Qualitative assessment of SARS-CoV-2-specific antibody avidity by lateral flow immunochromatographic IgG/IgM antibody assay.

Knowledge of the precise timing of SARS-CoV-2 infection may be of clinical and epidemiological relevance. The presence of low-avidity IgGs has conventionally been considered an indicator of recent infection. Here, we carried out qualitative assessment of SARS-CoV-2-specific antibody avidity using an urea (6M) dissociation test performed on a lateral flow immunochromatographic IgG/IgM device. We included a total of 76 serum specimens collected from 57 COVID-19 patients, of which 39 tested positive for both IgG and IgM and 37 only for IgG. Sera losing IgG reactivity after urea treatment (n = 28) were drawn significantly earlier (P = .04) after onset of symptoms than those which preserved it (n = 48). This assay may be helpful to estimate the time of acquisition of infection in patients with mild to severe COVID-19.

Long-Term Potassium Monitoring and Dynamics in Heart Failure and Risk of Mortality.

BACKGROUND: The prognostic value of long-term potassium monitoring and dynamics in heart failure has not been characterized completely. We sought to determine the association between serum potassium values collected at follow-up with all-cause mortality in a prospective and consecutive cohort of patients discharged from a previous acute heart failure admission. METHODS: Serum potassium was measured at every physician-patient encounter, including hospital admissions and ambulatory settings. The multivariable-adjusted association of serum potassium with mortality was assessed by using comprehensive state-of-the-art regression methods that can accommodate time-dependent exposure modeling. RESULTS: The study sample included 2164 patients with a total of 16 116 potassium observations. Mean potassium at discharge was 4.3±0.48 mEq/L. Hypokalemia (<3.5 mEq/L), normokalemia (3.5-5.0 mEq/L), and hyperkalemia (>5 mEq/L) were observed at the index admission in 77 (3.6%), 1965 (90.8%), and 122 (5.6%) patients, respectively. At a median follow-up of 2.8 years (range, 0.03-12.8 years), 1090 patients died (50.4%). On a continuous scale, the multivariable-adjusted association of potassium values and mortality revealed a nonlinear association (U-shaped) with higher risk at both ends of its distribution (omnibus P=0.001). Likewise, the adjusted hazard ratios for hypokalemia and hyperkalemia, normokalemia as reference, were 2.35 (95% confidence interval, 1.40-3.93; P=0.001) and 1.55 (95% confidence interval, 1.11-2.16; P=0.011), respectively (omnibus P=0.0003). Furthermore, dynamic changes in potassium were independently associated with substantial differences in mortality risk. Potassium normalization was independently associated with lower mortality risk (P=0.001). CONCLUSIONS: Either modeled continuously or categorically, serum potassium levels during long-term monitoring were independently associated with mortality in patients with heart failure. Likewise, persistence of abnormal potassium levels was linked to a higher risk of death in comparison with patients who maintained or returned to normal values.

Hydrogen- and Methane-Based Breath Testing and Outcomes in Patients With Heart Failure.

BACKGROUND: Recent evidence endorses gut microbiota dysregulation in the pathophysiology of heart failure (HF). Small intestinal bacterial overgrowth (SIBO) might be present in HF and associated with poor clinical outcomes. Lactulose breath testing is a simple noninvasive test that has been advocated as a reliable indicator of SIBO. In patients with HF, we aimed to evaluate the association with clinical outcomes of the exhaled hydrogen (H2) and methane (CH4) concentrations through the lactulose breath test. METHODS AND RESULTS: We included 102 patients with HF in which lactulose SIBO breath tests were assessed. Cumulative gas was quantified by the area under the receiver operating characteristic curve of CH4 (AUC-CH4) and H2 (AUC-H2). Clinical end points included the composite of all-cause death with either all-cause or HF hospitalizations, recurrent all-cause hospitalizations, and recurrent HF hospitalizations. Medians (interquartile ranges) of AUC-H2 and AUC-CH4 were 1290 U (520-2430) and 985 U (450-2120), respectively. In multivariable analysis, AUC-H2 (per 1000 U) was associated with all-cause death/all-cause hospitalization (hazard ratio [HR] 1.21, 95% CI 1.04-1.40; P = .012), all-cause death/HF hospitalization (HR 1.20, 95% CI 1.03-1.40; P = .021), and an increase in the rate of recurrent all-cause (incidence rate ratio [IRR] 1.31, 95% CI 1.14-1.51; P < .001) and HF (IRR 1.41, 95% CI 1.15-1.72; P = .001) hospitalizations. AUC-CH4 was not associated with any of these end points. CONCLUSIONS: AUC-H2, a safe and noninvasive method for SIBO estimation, is associated with higher risk of long-term adverse clinical events in patients with HF. In contrast, AUC-CH4 did not show any prognostic value.

