Usefulness of T-axis deviation as an independent risk indicator for incident cardiac events in older men and women free from coronary heart disease (the Cardiovascular Health Study).

T-axis shift has been reported to be an indicator of increased mortality risk. We evaluated the association of spatial T-axis deviation with incident coronary heart disease (CHD) events in older men and women free from clinically overt CHD. Spatial T-axis deviation was measured from the standard 12-lead electrocardiogram of a subgroup of 4,173 subjects considered free of CHD at baseline in the Cardiovascular Health Study, a prospective cohort study of risk factors for CHD and stroke in older men and women. Cox regression analysis was used to evaluate the association of altered repolarization with the risk of incident CHD events. The prevalence of marked T-axis deviation (> or =45 degrees ) was 12%. During the median follow-up of 7.4 years, there were 161 CHD deaths, 743 deaths from all causes, and 679 incident CHD events. Adjusting for demographic and clinical risk factors, including other electrocardiographic abnormalities, there was a nearly twofold excess risk of CHD death, and approximately a 50% excess risk of incident CHD and all-cause mortality for those with marked T-axis deviation. From other electrocardiographic abnormalities, only QT prolongation was associated with excess risk for incident CHD comparable to that for abnormal T-axis deviation. These results suggest that T-axis deviation is an easily quantified marker for subclinical disease and an independent indicator for the risk of incident CHD events in older men and women free of CHD.

Independent risk for cardiovascular disease predicted by modified continuous score electrocardiographic criteria for 6-year incidence and regression of left ventricular hypertrophy among clinically disease free men: 16-year follow-up for the multiple risk factor intervention trial.

Risk prediction for electrocardiographic (ECG) left ventricular hypertrophy related criteria, used in clinical trials, and epidemiologic studies of clinically healthy people, has depended in the past on dichotomous classification of ECG LVH criteria. Recent analyses have shown that more sensitive methods of LVH ECG classification without loss of specificity are needed to improve on dichotomous classification. This was done by relating six year incident significant change in continuous score criteria of ECG LVH to the 16 year (10 year post trial) coronary heart disease (CHD) and cardiovascular disease (CVD) mortality among 12,866 men, free of clinical disease, aged 35 to 57 years at baseline in the Multiple Risk Factor Intervention Trial. It was found that significant change in continuous ECG LVH criteria was a stronger independent predictor of future CHD and CVD mortality than was use of dichotomous classification of the same criteria. It was also demonstrated that increase in continuous ECG LVH indexes, below previous dichotomous thresholds independently (of standard CVD risk factors, including increase in obesity-indicated by an increase in adult BMI) predicted excess CHD and CVD mortality and that combinations of continuous indices increases the specificity and relative risk in clinically disease-free middle-aged men.

Familial aggregation of QT-interval variability in a general population: results from the NHLBI Family Heart Study.

QT-interval prolongation is associated with increased risk of cardiac death. Although information on genetics and molecular mechanisms of the congenital long QT syndrome is mounting, limited data are available on the genetics of QT interval in the general population. Heart rate adjusted QT intervals (Bazett's QTc, and QT index (QTI)) were assessed by electrocardiography in 2399 members aged 25-91 years of 468 randomly selected families participating in the NHLBI Family Heart Study. Familial correlation and segregation analyses were performed to evaluate the genetics of the variability of QT interval in this population. The parent-offspring (0.14+/-0.03) and sibling (0.18+/-0.03) correlations for age and sex-adjusted QTc were moderate, while the spouse correlation was close to zero (0.09+/-0.06). This suggests that there are familial/genetic influences on QT-interval variability. Segregation analysis results suggest that there is a major effect in addition to heritable multifactorial effects (h2=0.34), but the major effect did not follow Mendelian inheritance. Further adjustments of QTc for other major cardiovascular risk factors did not significantly change the results. Similar results were found for QTI. The QT-interval variation in the general population is influenced by moderate heritable multifactorial effects in addition to a major effect. A major gene effect is not directly supported.

RR interval variation, the QT interval index and risk of primary cardiac arrest among patients without clinically recognized heart disease.

