T-wave Morphology Parameters Research Articles

Normal ranges and potential modifiers of T-wave morphology parameters among healthy individuals: A meta-analysis.

T-wave morphology parameters, such as total cosine R-to-T (TCRT), T-wave loop dispersion (TWLD), T-wave morphology dispersion (TMD), and T-wave residuum (TWR), were suggested to be robust markers for adverse cardiovascular outcomes. Yet, the normal range of these parameters is unknown. This study aimed to evaluate the weighted normal values of T-wave morphology parameters of healthy individuals and study the effect of potential modifiers. A systematic search of studies published in PubMed was conducted. Only those reporting on control groups of healthy individuals were included. Weighted means were calculated for TCRT, TWLD, TMD, and TWR. Linear regression analysis was conducted for age, percentage of males, heart rate, and QTc. The weighted TCRT was 0.40 ± 0.05, significantly higher than the various cutoffs previously suggested to identify high risk. There was some overlap between the results of weighted normal TMD (19.42 ± 6.77°), TWLD (38.51 ± 0.31), and relative TWR (0.118 ± 0.056%) and reports on the same parameters from patients with cardiovascular disease. Women were also characterized by higher TWLD, TMD, and relative TWR. TCRT was negatively correlated with age and heart rate, and positively correlated with QTc duration, although all associations were weak (R2 <0.9). T-wave morphology parameters reported in the medical literature span a broad range of values in healthy individuals. Seemingly abnormal values of TWLD, TMD, and relative TWR were often reported in healthy adults. The variability between studies may stem from methodological issues. Therefore, standardizing the methodology for measuring T-wave morphology is imperative.

T-wave morphology descriptors in patients with bulimia nervosa

Bulimia nervosa (BN) is associated with increased risk of cardiovascular disease and arrhythmias. Some reports found abnormal electrocardiographic markers of arrhythmias in BN, while others did not. This study investigated novel parameters of T-wave morphology that were reported to be associated with adverse cardiovascular outcomes in other patient groups, among patients with BN under medical care. Thirty-five BN patients and 76 healthy controls were included. Total cosine R to T (TCRT) and T-wave Morphology Dispersion (TMD) parameters were computed according to accepted standards for an average beat and a random beat. Patients were followed for 11.1 ± 0.1years for the emergence of arrhythmias or events of sudden death. Twenty-five (71.4%) BN patients were hospitalized when enrolled, for a mean duration of 1.1 ± 0.2months. The rest were ambulatory patients. The BN group had lower blood pressure, more smokers, and used antidepressants, neuroleptic drugs and benzodiazepines more than controls did. Other demographic parameters were comparable between groups. TCRT and TMD parameters were statistically similar and within the normal ranges reported by other research groups. None of the BN patients had prolonged QTc interval or electrolyte abnormalities on inclusion. During the follow-up period, no clinical symptoms suggestive of arrhythmias were reported, and no cardiovascular-related hospitalizations or deaths occurred in either group. Medically treated BN patients have normal T-wave morphology parameters and hence, low risk for repolarization-associated malignant ventricular arrhythmias. The prognostic importance of these novel repolarization parameters remains to be explored among untreated patients, those who ingest emetic substances and patients with electrolyte imbalance. Level III.

Improving long QT syndrome diagnosis by a polynomial-based T-wave morphology characterization

Diagnosing long QT syndrome (LQTS) remains challenging because of a considerable overlap in QT interval between patients with LQTS and healthy subjects. Characterizing T-wave morphology might improve LQTS diagnosis. The purpose of this study was to improve LQTS diagnosis by combining new polynomial-based T-wave morphology parameters with the corrected QT interval (QTc), age, and sex in a model. A retrospective cohort consisting of 333 patients with LQTS and 345 genotype-negative family members was used in this study. For each patient, a linear combination of the first 2 Hermite-Gauss (HG) polynomials was fitted to the STT segments of an average complex of all precordial leads and limb leads I and II. The weight coefficients as well as the error of the best fit were used to characterize T-wave morphology. Subjects were classified as patients with LQTS or controls by clinical QTc cutoffs and 3 support vector machine models fed with different features. An external cohort consisting of 72 patients and 45 controls was finally used to check the robustness of the models. Baseline QTc cutoffs were specific but had low sensitivity in diagnosing LQTS. The model with T-wave morphology features, QTc, age, and sex had the best overall accuracy (84%), followed by a model with QTc, age, and sex (79%). The model with T-wave morphology features especially performed better in LQTS type 3 patients (69%). T-wave morphologies can be characterized by fitting a linear combination of the first 2 Hermite-Gauss polynomials. Adding T-wave morphology characterization to age, sex, and QTc in a support vector machine model improves LQTS diagnosis.

