Biomedical subjects

Katerina Hnatkova

Publications and source records attributed to Katerina Hnatkova.

At least 19 recordsLinked to original sources

PubMed2006

Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study.

BACKGROUND: Decreased vagal activity after myocardial infarction results in reduced heart-rate variability and increased risk of death. To distinguish between vagal and sympathetic factors that affect heart-rate variability, we used a signal-processing algorithm to separately characterise deceleration and acceleration of heart rate. We postulated that diminished deceleration-related modulation of heart rate is an important prognostic marker. Our prospective hypotheses were that deceleration capacity is a better predictor of risk than left-ventricular ejection fraction (LVEF) and standard deviation of normal-to-normal intervals (SDNN). METHODS: We quantified heart rate deceleration capacity by assessing 24-h Holter recordings from a post-infarction cohort in Munich (n=1455). We blindly validated the prognostic power of deceleration capacity in post-infarction populations in London, UK (n=656), and Oulu, Finland (n=600). We tested our hypotheses by assessment of the area under the receiver-operator characteristics curve (AUC). FINDINGS: During a median follow-up of 24 months, 70 people died in the Munich cohort and 66 in the London cohort. The Oulu cohort was followed-up for 38 months and 77 people died. In the London cohort, mean AUC of deceleration capacity was 0.80 (SD 0.03) compared with 0.67 (0.04) for LVEF and 0.69 (0.04) for SDNN. In the Oulu cohort, mean AUC of deceleration capacity was 0.74 (0.03) compared with 0.60 (0.04) for LVEF and 0.64 (0.03) for SDNN (p<0.0001 for all comparisons). Stratification by dichotomised deceleration capacity was especially powerful in patients with preserved LVEF (p<0.0001 in all cohorts). INTERPRETATION: Impaired heart rate deceleration capacity is a powerful predictor of mortality after myocardial infarction and is more accurate than LVEF and the conventional measures of heart-rate variability.

Aged↗

PubMed2006

Usefulness of T-wave loop and QRS complex loop to predict mortality after acute myocardial infarction.

The aim of the study was to assess whether parameters based on the T-wave loop and QRS loop predict mortality, and cardiac mortality in particular, during follow-up of consecutive survivors of acute myocardial infarction (AMI). Patients with AMI (n = 437), treated according to contemporary guidelines, underwent digital high-resolution electrocardiography in orthogonal Frank leads (X, Y, Z) 5 to 14 days after AMI. Several T-wave and QRS loop parameters, such as the width and height of the loops and their ratio, T-wave loop dispersion (TWLD), QRS loop dispersion, and co-sine of the angle between the main vectors of the T-wave and QRS loops (TCRT), were calculated using a custom-made software package. During an average follow-up period of 43 +/- 14 months, 53 patients (12%) died. Of these 53 deaths, 35 were cardiac. TWLD and TCRT were the T-wave loop/QRS loop parameters that best predicted for cardiac mortality on univariate comparison (35.4 +/- 5.62 vs 32.8 +/- 2.87 for TWLD, p < 0.001 and -0.135 +/- 0.665 vs -0.657 +/- 0.518 for TCRT, p < 0.001, alive vs cardiac death, respectively). After adjustment for clinical risk markers in the Cox regression analysis, TWLD still significantly predicted for cardiac mortality (p < 0.05); however, TCRT had lost its predictive power. TWLD did not have significant univariate or multivariate association with noncardiac mortality. In conclusion, TWLD that describes the shape of the T-wave loop is a specific predictor of cardiac death and independent of the clinical risk markers in the current treatment era of patients with AMI.

Aged↗

PubMed2006

HRV scaling exponent identifies postinfarction patients who might benefit from prophylactic treatment with amiodarone.

