Power modulation spectrum - a promising approach for the indispensable quality control of electrocardiogram signals from monitoring units for the detection of autonomic dysfunction.

OBJECTIVE: Electrocardiogram (ECG) is essential for evaluating the autonomic nervous system. Ensuring the quality of real-world ECG datasets is critical, but manual control of large datasets is impractical. Thus, automated quality control is necessary. This paper introduces a new quality index, the peak-distance quality index (PDQI), based on the modulation spectrum approach. METHODS: Real-life data from 1000 ECG recordings, each 600 s long, were collected at the stroke unit of the University Hospital Tulln. Each ECG was visually evaluated, including the duration of the signal, artefacts and noise, and the number of extrasystoles. The power-modulation spectrum, the percentage of ECG in each signal, and modulation spectrum-based quality index (MS-QI) and PDQI were calculated. The area under the curve (AUC) for the detection of high-quality ECGs was calculated for both quality indices, as well as the optimal threshold for each index. RESULTS: The percentage of ECG signals in the recordings based on the modulation spectrum correlates with expert rating (r = 0.99, p < 0.001). The AUC for PDQI for the detection of extrasystoles is 0.96, and the AUC for MSQI for the detection of artefacts is 0.83. The optimal thresholds for PDQI and MSQI are 0.44 and 0.17, respectively CONCLUSION: The power modulation spectrum can be applied to large amounts of data to detect ECG signals within biosignals and calculate quality indices. MSQI can be used for artefact detection and PDQI for extrasystole detection in ECG signals. A combined approach using both quality indices can provide a picture of the underlying data quality.

Screening for Atrial Fibrillation: US Preventive Services Task Force Recommendation Statement.

Importance: Atrial fibrillation (AF) is the most common cardiac arrhythmia. The prevalence of AF increases with age, from less than 0.2% in adults younger than 55 years to about 10% in those 85 years or older, with a higher prevalence in men than in women. It is uncertain whether the prevalence of AF differs by race and ethnicity. Atrial fibrillation is a major risk factor for ischemic stroke and is associated with a substantial increase in the risk of stroke. Approximately 20% of patients who have a stroke associated with AF are first diagnosed with AF at the time of the stroke or shortly thereafter. Objective: To update its 2018 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on the benefits and harms of screening for AF in older adults, the accuracy of screening tests, the effectiveness of screening tests to detect previously undiagnosed AF compared with usual care, and the benefits and harms of anticoagulant therapy for the treatment of screen-detected AF in older adults. Population: Adults 50 years or older without a diagnosis or symptoms of AF and without a history of transient ischemic attack or stroke. Evidence Assessment: The USPSTF concludes that evidence is lacking, and the balance of benefits and harms of screening for AF in asymptomatic adults cannot be determined. Recommendation: The USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of screening for AF. (I statement).

Screening for Atrial Fibrillation: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

Importance: Atrial fibrillation (AF), the most common arrhythmia, increases the risk of stroke. Objective: To review the evidence on screening for AF in adults without prior stroke to inform the US Preventive Services Task Force. Data Sources: PubMed, Cochrane Library, and trial registries through October 5, 2020; references, experts, and literature surveillance through October 31, 2021. Study Selection: Randomized clinical trials (RCTs) of screening among asymptomatic persons without known AF or prior stroke; test accuracy studies; RCTs of anticoagulation among persons with AF; systematic reviews; and observational studies reporting harms. Data Extraction and Synthesis: Two reviewers assessed titles/abstracts, full-text articles, and study quality and extracted data; when at least 3 similar studies were available, meta-analyses were conducted. Main Outcomes and Measures: Detection of undiagnosed AF, test accuracy, mortality, stroke, stroke-related morbidity, and harms. Results: Twenty-six studies (N = 113 784) were included. In 1 RCT (n = 28 768) of twice-daily electrocardiography (ECG) screening for 2 weeks, the likelihood of a composite end point (ischemic stroke, hemorrhagic stroke, systemic embolism, all-cause mortality, and hospitalization for bleeding) was lower in the screened group over 6.9 years (hazard ratio, 0.96 [95% CI, 0.92-1.00]; P = .045), but that study had numerous limitations. In 4 RCTs (n = 32 491), significantly more AF was detected with intermittent and continuous ECG screening compared with no screening (risk difference range, 1.0%-4.8%). Treatment with warfarin over a mean of 1.5 years in populations with clinical, mostly persistent AF was associated with fewer ischemic strokes (pooled risk ratio [RR], 0.32 [95% CI, 0.20-0.51]; 5 RCTs; n = 2415) and lower all-cause mortality (pooled RR, 0.68 [95% CI, 0.50-0.93]) compared with placebo. Treatment with direct oral anticoagulants was also associated with lower incidence of stroke (adjusted odds ratios range, 0.32-0.44) in indirect comparisons with placebo. The pooled RR for major bleeding for warfarin compared with placebo was 1.8 (95% CI, 0.85-3.7; 5 RCTs; n = 2415), and the adjusted odds ratio for major bleeding for direct oral anticoagulants compared with placebo or no treatment ranged from 1.38 to 2.21, but CIs did not exclude a null effect. Conclusions and Relevance: Although screening can detect more cases of unknown AF, evidence regarding effects on health outcomes is limited. Anticoagulation was associated with lower risk of first stroke and mortality but with increased risk of major bleeding, although estimates for this harm are imprecise; no trials assessed benefits and harms of anticoagulation among screen-detected populations.

