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The 12-lead electrocardiogram (ECG) is a complex set of cardiac signals that require a high degree of skill and clinical knowledge to interpret. Therefore, it is imperative to record and understand how expert readers interpret the 12-lead ECG. This short paper showcases how eye tracking technology and audio data can be fused together and visualised to gain insight into the interpretation techniques employed by an eminent ECG champion, namely Dr Rory Childers.

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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 60Hz, eye gaze coordinates were acquired every 16.7ms. 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 58s (SD=23). Fleiss' generalized kappa coefficient (Pa=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 (4.29s), followed by leads V2 (3.83s), the rhythm strip (3.47s), II (2.74s), V3 (2.63s), I (2.53s), aVL (2.45s), V5 (2.27s), aVF (1.74s), aVR (1.63s), V6 (1.39s), III (1.32s) and V4 (1.19s). It was also found that on average the annotator spends an equal amount of time studying leads in the frontal plane (15.89s) when compared to leads in the transverse plane (15.70s). 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.

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Spontaneous occurrence of an interpolated atrial premature complex, an unusual finding outside of the experimental electrophysiology laboratory, was detected and confirmed by evaluation of P-wave morphology in a patient who underwent 12-lead ambulatory electrocardiography.

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The clinically useful prognostic value of precordial QT dispersion in patients with heart disease is generally attributed to its measurement of regional heterogeneity of ventricular repolarization. However, when repolarization is abnormal, differences in measured QT intervals might result simply from variation in projection of the T-wave loop. To provide insight into the mechanism of QT dispersion, we used an analog device to transform conventional 12-lead electrocardiograms (ECGs) of 78 patients to derived 12-lead ECGs based on the heart vector. Because the electrical activity of the heart is represented by a single dipole, all QT dispersion in the transformed ECGs results from variation in projection of the T-wave loop and cannot be due to local heterogeneity of repolarization. Measured as the difference between the longest and shortest precordial QT intervals, QT dispersion in the derived ECGs, with no local heterogeneity of repolarization, was 53 +/- 49 ms (mean +/- SD). QT dispersion in these derived ECGs was similar in magnitude to that measured from the original standard 12-lead ECGs in these patients (49 +/- 23 ms, p = NS). Therefore, the precordial QT dispersion measured from standard ECGs of patients with coronary artery disease can be explained by interlead variation in precordial projection of the T-wave loop. Although regional heterogeneity might still contribute to precordial repolarization findings and to prognosis, this is not required to explain the QT dispersion observed in patients with coronary artery disease. Therefore, QT interval dispersion is not equivalent to heterogeneity of repolarization.

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BACKGROUND: Transmyocardial laser revascularization, a new strategy for the treatment of diffuse ischemic heart disease, uses laser technology for the theoretical purpose of forming transmyocardial channels in the heart to increase perfusion to ischemic zones. This report summarizes our initial clinical experience with the procedure. METHODS: Excimer transmyocardial laser revascularization was performed in a reversibly ischemic region of the heart in 15 patients. Ischemia and myocardial viability were evaluated by assessment of symptoms and of results of radionuclide single photon emission computed tomography imaging, exercise tolerance testing, and 24-hour Holter monitoring. RESULTS: No adverse events occurred as a result of the laser revascularization, although 1 patient with preoperative ventricular arrhythmias died 48 hours postoperatively as a result of refractory ventricular tachycardia. Angina class decreased significantly from base line values in patients who had undergone the procedure (mean Canadian Cardiovascular Association angina class, 3.5+/-0.5 at base line, 1.6+/-0.6 at 1 month, 1.5+/-0.8 at 3 months, 1.9+/-0.9 at 6 months, 1.8+/-0.8 at 12 months; p<0.002), and nitroglycerin requirements were similarly decreased in patients who had undergone laser revascularization (mean g/wk of sublingual nitroglycerin, 19+/-4 at baseline, 5+/-3 at 1 month, 4+/-2 at 3 months, 4+/-2 at 6 months, 2+/-1 at 12 months; p<0.02). Exercise tolerance testing demonstrated increase in exercise duration compared with base line values (mean minutes, 7.4+/-3.1 at base line, 8.0+/-3.9 at 1 month, 8.5+/-4.4 at 3 months, and 9.0+/-3.9 at 12 months; p>0.05); those increases were not large enough to be statistically significant, however. CONCLUSIONS: Our data are consistent with the concept that excimer transmyocardial laser revascularization in individuals with significant ischemic heart disease appears to be well tolerated, can be performed safely, and may lead to a reduction in ischemic symptomatology.

