Electrocardiographic QRS-T angle and the risk of incident silent myocardial infarction in the Atherosclerosis Risk in Communities study.

BACKGROUND: Silent myocardial infarction (SMI) accounts for about half of the total number of MIs, and is associated with poor prognosis as is clinically documented MI (CMI). The electrocardiographic (ECG) spatial QRS/T angle has been a strong predictor of cardiovascular outcomes. Whether spatial QRS/T angle also is predictive of SMI, and the easy-to-obtain frontal QRS/T angle will show similar association are currently unknown. METHODS: We examined the association between the spatial and frontal QRS/T angles, separately, with incident SMI among 9498 participants (mean age 54years, 57% women, and 20% African-American), who were free of cardiovascular disease at baseline (visit 1, 1987-1989) from the Atherosclerosis Risk in Communities (ARIC) study. Incident SMI was defined as MI occurring after the baseline until visit 4 (1996-1998) without CMI. The frontal plane QRS/T angle was defined as the absolute difference between QRS axis and T axis. Values greater than the sex-specific 95th percentiles of the QRS/T angles were considered wide (abnormal). RESULTS: A total of 317 (3.3%) incident SMIs occurred during a 9-year median follow-up. In a model adjusted for demographics, cardiovascular risk factors and potential confounders, both abnormal frontal (HR 2.28, 95% CI 1.58-3.29) and spatial (HR 2.10, 95% CI 1.44-3.06) QRS/T angles were associated with an over 2-fold increased risk of incident SMI. Similar patterns of associations were observed when the results were stratified by sex. CONCLUSIONS: Both frontal and spatial QRS/T angles are predicative of SMI suggesting a potential use for these markers in identifying individuals at risk.

Race and Sex Differences in the Incidence and Prognostic Significance of Silent Myocardial Infarction in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Race and sex differences in silent myocardial infarction (SMI) are not well established. METHODS AND RESULTS: The analysis included 9498 participants from the Atherosclerosis Risk in Communities (ARIC) study who were free of cardiovascular disease at baseline (visit 1, 1987-1989). Incident SMI was defined as ECG evidence of MI without clinically documented MI (CMI) after the baseline until ARIC visit 4 (1996-1998). Coronary heart disease and all-cause deaths were ascertained starting from ARIC visit 4 until 2010. During a median follow-up of 8.9 years, 317 participants (3.3%) developed SMI and 386 (4.1%) developed CMI. The incidence rates of both SMI and CMI were higher in men (5.08 and 7.96 per 1000-person years, respectively) than in women (2.93 and 2.25 per 1000-person years, respectively; P<0.0001 for both). Blacks had a nonsignificantly higher rate of SMI than whites (4.45 versus 3.69 per 1000-person years; P=0.217), but whites had higher rate of CMI than blacks (5.04 versus 3.24 per 1000-person years; P=0.002). SMI and CMI (compared with no MI) were associated with increased risk of coronary heart disease death (hazard ratio, 3.06 [95% confidence interval, 1.88-4.99] and 4.74 [95% confidence interval, 3.26-6.90], respectively) and all-cause mortality (hazard ratio, 1.34 [95% confidence interval, 1.09-1.65] and 1.55 [95% confidence interval, 1.30-1.85], respectively). However, SMI and CMI were associated with increased mortality among both men and women, with potentially greater increased risk among women (interaction P=0.089 and 0.051, respectively). No significant interactions by race were detected. CONCLUSIONS: SMI represents >45% of incident MIs and is associated with poor prognosis. Race and sex differences in the incidence and prognostic significance of SMI exist that may warrant considering SMI in personalized assessments of coronary heart disease risk.

Eyewitness to history: Landmarks in the development of computerized electrocardiography.

The use of digital computers for ECG processing was pioneered in the early 1960s by two immigrants to the US, Hubert Pipberger, who initiated a collaborative VA project to collect an ECG-independent Frank lead data base, and Cesar Caceres at NIH who selected for his ECAN program standard 12-lead ECGs processed as single leads. Ray Bonner in the early 1970s placed his IBM 5880 program in a cart to print ECGs with interpretation, and computer-ECG programs were developed by Telemed, Marquette, HP-Philips and Mortara. The "Common Standards for quantitative Electrocardiography (CSE)" directed by Jos Willems evaluated nine ECG programs and eight cardiologists in clinically-defined categories. The total accuracy by a representative "average" cardiologist (75.5%) was 5.8% higher than that of the average program (69.7, p<0.001). Future comparisons of computer-based and expert reader performance are likely to show evolving results with continuing improvement of computer-ECG algorithms and changing expertise of ECG interpreters.

