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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.

The History of Exercise Testing chapter reviews the development of the exercise test from Einthoven to the contributions of Bruce and Ellestad. Feil and Siegel recognized that myocardial ischemia and thus coronary artery disease (CAD) could be diagnosed by ST depression during exercise. Master and Oppenheimer developed the first standardized exercise test, a 1.5-minute step test to evaluate cardiac capacity and cardiovascular disease. Goldhammer and Scherf recommended the use of exercise testing for the diagnosis of chest pain or angina. Wilson’s development of the six chest leads increased the opportunity to detect ischemia with 12 lead electrocardiography. Bruce developed the multi-stage treadmill test now termed the Bruce protocol. An outcome study of Ellestad demonstrated that 1 mm of ST depression predicted cardiac events and death. Following one hundred years of development, the exercise test remains the foundation of stress testing.

BACKGROUND: The utility of exercise‐induced ST‐segment depression for diagnosing ischemic heart disease (IHD) in women is unclear. HYPOTHESIS: Based 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. METHODS: Twenty‐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. RESULTS: Mean age was 54 ± 7 years, body mass index 25 ± 4 kg/m(2), and RHI 2.51 ± 0.66. Three women (10%) had RHI 0.05). RHI did not predict ST‐segment depression. CONCLUSIONS: Our 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.

Background: \ud 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.\ud \ud Methods: \ud 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).\ud \ud Results: \ud 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 3.6 milliseconds for the PR interval, 0.1 to 8.1 milliseconds for QRS duration, and 0.1 to 9.3 milliseconds 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 13.3 milliseconds in the LQT1 subjects and from 0.2 to 11.0 milliseconds in the LQT2 subjects. Differences in measured QT duration (not corrected for heart rate) ranged from 0.2 to 10.5 milliseconds in the LQT1 subjects and from 0.9 to 12.8 milliseconds in the LQT2 subjects.\ud \ud Conclusions: \ud 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.

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.

Purpose Arsenic trioxide (ATO) is a highly effective agent for the treatment of acute promyelocytic leukemia (APL). QT interval prolongation is common with ATO and can pose a barrier to effective administration. The objective of this study was to characterize the prevalence, management, and clinical consequences of QT prolongation in a large cohort of patients treated with ATO. Patients and Methods We analyzed 3,011 electrocardiograms from 113 patients with non-APL acute myeloid leukemia and myelodysplastic syndrome who were treated on a previously reported clinical trial. QT intervals were assessed using four different correction formulas, and data were correlated with clinical parameters and treatment with ATO. Results There were no clinically significant cardiac events in the study population. Of those receiving ATO therapy, 29 patients (26%) had rate-uncorrected QT values above 470 ms and 13 (12%) had values exceeding 500 ms. With the commonly used Bazett rate correction formula, 102 patients (90%) had QTc greater than 470 ms, including 74 (65%) above 500 ms. By using alternative rate correction formulas, only 24% to 32% of patients had rate-corrected QT intervals above 500 ms. Conclusion QT interval prolongation is common with ATO treatment, but clinically significant arrhythmias are rare and can be avoided with appropriate precautions. Use of the Bazett correction may result in unnecessary interruptions in ATO therapy, and alternative rate correction formulas should be considered for routine electrocardiographic monitoring.

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 (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 (4.29 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.

The electrocardiogram (ECG) is the most widely used imaging tool helping in diagnosis and initial management of patients presenting with symptoms compatible with acute coronary syndrome. Acute ischemia affects the configuration of the QRS complexes, the ST segments and the T waves. The ECG should be read along with the clinical assessment of the patient. ST segment elevation (and ST depression in leads V1 -V3 ) in patients with active symptoms usually indicates acute occlusion of an epicardial artery with ongoing transmural ischemia. These patients should be triaged for emergent reperfusion therapy per current guidelines. However, many patients have ST segment elevation secondary to nonischemic causes. ST depression in leads other than V1 -V3 usually are indicative of subendocardial ischemia secondary to subocclusion of the epicardial artery, distal embolization to small arteries or spasm supply/demand mismatch. ST depression may also be secondary to nonischemic etiologies, such as left ventricular hypertrophy, cardiomyopathies, etc. Knowing the clinical scenario, comparison to previous ECG and subsequent ECGs (in cases that there are changes in the quality or severity of symptoms) may add in the diagnosis and interpretation in difficult cases. This review addresses the different ECG patterns, typically seen in patients with active symptoms, after resolution of symptoms and the significance of such changes when seen in asymptomatic patients.