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Patients with mitral valve prolapse (MVP) may develop severe mitral regurgitation (MR) and require valve surgery. Preliminary data suggest that high body weight and blood pressure might add to the irreversible factors of older age and male gender in increasing risk of these complications. Fifty-four patients with severe MR due to MVP were compared with 117 control subjects with uncomplicated MVP to elucidate factors independently associated with severe MR: the need for valve surgery and the cumulative risk of requiring mitral valve surgery. Patients with severe MR were older (p<0.00005), more overweight (p = 0.002), had higher systolic (p = 0.0003) and diastolic (p = 0.007) blood pressures, and were more likely to have hypertension (p = 0.0001) and to be men (p<0.001). In both groups, men had higher blood pressure and relative body weight than women. In multivariate analysis, older age was most strongly associated with MR; higher body mass index, hypertension, and gender were independent predictors of severe MR in analyses that excluded age. Among the 54 patients with severe MR, the 32 (59%) who underwent mitral valve surgery during 11 years of follow-up were older, more overweight, and more likely to be hypertensive than those not requiring surgery. Among patients undergoing mitral valve surgery in 3 centers, mitral prolapse was the etiology in 25%, 67% of whom were men. Using these data and national statistics, we estimate that the gender-specific cumulative risk for requiring valvular surgery for severe MR in subjects with MVP is 0.8% in women and 2.6% in men before age 65, and 1.4% and 5.5% by age 75. Thus, subjects with MVP who are older, more overweight, and hypertensive are at greater risk for severe MR and valve surgery. Higher blood pressure and relative weight in men with MVP appear to contribute to the gender difference in risk for severe MR.

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Among patients with chronic nonischemic mitral regurgitation (MR), high short-term mortality risk can be identified by left (LV) and/or right ventricular (RV) ejection fraction (EF) criteria (LVEF 20%, MVR significantly improved survival versus medical treatment (rest: p < 0.0001, exercise: p = 0.0003). In high risk MR patients, MVR improves survival; preoperative RV performance can define subgroups with different long-term postoperative survival.

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UNLABELLED: Perioperative myocardial ischemia (MI) is associated with postoperative cardiac morbidity. Postoperative sympatholysis may reduce the incidence of MI. This study evaluated such a reduction postoperatively with the administration of prophylactic beta-blockers in patients undergoing elective total knee arthroplasty with epidural anesthesia and postoperative epidural analgesia. One hundred seven patients were preoperatively randomized into two groups, control and beta-blockers, who received postoperative esmolol infusions on the day of surgery and metoprolol for the next 48 h to maintain a heart rate less than 80 bpm. Patients were followed for ST segment depression by using a Holter monitor and adverse cardiac outcomes. Postoperative electrocardiographic ischemia was significantly more prevalent in the control group compared with the beta-blocker group during esmolol blockade (0 of 52 vs 4 of 55; P = 0.04) and tended to be more common in the control group the next two days (8 of 55 vs 3 of 52; P = 0.135). In addition, the number of ischemic events (control, 50; beta-blockers, 16) and total ischemic time (control, 709 min; beta-blocker, 236 min) were also significantly different from the control group. Myocardial infarctions and cardiac events were more common in the control group, but these differences were not significant. Our results suggest that the use of prophylactic beta-blocker therapy may reduce the incidence of postoperative MI. IMPLICATIONS: Prophylactic beta adrenergic blockade administered after elective total knee arthroplasty was associated with a reduced prevalence and duration of postoperative myocardial ischemia detected with Holter monitoring.

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OBJECTIVE: To summarize the 6-month follow-up of a cohort of patients with clinically significant coronary artery disease who received direct myocardial injection of an E1-E3- adenovirus (Ad) gene transfer vector (Ad(GV)VEGF121.10) expressing the human vascular endothelial growth factor (VEGF) 121 cDNA to induce therapeutic angiogenesis. BACKGROUND: Therapeutic angiogenesis describes a novel approach to the treatment of vascular occlusive disease that uses the administration of growth factors known to induce neovascularization of ischemic tissues. METHODS: Direct myocardial injection of Ad(GV)VEGF121.10 into an area of reversible ischemia was carried out in 21 patients as an adjunct to conventional coronary artery bypass grafting (group A, n = 15) or as sole therapy using a minithoracotomy (group B, n = 6). RESULTS: No evidence of systemic or cardiac-related adverse events related to vector administration was observed up to 6 months after therapy. Trends toward improvement in angina class and exercise treadmill testing at 6-month follow-up in the sole therapy group suggest the effects of this therapy are persistent for > or =6 months. CONCLUSIONS: This study suggests that direct myocardial administration of Ad(GV)VEGF121.10 appears to be well tolerated in patients with clinically significant coronary artery disease. Initiation of phase II evaluation of this therapy appears warranted.