Prognostic value of T-wave morphology parameters in coronary artery disease in current treatment era.

The prognostic value of T-wave morphology parameters in coronary artery disease in the current treatment era is not well established. The Innovation to reduce Cardiovascular Complications of Diabetes at the Intersection (ARTEMIS) study included 1,946 patients with angiographically verified coronary artery disease (CAD). The study patients underwent thorough examinations including 12-lead digital electrocardiogram (ECG) at baseline. During a follow-up period of 73±22months, a total of 201 (10.3%) patients died. Of the study patients, 95 (4.9%) experienced cardiac death (CD) consisting of 44 (2.3%) sudden cardiac deaths (SCD) and 51 (2.6%) nonsudden cardiac deaths (NSCD), and 106 (5.4%) patients experienced noncardiac death (NCD). T-wave morphology dispersion (TMD), T-wave area dispersion (TWAD), and total cosine R-to-T (TCRT) had a significant association with CD even after adjustment with relevant clinical risk markers in the Cox regression analysis (multivariate HRs: 1.015, 95% CI 1.007-1.023, p=.0003; 0.474, 95% CI 0.305-0.737, p=.0009; 0.598, 95% CI 0.412-0.866, p=.006, respectively). When including these parameters to the clinical risk model for CD, the C-index increased from 0.810 to 0.823 improving the discrimination significantly (integrated discrimination index [IDI]=0.0118, 95% CI 0.0028-0.0208, p=.01). These parameters were more closely associated with NSCD (multivariate p-values from .016 to .001) than with SCD (univariate/multivariate p-values for TMD .015/.197 and for TCRT .012/.43). T-wave morphology parameters describing repolarization heterogeneity improve the predictive power of the clinical risk model for CD in patients with CAD in the current treatment era.

Repolarisation descriptors and heart rate variability in hemodialysed patients.

T wave morphology (TWM) descriptors derived from Holter electrocardiograms during hemodialysis (HD) are of potential value for cardiac risk assessment in HD patients. Our knowledge on autonomic regulation of TWM descriptors is limited. The purpose of this study was to investigate the association between TWM parameters and heart rate variability (HRV) during intradialytic monitoring. In each of 81 patients on maintenance HD, continuous electrocardiograms were recorded 5 times during HD on alternate weeks. TWM descriptors were calculated every 5 s in overlapping 10-s ECG segments and Low Frequency (LF) (0.04 Hz to 0.15 Hz), High Frequency (HF) (0.15 Hz to 0.40 Hz) powers of the spectrum of HRV were calculated every five min. The calculated values of TWM and HRV were averaged during the first hour of the recordings and subsequently over all recordings in each subject. Analyzable data for HRV and TWM were available in 71 HD patients (aged 61+/-15, 36 % diabetics, 32 % females). LF in normalized units correlated positively with Total Cosine R to T (r=0.374, p=0.001) and negatively with T wave morphology dispersion (r=-0.253, p=0.033) after adjusting for heart rate. A heart rate independent association between repolarisation descriptors and HRV exists in HD patients. Autonomic modulation needs to be considered when using TWM characteristics for risk profiling of HD patients.

Predictive Value of Electrocardiographic T-Wave Morphology Parameters and T-Wave Peak to T-Wave End Interval for Sudden Cardiac Death in the General Population

Previous population studies have found an association between electrocardiographic T-wave morphology parameters and cardiovascular mortality, but their relationship to sudden cardiac death (SCD) is not clear. To our knowledge, there are no follow-up studies assessing the association between electrocardiographic T-wave peak to T-wave end interval (TPE) and SCD. We assessed the predictive value of electrocardiographic T-wave morphology parameters and TPE for SCD in an adult general population sample. A total of 4 T-wave morphology parameters (principal component analysis ratio, T-wave morphology dispersion, total cosine R-to-T, T-wave residuum) as well as TPE were measured from digital standard 12-lead ECGs in 5618 adults (46% men; mean age 50.9±12.5 years) participating in the Finnish population-based Health 2000 Study. After a mean follow-up time of 7.7±1.4 years, 72 SCDs had occurred. In univariable analyses, all T-wave morphology parameters were associated with an increased SCD risk. In multivariable Cox models, T-wave morphology dispersion and total cosine R-to-T remained as predictors of SCD, with T-wave morphology dispersion showing the highest SCD risk (hazard ratio of 1.4 [95% confidence interval 1.1-1.7, P=0.001] per 1 SD increase in the loge T-wave morphology dispersion). In contrast, TPE was not associated with SCD in univariable or multivariable analyses. Electrocardiographic T-wave morphology parameters describing the 3-dimensional shape of the T-wave stratify SCD risk in the general population, but we did not find an association between TPE and SCD.