Background For many years was considered that negative T wave in ischemic heart disease represents ischemia and for many authors located in subepicardial area. Methods We performed a review based in the literature and in the experience of the authors commenting the real significance of the presence of negative T wave in patients with ischemic heart disease. Results The negative T wave may be of primary or secondary type. Negative T wave observed in ischemic heart disease are of primary origin, therefore not a consequence of abnormal repolarization pattern. The negative T wave of ischemic origin presents the following characteristics: (1) are symmetrical and of variable deepness; (2) present mirror patterns; (3) starts in the second part of repolarization; and (4) may be accompanied by positive or negative U wave. The negative T wave of ischemic origin may be seen in the following clinical settings: (1) postmyocardial infarction due to a window effect of necrotic zone and (2) as a consequence of reperfusion in case of aborted MI when the artery has opened spontaneously, or after fibrinolysis, PCI, or coronary spasm. Conclusion Acute ongoing ischemia do not cause negative T wave. This pattern appears when the ongoing ischemia is vanishing or in the chronic phase. In all these cases the cause of negative T wave is not located in the subepicardial area. Furthermore, positive exercise testing is expressed by ST depression never by isolated negative T wave. There are many circumstances that may present negative T wave outside ischemic heart disease and that have been discussed in this paper.

Exercise duration during exercise treadmill testing (ETT) predicts long-term outcome among asymptomatic patients with mitral regurgitation. However, the prognostic value of preoperative exercise duration in patients who undergo mitral valve surgery is unknown. We examined findings among 45 prospectively followed (average 9.2 ± 4.3 years) patients (aged 54.8 ± 12.0 years, 45% men) with chronic isolated severe MR who underwent ETT before mitral valve surgery to test the hypotheses that exercise duration predicts long-term postoperative survival and persistent symptoms within 2 years after operation. During follow-up, 11 patients died; of these, 8 had persistent symptoms. Among patients who exercised7 minutes, average annual postoperative all-cause and cardiovascular mortality risks were 0.75% (both endpoints) versus 5.4% and 4.8%, respectively, versus those who exercised ≤7 minutes (p = 0.003 all-cause, p = 0.007 cardiovascular). Exercise duration predicted postoperative deaths (p.02 all cause, p.04 cardiovascular) even when analysis was adjusted for preoperative variations in age, gender, medications, history of atrial fibrillation, and peak exercise heart rates. Other ETT, echocardiographic, and clinical variables were not independently associated with these outcomes when exercise duration was considered in the analysis. Preoperative exercise duration also predicted postoperative (New York Heart Association functional class ≥II) symptom persistence (p = 0.012), whereas other ETT, echocardiographic and clinical variables did not (NS, all). In conclusion, among patients who undergo surgery for chronic nonischemic mitral regurgitation, preoperative exercise duration, unlike many commonly used descriptors, is useful for predicting postoperative mortality and symptom persistence. Future research should determine whether interventions to improve exercise tolerance before mitral valve surgery can modify these postoperative outcomes.

Background: Nonsustained ventricular tachycardia (VT), frequent in unoperated severe mitral regurgitation (MR), confers mortality risk [sudden death (SD) and cardiac death (CD)]. The prognostic value of VT after mitral valve surgery (MVS) is unknown; we aimed to define this prognostic value and to assess its modulation by left (LV) and/or right (RV) ventricular ejection fraction (EF) for mortality after MVS. Methods: In 57 patients (53% females, aged 58 ± 12 years) with severe MR prospectively followed before and after MVS, we performed 24-hour ambulatory electrocardiograms approximately annually. LVEF and RVEF were determined within 1 year after MVS by radionuclide cineangiography. Results: During 9.52 ± 3.49 endpoint-free follow-up years, late postoperative CD occurred in 11 patients (7 SD, 4 heart failures). In univariable analysis, >1 VT episode after MVS predicted SD (p < 0.01) and CD (SD or heart failure; p < 0.04). Subnormal postoperative RVEF predicted CD (p < 0.04). When adjusted for preoperative age, gender, etiology or antiarrhythmics, both postoperative VT and RVEF predicted CD (p ≤ 0.05). When postoperative VT and RVEF were both in the multivariable model, only subnormal RVEF predicted CD (p < 0.04). Among those with normal RVEF, VT >1 episode predicted SD (p = 0.03). Conclusion: Postoperative VT and subnormal RVEF predict late postoperative deaths in nonischemic MR. Their assessment may aid patient management.