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BACKGROUND: Therapeutic angiogenesis, a new experimental strategy for the treatment of vascular insufficiency, uses the administration of mediators known to induce vascular development in embryogenesis to induce neovascularization of ischemic adult tissues. This report summarizes a phase I clinical experience with a gene-therapy strategy that used an E1(-)E3(-) adenovirus (Ad) gene-transfer vector expressing human vascular endothelial growth factor (VEGF) 121 cDNA (Ad(GV)VEGF121.10) to induce therapeutic angiogenesis in the myocardium of individuals with clinically significant coronary artery disease. METHODS AND RESULTS: Ad(GV)VEGF121.10 was administered to 21 individuals by direct myocardial injection into an area of reversible ischemia either as an adjunct to conventional coronary artery bypass grafting (group A, n=15) or as sole therapy via a minithoracotomy (group B, n=6). There was no evidence of systemic or cardiac-related adverse events related to vector administration. In both groups, coronary angiography and stress sestamibi scan assessment of wall motion 30 days after therapy suggested improvement in the area of vector administration. All patients reported improvement in angina class after therapy. In group B, in which gene transfer was the only therapy, treadmill exercise assessment suggested improvement in most individuals. CONCLUSIONS: The data are consistent with the concept that direct myocardial administration of Ad(GV)VEGF121.10 to individuals with clinically significant coronary artery disease appears to be well tolerated, and initiation of phase II evaluation of this therapy is warranted.

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Heart rate (HR) adjustment of ST depression (STD) has been shown to correctly classify exercise test findings in up to 85% of normal subjects and patients with "equivocal" electrocardiographic (ECG) responses (> or =100 microV upsloping STD), but the performance of these methods in patients with truly negative ECG responses (<100 microV STD) has not been examined in detail. We reviewed negative standard exercise ECGs in 54 men and women (mean age 61 years) with coronary disease, comprising 16% of consecutive treadmill tests that were performed in 337 patients with angiographic coronary artery disease or stable angina. Mean STD was only 63 +/- 21 microV (0.63 mm) in these negative tests. Despite these subthreshold values for STD, the ST/HR index was abnormal (> or =1.6 microV/bpm) in 27 of 54 patients (50%) when STD was adjusted for the change in HR during exercise. Compared with patients with normal values for HR-adjusted STD, patients with an abnormal ST/HR index were slightly older (64 vs. 58 years, P < 0.05) and demonstrated a trend toward lower exercise duration (10.0 vs. 11.8 min). An abnormal ST/HR index was associated with greater subthreshold STD (73 vs. 53 microV, P < 0.0005) and smaller HR change (35 vs. 56 bpm, P < 0.0001) with exercise. Among the 27 patients with a normal ST/HR index by simple HR adjustment, 11 (44%) had abnormal ST/HR slopes (> or =2.4 microV/bpm) by the more complex linear regression method. Therefore, HR adjustment of STD contributes to the improved sensitivity of the exercise ECG by correct classification of some patients with truly negative standard tests. The magnitude of subthreshold STD and the extent of HR change with exercise both contribute to improved test performance. The increased sensitivity afforded by HR adjustment of STD highlights the importance of the precise measurement of subthreshold STD that is afforded by computerized ECG during exercise testing.

