Yabing Li

The relationship between high resting heart rate and ventricular arrhythmogenesis in patients referred to ambulatory 24 h electrocardiographic recording

AIMS High resting heart rate (HR) has been associated with sudden cardiac death (SCD). This association is not fully explained by the reported association between HR with coronary heart disease (CHD) or left ventricular systolic dysfunction, the major pathological substrates for SCD. Ventricular arrhythmia is the most common antecedent event before SCD. Examining associations between resting HR and ventricular arrhythmogenesis may enhance our understanding of the association between high resting HR and SCD. METHODS AND RESULTS This study included 867 patients (age 54 +/- 5, 57% females) who underwent 24 h ambulatory electrocardiographic (ECG) recording (Holter) in the period from 1998 to 2000. We examined the unadjusted and multivariable-adjusted associations between resting HR with factors involved in ventricular arrhythmogenesis [ventricular late potentials (LPs) detected by signal-averaged ECG, heart rate variability (HRV), and premature ventricular complexes (PVCs)]. Linear regression models were used for continuous outcomes and logistic regression analysis was used for categorical outcomes. The multivariable models included first age and sex, then history of hypertension, diabetes, hypercholesterolaemia, CHD, heart failure, left ventricular ejection fraction (LVEF), smoking, body mass index, the use of anti-arrhythmic drugs, and ST-depression in the 24 h ambulatory ECG recording (Holter) were included in the final models. In the unadjusted and multivariable-adjusted analysis, high resting HR was significantly associated with positive ventricular LPs, depressed HRV indices, and increased prevalence of PVCs/24 h independently from demographic and clinical variables including LVEF, history of CHD, and the presence of ST-depression in Holter (P-value <0.05 in all comparisons and models). CONCLUSION High resting HR is independently associated with ventricular arrhythmogenesis, the major cause of SCD. These findings could partially explain the reported association between increased HR and SCD.

Explaining the inconsistent associations of PR interval with mortality: The role of P-duration contribution to the length of PR interval

BACKGROUND There is a strong interest in PR interval as a predictor for adverse outcomes. However, inconsistent reports have emerged. OBJECTIVE The purpose of this study was to test the hypothesis that the significance of PR interval as a predictor depends on the level of contribution of P duration to its length, a contribution that varies across populations. METHODS We tested our hypothesis in 7501 participants from the Third National Health and Nutrition Examination Survey (NHANES III). Participants were divided into two subgroups based on the median P-duration contribution to PR interval (P duration/PR interval * 100). The risk of mortality associated with prolonged (>200 ms) and short (<120 ms) PR interval compared with normal PR interval was examined in all participants and each subgroup. RESULTS P-duration contribution to the length of PR interval ranged from 30% to 90% (median 70%). During median follow-up of 13.8 years, 2541 deaths occurred. In a multivariable adjusted model, short but not prolonged PR interval was associated with mortality (hazard ratio [HR], (95% confidence interval [CI]): 1.54 (1.18, 2.00) and 1.02 (0.90, 1.16), respectively). However, in a stratified analysis by P-duration contribution to PR interval, both short and prolonged PR interval were associated with mortality in participants with high P-duration contribution (HR (95% CI):1.46 (1.10, 1.94) and 2.00 (1.34, 2.99), respectively) but not in participants with low P-duration contribution (HR (95% CI):1.53 (0.68, 3.41) and 0.99 (0.87, 1.13), respectively); interaction P = .008. CONCLUSION PR-interval associations with outcomes are dictated by the level of contribution of P duration to its length, a contribution that has a wide range and is expected to vary across populations. These findings could explain the inconsistent reports of PR-interval associations in different studies and call for caution when using PR interval in risk prediction models.

The Romhilt-Estes left ventricular hypertrophy score and its components predict all-cause mortality in the general population

BACKGROUND The same electrocardiographic (ECG) criteria that have been used for detection of left ventricular hypertrophy (LVH) have recently been recognized as predictors of adverse clinical outcomes, but this predictive ability is inadequately explored and understood. METHODS A total of 14,984 participants from the ARIC study were included in this analysis. Romhilt-Estes (R-E) LVH score was measured from the automatically processed baseline (1987-1989) ECG data. All-cause mortality was ascertained up to December 2010. Cox proportional hazard models were used to examine the association between baseline R-E score, overall and each of its 6 individual components separately, with all-cause mortality. The associations between change in R-E score between baseline and first follow-up visit with mortality were also examined. RESULTS During a median follow-up of 21.7 years, 4,549 all-cause mortality events occurred during follow-up. In multivariable-adjusted models, increasing levels of the R-E score was associated with increasing risk of mortality both as a baseline finding and as a change between the baseline and the first follow-up visit. Of the 6 ECG components of the score, 4 were predictive of all-cause mortality (P-terminal force, QRS amplitude, LV strain, and intrinsicoid deflection), whereas 2 of the components were not (left axis deviation and prolonged QRS duration). Differences in the strengths of the associations between the individual components of the score and mortality were observed. CONCLUSIONS The R-E score, traditionally used for detection of LVH, could be used as a useful tool for predication of adverse outcomes.

