T-wave Morphology Analysis Research Articles

Extraction and Digitization of ECG Signals from Standard Clinical Portable Document Format Files for the Principal Component Analysis of T-wave Morphology.

T-wave analysis from standard electrocardiogram (ECG) remains one of the most available clinical and research methods for evaluating myocardial repolarization. T-wave morphology was recently evaluated to aid with diagnosis and characterization of diastolic dysfunction. Unfortunately, PDF stored ECG datasets limit additional numerical post-processing of ECG waveforms. In this study, we apply a simple custom process pipeline to extract and re-digitize T-wave signals and subject them to principal component analysis (PCA) to define primary T-wave shape variations. We propose simple pre-processing and digitization algorithms programmable as a MATLAB tool using standard thresholding functions without the need for advanced signal analysis. To validate digitized datasets, we compared clinically standard measurements in 20 different ECGs with the original ECG machine interpreted values as a gold standard. Afterwards, we analyzed 212 individual ECGs for T-wave shape analysis using PCA. The re-digitized signal was shown to preserve the original information as evidenced by excellent agreement between original - machine interpreted and re-digitized clinical variables including heart rate: bias ~ 1bpm (95% CI: -1.0 to 3.5), QT interval: bias ~ 0.000 ms (95% CI: -0.012 to 0.012), PR interval: bias = -0.015 ms (95% CI: -0.015 to 0.003), and QRS duration: bias = -0.001 ms (95% CI: -0.007 to 0.006). PCA revealed that the first principal component universally modulates the T-wave height or amount of repolarization voltage regardless of the investigated ECG lead. The second and third principal components described variation in the T-wave peak onset and the T-wave peak morphology, respectively. This study presents a straightforward method for re-digitizing ECGs stored in the PDF format utilized in many academic electronic medical record systems. This process can yield re-digitized lead specific signals which can be retrospectively analyzed using advanced custom post-processing numerical analysis independent of commercially available platforms.

Increases in repolarization heterogeneity predict left ventricular systolic dysfunction and response to cardiac resynchronization therapy in patients with left bundle branch block.

This study aimed to investigate the association between T-wave morphology and impaired left ventricular ejection fraction (LVEF) in patients with complete left bundle branch block (cLBBB), and the predictive value of T-wave morphology for response to cardiac resynchronization therapy (CRT). We enrolled 189 patients with cLBBB on electrocardiogram performed between January 2007 and December 2011 who underwent standard echocardiography. Repolarization parameters, including the QRS-to-T angle (TCRT), T-wave morphology dispersion (TMD), T-wave loop area (PL), and T-wave residuum (TWR), were reconstructed from digital standard 12-lead electrocardiograms by T-wave morphology analysis. CRT response was defined as ≥15% reduction in left ventricular end-systolic volume at 12 months after CRT implantation. The clinical outcome endpoint was a composite of heart failure hospitalization, heart transplantation, or death during follow up (mean, 5.8 years). On logistic regression, a higher heart rate, longer QRS duration, increased TMD, and larger TWR were all independently associated with LVEF < 40%. Among 40 patients who underwent CRT, those with a larger TMD (P = .007), larger PL (P = .025), and more negative TCRT (P = .015) had better response to CRT. A large TMD (P = .018) and large PL (P = .003) were also independent predictors of the clinical outcome endpoint. Increases in repolarization heterogeneity in patients with cLBBB are associated with impaired LVEF. A large TMD and large PL may be useful as additional predictors of response to CRT, improving patient selection for CRT.

T-Wave Morphology Analysis in CongenitalLong QT Syndrome Discriminates Patients From HealthyIndividuals.