Analysing the Holter recordings collected at baseline during the European Myocardial Infarction Amiodarone Trial (EMIAT), we evaluate the possibility of using alpha, the slope of the power spectrum of heart rate variability signals (HRV) in the vicinity of f = 0, for postinfarction risk stratification. We found no relevant difference in the values of alpha for the placebo population. On the contrary, in the amiodarone arm, the distinction in the survival rates of those with high or low alpha-values was highly significant. Moreover, high risk patients with respect to alpha (higher values) did not seem to benefit from amiodarone. The results suggest that alpha might convey physiologic information that is different than what is expressed by other HRV characteristics, such as the triangular index. When combining high risk patients in term of triangular index (<20) and low risk patients with respect to alpha (<median), the difference in survival on placebo and amiodarone became very substantial (24.2% mortality on placebo, 8.7% on amiodarone, p = 0.017). This might offer a possibility of selecting patients likely to benefit from a prophylactic antiarrhythmic treatment after acute myocardial infarction.

Adolescent↗

PubMed2006

Precision of QT interval measurement by advanced electrocardiographic equipment.

The costs of clinical investigations of drug-induced QT interval prolongation are mainly related to manual processing of electrocardiographic (ECG) recordings. Potentially, however, these costs can be decreased by automatic ECG measurement. To investigate the improvements in measurement accuracy of the modern ECG equipment, this study investigated QT interval measurement by the "old" and "new" versions of the 12SL ECG algorithm by GE Healthcare (Milwaukee, WI, USA) and compared the results to carefully validated and reconciled manual measurements. The investigation used two sets (A and B) of ECG recordings that originated from large clinical studies. Sets A and B consisted of 15,194, and 29,866 10-second ECG recordings, respectively. All the recordings were obtained with GE Healthcare recorders and were available in digital format compatible with ECG processing software by GE Healthcare. The two sets of recordings differed significantly in ECG quality with set B being substantially more noise polluted. Compared to careful manual QT interval readings in recording set A, the errors of the automatic QT interval measurement were (mean +/- SD) +3.95 +/- 5.50 ms, and +0.51 +/- 12.41 ms for the "new" and "old" 12SL algorithm, respectively. In recording set B, these numbers were +2.41 +/- 9.47 ms, and -0.17 +/- 14.89 ms, respectively (both differences were highly statistically significant, P < 0.000001). In recording set A, 95.9% and 76.6% of ECGs were measured automatically within 10 ms of the manual measurement by the "new" and "old" versions of the 12SL algorithm, In recording set B, these numbers were 83.9% and 59.5%. The errors made by the "new" and "old" version of 12SL algorithm were practically independent each of the other (correlation coefficients of 0.031 and 0.281 in recording sets A and B, respectively). The study shows that (a) compared to the "old" version of the 12SL algorithm, the QT interval measurement by the "new" version implemented in the most recent ECG equipment by GE Healthcare is significantly better, and (b) the precision of automatic measurement by the 12SL algorithm is substantially dependent on the quality of processed ECG recordings. The improved accuracy of the "new" 12SL algorithm makes it feasible to use modern ECG equipment without any manual intervention in selected parts of drug-development program.

Algorithms↗

PubMed2006

Characteristics of a new repolarization descriptor substituted for T-wave morphology analysis in patients with cardiomyopathy and myocardial infarction.

BACKGROUND: 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. METHODS AND RESULTS: 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). CONCLUSION: The VG-index is significantly correlated with TCRT, and both descriptors distinguish patients with MI from those with cardiomyopathy.

Adult↗

PubMed2005

Repolarization abnormality for prediction of all-cause and cardiovascular mortality in American Indians: the Strong Heart Study.