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Identification of left ventricular hypertrophy (LVH) using 12-lead ECG criteria based primarily on QRS amplitudes has been limited by poor sensitivity at acceptable levels of specificity. Because the product of QRS voltage and duration, as an approximation of the time-voltage area of the QRS complex, can improve accuracy of the 12-lead ECG for LVH, we examined the diagnostic value of true time-voltage area measurements of QRS complexes from the standard 12-lead ECG. Standard 12-lead ECGs and echocardiograms were obtained in 175 control subjects without LVH and in 74 patients with regurgitant valvular heart disease and LVH defined by echocardiographic criteria (indexed LV mass >110 g/m2 in women and >125 g/m2 in men). Standard voltage criteria, voltage-duration products (voltage multiplied by QRS duration), and true time-voltage areas of the QRS were calculated for Sokolow-Lyon criteria (SV1 +RV(5/6)) and the 12-lead sum of voltage criteria. Test sensitivities were compared using gender-specific partitions with matched specificity of 98% in the 175 subjects without LVH. Measurement of the time-voltage area significantly improved sensitivity for both criteria. The 76% sensitivity of the 12-lead sum area and 65% sensitivity of Sokolow-Lyon area were significantly greater than the 54% sensitivity of the approximation of QRS area provided by each voltage-duration product (P<.001 and P=.021) and than the 46% and 43% sensitivities of the respective simple voltage criteria (each P<.001). Comparison of receiver operating characteristic curves confirmed the superior overall performance of time-voltage area criteria compared with both voltage-duration products and simple voltage criteria. These results suggest that use of time-voltage areas can dramatically improve identification of LVH by 12-lead ECG. Further study of this approach is needed to identify optimal criteria for LVH based on the time-voltage area measurements from the 12-lead ECG.

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BACKGROUND: Optimal criteria for valve replacement are unclear in asymptomatic/minimally symptomatic patients with aortic regurgitation (AR) and normal left ventricular (LV) performance at rest. Moreover, previous studies have not assessed the prognostic capacity of load-adjusted LV performance ("contractility") variables, which may be fundamentally related to clinical state. Therefore, 18 years ago, we set out to test prospectively the hypothesis that objective noninvasive measures of LV size and performance and, specifically, of load-adjusted variables, assessed at rest and during exercise (ex), could predict the development of currently accepted indications for operation for AR. METHODS AND RESULTS: Clinical variables and measures of LV size, performance, and end-systolic wall stress (ESS) were assessed annually in 104 patients by radionuclide cineangiography at rest and maximal ex and by echocardiography at rest; ESS was derived during ex. During an average 7.3-year follow-up among patients who had not been operated on, 39 of 104 patients either died suddenly (n = 4) or developed operable symptoms only (n = 22) or subnormal LV performance with or without symptoms (n = 13) (progression rate=6.2%/y). By multivariate Cox model analysis, change (delta) in LV ejection fraction (EF) from rest to ex, normalized for deltaESS from rest to ex (deltaLVEF-deltaESS index), was the strongest predictor of progression to any end point or to sudden cardiac death alone. Unadjusted deltaLVEF was almost as efficient. Symptom status modified prediction on the basis of the deltaLVEF-deltaESS index. The population tercile at highest risk by deltaLVEF-deltaESS progressed to end points at a rate of 13.3%/y, and the lowest-risk tercile progressed at 1.8%/y. CONCLUSIONS: Currently accepted symptom and LV performance indications for valve replacement, as well as sudden cardiac death, can be predicted in asymptomatic/minimally symptomatic patients with AR by load-adjusted deltaLVEF-deltaESS index, which includes data obtained during exercise.

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Dispersion of precordial QT intervals has been attributed to delay in the recovery process in the myocardium under the exploring electrode, a local effect. However, the phenomenon also could be explained by different projections of the heart vector, in which case the 12-lead electrocardiogram (ECG) derived from the heart vector would show similar dispersion that could not be local in nature because the electrical activity of the heart is represented by a single dipole. Using an analog device that switched between the two, conventional and derived ECGs were obtained from 129 normal subjects. Measured as the difference between the longest and shortest precordial QT intervals, QT dispersion from the derived ECGs (mean +/- SD, 40 +/- 20 ms) was nearly identical in magnitude to that from the standard ECGs (41 +/- 18 ms, P = NS). Further analysis of the derived ECGs revealed nonuniform distributions of both the maximal and minimal QT intervals across the precordial leads. In addition, a weak correlation was found between the QT interval and the T wave amplitude in the two precordial leads with the lowest T-wave amplitudes (r = -0.303 in V1, P = .001, and r = 0.253 in V6, P = .005). While findings in patients with disease or with abnormal ECGs may differ and require separate examination, these data suggest that the observed magnitude of precordial QT dispersion in normal subjects can be explained by differences in precordial projection of the end of the T wave rather than by local effect.

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