Baseline NT-ProBNP level predicts success of cardioversion of atrial fibrillation with flecainide

BackgroundPatients with acute-onset symptomatic atrial fibrillation (AF) can be treated with flecainide. However, flecainide may induce arrhythmias and/or exaggerate heart failure. Therefore, validated markers to predict the efficacy of flecainide and prevent adverse effects are required. We hypothesised that lower NT-proBNP plasma levels correlate with higher success rates of cardioversion with flecainide in patients with AF.MethodsIn this prospective single-centre study, we included 112 subsequent patients with acute-onset (< 24 h) symptomatic AF. Patients with symptoms of heart failure and ECG signs of ischaemia were excluded. Baseline laboratory measurements, including NT-proBNP, were done. Echocardiograms were performed ~ 2 weeks after restoration of SR.ResultsCardioversion with flecainide was successful in 91 patients (87 %). NT-proBNP was lower in patients with successful cardioversion (P < 0.001). Logistic regression indicated NT-proBNP as an independent predictor of successful cardioversion. A cut-off NT-proBNP value of 1550 pg/ml provided optimal test accuracy to predict successful cardioversion.ConclusionIn patients with < 24 h of symptomatic AF, NT-proBNP levels up to 1550 pg/ml correlate with high success rates (94 %) of cardioversion with flecainide. Conversely, NT-proBNP higher than 1550 pg/ml correlates with poor success rates (36 %). Further research is needed to validate the predictive value of NT-proBNP for successful cardioversion with flecainide.     

Aortic valve implantation-induced conduction block as a framework towards a uniform electrocardiographic definition of left bundle branch block

IntroductionNew-onset left bundle branch block (LBBB) following transcatheter or surgical aortic valve replacement (LBBB_AVI) implies a proximal pathogenesis of LBBB. This study compares electrocardiographic characteristics and concordance with LBBB definitions between LBBB_AVI and non-procedure-induced LBBB controls (LBBB_control).MethodsAll LBBB_AVI patients at Ghent University Hospital between 2013 and 2019 were enrolled in the study. LBBB_AVI patients were matched for age, sex, ischaemic heart disease and ejection fraction to LBBB_control patients in a 1:2 ratio. For inclusion, a non-strict LBBB definition was used (QRS duration ≥ 120 ms, QS or rS in V1, absence of Q waves in V5-6). Electrocardiograms were digitally analysed and classified according to three LBBB definitions: European Society of Cardiology (ESC), Strauss and American Heart Association (AHA).ResultsA total of 177 patients (59 LBBB_AVI and 118 LBBB_control) were enrolled in the study. LBBB_AVI patients had more lateral QRS notching/slurring (100% vs 85%, p = 0.001), included a higher percentage with a QRS duration ≥ 130 ms (98% vs 86%, p = 0.007) and had a less leftward oriented QRS axis (−15° vs −30°, p = 0.013) compared to the LBBB_control group. ESC and Strauss criteria were fulfilled in 100% and 95% of LBBB_AVI patients, respectively, but only 18% met the AHA criteria. In LBBB_control patients, concordance with LBBB definitions was lower than in the LBBB_AVI group: ESC 85% (p = 0.001), Strauss 68% (p < 0.001) and AHA 7% (p = 0.035). No differences in electrocardiographic characterisation or concordance with LBBB definitions were observed between LBBB_AVI and LBBB_control patients with lateral QRS notching/slurring.ConclusionNon-uniformity exists among current LBBB definitions concerning the detection of proximal LBBB. LBBB_AVI may provide a framework for more consensus on defining proximal LBBB.Supplementary InformationThe online version of this article (10.1007/s12471-021-01565-8) contains supplementary material, which is available to authorized users.     

Evaluation of Parasiticide Treatment with Benznidazol in the Electrocardiographic,Clinical, and Serological Evolution of Chagas Disease

IntroductionChagas disease is one of the most important endemic parasitic diseases in Latin America. In its chronic phase, progression to cardiomyopathy has high morbidity and mortality. The persistence of a normal electrocardiogram (ECG) provides a similar prognosis to that of a non-diseased population. Benznidazole (BNZ) is the only drug with trypanocidal action available in Brazil.Materials/Methods/ResultsA group of 310 patients with chronic Chagas disease who had normal ECGs at the first medical visit performed before 2002 were included. There were 263 patients treated with BNZ and 47 untreated. The follow-up period was 19.59 years. Univariate analyses showed that those treated were younger and predominantly male. As many as 79.08% of those treated and 46.81% of those untreated continued with normal electrocardiograms (p <0.0001). The occurrence of electrocardiographic abnormalities and relevant clinical events (heart failure, stroke, total mortality, and cardiovascular death) was less prevalent in treated patients (p <0.001, p: 0.022, p: 0.047 respectively). In multivariate analyses, the parasiticide treatment was an independent variable for persistence of a normal ECG pattern, which was an independent variable in the prevention of significant clinical events. The immunofluorescence titers decreased with the parasitological treatment. However, the small number of tests in untreated patients did not allow the correlation of the decrease of these titers with electrocardiographic alterations.ConclusionThese data suggest that treatment with benznidazole prevents the occurrence of electrocardiographic alterations. On the other hand, patients who develop ECG abnormalities present with more significant clinical events.     