Urinary KIM-1, NGAL and L-FABP for the diagnosis of AKI in patients with acute coronary syndrome or heart failure undergoing coronary angiography.

Acute kidney injury (AKI) is a common complication after coronary angiography. Early biomarkers of this disease are needed since increase in serum creatinine levels is a late marker. To assess the usefulness of urinary kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL) and liver-type fatty acid-binding protein (uL-FABP) for early detection of AKI in these patients, comparing their performance with another group of cardiac surgery patients. Biomarkers were measured in 193 patients, 12 h after intervention. In the ROC analysis, AUC for KIM-1, NGAL and L-FABP was 0.713, 0.958 and 0.642, respectively, in the coronary angiography group, and 0.716, 0.916 and 0.743 in the cardiac surgery group. Urinary KIM-1 12 h after intervention is predictive of AKI in adult patients undergoing coronary angiography, but NGAL shows higher sensitivity and specificity. L-FABP provides inferior discrimination for AKI than KIM-1 or NGAL in contrast to its performance after cardiac surgery. This is the first study showing the predictive capacity of KIM-1 for AKI after coronary angiography. Further studies are still needed to answer relevant questions about the clinical utility of biomarkers for AKI in different clinical settings.

Lipoprotein(a) and Long-Term Recurrent Infarction After an Acute Myocardial Infarction.

Lipoprotein(a) (Lp[a]) is an emerging risk factor for incident ischemic heart disease. However, its role in risk stratification in in-hospital survivors to an index acute myocardial infarction (AMI) is scarcer, especially for predicting the risk of long-term recurrent AMI. We aimed to assess the relation between Lp(a) and very long-term recurrent AMI after an index episode of AMI. It is a retrospective analysis that included 1,223 consecutive patients with an AMI discharged from October 2000 to June 2003 in a single-teaching center. Lp(a) was assessed during index admission in all cases. The relation between Lp(a) at discharge and total recurrent AMI was evaluated through negative binomial regression. The mean age of the patients was 67.0 ± 12.3 years, 379 (31.0%) were women, and 394 (32.2%) were diabetic. The index event was more frequently non-ST-segment elevation myocardial infarction (66.0%). The median Lp(a) was 28.8 (11.8 to 63.4) mg/100 ml. During a median follow-up of 9.9 (4.6 to 15.5) years, 813 (66.6%) deaths and 1,205 AMI in 532 patients (43.5%) occurred. Lp(a) values were not associated with an increased risk of long-term all-cause mortality (p = 0.934). However, they were positively and nonlinearly associated with an increased risk of total long-term reinfarction (p = 0.016). In the subgroup analysis, there was no evidence of a differential effect for the most prevalent subgroups. In conclusion, after an AMI, elevated Lp(a) values assessed during hospitalization were associated with an increased risk of recurrent reinfarction in the very long term. Further prospective studies are warranted to evaluate their clinical implications.

Role of spot urinary sodium in outpatients with heart failure.