Bundle branch blocks and the risk of mortality in the Atherosclerosis Risk in Communities study.

AIMS: The main objective of our study was to evaluate the associations between different categories of bundle branch blocks (BBBs) and mortality and to consider possible impact of QRS prolongation in these associations. METHODS: This analysis included 15 408 participants (mean age 54 years, 55.2% women, and 26.9% blacks) from the Atherosclerosis Risk in Communities study. We used Cox regression to examine associations between left BBB (LBBB), right BBB (RBBB) and indetermined type of ventricular conduction defect [intraventricular conduction defect (IVCD)] with coronary heart disease (CHD) death and all-cause mortality. RESULTS: During a mean 21 years of follow-up, 4767 deaths occurred; of these, 728 were CHD deaths. Compared to No-BBB, LBBB and IVCD were strongly associated with increased CHD death (hazard ratios 4.11 and 3.18, respectively; P < 0.001 for both). Furthermore, compared to No-BBB with QRS duration less than 100 ms, CHD mortality risk was increased 1.33-fold for the No-BBB group with QRS duration 100-109 ms, and 1.48-fold with QRS duration 110-119 ms, 3.52-fold for pooled LBBB-IVCD group with QRS duration less than 140 ms and 4.96-fold for pooled LBBB-IVCD group with QRS duration at least 140 ms (P < 0.001). However, mortality risk was not significantly increased for lone RBBB. For all-cause mortality, trends similar to those for CHD death were observed within the BBB groups, although at lower levels of risk. CONCLUSION: Prevalent LBBB and IVCD, but not RBBB, are associated with increased risk of CHD death and all-cause mortality. Mortality risk is further increased as the QRS duration is prolonged above 140 ms.

A wide QRS/T angle in bundle branch blocks is associated with increased risk for coronary heart disease and all-cause mortality in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Repolarization abnormality in bundle branch blocks (BBB) is traditionally ignored. This study evaluated the prognostic value of QRS/T angle for mortality in the presence and absence of BBB. METHODS AND RESULTS: Total 15,408 participants (mean age 54 years, 55.2% women, 26.9% blacks, 2.8% with BBB) were from the Arteriosclerosis Risk in Communities Study. Sex stratified Cox regression models were used to compute hazard ratios (HRs) with 95% confidence intervals (CIs) for coronary heart disease (CHD) and all-cause mortality for wide spatial QRS/T angle with and without BBB including right BBB (RBBB), left BBB (LBBB) and indetermined-type ventricular conduction defect (IVCD) and RBBB combined with left anterior fascicular block. During a median 22-year follow-up, 4767 deaths occurred, 728 of them CHD deaths. Using the No-BBB with QRS/T angle below median value as gender-specific reference groups, the mortality risk increase was significant for both women and men with No-BBB and QRS/T angle above the median value. In the pooled ICVD/LBBB group, the risk for CHD death was increased 15.9-fold in women and 6.04 fold in men, and for all-cause deaths 3.01-fold in women and 1.84-fold in men. However, the mortality risk in isolated RBBB group was only significantly increased in women but not in men. CONCLUSION: A wide spatial QRS/T angle in BBB is associated with increased risk for CHD and all-cause mortality over and above the predictive value for BBB alone. The risk for women is as high as or higher than that in men.

