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.

Abnormal electrocardiographic QRS transition zone and risk of mortality in individuals free of cardiovascular disease.

AIMS: We examined the prognostic significance of abnormal electrocardiographic QRS transition zone (clockwise and counterclockwise horizontal rotations) in individuals free of cardiovascular disease (CVD). METHODS AND RESULTS: A total of 5541 adults (age 53 ± 10.4 years, 54% women, 24% non-Hispanic black, 25% Hispanic) without CVD or any major electrocardiogram (ECG) abnormalities from the US Third National Health and Nutrition Examination Survey were included in this analysis. Clockwise and counterclockwise horizontal rotations were defined from standard 12-lead ECG using Minnesota ECG Classification. Mortality and cause of death were assessed through 2006. At baseline, 282 participants had clockwise rotation and 3500 had counterclockwise rotation. During a median follow of 14.6 years, 1229 deaths occurred of which 415 were due to CVD. In multivariable-adjusted Cox proportional hazard analysis and compared with normal rotation, clockwise rotation was significantly associated with increased risk of all-cause mortality {hazard ratio (HR) [95% confidence interval (CI)]: 1.43 (1.15-1.78); P = 0.002} and CVD mortality [HR (95% CI): 1.61 (1.09, 2.37) P = 0.016]. In contrast, counterclockwise rotation was associated with significantly lower risk of all-cause mortality [HR (95% CI): 0.86 (0.76, 0.97); P = 0.017] and non-significant association with CVD mortality [HR (95% CI): 1.07 (0.86, 1.33); P = 0.549]. These results were consistent in subgroup analysis stratified by age, sex, and race. CONCLUSION: In a diverse community-based population free of CVD and compared with normal rotation, clockwise rotation was associated with increased risk of all-cause and CVD mortality while counterclockwise rotation was associated with lower risk of all-cause mortality and non-significant association with CVD mortality. These findings call for attention to these often neglected ECG markers, and probably call for revising the current definition of normal rotation.

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.

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.

Reduction of RV pacing by continuous optimization of the AV interval.

BACKGROUND: In patients requiring permanent pacing, preservation of intrinsic ventricular activation is preferred whenever possible. The Search AV+ (SAV+) algorithm in Medtronic EnPulsetrade mark dual-chamber pacemakers can increase atrioventricular (AV) intervals to 320 ms in patients with intact or intermittent AV conduction. This prospective, multicenter study compared the percentage of ventricular pacing with and without AV interval extension. METHODS: Among 197 patients enrolled in the study, the percentage of ventricular-paced beats was evaluated via device diagnostics at the 1-month follow-up. Patient cohorts were defined by clinician assessment of conduction via a 1:1 AV conduction test at the 2-week follow-up. The observed percentage of ventricular pacing with SAV + ON and the predicted percentage of ventricular pacing with SAV + OFF were determined from the SAV + histogram data for the period between the 2-week and 1-month follow-up visits. RESULTS: Of 197 patients, 110 (55.8%) had intact 1:1 AV conduction, of which 109 had 1-month data. SAV + remained ON in 99/109 patients; 10 patients had intrinsic A-V conduction intervals beyond SAV + nominal and therefore SAV + disabled. The mean percentage of ventricular pacing in the 109 patients was SAV+ ON = 23.1% (median 3.7%) versus SAV + OFF = 97.2% (median 99.7%). In 87 patients without 1:1 AV conduction, SAV + was programmed OFF in 6, automatically disabled in 52, and remained ON in 29. In 8 of these patients, 80-100% reduction in ventricular pacing was observed with SAV + ON. CONCLUSION: The Search AV+ algorithm in the EnPulse pacemaker effectively promotes intrinsic ventricular activation and substantially reduces unnecessary ventricular pacing.

Automatic measurement of atrial pacing thresholds in dual-chamber pacemakers: clinical experience with atrial capture management.