A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons Published by Elsevier Inc. http://dx.doi.org/10.1016/j.jacc.2012.07.012

In this study, we consider the proposition that the criteria for the electrocardiographic (ECG) diagnosis of left bundle-branch block (LBBB) be revised, a proposition born from analysis of results of cardiac resynchronization therapy trials. The various ECG definitions for LBBB (or lack thereof) used in these trials are reviewed as are the results of the analysis of ECGs from patients with left ventricular conduction disturbances by Grant and Dodge (Am J Med. 1956;20:834-852) and the criteria for the ECG diagnosis of LBBB recommended by the World Health Organization and the International Society and Federation for Cardiology in 1985. These criteria stress that the QRS complex be notched or slurred, that the initial portion of the QRS complex (the "septal Q waves") be absent, and that the QRS duration be at least 120 milliseconds in duration. This is in contrast to the recent suggestion that the QRS complex has a minimum duration of 130 to 140 milliseconds. We conclude that the criteria for the ECG diagnosis of LBBB should be standardized to that recommended by the World Health Organization and International Society and Federation for Cardiology with retention of the minimum duration of 120 milliseconds and that the QRS prolongation should be not be gradual. However, we also conclude that in patients with LBBB being considered for cardiac resynchronization therapy, the duration of the QRS complex should be at least 130 milliseconds.

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 P 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.

TdP is an uncommon but potentially fatal arrhythmia that can be caused by drugs that cause selective prolongation of action potential durations in certain layers of the ventricular myocardium, which creates dispersion of repolarization and a long, distorted QT-U interval on the ECG. A summary of key points to remember is provided in Table 3. Table 3 Summary of Key Points For patients who receive QT-prolonging drugs in hospital units with continuous ECG monitoring, TdP should be avoidable if there is an awareness of individual risk factors and the ECG signs of drug-induced LQTS. Particularly important are the ECG risk factors for TdP, including marked QTc prolongation to >500 ms (with the exception of amiodarone- or verapamil-induced QT prolongation), marked QT-U prolongation and distortion after a pause, onset of ventricular ectopy and couplets, macroscopic T-wave alternans, or episodes of polymorphic ventricular tachycardia that are initiated with a short-long-short R-R cycle sequence (typically, PVC– compensatory pause–PVC). Recognition of these ECG harbingers of TdP allows for treatment with intravenous magnesium, removal of the offending agent, and correction of electrolyte abnormalities and other exacerbating factors, including the prevention of bradycardia and long pauses with temporary pacing if necessary.

Guidelines recommend that patients with suggestive symptoms of myocardial ischemia and ST-segment elevation (STE) inor =2 adjacent electrocardiographic leads should receive immediate reperfusion therapy. Novel strategies aimed to reduce door-to-balloon time, such as prehospital wireless electrocardiographic transmission, may be dependent on the interpretation accuracy of the electrocardiogram (ECG) readers. We assessed the ability of experienced electrocardiographers to differentiate among STE, acute STE myocardial infarction (STEMI), and nonischemic STE (NISTE). A total of 116 consecutive ECGs showing STE were studied. Fifteen experienced cardiologists were asked to decide, based on the ECG and assuming that the patient had compatible symptoms, whether they would send each patient for primary percutaneous coronary intervention (PPCI). If NISTE was chosen, the reader selected 1 or more 12 possible options to explain the choice. Of 116 patients, only 8 had STEMI. The percentage of ECGs for which PPCI was recommended for the patient by the individual readers varied widely (7.8% to 33%). There was no significant difference between the North American and Other Countries readers (p = 0.13). The sensitivity and specificity of the individual readers ranged from 50% to 100% (average 75%) and 73% to 97% (average 85%), respectively. There were broad inconsistencies among the readers in the chosen reasons used to classify NISTE. In conclusion, we found wide variations among experienced electrocardiographers in reading ECGs with STE and differentiating STEMI with need for PPCI from NISTE. There is a need to revise our current electrocardiographic criteria for differentiating STEMI from NISTE.

To assess the utility of stress electrocardiography (ECG) for identifying the presence and severity of obstructive coronary artery disease (CAD) defined by coronary computed tomographic angiography (CCTA) among patients with normal nuclear myocardial perfusion imaging (MPI).The study population comprised 119 consecutive patients with normal MPI who also underwent CCTA (interval 3.5+/-3.8 months). Stress ECG was performed at the time of MPI. CCTA and MPI were interpreted using established scoring systems, and CCTA was used to define the presence and extent of CAD, which was quantified by a coronary artery jeopardy score.Within this population, 28 patients (24%) had obstructive CAD identified by CCTA. The most common CAD pattern was single-vessel CAD (61%), although proximal vessel involvement was present in 46% of patients. Patients with CAD were nearly three times more likely to have positive standard test responses (1 mm ST-segment deviation) than patients with patent coronary arteries (36 vs. 13%, P=0.007). In multivariate analysis, a positive ST-segment test response was an independent marker for CAD (odds ratio: 2.02, confidence interval: 1.09-3.78, P=0.03) even after adjustment for a composite of clinical cardiac risk factors (odds ratio: 1.85, confidence interval: 1.05-3.23, P=0.03). Despite uniformly normal MPI, mean coronary jeopardy score was three-fold higher among patients with positive compared to those with negative ST-segment response to exercise or dobutamine stress (1.9+/-2.7 vs. 0.5+/-1.4, P=0.03).Stress-induced ST-segment deviation is an independent marker for obstructive CAD among patients with normal MPI. A positive stress ECG identifies patients with a greater anatomic extent of CAD as quantified by coronary jeopardy score.