Ventricular conduction defects and the risk of incident heart failure in the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: We evaluated the risk of incident heart failure (HF) associated with various categories of ventricular conduction defects (VCDs) and examined the impact of QRS duration on the risk of HF. METHODS AND RESULTS: This analysis included 14,478 participants from the Atherosclerosis Risk in Communities (ARIC) study who were free of HF at baseline. VCDs (n = 377) were categorized into right and left bundle branch blocks (RBBB and LBBB, respectively), bifascicular BBB (RBBB with fascicular block), indeterminate-type VCD (IVCD), and pooled VCD group excluding lone RBBB. During an average of 18 years' follow-up, 1,772 participants were hospitalized for incident HF. Compared with no VCD, LBBB and pooled VCD were strongly associated with increased risk of incident HF (multivariable hazard ratios 2.87 and 2.29, respectively). Compared with no VCD with QRS duration <100 ms, HF risk was 1.17-fold for the no VCD group with QRS duration 100-119 ms, 1.97-fold for the pooled VCD group with QRS duration 120-139 ms, and 3.25-fold for the pooled VCD group with QRS duration ≥140 ms. HF risk for the pooled VCD group remained significant (1.74-fold for QRS duration 120-139 ms and 2.81-fold for QRS duration ≥140 ms) in the subgroup free from cardiovascular disease at baseline. Lone RBBB was not associated with incident HF. CONCLUSIONS: VCDs except for isolated RBBB are strong predictors of incident HF, and HF risk is further increased as the QRS duration is prolonged >140 ms.

Electrocardiographic repolarization-related predictors of coronary heart disease and sudden cardiac deaths in men and women with cardiovascular disease in the Atherosclerosis Risk in Communities (ARIC) study.

INTRODUCTION: We evaluated repolarization-related predictors of coronary heart disease (CHD) death and sudden cardiac death (SCD) in men and women with cardiovascular disease (CVD) in the Atherosclerosis Risk in Communities (ARIC) study. METHODS AND RESULTS: Hazard ratios (HR) from Cox regression were computed for 11 ECG measures of repolarization in 1384 subjects (50% women) 45 to 65years of age. The average follow-up was 14years. Based on electrophysiological considerations the spatial angle between Tpeak and normal repolarization reference vector [Ѳ(Tp|Tref)], STJV6 amplitude, QRS duration and Tonset and Tpeak vector magnitude ratio (ToV/TpV) were considered as primary candidates for independent mortality predictors, and as an alternative set TaVR and TV1 amplitudes and the spatial angle between the initial and terminal T vectors [Ѳ(Tinit|Tterm)]. From the primary set [Ѳ(Tp|Tref)] was a strong independent predictor for CHD death (nearly 4-fold increased risk in men and 2-fold increased risk in women) and for SCD [Ѳ(Tinit|Tterm)] in men (3.4-fold increased risk) and (ToV/TpV) in women (7.76-fold increased risk). From the alternative set of independent predictors TaVR amplitude negativity reduced to less than 150µV (1.5mm) was a strong mortality predictor with an approximately 3-fold increased risk for CHD death and SCD in men and women. CONCLUSIONS: The strongest independent predictors of CHD death were [Ѳ(Tp|Tref)] in men and TaVR in women and of SCD were [Ѳ(Tp|Tref)] in men and ToV/TpV in women. Overall, TaVR amplitude negativity reduced to less than 150µV (1.5mm) was the most consistent mortality predictor in all subgroups. These ECG variables may warrant consideration for identification of high risk men and women for more intense preventive intervention.

Subclinical myocardial injury identified by cardiac infarction/injury score and the risk of mortality in men and women free of cardiovascular disease.

Previous studies have explored the ability of the Cardiac Infarction/Injury Score (CIIS) to identify individuals who are high risk for cardiovascular disease (CVD) mortality. However, its prognostic significance among those without CVD in the United States general population has not been established. This analysis included 6,298 participants (mean age 59±13 years, 53% women, 51% nonwhites) from the Third National Health and Nutrition Examination Survey, excluding participants with a history of CVD or electrocardiographic evidence of old myocardial infarction or ischemic ST depression at baseline. Subclinical myocardial injury was defined as CIIS≥10. Mortality data were ascertained using the National Death Index. Cox proportional hazards regression was used to compute hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between subclinical myocardial injury and CVD and all-cause mortalities. Subclinical myocardial injury was detected in 1,376 participants (22%). A total of 1,928 deaths occurred during a median follow-up of 14 years of which 765 (40%) were due to CVD. In a multivariate model adjusted for demographics, traditional CVD risk factors, and other medical co-morbidities, subclinical myocardial injury was associated with an increased risk of CVD (HR 1.26, 95% CI 1.02 to 1.56) and all-cause (HR 1.42, 95% CI 1.23 to 1.63) mortalities. In conclusion, subclinical myocardial injury in those without manifestations of CVD is associated with an increased risk of CVD and all-cause mortalities. These findings highlight the important role of CIIS to identify subclinical myocardial injury and its association with mortality among men and women in the United States.