AIMS: Autonomic tone influences RR interval variation (RRV) and the heart rate-corrected QT interval index (QTI). Together, QTI and RRV may improve characterization of sympathovagal control and estimation of risk of primary cardiac arrest. We therefore examined effects of QTI and short-term RRV from standard, 12-lead electrocardiograms on risk of primary cardiac arrest among persons without clinically recognized heart disease. METHODS AND RESULTS: We analysed data from a case-control study of risk factors for primary cardiac arrest among enrollees in a large health plan. Cases (n=505) were enrollees aged 18 to 79 years without history of heart disease who had primary cardiac arrest between 1980 and 1994. Controls (n=529) were a demographically similar, stratified random sample of enrollees. We determined enrollee characteristics from ambulatory medical records, QTI and RRV from standard, 12-lead electrocardiograms, and medication use from automated pharmacy files. Low and high values of QTI and RRV were designated as the first and fifth quintiles of QTI (96% and 107%) and RRV (35 ms and 120 ms) among controls. In a model adjusting for clinical predictors of primary cardiac arrest, RRV modified the association between QTI and risk of primary cardiac arrest (P=0.05). Compared to high RRV and low QTI, the risk of primary cardiac arrest (odds ratio [95% CI]) was 0.95 [0.73-1.23] at low RRV and QTI, 1.23 [0.97-1.57] at high RRV and QTI, and 1.55 [1.16-2.06] at low RRV and high QTI. Risk remained elevated after adjustment for other electrocardiographic predictors and medication use. CONCLUSION: Autonomic dysfunction, characterized by high QTI and low RRV on the standard, 12-lead electrocardiogram, is associated with an increased risk of primary cardiac arrest among persons without clinically recognized heart disease.

Association of ventricular premature complexes with electrocardiographic-estimated left ventricular mass in a population of African-American and white men and women (The Atherosclerosis Risk in Communities.

Increased left ventricular (LV) mass is often found in adults and is a powerful predictor of cardiovascular mortality. To test the hypothesis that an electrocardiographic estimate of LV mass--the Cornell voltage--is associated with ventricular premature complexes (VPCs) in free-living adults, a cross-sectional analysis of the predictors of VPCs on a 2-minute rhythm strip in a population-based sample of 13,606 middle-aged, African-American and white men and women from 4 US communities in the Atherosclerosis Risk in Communities Study baseline examinations was performed. In adults without known coronary artery disease, the prevalence of VPCs increases monotonically with increasd Cornell voltages within ethnicity and gender groups. Independent of systemic hypertension, serum electrolytes, age, heart rate, educational attainment, gender, and ethnicity, a millivolt increase in Cornell voltage was associated with a 20% to 30% increase in the prevalence odds ratio of VPCs on the 2-minute electrocardiogram. Thus, Cornell voltage is associated with VPCs on a 2-minute electrocardiogram. The association is consistent in African-Americans, whites, men, and women.

Association between new electrocardiographic abnormalities after coronary revascularization and five-year cardiac mortality in BARI randomized and registry patients.

There are few data comparing the relative frequency of new electrocardiographic (ECG) abnormalities after coronary artery bypass grafting (CABG) compared with percutaneous transluminal coronary angioplasty (PTCA) and their association with long-term cardiac mortality. The study population consisted of 3,373 patients who were either randomized or eligible to be randomized to CABG or PTCA in the BARI trial. The frequency of new postprocedural ECG abnormalities was significantly greater after a CABG procedure than after PTCA. The incidence of new postprocedural major Q waves, ST-segment elevation, and T-wave abnormalities were significantly more frequent after CABG. After PTCA (n = 1,869), the 5-year cardiac mortality rates associated with the new development of major Q waves, ST-segment elevation, ST-segment depression, T-wave abnormalities, or no abnormality was 18.1%, 8.5%, 8.9%, 6.0%, and 5.4%, respectively. After CABG (n = 1,427), 5-year cardiac mortality rates were 8.0%, 4.2%, 3.8%, 2.8%, and 3.7%, respectively. The adjusted relative risk of 5-year cardiac mortality for new Q-wave abnormalities was 2.6 after CABG (p <0.04) and 4.6 after PTCA (p <0.01). Thus, patients who undergo CABG have more postinitial procedural ECG abnormalities than patients who undergo PTCA. Cardiac mortality is significantly increased by the new development of postprocedural Minnesota code Q-wave abnormalities regardless of whether patients undergo CABG or PTCA.

