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BackgroundThe utility of exercise-induced ST-segment depression for diagnosing ischemic heart disease (IHD) in women is unclear.HypothesisBased on evidence that IHD pathophysiology in women involves coronary vascular dysfunction, we hypothesized that coronary vascular dysfunction contributes to exercise electrocardiography (Ex-ECG) ST-depression in the absence of obstructive coronary artery disease, so-called false positive results. We tested our hypothesis in a pilot study evaluating the relationship between peripheral vascular endothelial function and Ex-ECG.MethodsTwenty-nine asymptomatic women without cardiac risk factors underwent maximal Bruce protocol exercise treadmill testing and peripheral endothelial function assessment using peripheral arterial tonometry (Itamar EndoPAT 2000) to measure reactive hyperemia index (RHI). The relationship between RHI and Ex-ECG ST-segment depression was evaluated using logistic regression and differences in subgroups using 2-tailed t tests.ResultsMean age was 54 ± 7 years, body mass index 25 ± 4 kg/m2 , and RHI 2.51 ± 0.66. Three women (10%) had RHI 0.05). RHI did not predict ST-segment depression.ConclusionsOur pilot study demonstrates high prevalence of exercise-induced ST-segment depression in asymptomatic, middle-aged, overweight women. Peripheral vascular endothelial dysfunction did not predict Ex-ECG ST-segment depression. Further work is needed to investigate the utility of vascular endothelial testing and Ex-ECG for IHD diagnostic and management purposes in women.

Aim: To evaluate the interaction between sex and rate corrected QT interval (QTc) duration in normal subjects after drug-induced QT prolongation and in LQTS patients.Methods: Semi-automated measurements were performed on 875 digital ECGs (200 normal subjects off drugs (100 females), 200 normal subjects on Moxifloxacin (100 females), 259 LQT1 patients (161 females), 183 LQT2 patients (100 females) and 33 LQT3 patients (15 females)). A sex specific coefficient was calculated in each group and was used to calculate group specific corrected QT intervals (QTci).Results: The mean sex difference (female minus male) in QTci interval duration was 17 ms 95%CI(12.7; 21.3) in normal subjects, 19 ms (14.5; 23.5) on Moxifloxacin, and 13 ms (4.8; 21.2) in LQT1 patients. The mean difference was 2 ms (-7.9; 11.9) in LQT2 and - 5 ms (-32.2; 22.2) in LQT3 patients (p = 0.0067 for the group and sex interaction). In the subgroup of patients above 15 years and without beta blocker treatment, the sex effect (female minus male) on QTci interval duration was 17 ms (4.1; 29.9) in LQT1 patients. QTc duration was not different between sex in LQT2 and in LQT3 patients (mean difference - 3 ms (-21.6; 15.6) and 12 ms (-28.4; 52.4), respectively) (p = 0.0191 for group and sex interaction).Conclusions: The interaction between sex and QTc interval is preserved in type 1 LQTS and drug-induced QTc prolongation but blurred in type 2 LQTS. Further experimental studies are warranted to better understand the interaction of sexual hormones with malfunctioning KCNH2 encoded repolarizing potassium channel. [ABSTRACT FROM AUTHOR]