Electrocardiographic repolarization-related variables as predictors of coronary heart disease death in the women's health initiative study.

BACKGROUND: We evaluated 25 repolarization-related ECG variables for the risk of coronary heart disease (CHD) death in 52 994 postmenopausal women from the Women's Health Initiative study. METHODS AND RESULTS: Hazard ratios from Cox regression were computed for subgroups of women with and without cardiovascular disease (CVD). During the average follow-up of 16.9 years, 941 CHD deaths occurred. Based on electrophysiological considerations, 2 sets of ECG variables with low correlations were considered as candidates for independent predictors of CHD death: Set 1, Ѳ(Tp|Tref), the spatial angle between T peak (Tp) and normal T reference (Tref) vectors; Ѳ(Tinit|Tterm), the angle between the initial and terminal T vectors; STJ depression in V6 and rate-adjusted QTp interval (QTpa); and Set 2, TaVR and TV1 amplitudes, heart rate, and QRS duration. Strong independent predictors with over 2-fold increased risk for CHD death in women with and without CVD were Ѳ(Tp|Tref) >42° from Set 1 and TaVR amplitude >-100 µV from Set 2. The risk for these CHD death predictors remained significant after multivariable adjustment for demographic/clinical factors. Other significant predictors for CHD death in fully adjusted risk models were Ѳ(Tinit|Tterm) >30°, TV1 >175 µV, and QRS duration >100 ms. CONCLUSIONS: Ѳ(Tp|Tref) angle and TaVR amplitude are associated with CHD mortality in postmenopausal women. The use of these measures to identify high-risk women for further diagnostic evaluation or more intense preventive intervention warrants further study. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.

Electrocardiographic left ventricular hypertrophy and the risk of adverse cardiovascular events: a critical appraisal.

This review covers selected electrocardiographic left ventricular hypertrophy (ECG-LVH) studies which have evaluated their prognostic value for adverse cardiovascular (CVD) events. Most ECG-LVH studies have used echocardiographic left ventricular mass (Echo-LVM) as the gold standard for evaluating ECG-LVH criteria. More recently, LVM from magnetic resonance imaging (MRI-LVM) has evolved as the new gold standard. The reported risk of adverse CVD events is generally highest for ECG-LVH criteria which combine high amplitude QRS criteria with repolarization abnormalities such as in LV strain pattern. Evolving coronary heart disease (CHD) may account in part for the increased risk for ECG-LVH. However, one large coronary arteriography study found that 5-year survival was significantly lower in coronary artery disease (CAD) patients with ECG-LVH than without LVH regardless of CAD status. The utility of Echo-LVH as a standard is limited by the large intra- and inter-reader variability and the lack of standardization of allometric formulations for adjustment of LVM to body size. Newer evaluation data with MRI-LVM as the standard show that for most ECG criteria CVD event rates are significantly higher for study subgroups with ECG-LVH than those without ECG-LVH. However, the performance results differ when comparing the risk for CVD events from those for the overall LVH classification accuracy according to sensitivity and specificity. Large short-term variability of ECG amplitudes due to electrode placement variability is a common limiting factor for ECG-LVH criteria performance regardless of the gold standard. Clinical trials for hypertension control rely largely on monitoring Echo-LVH rather than ECG-LVH.

Usefulness of electrocardiographic QRS/T angles with versus without bundle branch blocks to predict heart failure (from the Atherosclerosis Risk in Communities Study).

Repolarization abnormalities in the setting of bundle branch blocks (BBB) are generally ignored. We used Cox regression models to determine hazard ratios (HRs) with 95% confidence intervals (CIs) for incident heart failure (HF) associated with wide spatial and frontal QRS/T angle (upper twenty-fifth percentile of each) in men and women with and without BBB. This analysis included 14,478 participants (54.6% women, 26.4% blacks, 377 [2.6%] with BBB) from the Atherosclerosis Risk in Communities Study who were free of HF at baseline. Using No-BBB with normal spatial QRS/T angle as the reference group, the risk for HF in multivariable adjusted models was increased 51% for No-BBB with wide spatial QRS/T angle (HR 1.51, 95% CI 1.37 to 1.66), 48% for BBB with normal spatial QRS/T angle (HR 1.48, 95% CI 1.17 to 1.88), and the risk for incident HF was increased more than threefold for BBB with wide spatial QRS/T angle (HR 3.37, 95% CI 2.47 to 4.60). The results were consistent across subgroups by gender. Similar results were observed for the frontal plane QRS/T angle. In the pooled BBB group excluding right BBB, a positive T wave in lead aVR and heart rate 70 bpm and higher were also potent predictors of incident HF similar to the QRS/T angles. In conclusion, both BBB and wide QRS/T angles are predictive of HF, and concomitant presence of both carries a much higher risk than for either predictor alone. These findings suggest that repolarization abnormalities in the setting of BBB should not be considered benign or an expected consequence of BBB.