Sharing and Teaching Electrocardiograms to Minimize Infarction (STEMI): reducing diagnostic time for acute coronary occlusion in the emergency department.

BACKGROUND: Limits to ST-Elevation Myocardial Infarction (STEMI) criteria may lead to prolonged diagnostic time for acute coronary occlusion. We aimed to reduce ECG-to-Activation (ETA) time through audit and feedback on STEMI-equivalents and subtle occlusions, without increasing Code STEMIs without culprit lesions. METHODS: This multi-centre, quality improvement initiative reviewed all Code STEMI patients from the emergency department (ED) over a one-year baseline and one-year intervention period. We measured ETA time, from the first ED ECG to the time a Code STEMI was activated. Our intervention strategy involved a grand rounds presentation and an internal website presenting weekly local challenging cases, along with literature on STEMI-equivalents and subtle occlusions. Our outcome measure was ETA time for culprit lesions, our process measure was website views/visits, and our balancing measure was the percentage of Code STEMIs without culprit lesions. RESULTS: There were 51 culprit lesions in the baseline period, and 64 in the intervention period. Median ETA declined from 28.0 min (95% confidence interval [CI] 15.0-45.0) to 8.0 min (95%CI 6.0-15.0). The website garnered 70.4 views/week and 27.7 visitors/week in a group of 80 physicians. There was no change in percentage of Code STEMIs without culprit lesions: 28.2% (95%CI 17.8-38.6) to 20.0% (95%CI 11.2-28.8%). Conclusions Our novel weekly web-based feedback to all emergency physicians was associated with a reduction in ETA time by 20 min, without increasing Code STEMIs without culprit lesions. Local ECG audit and feedback, guided by ETA as a quality metric for acute coronary occlusion, could be replicated in other settings to improve care.

The New S7B/E14 Question and Answer Draft Guidance for Industry: Contents and Commentary.

In August 2020, the International Council on Harmonisation (ICH) released a new draft document, which for the first time combined nonclinical (S7B) and clinical (E14) Questions and Answers (Q&As) into 1 document. FDA describes the revision as a "value proposition": if the human ether-à-go-go assay and the in vivo study are performed in a standardized way, the number of dedicated thorough QT (TQT) studies can be reduced. In this article, we describe and discuss the Q&As that relate to clinical ECG evaluation. If supported by negative standardized nonclinical assays, Q&A 5.1 will obviate the need for a TQT study in the case that a >2-fold exposure margin vs high clinical scenario cannot be obtained. Q&A 6.1 addresses drugs that are poorly tolerated in healthy subjects and cannot be studied at high doses or in placebo-controlled studies; it therefore mainly applies to oncology drugs. It will enable sponsors to claim that a new drug has a "low likelihood of proarrhythmic effects" in the case that the mean corrected QT effect is <10 milliseconds at the time of market application. The E14 2015 revision allowed application of concentration-corrected QT analysis on data from routinely performed clinical pharmacology studies, for example, the first-in-human study and the proportion of dedicated TQT studies has since steadily decreased. It can be foreseen that the proposed new revision will further reduce the number of TQT studies. To achieve harmonization across regulatory regions, it seems important to reach consensus within the International Council on Harmonisation group on the new threshold proposed in 6.1. For this purpose, the Implementation Working Group has asked for public comments.

Parameter variations in personalized electrophysiological models of human heart ventricles.