Study of T-wave morphology parameters based on Principal Components Analysis during acute myocardial ischemia

Electrocardiographic repolarization abnormalities can be detected by Principal Components Analysis of the T-wave. In this work we studied the efect of signal averaging on the mean value and reproducibility of the ratio of the 2nd to the 1st eigenvalue of T-wave (T21W) and the absolute and relative T-wave residuum (TrelWR and TabsWR) in the ECG during ischemia induced by Percutaneous Coronary Intervention. Also, the intra-subject and inter-subject variability of T-wave parameters have been analyzed. Results showed that TrelWR and TabsWR evaluated from the average of 10 complexes had lower values and higher reproducibility than those obtained from 1 complex. On the other hand T21W calculated from 10 complexes did not show statistical diferences versus the T21W calculated on single beats. The results of this study corroborate that, with a signal averaging technique, the 2nd and the 1st eigenvalue are not afected by noise while the 4th to 8th eigenvalues are so much afected by this, suggesting the use of the signal averaged technique before calculation of absolute and relative T-wave residuum. Finally, we have shown that T-wave morphology parameters present high intra-subject stability.

Heritability of Tpeak-Tend Interval and T-Wave Amplitude

Background— Tpeak-Tend interval (TpTe) and T-wave amplitude (Tamp) carry diagnostic and prognostic information regarding cardiac morbidity and mortality. Heart rate and QT interval are known to be heritable traits. The heritability of T-wave morphology parameters such as TpTe and Tamp is unknown. TpTe and Tamp were evaluated in a large sample of twins. Methods and Results— Twins from the GEMINAKAR study (611 pairs, 246 monozygotic, 365 dizygotic; mean age, 38±11 years; 49% men) who had an ECG performed during 1997 to 2000 were included. Tamp was measured in leads V1 and V5. Duration variables (RR interval, QTpeak and QTend interval) were measured and averaged over 3 consecutive beats in lead V5. TpTe was calculated as the QTend- and QTpeak-interval difference. Heritability was assessed using structural equation models adjusting for age, sex, and body mass index. All models were reducible to a model of additive genetics and unique environment. All variables had considerable genetic components. Adjusted heritability estimates were as follows: TpTe, 46%; Tamp lead V1, 34%; Tamp lead V5, 47%; RR interval, 55%; QT interval, 67%; and Bazett-corrected QT interval, 42%. Conclusions— RR interval, QT interval, Tamp, and TpTe interval are heritable ECG parameters.

Extraction and Analysis of $\hbox{T}$ Waves in Electrocardiograms During Atrial Flutter

Analysis of T waves in the ECG is an essential clinical tool for diagnosis, monitoring, and follow-up of patients with heart dysfunction. During atrial flutter, this analysis has been so far limited by the perturbation of flutter waves superimposed over the T wave. This paper presents a method based on missing data interpolation for eliminating flutter waves from the ECG during atrial flutter. To cope with the correlation between atrial and ventricular electrical activations, the CLEAN deconvolution algorithm was applied to reconstruct the spectrum of the atrial component of the ECG from signal segments corresponding to TQ intervals. The locations of these TQ intervals, where the atrial contribution is presumably dominant, were identified iteratively. The algorithm yields the extracted atrial and ventricular contributions to the ECG. Standard T-wave morphology parameters (T-wave amplitude, T peak-T end duration, QT interval) were measured. This technique was validated using synthetic signals, compared to average beat subtraction in a patient with a pacemaker, and tested on pseudo-orthogonal ECGs from patients in atrial flutter. Results demonstrated improvements in accuracy and robustness of T-wave analysis as compared to current clinical practice.