Comparison of computer-assigned Minnesota Codes with the visual standard method for new coronary heart disease events.

The Minnesota Code is the most widely used electrocardiogram (ECG) classification system for epidemiologic studies and has been incorporated into several Computer algorithms. The authors compared the Modular ECG Analysis System (MC-MEANS) and NOVACODE computer ECG findings with the Visual coding standard for agreement and prognostic associations with coronary heart disease (CHD) events occurring during follow-up from 1987 to 1995 in 2,116 individuals participating in the Atherosclerosis Risk in Communities (ARIC) Study. The exact agreement between Visual and computer findings was greater than 90% for all Minnesota Code categories except Q-code, which was 77% for MC-MEANS and 81% for NOVACODE. Approximately 60% of all Q-codes were assigned by computer methods only. Among the 2,116 participants, there were 246 (11.6%) new coronary events. Unadjusted relative risks for codes assigned by the three methods were similar. When computer methods disagreed on code severity, the CHD occurrence rates for MC-MEANS-detected severer code versus NOVACODE-detected severer code were 21% and 7%, respectively. This study provides clear evidence that computers assign more and severer Minnesota Codes with similar prognostic importance as does the Visual method; it also alerts researchers to potential problems in pooling Minnesota Code data read by different methods.

Race- and sex-specific ECG models for left ventricular mass in older populations. Factors influencing overestimation of left ventricular hypertrophy prevalence by ECG criteria in African-Americans.

The validity of the reported high prevalence of left ventricular hypertrophy (LVH) among African-American men and women has been questioned owing to conflicting echocardiographic evidence. We used echocardiographic left ventricular mass (LVM) from M-mode measurements to evaluate associations between LVM, body size, and electrocardiographic (ECG) variables in 3,627 white and African-American men and women 65 years of age and older who were participants of the Cardiovascular Health Study (CHS), a multicenter cohort study of risk factors for coronary heart disease and stroke. ECG amplitudes used in LVH criteria were substantially higher in African-Americans, with apparent LVH prevalence 2 to 3 times higher in African American men and women than in white men and women, although there was no significant racial difference in echocardiographic LVM. The higher apparent LVH prevalence by Sokolow-Lyon criteria in African-American men is in part owing to smaller lateral chest diameter. In women, reasons for racial differences in ECG LVH prevalence remain largely unexplained although a small part of the excess LVH in African-American women by the Sokolow-Lyon criteria appears to be owing to a larger lateral chest semidiameter in white women. ECG variables alone were too inaccurate for LVM prediction, and it was necessary to incorporate in all ECG models body weight that was properly adjusted for race and sex. This resulted in modest LVM prediction accuracy, with R-square values ranging from .22 to .36. Race- and sex-specific ECG models introduced for LVM estimation with an appropriate adjustment for body size differences are expected to facilitate evaluation of LVH status in contrasting racial population groups.

Traditional risk factors and subclinical disease measures as predictors of first myocardial infarction in older adults: the Cardiovascular Health Study.

BACKGROUND: Risk factors for myocardial infarction (MI) have not been well characterized in older adults, and in estimating risk, we sought to assess the individual and joint contributions made by both traditional risk factors and measures of subclinical disease. METHODS: In the Cardiovascular Health Study, we recruited 5888 adults aged 65 years and older from 4 US centers. At baseline in 1989-1990, participants underwent an extensive examination that included traditional risk factors such as blood pressure and fasting glucose level and measures of subclinical disease as assessed by electrocardiography, carotid ultrasonography, echocardiography, pulmonary function, and ankle-arm index. Participants were followed up with semiannual contacts, and all cardiovascular events were classified by the Morbidity and Mortality Committee. The main analytic technique was the Cox proportional hazards model. RESULTS: At baseline, 1967 men and 2979 women had no history of an MI. After follow-up for an average of 4.8 years, there were 302 coronary events, which included 263 patients with MI and 39 with definite fatal coronary disease. The incidence was higher in men (20.7 per 1000 person-years) than women (7.9 per 1000 person-years). In all subjects, the incidence was strongly associated with age, increasing from 7.8 per 1000 person-years in subjects aged 65 to 69 years to 25.6 per 1000 person-years in subjects aged 85 years and older. Glucose level and systolic blood pressure were associated with the incidence of MI, but smoking and lipid measures were not. After adjustment for age and sex, the significant subclinical disease predictors of MI were borderline or abnormal ejection fraction by echocardiography, high levels of intimal-medial thickness of the internal carotid artery, and a low ankle-arm index. Forced vital capacity and electrocardiographic left ventricular mass did not enter the stepwise model. Excluding subjects with clinical cardiovascular diseases such as prior angina or congestive heart failure at baseline had little effect on these results. Risk factors were generally similar in men and women. CONCLUSIONS: After follow-up of 4.8 years, systolic blood pressure, fasting glucose level, and selected subclinical disease measures were important predictors of the incidence of MI in older adults. Uncontrolled high blood pressure may explain about one quarter of the coronary events in this population.