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, V2, and V3, 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, V2, and V3, 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.

This statement provides a concise list of diagnostic terms for ECG interpretation that can be shared by students, teachers, and readers of electrocardiography. This effort was motivated by the existence of multiple automated diagnostic code sets containing imprecise and overlapping terms. An intended outcome of this statement list is greater uniformity of ECG diagnosis and a resultant improvement in patient care. The lexicon includes primary diagnostic statements, secondary diagnostic statements, modifiers, and statements for the comparison of ECGs. This diagnostic lexicon should be reviewed and updated periodically.

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.

Short-term and longitudinal applications of electrocardiography have led to a convergence of technologies that blur distinctions among standard 12-lead recording, exercise testing, ambulatory monitoring, and bedside monitoring. Although there are bgold standardQ applications of the resting 12-lead ECG, challenges to this standard include imperfect criteria, diagnostic advances in other areas of cardiac imaging, and increasing use of activity-compatible recording. Longer term ECG recording with activity-compatible electrode placement has become

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.

Background: Current guidelines do not endorse exercise electrocardiography (Ex-ECG) screening in asymptomatic adults due to poor diagnostic accuracy for clinical coronary artery disease (CAD), however Ex-ECG combined with other variables paradoxically has strong prognostic accuracy for cardiovascular mortality. Ex-ECG ST segment depression “false positive” results are common in women, who have higher rates of vascular dysfunction such as Raynaud’s and migraines compared to men. We hypothesized that ST segment depression indicates endothelial vascular dysfunction, which is known to predict an adverse prognosis. To test this hypothesis, we evaluated the relationship between Ex-ECG and peripheral endothelial vascular function in asymptomatic women. Methods: Asymptomatic women with no cardiac risk factors and normal resting ECG underwent maximal Bruce protocol Ex-ECG testing (GE Healthcare). Computer-generated Ex-ECG ST segment values were independently verified by 2 cardiologists. Based on established methods, endothelial vascular function was assessed by calculating reactive hyperemia index (RHI) using peripheral vascular testing (Endopat, Itamar). As established previously, RHI Results: Among 35 women, mean age 54±8 years and BMI 24±4, there were 5 (14%) women with abnormal RHI. Women with abnormal RHI had a greater (more abnormal) ST/HR slope, a trend toward greater peak ST depression, and achieved lower METs than women with normal RHI (Table 1). Conclusion: Among asymptomatic women, endothelial vascular dysfunction was associated with abnormal Ex-ECG results characterized by greater ST/HR slope, greater ST depression, and lower exercise capacity. These findings suggest that “false positive” ST-segment depression in the absence of clinical CAD in women may be explained by endothelial vascular dysfunction. Our study further suggests that endothelial vascular dysfunction may explain the Ex-ECG diagnostic/prognostic paradox.

Exercise testing remains the most widely accessible and relatively inexpensive method for initial evaluation of suspected coronary disease and for evaluation of its severity.1–3 Clinical usefulness has been limited, however, by poor sensitivity of standard ST-segment depression criteria for assessment of anatomic and functional coronary disease severity and for prediction of risk.1,2,4–6 Recent data make it clear that symptomatic obstructive plaques that typically result in exercise-mediated ischemia may be less relevant to infarction and sudden death than less obstructive unstable plaques.7 These limitations mandate a rethinking of the exercise ECG along 2 distinct lines: First, is it possible to improve the diagnostic value of the exercise ECG? Second, separate from its ability to diagnose obstructive coronary artery lesions, can the exercise test be used as a prognostic tool that can encourage effective prevention of premature deaths or coronary events? Both goals take us beyond the ST segment. Reversible ST-segment depression is the characteristic finding associated with exercise-induced, demand-driven ischemia in patients with significant coronary obstruction but no flow limitation at rest. This process differs from the flow-limited acute coronary syndromes because exercise-related ischemia is generally limited to the subendocardium and is proportional to increases in myocardial oxygen demand. Ventricular waveforms of the ECG can be related to the net uncanceled transmural gradients between endocardial and epicardial myocardium, as extrapolated from the work of Holland and Brooks, among others.8–10 Accordingly, isoelectric TQ and ST segments in normal and in nonischemic patients can be related to comparable resting membrane and action potential plateau voltages in endocardial and epicardial action potentials. During exercise, progressive ischemia results in changing endocardial action potentials during both diastole and systole. Less negative endocardial cell resting membrane potential leads to current flow across the ischemic boundary during diastole, leading to elevation of the TQ …