Relationship of common candidate gene variants to electrocardiographic T-wave peak to T-wave end interval and T-wave morphology parameters

Single-nucleotide polymorphisms (SNPs) in genes encoding cardiac ion channels and nitric oxide synthase-1 adaptor protein (NOS1AP) are associated with electrocardiographic (ECG) QT-interval duration, but the association of these SNPs with new, prognostically important ECG measures of ventricular repolarization is unknown. The purpose of this study was to examine the relationship of SNPs to ECG T-wave peak to T-wave end (TPE) interval and T-wave morphology parameters. We studied 5,890 adults attending the Health 2000 Study, a Finnish epidemiologic survey. TPE interval and four T-wave morphology parameters were measured from digital 12-lead ECGs and related to the seven SNPs showing a phenotypic effect on QT-interval duration in the Health 2000 Study population. In multivariable analyses, the KCNH2 K897T minor allele was associated with a 1.2-ms TPE-interval shortening (P = .00005) and the KCNH2 intronic rs3807375 minor allele was associated with a 0.8-ms TPE-interval prolongation (P = .001), whereas the KCNE1 D85N variant had no TPE-interval effect (P = .20). NOS1AP minor alleles (rs2880058, rs4657139, rs10918594, rs10494366) were associated with a shorter TPE interval (effects from 0.5 to 0.8 ms, P from .032 to .002), which resulted from their stronger effects on QT(peak) than QT(end) interval. None of the SNPs showed a consistent association with T-wave morphology parameters. KCNH2 K897T and rs3807375 as well as the four studied NOS1AP variants have modest effects on ECG TPE interval but are not related to T-wave morphology measures. The previously observed prognostic value of T-wave morphology parameters likely is not based on these SNPs.

The Association between T‐Wave Morphology and Life‐Threatening Ventricular Tachyarrhythmias in Patients with Congestive Heart Failure

Whether T-wave morphology descriptors on the 12-lead electrocardiogram (ECG) can predict the occurrence of life-threatening ventricular arrhythmia in patients with advanced congestive heart failure is unclear. Standard 12-lead ECGs were photoscanned and digitized for analysis in 27 heart failure patients with ventricular tachycardia/ventricular fibrillation (VT/VF; study group), as well as in 54 age- and sex-matched heart failure patients without life-threatening ventricular arrhythmia as a control group. Novel T-wave morphology descriptors were compared. The results showed that the temporal descriptor, the lead dispersion (LD; 426.5 +/- 279.8 vs 189.0 +/- 125.7, P < 0.001), was significantly higher in the study than in the control group. The other T-wave morphology parameters, such as the T-wave morphology dispersion (45.7 +/- 20.1 vs 44.9 +/- 18.6), the total cosine between QRS and T wave (TCRT; -0.4 +/- 0.4 vs -0.5 +/- 0.3), and the normalized T-loop area (NTLA; 0.5 +/- 0.1 vs 0.4 +/- 0.1), were not significantly different between the two groups (all P value > 0.05). After an adjustment for other clinical variables, increased LD (odds ratio: 9.9, 95% confidence interval [CI]: 2.9-33.4, P < 0.001) or decreased NTLA (odds ratio: 0.4, 95% CI: 0.1-1.0, P =0.05) was associated with VT/VF. The novel T-wave morphology analysis may help in identifying heart failure patients at high risk for VT/VF.

T‐Wave Morphology in Short QT Syndrome

Short QT syndrome (SQTS) is an inherited disorder characterized by a short QT interval and vulnerability to ventricular tachyarrhythmias. The diagnostic criteria for this syndrome are not well defined, since there is uncertainty about the lowest normal limits for the corrected QT (QTc) interval. The aim of this study was to determine whether T-wave morphology parameters are abnormal in short QT subjects and whether those parameters can help in the diagnosis of SQTS. We describe three families (10 patients) with short QT intervals (QTc 310 +/- 32 ms). Seven subjects had suffered serious arrhythmic events and three were asymptomatic. T-wave morphology was assessed using the principal component analysis (PCA). QTc was significantly shorter and T-wave amplitude in lead V2 higher in the short QT subjects compared to healthy controls (n=149), (P < 0.001 for both). The total cosine of the angle between the main vectors of the QRS and T-wave loops (TCRT) was markedly abnormal among the symptomatic patients with short QT syndrome (n=7) (TCRT -0.14 +/- 0.55 vs 0.36 +/- 0.51, P=0.019). None of the three asymptomatic patients with short QT but without a history of arrhythmic events had an abnormally low TCRT. Our observations suggest that patients with a short QT interval and a history of arrhythmic events have abnormal T-wave loop parameters. These electrocardiogram (ECG) features may help in the diagnosis of SQTS in addition to the measurement of the duration of QT interval from the 12-lead ECG.