Electrocardiographic Deep Terminal Negativity of the P Wave in V1 and Risk of Mortality: The National Health and Nutrition Examination Survey III

Deep terminal negativity of P wave in V1 (DTNPV1), defined as negative P prime larger than one small box (1 mm, or 0.1 mV), could be easily detected by simple visual inspection of the resting 12‐lead ECG. The objective of this study was to determine the relationship between DTNPV1 and all‐cause‐, cardiovascular disease (CVD), and ischemic heart disease (IHD) mortality in the National Health and Nutrition Examination Survey III (NHANES III).

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.

Early repolarization and markers of ventricular arrhythmogenesis in patients referred to ambulatory 24-hour ECG recording

BACKGROUND Recent reports suggest that early repolarization, a common electrocardiographic (ECG) pattern that has been always considered benign, could be a substrate for ventricular arrhythmias and sudden cardiac arrest. METHODS We examined the associations between early repolarization and markers of ventricular arrhythmogenesis as defined by presence of ventricular late potentials (LPs) in the Signal Averaged ECG (SA-ECG), depressed heart rate variability (HRV) and/or presence of ventricular ectopy in patients referred to ambulatory 24-hour ECG recording (Holter). RESULTS This study included 687 patients (57% females) who were 51.2 ± 5.1 years. In unadjusted and multivariable adjusted analyses, early repolarization was not significantly associated with any of the measures of SA-ECG, HRV or ventricular ectopy. The lack of significant associations persisted in all subgroup analyses where different definitions of early repolarization in different groups of ECG leads were tested. CONCLUSIONS Early repolarization has no significant association with markers of ventricular arrhythmogenesis as detected by SA-ECG, HRV and ventricular ectopy. These findings suggest that the mechanisms of arrhythmic events in early repolarization (if they truly exist), are not likely to be through pathological pathways that could be detected by these markers.

Automated J wave detection from digital 12-lead electrocardiogram.

In this report we provide a method for automated detection of J wave, defined as a notch or slur in the descending slope of the terminal positive wave of the QRS complex, using signal processing and functional data analysis techniques. Two different sets of ECG tracings were selected from the EPICARE ECG core laboratory, Wake Forest School of Medicine, Winston Salem, NC. The first set was a training set comprised of 100 ECGs of which 50 ECGs had J-wave and the other 50 did not. The second set was a test set (n=116 ECGs) in which the J-wave status (present/absent) was only known by the ECG Center staff. All ECGs were recorded using GE MAC 1200 (GE Marquette, Milwaukee, Wisconsin) at 10mm/mV calibration, speed of 25mm/s and 500HZ sampling rate. All ECGs were initially inspected visually for technical errors and inadequate quality, and then automatically processed with the GE Marquette 12-SL program 2001 version (GE Marquette, Milwaukee, WI). We excluded ECG tracings with major abnormalities or rhythm disorder. Confirmation of the presence or absence of a J wave was done visually by the ECG Center staff and verified once again by three of the coauthors. There was no disagreement in the identification of the J wave state. The signal processing and functional data analysis techniques applied to the ECGs were conducted at Duke University and the University of Toronto. In the training set, the automated detection had sensitivity of 100% and specificity of 94%. For the test set, sensitivity was 89% and specificity was 86%. In conclusion, test results of the automated method we developed show a good J wave detection accuracy, suggesting possible utility of this approach for defining and detection of other complex ECG waveforms.

Minor isolated Q waves and cardiovascular events in the MESA study.