The ECG is the key clinical test available for the emergency determination of which patients who presenting with acute coronary syndromes indeed have acute myocardial ischemia/infarction. Because typically the etiology is thrombosis, the correct clinical decision regarding reperfusion therapy is crucial. This review follows the efforts of an AHA working group to develop new standards for clinical application of electrocardiology. The pitfalls in the current diagnostic standards regarding ischemia/infarction that have been identified by sufficiently documented studies are corrected in their report. This article focuses on the pitfalls for which new standards will emerge in future years.

Background: Although right bundle branch block (RBBB) delays right ventricular depolarization, its effect on cancellation of right and left ventricular forces within the QRS complex has not been quantified during stable temporal and physiological conditions. Systematic changes in QRS amplitude during transient RBBB bear directly on performance of standard ECG criteria for left ventricular hypertrophy (LVH), and these changes require quantification. Methods: We examined the instantaneous effect of RBBB on QRS amplitudes and LVH voltages in 40 patients who had intermittent complete RBBB during a single 10 sec standard 12-lead ECG recording, comprising 0.1% of approximately 400,000 consecutive ECGs in a university teaching hospital setting. Amplitudes were measured by magnifying graticule to the nearest 25 microvolts, averaged for up to 3 normal and 3 RBBB complexes, and compared by paired t test. Results: RBBB was associated with an increase in initial QRS forces (RV1, RV2, and QV6) but significant decreases in mean mid-QRS amplitudes that reflect left ventricular depolarization (RaVL [−75 microvolts], SV1 [−389 microvolts], SV3 [−617 microvolts], RV5 [−100 microvolts], and RV6 [−123 microvolts]). All late QRS forces were increased with RBBB (R'V1, SV5, SI). As a result, combined voltages used for LVH criteria were significantly reduced by RBBB: Sokolow-Lyon voltage decreased from 1520 ± 739 to 1014 ± 512 microvolts (p < 0.001), and Cornell voltage decreased from 1438 ± 683 to 746 ± 399 microvolts (p < 0.001). Conclusions: RBBB is associated with significant reduction in "left ventricular" QRS amplitudes of the standard ECG, consistent with cancellation, rather than unmasking, of left ventricular mid-QRS forces by altered septal and delayed right ventricular depolarization. Because QRS voltages that are routinely combined for the detection of LVH are reduced in RBBB, standard LVH criteria will perform with lower sensitivity in patients with RBBB.

Cardiac single-photon emission computed tomographic correlates of ST depression were examined in 129 subjects who had inducible ST depression of > or =0.1 mV and reversible perfusion defects. Patients were separated on the basis of single-photon emission computed tomographic defect distribution into a group with anatomically contiguous ischemia (anterior or posterior/inferior defects, n = 68) and a group with anatomically opposed ischemia (anterior and posterior/inferior defects, n = 61). ST depression in the contiguous ischemia group correlated with defect size (r = 0.40, p = 0.001) and severity (r = 0.38, p = 0.002); multivariate regression demonstrated each to be independent determinants of ST-depression magnitude (r = 0.51, p

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.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.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.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.

Along with coronary artery calcium scanning, ankle-brachial index measurement, and carotid artery ultrasound, exercise electrocardiography has been proposed as a screening tool for asymptomatic subjects thought to be at intermediate risk for developing clinical coronary disease. A wealth of data indicate that exercise testing can be used to assess and refine prognosis, particularly when emphasis is placed on nonelectrocardiographic measures such as exercise capacity, chronotropic response, heart rate recovery, and ventricular ectopy. Nevertheless, randomized trial data on the clinical value of screening exercise testing are absent; that is, it is not known whether a strategy of routine screening exercise testing in selected subjects reduces the risk for premature mortality or major cardiac morbidity. The writing group believes that a large-scale randomized trial of such a strategy should be performed.

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.

This year marks the bicentennial of the invention of the stethoscope by Rene Theophile Hyacinthe Laennec in 1816, working at the Necker Hospital in Paris. Mediate auscultation was a logical evolution within French clinical empiricism that combined elucidated physical signs with autopsy correlation to provide diagnostic insight into diseases of the lungs and heart. Over the past 2 centuries, the stethoscope has brought the doctor and patient closer together, and it has become a fundamental tool in medical practice and the symbol of the clinician.

The effect of exercise training on the heart rate recovery (HRR) response to submaximal effort was examined in 81 patients during 12 weeks of phase II cardiac rehabilitation. Although HRR after submaximal effort was relatively reduced in older patients with heart disease and in women, its increase during exercise training in men and women of all ages was consistent with enhancement of parasympathetic tone during activities of daily living.