BACKGROUND: Analysis of electrocardiographic (ECG) repolarization abnormality using QTc interval and principal component analysis (PCA) of the T-wave vector predict all-cause and cardiovascular (CV) mortality. Novel descriptors of T-wave morphology have been suggested as measures of repolarization heterogeneity and adverse prognosis. However, whether these T-wave descriptors provide prognostic information beyond QTc and the PCA ratio has not been examined. METHODS AND RESULTS: Predictive values of QTc, PCA, and novel ECG variables characterizing the T-wave loop were assessed in 1,729 American Indian participants in the first Strong Heart Study exam. T-loop morphology was quantified by the ratio of the second to first eigenvalues of the T-wave vector (PCA ratio), T-loop area (TLA) projected onto the dominant vector plane, T-wave morphology dispersion (TMD) and by the sum of the squares of the fourth to eighth eigenvalues, the T-wave residuum (TWR). After mean follow-up of 4.8 +/- 0.8 years, there were 183 deaths from all causes, including 51 CV deaths. In univariate Cox analyses, prolonged QTc, increased PCA ratio, TLA, TMD, and TWR were significant predictors of all-cause and CV mortality (P < 0.001). In multivariate Cox analyses adjusting for demographic and clinical risk factors for mortality, increased PCA ratio (chi-square = 7.9, P = 0.005) and TWR (chi-square = 5.3, P = 0.022) remained significant predictors of CV mortality and increased QTc (chi-square = 12.1, P < 0.001) and TWR (chi-square = 6.0, P = 0.014) of all-cause mortality. Addition of TWR to the model with clinical variables and the PCA ratio for CV mortality and to the model with clinical variables and prolonged QTc for all-cause mortality increased prognostic value of each model (increase in overall chi-square from 287.5 to 301.9 and from 221.5 to 230.3, respectively). CONCLUSION: Novel descriptors of T-wave complexity provide additional prognostic information beyond QTc and PCA ratio for prediction of all-cause and CV mortality.

Arrhythmias, Cardiac↗

PubMed2005

Clinical implication of T-wave morphology analysis as a new repolarization descriptor.

BACKGROUND: 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. METHODS AND RESULTS: 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). CONCLUSION: There are gender differences in TMD. Abnormal values for TMA could reflect abnormalities of ventricular repolarization.

Aged↗

PubMed2004

Mental stress and sudden cardiac death: asymmetric midbrain activity as a linking mechanism.

Patients with specific neurological, psychiatric or cardiovascular conditions are at enhanced risk of cardiac arrhythmia and sudden death. The neurogenic mechanisms are poorly understood. However, in many cases, stress may precipitate cardiac arrhythmia and sudden death in vulnerable patients, presumably via centrally driven autonomic nervous system responses. From a cardiological perspective, the likelihood of arrhythmia is strongly associated with abnormalities in electrical repolarization (recovery) of the heart muscle after each contraction. Inhomogeneous and asymmetric repolarization, reflected in ECG T-wave abnormalities, is associated with a greatly increased risk of arrhythmia, i.e. a proarrhythmic state. We therefore undertook a study to identify the brain mechanisms by which stress can induce cardiac arrhythmia through efferent autonomic drive. We recruited a typical group of 10 out-patients attending a cardiological clinic. We simultaneously measured brain activity, using H2(15)O PET, and the proarrhythmic state of the heart, using ECG, during mental and physical stress challenges and corresponding control conditions. Proarrhythmic changes in the heart were quantified from two ECG-derived measures of repolarization inhomogeneity and were related to changes in magnitude and lateralization of regional brain activity reflected in regional cerebral blood flow. Across the patient group, we observed a robust positive relationship between right-lateralized asymmetry in midbrain activity and proarrhythmic abnormalities of cardiac repolarization (apparent in two independent ECG measures) during stress. This association between stress-induced lateralization of midbrain activity and enhanced arrhythmic vulnerability provides empirical support for a putative mechanism for stress-induced sudden death, wherein lateralization of central autonomic drive during stress results in imbalanced activity in right and left cardiac sympathetic nerves. A right-left asymmetry in sympathetic drive across the surface of the heart disrupts the electrophysiological homogeneity of ventricular repolarization, predisposing to arrhythmia. Our findings highlight a proximal brain basis for stress-induced cardiac arrhythmic vulnerability.