Evaluation of the Accuracy of Anthropometric Clinical Indicators of Visceral Fat in Adults and Elderly

BackgroundVisceral obesity is associated with higher occurrence of cardiovascular events. There are few studies about the accuracy of anthropometric clinical indicators, using Computed Tomography (CT) as the gold standard. We aimed to determine the accuracy of anthropometric clinical indicators for discrimination of visceral obesity.MethodsCross-sectional study with 191 adults and elderly of both sexes. Variables: area of visceral adipose tissue (VAT) identified by CT, Waist-to-Height Ratio (WHtR), Conicity index (C index), Lipid Accumulation Product (LAP) and Visceral Adiposity Index (VAI). ROC analyzes.ResultsThere were a strong correlation between adiposity indicators and VAT area. Higher accuracy of C index and WHtR (AUC≥0.81) than the LAP and the VAI was observed. The higher AUC of LAP and VAI were observed among elderly with areas of 0.88 (CI: 0.766–0.944) and 0.83 (CI: 0.705–0.955) in men and 0.80 (CI: 0.672–0.930) and 0.71 (CI: 0.566–0.856) in women, respectively. The cutoffs of C index were 1.30 in elderly, in both sexes, with sensitivity ≥92%, the LAP ranged from 26.4 to 37.4 in men and from 40.6 to 44.0 in women and the VAI was 1.24 to 1.45 (sens≥76.9%) in men and 1.46 to 1.84 in women.ConclusionBoth the anthropometric indicators, C Index and WHtR, as well as LAP and VAI had high accuracy in visceral obesity discrimination. So, they are effective in cardiovascular risk assessment and in the follow-up for individual and collective clinical practice.     

Chagas disease is not associated with diabetes,metabolic syndrome,insulin resistance and beta cell dysfunction at baseline of Brazilian Longitudinal Study of Adult Health (ELSA-Brasil)

Chagas disease (ChD) affects millions of people worldwide, being endemic in Latin America and emerging in the United States and Europe. Classically described as targeting the heart and gastrointestinal tract, Trypanosoma cruzi parasitism leads to structural and pro-inflammatory changes in the adipose tissue and pancreas. The effects of these changes on insulin resistance (IR), beta cell dysfunction, diabetes mellitus (DM),and metabolic syndrome (MS) are unclear. We aim to evaluate the association of ChD with DM, IR, beta cell dysfunction and MS in the baseline of multi-centric cohort study ‘Brazilian Longitudinal Study of Adult Health’ (ELSA-Brasil). This cross-sectional analysis included 14,922 (98%) participants of ELSA-Brasil at baseline. To investigate the associations of ChD with DM, IR (assessed by HOMA-IR) and beta cell dysfunction (assessed by HOMA beta), and MS we fitted logistic regression models including socio-demographic and anthropometric variables, health-related conditions and laboratory results. ChD, defined by positive serology, was prevalent in 1.9% (n = 283) of the sample, 17.3% (n = 49) of whom had cardiomyopathy. DM prevalence was 17.25% (n = 2574) and was not different among those with and without ChD (20.5% vs 17.2%; p = 0.28). Fasting and 2 h-blood glucose after a 75 g anhydrous glucose were slightly higher among participants positive for ChD, when compared with those with negative serology (102 mg/dL versus 100 mg/dL, respectively; and 127 mg/dL versus 124 mg/dL, respectively), only in univariate analysis. There was no significant association between these variables and ChD after adjustments. In addition, there was no significant association between DM, IR, beta cell dysfunction or MS and ChD (without and with cardiomyopathy). Our results showed that ChD, regardless of the presence of cardiomyopathy, is not associated with DM, IR, beta cell dysfunction or MS. These findings suggest the parasitism of the adipose tissue and pancreas in Chagas disease do not translate into clinically relevant glucose abnormalities.     