New age- and sex-specific criteria for QT prolongation based on rate correction formulas that minimize bias at the upper normal limits.

BACKGROUND: Existing formulas for rate-corrected QT (QTc) commonly fail to properly adjust the upper normal limits which are more critical than the mean QTc for evaluation of prolonged QT. Age- and sex-related differences in QTc are also often overlooked. Our goal was to establish criteria for prolonged QTc using formulas that minimize QTc bias at the upper normal limits. METHODS AND RESULTS: Strict criteria were used in selecting a study group of 57,595 persons aged 5 to 89 years (54% women) and to exclude electrocardiograms (ECG) with possible disease-associated changes. Two QT rate adjustment formulas were identified which both minimized rate-dependency in the 98 th percentile limits: QTcmod, based on an electrophysiological model (QTcMod = QTx(120 + HR)/180)), and QTcLogLin, a power function of the RR interval with exponents 0.37 for men and 0.38 for women. QTc shortened in men during adolescence and QTcMod became 13 ms shorter than in women at age 20-29 years. The sex difference was maintained through adulthood although decreasing with age. The criteria established for prolonged QTc were: Age < 40 years, men 430 ms, women 440 ms; Age 40 to 69, men 440 ms, women 450 ms; Age ≥ 70 years, men 455 ms, and women 460 ms. CONCLUSIONS: Sex difference in QTc originates from shortened QT in adolescent males. Upper normal limits for QTc vary substantially by age and sex, and it is essential to use age- and sex-specific criteria for evaluation of QT prolongation.

Inter-relationship between electrocardiographic left ventricular hypertrophy and QT prolongation as predictors of increased risk of mortality in the general population.

BACKGROUND: Prolonged-QT commonly coexists in the ECG with left ventricular hypertrophy (ECG-LVH). However, it is unclear whether to what extent QT prolongation coexisting with ECG-LVH can explain the prognostic significance of ECG-LVH, and whether prolonged-QT coexisting with ECG-LVH should be considered as an innocent consequence of ECG-LVH. METHODS AND RESULTS: The study population consisted of 7506 participants (mean age, 59.4±13.3 years; 49% whites; and 47% men) from the US Third National Health and Nutrition Examination Survey. ECG-LVH was defined by Cornell voltage criteria. Prolonged heart-rate-adjusted QT (prolonged-QTa) was defined as QTa≥460 ms in women or 450 ms in men. Cox proportional hazards analysis was used to calculate the hazard ratios with 95% confidence intervals for the risk of all-cause mortality for various combinations of ECG-LVH and prolonged-QTa. ECG-LVH was present in 4.2% (N=312) of the participants, of whom 16.4% had prolonged-QTa. In a multivariable-adjusted model and compared with the group without ECG-LVH or prolonged-QTa, mortality risk was highest in the group with concomitant ECG-LVH and prolonged-QTa (hazard ratio, 1.63; 95% confidence interval, 1.12-2.36), followed by isolated ECG-LVH (1.48; 1.24-1.77), and then isolated prolonged-QTa (1.27; 1.12-1.46). In models with similar adjustment where ECG-LVH and prolonged-QTa were entered as 2 separate variables and subsequently additionally adjusted for each other, the mortality risk was essentially unchanged for both variables. CONCLUSIONS: Although prolonged-QT commonly coexists with LVH, both are independent markers of poor prognosis. Concomitant presence of prolonged-QT and ECG-LVH carries a higher risk than either predictor alone.

Race- and sex-associated differences in rate-adjusted QT, QTpeak, ST elevation and other regional measures of repolarization: the Atherosclerosis Risk in Communities (ARIC) Study.