Aged↗

PubMed2004

Prognostic value of heterogeneity of ventricular repolarization in survivors of acute myocardial infarction.

BACKGROUND: The expansion of indications for implantation of cardioverter-defibrillators (ICD) has enhanced the need for risk stratification of patients post myocardial infarction (MI), while the improved treatment of acute MI has decreased mortality and diminished the prognostic power of traditional risk variables. HYPOTHESIS: Increased heterogeneity of ventricular repolarization quantified by TCRT (total cosine R-to-T, angular difference between spatial QRS and T loops, decreased with increase in repolarization heterogeneity) is an independent predictor of mortality in patients post MI. METHODS: Left ventricular ejection fraction (EF), QRS duration on signal-averaged ECG, number of ventricular ectopic beats (VE)/h, heart rate variability (HRV) triangular index, heart rate turbulence slope on 24-h Holter recording, and TCRT were analyzed in 334 survivors of acute MI followed up for 41 +/- 20 months. RESULTS: In multivariate analysis, EF < 35% (relative risk [RR] 2.3, 95% confidence interval [CI] 1.1-4.7, p = 0.023), VE > 10/h (RR 2.2, CI 1.0-4.6, p = 0.044), HRV < 20 U (RR 2.2, CI 1.1-4.5, p = 0.032), and TCRT < -0.896 (RR 4.3, CI 2.2-8.5, p = 0.00001) were independent predictors of cardiac mortality (11%). Independent predictors of arrhythmic mortality (5%) were VE, HRV, and TCRT (RR 5.8, CI 2.1-15.6, p = 0.0004). Cardiac and arrhythmic mortality of patients with both EF <35% and TCRT < -0.896 were >60 and >30%, respectively, compared with 17 and 7% in those with only EF <35% or TCRT < -0.896. CONCLUSION: Decreased TCRT, which reflects increased repolarization heterogeneity, is a strong and independent predictor of cardiac and arrhythmic death in patients post MI.

Action Potentials↗

PubMed2004

Post infarction risk stratification using the 3-D angle between QRS complex and T-wave vectors.

Present experience with prospective identification of patients who might benefit from prophylactic antiarrhythmic intervention is restricted to risk stratification using left ventricular ejection fraction (LVEF). The precision of LVEF-based identification of high risk patients is neither highly sensitive nor highly specific. This study investigated risk stratification of 466 survivors of acute myocardial infarction (86 women, mean age 57.5 years) for whom a 5-year follow-up was available. During the follow-up 67 patients died and 24 of these events were sudden arrhythmic deaths. In addition to LVEF, patients were stratified by mean heart rate, heart rate variability and the slope of heart rate turbulence, all derived from 24-hour Holter recording obtained before hospital discharge, and by the 3D angle between QRS complex and T wave vectors (total cosine R-to-T, TCRT) obtained from digital resting electrocardiogram before hospital discharge. Individual risk characteristics and their combinations were evaluated by calculating the areas under the receiver operator characteristics (ROC). The bootstrap technology was used to investigate these statistically. For the stratification of both all cause mortality and sudden arrhythmic death, TCRT was the strongest risk stratifier (area under ROC of 0.6857 +/- 0.0367, and 0.7275 +/- 0.0544, respectively) that compared very favourably to LVEF (area under the ROC of 0.6610 +/- 0.0362 and 0.6346 +/- 0.0595, for all cause and arrhythmic death prediction, both P < 10(-10) for the comparison with TCRT). TCRT was also stronger in combination with other stratifiers, eg, TCRT + LVEF (area under ROC of 0.7631 +/- 0.0325 and 0.8057 +/- 0.0473, for all cause and arrhythmic death prediction) was stronger than mean heart rate + LVEF (area under ROC of 0.7396 +/- 0.0298 and 0.7673 +/- 0.0445, respectively, both P < 10(-10) for comparison with TCRT + LVEF). Hence the 3D QRS-T angle is a very powerful risk stratifier especially suited for the prediction of sudden arrhythmic death. It should be prospectively investigated in future trials of prophylactic antiarrhythmic interventions.