Background: Automated measurements of electrocardiographic (ECG) intervals by current-generation digital electrocardiographs are critical to computer-based ECG diagnostic statements, to serial comparison of ECGs, and to epidemiological studies of ECG findings in populations. A previous study demonstrated generally small but often significant systematic differences among 4 algorithms widely used for automated ECG in the United States and that measurement differences could be related to the degree of abnormality of the underlying tracing. Since that publication, some algorithms have been adjusted, whereas other large manufacturers of automated ECGs have asked to participate in an extension of this comparison.Methods: Seven widely used automated algorithms for computer-based interpretation participated in this blinded study of 800 digitized ECGs provided by the Cardiac Safety Research Consortium. All tracings were different from the study of 4 algorithms reported in 2014, and the selected population was heavily weighted toward groups with known effects on the QT interval: included were 200 normal subjects, 200 normal subjects receiving moxifloxacin as part of an active control arm of thorough QT studies, 200 subjects with genetically proved long QT syndrome type 1 (LQT1), and 200 subjects with genetically proved long QT syndrome Type 2 (LQT2).Results: For the entire population of 800 subjects, pairwise differences between algorithms for each mean interval value were clinically small, even where statistically significant, ranging from 0.2 to 3.6milliseconds for the PR interval, 0.1 to 8.1milliseconds for QRS duration, and 0.1 to 9.3milliseconds for QT interval. The mean value of all paired differences among algorithms was higher in the long QT groups than in normals for both QRS duration and QT intervals. Differences in mean QRS duration ranged from 0.2 to 13.3milliseconds in the LQT1 subjects and from 0.2 to 11.0milliseconds in the LQT2 subjects. Differences in measured QT duration (not corrected for heart rate) ranged from 0.2 to 10.5milliseconds in the LQT1 subjects and from 0.9 to 12.8milliseconds in the LQT2 subjects.Conclusions: Among current-generation computer-based electrocardiographs, clinically small but statistically significant differences exist between ECG interval measurements by individual algorithms. Measurement differences between algorithms for QRS duration and for QT interval are larger in long QT interval subjects than in normal subjects. Comparisons of population study norms should be aware of small systematic differences in interval measurements due to different algorithm methodologies, within-individual interval measurement comparisons should use comparable methods, and further attempts to harmonize interval measurement methodologies are warranted. [ABSTRACT FROM AUTHOR]

Although automated ECG analysis has been available for many years, there are some aspects which require to be re-assessed with respect to their value while newer techniques which are worthy of review are beginning to find their way into routine use. At the annual International Society of Computerized Electrocardiology conference held in April 2017, four areas in particular were debated. These were a) automated 12 lead resting ECG analysis; b) real time out of hospital ECG monitoring; c) ECG imaging; and d) single channel ECG rhythm interpretation. One speaker presented the positive aspects of each technique and another outlined the more negative aspects. Debate ensued. There were many positives set out for each technique but equally, more negative features were not in short supply, particularly for out of hospital ECG monitoring. [ABSTRACT FROM AUTHOR]

At the April, 2015 International Society for Computerized Electrocardiology (ISCE) Annual Conference in San Jose, CA, a special session entitled Remembering Ron & Rory was held to pay tribute to the extraordinary work and lives of two experts in electrocardiology. The session was well attended by conference attendees, Childers' family members and friends, and additional colleagues who traveled to San Jose solely to participate in this session. The purpose of the present paper is to document the spirit of this special session as faithfully as possible using the words of the session speakers. [ABSTRACT FROM AUTHOR]

