Optimal method of measuring the T-peak to T-end interval for risk stratification in primary prevention.

Aims: Several published investigations demonstrated that a longer T-peak to T-end interval (Tpe) implies increased risk for ventricular tachyarrhythmia (VT/VF) and mortality. Tpe has been measured using diverse methods. We aimed to determine the optimal Tpe measurement method for screening purposes. Methods and results: We evaluated 305 patients with LVEF ≤ 35% and an implantable cardioverter-defibrillator implanted for primary prevention. Tpe was measured using seven different methods described in the literature, including six manual methods and the automated algorithm '12SL', and was corrected for heart rate. Endpoints were VT/VF and death. To account for differences in the magnitude of Tpe measurements, results are expressed in standard deviation (SD) increments. We evaluated the clinical utility of each measurement method based on predictive ability, fraction of immeasurable tracings, and intra- and interobserver correlation. >Over 31 ± 23 months, 82 (27%) patients had VT/VF, and over 49 ± 21 months, 91 (30%) died. Several rate-corrected Tpe measurement methods predicted VT/VF (HR per SD 1.20-1.34; all P < 0.05), and nearly all methods (both corrected and uncorrected) predicted death (HR per SD 1.19-1.35; all P < 0.05). Optimal predictive ability, readability, and correlation were found in the automated 12SL method and the manual tangent method in lead V2. Conclusion: For the prediction of VT/VF, the utility of Tpe depends upon the measurement method, but for the prediction of mortality, most published Tpe measurement methods are similarly predictive. Heart rate correction improves predictive ability. The automated 12SL method performs as well as any manual measurement, and among manual methods, lead V2 is most useful.

T-peak to T-end interval for prediction of ventricular tachyarrhythmia and mortality in a primary prevention population with systolic cardiomyopathy.

BACKGROUND: The electrocardiographic T-wave peak to T-wave end interval (Tpe) correlates with dispersion of ventricular repolarization (DVR). Increased DVR increases propensity toward electrical reentry that can cause ventricular tachyarrhythmia. The baseline rate-corrected Tpe (Tpec) has been shown to predict ventricular tachyarrhythmia and death in multiple patient populations but not among cardiomyopathic patients undergoing insertion of an implantable cardioverter-defibrillator (ICD) for primary prevention. OBJECTIVE: The purpose of this study was to assess the risk stratification ability of the Tpec in patients with systolic cardiomyopathy without prior ventricular tachyarrhythmia (ie, the primary prevention population). METHODS: We performed prospective follow-up of 305 patients (73% men; left ventricular ejection fraction [LVEF] 23 ± 7%) with LVEF ≤35% and an ICD implanted for primary prevention. Baseline ECGs were analyzed with automated algorithms. Endpoints were ventricular tachycardia (VT)/ventricular fibrillation (VF), death, and a combined endpoint of VT/VF or death, assessed by device follow-up and Social Security Death Index query. RESULTS: The average Tpec was 107 ± 22 ms. During device clinic follow-up of 31 ± 23 months, 82 patients (27%) had appropriate ICD therapy for VT/VF, and during mortality follow-up of 49 ± 21 months, 91 patients (30%) died. On univariable analysis, Tpec predicted VT/VF, death, and the combined endpoint of VT/VF or death (P < .05 for each endpoint). Multivariable analysis included univariable predictors among demographics, clinical data, laboratory data, medications used, and electrocardiography parameters. After correction, Tpec remained predictive of VT/VF (hazard ratio [HR] per 10-ms increase 1.16, P = .009), all-cause mortality (HR per 10 ms 1.13, P = .05), and the combined endpoint (HR per 10 ms 1.17, P = .001). CONCLUSION: Tpec independently predicts both VT/VF and overall mortality in patients with systolic dysfunction and ICDs implanted for primary prevention.

P-pulmonale and the development of atrial fibrillation.