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 ≤45% and/or RVEF ≤30%). Mitral valve replacement or repair (MVR) significantly improves outcome in this subgroup, but predictors of late postoperative survival are not known, and the benefit of MVR has not been defined in patients matched for severity of LV and RV dysfunction. Therefore, prospective assessment of 14 consecutive high risk MR patients was performed before MVR and during 9 years (average) postoperatively to define echocardiographic and radionuclide angiographic predictors of survival; survival also was evaluated in a contemporaneous series of 9 high risk unoperated MR patients, and in subgroups of operated and unoperated patients matched for EF. Of 14 MVR patients, 4 died (3 cardiac: 1 sudden, 2 congestive heart failure). Only preoperative RVEF ≤20% significantly predicted postoperative deaths (rest p = 0.032; exercise p = 0.05). Of 9 unoperated patients, 8 died. Mortality risk of unoperated patients remained higher than that of MVR patients when groups were matched for preoperative LVEF (p = 0.0001). Among patients with RVEF >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.

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.

Since Einthoven introduced the string galvanometer in 1902, electrocardiography has evolved as one of the most widely used tests in the practice of medicine. The routine 12-lead electrocardiogram (ECG), comprising limb leads, augmented frontal plane leads, and precordial leads, has been standardized for half a century. Routine electrocardiography is a fundamental tool for establishing cardiac rhythm and for the diagnosis of acute and chronic diseases of the heart. Comparison of serial ECGs is important in clinical decision making, and this requires technical consistency to minimize nonbiologic variability. Important elements of technical consistency include choice of leads and accuracy of electrode placement. To identify Q waves of prior myocardial infarction and to quantify QRS amplitudes to diagnose ventricular hypertrophy, proper lead placement of the standard electrodes can be extremely important. Electrode placement can have a profound effect on the quantitative variability of serial ECG findings. For example, to evaluate changing ST-segment deviation in patients with acute coronary syndromes, consistent electrode placement is essential. For most rhythm diagnoses, precise lead placement is less critical, but electrode placement is important when QRS morphology is used to determine whether a wide QRS complex tachycardia is ventricular tachycardia or supraventricular tachycardia with aberrancy or bundle branch block. Before the modern era of acute coronary care and hospital-based monitoring and telemetry, nearly all ECGs recorded in the course of practice used a standard 12-lead electrode array that evolved by empirical consensus in the 1930s and 1940s. Early exercise tests conducted with the master 2-step protocol used supine limb lead tracings recorded before and after effort, but exceptions began to occur in the last third of the 20th century when bipolar torso electrodes were introduced to allow activity-compatible

Abstract —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/m 2 in women and >125 g/m 2 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 (SV 1 +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 P =.021) and than the 46% and 43% sensitivities of the respective simple voltage criteria (each P

Background Whether subjects identified as being at increased risk of coronary heart disease (CHD) death by heart rate adjustment of exercise-induced ST-segment depression will benefit from therapy aimed at reducing risk factors has not been examined. Methods and Results Exercise ECGs were performed in 11 880 men from the Usual Care (UC) and Special Intervention (SI) groups of the Multiple Risk Factor Intervention Trial. UC men were referred to customary sources of care in the community; SI men received counseling on smoking cessation and dietary reduction of cholesterol, and stepped-care therapy for hypertension. An abnormal ST-segment response to exercise was defined according to standard criteria as ≥100 μV of additional horizontal or downsloping ST-segment depression and by an ST-segment/heart rate (ST/HR) index >1.60 μV/bpm. After 7 years of follow-up, CHD mortality was significantly lower in SI than UC men with an abnormal ST/HR index (2.4%, 19/786 versus 5.3%, 39/729, P =.005) but was comparable in SI and UC men with a normal ST/HR index (1.6%, 84/5154 versus 1.3%, 70/5211, P =NS). Risk reduction in SI men with an abnormal ST/HR index was independent of age and other cardiac risk factors. In contrast, there was no significant difference in CHD death rate between the smaller groups of SI and UC men with an abnormal test by standard criteria (3.6%, 7/192 versus 2.7%, 5/186, P =NS). Conclusions An abnormal ST/HR index identifies men in whom therapy aimed at reducing CHD risk factors reduces the risk of CHD death by 61%. These findings support the application of heart rate adjustment of ST depression for screening of asymptomatic subjects at increased risk of CHD to identify those who will benefit most from risk factor–reduction programs.