The objectives of this study were to evaluate the accuracy of personalized numerical simulations of the electrical activity in human ventricles by comparing simulated electrocardiograms (ECGs) with real patients' ECGs and analyzing the sensitivity of the model output to variations in the model parameters. We used standard 12-lead ECGs and up to 224 unipolar body-surface ECGs to record three patients with cardiac resynchronization therapy devices and three patients with focal ventricular tachycardia. Patient-tailored geometrical models of the ventricles, atria, large vessels, liver, and spine were created using computed tomography data. Ten cases of focal ventricular activation were simulated using the bidomain model and the TNNP 2006 cellular model. The population-based values of electrical conductivities and other model parameters were used for accuracy analysis, and their variations were used for sensitivity analysis. The mean correlation coefficient between the simulated and real ECGs varied significantly (from r = 0.29 to r = 0.86) among the simulated cases. A strong mean correlation (r > 0.7) was found in eight of the ten model cases. The accuracy of the ECG simulation varied widely in the same patient depending on the localization of the excitation origin. The sensitivity analysis revealed that variations in the anisotropy ratio, blood conductivity, and cellular apicobasal heterogeneity had the strongest influence on transmembrane potential, while variation in lung conductivity had the greatest influence on body-surface ECGs. Futhermore, the anisotropy ratio predominantly affected the latest activation time and repolarization time dispersion, while the cellular apicobasal heterogeneity mainly affected the dispersion of action potential duration, and variation in lung conductivity mainly led to changes in the amplitudes of ECGs and cardiac electrograms. We also found that the effects of certain parameter variations had specific regional patterns on the cardiac and body surfaces. These observations are useful for further developing personalized cardiac models.

Transfer learning for ECG classification.

Remote monitoring devices, which can be worn or implanted, have enabled a more effective healthcare for patients with periodic heart arrhythmia due to their ability to constantly monitor heart activity. However, these devices record considerable amounts of electrocardiogram (ECG) data that needs to be interpreted by physicians. Therefore, there is a growing need to develop reliable methods for automatic ECG interpretation to assist the physicians. Here, we use deep convolutional neural networks (CNN) to classify raw ECG recordings. However, training CNNs for ECG classification often requires a large number of annotated samples, which are expensive to acquire. In this work, we tackle this problem by using transfer learning. First, we pretrain CNNs on the largest public data set of continuous raw ECG signals. Next, we finetune the networks on a small data set for classification of Atrial Fibrillation, which is the most common heart arrhythmia. We show that pretraining improves the performance of CNNs on the target task by up to [Formula: see text], effectively reducing the number of annotations required to achieve the same performance as CNNs that are not pretrained. We investigate both supervised as well as unsupervised pretraining approaches, which we believe will increase in relevance, since they do not rely on the expensive ECG annotations. The code is available on GitHub at https://github.com/kweimann/ecg-transfer-learning .

The Groningen electrocardiographic criteria for left ventricular hypertrophy: a sex-specific analysis.

The sensitivity of electrocardiogram (ECG) criteria to detect left ventricular hypertrophy (LVH) is low, especially in women. We determined sex-specific sensitivities of ECG-LVH criteria, and developed new criteria, using cardiovascular magnetic resonance imaging (CMR). Sensitivities of ECG-LVH criteria were determined in participants of the UK Biobank (N = 3632). LVH was defined when left ventricular mass was > 95% confidence interval (CI) according to age and sex. In a training cohort (75%, N = 2724), sex-specific ECG-LVH criteria were developed by investigating all possible sums of QRS-amplitudes in all 12 leads, and selecting the sum with the highest pseudo-R2 and area under the curve to detect LVH. Performance was assessed in a validation cohort (25%, N = 908), and association with blood pressure change was investigated in an independent cohort. Sensitivities of ECG-LVH criteria were low, especially in women. Newly developed Groningen-LVH criterion for women (QV2 + RI + RV5 + RV6 + SV2 + SV4 + SV5 + SV6) outperformed all ECG-LVH criteria with a sensitivity of 42% (95% CI 35-49%). In men, newly developed criterion ((RI + RV5 + SII + SV2 + SV6) × QRS duration) was equally sensitive as 12-lead sum with a sensitivity of 44% (95% CI 37-51%) and outperformed the other criteria. In an independent cohort, the Groningen-LVH criteria were strongest associated with change in systolic blood pressure. Our proposed CMR sex-specific Groningen-LVH criteria improve the sensitivity to detect LVH, especially in women. Further validation and its association with clinical outcomes is warranted.

Admission ECG changes predict short term-mortality after acute myocardial infarction less reliable in patients with diabetes.