Introduction It is well known that accurate interpretation of the 12-lead electrocardiogram (ECG) requires a high degree of skill. There is also a moderate degree of variability among those who interpret the ECG. While this is the case, there are no best practice guidelines for the actual ECG interpretation process. Hence, this study adopts computerized eye tracking technology to investigate whether eye-gaze can be used to gain a deeper insight into how expert annotators interpret the ECG. Annotators were recruited in San Jose, California at the 2013 International Society of Computerised Electrocardiology (ISCE). Methods Each annotator was recruited to interpret a number of 12-lead ECGs ( N = 12) while their eye gaze was recorded using a Tobii X60 eye tracker. The device is based on corneal reflection and is non-intrusive. With a sampling rate of 60 Hz, eye gaze coordinates were acquired every 16.7 ms. Fixations were determined using a predefined computerized classification algorithm, which was then used to generate heat maps of where the annotators looked. The ECGs used in this study form four groups (3 = ST elevation myocardial infarction [STEMI], 3 = hypertrophy, 3 = arrhythmias and 3 = exhibiting unique artefacts). There was also an equal distribution of difficulty levels (3 = easy to interpret, 3 = average and 3 = difficult). ECGs were displayed using the 4x3 + 1 display format and computerized annotations were concealed. Results Precisely 252 expert ECG interpretations (21 annotators × 12 ECGs) were recorded. Average duration for ECG interpretation was 58 s (SD = 23). Fleiss' generalized kappa coefficient ( P a = 0.56) indicated a moderate inter-rater reliability among the annotators. There was a 79% inter-rater agreement for STEMI cases, 71% agreement for arrhythmia cases, 65% for the lead misplacement and dextrocardia cases and only 37% agreement for the hypertrophy cases. In analyzing the total fixation duration, it was found that on average annotators study lead V1 the most (4.29 s), followed by leads V2 (3.83 s), the rhythm strip (3.47 s), II (2.74 s), V3 (2.63 s), I (2.53 s), aVL (2.45 s), V5 (2.27 s), aVF (1.74 s), aVR (1.63 s), V6 (1.39 s), III (1.32 s) and V4 (1.19 s). It was also found that on average the annotator spends an equal amount of time studying leads in the frontal plane (15.89 s) when compared to leads in the transverse plane (15.70 s). It was found that on average the annotators fixated on lead I first followed by leads V2, aVL, V1, II, aVR, V3, rhythm strip, III, aVF, V5, V4 and V6. We found a strong correlation ( r = 0.67) between time to first fixation on a lead and the total fixation duration on each lead. This indicates that leads studied first are studied the longest. There was a weak negative correlation between duration and accuracy ( r = − 0.2) and a strong correlation between age and accuracy ( r = 0.67). Conclusions Eye tracking facilitated a deeper insight into how expert annotators interpret the 12-lead ECG. As a result, the authors recommend ECG annotators to adopt an initial first impression/pattern recognition approach followed by a conventional systematic protocol to ECG interpretation. This recommendation is based on observing misdiagnoses given due to first impression only. In summary, this research presents eye gaze results from expert ECG annotators and provides scope for future work that involves exploiting computerized eye tracking technology to further the science of ECG interpretation. [ABSTRACT FROM AUTHOR]

Background: The Cardiac Safety Research Consortium (CSRC) provides both “learning” and blinded “testing” digital electrocardiographic (ECG) data sets from thorough QT (TQT) studies annotated for submission to the US Food and Drug Administration (FDA) to developers of ECG analysis technologies. This article reports the first results from a blinded testing data set that examines developer reanalysis of original sponsor-reported core laboratory data. Methods: A total of 11,925 anonymized ECGs including both moxifloxacin and placebo arms of a parallel-group TQT in 181 subjects were blindly analyzed using a novel ECG analysis algorithm applying intelligent automation. Developer-measured ECG intervals were submitted to CSRC for unblinding, temporal reconstruction of the TQT exposures, and statistical comparison to core laboratory findings previously submitted to FDA by the pharmaceutical sponsor. Primary comparisons included baseline-adjusted interval measurements, baseline- and placebo-adjusted moxifloxacin QTcF changes (ddQTcF), and associated variability measures. Results: Developer and sponsor-reported baseline-adjusted data were similar with average differences <1 ms for all intervals. Both developer- and sponsor-reported data demonstrated assay sensitivity with similar ddQTcF changes. Average within-subject SD for triplicate QTcF measurements was significantly lower for developer- than sponsor-reported data (5.4 and 7.2 ms, respectively; P < .001). Conclusion: The virtually automated ECG algorithm used for this analysis produced similar yet less variable TQT results compared with the sponsor-reported study, without the use of a manual core laboratory. These findings indicate that CSRC ECG data sets can be useful for evaluating novel methods and algorithms for determining drug-induced QT/QTc prolongation. Although the results should not constitute endorsement of specific algorithms by either CSRC or FDA, the value of a public domain digital ECG warehouse to provide prospective, blinded comparisons of ECG technologies applied for QT/QTc measurement is illustrated. [Copyright &y& Elsevier]

