Velislav Batchvarov | St George's, University of London (original) (raw)

Papers by Velislav Batchvarov

Research paper thumbnail of Computed quadripolar electrocardiographic leads for prediction of ventricular tachycardia

We present an excerpt from a continuous 15-lead electrocardiogram (standard 12 leads without lead... more We present an excerpt from a continuous 15-lead electrocardiogram (standard 12 leads without lead V 3 plus leads V 1 and V 2 from the third and the second intercostal space, 12.5 mm/s, 1 mV/cm) acquired during a negative diagnostic ajmaline test for the Brugada syndrome in a 43-year-old man with congenital long QT syndrome carrying the SCN5A-E1784K mutation. Fifteen seconds after the end of ajmaline administration (1 mg/kg for 5 minutes) and following marked QRS prolongation from 103 ms at baseline to 170 ms, the patient developed ventricular bigeminy with right bundle branch block morphology (likely originating from the left ventricle; and , top panel), which 1 minute and 30 seconds later degenerated into sustained polymorphic ventricular tachycardia (VT; , bottom panel).

Research paper thumbnail of Clinical utility of computed electrocardiographic leads

The standard 12-lead electrocardiogram (ECG) is only one of the possible ways to present the volt... more The standard 12-lead electrocardiogram (ECG) is only one of the possible ways to present the voltage differences between the nine recording electrodes. Other "non-conventional" leads may be constructed by physically connecting two or more electrodes in a different manner or by computation from the digital 12-lead ECG. Examples include bipolar or multipolar precordial leads and bipolar chest leads (between one precordial and one limb electrode). Such leads can remove or decrease noise originating from a limb cable/electrode that is present in the unipolar precordial leads. They can be diagnostically useful in Brugada syndrome and can display QRS fractionation that is not visible in the respective unipolar precordial or limb leads. Multipolar precordial leads sometimes display potentially useful information that is not visible in the respective unipolar leads and in bipolar leads computed from them. In conclusion, these computed ECG leads represent a potentially useful supplement to the conventional 12-lead ECG.

Research paper thumbnail of Prognostic value of corrected QT-interval prolongation in patients with unstable angina pectoris

American Journal of Cardiology, 2003

Research paper thumbnail of Inhibition of Atrial Electrical Activity by Ventricular Pacing Mediated by Vagal Stimulation

Pace-pacing and Clinical Electrophysiology, 1995

In the absence of retrograde (VA) conduction, ventricular pacing does not exert any appreciable e... more In the absence of retrograde (VA) conduction, ventricular pacing does not exert any appreciable effect upon atrial electrical activity. We report three patients (2 with complete AV block and 1 with preserved AV conduction) in which, during EP study, no VA conduction was present and, in spite of that, excessive suppression (for more than 15 secs in the first patient) of sinus (atrial) electrical activity during RV pacing was observed. The sinus node suppression was reproducible in two patients. In all patients the suppression phenomenon was not observed after intravenous administration of atropine, which suggests that it was mediated by enhanced vagal tone.

Research paper thumbnail of The Morphology of the Electrocardiogram

Research paper thumbnail of Comparison between ventricular gradient and a new descriptor of the wavefront direction of ventricular activation and recovery

Clinical Cardiology, 2002

Background: Total R T cosine (TCRT) is a new descriptor of repolarization heterogeneity that quan... more 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) [°] 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). VGM 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 non-redundant 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.

Research paper thumbnail of Precision of QT Interval Measurement by Advanced Electrocardiographic Equipment

Pace-pacing and Clinical Electrophysiology, 2006

The costs of clinical investigations of drug-induced QT interval prolongation are mainly related ... more 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.

Research paper thumbnail of Assessment of Noise in Digital Electrocardiograms

Pace-pacing and Clinical Electrophysiology, 2002

Technically related noise in 12-lead ECGs recorded with ambulatory recorders has never been syste... more 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 &amp;amp;amp;amp;amp;amp;amp;amp;quot;residuum&amp;amp;amp;amp;amp;amp;amp;amp;quot; 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 &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.003 and p &amp;amp;amp;amp;amp;amp;amp;amp;lt; 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.