Identifying Drug-Induced Repolarization Abnormalities from Distinct ECG Patterns in Congenital Long QT Syndrome

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. 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. 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. 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. 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.

Predictive value of electrocardiographic QT interval and T-wave morphology parameters for all-cause and cardiovascular mortality in a general population sample

The predictive value of ECG QT interval for mortality in the general population has been weak. Only a few population studies on the predictive value of ECG T-wave morphology parameters for mortality have been reported. The purpose of this study was to examine the predictive value of ECG QT interval and T-wave morphology parameters for all-cause and cardiovascular mortality in the general population. The prognostic values of ECG QT interval and four T-wave morphology parameters (principal component analysis ratio, T-wave morphology dispersion, total cosine R-to-T, T-wave residuum) were assessed in 5,917 adults (45% men; age 52 +/- 14 years) participating in the Finnish population-based Health 2000 Study. After a mean follow-up of 5.9 +/- 0.8 years, 335 deaths had occurred, including 131 cardiovascular deaths. QT interval and, with a few exceptions, all T-wave morphology parameters were significant univariate mortality predictors. In men, in Cox multivariate analyses, principal component analysis ratio and T-wave morphology dispersion remained as independent predictors of all-cause and cardiovascular mortality, with the above-median T-wave morphology dispersion group showing the highest risk of cardiovascular death (hazard ratio [HR] 4.4, 95% confidence interval [CI] 2.1-9.4). In women, independent mortality predictors were total cosine R-to-T (cardiovascular mortality) and T-wave residuum (all-cause and cardiovascular mortality), with the above-median T-wave residuum group showing the highest risk of cardiovascular death (HR 2.2, 95% CI 1.1-4.2). In the general population, T-wave morphology parameters, but not heart rate-corrected QT interval, provide independent prognostic information on mortality. The prognostic value of T-wave morphology parameters is specifically related to cardiovascular mortality and seems to be gender specific.

ECG Evaluation of Ventricular Properties: The Importance of Cardiac Cycle Length

Ventricular repolarization properties are dependent on cardiac cycle length. The aim of this article is to emphasize the importance of taking into account heart rate influences on QT duration but also on current and future T-wave morphology parameters. The relationship between QT interval duration and RR interval is a fundamental property of the myocardium that is impaired by the presence of channelopathies such as the LQTS or SQTS, but also by the presence of a cardiomyopathy. Assessing this property is also important when the individual QT/RR relationship is used for individual QT correction in the setting of evaluation of drugs' effect on QT duration. T-wave descriptors such as the relative weight of the terminal part of the T-wave, the amplitude of T-wave apex and Principal Component Analysis parameters are also dependent on heart rate. Assessing ventricular repolarisation ECG parameters at different heart rates avoids the need for difficult rate-correction and helps to better understand and characterize ventricular repolarisation properties.

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.

Improving the Detection of Subtle IKr-Inhibition

QT prolongation is an incomplete measure of drug-induced changes in repolarization. In this study, we investigated a novel, automatic ECG technique for describing ventricular repolarization morphology and we compared these results to corrected QT (QTc) prolongation for identifying ECGs of healthy individuals on moxifloxacin. We analysed data from the US FDA ECG Warehouse involving 160 standard ECGs from 40 healthy subjects enrolled in a randomized, parallel, placebo-controlled, 'thorough QT' study. Computerized ECG analysis included a series of scalar and vectorial parameters describing duration of repolarization segments and T-wave/loop morphology including its symmetry, amplitude and shape. Binary logistic models for the identification of moxifloxacin-induced abnormalities of the repolarization were developed. Moxifloxacin induced significant changes in several ECG parameters including QT and QT apex and early repolarization duration (ERD)(30)(%), T-wave amplitude and slopes of the ascending and descending arm of the T-wave. The logistic model based only on T-wave morphology parameters outperformed the model based on QTc interval for identifying the presence of moxifloxacin. Combining information about repolarization interval duration with T-wave morphology significantly improved the detection of presence of moxifloxacin (p < 0.01). The increased sensitivity of our novel ECG method contributes to a >40% reduction in the sample size required to detect significant QTc prolongation induced by moxifloxacin. Repolarization morphology is significantly altered by moxifloxacin. The computerized ECG technique provides a novel method for quantifying morphological changes of repolarization segment. Our new parameters reflecting the morphology of the T-wave outperformed QTc measurements when identifying moxifloxacin-induced blockade of the outward rapid components of the delayed rectifier repolarizing potassium current (I(Kr)). These data indicate that the analysis of T-wave morphology could play a role in the assessment of drug toxicity.