Prior studies examined association between short-term mortality and certain changes in the admission ECG in acute myocardial infarction (AMI). Nevertheless, little is known about possible differences between patients with diabetes and without diabetes in this regard. So the aim of the study was to investigate the association between 28-day case fatality according to certain ECG changes comparing AMI cases with and without diabetes from the general population. From 2000 until 2017 a total of 9756 AMI cases was prospectively recorded in the study Area of Augsburg, Germany. Each case was assigned to one of the following groups according to admission ECG: 'ST-elevation', 'ST-depression', 'only T-negativity', 'predominantly bundle branch block', 'unspecific changes' and 'normal ECG' (the last two were put together for regression analyses). Multivariable adjusted logistic regression models were calculated to compare 28-day case-fatality between the ECG groups for the total sample and separately for diabetes and non-diabetes cases. For the non-diabetes group, the parsimonious logistic regression model revealed significantly better 28-day-outcome for the 'normal ECG / unspecific changes' group (OR: 0.47 [0.29-0.76]) compared to the reference group (STEMI). Contrary, in AMI cases with diabetes the category 'normal ECG / unspecific changes' was not significantly associated with lower short-term mortality (OR: 0.87 [0.49-1.54]). Neither of the other ECG groups was significantly associated with 28-day-mortality in the parsimonious logistic regression models. Consequently, the absence of AMI-typical changes in the admission ECG predicts favorable short-term mortality only in non-diabetic cases, but not so in patients with diabetes.

Validation of Normal P-Wave Parameters in a Large Unselected Pediatric Population of North-Western Romania: Results of the CARDIOPED Project.

AIMS: Reference values of the P-wave on 12 lead electrocardiograms are lacking for children and adolescents in Eastern Europe. Hence, the present study is aimed at determining the standard values of the P-wave in children and adolescents based on ECG data from the CARDIOPED project, a large-scale general population of children who participated in a screening program in Transylvania, Romania. METHODS AND RESULTS: A total of 22,411 ECGs of participants aged 6 to 18 years old from a school-based ECG screening were obtained between February 2015 and December 2015 in Transylvania, Romania. Three pediatric cardiologists manually reviewed each ECG. P-wave duration, voltage, axis, and correlation with gender and age were analyzed. The mean P-wave duration was 88 ± 10.7 ms, with a maximum duration of 128 ms. P-wave showed a positive correlation with age but did not differ between sexes. There was a positive correlation between the P-wave duration and the heart rate, but not with the body max index. The mean P-wave axis was 40.4 ± 31.1, and the mean P-wave amplitude was 0.12 ± 0.03 mV. CONCLUSION: In this study on many pediatric subjects, we have provided normal limits for the P-wave in Romanian children aged 6-18 years. Our findings are useful for creating interpretation guidelines for pediatric ECG.

Reference values of electrographic and cardiac ultrasound parameters in Russian healthy children and adolescents.

Between 2009 and 2013, a large cross-sectional study on the health consequences of the Chernobyl nuclear accident was performed in the contaminated and uncontaminated territories of the Bryansk Oblast (Russian Federation). The objective of this work was to confirm or refute a possible association between childhood cardiac arrhythmia and a chronic exposure to caesium-137. As part of this study, a large number of electrocardiographic and cardiac ultrasound parameters were collected from 18,152 children aged 2-18 years including 12,512 healthy ones not contaminated with caesium-137. It seemed therefore relevant for us to share in a second publication these medical data based on healthy and uncontaminated children with the scientific community because of the large quantities and the limited availability of such kind of data. In the present study, relating to electrocardiographic parameters, the measurements performed fully reflect the expected evolution of the paediatric electrocardiogram between 5 and 18 years of age. Thus, the median values were generally quite close to those available in the literature. In contrast, differences in the 2nd and 98th percentiles were notable and could be explained in particular by the type of equipment used, the number of subjects included in the study and racial disparities. As for echocardiographic parameters, the evolution of the measured values in age groups is consistent with what was expected considering factors such as growth. In comparison with other scientific studies that have investigated these echocardiographic parameters, some differences by age groups have been identified. The ethnic factor truly appears to be a relevant feature to consider. In view of the results, it appeared essential to the authors to approach the methodological conditions of the scientific studies already published on the topic to be truly comparable and thus to provide a reliable answer on a topic for which real expectations in terms of medical care are required.

Standardization in Performing and Interpreting Electrocardiograms.

Excellence in recording and interpretation of electrocardiogram (ECG) is a necessity for optimal electrocardiography. This includes data to properly interpret the ECG, including data on age, gender, cardiovascular diagnosis, medications, abnormal laboratory findings (eg, data on electrolytes), and the indications for the electrocardiogram. The ECG needs to be performed by a qualified technician and interpreted by an experienced physician.

Post-arrest wide complex rhythm: What is the cause of death?