Human Papillomavirus Vaccine Uptake among Individuals with Systemic Inflammatory Diseases

ObjectivesThe human papillomavirus (HPV) vaccine is safe and efficacious in patients with systemic inflammatory diseases (SID) who have higher rates of persistent HPV infection. We compared HPV vaccine uptake among SID and non-SID patients.MethodsUsing a U.S. insurance claims database (2006–2012), we identified individuals 9–26 years with ≥2 SID diagnosis codes ≥7 days apart with ≥12 months of continuous enrollment prior to the second code (index date). We matched SID patients by age, sex and index date to randomly selected non-SID subjects and selected those with ≥24 months of post-index date continuous follow-up. We also identified a non-SID subcohort with ≥1 diagnosis code for asthma. We defined initiation as ≥1 HPV vaccination claim after 2007, and completion as 3 claims. We used multivariable logistic regression to assess uptake in females 11–26 years comparing SID, non-SID and asthma cohorts, adjusting for demographics, region, comorbidities, and healthcare utilization.ResultsWe identified 5,642 patients 9–26 years with SID and 20,643 without. The mean age was 18.1 years (SD 4.9). We identified 1,083 patients with asthma; the mean age was 17.2 (SD 5.1). Among females, 20.6% with SID, 23.1% without SID and 22.9% with asthma, received ≥1 HPV vaccine. In our adjusted models, the odds of receipt of ≥1 vaccine was 0.87 times lower in SID (95% CI 0.77–0.98) compared to non-SID and did not differ for 3 vaccines (OR 1.03, 95% CI 0.83–1.26). The odds of initiation and completion were not statistically different between SID and non-SID asthma cohorts.ConclusionsIn this nationwide cohort, HPV vaccine uptake was extremely low. Despite the heightened risk of persistent HPV infection among those with SID, no increase in HPV vaccine uptake was observed. Public health efforts to promote HPV vaccination overall are needed, and may be particularly beneficial for those at higher risk.     

NT-ProBNP Levels in Saliva and Its Clinical Relevance to Heart Failure

Background

Current blood based diagnostic assays to detect heart failure (HF) have large intra-individual and inter-individual variations which have made it difficult to determine whether the changes in the analyte levels reflect an actual change in disease activity. Human saliva mirrors the body’s health and well being and ∼20% of proteins that are present in blood are also found in saliva. Saliva has numerous advantages over blood as a diagnostic fluid which allows for a non-invasive, simple, and safe sample collection. The aim of our study was to develop an immunoassay to detect NT-proBNP in saliva and to determine if there is a correlation with blood levels.

Methods

Saliva samples were collected from healthy volunteers (n = 40) who had no underlying heart conditions and HF patients (n = 45) at rest. Samples were stored at −80°C until analysis. A customised homogeneous sandwich AlphaLISA^(R) immunoassay was used to quantify NT-proBNP levels in saliva.

Results

Our NT-proBNP immunoassay was validated against a commercial Roche assay on plasma samples collected from HF patients (n = 37) and the correlation was r² = 0.78 (p<0.01, y = 1.705× +1910.8). The median salivary NT-proBNP levels in the healthy and HF participants were <16 pg/mL and 76.8 pg/mL, respectively. The salivary NT-proBNP immunoassay showed a clinical sensitivity of 82.2% and specificity of 100%, positive predictive value of 100% and negative predictive value of 83.3%, with an overall diagnostic accuracy of 90.6%.

Conclusion

We have firstly demonstrated that NT-proBNP can be detected in saliva and that the levels were higher in heart failure patients compared with healthy control subjects. Further studies will be needed to demonstrate the clinical relevance of salivary NT-proBNP in unselected, previously undiagnosed populations.     

Prediction of Perioperative Cardiac Events through Preoperative NT-pro-BNP and cTnI after Emergent Non-Cardiac Surgery in Elderly Patients

Objectives

Clinical risk stratification has an important function in preoperative evaluation of patients at risk for cardiac events prior to non-cardiac surgery. The aim of this study was to determine whether the combined measurement of pre-operative N-terminal pro-brain natriuretic peptide (NT-pro-BNP) and cardiac troponin I (cTnI) could provide useful prognostic information about postoperative major adverse cardiac events (MACE) within 30 days in patients aged over 60 years undergoing emergent non-cardiac surgery.

Methods

The study group comprised 2519 patients aged over 60 years that were undergoing emergent non-cardiac surgery between December 2007 and December 2013. NT-pro-BNP and cTnI were measured during hospital admission. The patients were monitored for MACE (cardiac death, non-fatal myocardial infarction, or cardiac arrest) during the 30-day postoperative follow-up period.