BACKGROUND The significance of minor isolated Q waves in the resting electrocardiograms (ECGs) of apparently healthy individuals is unknown. OBJECTIVE To examine the association between minor isolated Q waves and incident cardiovascular disease events in the Multi-Ethnic Study of Atherosclerosis (MESA). DESIGN This analysis included 6551 MESA participants (38% white, 28% black, 22% Hispanic, 12% Chinese) who were free of cardiovascular disease at enrollment. Cox proportional hazards models were used to examine the association between minor isolated Q waves defined by the Minnesota ECG Classification with adjudicated incident cardiovascular events. RESULTS During up to 7.8 years of follow-up, 423 events occurred, with a rate of 10.7 events per 1000 person-years. A significant interaction between minor isolated Q waves and race/ethnicity was observed (P=.030). In models stratified by race/ethnicity and adjusted for demographics, socioeconomic status, common cardiovascular risk factors, and other ECG abnormalities, presence of isolated minor Q waves was significantly associated with incident cardiovascular events in Hispanics (hazard ratio [HR] 2.62; 95% confidence interval [CI], 1.42-4.82), but not in whites (HR 0.65; 95% CI, 0.32-1.33) or blacks (HR 1.46; 95% CI, 0.74-2.89). Despite the statistically significant association in the Chinese population, the small number of events precluded solid conclusions in this race/ethnicity. CONCLUSION The prognostic significance of minor isolated Q waves varies across races/ethnicities; they carry a high risk for future cardiovascular events in apparently healthy Hispanics, but not in whites or blacks.

Progression of Electrocardiographic Abnormalities in Type 1 Diabetes During 16 Years of Follow‐up: The Epidemiology of Diabetes Interventions and Complications (EDIC) Study

Background The electrocardiogram (ECG) is an objective tool for cardiovascular disease (CVD) risk assessment. Methods and Results We evaluated distribution of ECG abnormalities and risk factors for developing new abnormalities in 1314 patients with type 1 diabetes (T1D) from the Epidemiology of Diabetes Interventions and Complications (EDIC) study. Annual ECGs were centrally read. ECG abnormalities were classified as major and minor according to the Minnesota ECG Classification. At EDIC year 1 (baseline), 356 (27.1%) of the participants had at least 1 ECG abnormality (major or minor) whereas 26 (2%) had at least one major abnormality. During 16 years of follow‐up, 1016 (77.3%) participants developed at least 1 new ECG abnormality (major or minor), whereas 172 (13.1%) developed at least 1 new major abnormality. Independent risk factors for developing new major ECG abnormalities were: age, current smoking, increased systolic blood pressure, and higher glycosylated hemoglobin (hazard ratio [HR] [95% CI]: 1.04 [1.02–1.06] per 1‐year increase, 1.75 [1.22–2.53], 1.03 [1.01–1.05] per 1 mm Hg increase, and 1.16 [1.04–1.29] per 10% increase, respectively). Independent risk factors for developing any new ECG abnormalities (major or minor) were age and systolic blood pressure (HR [95% CI]: 1.02 [1.01–1.03] per 1‐year increase and 1.01 [1.00–1.02] per 1 mm Hg increase, respectively). Conclusions New ECG abnormalities commonly occur in the course of T1D, consistent with the recognized increasing risk for CVD as patients age. Advanced age, increased systolic blood pressure, smoking, and higher HbA1c are independent risk factor for developing major ECG abnormalities, which underscores the importance of tight glucose control in T1D in addition to management of common CVD risk factors.

Tobacco Exposure as Determined by Serum Cotinine and Subclinical Myocardial Injury in Individuals Free from Cardiovascular Disease.

Tobacco exposure including second-hand smoke is the leading preventable cause of premature death in the United States. Serum cotinine, a highly sensitive and specific biomarker for tobacco exposure, is a more accurate measure of tobacco exposure than self-reported smoking status. Although the harmful effect of tobacco exposure on cardiovascular disease (CVD) risk factors (e.g., atherosclerosis) or hard CVD outcomes (e.g., myocardial infarction) is well established, its effect on intermediate outcomes such as subclinical myocardial injury (SMI), especially in nonsmokers, is not clear. Therefore, we examined the risk of SMI, defined as a Cardiac Infarction/Injury Score of ≥10 points on the 12-lead electrocardiogram with abnormal serum cotinine levels (>15 ng/ml) in 6,264 smokers and nonsmokers who were free from CVD enrolled in the Third National Health and Nutrition Examination Survey. SMI was more common in those with abnormal compared with normal serum cotinine levels (25.9% vs 19.6%, respectively; p <0.01). In a multivariable logistic regression model adjusted for age, gender, race, obesity, diabetes, hypertension, and dyslipidemia, abnormal (vs normal) serum cotinine was associated with a 61% increased risk of SMI (odds ratio 1.61, 95% confidence interval 1.40 to 1.85, p <0.01). This association was stronger in smokers, in women, and in nondiabetic and nonobese participants. In conclusion, elevated serum cotinine levels are associated with an increased risk of SMI in participants free from CVD, and this association is stronger in certain groups of participants. These findings underscore the harmful effect of both active and passive tobacco exposures on the cardiovascular system, and highlight the need for a personalized risk assessment that takes into account groups at high risk.