This document examines the formation, structure, and principles guiding the use of electrocardiogram (ECG) data sets obtained during thorough QT studies that have been derived from the ECG Warehouse of the Cardiac Safety Research Consortium (CSRC). These principles are designed to preserve the fairness and public interest of access to these data, commensurate with the mission of the CSRC. The data sets comprise anonymized XML formatted digitized ECGs and descriptive variables from placebo and positive control arms of individual studies previously submitted on a proprietary basis to the US Food and Drug Administration by pharmaceutical sponsors. Sponsors permit the release of these studies into the public domain through the CSRC on behalf of the Food and Drug Administration''s Critical Path Initiative and public health interest. For algorithm research protocols submitted to and approved by CSRC, unblinded “training” ECG data sets are provided for algorithm development and for initial evaluation, whereas separate blinded “testing” data sets are used for formal algorithm evaluation in cooperation with the CSRC according to methods detailed in this document. [Copyright &y& Elsevier]

Background: The global QT interval, emerging as a standard measurement provided by digital electrocardiographs, is defined by the earliest QRS onset and latest T-wave offset that occur in any of the standard leads. Differences between global ECG measurements and those from individual ECG leads have implications for the redefinition of normal values, for recognition of disease, and for drug safety. This study sought to quantify the differences between global QT intervals measured from 12 superimposed ECG leads with QT intervals and from single lead complexes, to examine the separate effects of QRS onset and T-wave offset on these differences, and to examine the reproducibility of these measurements.Methods: QTo intervals (Q onset to T offset) from 50 digitized ECGs sampled at 500 Hz were examined by computer assisted derivation of representative complexes from standard leads II, V(2), and V(3), by both baseline and tangent methods. Global QTo intervals were measured from superimposition of the representative complexes of all 12 leads. A time-coherent matrix of waveform onset and offset points allowed direct comparison of the components of the differences.Results: Global QTo and Bazett-adjusted global QTc were greater than each of the baseline and tangent measurements in representative leads II, V(2), and V(3), with mean differences ranging from 8 to 18 ms. QRS onset was earlier in the global complex than in each of the representative leads, with mean differences of 3-5 ms, whereas T-wave offset was significantly later in the global complex than in each of the representative leads, with mean differences of 5-11 ms. Remeasurement of all ECGs after an interval of 6 months confirmed the relative magnitudes of the global and individual lead QTo durations and small mean differences between pairs (-0.9 to 2.7 ms). Although global QTo had the largest mean difference (only 2.7 ms), it had the smallest standard deviation of the mean difference and lowest coefficient of variability (1.58%) of all measurements.Conclusion: Global QT measurements are systematically larger than measurements from representative complexes of individual leads. These differences result from the combined effects of earlier QRS onset and later T-wave offset in the global complex, with T-wave offset the more dominant component of the difference. [ABSTRACT FROM AUTHOR]

Abstract: This statement examines the relation of the resting ECG to its technology. Its purpose is to foster understanding of how the modern ECG is derived and displayed and to establish standards that will improve the accuracy and usefulness of the ECG in practice. Derivation of representative waveforms and measurements based on global intervals are described. Special emphasis is placed on digital signal acquisition and computer-based signal processing, which provide automated measurements that lead to computer-generated diagnostic statements. Lead placement, recording methods, and waveform presentation are reviewed. Throughout the statement, recommendations for ECG standards are placed in context of the clinical implications of evolving ECG technology. [Copyright &y& Elsevier]

Background: Enhanced external counterpulsation (EECP) reduces angina and extends time to exercise-induced ischemia in patients with symptomatic coronary disease. One- and two-center studies and a retrospective case series reported that EECP improves myocardial perfusion in stable angina pectoris. We sought to critically evaluate and quantify the effect of EECP on myocardial perfusion. Methods: In 6 US university hospitals, EECP was performed for 35 hours in patients with class II to IV angina who had exercise-induced myocardial ischemia. Symptom-limited quantitative gated technetium Tc 99m sestamibi single photon emission computed tomography exercise perfusion imaging was performed at baseline and 1 month post-EECP. Sestamibi was injected at the same heart rate in both stress tests. Single photon emission computed tomography images were read at a blinded core laboratory. Results: Thirty-seven patients were enrolled, 34 of whom completed pre- and post-EECP stress testing. The mean age was 61 +/- 10 years, 81% were male, 78% had prior revascularization, and 68% had 3-vessel disease. The mean angina class decreased from 2.7 +/- 0.7 at baseline to 1.7 +/- 0.7 after EECP (P < .001). Exercise duration increased from 9.1 +/- 3.7 minutes at baseline to 10.2 +/- 3.6 minutes post-EECP (P = .03). The average percentage of tracer uptake, magnitude of reversibility, average thickening fraction, and the left ventricular ejection fraction remained unchanged after EECP. Conclusions: We confirm previous report that EECP reduces angina and improves exercise capacity. There were no significant changes in mean defect magnitude, amount of reversibility, thickening fraction, and ejection fraction measured using myocardial quantitative single photon emission computed tomography imaging when compared at identical pre- and post-EECP heart rates. [ABSTRACT FROM AUTHOR]