INTRODUCTION AND OBJECTIVES: Spot determination of urinary sodium (UNa+) has emerged as a useful tool for monitoring diuretic response in patients with acute heart failure (AHF). However, the evidence in outpatients is scarce. We aimed to examine the relationship between spot UNa+ levels and the risk of mortality and worsening heart failure (WHF) events in individuals with chronic HF. METHODS: This observational and ambispective study included 1145 outpatients with chronic HF followed in a single center specialized HF clinic. UNa+ assessment was carried out 1-5 days before each visit. The endpoints of the study were the association between UNa+ and risk of a) long-term death and b) AHF-hospitalization and total WHF events (including AHF-hospitalization, emergency department visits or parenteral loop-diuretic administration in HF clinic), assessed by multivariate Cox and negative binomial regressions. RESULTS: The mean ± standard deviation of age was 73 ± 11 years, 670 (58.5%) were men, 902 (78.8%) were on stable NYHA class II, and 595 (52%) had LFEF ≥ 50%. The median (interquartile range) UNa+ was 72 (51-94) mmol/L. Over a median follow-up of 2.63 (1.70-3.36) years, there were 293 (25.6%) deaths and 382 WHF events (244 AHF-admissions) in 233 (20.3%) patients. After multivariate adjustment, baseline UNa+ was inverse and linearly associated with the risk of total WHF (IRR, 1.07; 95%CI, 1.02-1.12; P = .007) and AHF-admissions (IRR, 1.08; 95%CI, 1.02-1.14; P = .012) and borderline associated with all-cause mortality (HR, 1.04; 95%CI, 0.99-1.09; P = .068). CONCLUSIONS: In outpatients with chronic HF, lower UNa+ was associated with a higher risk of recurrent WHF events.

Procalcitonin and C-reactive protein as early predictors of anastomotic leak in colorectal surgery: a prospective observational study.

BACKGROUND: Although the early diagnosis of anastomotic leak is a key point in reducing its clinical consequences, in daily practice, anastomotic leak diagnosis is often late. OBJECTIVE: The aim of this study was to determine whether procalcitonin and C-reactive protein are good predictors of anastomotic leak in colorectal surgery. DESIGN: This is a prospective observational study. SETTINGS: This study was conducted by a specialized colorectal multidisciplinary team of a tertiary teaching hospital. PATIENTS: A series of 205 consecutive patients who underwent elective colorectal surgery in a specialized unit was prospectively analyzed. The following data were collected: demographic, surgical, ASA class, POSSUM, and morbidity. During the first 5 postoperative days, procalcitonin, C-reactive protein, leukocytes, platelets, and vital signs were evaluated daily. INTERVENTIONS: Daily assessment of clinical variable and serological data were conducted in the first 5 postoperative days. MAIN OUTCOME MEASURES: The primary outcome measure was the area under the curve at receiving operating characteristic curve analysis of the different variables in relation to the anastomotic leak. RESULTS: Anastomotic leak was detected in 17 (8.3%) patients; 11(5.4%) of the patients had a major anastomotic leak (need for drainage or reoperation). None of the variables evaluated were shown to be reliable in the early detection of anastomotic leak, considering both minor and major (maximum area under the curve <0.80). In contrast, when considering only major anastomotic leaks, procalcitonin and C-reactive protein were reliable predictors on postoperative days 3 to 5 (p < 0.0001, area under the curve >0.80). The best combination was procalcitonin at postoperative day 5 (area under the curve = 0.86), with a cutoff of 0.31 ng/mL, resulting in a 100% sensitivity, 72% specificity, 100% negative predictive value, and 17% positive predictive value. LIMITATIONS: Only symptomatic patients were investigated to rule out anastomotic leakage. CONCLUSIONS: Procalcitonin and C-reactive protein are both reliable predictors of major anastomotic leak after colorectal resection, although procalcitonin is more accurate. Raised procalcitonin and C-reactive protein serum concentration on postoperative days 3 to 5 renders necessary a careful evaluation of the patient before discharge.

Predictive Biochemical Model of Frailty and Mortality After Acute Myocardial Infarction.