This study aims to assess the capability of T-wave analysis to: 1) identify genotype-positive long QT syndrome (LQTS) patients; 2) identify LQTS patients with borderline or normal QTc interval (≤460 ms); and 3) classify LQTS subtype. LQTS often presents with a nondiagnostic electrocardiogram (ECG). T-wave abnormalities may be the only marker of this potentially lethal arrhythmia syndrome. ECGs taken at rest in 108 patients (43 with LQTS1, 20 with LQTS2, and 45 control subjects) were evaluated for T-wave flatness, asymmetry, and notching, which produces a morphology combination score (MCS) of the 3 features (MCS= 1.6× flatness+ asymmetry+ notch) using QT Guard Plus Software (GE Healthcare, Milwaukee, Wisconsin). Toassess for heterogeneity of repolarization, the principal component analysis ratio 2 (PCA-2) was calculated. Mean QTc intervals were 486 ± 50 ms (LQTS1), 479 ± 36 ms (LQTS2), and 418 ± 24 ms (control subjects) (p< 0.05). MCS and PCA-2 differed between LQTS patients and control subjects (MCS: 117.8 ± 57.4 vs. 71.9 ± 16.2; p<0.001; PCA-2: 20.2 ± 10.4% vs. 14.6 ± 5.5%; p< 0.001), LQTS1 and LQTS2 patients (MCS: 96.3 ± 28.7 vs. 164 ± 75.2; p< 0.001; PCA-2: 17.8 ± 8.3% vs. 25 ± 12.6%; p< 0.001), and between LQTS patients with borderline or normalQTc intervals (n= 17) and control subjects (MCS: 105.7 ± 49.9 vs. 71.9 ± 16.2; p< 0.001; PCA-2: 18.1 ± 7.2% vs. 14.6 ± 5.5%; p< 0.001). T-wave metrics were consistent across multiple ECGs from individual patients based on theaverage intraclass correlation coefficient (MCS: 0.96; PCA-2: 0.86). Automated T-wave morphology analysis accurately discriminates patients with pathogenic LQTS mutations from control subjects and between the 2 most common LQTS subtypes. Mutation carriers without baseline QTc prolongation were also identified. This may be a useful tool for screening families of LQTS patients, particularly when the QTc interval is subthreshold and genetic testing is unavailable.

T-wave morphology can distinguish healthy controls from LQTS patients

Long QT syndrome (LQTS) is an inherited disorder associated with prolongation of the QT/QTc interval on the surface electrocardiogram (ECG) and a markedly increased risk of sudden cardiac death due to cardiac arrhythmias. Up to 25% of genotype-positive LQTS patients have QT/QTc intervals in the normal range. These patients are, however, still at increased risk of life-threatening events compared to their genotype-negative siblings. Previous studies have shown that analysis of T-wave morphology may enhance discrimination between control and LQTS patients. In this study we tested the hypothesis that automated analysis of T-wave morphology from Holter ECG recordings could distinguish between control and LQTS patients with QTc values in the range 400–450 ms. Holter ECGs were obtained from the Telemetric and Holter ECG Warehouse (THEW) database. Frequency binned averaged ECG waveforms were obtained and extracted T-waves were fitted with a combination of 3 sigmoid functions (upslope, downslope and switch) or two 9th order polynomial functions (upslope and downslope). Neural network classifiers, based on parameters obtained from the sigmoid or polynomial fits to the 1 Hz and 1.3 Hz ECG waveforms, were able to achieve up to 92% discrimination between control and LQTS patients and 88% discrimination between LQTS1 and LQTS2 patients. When we analysed a subgroup of subjects with normal QT intervals (400–450 ms, 67 controls and 61 LQTS), T-wave morphology based parameters enabled 90% discrimination between control and LQTS patients, compared to only 71% when the groups were classified based on QTc alone. In summary, our Holter ECG analysis algorithms demonstrate the feasibility of using automated analysis of T-wave morphology to distinguish LQTS patients, even those with normal QTc, from healthy controls.

Major rapid weight loss induces changes in cardiac repolarization

IntroductionObesity is associated with increased all-cause mortality, but weight loss may not decrease cardiovascular events. In fact, very low calorie diets have been linked to arrhythmias and sudden death. The QT interval is the standard marker for cardiac repolarization, but T-wave morphology analysis has been suggested as a more sensitive method to identify changes in cardiac repolarization. We examined the effect of a major and rapid weight loss on T-wave morphology. Methods and ResultsTwenty-six individuals had electrocardiograms (ECG) taken before and after eight weeks of weight loss intervention along with plasma measurements of fasting glucose, HbA1c, and potassium. For assessment of cardiac repolarization changes, T-wave Morphology Combination Score (MCS) and ECG intervals: RR, PR, QT, QTcF (Fridericia-corrected QT-interval), and QRS duration were derived.The participants lost on average 13.4% of their bodyweight. MCS, QRS, and RR intervals increased at week 8 (p<0.01), while QTcF and PR intervals were unaffected. Fasting plasma glucose (p<0.001) and HbA1c both decreased at week 8 (p<10−5), while plasma potassium was unchanged. MCS but not QTcF was negatively correlated with HbA1c (p<0.001) and fasting plasma glucose (p<0.01). ConclusionRapid weight loss induces changes in cardiac repolarization. Monitoring of MCS during calorie restriction makes it possible to detect repolarization changes with higher discriminative power than the QT-interval during major rapid weight loss interventions. MCS was correlated with decreased HbA1c. Thus, sustained low blood glucose levels may contribute to repolarization changes.