Adult↗

PubMed2004

Individual patterns of dynamic QT/RR relationship in survivors of acute myocardial infarction and their relationship to antiarrhythmic efficacy of amiodarone.

INTRODUCTION: Amiodarone is an effective antiarrhythmic drug, but it has serious side effects and conducted trials did not support its prophylactic use in survivors of acute myocardial infarction. It is possible that the prophylactic use of the drug has not been tested effectively. To optimize therapy outcome, markers of drug efficacy might be developed to identify patients who, although at arrhythmic risk, would not benefit from amiodarone treatment. We investigated descriptors of QT/RR relationship for their potential value in predicting inefficient amiodarone treatment. METHODS AND RESULTS: The study used 866 Holter recordings (462 amiodarone, 404 placebo) obtained 1 month after randomization in the European Myocardial Infarct Amiodarone Trial (EMIAT). A commercial Holter system was used to measure RR and QT intervals. Subject-specific descriptors of QT/RR relationship were calculated. Comparison was performed in amiodarone- and placebo-treated patients, distinguishing patients who did and did not suffer from arrhythmic death. QT/RR relationship and individually corrected QTc interval differed significantly, not only between amiodarone- and placebo-treated postmyocardial infarction patients but also between patients with and without arrhythmic death on amiodarone (QTc with vs without arrhythmic death 426.30 +/- 33.93 ms vs 444.23 +/- 36.65 ms, P = 6.5 x 10(-3)). In a multivariate analysis, reduced optimum regression residuum (14.33 +/- 7.08 vs 20.11 +/- 9.39, P = 4.4 x 10(-3)) and flatter slope (0.44 +/- 0.19 vs 0.55 +/- 0.24, P = 4.0 x 10(-2)) of the QT/RR relationship independently predicted arrhythmic death during follow-up. CONCLUSION: Chronic amiodarone treatment markedly affects the QT/RR relationship. The lack of treatment-related QT/RR changes predicts arrhythmic death. Descriptors of complexity of QT/RR relation seem to be potent markers of treatment efficiency.

Adolescent↗

PubMed2004

Preoperative electrocardiographic risk assessment of atrial fibrillation after coronary artery bypass grafting.

INTRODUCTION: This study evaluated the role of surface ECG in assessment of risk of new-onset atrial fibrillation (AF) after coronary artery bypass grafting surgery (CABG). METHODS AND RESULTS: One hundred fifty-one patients (126 men and 25 women; age 65 +/- 10 years) without a history of AF undergoing primary elective and isolated CABG were studied. Standard 12-lead ECGs and P wave signal-averaged ECG (PSAE) were recorded 24 hours before CABG using a MAC VU ECG recorder. In addition to routine ECG measurements, two P wave (P wave complexity ratio [pCR]; P wave morphology dispersion [PMD]) and six T wave morphology descriptors (total cosine R to T [TCRT]; T wave morphology dispersion of ascending and descending part of the T wave [aTMD and dTMD], and others), and three PSAE indices (filtered P wave duration [PD]; root mean square voltage of terminal 20 msec of averaged P wave [RMS20]; and integral of P wave [Pi]) were investigated. During a mean hospital stay of 7.3 +/- 6.2 days after CABG, 40 (26%) patients developed AF (AF group) and 111 remained AF-free (no AF group). AF patients were older (69 +/- 9 years vs 64 +/- 10 years, P = 0.005). PD (135 +/- 9 msec vs 133 +/- 12 msec, P = NS) and RMS20 (4.5 +/- 1.7 microV vs 4.0 +/- 1.6 microV, P = NS) in AF were similar to that in no AF, whereas Pi was significantly increased in AF (757 +/- 230 microVmsec vs 659 +/- 206 microVmsec, P = 0.007). Both pCR (32 +/- 11 vs 27 +/- 10) and PMD (31.5 +/- 14.0 vs 26.4 +/- 12.3) were significantly greater in AF (P = 0.012 and 0.048, respectively). TCRT (0.028 +/- 0.596 vs 0.310 +/- 0.542, P = 0.009) and dTMD (0.63 +/- 0.03 vs 0.64 +/- 0.02, P = 0.004) were significantly reduced in AF compared with no AF. Measurements of aTMD and three other T wave descriptors were similar in AF and no AF. Significant variables by univariate analysis, including advanced age (P = 0.014), impaired left ventricular function (P = 0.02), greater Pi (P = 0.012), and lower TCRT (P = 0.007) or dTMD, were entered into multiple logistic regression models. Increased Pi (P = 0.038), reduced TCRT (P = 0.040), and lower dTMD (P = 0.014) predicted AF after CABG independently. In patients <70 years, a linear combination of increased pCR and lower TCRT separated AF and no AF with a sensitivity of 74% and specificity of 62% (P = 0.005). CONCLUSION: ECG assessment identifies patients vulnerable to AF after CABG. Combination of ECG parameters assessed preoperatively may play an important role in predicting new-onset AF after CABG.