Electrocardiographic left ventricular hypertrophy by five criteria among civil servants in Benin City, Nigeria: prevalence and correlates.

Although increasing hypertension rates have been reported in several African populations, little is known about the frequency of resulting hypertensive complications in these populations. We recorded the electrocardiograms of 482 male and 284 female civil servants in Benin City, Nigeria. Five different criteria were used to detect the presence of electrocardiographic left ventricular hypertrophy. Associations between electrocardiographic left ventricular hypertrophy and demographic, anthropometric and blood pressure characteristics were assessed. The prevalence of electrocardiographic left ventricular hypertrophy ranged from 3 to 29% in the total population, depending on the criteria used, with four of the five criteria resulting in prevalence estimates of less than 10%. The prevalence of electrocardiographic left ventricular hypertrophy was significantly greater among those with hypertension (19% of the total population), ranging from 11 to 49%. The prevalence of electrocardiographic left ventricular hypertrophy increased with blood pressure level in both normotensives and hypertensives. Among hypertensives with systolic blood pressure > or =180 mm Hg or diastolic blood pressure > or =110 mm Hg, the prevalence exceeded 50% by four of the five criteria. We conclude that left ventricular hypertrophy may be affecting many hypertensives in this Nigerian population, potentially resulting in a substantial future burden of cardiovascular disease and death.

The Novacode criteria for classification of ECG abnormalities and their clinically significant progression and regression.

Electrocardiographic (ECG) manifestations of clinical and subclinical cardiovascular disease are used as an important component in the evaluation of clinical trials, and there is an increasing demand for well-defined criteria for clinically significant evolution of ECG abnormalities. The Novacode ECG classification system provides a comprehensive hierarchical set of criteria for prevalent ECG abnormalities and for clinically significant serial ECG changes, both adverse and favorable, as a response to pharmacologic, surgical, and other interventions. These criteria are used to grade Q wave and ischemic abnormalities in order to achieve stable classification of both prevalent and incident myocardial infarctions by minimizing false classifications due to clinically insignificant ECG variations. This approach differs from the traditional Minnesota Code classification system, in which incident events are determined by changes in classification categories, with the application of additional elaborate validation rules to exclude frequent false classifications. Novacode hierarchy is so structured that for each abnormality, a general class is first determined with the simplest possible classification criteria and more specific abnormality subgroups are then classified with more elaborate criteria. This approach will satisfy differing needs of clinical trials for detail in classification. Explicit definition of ECG variables and condition statements for the classification criteria facilitate implementation of the Novacode with computer ECG programs.

NHLBI workshop on the utilization of ECG databases: preservation and use of existing ECG databases and development of future resources.

