or angiogram (68.6%[95%CI:62.9%-74.0%] vs 22.9%[95%CI:17.1%-29.6%], p<.001). Those tested had less cardiac rehospitalizations during follow-up (1.7% vs 5.1%, p=.040). CONCLUSIONS: In conclusion, patients with a normal electrocardiogram, troponin and copeptin at presentation and after 2 h are at low risk for MI and death over 180days. These low risk patients may be candidates for early outpatient testing and cardiology follow-up thereby reducing hospitalization.

Effectiveness of barcoding for reducing patient specimen and laboratory testing identification errors: a Laboratory Medicine Best Practices systematic review and meta-analysis.

OBJECTIVES: This is the first systematic review of the effectiveness of barcoding practices for reducing patient specimen and laboratory testing identification errors. DESIGN AND METHODS: The CDC-funded Laboratory Medicine Best Practices Initiative systematic review methods for quality improvement practices were used. RESULTS: A total of 17 observational studies reporting on barcoding systems are included in the body of evidence; 10 for patient specimens and 7 for point-of-care testing. All 17 studies favored barcoding, with meta-analysis mean odds ratios for barcoding systems of 4.39 (95% CI: 3.05-6.32) and for point-of-care testing of 5.93 (95% CI: 5.28-6.67). CONCLUSIONS: Barcoding is effective for reducing patient specimen and laboratory testing identification errors in diverse hospital settings and is recommended as an evidence-based "best practice." The overall strength of evidence rating is high and the effect size rating is substantial. Unpublished studies made an important contribution comprising almost half of the body of evidence.

Left ventricular ejection fraction assessment in older adults: an adjunct to natriuretic peptide testing to identify risk of new-onset heart failure and cardiovascular death?

OBJECTIVES: The goal of this paper was to determine whether assessment of left ventricular ejection fraction (LVEF) enhances prediction of new-onset heart failure (HF) and cardiovascular mortality over and above N-terminal pro-B-type natriuretic peptide (NT-proBNP) level in older adults. BACKGROUND: Elevated NT-proBNP levels are common in older adults and are associated with increased risk of HF. METHODS: NT-proBNP and LVEF were measured in 4,137 older adults free of HF. Repeat measures of NT-proBNP were performed 2 to 3 years later and echocardiography was repeated 5 years later (n = 2,375), with a median follow-up of 10.7 years. The addition of an abnormal (<55%) LVEF (n = 317 [7.7%]) to initially elevated or rising NT-proBNP levels was evaluated to determine risk of HF or cardiovascular mortality. Changes in NT-proBNP levels were also assessed for estimating the risk of conversion from a normal to abnormal LVEF. RESULTS: For participants with a low baseline NT-proBNP level (<190 pg/ml; n = 2,918), addition of an abnormal LVEF did not improve the estimation of risk of HF and identified a moderate increase in adjusted risk for cardiovascular mortality (hazard ratio: 1.69 [95% confidence interval: 1.22 to 2.31]). Among those whose NT-proBNP subsequently increased ≥25% to ≥190 pg/ml, an abnormal LVEF was likewise associated with an increased risk of cardiovascular mortality but not HF. Participants with an initially high NT-proBNP level (≥190 pg/ml) were at greater risk overall for both outcomes, and those with an abnormal LVEF were at the highest risk. However, an abnormal LVEF did not improve model classification or risk stratification for either endpoint when added to demographic factors and change in NT-proBNP. An initially elevated NT-proBNP or rising level was associated with an increased risk of developing an abnormal LVEF. CONCLUSIONS: Assessment of LVEF in HF-free older adults based on NT-proBNP levels should be considered on an individual basis, as such assessments do not routinely improve prognostication.

Dynamic cardiovascular risk assessment in elderly people. The role of repeated N-terminal pro-B-type natriuretic peptide testing.

OBJECTIVES: This study sought to determine whether serial measurement of N-terminal pro-B-type natriuretic peptide (NT-proBNP) in community-dwelling elderly people would provide additional prognostic information to that from traditional risk factors. BACKGROUND: Accurate cardiovascular risk stratification is challenging in elderly people. METHODS: NT-proBNP was measured at baseline and 2 to 3 years later in 2,975 community-dwelling older adults free of heart failure in the longitudinal CHS (Cardiovascular Health Study). This investigation examined the risk of new-onset heart failure (HF) and death from cardiovascular causes associated with baseline NT-proBNP and changes in NT-proBNP levels, adjusting for potential confounders. RESULTS: NT-proBNP levels in the highest quintile (>267.7 pg/ml) were independently associated with greater risks of HF (hazard ratio [HR]: 3.05; 95% confidence interval [CI]: 2.46 to 3.78) and cardiovascular death (HR: 3.02; 95% CI: 2.36 to 3.86) compared with the lowest quintile (<47.5 pg/ml). The inflection point for elevated risk occurred at NT-proBNP 190 pg/ml. Among participants with initially low NT-proBNP (<190 pg/ml), those who developed a >25% increase on follow-up to >190 pg/ml (21%) were at greater adjusted risk of HF (HR: 2.13; 95% CI: 1.68 to 2.71) and cardiovascular death (HR: 1.91; 95% CI: 1.43 to 2.53) compared with those with sustained low levels. Among participants with initially high NT-proBNP, those who developed a >25% increase (40%) were at higher risk of HF (HR: 2.06; 95% CI: 1.56 to 2.72) and cardiovascular death (HR: 1.88; 95% CI: 1.37 to 2.57), whereas those who developed a >25% decrease to