Adult↗

PubMed2004

Differences between study-specific and subject-specific heart rate corrections of the QT interval in investigations of drug induced QTc prolongation.

A computational study was designed to investigate the differences between the so-called study-specific and subject-specific heart rate corrections of QT interval. In 53 healthy subjects (25 women, mean age 26.7 +/- 8.7 years), serial 10-second electrocardiograms (ECG) were obtained during daytime hours. In each subject, 200 ECGs were selected representative of the individual QT/RR relationship. Of the population of 53 subjects, 30,000 different subgroups of 16 subjects were considered and their data used to model drug induced QT interval prolongation by 0, 5, 10, and 20 ms combined with drug induced heart rate acceleration and deceleration. In each modeled study, QTc changes were assessed by: (1) Six study-specific heart rate corrections designed by regression modeling of the baseline QT/RR data pooled from all subjects; (2) Six subject-specific heart rate corrections designed by the same regression modeling of the baseline QT/RR data in each subject separately; (3) subject optimized correction that selected the best fitting regression model for each individual; and (4) by Bazett and Fridericia corrections. In each modeled study, the errors of the correction approaches were estimated and statistically summarized over all modeled studies. The subject-specific corrections led to maximum errors in single milliseconds (error range of 2.4, 5.7, and 2.6 ms with linear, log/log linear, and exponential models, respectively) while the study-specific corrections led to substantially greater errors (error range of 17.8, 19.4, and 16.9 ms with linear, log/log linear, and exponential models, respectively). Both Bazett and Fridericia corrections led not only to substantial errors (error range of 28.3 and 16.9 ms) but also to regular bias with systematically false negative and false positive conclusions dependent on modeled heart rate acceleration and deceleration. Thus, subjects-specific corrections should be used in the intensive and definite studies aimed at providing the final answer on the ability of a drug to prolong the QT interval.

Adolescent↗

PubMed2004

Sample size, power calculations, and their implications for the cost of thorough studies of drug induced QT interval prolongation.