T-wave morphology analysis of competitive athletes

BackgroundT-wave morphology has been shown to be more sensitive than QT and QTc interval to describe repolarization abnormalities. The electrocardiogram (ECG) performed in athletes may manifest abnormalities, including repolarization alterations. The aim of this study was to investigate the characteristics of T-wave morphology features in athletes. MethodsEighty male elite athletes, consisting of 40 Tour de France cyclists (age 27±5years), 40 soccer players (age 26±6years) and 40 healthy men (age 27±5years) were included. ResultsSinus bradycardia, left ventricular (LV) hypertrophy, incomplete right bundle branch block and early repolarization were documented in 25 %, 20%, 13% and 14% of athletes, respectively. ECG criteria for LV hypertrophy in 12-lead ECG were more common in cyclists (35%) than in soccer players (5%), P<0.0001. Cyclists and soccer players had significantly longer RR interval, and repolarization features than the control group. ConclusionsT-wave morphology of athletes is different from non-athletes, depending of the sport. Decreased potassium current in cardiomyocytes associated with LVH may contribute to these changes.

ECG T-Wave Monitor for Potential Early Detection and Diagnosis of Cardiac Arrhythmias

T-wave abnormalities are gaining significance in the realm of electrocardiogram diagnostics. In particular, T-wave alternans are proving to be powerful predictive indicators of potentially fatal arrhythmias. T-wave morphology monitoring and analysis are the means by which alternans and other abnormalities are detected. We have presented a preliminary design of an analog T-wave monitor to provide a characteristic description of the beat-to-beat T-wave morphology in terms of its maximum leading edge and trailing edge slopes, and its area. Experimental results showed that data from the analog T-wave monitor compared well with those predicted theoretically. Current design of the T-wave monitor, once improved, can find use in the screening, diagnosis, and early detection of T-wave abnormalities in clinical settings.

Covariate Analysis of QTc and T-Wave Morphology: New Possibilities in the Evaluation of Drugs That Affect Cardiac Repolarization

This study adds the dimension of a T-wave morphology composite score (MCS) to the QTc interval-based evaluation of drugs that affect cardiac repolarization. Electrocardiographic recordings from 62 subjects on placebo and 400 mg moxifloxacin were compared with those from 21 subjects on 160 and 320 mg D,L-sotalol. T-wave morphology changes, as assessed by DeltaMCS, are larger after 320 mg D,L-sotalol than after 160 mg D,L-sotalol; and the changes associated with 160 mg D,L-sotalol are, in turn, larger than those associated with moxifloxacin and placebo. Covariate analyses of DeltaQTc and DeltaMCS showed that changes in T-wave morphology are a significant effect of D,L-sotalol. By contrast, moxifloxacin was found to have no significant effect on T-wave morphology (DeltaMCS) at any given change in QTc. This study offers new insights into the repolarization behavior of a drug associated with low cardiac risk vs. one associated with a high risk and describes the added benefits of a T-wave MCS as a covariate to the assessment of the QTc interval.

Reference values of electrocardiogram repolarization variables in a healthy population

Introduction Reference values for T-wave morphology analysis and evaluation of the relationship with age, sex, and heart rate are lacking in the literature. In this study, we characterized T-wave morphology in a large sample of healthy individuals. Method A total of 1081 healthy subjects (83% men; range, 17-81 years) were included. T-wave morphology variables describing the duration, area, slopes, amplitude, and distribution were calculated using 10-second digital electrocardiogram recordings. Multivariate regression was used to test for dependence of T-wave variables with the subject age, sex, and heart rate. Results Lead V5 (men vs women) T-wave variables were as follows: amplitude, 444 versus 317 μV; area, 48.4 versus 33.2 ms ⁎ mV; Tpeak-Tend interval, 94 versus 92 milliseconds; maximal descending slope, −5.15 versus −3.69 μV/ms; skewness, −0.24 versus −0.22; and kurtosis, −0.36 versus −0.35. Tpeak-Tend interval, skewness, and kurtosis were independent of age, sex, and heart rate ( r 2 < 0.05), whereas Bazett-corrected QT-interval was more dependent ( r 2 = 0.40). Conclusion A selection of T-wave morphology variables is found to be clinically independent of age, sex, and heart rate, including Tpeak-Tend interval, skewness, and kurtosis.