BACKGROUND: P wave ≥0.25mV in inferior leads (P pulmonale) occurs in chronic lung diseases that underlie atrial fibrillation (AF). The purpose of this study was to elucidate the prognostic value of P pulmonale for development of AF. METHODS AND RESULTS: Digital analysis of 12-lead electrocardiogram (ECG) was conducted to enroll patients with P pulmonale from among a database containing 308,391 ECGs. In a total of 591 patients (382 men; 56.4±14.8 years) with P pulmonale (follow-up, 46.7±65.6 months), AF occurred in 61 patients (AF group), but did not occur in 530 patients (non-AF group). Male gender was significantly more prevalent in the AF group than in the non-AF group (80.3% vs. 62.8%, P=0.0047). P-wave duration and PQ interval were significantly longer in the AF group than in the non-AF group (115.4±17.2ms vs. 107.0±17.2ms, P=0.0003 and 166.3±23.9ms vs. 153.2±25.4ms, P=0.0001, respectively). In the total patient group, multivariate Cox proportional-hazards analysis confirmed that male gender (hazard ratio [HR], 2.24; 95% confidence interval [CI]: 1.02-5.49; P=0.045), PQ interval >150ms (HR, 6.89; 95% CI: 2.39-29.15; P<0.0001), and P-wave axis <74° (HR, 2.55; 95% CI: 1.20-5.41; P=0.016) were associated with AF development. In medication-free patients (n=400), only PQ interval >150ms (HR, 9.26; 95% CI: 1.75-170.65; P=0.0055) was independently and significantly associated with AF development. CONCLUSIONS: PQ interval is the strongest stratifier for AF development in P pulmonale.

Prognostic implications of progressive cardiac conduction disease.

BACKGROUND: Progressive cardiac conduction disease (PCCD), characterized by temporal increase in PR interval and QRS duration, may be attributed to diverse pathophysiological mechanisms. This study aimed to investigate whether PCCD is associated with increased risk of cardiovascular morbidity and mortality. METHODS AND RESULTS: Digital analysis of 12-lead ECG was performed to select patients with PCCD from among a database containing 359,737 ECGs. Long-term prognosis of PCCD was assessed in a large hospital-based population: 458 patients (341 males; mean age, 57.9 ± 14.7 years) with PCCD were enrolled. During a mean follow-up of 13.3 ± 6.4 years, 109 patients were hospitalized for heart failure (HF), and there were 16 and 59 deaths from cardiovascular diseases and all causes, respectively. Multivariate Cox proportional hazards analysis confirmed (1) a significant association of temporal incremental rate of PR interval (≥ 2 ms/year) and QRS duration (≥ 3 ms/year) with HF hospitalization (hazard ratio [HR], 2.34; 95% confidence interval [CI], 1.36-4.05; P=0.002 and HR, 2.08; 95% CI, 1.25-3.53; P=0.01, respectively) and (2) a significant association of temporal incremental rate of PR interval (≥ 4 ms/year) and QRS duration (≥ 5 ms/year) with cardiovascular mortality (HR, 6.9; 95% CI, 1.47-36.96; P=0.02 and HR, 4.31; 95% CI, 1.19-16.5; P=0.03, respectively). CONCLUSIONS: The severity of PCCD was independently and significantly associated with HF hospitalization and cardiovascular mortality.

Relationships between the T-peak to T-end interval, ventricular tachyarrhythmia, and death in left ventricular systolic dysfunction.

AIMS: The interval between the T-wave's peak and end (Tpe), an electrocardiographic (ECG) index of ventricular repolarization, has been proposed as an indicator of arrhythmic risk. We aimed to clarify the clinical usefulness of Tpe for risk stratification. METHODS AND RESULTS: We evaluated 327 patients with left ventricular ejection fraction (LVEF) ≤ 35% (75% male, LVEF 23 ± 7%). All patients had an implanted implantable cardioverter-defibrillator (ICD). Clinical data and ECGs were analysed at baseline. Prospective follow-up for the endpoints of appropriate ICD therapy and mortality was conducted via periodic device interrogation, chart review, and the Social Security Death Index. During device clinic follow-up of 17 ± 12 months, 59 (18%) patients had appropriate ICD therapy, and during mortality follow-up of 30 ± 13 months, 67 (21%) patients died. A longer Tpe(c) predicted appropriate ICD therapy, death, and the combination of appropriate ICD therapy or death (P< 0.01 for each endpoint). On multivariable analysis correcting for other univariable predictors, Tpe(c) remained predictive of ICD therapy [hazard ratio (HR) per 10 ms increase: 1.16, P= 0.02], all-cause mortality (HR per 10 ms: 1.14, P= 0.03), and the composite endpoint of ICD therapy or death (HR per 10 ms: 1.16, P< 0.01). CONCLUSIONS: In patients with left ventricular systolic dysfunction and an implanted ICD, Tpe(c) independently predicts both ventricular tachyarrhythmia and overall mortality.