T‐Wave Morphology Parameters Based on Principal Component Analysis Reproducibility and Dependence on T−Offset Position

T-wave morphology parameters based on principal component analysis (PCA) are candidate to better understand the relation between QT prolongation and torsades de pointes. We aimed to assess the repeatability and to determine the influence of T-end position on PCA parameters. Digital ECGs recorded from 30 subjects were used to assess short term (5 minutes), circadian and long-term (28 days) repeatability of PCA parameters. The T-end cursor position was moved backward and forward (+/- 8 ms) from its optimal position. We calculated QRS-T angle, PCA ratio, and T-wave residuum (TWR). At long-term evaluation, coefficients of variation were 11.3 +/- 9.9%, 11.7 +/- 7.1%, and 23.0 +/- 22.0% for the QRS-T angle, PCA ratio, TWR, respectively. After moving the T-end cursor, repeatability was 0.42 +/- 0.2%, 1.00 +/- 1.04%, 4.0 +/- 4.2% for the same PCA parameters. T-wave morphology parameters based on PCA are reproducible with the exception of TWR and QRS-T angle. In addition, PCA is robust, showing only little dependence on T-end cursor position. These data should be taken into account for safety pharmacology trials.

Relationship of electrocardiographic repolarization measures to echocardiographic left ventricular mass in men with hypertension

Arterial hypertension often leads to an increase in left ventricular mass (LVM). Marked left ventricular hypertrophy (LVH) is associated with potentially arrhythmogenic ventricular repolarization abnormalities, which may contribute to the increased risk of sudden cardiac death in this disorder. We studied whether electrocardiographic repolarization changes are already detectable in mild LVM increase associated with hypertension. In 220 men (mean age 51+/-6 years) attending the GENRES hypertension study, we measured QT intervals (QTend and QTpeak), T-wave peak to T-wave end (TPE) intervals, and novel T-wave morphology parameters (principal component analysis ratio, T-wave morphology dispersion, total cosine R-to-T, and T-wave residuum) from a digital standard 12-lead electrocardiogram, and related them to echocardiographically determined LVM. In this group of moderately hypertensive men, the mean LVM index (LVMI; LVM divided by body surface area) was 99+/-19 g/m2, with only 18% of the subjects showing evidence of echocardiographic LVH (LVMI>116 g/m2). LVMI correlated significantly with QT intervals (r=0.16-0.21, P=0.018-0.002), TPE intervals (r=0.23-0.27, P<0.001), and T-wave morphology parameters (r=0.22-0.39, P<0.001). Except for the QTpeak interval, the relationship between LVMI and electrocardiographic repolarization parameters was independent in multivariate analyses. Altered electrocardiographic ventricular repolarization, indicating reduced repolarization reserve and possibly increased repolarization heterogeneity, is already present in hypertensive men with only mild LVM increase. At a population level, this may carry important risk implications for the large group of hypertensive patients.

The effect of signal averaging on the reproducibility and reliability of measures of T-wave morphology

Electrocardiographic repolarization abnormalities characterized by T-wave morphology parameters such as the principal component analysis ratio and the relative and the absolute T-wave residuum (TWR rel and TWR abs) are predictive of cardiovascular and/or all-cause mortality. However, when using a “10-second median beat” for analysis, the reported mean values for TWR rel vary widely and parameter reproducibility is somewhat suspect. In repeated electrocardiographic recordings conducted 1 month and 1 year apart on 15 and 27 healthy individuals, respectively, we studied the said T-wave morphology parameters in single complexes and in reduced noise signal averages containing 10 and 200 complexes. Considering all subjects, the mean (±SD) TWR rel was highest in a single complex (0.0345% ± 0.0183%), intermediate in the 10-beat signal-averaged complexes (0.0125% ± 0.0051%), and lowest in the 200-beat signal-averaged complexes (0.0078% ± 0.0036%) ( P < .0001), with the same trend also observed in the TWR abs but not in the principal component analysis ratio. Reproducibility as quantified by within-subject variance and reliability as quantified by the intraclass (intrasubject) correlation coefficient also improved as the number of T-wave complexes analyzed increased. We conclude that signal averages consisting of more than 10 complexes (or more than 10 seconds worth of complexes) are required to produce reproducible and reliable values for TWR rel and TWR abs.