Regulatory authorities require new drugs to be investigated using a so-called "thorough QT/QTc study" to identify compounds with a potential of influencing cardiac repolarization in man. Presently drafted regulatory consensus requires these studies to be powered for the statistical detection of QTc interval changes as small as 5 ms. Since this translates into a noticeable drug development burden, strategies need to be identified allowing the size and thus the cost of thorough QT/QTc studies to be minimized. This study investigated the influence of QT and RR interval data quality and the precision of heart rate correction on the sample sizes of thorough QT/QTc studies. In 57 healthy subjects (26 women, age range 19-42 years), a total of 4,195 drug-free digital electrocardiograms (ECG) were obtained (65-84 ECGs per subject). All ECG parameters were measured manually using the most accurate approach with reconciliation of measurement differences between different cardiologists and aligning the measurements of corresponding ECG patterns. From the data derived in this measurement process, seven different levels of QT/RR data quality were obtained, ranging from the simplest approach of measuring 3 beats in one ECG lead to the most exact approach. Each of these QT/RR data-sets was processed with eight different heart rate corrections ranging from Bazett and Fridericia corrections to the individual QT/RR regression modelling with optimization of QT/RR curvature. For each combination of data quality and heart rate correction, standard deviation of individual mean QTc values and mean of individual standard deviations of QTc values were calculated and used to derive the size of thorough QT/QTc studies with an 80% power to detect 5 ms QTc changes at the significance level of 0.05. Irrespective of data quality and heart rate corrections, the necessary sample sizes of studies based on between-subject comparisons (e.g., parallel studies) are very substantial requiring >140 subjects per group. However, the required study size may be substantially reduced in investigations based on within-subject comparisons (e.g., crossover studies or studies of several parallel groups each crossing over an active treatment with placebo). While simple measurement approaches with ad-hoc heart rate correction still lead to requirements of >150 subjects, the combination of best data quality with most accurate individualized heart rate correction decreases the variability of QTc measurements in each individual very substantially. In the data of this study, the average of standard deviations of QTc values calculated separately in each individual was only 5.2 ms. Such a variability in QTc data translates to only 18 subjects per study group (e.g., the size of a complete one-group crossover study) to detect 5 ms QTc change with an 80% power. Cost calculations show that by involving the most stringent ECG handling and measurement, the cost of a thorough QT/QTc study may be reduced to approximately 25%-30% of the cost imposed by the simple ECG reading (e.g., three complexes in one lead only).

Adult↗

PubMed2003

Effect of amiodarone on the descending limb of the T wave.

Comparing patients treated after myocardial infarction with amiodarone or with placebo, we found a significant rate-dependent prolongation of TpTe interval in patients who received amiodarone. Patients who had arrhythmic death had significantly longer TpTe intervals than others on placebo but not on amiodarone. Assuming that TpTe reflects transmural repolarization heterogeneity, our findings suggest that heterogeneity and arrhythmic risk are increased by amiodarone. This contradicts the finding of decreased transmural repolarization heterogeneity by amiodarone and the appreciated antiarrhythmic efficacy of this drug.

Adolescent↗

PubMed2003

Ventricular gradient and nondipolar repolarization components increase at higher heart rate.

Differences in action potential duration reflect differences in ion channel properties. These properties also determine rate dependence of action potential duration, and transmural dispersion was confirmed experimentally to increase with cycle length. While several electrocardiographic indexes characterizing repolarization abnormalities have been proposed, studies of their heart rate dependence are missing. This study therefore investigated rate relationship of two repolarization descriptors, namely, the so-called total cosine of the QRS-T angle (TCRT), proposed to characterize global repolarization heterogeneity, and the so-called relative T wave residuum (TWR), linked to regional repolarization dispersion. During 24-h holter recordings in 60 healthy subjects (27 males), a 12-lead ECG was obtained every 30 s. RR intervals, QT intervals, and TCRT and TWR were calculated in each ECG and averaged over RR interval bins ranging from 550 to 1,150 ms in 10-ms steps. Women had uniformly greater TCRT and TWR values than men did over the entire range of investigated RR intervals. Whereas the TCRT in both sexes showed marked rate dependence with higher values at long RR intervals (550 vs. 1,150 ms: women, 0.46 +/- 0.31 vs. 0.76 +/- 0.18, P = 9 x 10(-7); men, 0.08 +/- 0.45 vs. 0.49 +/- 0.35, P = 9 x 10(-8)), the rate dependence of TWR was more marked in women than in men, showing higher values at shorter RR intervals (550 ms vs. 1,150 ms: women: 0.29 +/- 0.14% vs. 0.08 +/- 0.06%, P = 2 x 10(-8); men: 0.14 +/- 0.12% vs. 0.04 +/- 0.02%, P = 2 x 10(-15)). This suggests that both global and regional repolarization heterogeneity are increased at faster heart rates. Whereas in women at all heart rates the sequence of repolarization more closely replicates the sequence of depolarization, localized repolarization is more heterogeneous than in men especially at fast heart rates.