Clinical and electrocardiographic characteristics of patients with short QT interval in a large hospital-based population.

BACKGROUND: Short QT syndrome is one of the underlying disorders associated with ventricular fibrillation. However, the precise prognostic implication of a short QT interval remains unclear. OBJECTIVE: The purpose of this study was to investigate the prevalence and long-term prognosis in patients with a shorter-than-normal QT interval in a large hospital-based population. METHODS: We chose patients with a short Bazett QTc interval from a database consisting of 114,334 patients to determine the clinical characteristics and prognostic value of a short QT interval. RESULTS: A total of 427 patients (mean age 43.4 ± 22.4 years) had a short QT interval with about a 1.2 times higher male predominance (234 men). The QTc interval was significantly longer in female than in male patients (363.8 ± 6.1 ms vs 357.1 ± 5.8 ms, P <.0001). The age-specific prevalence of patients with short QT interval was biphasic, peaking at young and old age. Atrial fibrillation and early repolarization were complicated with short QT interval in 39 (9.1%) and 26 (6.1%) patients, respectively. The prognosis of 327 patients (182 men; mean age, 46.4 ± 27.3 years) with a short QT interval could be assessed (mean follow-up period, 54.0 ± 62.0 months). During the follow-up, 2 patients, 1 of whom had early repolarization, developed life-threatening events, in contrast to 6 patients who died of noncardiac causes and did not have early repolarization. CONCLUSION: The prevalence of a short QT interval showed a slight male preponderance and biphasic age-dependent distribution in both genders. The complication rate of atrial fibrillation was higher in those with a short QT interval than in general populations. The long-term outcome suggested that early repolarization in a short QT interval might be associated with potential risk of lethal arrhythmia.

Risk determinants in individuals with a spontaneous type 1 Brugada ECG.

BACKGROUND: Spontaneous coved ST-segment elevation ≥2 mm followed by a negative T-wave in the right precordial leads (type 1 Brugada ECG) is diagnostic of Brugada syndrome (BS), but there is a false-positive rate. METHODS AND RESULTS: Computer-processed analysis of a 12-lead ECG database containing 49,286 females and 52,779 males was performed to select patients with a spontaneous type 1 Brugada ECG for an examination of the association of this ECG characteristic with long-term prognosis. There were 185 patients with a spontaneous type 1 Brugada ECG and of these, 16 (15 males; mean age, 46.7±14.0 years) were diagnosed with BS and 15 patients (all males; mean age, 50.1±13.4 years) were undiagnosed. The PQ interval was significantly longer in the diagnosed patients than in the undiagnosed patients (187.4±28.3 ms vs. 161.2±21.5 ms; P=0.0073). The T-wave in lead V(1) was more negative in the diagnosed patients than in the undiagnosed patients (-170.2±174.6 µV vs. -43.2±122.3 µV, P=0.027). Multivariate analysis revealed that a PQ interval ≥170 ms and T-wave amplitude <105 µV in lead V(1) were independent risk stratifiers of life-threatening events. Survival analysis (mean follow-up, 78.6±81.8 months) showed that the PQ interval and a negative T-wave in lead V(1) were significantly associated with poor prognosis. CONCLUSIONS: Analysis of a standard 12-lead ECG can stratify the prognosis of patients with a spontaneous type 1 Brugada ECG.

Identifying drug-induced repolarization abnormalities from distinct ECG patterns in congenital long QT syndrome: a study of sotalol effects on T-wave morphology.