Background and Purpose Automated measurements of electrocardiographic (ECG) intervals are widely used by clinicians for individual patient diagnosis and by investigators in population studies. We examined whether clinically significant systematic differences exist in ECG intervals measured by current generation digital electrocardiographs from different manufacturers and whether differences, if present, are dependent on the degree of abnormality of the selected ECGs. Methods Measurements of RR interval, PR interval, QRS duration, and QT interval were made blindly by 4 major manufacturers of digital electrocardiographs used in the United States from 600 XML files of ECG tracings stored in the US FDA ECG warehouse and released for the purpose of this study by the Cardiac Safety Research Consortium. Included were 3 groups based on expected QT interval and degree of repolarization abnormality, comprising 200 ECGs each from (1) placebo or baseline study period in normal subjects during thorough QT studies, (2) peak moxifloxacin effect in otherwise normal subjects during thorough QT studies, and (3) patients with genotyped variants of congenital long QT syndrome (LQTS). Results Differences of means between manufacturers were generally small in the normal and moxifloxacin subjects, but in the LQTS patients, differences of means ranged from 2.0 to 14.0 ms for QRS duration and from 0.8 to 18.1 ms for the QT interval. Mean absolute differences between algorithms were similar for QRS duration and QT intervals in the normal and in the moxifloxacin subjects (mean ≤6 ms) but were significantly larger in patients with LQTS. Conclusions Small but statistically significant group differences in mean interval and duration measurements and means of individual absolute differences exist among automated algorithms of widely used, current generation digital electrocardiographs. Measurement differences, including QRS duration and the QT interval, are greatest for the most abnormal ECGs.

Patients with carotid atherosclerosis have an increased risk of coronary events and an increased prevalence of echocardiographic left ventricular hypertrophy. However, little is known regarding the association between electrocardiographic abnormalities and carotid atherosclerosis. The relationship of electrocardiographic evidence of myocardial ischemia and left ventricular hypertrophy to the presence of carotid atherosclerosis was prospectively studied in 349 asymptomatic subjects who underwent echocardiography and carotid ultrasonography. Myocardial ischemia on the electrocardiogram was defined by the presence of localized T-wave inversions, and electrocardiographic hypertrophy was defined by the product of Cornell voltage and QRS duration. Carotid atherosclerosis was present in 21% (72/349) of subjects and was associated with older age, higher systolic and pulse pressures, and greater left ventricular mass. Both ischemia and hypertrophy on the electrocardiogram were strongly associated with carotid plaque. Carotid atherosclerosis was more than three times more prevalent in subjects with electrocardiographic ischemia (69% [11/16] versus 18% [61/333], P P =.0003) than in subjects without these findings. Logistic regression analysis, including standard risk factors, revealed that both ischemia and hypertrophy on the electrocardiogram remained significant independent predictors of the presence of carotid atherosclerosis, along with age and echocardiographic left ventricular mass. These findings suggest that the associations of ischemia and left ventricular hypertrophy with carotid atherosclerosis may contribute to the increased incidence of coronary events in patients with carotid atherosclerosis.

Objectives.We sought to assess the effect of heart rate adjustment of ST segment depression on risk stratification for the prediction of death from coronary artery disease. Background.Standard analysis of the ST segment response to exercise based on a fixed magnitude of horizontal or downsloping ST segment depression has demonstrated only limited diagnostic sensitivity for the detection of coronary artery disease and has variable test performance in predicting coronary artery disease mortality. Heart rate adjustment of the magnitude of ST segment depression has been proposed as an alternative approach to increase the diagnostic and prognostic accuracy of the exercise electrocardiogram (ECG). Methods.Exercise ECGs were performed in 5,940 men from the Usual Care Group of the Multiple Risk Factor Intervention Trial at entry into the study. An abnormal ST segment response to exercise was defined according to standard criteria as ≥ 100 μV of additional horizontal or downsloping ST segment depression at peak exercise. The ST segment/heart rate index was calculated by dividing the change in ST segment depression from rest to peak exercise by the exercise-induced change in heart rate. An abnormal ST segment/heart rate index was defined as >1.60 μV/beats per min. Results.After a mean follow-up of 7 years there were 109 coronary artery disease deaths. Using a Cox proportional hazards model, a positive exercise ECG by standard criteria was not predictive of coronary mortality (age-adjusted relative risk [RR] 1.5,95% condence interval [CI] 0.6 to 3.6, p = 0.39). In contrast, an abnormal ST segment/heart rate index significantly increased the risk of death from coronary artery disease (age-adjusted RR 4.1, 95% CI 2.7 to 6.0, p < 0.0001). Excess risk of death was confined to the highest quintile of ST segment/heart rate index values, and within this quintile, risk was directly related to the magnitude of test abnormality. After multivariate adjustment for age, diastolic blood pressure, serum cholesterol and cigarettes smoked per day, the ST segment/heart rate index remained a significant independent predictor of coronary death (RR 3.6, 95% CI 2.4 to 5.4, p < 0.001). Conclusions.Simple heart rate adjustment of the magnitude of ST segment depression improves the prediction of death from coronary artery disease in relatively high risk, asymptomatic men. These findings strongly support the use of heart rate-adjusted indexes of ST segment depression to improve the predictive value of the exercise ECG.