BACKGROUND: Data are limited about race-and sex-associated differences in prognostically important ECG measures of regional repolarization. METHODS AND RESULTS: The normal reference group from the Atherosclerosis Risk in Communities (ARIC) study included 8,676 white and African-American men and women aged 40-65 years. Exclusion criteria included cardiovascular disease, hypertension, diabetes and major ECG abnormalities. Notable sex differences (p<0.001) were observed in the upper 98% limits for rate-adjusted QTend (QTea) which was 435 ms in white and African-American men and 445 ms in white and African-American women, and for left ventricular epicardial repolarization time (RTepi) which was 345 ms in white and African-American men and 465 ms in white and African-American women. These sex differences reflect earlier onset and end of repolarization in men than in women. Upper normal limits for STJ amplitude in V2-V3 were 100 µV in white and African-American women, 150 µV in white men and 200 µV in African-American men (p<0.001 for sex differences), and for other chest leads, aVL and aVF 50 µV in white women, 100 µV in African-American women, 100 µV in white men and 150 µV in African-American men (p<0.001 for sex and race differences). CONCLUSIONS: Shorter QTea and RTepi in men than in women reflect earlier onset and end of repolarization in men. STJ amplitudes in African-American men were higher than in other subgroups by race and sex. These sex and race differences need to be considered in clinical and epidemiological applications of normal standards.

Normal standards for computer-ECG programs for prognostically and diagnostically important ECG variables derived from a large ethnically diverse female cohort: the Women's Health Initiative (WHI).

BACKGROUND: Substantial new information has emerged recently about the prognostic value for a variety of new ECG variables. The objective of the present study was to establish reference standards for these novel risk predictors in a large, ethnically diverse cohort of healthy women from the Women's Health Initiative (WHI) study. METHODS AND RESULTS: The study population consisted of 36,299 healthy women. Racial differences in rate-adjusted QT end (QT(ea)) and QT peak (QT(pa)) intervals as linear functions of RR were small, leading to the conclusion that 450 and 390 ms are applicable as thresholds for prolonged and shortened QT(ea) and similarly, 365 and 295 ms for prolonged and shortened QT(pa), respectively. As a threshold for increased dispersion of global repolarization (T(peak)T(end) interval), 110 ms was established for white and Hispanic women and 120 ms for African-American and Asian women. ST elevation and depression values for the monitoring leads of each person with limb electrodes at Mason-Likar positions and chest leads at level of V1 and V2 were first computed from standard leads using lead transformation coefficients derived from 892 body surface maps, and subsequently normal standards were determined for the monitoring leads, including vessel-specific bipolar left anterior descending, left circumflex artery and right coronary artery leads. The results support the choice 150 µV as a tentative threshold for abnormal ST-onset elevation for all monitoring leads. Body mass index (BMI) had a profound effect on Cornell voltage and Sokolow-Lyon voltage in all racial groups and their utility for left ventricular hypertrophy classification remains open. CONCLUSIONS: Common thresholds for all racial groups are applicable for QT(ea), and QT(pa) intervals and ST elevation. Race-specific normal standards are required for many other ECG parameters.

Different patterns of bundle-branch blocks and the risk of incident heart failure in the Women's Health Initiative (WHI) study.

BACKGROUND: We evaluated the risk of incident heart failure (HF) associated with bundle-branch blocks (BBBs) in postmenopausal women. METHODS AND RESULTS: Cox's regression was used to evaluate hazard ratios with 95% confidence intervals for HF among 65975 participants of the Women's Health Initiative (WHI) study during an average follow-up of 14 years. BBBs observed in 1676 women at baseline were categorized into left, right, and indetermined-type BBBs (LBBB, RBBB, and intraventricular conduction defect, respectively). Compared with women with no BBB, LBBB, and intraventricular conduction defect were strong predictors of incident HF in multivariable-adjusted risk models (hazard ratio, 3.79; confidence interval, 2.95-4.87 for LBBB and hazard ratio, 3.53; confidence interval, 2.14-5.81 for intraventricular conduction defect). RBBB was not a significant predictor of incident HF in multivariable-adjusted risk model, but the combination of RBBB and left anterior fascicular block was a strong predictor (hazard ratio, 2.96; confidence interval, 1.77-4.93). QRS duration was an independent predictor of incident HF only in LBBB, with more pronounced risk at QRS ≥ 140 ms than at <140 ms. QRS nondipolar voltage (RNDPV) was an independent predictor in both RBBB and LBBB and, in addition, in LBBB, QRS/STT angle and ST J-point depression in aVL were independent predictors. CONCLUSIONS: LBBB, intraventricular conduction defect, and RBBB combined with left anterior fascicular block are strong predictors of incident HF in multivariable-adjusted risk models, but RBBB is not a significant predictor. QRS duration ≥ 140 ms may warrant consideration in LBBB as an indication for further diagnostic evaluation for possible therapeutic and preventive action. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000611.

