PubMed Health⌕ Search

Biomedical subjects

Velislav Batchvarov

Publications and source records attributed to Velislav Batchvarov.

13 recordsLinked to original sources
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

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

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

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↗
PubMed2003

Circadian rhythm of the corrected QT interval: impact of different heart rate correction models.

A reduced circadian pattern in the QTc interval has been repeatedly reported to provide prognostic information in cardiac patients. However, the results of studies in healthy subjects in which different heart rate correction formulas were used are inconsistent regarding the presence and extent of diurnal variations in QTc. This study compared the diurnal variations in QTc obtained with four frequently used heart rate correction models with those based on individually optimized heart rate correction. In 53 subjects (25 men aged 27 +/- 7 years and 28 women aged 27 +/- 9 years) 12-lead digital ECGs were obtained every 30 seconds during 24 hours. The QT interval was measured automatically by six different algorithms provided by a commercially available device. The QT/RR relation was estimated by four common heart rate correction models and by an individually optimized correction model, QTc = QT/RR alpha. In each 24-hour recording, RR, QT, and WTc intervals of separate ECG samples were averaged over 10-minute intervals. Marked differences were found in the extent of the circadian pattern of QTc obtained with different formulas for heart rate correction. Under and overcorrection of the QT interval resulted in significant over- or underestimation of the circadian pattern. Thus, the extent of circadian variation in QTc depends highly on the heart rate correction formula used. To obtain proper insight regarding diurnal variation in QTc prolongation during pharmacologic therapy and/or to assess higher risk due to impaired autonomic regulation of ventricular repolarization, individualized heart rate correction is necessary.

Adolescent↗
PubMed2002

Comparison between ventricular gradient and a new descriptor of the wavefront direction of ventricular activation and recovery.

BACKGROUND: Total R T cosine (TCRT) is a new descriptor of repolarization heterogeneity that quantifies the deviation between the directions of ventricular depolarization and repolarization. It revives the old concept of ventricular gradient (VG). HYPOTHESIS: Our goal was to examine whether TCRT and VG contain nonredundant information by comparing their reaction to autonomic tests, namely, postural changes and Valsalva maneuver. METHODS: Digital 12-lead electrocardiograms were recorded in 16 patients with cardiovascular syndrome X (SX, chest pain, exercise-induced ST-depression, normal coronary arteries, 3 men, age 60 +/- 9 years) and 40 healthy volunteers (31 men, age 33 +/- 7 years) during postural changes and Valsalva maneuver. The angle (VGA) [degrees] and magnitude (VGM) [ms.mV] of VG in reconstructed XYZ leads and TCRT (average cosine of the angles between the QRS and T vectors in mathematically reconstructed three-dimensional space) were calculated. RESULTS: (mean +/- standard of the mean): In healthy subjects, VGM and TCRT decreased, whereas VGA increased in the sitting and standing compared with supine position (TCRT: 0.61 +/- 0.05,0.47 +/- 0.06,0.29 +/- 0.08, supine, sitting, and standing, p < 0.05) and during phase II Valsalva (TCRT: 0.47 +/- 0.06 vs. 0.61 +/- 0.05, p < 0.01 in supine, 0.24 +/- 0.08 vs. 0.37 +/- 0.07, p < 0.01 in standing). In patients with SX, VGM decreased in the standing position, VGA did not change significantly, while TCRT decreased only in patients without T-wave abnormalities (n = 9) (TCRT in standing and supine: 0.55 +/- 0.09 vs. 0.68 +/- 0.08, p < 0.05). VG(M) increased during Valsalva in patients with SX. Total R T cosine correlated strongly with VGA (r = -0.84, p < 0.00001) and, unlike VGM, did not correlate with heart rate. CONCLUSIONS: Ventricular gradient and TCRT contain nonredundant information. In healthy subjects, they react sensitively to autonomic provocation. In patients with SX, their reaction is attenuated, which suggests disturbance of the autonomic control of repolarization.

Adult↗
PubMed2002

Individual patterns of QT/RR relationship.

In clinical practice, an imprecision introduced by ad hoc selected heart rate correction formula of the QT interval is unlikely to lead to erroneous conclusions if all borderline cases are carefully considered. On the contrary, in clinical investigations (e.g., studies of drug effects) the over- or undercorrection of QTc may lead to significant and systematic bias with both false positive and false negative findings. None of the previously published "global" heart rate correction formulae has been universally successful because the QT/RR relationship is different between different subjects and a formula that corrects the QT interval for heart rate acceptably in one individual may be very misleading in another individual. Moreover, it has been recently established that the QT/RR patterns not only exhibit a substantial inter-subject variability but also a high intra-subject stability. Thus, in precise investigations, individual QT/RR relationship should be first established in each subject and subsequently translated into individual heart rate correction formula.

Adult↗
PubMed2002

Assessment of noise in digital electrocardiograms.

Technically related noise in 12-lead ECGs recorded with ambulatory recorders has never been systematically compared with that in ECGs recorded with conventional ECGs. This study compared serial 10-second ECGs obtained in ten healthy men, age 22-45 years, who were recorded in the supine resting position using a (1) MAC VU recorder, (2) digital ambulatory SEER MC recorder with a Multi-Link detachable ECG cable, and (3) digital ambulatory SEER MC recorder with a light ambulatory ECG cable. In each ECG, averaged sinus rhythm cycles of the entire recording were realigned with the native signal and subtracted. The resulting "residuum" was quantified by computing its standard deviation and root mean square of successive differences (RMSSD). While the RMSSD residuum values were significantly lower with the MAC VU recorder (6.27 +/- 0.98 microV) than with the SEER MC recorder with either ECG cables (7.29 +/- 1.31 and 7.17 +/- 1.31 microV, P < 0.003 and p < 0.02), the difference was practically negligible and there was no detectable difference in the standard deviation residuum values. The study concludes that valid ECG investigations of serial ECG testing may be conducted using the ambulatory SEER MC recorders providing the biological sources of ECG noise are controlled. The available technology for noise assessment suggests that studies involving advanced analysis of serial ECGs (e.g., of drug related changes), should incorporate objective characterisation of ECG quality.

Adult↗