Objectives.This study sought to assess a test performance of the electrocardiogram (ECG) in relation to 1) varying definitions of left ventricular hypertrophy based on different methods of adjusting left ventricular mass for body size, and 2) the presence or absence of obesity.Background.Although left ventricular mass is most commonly indexed for body surface area or height when defining left ventricular hypertrophy, recent work suggests that normalization for height to the power of 2.7 (height2.7) may decrease variability among normal subjects and correctly identify the impact of obesity on hypertrophy.Methods.The product of Cornell voltage and QRS duration (Cornell product) and Framingham-adjusted Cornell voltage were determined from 12-lead ECGs in 212 patients. Left ventricular hypertrophy was defined on the basis of left ventricular mass indexed to body surface area, height and height2.7.Results.Using partitions with matched specificity of 95%, the sensitivity of ECG criteria varied with the definition of hypertrophy, ranging from 39% to 52% for the Cornell product and from 24% to 33% for adjusted Cornell voltage. When left ventricular mass was indexed to body surface area or to height2.7, the 52% and 39% sensitivities of the Cornell product were significantly greater than the 24% (p < 0.001) and 29% (p < 0.05) sensitivities of adjusted Cornell voltage, with a similar trend when left ventricular mass was indexed to height (43% vs. 33%, p = 0.10). Comparison of receiver operating characteristic curves confirmed the superior overall performance of the Cornell product relative to adjusted Cornell voltage for hypertrophy defined by body surface area and height2.7and demonstrated greater reproducibility of overall performance, as measured by the coefficient of variability, for the Cornell product (1.7%) than for adjusted Cornell voltage (5.8%). Sensitivity of adjusted Cornell voltage was significantly greater in obese than in nonobese subjects (50% to 59% vs. 18% to 24%, p < 0.01), but the Cornell product had only minimally higher sensitivity in nonobese than in obese subjects (40% to 54% vs. 32% to 44%, p = NS).Conclusions.The ability of ECG criteria to detect left ventricular hypertrophy differs depending on the method of indexing left ventricular mass for body size and with the presence or absence of obesity. Further, the Cornell product provides the best combination of overall accuracy and low variability of performance between definitions of hypertrophy. These findings have important implications for the clinical and epidemiologic use of 12-lead ECG criteria for the detection of left ventricular hypertrophy.

Obesity is associated with the presence of left ventricular hypertrophy (LVH) and, conversely, with decreased sensitivity of the electrocardiogram (ECG) for LVH due to attenuating effects on QRS amplitudes. Although the Framingham-adjusted Cornell voltage, incorporating age, sex, and body mass index (BMI), was developed to correct for the effects of obesity on the accuracy of the ECG, the impact of body habitus on ECG detection of LVH for newer, more accurate ECG criteria based on the time-voltage area under the QRS complex has not been determined. The authors examined the test accuracy of the Sokolow-Lyon voltage, Cornell voltage, Cornell product (product of QRS duration and Cornell voltage), Framingham-adjusted Cornell voltage, and time-voltage area of the horizontal plane vector QRS for the detection of echocardiographic LVH in relation to body habitus in 250 patients. Normal-weight or overweight status was based on sex-specific population-based BMI partitions. Using partitions with a matched specificity of 98% in the overall population without LVH, the sensitivity of standard ECG criteria varied according to body habitus. Sensitivity of the Framingham-adjusted Cornell voltage was less in normal-weight than in overweight patients (49 vs 59%, P = .0004); there were also trends toward lower sensitivity in normal-weight patients for the Cornell voltage (40 vs 65%, P = .10) and the Cornell product (43 vs 65%, P = NS), but sensitivity of the Sokolow-Lyon voltage was lower in obese than in nonobese patients (18 vs 50%, P = .025). In contrast, the horizontal plane vector area had similar sensitivity in obese and normal-weight patients (76 vs 74%, P = NS). Specificity varied with body habitus only for the Framingham-adjusted Cornell voltage: 100% in normal-weight vs 95% in overweight patients (P < .05). Thus, accuracy of the Framingham-adjusted Cornell voltage and Sokolow-Lyon voltage varies significantly with body habitus. In contrast, accuracy of the Cornell voltage and the Cornell product appears less dependent on BMI, and the time-voltage area of the QRS minimizes the effects of obesity on the accuracy of the ECG for LVH.