Adult↗

PubMed2003

Sex differences in the rate dependence of the T wave descending limb.

OBJECTIVE: The interval from the peak to the end of the T wave (TpTe) has been proposed to reflect the heterogeneity of action potential durations within the ventricular wall. Several studies have previously described TpTe to be independent of heart rate, which contradicts the in vitro observation of marked changes in transmural repolarisation heterogeneity due to cycle length changes. Because of this inconsistency, we investigated heart rate related changes of TpTe interval. METHODS: During 24-h recordings (SEER MC, Marquette GE) in healthy young women (n=25, 26+/-7 years) and men (n=25, 27+/-8 years), a 10-s 12-lead ECG was obtained every 30 s. Recordings were repeated after 1 day, 1 week, and 1 month and results in each subject were pooled together and grouped for women and men. The QT and QT(peak) intervals were obtained automatically using QT Guard software (Marquette) and TpTe was computed as the difference between QT and QT(peak). In each subject TpTe values were averaged over 10-ms RR interval bands from 550 to 1150 ms. RESULTS: In both sexes, TpTe interval showed marked rate dependence with prolongation at long RR intervals. TpTe intervals in men were significantly longer over the entire range of investigated RR intervals (P=1.4x10(-25)). However, whereas the difference between sexes was marked at short cycle length (RR interval bin 540-550 ms: women 87+/-5 vs. men 95+/-9, P=5.1x10(-4)) it decreased at long cycle lengths (RR interval bin 1140-1150 ms: women 99+/-5 vs. men 106+/-6, P=9.3x10(-4)). CONCLUSION: There is a marked rate dependence of TpTe interval, which differs between women and men. The finding is consistent with the TpTe interval being an approximate surrogate of the intraventricular repolarisation gradient. The rate dependent increase in transmural repolarisation heterogeneity might be one of the reasons for the increased propensity of torsades de pointes in women.

Adult↗

PubMed2003

Ventricular gradient as a risk factor in survivors of acute myocardial infarction.

The total cosine between R and T (TCRT) (angular difference between the spatial QRS and T wave loops) is a technical elaboration of the concept of ventricular gradient (VG), whose power as a risk stratifier in post-MI patients has already been demonstrated. Recently, it was reported that TCRT differed significantly between healthy men and women, which suggested that its predictive power might be gender dependent. The aim of the study was to investigate TCRT and its association with cardiac mortality in male and female survivors of acute MI. TCRT was measured from digital Frank orthogonal XYZ-lead ECGs recorded before hospital discharge in 681 survivors of acute MI (82% men, age: men 57.0 +/- 8.4 years, women 59.6 +/- 8.1 years, P = 0.002). During a follow-up censored at 5 years, cardiac mortality rates were 9.7% and 12.1% in men and women, respectively (P = 0.42). There were no significant difference in TCRT between men and women (-0.150 +/- 0.704 vs -0.070 +/- 0.731, P = 0.26). In univariate Cox regression analysis, TCRT < -0.88 was related to a 5-year cardiac mortality in men (relative risk [RR] 3.67, 95% confidence interval [CI] 2.13-6.34, P = 1.9 x 10(-6)), and women (RR 5.16, 95% CI 1.83-14.56, P = 0.0015). Depressed TCRT was strongly associated with increased long-term cardiac mortality in survivors of acute MI. Its predictive power did not differ significantly between the sexes. The role of TCRT as a risk-stratifier in post-MI patients deserves further prospective assessment in multivariate models with established risk factors.

Electrocardiography↗