Results

MACE occurred in 251 patients (10.0%). Preoperative NT-pro-BNP and cTNI level were significantly higher in the individuals that experienced MACE than in those who did not (P < 0.001). The confounding factors of age, sex, co-morbidities and preoperative medications were adjusted in a multivariate logistic regression analysis. This analysis showed that preoperative NT-proBNP level > 917 pg/mL (OR 4.81, 95% CI 3.446–6.722, P < 0.001) and cTnI ≥ 0.07 ng/mL (OR 8.74, 95% CI 5.881–12.987, P < 0.001) remained significantly and independently associated with MACE after the adjustment of the confounding factors. Kaplan-Meier event-free survival curves demonstrated that patients with preoperative simultaneous NT-proBNP level > 917 pg/mL and cTnT ≥0.07 ng/mL had worse event-free survival than individual assessments of either biomarker.

Conclusion

Preoperative plasma NT-proBNP and cTnI are both independently associated with an increased risk of MACE in elderly patients after emergent non-cardiac surgery. The combination of these biomarkers provides better prognostic information than using either biomarker separately.     

Impact of Body Mass Index on Plasma N-Terminal ProB-Type Natriuretic Peptides in Chinese Atrial Fibrillation Patients without Heart Failure

Background

An inverse relationship between body mass index (BMI) and circulating levels of N-terminal proB-type natriuretic peptide (NT-proBNP) has been demonstrated in subjects with and without heart failure. Obesity also has been linked with increased incidence of atrial fibrillation (AF), but its influence on NT-proBNP concentrations in AF patients remains unclear. This study aimed to investigate the effect of BMI on NT-proBNP levels in AF patients without heart failure.

Methods

A total of 239 consecutive patients with AF undergoing catheter ablation were evaluated. Levels of NT-proBNP and clinical characteristics were compared in overweight or obese (BMI≥25 kg/m²) and normal weight (BMI<25 kg/m²) patients.

Results

Of 239 patients, 129 (54%) were overweight or obese. Overweight or obese patients were younger, more likely to have a history of nonparoxysmal AF, hypertension, and diabetes mellitus. Levels of NT-proBNP were significantly lower in overweight or obese than in normal weight subjects (P<0.05). The relationship of obesity and decreased NT-proBNP levels persisted in subgroup of hypertension, both gender and both age levels (≥65 yrs and <65 yrs).Multivariate linear regression identified BMI as an independent negative correlate of LogNT-proBNP level.

Conclusions

An inverse relationship between BMI and plasma NT-proBNP concentrations have been demonstrated in AF patients without heart failure. Overweight or obese patients with AF appear to have lower NT-proBNP levels than normal weight patients.     

Performance of a simplified HEART score and HEART-GP score for evaluating chest pain in urgent primary care

BackgroundChest pain is a common symptom in urgent primary care. The distinction between urgent and non-urgent causes can be challenging. A modified version of the HEART score, in which troponin is omitted (‘simplified HEART’) or replaced by the so-called ‘sense of alarm’ (HEART-GP), may aid in risk stratification.MethodThis study involved a retrospective, observational cohort of consecutive patients evaluated for chest pain at a large-scale, out-of-hours, regional primary care facility in the Netherlands, with 6‑week follow-up for major adverse cardiac events (MACEs). The outcome of interest is diagnostic accuracy, including positive predictive value (PPV) and negative predictive value (NPV).ResultsWe included 664 patients; MACEs occurred in 4.8% (n = 32). For  simplified HEART and HEART-GP, we found C‑statistics of 0.86 (95% confidence interval (CI) 0.80–0.91) and 0.90 (95% CI 0.85–0.95), respectively. Optimal diagnostic accuracy was found for a simplified HEART score ≥2 (PPV 9%, NPV 99.7%), HEART-GP score ≥3 (PPV 11%, NPV 99.7%) and HEART-GP score ≥4 (PPV 16%, NPV 99.4%). Physicians referred 157 patients (23.6%) and missed 6 MACEs. A simplified HEART score ≥2 would have picked up 5 cases, at the expense of 332 referrals (50.0%, p < 0.001). A HEART-GP score of ≥3 and ≥4 would have detected 5 and 3 MACEs and led to 293 (44.1%, p < 0.001) and 186 (28.0%, p = 0.18) referrals, respectively.ConclusionHEART-score modifications including the physicians’ ‘sense of alarm’ may be used as a risk stratification tool for chest pain in primary care in the absence of routine access to troponin assays. Further validation is warranted.Supplementary InformationThe online version of this article (10.1007/s12471-020-01529-4) contains supplementary material, which is available to authorized users.     

What is The Utility of Electrophysiological Study in Elderly Patients with Syncope and Heart Disease?