Research paper thumbnail of Individual Patterns of QT/RR Relationship

Cardiac Electrophysiology Review, 2002

In clinical practice, an imprecision introduced by ad hoc selected heart rate correction formula ... more In clinical practice, an imprecision introduced by ad hoc selected heart rate correction formula of the QTinterval is unlikely to lead to erroneous conclusions if all borderline cases are carefully considered. On thecontrary, in clinical investigations (e.g., studies of drug effects) the over- or undercorrection of QTcmay 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 universallysuccessful because the QT/RR relationship is different between different subjects and a formula that correctsthe 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 substantialinter-subject variability but also a high intra-subject stability. Thus, in precise investigations, individualQT/RR relationship should be first established in each subject and subsequently translated into individualheart rate correction formula.

Research paper thumbnail of Comparison of Different Methods for Manual P Wave Duration Measurement in 12Lead Electrocardiograms

Pace-pacing and Clinical Electrophysiology, 1999

To determine whether different methods for the manual measurement of P wave duration are mutually... more To determine whether different methods for the manual measurement of P wave duration are mutually consistent, we evaluated the intraobserver and interobserver errors of P wave measurements obtained in three different ways: (1) by cursor on a high resolution computer screen (on screen), (2) by calipers and a magnifying glass (on paper), and (3) by a high resolution digitizing board (on board). The agreement between the methods was assessed in 30 normal subjects and 30 patients with a history of atrial fibrillation. The maximum P wave duration (P maximum), the minimum P wave duration (P minimum), mean P wave duration (P mean), P wave dispersion (P dispersion = P maximum - P minimum), and the standard deviation of the P wave duration in all measured leads (P SD) were calculated from a 12-lead electrocardiogram in each subject. Only P maximum, P mean, and P dispersion were significantly higher in patients than in controls with all three methods. Intraobserver and interobserver relative errors were significantly different among the three methods; the lowest errors were associated with the on-screen measurement. The agreement between the three different methods was acceptable for P maximum, P mean, and P SD and rather poor for P minimum and P dispersion in both groups. The differences of the measurement by different methods did not consistently differ between the two groups. Hence, the on-screen measurements are consistent with other manual methods and provide more stable results. Manual measurement of ECG patterns should be preferably performed with digital ECG recordings displayed on a high resolution computer screen.

Research paper thumbnail of Mental stress and sudden cardiac death: asymmetric midbrain activity as a linking mechanism

Patients with specific neurological, psychiatric or cardiovascular conditions are at enhanced ris... more 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 H 2 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 rightlateralized 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.

Research paper thumbnail of Brugada-Like Changes in the Peripheral Leads during Diagnostic Ajmaline Test in Patients with Suspected Brugada Syndrome

Pace-pacing and Clinical Electrophysiology, 2009

Background: Although cases of Brugada-type electrocardiographic (ECG) pattern in peripheral (limb... more Background: Although cases of Brugada-type electrocardiographic (ECG) pattern in peripheral (limb) leads have been reported (“atypical” Brugada syndrome [BS]), their incidence in patients investigated for BS is unknown.Methods: We retrospectively analyzed an ECG database collected during ajmaline test in 143 patients (89 men) with suspected BS. In 42 patients, 12-lead ECGs were recorded, whereas in 101 patients, leads V1–V3 from the third intercostal space were also recorded. The presence of types 1, 2, and 3 Brugada pattern in each limb and precordial lead was noted and the PR, QRS, and QTc intervals were calculated.Results: There were 114 (79.7%) negative and 29 (20.3%) positive tests. Type 1 pattern developed in ≥1 limb lead in six patients (4.2%) (3/29 with positive tests, 10.3%); all of them were male, symptomatic, and/or with family history of BS or sudden cardiac death. Their pre- and posttest QRS were significantly longer compared with the rest with positive (n = 26) or negative (n = 111) test (pretest: 129 ± 31 ms vs 101 ± 11 ms and 97 ± 12 ms, P < 0.001; posttest: 175 ± 44 ms vs 134 ± 14 ms and 131 ± 19 ms, P < 0.001). The posttest QTc was longer in patients with peripheral changes compared with the rest (507 ± 47 ms vs 453 ± 22 ms and 447 ± 24 ms, P < 0.001). The pretest QTc and pre- and posttest heart rate and PR intervals were not significantly different between the three groups.Conclusions: Type 1 Brugada pattern in the peripheral leads was observed in 4.2% of patients during ajmaline test (10.3% of positive tests) and was associated with longer QRS and greater QTc prolongation compared with the rest of the patients.