Frailty, characterized by reduced resistance to stressors, is associated with adverse outcomes in patients with myocardial infarction. The Fried score is commonly used to assess frailty but has several limitations. This study aimed to evaluate the relation between frailty and blood biomarkers and their predictive value for long-term mortality using a biochemical model. A total of 2 cohorts of elderly patients (>65 years old) hospitalized for acute coronary syndrome were included. Geriatric assessments and several blood biomarkers were measured. The predictive models for frailty were developed using logistic regression. The survival models were also developed using Cox regression. Among 466 patients, 9 biomarkers were significantly associated with frailty. Between these biomarkers, white blood cells count, hemoglobin, and fibrinogen showed the highest predictive power. Model 1, without growth differentiation factor 15 (GDF-15), showed a better accuracy in predicting the mortality than the Fried score. Model 2, with GDF-15, had a stronger correlation with frailty but had a lower predictive power for survival. Frailty is associated with dysregulation in the physiological systems and several biomarkers were linked to this fact in our study. However, the inclusion of GDF-15 did not significantly improve the model's predictive ability. Frailty assessment using blood biomarkers can provide valuable prognostic information in elderly patients with acute coronary syndrome.

Early glomerular filtration rates changes and risk of mortality in acute heart failure. The modifying role of admission renal function and decongestion.

BACKGROUND: The pathophysiology of changes in estimated glomerular filtration rate (eGFR) in acute heart failure (AHF) is complex and multifactorial. We evaluated the associated mortality risk of early changes in eGFR across baseline renal function on admission and early changes in natriuretic peptides in patients admitted with AHF. METHODS: We retrospectively evaluated 2,070 patients admitted with AHF. Renal dysfunction on admission was defined as eGFR<60 ml/min/1.73m2 and successful decongestion as NT-proBNP decreased >30% from baseline. We assessed the mortality risk associated with eGFR changes from baseline at 48-72 h after admission (ΔeGFR%) according to baseline renal function, and NT-proBNP changes at 48-72 h through Cox regression analyses. RESULTS: The mean age was 74.4 ± 11.2 years, and 930 (44.9%) were women. The proportion of admission eGFR<60 ml/min/1.73m2 and 48-72 h changes in NT-proBNP>30% were 50.5% and 32.8%, respectively. At a median follow-up of 1.75 years, 928 deaths were registered. In the whole sample, changes in renal function were not associated with mortality (p = 0.208). The adjusted analysis revealed that the risk of mortality related to ΔeGFR% was heterogeneous across baseline renal function and changes in NT-proBNP (p-value for interaction=0.003). ΔeGFR% was not associated with mortality in patients with baseline eGFR≥60 ml/min/1.73m2. In those with eGFR<60 ml/min/1.73m2, a decrease in eGFR was associated with higher mortality, particularly in those with a reduction in NT-proBNP<30%. CONCLUSION: In patients with AHF, early ΔeGFR% was associated with the risk of long-term mortality only in patients with renal dysfunction on admission and no early decline in NT-proBNP.

An update on utilising brain natriuretic peptide for risk stratification, monitoring and guiding therapy in heart failure.

INTRODUCTION: Heart failure (HF) is a dominant health problem with an overall poor prognosis. Natriuretic peptides (NPs) are upregulated in HF as a compensatory mechanism. They have been extensively used for diagnosis and risk stratification. AREAS COVERED: This review addresses the history and physiology of NPs in order to understand their current role in clinical practice. It further provides a detailed and updated narrative review on the utility of those biomarkers for risk stratification, monitoring, and guiding therapy in HF. EXPERT OPINION: NPs show excellent predictive ability in heart failure patients, both in acute and chronic settings. Understanding their pathophysiology and their modifications in specific situations is key for an adequate interpretation in specific clinical scenarios in which their prognostic value may be weaker or less well evaluated. To better promote risk stratification in HF, NPs should be integrated with other predictive tools to develop multiparametric risk models. Both inequalities of access to NPs and evidence caveats and limitations will need to be addressed by future research in the coming years.