BackgroundSyncope in elderly patients with heart disease is a growing problem. Its aetiological diagnosis is often difficult. We intended to investigate the value of the electrophysiological study (EPS) in old patients with syncope and heart disease.MethodsEPS was performed in 182 consecutive patients with syncope and heart disease, among whom 62 patients were ≥75 years old and 120 patients <75.ResultsLeft ventricular ejection fraction was 43.9±11.7% in patients ≥75 and 41.1±12.6% in patients <75. During EPS, induced sustained ventricular arrhythmias were as frequent in both groups (27.4% in patients ≥75 versus 27.5% in patients <75, p=0.99) whereas AV conduction abnormalities were more frequent in older patients (37.1% in patients ≥75 versus 18.3% in patients<75, p<0.005). Syncope remained unexplained in 35.5% of patients ≥75 and in 51.7% of patients <75 (p<0.04). ICD was more likely to be implanted in younger patients than in patients ≥75 years (37.5% vs 21% respectively, p<0.009). During a mean follow-up period of 3.3±3 years, the 4-year-survival rate was 66.9±6.8 % in patients ≥75 and 75.9±6.2 % in patients <75 years. The main cause of death was heart failure in both groups. The factors related to a worse outcome in a multivariate analysis were low LVEF and higher age.ConclusionComplete EPS allows the identification of treatable causes in a high proportion of elderly patients with syncope and heart disease. Yet, the prognosis of these patients is mainly related to LVEF and age.     

Diagnostic utility of MR-proANP and NT-proBNP in elderly outpatients with a high risk of heart failure: the Copenhagen heart failure risk study

Abstract

Background: Amino-terminal-pro-B-type-natriuretic-peptide (NT-proBNP) is a diagnostic biomarker for heart failure (HF), but plasma concentrations are influenced by numerous factors. Mid-regional-pro-atrial-natriuretic-peptide (MR-proANP) have comparable diagnostic value in acute HF. However, data are lacking in the non-acute setting. This study sought to assess the diagnostic utility of MR-proANP in outpatients with a high risk of HF.

Methods: This prospective study included 399 outpatients. Inclusion criteria were: age?≥?60?years, ≥1 risk factor for HF (diabetes, chronic kidney disease, vascular disease, atrial fibrillation, hypertension), without known or suspected HF. Unrecognized HF was diagnosed based on clinical signs, patient-reported symptoms and echocardiography. Plasma concentrations of MR-proANP and NT-proBNP were analysed.

Results: In total, 65 patients were diagnosed with HF or asymptomatic left ventricular systolic dysfunction (N?=?12 LVEF?≤?40%, N?=?7 LVEF?>?40% to ≤50%, N?=?46 LVEF?>?50%). Both MR-proANP (odds-ratio: 1.77; 95% CI:1.16–2.72; p?=?0.009) and NT-proBNP (odds-ratio: 1.49; 95% CI:1.22–1.82; p?<?0.001) were associated with HF. Area under receiver-operator characteristics curve (AUC) for the diagnosis of HF or asymptomatic left ventricular systolic dysfunction was higher for MR-proANP (AUC?=?0.886; p?<?0.001) and NT-proBNP (AUC?=?0.910; p?<?0.001) compared to patient-reported symptoms of HF (AUC?=?0.830), but NT-proBNP added more diagnostic information compared to MR-proANP (p?=?0.022).

Conclusions: Both NT-proBNP and MR-proANP are useful biomarkers in the diagnosis of HF or asymptomatic left ventricular systolic dysfunction in a non-acute setting. However, NT-proBNP added more diagnostic information compared to MR-proANP.     

Risk and Outcome after Ablation of Isthmus-Dependent Atrial Flutter in Elderly Patients

MethodsA total of 1187 patients with a mean age 65±12 years consecutively referred for AFL ablation were retrospectively analyzed in the study.Results445 (37.5%) patients were aged ≥70 (range 70 to 93) among which 345 were aged 70 to 79 years (29.1%) and 100 were aged ≥80 (8.4%). In multivariable analysis, AFL-related rhythmic cardiomyopathy and presentation with 1/1 AFL were less frequent (respectively adjusted OR = 0.44, 0.27–0.74, p = 0.002 and adjusted OR = 0.29, 0.16–0.52, p<0.0001). AFL ablation-related major complications were more frequent in patients ≥70 although remained lower than 10% (7.4% in ≥70 vs. 4.2% in <70, adjusted OR = 1.74, 1.04–2.89, p = 0.03). After 2.1±2.7 years, AFL recurrence was less frequent in patients ≥70 (adjusted OR = 0.54, 0.37–0.80, p = 0.002) whereas atrial fibrillation (AF) occurrence was as frequent in the 70–79 and ≥80 age subsets. As expected, cardiac mortality was higher in older patients. Patients aged ≥80 also had a low probability of AFL recurrence (5.0%) and AF onset (19.0%).ConclusionsOlder patients represent 37.5% of patients referred for AFL ablation and displayed a <10% risk of ablation-related complications. Importantly, AFL recurrences were less frequent in patients ≥70 while AF occurrence was as frequent as in patients <70. Similar observations were made in patients ≥80 years. AFL ablation appears to be safe and efficient and should not be ruled out in elderly patients.     