Baseline examinations and periodic reexaminations in longitudinal population studies, together with ongoing surveillance for morbidity and mortality, provide unique opportunities for seeking ways to enhance the value of the electrocardiogram (ECG) recorded with digital technology as an inexpensive and noninvasive tool for prognosis and diagnosis. Clinicians, epidemiologists, and engineers from industry, government, and academic medical centers gathered at a workshop sponsored by the National Heart, Lung, and Blood Institute (NHLBI) on June 11-12, 1997, to discuss the research potential of ECG databases, their preservation and accession, and standards for recording and storage. Databases considered were those acquired in ongoing and future NHLBI-funded studies and in clinical settings in which the ECG continues to provide valuable information for evaluation and treatment. The accessibility of existing databases, the quality of their data, and the availability of ancillary demographic and clinical information were major themes. Also discussed were appropriate statistical methodologies to be used with these data for developing and testing ECG algorithms. The workshop participants affirmed the value of these databases and urged the establishment of an ECG advisory and review group to (1) resolve technical and proprietary issues for the utilization of currently existing databases; (2) develop standards for recording, storage, and utilization of ECGs in future NHLBI-supported studies; (3) oversee the creation of a national ECG database resource, consisting of an archive of ECG databases from past and ongoing NHLBI-supported studies, and a registry of ECG databases that would eventually include digital ECGs from populations currently underrepresented in the demographic spectrum of the NHLBI databases.

Comparison of the various electrocardiographic scoring codes for estimating anatomically documented sizes of single and multiple infarcts of the left ventricle.

It is clinically important to estimate the size of a myocardial infarction (MI) to predict patient prognosis, to determine the ability of a therapy to limit its size, and to evaluate its effect on left ventricular function. Various electrocardiographic methods have been used for these purposes but their accuracies have not been compared with each other using an identical reference population of anatomically measured infarcts. The capability of 4 electrocardiographic scoring methods (the Selvester score, the Minnesota code, the Novacode, and the Cardiac Infarction Injury Score) to estimate MI size was compared using anatomic MI size in a group of 100 deceased patients. All patients had a standard 12-lead electrocardiogram of sufficient quality to perform manual waveform measurements and without confounding factors such as ventricular hypertrophy, fascicular block, or bundle branch block. The location and size of the left ventricular infarction was measured postmortem using the anatomic method of Ideker et al. All methods' size estimates correlated best with anatomic MI size in the anterior location (r = 0.65 to 0.89). The Selvester score was superior in estimating the sizes of inferior (r = 0.70) and posterolateral (r = 0.74) infarcts. For multiple infarcts all methods performed poorly (r = 0.18 to 0.44).

A standardized procedure for locating and documenting ECG chest electrode positions: consideration of the effect of breast tissue on ECG amplitudes in women.

Continuing uncertainty exists about standardized procedures for the placement of electrocardiographic (ECG) chest electrodes, technical variability being the largest error source for short-term variations in amplitudes and waveforms of the chest lead ECGs. To avoid presumed attenuation of ECG amplitudes by abundant breast tissue, anterolateral chest electrodes in women are often placed under the breasts and too low. There is also considerable uncertainty about locating the midclavicular line and the V4 electrode, particularly in obese persons and in women. We examined the effect of breast tissue protuberance on ECG amplitudes using ECG and anthropometric data on 6,814 women included in the Atherosclerosis Research in Communities Study (ARIC). The R wave amplitudes in anterolateral chest leads and the Sokolow-Lyon voltage decreased (P < .001 for all), and RaVL and the Cornell voltage increased significantly with increasing breast protuberance (P < .001 for all). However, these effects were small (15 microV or less for each 1-cm increment in breast protuberance), and R2 values were less than .01, indicating that breast protuberance alone explained less than 1% of ECG amplitude variations. When chest size and breast protuberance estimates were entered simultaneously into a multivariate regression model, chest size appeared to dominate, and model R2 values increased for positive associations with RaVL (R2 = .12) and the Cornell voltage (R2 = .04). Combined model R2 values remained < or =.01 for all other ECG amplitudes. A detailed step-by-step standardized electrode placement procedure was formulated. Because of the difficulties encountered in locating the left midclavicular line by visual inspection, we introduced well-defined procedures for identification and documentation of lateral chest electrode placement locations as a quality control method for clinical trials. Population data from the Third National Health and Nutrition Survey on the distributions by sex and race of chest electrode V4 and V6 locations and anthropometric data on chest size and shape are presented in order to facilitate evaluation of the comparability of electrode placement procedures in various studies and for quality control in clinical trials. It is concluded that standardized procedures to document chest electrode placement locations are feasible. Breast tissue appears to have a practically negligible effect on ECG amplitudes, and in women, the placement of chest electrodes on the breast rather than under the breast is recommended in order to facilitate the precision of electrode placement at the correct horizontal level and at the correct lateral positions.