BACKGROUND: The Medtronic EnPulse pacemaker incorporates the new atrial capture management (ACM) algorithm to automatically measure atrial capture thresholds and subsequently manage atrial pacing outputs. OBJECTIVES: The purpose of this study was to evaluate the clinical performance of ACM. METHODS: Two hundred patients with an indication for a dual-chamber pacemaker underwent implantation. ACM thresholds and manually measured atrial pacing thresholds were assessed at follow-up visits. Clinical equivalence was defined as the ACM-measured threshold being within -0.25 V to +0.5 V of the manually measured threshold. The clinician analyzed all ACM measurements performed in-office for evidence of proarrhythmia. RESULTS: All 200 implanted patients had a 1-month visit, and validated manual and in-office ACM threshold data were available for 123 patients. The ACM threshold was 0.595 +/- 0.252 V, and the manual threshold was 0.584 +/- 0.233 V. The mean difference was 0.010 V with a 95% confidence interval of (-0.001, 0.021). The mean difference over all visits was 0.011 V. For all patients, the individual threshold differences were within the range of clinical equivalence at all visits. No atrial arrhythmias were observed during 892 ACM tests in 193 patients. CONCLUSION: This study demonstrated that the ACM algorithm is safe, accurate, and reliable over time. ACM was demonstrated to be clinically equivalent to the manual atrial threshold test in all patients at 1 month and over the entire follow-up period of up to 6 months. ACM ensures atrial capture, may save time during follow-up, and can be used to manage atrial pacing outputs.

Rate-dependent slow conduction velocity in the cavo-tricuspid isthmus and septum in patients with atrial flutter.

PURPOSE: To evaluate and compare the effects of heart rate on conduction velocity in the cavotricuspid isthmus (CTI) and septum in patients with and without typical atrial flutter (AF) using electro-anatomic mapping (EAM) of the right atrium (RA). METHODS: Ten patients (age 53+/-10 yrs, 7M/3F) with AF and 13 patients (age 51+/-11 yrs, 5M/8F) with atrioventricular nodal reentrant tachycardia (AVNRT) underwent conventional electrophysiological study, electro-anatomic mapping and radiofrequency ablation. Using EAMs obtained during coronary sinus pacing at pacing cycle length (PCL) 600 ms, 400 ms, and 300 ms, we evaluated conduction velocities in the CTI and septum of RA in 10 patients with AF and compared EAMs to 13 patients with AVNRT to determine whether the conduction slowing required to maintain AFL was related to changes in volume alone or altered RA electrophysiology. RESULTS: Conduction velocities in CTI and septum were significantly slower at all PCL when AF was compared to AVNRT (*P<0.05). Additionally, in the AF group, septal conduction velocities were slower at PCL 600 ms and 400 ms, but not at 300 ms compared to CTI (*P<0.05). In AF, during PCL 300, conduction in CTI slowed significantly compared to PCL 600 and 400 ms such that there was no difference between CTI and septum at PCL 300. CONCLUSIONS: There is slower conduction in the septum compared to the CTI in all patients. However, in patients with AF, there is significant slowing of conduction in the CTI and septum as well as decremental rate-dependent slowing of conduction in the CTI. These findings indicate that in addition to RA enlargement, changes in atrial electrophysiology distinguish AF patients from patients with AVNRT.

Electro-anatomic mapping of the right atrium: anatomic abnormality is an important substrate.

OBJECTIVE: To map and compare the right atrium in patients with AF to those with atrioventricular nodal reentrant tachycardias (AVNRT, as control group) and to investigate the anatomical and electrophysiological abnormality of the right atrium in AF. METHODS: The anatomy and electrophysiology of right atrium and cavotricuspid isthmus were evaluated in 20 patients with AF (16 M/4 F, mean age 55.9 +/- 10.68 years) and 26 patients with AVNRT (9 M/17 F, mean age 47.50 +/- 19.56 years) during coronary sinus pacing at 600 ms prior to ablation with electro-anatomical mapping system. Right atrial volume (RAV), the length and width of cavotricuspid isthmus (IsL, IsW), unipolar and bipolar voltage in the right atrium (UniV-RA, BiV-RA) were measured and compared between patients with AF and those with AVNRT. RESULTS: RAV, IsL, IsW, UniV-RA, and BiV-RA were 143.22 +/- 40.72 vs 104.35 +/- 21.06 ml, 39.31 +/- 8.10 vs 32.42 +/- 9.77 mm, 30.54 +/- 7.48 vs 23.15 +/- 6.61 mm, 1.96 +/- 1.24 vs 1.53 +/- 0.91 mv and 1.47 +/- 1.47 vs 1.29 +/- 1.12 mv in AF and AVNRT respectively. CONCLUSION: The right atrial volume is larger; both the length and width of cavotricuspid isthmus are greater. Unipolar and bipolar voltages in the right atrium are higher in AF than in AVNRT, suggesting that the enlarged right atrium, increased length and width of cavotricuspid isthmus, and concomitant atrial hypertrophy are important substrates for initiation and perpetuation of typical AF.