心脏瓣膜疾病患者术后危险因素及潜在预测指标初探

目的:评价心肌肌钙蛋白(cardiac troponin,c Tn T)、氨基末端脑钠肽前体(N-terminal pro·-brain natriuretic peptide,NT-pro BNP)对于心瓣膜疾病手术患者术后并发症的预测价值。方法:选取我院2014年1月~2015年12月收治的心瓣膜病患者共108例,入院即记录其年龄、性别、BMI指数、NYHA等,于患者出院1个月后开始随访,随访时间为18个月,根据随访结局分为预后良好组与预后不良组。生存曲线显示随访后的不良预后率;单因素、多因素Cox回归评价各因素对患者预后情况的影响程度;ROC曲线分析其对疾病预后的预测价值。结果:多因素Cox回归分析显示左心室舒张末期内径(left ventricular end-diastolic dimension,LVEDD)(P=0.022)、c Tn T(P=0.023)和NT-pro BNP(P=0.016)对患者术后不良预后存在影响,其中,LVEDD的影响程度最高(RR=2.142),其次为NT-pro BNP(RR=2.046);ROC曲线下NT-pro BNP联合c Tn T预测的AUC为0.856,其特异性为83.6%,敏感性为79.3%。结论:NT-pro BNP联合BNP对心瓣膜置换术后患者的预后有较好的预测价值。     

Quantification of fibroblast growth factor 23 and N-terminal pro-B-type natriuretic peptide to identify patients with atrial fibrillation using a high-throughput platform: A validation study

BackgroundLarge-scale screening for atrial fibrillation (AF) requires reliable methods to identify at-risk populations. Using an experimental semi-quantitative biomarker assay, B-type natriuretic peptide (BNP) and fibroblast growth factor 23 (FGF23) were recently identified as the most suitable biomarkers for detecting AF in combination with simple morphometric parameters (age, sex, and body mass index [BMI]). In this study, we validated the AF model using standardised, high-throughput, high-sensitivity biomarker assays.Methods and findingsFor this study, 1,625 consecutive patients with either (1) diagnosed AF or (2) sinus rhythm with CHA₂DS₂-VASc score of 2 or more were recruited from a large teaching hospital in Birmingham, West Midlands, UK, between September 2014 and February 2018. Seven-day ambulatory ECG monitoring excluded silent AF. Patients with tachyarrhythmias apart from AF and incomplete cases were excluded. AF was diagnosed according to current clinical guidelines and confirmed by ECG. We developed a high-throughput, high-sensitivity assay for FGF23, quantified plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and FGF23, and compared results to the previously used multibiomarker research assay. Data were fitted to the previously derived model, adjusting for differences in measurement platforms and known confounders (heart failure and chronic kidney disease). In 1,084 patients (46% with AF; median [Q1, Q3] age 70 [60, 78] years, median [Q1, Q3] BMI 28.8 [25.1, 32.8] kg/m², 59% males), patients with AF had higher concentrations of NT-proBNP (median [Q1, Q3] per 100 pg/ml: with AF 12.00 [4.19, 30.15], without AF 4.25 [1.17, 15.70]; p < 0.001) and FGF23 (median [Q1, Q3] per 100 pg/ml: with AF 1.93 [1.30, 4.16], without AF 1.55 [1.04, 2.62]; p < 0.001). Univariate associations remained after adjusting for heart failure and estimated glomerular filtration rate, known confounders of NT-proBNP and FGF23. The fitted model yielded a C-statistic of 0.688 (95% CI 0.656, 0.719), almost identical to that of the derived model (C-statistic 0.691; 95% CI 0.638, 0.744). The key limitation is that this validation was performed in a cohort that is very similar demographically to the one used in model development, calling for further external validation.ConclusionsAge, sex, and BMI combined with elevated NT-proBNP and elevated FGF23, quantified on a high-throughput platform, reliably identify patients with AF.Trial registrationRegistry IRAS ID 97753 Health Research Authority (HRA), United Kingdom

Winnie Chua and colleagues identify and validate biomarkers for atrial fibrillation     

Sensitivity and Specificity of two rapid tests for the diagnosis of infection by Trypanosoma cruzi in a Colombian population