Usefulness of high-sensitivity troponin T for the evaluation of patients with acute chest pain and no or minimal myocardial damage.

BACKGROUND: Although high-sensitivity troponins allow early diagnosis of acute myocardial infarction, their role for identification of acute coronary syndrome in patients with normal conventional troponin remains unclear. METHODS AND RESULTS: A total of 446 patients presenting to the emergency department with chest pain and normal troponin (common practice assays) in 2 serial samples were included. Both samples were also centrally analyzed for high-sensitivity troponin T (hs-TnT) (Roche Diagnostics, Basel, Switzerland). Detection (>3 ng/L) and 99th percentile (≥ 14 ng/L) cutoffs of the maximum hs-TnT levels (hs-TnTmax) were considered. The end points were acute coronary syndrome diagnosis and the composite of in-hospital revascularization or 30-day cardiac events. RESULTS: Acute coronary syndrome was adjudicated to 84 patients (19%), and 62 (14%) had the composite end point. In univariate setting, hs-TnTmax >3 ng/L exhibited high sensitivity (87% and 92%, respectively) and negative predictive value (93% and 97%) for both end points, whereas hs-TnTmax ≥ 14 ng/L provided high specificity (90% and 89%), although low positive predictive values (40% and 33%). After adjusting for clinical (pain characteristics and risk factors) and electrocardiographic data, there was a stepped increase of risk across hs-TnTmax categories (≤ 3, >3 but <14, and ≥ 14 ng/L) for both end points; however, the discriminative capacity added was marginal (integrated discrimination improvement of 2.6% and 3.5%, respectively). CONCLUSIONS: Clinical and electrocardiographic data remain the most important tools for the evaluation of patients with chest pain and with no or minimal myocardial damage. The main contribution of hs-TnT is the high negative predictive value of undetectable levels (≤ 3 ng/L).

Cardioprotective effect of sevoflurane and propofol during anaesthesia and the postoperative period in coronary bypass graft surgery: a double-blind randomised study.

CONTEXT: Volatile anaesthetics may have direct cardioprotective properties due to effects similar to ischaemic preconditioning and postconditioning. Clinical results in cardiac surgery patients are controversial and may be related to the timing of administration of anaesthetics intraoperatively. OBJECTIVE: We hypothesised that the cardioprotective effect of sevoflurane in coronary bypass graft surgical patients would be greater if administration during anaesthesia continued in the ICU for at least 4 h postoperatively until weaning from mechanical ventilation. DESIGN: Double-blind, double-dummy, prospective, randomised and controlled clinical trial. SETTING: In a single centre between June 2006 and June 2007. PATIENTS: Seventy-five adult patients were assigned randomly to receive anaesthesia and postoperative sedation either with propofol (control, n = 37) or sevoflurane (n = 36). INTERVENTIONS: Myocardial biomarkers were measured before surgery, at the time of admission to the intensive care unit and at 6, 24, 48 and 72 h. The need for inotropic support, and lengths of stay in the intensive care unit and hospital were also recorded. MAIN OUTCOME MEASURES: Elevation of myocardial biomarkers was the primary endpoint. The secondary endpoints were haemodynamic events and lengths of stay in the intensive care unit and hospital. RESULTS: Necrosis biomarkers increased significantly in the postoperative period in both groups with no significant differences at any time. Inotropic support was needed in 72.7 and 54.3% of patients in the propofol and sevoflurane groups, respectively (P = 0.086). There were no significant differences in haemodynamic variables, incidence of arrhythmias, myocardial ischaemia or and lengths of stay in the ICU and hospital between the two groups. CONCLUSION: In patients undergoing coronary bypass graft surgery, continuous administration of sevoflurane as a sedative in the ICU for at least 4 h postoperatively did not yield significant improvements in the extent and time course of myocardial damage biomarkers compared to propofol.

Optimal carbohydrate antigen 125 cutpoint for identifying low-risk patients after admission for acute heart failure.