Abstract: We examined the accuracy of computer-based rhythm interpretation from one electrocardiograph manufacturer (GE Healthcare Technologies MUSE software 005C) in 4297 consecutive recordings in a university hospital setting. Overreading was performed by either of 2 experienced cardiologists, and all disagreements with the initial computer rhythm statement were reviewed by the second cardiologist to achieve physician consensus used as the “gold standard” for rhythm diagnosis. Overall, 13.2% (565/4297) of computer-based rhythm statements required revision, but excluding tracings with pacemakers, the revision rate was 7.8% (307/3954), including 3.8% involving the primary rhythm diagnosis and 3.9% involving definition of ectopic complexes. The false-negative rate for sinus rhythm was only 1.3%, but a computer diagnosis of sinus rhythm was incorrect in 9.9% of other rhythms. The false-negative rate for atrial fibrillation was 9.2%, whereas a computer diagnosis of atrial fibrillation was incorrect in 1.1% of other rhythms, including sinus. Computer diagnosis of paced rhythms remains problematic, and physician overreading to correct computer-based electrocardiogram rhythm diagnoses remains mandatory. [Copyright &y& Elsevier]

To assess the value and predictive limitations of the exercise ST/HR slope, exercise test results were compared in 50 patients with stable angina and in 17 normal subjects with those in two groups known to have a high prevalence of inaccurate electrocardiographic responses to exercise. The last two groups included 51 patients tested within three weeks of acute myocardial infarction and 17 with important aortic regurgitation but no coronary disease. Of the normal subjects, 16 (94%) had ST/HR values less than or equal to 1 X 1 microV/beat/min. Of those with stable angina pectoris, 42 of 46 (91%) patients with coronary artery disease had ST/HR slopes ranging from 1 X 2 to 20 X 0 microV/beat/min, with false negative findings (slopes less than or equal to 1 X 1 microV/beat/min) in only four (9%). In contrast, of those with recent myocardial infarction, 15 of 42 (36%) with coronary disease had false negative slopes, including 12 of 20 (60%) with anterior wall injury. Of those with aortic regurgitation, conversely, 14 of 16 (88%) patients with calculable ST/HR slopes had values greater than 1 X 1 microV/beat/min despite the absence of coronary disease. Despite the accuracy of the test in patients with stable angina, false negative results are common in those after recent myocardial infarction, and false positive results occur often in those with abnormal volume loading due to aortic regurgitation. [ABSTRACT FROM PUBLISHER]

Since recognition of factors which modify the duration of ejection in aortic stenosis is of clinical importance, the relations among rate-corrected left ventricular ejection time, aortic valve area, and determinants of ventricular performance were studied in 54 catheterised patients. In patients with a normal cardiac index, increasing duration of ejection was linearly related to increasing obstruction. In patients with failing ventricles, on the other hand, the ejection time was less prolonged, and the duration of ejection was unrelated to valve area. At fixed valve area, relation with cardiac output, stroke volume, heart rate, mean aortic valve pressure gradient, mean aortic pressure, and left ventricular end-diastolic pressure could not adequately explain the observed scatter in ejection time. This suggests a multifactorial basis for the wide range of ejection times observed with severe aortic stenosis. [ABSTRACT FROM PUBLISHER]