ObjectiveTo evaluate diagnostic precision of two rapid diagnostic tests (RDT’s) on patients with chronic Chagas disease.MethodologyProspective study with the following inclusion criteria: subjects older than 3 years, signed informed consent. Exclusion criterion: subjects could not have previously received treatment for infection with T. cruzi. The study population were participants in a screening process undertaken in rural and urban zones of the department Boyacá, Colombia. Two RDT’s were performed to all participants: the Chagas Detect Plus InBios (CDP) and the Chagas Stat-Pak (CSP) and as a reference standard the ELISA Chagas III GrupoBios and the Chagas ELISA IgG+IgM I Vircell tests were used. In the case of discordant results between the two ELISA tests, an indirect immunofluorescence was done.ResultsThree hundred-five (305) subjects were included in the study (38 patients with leishmaniasis), of which 215 tested negative for T cruzi and 90 tested positive according to the reference standard. The sensitivity of the RDT’s were 100% (CI 95% 95.9–100), and the specificity of the CDP was 99.1% (CI 95% 96.6–99.8) and for CSP was 100% (CI 95% 98.3–100). The agreement of CDP was 99.5% and for CSP was 100% with Kappa values of (k = 99.1; CI 95% 92.6–99.8%) and (k = 100; CI 95% 94.3–100), respectively. RDT’s did not present cross-reactions with samples from patients who were positive for leishmaniasis.ConclusionsThe findings demonstrate excellent results from the RDT’s in terms of validity, safety, and reproducibility. The results obtained provide evidence for the recommendation for using these tests in a Colombian epidemiological context principally in endemic areas in which laboratory installations necessary to perform conventional tests are not available, or they are scarce and to help in diagnosing chronic Chagas disease in order to provide access to treatment as soon as possible.     

An Efficient Automated Algorithm for Distinguishing Normal and Abnormal ECG Signal

ObjectiveThe present study aims to simulate an alarm system for online detecting normal electrocardiogram (ECG) signals from abnormal ECG so that an individual's heart condition can be accurately and quickly monitored at any moment, and any possible serious dangers can be prevented.Materials and methodsFirst, the data from Physionet database were used to analyze the ECG signal. The data were collected equally from both males and females, and the data length varied between several seconds to several minutes. The heart rate variability (HRV) signal, which reflects heart fluctuations in different time intervals, was used due to the low spatial accuracy of ECG signal and its time constraint, as well as the similarity of this signal with the normal signal in some diseases. In this study, the proposed algorithm provided a return map as well as extracted nonlinear features of the HRV signal, in addition to the application of the statistical characteristics of the signal. Then, artificial neural networks were used in the field of ECG signal processing such as multilayer perceptron (MLP) and support vector machine (SVM), as well as optimal features, to categorize normal signals from abnormal ones.ResultsIn this paper, the area under the curve (AUC) of the ROC was used to determine the performance level of introduced classifiers. The results of simulation in MATLAB medium showed that AUC for MLP and SVM neural networks was 89.3% and 94.7%, respectively. Also, the results of the proposed method indicated that the more nonlinear features extracted from the ECG signal could classify normal signals from the patient.ConclusionThe ECG signal representing the electrical activity of the heart at different time intervals involves some important information. The signal is considered as one of the common tools used by physicians to diagnose various cardiovascular diseases, but unfortunately the proper diagnosis of disease in many cases is accompanied by an error due to limited time accuracy and hiding some important information related to this signal from the physicians' vision leading to the risks of irreparable harm for patients. Based on the results, designing the proposed alarm system can help physicians with higher speed and accuracy in the field of diagnosing normal people from patients and can be used as a complementary system in hospitals.     

The Prognostic Value of the Work Ability Index for Sickness Absence among Office Workers

BackgroundThe work ability index (WAI) is a frequently used tool in occupational health to identify workers at risk for a reduced work performance and for work-related disability. However, information about the prognostic value of the WAI to identify workers at risk for sickness absence is scarce.ObjectivesTo investigate the prognostic value of the WAI for sickness absence, and whether the discriminative ability differs across demographic subgroups.MethodsAt baseline, the WAI (score 7-49) was assessed among 1,331 office workers from a Dutch financial service company. Sickness absence was registered during 12-months follow-up and categorised as 0 days, 0<days<5, 5≤days<15, and ≥15 days in one year. Associations between WAI and sickness absence were estimated by multinomial regression analyses. Discriminative ability of the WAI was assessed by the Area Under the Curve (AUC) and Ordinal c-index (ORC). Test characteristics were determined for dichotomised outcomes. Additional analyses were performed for separate WAI dimensions, and subgroup analyses for demographic groups.ResultsA lower WAI was associated with sickness absence (≥15 days vs. 0 days: per point lower WAI score OR=1.27; 95%CI 1.21-1.33). The WAI showed reasonable ability to discriminate between categories of sickness absence (ORC=0.65; 95%CI 0.63-0.68). Highest discrimination was found for comparing workers with ≥15 sick days with 0 sick days (AUC=0.77) or with 1-5 sick days (AUC=0.69). At the cut-off for poor work ability (WAI≤27) the sensitivity to identify workers at risk for ≥15 sick days was 7.5%, the specificity 99.6%, and the positive predictive value 82%. The performance was similar across demographic subgroups.ConclusionsThe WAI could be used to identify workers at high risk for prolonged sickness absence. However, due to low sensitivity many workers will be missed. Hence, additional factors are required to better identify workers at highest risk.     