INTRODUCTION AND OBJECTIVES: Carbohydrate antigen 125 (CA125) has been shown to be useful for risk stratification in patients admitted with acute heart failure (AHF). We sought to determine a CA125 cutpoint for identifying patients at low risk of 1-month death or the composite of death/HF readmission following admission for AHF. METHODS: The derivation cohort included 3231 consecutive patients with AHF. CA125 cutoff values with 90% negative predictive value (NPV) and sensitivity up to 85% were identified. The adequacy of these cutpoints and the risk of 1-month death/HF readmission was then tested using the Royston-Parmar method. The best cutpoint was selected and externally validated in a cohort of patients hospitalized from BIOSTAT-CHF (n=1583). RESULTS: In the derivation cohort, the median [IQR] CA125 was 57 [25.3-157] U/mL. The optimal cutoff value was <23 U/mL (21.5% of patients), with NPVs of 99.3% and 94.1% for death and the composite endpoint, respectively. On multivariate survival analyses, CA125 <23 U/mL was independently associated with a lower risk of death (HR, 0.20; 95%CI, 0.08-0.50; P <.001), and the combined endpoint (HR, 0.63; 95%CI, 950.45-0.90; P=.009). The ability of this cutpoint to discriminate patients at a low 1-month risk was confirmed in the validation cohort (NPVs of 98.6% and 96.6% for death and the composite endpoint). The predicted ability of this cutoff remained significant at 6 months of follow-up. CONCLUSIONS: In patients admitted with AHF, CA125 <23 U/mL identified a subgroup at low risk of short-term adverse events, a population that may not require intense postdischarge monitoring.

Improvement in risk stratification with the combination of the tumour marker antigen carbohydrate 125 and brain natriuretic peptide in patients with acute heart failure.

AIM: Elevated brain natriuretic peptide (BNP) and tumour marker antigen carbohydrate 125 (CA125) levels have shown to be associated with higher risk for adverse outcomes in patients with acute heart failure (AHF). Nevertheless, no attempt has been made to explore the utility of combining these two biomarkers. We sought to assess whether CA125 adds prognostic value to BNP in predicting 6-month all-cause mortality in patients with AHF. METHODS AND RESULTS: We analysed 1111 consecutive patients admitted for AHF. Antigen carbohydrate 125 (U/mL) and BNP (pg/mL) were measured at a median of 72 +/- 12 h after instauration of treatment. Antigen carbohydrate 125 and BNP were dichotomized based on proposed prognostic cutpoints, and a variable with four categories was formed (BNP-CA125): C1 = BNP < 350 and CA125 < 60 (n = 394); C2 = BNP > or = 350 and CA125 < 60 (n = 165); C3 = BNP < 350 and CA125 > or = 60 (n = 331); and C4 = BNP > or = 350 and CA125 > or = 60 (n = 221). The independent association between BNP-CA125 and mortality was assessed with the Cox regression analysis, and their added predictive ability tested by the integrated discrimination improvement (IDI) index. At 6 months, 181 deaths (16.3%) were identified. The cumulative rate of mortality was lower for patients in C1 (7.8%), intermediate for C2 and C3 (17.8% and 16.9%, respectively), and higher for C4 (37.2%), and P-value for trend <0.001. After adjusting for established risk factors, the highest risk was observed when both biomarkers were elevated (C4 vs. C1: HR = 4.05, 95% CI = 2.54-6.45; P < 0.001) and intermediate when only one of them was elevated: (C2 vs. C1: HR = 1.71, 95% CI = 1.00-2.93; P = 0.050) and (C3 vs. C1: HR = 2.10, 95% CI = 1.30-3.39; P = 0.002). Moreover, when CA125 was added to the clinical model + BNP, a 10.4% (P < 0.0001) improvement in the IDI (on the relative scale) was found. CONCLUSION: In patients admitted with AHF, CA125 added prognostic value beyond the information provided by BNP, and thus, their combination enables better 6-month risk stratification.

Evaluation of PSA testing by general practitioners: regional study in the autonomic Community of Valencia.