Electrocardiographic predictors of incident heart failure in men and women free from manifest cardiovascular disease (from the Atherosclerosis Risk in Communities [ARIC] study).

The risk of incident hospitalized heart failure (HF) was evaluated for 23 electrocardiographic (ECG) variables in men and women free from cardiovascular disease. The hazard ratios with 95% confidence intervals were determined from Cox regression analysis for 13,428 participants 45 to 65 years old in the Atherosclerosis Risk in Communities (ARIC) study. New-onset HF during a 14-year follow-up period occurred in 695 men (11.9%) and 721 women (9.5%). Several ECG variables were significant predictors of incident HF when evaluated as single ECG variables. Predominant among them were spatial angles, reflecting deviations of the direction of the repolarization sequence from the normal reference direction. After controlling for collinearity among the ECG variables, the spatial angle between T peak and normal T reference vectors, Ó¨(Tp|Tref), was a significant independent predictor in men (HF risk increased 31%) and women (HF risk increased 46%). Other independent predictors in men included epicardial repolarization time (62% increased risk) and T wave peak to T wave end (TpTe) interval, reflecting global dispersion of repolarization (27% increased risk). The independent predictors in women, in addition to Ó¨(Tp|Tref), were Ó¨(R|STT) the spatial angle between the mean QRS and STT vectors (54% increased risk) and QRS nondipolar voltage (46% increased risk). In conclusion, wide Ó¨(Tp|Tref), wide Ó¨(R|STT), and increased QRS nondipolar voltage in women and wide Ó¨(Tp|Tref), increased epicardial repolarization time, prolonged TpTe interval and T wave complexity in men were independent predictors of incident HF, and the presence of these abnormal findings could warrant additional diagnostic evaluation for possible preventive action for HF.

Electrocardiographic predictors of coronary heart disease and sudden cardiac deaths in men and women free from cardiovascular disease in the Atherosclerosis Risk in Communities study.

BACKGROUND: We evaluated predictors of coronary heart disease (CHD) death and sudden cardiac death (SCD) in the Atherosclerosis Risk in Communities (ARIC) study. METHODS AND RESULTS: The study population included 13 621 men and women 45 to 65 years of age free from manifest cardiovascular disease at entry. Hazard ratios from Cox regression with 95% confidence intervals were computed for 18 dichotomized repolarization-related ECG variables. The average follow-up was 14 years. Independent predictors of CHD death in men were TaVR- and rate-adjusted QTend (QTea), with a 2-fold increased risk for both, and spatial angles between mean QRS and T vectors and between Tpeak (Tp) and normal R reference vectors [θ(Rm|Tm) and θ(Tp|Tref), respectively], with a >1.5-fold increased risk for both. In women, independent predictors of the risk of CHD death were θ(Rm|Tm), with a 2-fold increased risk for θ(Rm|Tm), and θ(Tp|Tref), with a 1.7-fold increased risk. Independent predictors of SCD in men were θ(Tp|Tref) and QTea, with a 2-fold increased risk, and θ(Tinit|Tterm), with a 1.6-fold increased risk. In women, θ(Tinit|Tterm) was an independent predictor of SCD, with a >3-fold increased risk, and θ(Rm|Tm) and TV1 were >2-fold for both. CONCLUSIONS: θ(Rm|Tm) and θ(Tp|Tref), reflecting different aspects of ventricular repolarization, were independent predictors of CHD death and SCD, and TaVR and TV1 were also independent predictors. The risk levels for independent predictors for both CHD death and SCD were stronger in women than in men, and QTea was a significant predictor in men but not in women.