Predictive Values of N-Terminal Pro-B-Type Natriuretic Peptide and Cardiac Troponin I for Myocardial Fibrosis in Hypertrophic Obstructive Cardiomyopathy

Background

Both high-sensitivity cardiac troponin T and B-type natriuretic peptide are useful in detecting myocardial fibrosis, as determined by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR), in patients with non-obstructive hypertrophic cardiomyopathy. However, their values to predict myocardial fibrosis in hypertrophic obstructive cardiomyopathy (HOCM) remain unclear. We investigated the role of N-Terminal Pro-B-Type Natriuretic Peptide (NT-proBNP) and cardiac troponin I (cTnI) to identify LGE-CMR in patients with HOCM.

Methods

Peripheral concentrations of NT-proBNP and cTnI were determined in patients with HOCM (n = 163; age = 47.2 ± 10.8 years; 38.7% females). Contrast-enhanced CMR was performed to identify and quantify myocardial fibrosis.

Results

LGE was detected in 120 of 163 patients (73.6%). Patients with LGE had significantly higher levels of NT-proBNP and cTnI than those without LGE (1386.2 [904.6–2340.8] vs. 866.6 [707.2–1875.2] pmol/L, P = 0.003; 0.024 [0.010–0.049] vs. 0.010 [0.005–0.021] ng/ml, P <0.001, respectively). The extent of LGE was positively correlated with log cTnI (r = 0.371, P <0.001) and log NT-proBNP (r = 0.211, P = 0.007). On multivariable analysis, both log cTnI and maximum wall thickness (MWT) were independent predictors of the presence of LGE (OR = 3.193, P = 0.033; OR = 1.410, P < 0.001, respectively), whereas log NT-proBNP was not. According to the ROC curve analysis, combined measurements of MWT ≥21 mm and/or cTnI ≥0.025ng/ml indicated good diagnostic performance for the presence of LGE, with specificity of 95% or sensitivity of 88%.

Conclusions

Serum cTnI is an independent predictor useful for identifying myocardial fibrosis, while plasma NT-proBNP is only associated with myocardial fibrosis on univariate analysis. Combined measurements of serum cTnI with MWT further improve its value in detecting myocardial fibrosis in patients with HOCM.     

Measurement of Glycosylated Alpha-Fetoprotein Improves Diagnostic Power over the Native Form in Hepatocellular Carcinoma

Serum alpha-fetoprotein (AFP) has long been used as a diagnostic marker for hepatocellular carcinoma (HCC), albeit controversially. Although it remains widely used in clinics, the value of AFP in HCC diagnosis has recently been challenged due to its significant rates of false positive and false negative findings. To improve the efficacy of AFP as HCC diagnostic marker, we developed a method of measuring total and glycosylated AFP by multiple reaction monitoring (MRM)-MS. In this study, we verified the total amount of AFP (nonglycopeptide levels) and the degree of glycosylated AFP (deglycopeptide levels) in 60 normal (41 men and 19 women; mean age 53 years; range 32–74 years), 35 LC (23 men and 12 women; mean age 56 years; range 43–78 years; HBV-related), and 60 HCC subjects (42 men and 18 women; mean age 58 years; range 38–76 years; HBV-related; 30 stage I, 15 stage II, and 10 stage III). By MRM-MS analysis, the nonglycopeptide had 56.7% sensitivity, 68.3% specificity, and an AUC of 0.687 [cutoff value: ≥0.02 (light/heavy ratio)], comparing the normal and HCC group, whereas the deglycopeptide had 93.3% sensitivity, 68.3% specificity, and an AUC of 0.859 [cutoff value: ≥0.02 (light/heavy ratio)]. In comparing the stage I HCC subgroup with the LC group, the nonglycopeptide had a sensitivity of 66.7%, specificity of 80.0%, and an AUC of 0.712 [cutoff value: ≥0.02 (light/heavy ratio)], whereas the deglycopeptide had a sensitivity of 96.7%, specificity of 80.0%, and an AUC of 0.918 [cutoff value: ≥0.02 (light/heavy ratio)]. These data demonstrate that the discriminatory power of the deglycopeptide is greater than that of the nonglycopeptide. We conclude that deglycopeptide can distinguish cancer status between normal subjects and HCC patients better than nonglycopeptide.