BACKGROUND: The electrocardiographic QT interval is used to identify drugs with potential harmful effects on cardiac repolarization in drug trials, but the variability of the measurement can mask drug-induced ECG changes. The use of complementary electrocardiographic indices of abnormal repolarization is therefore warranted. Most drugs associated with risk are inhibitors of the rapidly activating delayed rectifier potassium current (I(Kr)). This current is also inhibited in the congenital type 2 form of the long QT syndrome (LQT2). It is therefore possible that electrocardiographic LQT2 patterns might be used to identify abnormal repolarization patterns induced by drugs. OBJECTIVE: To develop distinct T-wave morphology parameters typical of LQT2 and investigate their use as a composite measure for identification of d,l-sotalol (sotalol)-induced changes in T-wave morphology. METHODS: Three independent study groups were included: a group of 917 healthy subjects and a group of 30 LQT2 carriers were used for the development of T-wave morphology measures. The computerized measure for T-wave morphology (morphology combination score, MCS) was based on asymmetry, flatness and notching, which are typical ECG patterns in LQT2. Blinded to labels, the new morphology measures were tested in a third group of 39 healthy subjects receiving sotalol. Over 3 days the sotalol group received 0, 160 and 320 mg doses, respectively, and a 12-lead Holter ECG was recorded for 22.5 hours each day. Drug-induced prolongation of the heart rate corrected QT interval (QTcF) was compared with changes in the computerized measure for T-wave morphology. Effect sizes for QTcF and MCS were calculated at the time of maximum plasma concentrations and for maximum change from baseline. Accuracy for separating baseline from sotalol recordings was evaluated by area under the receiver operating characteristic curves (AUCs) using all recordings from the time immediately post-dose to maximum change. RESULTS: MCS separated baseline recordings from sotalol treatment with higher accuracy than QTcF for the 160 mg dose: (AUC) 84% versus 72% and for the 320 mg dose: (AUC) 94% versus 87%, p < 0.001. At maximum serum-plasma concentrations and at maximum individual change from baseline, the effect sizes for QTcF were less than half the effect sizes for MCS, p < 0.001. Effect sizes at peak changes of the mean were up to 3-fold higher for MCS compared with QTcF, p < 0.001. In subjects receiving sotalol, T-wave morphology reached similarity to LQT2, whereas QTcF did not. CONCLUSION: Distinct ECG patterns in LQT2 carriers effectively quantified repolarization changes induced by sotalol. Further studies are needed to validate whether this measure has general validity for the identification of drug-induced disturbed repolarization.

Robust QT interval estimation--from algorithm to validation.

BACKGROUND: This article presents an effort of measuring QT interval with automatic computerized algorithms. The aims of the algorithms are consistency as well as accuracy. Multilead and multibeat information from a given segment of ECG are used for more consistent QT interval measurement. METHODS: A representative beat is generated from selected segment of each lead, and then a composite beat is formed by the representative beats of all independent leads. The end result of the QT measure is so-called global QT measurement, which usually correlates with the longest QT interval in multiple leads. Individual lead QT interval was estimated by using the global measurement as a starting point, and then adapted to the signal of the particular lead and beat. In general, beat-by-beat QT measurement is more prone to noise, therefore less reliable than the global estimation. It is usually difficult to know if difference of beat-by-beat QT interval is due to true physiological change or noise fluctuation. RESULTS: The algorithm was tested independently by a clinical database. It is also tested against action potential duration (APD) generated by a Cell-to-ECG forward-modeling based simulation signals. The modeling approach provided an objective test for the QT estimation. The modeling approach allowed us to evaluate the QT measurement versus APD. The mean error between the algorithm and cardiologist QT intervals is 3.95 +/- 5.5 ms, based on the large clinical trial database consisting of 15,910 ECGs. The mean error between QT intervals and maximum APD is 17 +/- 2.4, and the correlation coefficient is 0.99. CONCLUSIONS: The global QT interval measurement method presented in this study shows very satisfactory results against the CSE database and a large clinical trial database. The modeling test approach used in this study provides an alternative "gold standard" for QT interval measurement.

New descriptors of T-wave morphology are independent of heart rate.

T-wave morphology descriptors are sensitive to drug-induced changes and may be a useful addition to the QT interval in cardiac safety trials. Intrasubject heart rate dependence of T-wave morphology was investigated in a sample of 39 healthy individuals. Ten-second electrocardiograms were obtained from daytime Holter recordings. Duration parameters (QT, ToTe, TpTe, and others), a number of basic T-wave morphology parameters (amplitude, area, and others) as well as advanced morphology descriptors (asymmetry, flatness, and others) were measured automatically. Heart rate dependence was examined by means of analysis of covariance. The results showed clear heart rate dependence for the QT interval (R(2) = 0.53-0.57) and a moderate degree of heart rate dependence for the basic morphology parameters (amplitude, area, and others) (R(2) = 0.17-0.42). Both the advanced T-wave descriptors (asymmetry, flatness, and others), ToTe intervals and TpTe intervals, were practically independent of heart rate (R(2) = 0-0.08), making heart rate correction unnecessary for these parameters.