OBJECTIVES: The aim of the study is to compare the use of PSA testing among general practitioners (GPs). METHODS: The number of PSA tests ordered by general practitioners in the years 2008-2009 was examined in a cross-sectional study of nine health districts of Spain. The percentage of PSA ordered to men younger than 50 (PSA<50/PSAtotal) and 40 years (PSA<40/PSAtotal) was calculated. The percentage of men over 50 years who were attended was also calculated and this data was compared with the number of PSA ordered to this population. For two of the departments, these data were also compared between GPs and urologists. RESULTS: PSA testing in 2009 is higher than 2008 in seven health districts. PSA testing in men younger than 50 years was increased along the period of the study and in men younger than 40 years remained steady. The differences between the values of the indicators for urologists and GPs are significant. CONCLUSIONS: The number of PSA tests and the percentage performed to men younger 50 years has been increasing and the variability is high. These data are suggestive for interventions focused on PSA testing and prostate cancer screening in primary care settings.

Clinical History and Detectable Troponin Concentrations below the 99th Percentile for Risk Stratification of Patients with Chest Pain and First Normal Troponin.

Decision-making is challenging in patients with chest pain and normal high-sensitivity cardiac troponin T (hs-cTnT; <99th percentile; <14 ng/L) at hospital arrival. Most of these patients might be discharged early. We investigated clinical data and hs-cTnT concentrations for risk stratification. This is a retrospective study including 4476 consecutive patients presenting to the emergency department with chest pain and first normal hs-cTnT. The primary endpoint was one-year death or acute myocardial infarction, and the secondary endpoint added urgent revascularization. The number of primary and secondary endpoints was 173 (3.9%) and 252 (5.6%). Mean hs-cTnT concentrations were 6.9 ± 2.5 ng/L. Undetectable (<5 ng/L) hs-cTnT (n = 1847, 41%) had optimal negative predictive value (99.1%) but suboptimal sensitivity (90.2%) and discrimination accuracy (AUC = 0.664) for the primary endpoint. Multivariable analysis was used to identify the predictive clinical variables. The clinical model showed good discrimination accuracy (AUC = 0.810). The addition of undetectable hs-cTnT (≥ or <5 ng/L; HR, hazard ratio = 3.80; 95% CI, confidence interval 2.27-6.35; p = 0.00001) outperformed the clinical model alone (AUC = 0.836, p = 0.002 compared to the clinical model). Measurable hs-cTnT concentrations (between detection limit and 99th percentile; per 0.1 ng/L, HR = 1.13; CI 1.06-1.20; p = 0.0001) provided further predictive information (AUC = 0.844; p = 0.05 compared to the clinical plus undetectable hs-cTnT model). The results were reproducible for the secondary endpoint and 30-day events. Clinical assessment, undetectable hs-cTnT and measurable hs-cTnT concentrations must be considered for decision-making after a single negative hs-cTnT result in patients presenting to the emergency department with acute chest pain.

Randomized comparison between clinical evaluation plus N-terminal pro-B-type natriuretic peptide versus exercise testing for decision making in acute chest pain of uncertain origin.

BACKGROUND: Exercise testing constitutes the usual tool for decision making in chest pain units. This policy implies logistical constrains. Our aim was to evaluate a new strategy, combining a clinical risk score and N-terminal pro-B-type natriuretic peptide (NT-proBNP), in patients presenting to the emergency department with chest pain, without ischemic electrocardiogram changes or troponin elevation. METHODS: A total of 320 patients were randomized to either usual management, involving exercise testing, or a new strategy combining a clinical risk score and NT-proBNP without exercise testing. In the usual management, discharge decision was guided by the result of exercise test. In the new strategy, those patients with low clinical risk score and NT-proBNP were directly discharged. The primary outcome was hospitalization at the index episode. Secondary outcomes were cardiac events at 1 year. RESULTS: A total of 110 patients (69%) were hospitalized using usual management in comparison with 90 (56%) in the new strategy (P = .03). There were no differences in death or myocardial infarction (n = 11, 6.9% vs n = 6, 3.8%, P = .3) or cardiac events (n = 38, 24% vs n = 28, 18%, P = .2). Revascularizations at the index episode were more frequent under usual management (18% vs 8%, P = .01), although the new strategy was associated with higher rate of planned postdischarge revascularizations (0.6% vs 5%, P = .04). CONCLUSIONS: A strategy combining clinical history and NT-proBNP is simpler and reduced initial emergency hospitalizations in patients with chest pain, in comparison with the usual strategy involving exercise testing. Larger studies to assess its impact on long-term hard end points are needed.