Research paper thumbnail of Sample Size, Power Calculations, and Their Implications for the Cost of Thorough Studies of Drug Induced QT Interval Prolongation

Pace-pacing and Clinical Electrophysiology, 2004

Regulatory authorities require new drugs to be investigated using a so-called &amp;amp;amp;am... more Regulatory authorities require new drugs to be investigated using a so-called &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;thorough QT/QTc study&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;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).

Research paper thumbnail of The heart vector, the regional information in the electrocardiogram, and QT dispersion

American Journal of Cardiology, 2002

Research paper thumbnail of Increased QT dispersion in patients with Prinzmetal's variant angina and cardiac arrest

We sought to compare QT dispersion in patients presenting with Prinzmetal's variant angina compli... more We sought to compare QT dispersion in patients presenting with Prinzmetal's variant angina complicated by cardiac arrest or syncope and patients with uncomplicated variant angina. Background: Despite the usually benign course of treated Prinzmetal's variant angina, a proportion of vasospastic angina patients develop ventricular arrhythmias and sudden death in association with coronary spasm. Increased QT dispersion has been suggested to increase susceptibility to ventricular arrhythmias in patients with coronary artery spasm. Methods: We studied 25 consecutive patients (mean age 58 years; 14 men) with classical Prinzmetal's variant angina and documented coronary artery spasm. None of the patients had coronary artery stenoses #40%. Five patients had suffered a documented cardiac arrest, two had recurrent syncope and 18 had no arrhythmic events or syncopal episodes. In all patients QT dispersion (QT maximum2QT minimum in every ECG lead) was measured on the baseline 12-lead electrocardiogram at study entry using a digitising board. Results: Mean (6S.D.) QT dispersion of study patients was 62.3619.5 ms. QT dispersion in patients with cardiac arrest and syncope (79.4617.3 ms) was significantly higher compared to patients with no such events (56.3616.9 ms), (95% CI 7.5-38.8, P50.005). No significant clinical, biochemical or angiographic differences were found between patients with and those without cardiac arrest or syncope. Conclusion: QT dispersion is increased in patients with Prinzmetal's variant angina complicated by cardiac arrest and syncope compared to patients without such events. Increased QT dispersion may be both a substrate for sudden cardiac death and a marker of risk in patients with Prinzmetal's variant angina.

Research paper thumbnail of QT Interval and QT Dispersion Measured with the Threshold Method Depend on Threshold Level

Pace-pacing and Clinical Electrophysiology, 1998

Various computerized methods with multiple parameter options for measurements of the QT interval ... more Various computerized methods with multiple parameter options for measurements of the QT interval now are available. The optimum parameter setting for most algorithms is not known. This study evaluated the influence of the threshold level applied on the T wave differential on the QT interval and its dispersion measured in normal and abnormal electrocardiograms (ECGs). Seven hundred sixty ECGs recorded in 76 normal subjects and 630 in 63 patients with hypertrophic cardiomyopathy (HCM) (10 consecutive recordings in each individual) were analyzed. In each lead of each ECG, the QT interval was measured by the threshold method applied to the first differential of the T wave. The threshold level was varied between 5% and 30% of the T wave maximum in 1% steps, resulting in 26 different choices of QT measurements. With each choice the maximum QTc and the QT dispersion (QTd, standard deviation of the QT in all 12 leads) were obtained for each recording. The maximum QTc was significantly longer in HCM patients than in normal subjects (P < 0.001) at all threshold levels except between 5% and 7%. The QTd was significantly greater in HCM patients at all threshold levels. The QTc and QTd changed significantly with the threshold level. The maximum QTc varied up to 60 ms in normal subjects and up to 70 ms in HCM patients, depending on the threshold level. Thus, the QT intervai and its dispersion measured with the threshold method applied to the first T wave differential depended significantly on the threshold level in both normal and diseased hearts. All programmable options of available automatic instruments should be examined carefully before any study, and all algorithmic details should be systematically presented.