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.

Sertindole causes distinct electrocardiographic T-wave morphology changes

Sertindole's propensity to prolong the QT interval relates to blockade of the KCNH2 (HERG) encoded Ikr potassium channel, but there has been limited detailed data on T-wave morphology changes. Digital 12-lead ECG was recorded at baseline and at steady-state in 37 patients switched to sertindole. ECG was analyzed for quantitative T-wave morphology changes and Fridericia-corrected QT duration (QTcF). Prominent T-wave morphology changes occurred during sertindole treatment and in some cases without concomitant prolongation of the QTcF interval. Four patients developed notched T-waves during sertindole treatment. Mean QTc prolongation was 19 ms. The mean effect size was higher for T-wave morphology combination score (MCS) (ES=1.92; 95% CI: 1.35-2.49) compared to the mean effect size for QTcF (ES=0.88; 95% CI: 0.52-1.24). The use of T-wave morphology analysis may become clinically relevant, particularly if shown to be associated with drug-induced arrhythmia risk.

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.

Analysis of T-wave morphology from the 12-lead electrocardiogram for prediction of long-term prognosis in patients initiating haemodialysis

Cardiovascular disease remains the most common cause of death in end-stage renal disease (ESRD). Recently, novel descriptors of T-wave morphology have been suggested as measures of repolarization heterogeneity and adverse prognosis in non-uraemic populations. However, whether these T-wave descriptors provide prognostic information in uraemic populations has not been examined. The present study aimed to determine the prognostic value of novel T-wave morphology variables in predicting total, cardiovascular and arrhythmia-related mortality in ESRD patients initiating haemodialysis. The study was a retrospective cohort of adult ESRD patients starting haemodialysis between 1998 and 2005; follow-up was until September 2006. A total of 325 patients were studied. Novel ECG variables characterizing repolarization and the T-wave loop were analysed. Of 325 patients with technically analysable data, 154 (47.4%) died after a mean follow-up of 25.5+/-21.7 months. Direct comparison between cardiovascular death and non-cardiovascular death patients showed that the relative T-wave residuum (TWR) predicted cardiovascular mortality (0.20+/-0.21% vs 0.24+/-0.17%, P=0.005). In Cox modeling, relative TWR was an independent predictor of cardiovascular [relative risk (RR)=1.86; P=0.013] and arrhythmia-related mortality (RR=2.102; P=0.012). The heterogeneity of myocardial repolarization, measured by the relative T-wave residuum in the ECG, appears to be an independent predictor of cardiovascular and arrhythmia-related mortality in patients initiating haemodialysis.

Analysis of QTc interval and T-wave morphology during early transmural ischemia in humans

Analysis of QTc interval and T-wave morphology during early transmural ischemia in humans

Classification of the long-QT syndrome based on discriminant analysis of T-wave morphology

The long QT syndrome (LQTS) is a genetic disorder, typically characterized by a prolonged QT interval in the ECG due to abnormal cardiac repolarization. LQTS may lead to syncopal episodes and sudden cardiac death. Various parameters based on T-wave morphology, as well as the QT interval itself have been shown to be useful discriminators, but no single ECG parameter has been sufficient to solve the diagnostic problem. In this study we present a method for discrimination among persons with a normal genotype and those with mutations in the KCNQ1 (KvLQT1 or LQT1) and KCNH2 (HERG or LQT2) genes on the basis of parameters describing T-wave morphology in terms of duration, asymmetry, flatness and amplitude. Discriminant analyses based on 4 or 5 parameters both resulted in perfect discrimination in a learning set of 36 subjects. In both cases cross-validation of the resulting classifiers showed no misclassifications either.