Undetectable high-sensitivity troponin in combination with clinical assessment for risk stratification of patients with chest pain and normal troponin at hospital arrival.

BACKGROUND: Undetectable high-sensitivity cardiac troponin (hs-cTn) in a single determination upon admission may rule out acute coronary syndrome. We investigated undetectable hs-cTnT (

Similar Clinical Course and Significance of Circulating Innate and Adaptive Immune Cell Counts in STEMI and COVID-19.

This study aimed to assess the time course of circulating neutrophil and lymphocyte counts and their ratio (NLR) in ST-segment elevation myocardial infarction (STEMI) and coronavirus disease (COVID)-19 and explore their associations with clinical events and structural damage. Circulating neutrophil, lymphocyte and NLR were sequentially measured in 659 patients admitted for STEMI and in 103 COVID-19 patients. The dynamics detected in STEMI (within a few hours) were replicated in COVID-19 (within a few days). In both entities patients with events and with severe structural damage displayed higher neutrophil and lower lymphocyte counts. In both scenarios, higher maximum neutrophil and lower minimum lymphocyte counts were associated with more events and more severe organ damage. NLR was higher in STEMI and COVID-19 patients with the worst clinical and structural outcomes. A canonical deregulation of the immune response occurs in STEMI and COVID-19 patients. Boosted circulating innate (neutrophilia) and depressed circulating adaptive immunity (lymphopenia) is associated with more events and severe organ damage. A greater understanding of these critical illnesses is pivotal to explore novel alternative therapies.

CA125-Guided Diuretic Treatment Versus Usual Care in Patients With Acute Heart Failure and Renal Dysfunction.

BACKGROUND: The optimal diuretic treatment strategy for patients with acute heart failure and renal dysfunction remains unclear. Plasma carbohydrate antigen 125 (CA125) is a surrogate of fluid overload and a potentially valuable tool for guiding decongestion therapy. The aim of this study was to determine if a CA125-guided diuretic strategy is superior to usual care in terms of short-term renal function in patients with acute heart failure and renal dysfunction at presentation. METHODS: This multicenter, open-label study randomized 160 patients with acute heart failure and renal dysfunction into 2 groups (1:1). Loop diuretics doses were established according to CA125 levels in the CA125-guided group (n = 79) and in clinical evaluation in the usual-care group (n = 81). Changes in estimated glomerular filtration rate (eGFR) at 72 and 24 hours were the co-primary endpoints, respectively. RESULTS: The mean age was 78 ± 8 years, the median amino-terminal pro-brain natriuretic peptide was 7765 pg/mL, and the mean eGFR was 33.7 ± 11.3 mL/min/1.73m2. Over 72 hours, the CA125-guided group received higher furosemide equivalent dose compared to usual care (P = 0.011), which translated into higher urine volume (P = 0.042). Moreover, patients in the active arm with CA125 >35 U/mL received the highest furosemide equivalent dose (P <0.001) and had higher diuresis (P = 0.013). At 72 hours, eGFR (mL/min/1.73m2) significantly improved in the CA125-guided group (37.5 vs 34.8, P = 0.036), with no significant changes at 24 hours (35.8 vs 39.5, P = 0.391). CONCLUSION: A CA125-guided diuretic strategy significantly improved eGFR and other renal function parameters at 72 hours in patients with acute heart failure and renal dysfunction.