A 72-year-old man presented to the ED following witnessed cardiac arrest. After return of spontaneous circulation, an ECG was performed which demonstrated a wide complex rhythm with "shark fin" morphology. With careful examination it is possible to identify the J point and determine that the electrocardiogram (ECG) findings actually represent massive ST-elevation indicative of occlusion myocardial infarction (OMI). Initial troponin was undetectable. The patient underwent emergent cardiac catheterization and had a 100% proximal LAD occlusion that was successfully stented. The patient was discharged home neurologically intact several days later. This case highlights the importance of careful ECG interpretation and the limitations of troponin assays in the evaluation of acute coronary syndrome. Most importantly, we demonstrate how to evaluate for ST elevation in the context of a widened QRS complex.

Electrocardiogram Standards for Children and Young Adults Using Z-Scores.

BACKGROUND: Normative ECG values for children are based on relatively few subjects and are not standardized, resulting in interpersonal variability of interpretation. Recent advances in digital technology allow a more quantitative, reproducible assessment of ECG variables. Our objective was to create the foundation of normative ECG standards in the young utilizing Z-scores. METHODS: One hundred two ECG variables were collected from a retrospective cohort of 27 085 study subjects with no known heart condition, ages 0 to 39 years. The cohort was divided into 16 age groups by sex. Median, interquartile range, and range were calculated for each variable adjusted to body surface area. RESULTS: Normative standards were developed for all 102 ECG variables including heart rate; P, R, and T axis; R-T axis deviation; PR interval, QRS duration, QT, and QTc interval; P, Q, R, S, and T amplitudes in 12 leads; as well as QRS and T wave integrals. Incremental Z-score values between -2.5 and 2.5 were calculated to establish upper and lower limits of normal. Historical ECG interpretative concepts were reassessed and new concepts observed. CONCLUSIONS: Electronically acquired ECG values based on the largest pediatric and young adult cohort ever compiled provide the first detailed, standardized, quantitative foundation of traditional and novel ECG variables. Expression of ECG variables by Z-scores lends an objective and reproducible evaluation without interpreter bias that can lead to more confident establishment of ECG-disease correlations and improved automated ECG readings in high-volume cardiac screening efforts in the young. Graphic Abstract: A graphic abstract is available for this article.

Population-Based Screening for Atrial Fibrillation.

Atrial fibrillation (AF) is a common and morbid arrhythmia. Stroke is a major hazard of AF and may be preventable with oral anticoagulation. Yet since AF is often asymptomatic, many individuals with AF may be unaware and do not receive treatment that could prevent a stroke. Screening for AF has gained substantial attention in recent years as several studies have demonstrated that screening is feasible. Advances in technology have enabled a variety of approaches to facilitate screening for AF using both medical-prescribed devices as well as consumer electronic devices capable of detecting AF. Yet controversy about the utility of AF screening remains owing to concerns about potential harms resulting from screening in the absence of randomized data demonstrating effectiveness of screening on outcomes such as stroke and bleeding. In this review, we summarize current literature, present technology, population-based screening considerations, and consensus guidelines addressing the role of AF screening in practice.

The standardized 12-lead fetal electrocardiogram of the healthy fetus in mid-pregnancy: A cross-sectional study.

INTRODUCTION: The examination of the fetal heart in mid-pregnancy is by ultrasound examination. The quality of the examination is highly dependent on the skill of the sonographer, fetal position and maternal body mass index. An additional tool that is less dependent on human experience and interpretation is desirable. The fetal electrocardiogram (ECG) could fulfill this purpose. We aimed to show the feasibility of recording a standardized fetal ECG in mid-pregnancy and explored its possibility to detect congenital heart disease (CHD). MATERIALS AND METHODS: Women older than 18 years of age with an uneventful pregnancy, carrying a healthy singleton fetus with a gestational age between 18 and 24 weeks were included. A fetal ECG was performed via electrodes on the maternal abdomen. After removal of interferences, a vectorcardiogram was constructed. Based on the ultrasound assessment of the fetal orientation, the vectorcardiogram was rotated to standardize for fetal orientation and converted into a 12-lead ECG. Median ECG waveforms for each lead were calculated. RESULTS: 328 fetal ECGs were recorded. 281 were available for analysis. The calculated median ECG waveform showed the electrical heart axis oriented to the right and inferiorly i.e. a negative QRS deflection in lead I and a positive deflection in lead aVF. The two CHD cases show ECG abnormalities when compared to the mean ECG of the healthy cohort. DISCUSSION: We have presented a method for estimating a standardized 12-lead fetal ECG. In mid-pregnancy, the median electrical heart axis is right inferiorly oriented in healthy fetuses. Future research should focus on fetuses with congenital heart disease.