Characteristics of a New Repolarization Descriptor Substituted for T-Wave Morphology Analysis in Patients With Cardiomyopathy and Myocardial Infarction

Total cosine R-to-T (TCRT) is a descriptor of T-wave morphology analysis based on singular value decomposition of 12-lead electrocardiograms (ECGs), which is useful in risk stratification of patients with myocardial infarction (MI). A new marker of standard ECG substituted for TCRT is proposed and the aim of this study was to evaluate the correlation between the new index and TCRT in patients with cardiomyopathy and MI. Patients were divided into 2 groups: patients with cardiomyopathy (group CM, n=21, male =13), and patients with MI (group MI, n=36, male =28). TCRT was calculated using a custom software package. The ventricular gradient (VG)-index was defined as the total number of leads with opposite vectors for the QRS and T-wave. The value of TCRT was significantly lower in group CM than in group MI (-0.50+/-0.51 vs -0.04+/-0.65, p<0.01). The value for the VG-index was significantly greater in group CM than in group MI (5.9+/-3.4 vs 4.2+/-2.4, p<0.05). There was a significant correlation between TCRT and the VG-index in all of the patients (r(2)=0.47). The VG-index is significantly correlated with TCRT, and both descriptors distinguish patients with MI from those with cardiomyopathy.

Functional Significance of KCNH2 (HERG) K897T Polymorphism for Cardiac Repolarization Assessed by Analysis of T‐Wave Morphology

Although KCNH2 (HERG) K897T polymorphism has been shown to be associated with the QT interval measured from 12-lead electrocardiogram (ECG), the functional significance of K897T polymorphism has been debated. The aim of this study was to test whether the K897T polymorphism of the KCNH2 (HERG) gene coding for the rapidly activating delayed rectifier K+ channel influences cardiac repolarization assessed by principal component analysis (PCA) of T-wave morphology. Twelve-lead ECGs were digitized and T-wave morphology was analyzed with a PCA method in a population consisting of 228 healthy middle-aged subjects (121 women and 107 men). DNA samples were genotyped for the nucleotide 2690 A>C variation of the KCNH2 gene, corresponding to the KCNH2 K(lysine)897T(threonine) amino acid polymorphism. The allele frequencies were 0.86 (K) and 0.14 (T). The KCNH2 K897T polymorphism was associated with the total cosine R-to-T (TCRT), which reflects the wave front direction between depolarization and repolarization. TCRT was 0.421 in the genotype KK and 0.300 in the genotypes KT and TT (P = 0.04). The difference of TCRT was more marked between the KCNH2 K897T genotypes in women (P = 0.03) than in men (P = 0.52). The common K897T polymorphism of the cardiac potassium channel KCNH2 has functional significance for cardiac electrical properties. Subjects with a less common genotype, KT or TT, have smaller TCRT, which reflects dyssynchrony between depolarization and repolarization and is associated with an increased risk of cardiac mortality.

Clinical Implication of T-Wave Morphology Analysis as a New Repolarization Descriptor

T-wave morphology analysis (TMA) quantifies irregularities of ventricular repolarization based on singular value decomposition of the 12-lead electrocardiogram (ECG). Furthermore, TMA is useful for risk stratification of patients with myocardial infarction (MI), although gender differences in TMA and the relationship between TMA and heart diseases are unknown. The aim of this study was to evaluate the significance of TMA in healthy individuals and patients with heart diseases. Patients with heart disease and either with or without an implanted cardioverter defibrillator (ICD, n = 33, 57+/-16 years; non-ICD, n = 50, 67+/-10 years) were studied. Normal control ECGs (n = 114) were selected from Marquette's database (NC, 33+/-13 years) and the TMA descriptors, including T-wave morphology dispersion (TMD) and percentage of the loop area (PL), were calculated. TMD was significantly lower in group NC males than in the group NC females (11+/-5.9 vs 22+/-16, p < 0.0001). PL was significantly higher in group NC than in the ICD and non-ICD groups (0.63+/-0.12 vs 0.53+/-0.15, p < 0.0001). TMD of group NC was significantly lower than that of the ICD and non-ICD groups (14+/-11 vs 47+/-27, p < 0.0001). There are gender differences in TMD. Abnormal values for TMA could reflect abnormalities of ventricular repolarization.

P-071 Evaluation of the risk of ventricular tachyarrhythmia recurrence in patients with ischaemic heart disease by T-wave morphology analysis

P-071 Evaluation of the risk of ventricular tachyarrhythmia recurrence in patients with ischaemic heart disease by T-wave morphology analysis

P-071 Evaluation of the risk of ventricular tachyarrhythmia recurrence in patients with ischaemic heart disease by T-wave morphology analysis

P-071 Evaluation of the risk of ventricular tachyarrhythmia recurrence in patients with ischaemic heart disease by T-wave morphology analysis