Research paper thumbnail of Significance of QRS prolongation during diagnostic ajmaline test in patients with suspected Brugada syndrome

Heart Rhythm, 2009

BACKGROUND Current consensus documents on Brugada syndrome recommend the diagnostic intravenous a... more BACKGROUND Current consensus documents on Brugada syndrome recommend the diagnostic intravenous administration of a Na-channel blocker to be stopped when the QRS prolongs to Ն130% of baseline, presumably because of increased arrhythmic risk.

Research paper thumbnail of Individual Patterns of Dynamic QT/RR Relationship in Survivors of Acute Myocardial Infarction and Their Relationship to Antiarrhythmic Efficacy of Amiodarone

Journal of Cardiovascular Electrophysiology, 2004

Postinfarction QT/RR Dynamics. Introduction: Amiodarone is an effective antiarrhythmic drug, but ... more Postinfarction QT/RR Dynamics. 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.

Research paper thumbnail of Diagnostic utility of bipolar precordial leads during ajmaline testing for suspected Brugada syndrome

Heart Rhythm, 2010

Leads V(1) and V(2) recorded from the standard position (fourth intercostal space) have insuffici... more Leads V(1) and V(2) recorded from the standard position (fourth intercostal space) have insufficient sensitivity to detect the diagnostic type 1 Brugada ECG pattern. The purpose of this study was to compare the sensitivity of bipolar leads with a positive pole at V(2) and a negative pole at V(4) or V(5) with that of the standard unipolar lead V(2) for detection of the type 1 Brugada pattern. We analyzed digital 15-lead ECGs (12 standard leads plus leads V(1) to V(3) recorded from the third intercostal space [V(1h) to V(3h)]) acquired during diagnostic ajmaline testing in 128 patients (80 men, age 37 +/- 15 years) with suspected Brugada syndrome and standard 12-lead ECGs recorded in 229 healthy subjects (111 men, age 33 +/- 4 years). Bipolar leads between V(2) (positive pole) and V(4) or V(5) (leads V(2-4), V(2-5)) were derived by subtracting leads V(4) and V(5) from V(2). All ECGs were examined for the presence of type 1 Brugada pattern. During 21 (16.4%) positive ajmaline tests, type 1 pattern was observed in lead V(2h) during 20 tests (95.2%) and in V(2) during 10 tests (47.6%). Type 1 pattern appeared in lead V(2-4) or V(2-5) in all tests when it was present in V(2) and in seven tests during which it was observed in lead V(2h) but not V(2) (17 tests [81%]). Type 1-like pattern was observed in lead V(2-4) or V(2-5) during two nonpositive tests (1.9%) and in one healthy subject (0.4%). Bipolar leads V(2-4) and V(2-5) are more sensitive than lead V(2) for detection of the type 1 Brugada pattern.

Research paper thumbnail of Effect of moderate physical exercise on noninvasive cardiac autonomic tests in healthy volunteers

International Journal of Cardiology, 1999

In addition to the assessment of extreme cardiovascular reserve, new methodology is needed which ... more In addition to the assessment of extreme cardiovascular reserve, new methodology is needed which is sensitive enough to detect subtle improvement in cardiovascular fitness in cardiac patients. This study modelled subtle clinical improvement by a moderate physical activity programme in healthy volunteers and investigated whether the improved fitness is detectable by non-invasive tests of cardiac autonomic status. Twenty healthy volunteers (ten women, mean age 39.6+/-7.8 years) were divided into two groups of five women and five men in each. One group (the active group) was subjected to a moderate physical training programme for 6 months. The other group (the passive group) served as controls and continued with a predominantly sedentary lifestyle. Twice before commencing the exercise programme and regularly afterwards, subjects were investigated by a series of non-invasive autonomic tests including controlled respiration, active postural change, isometric handgrip, and Valsalva manoeuvre. A continuous three lead semi-orthogonal electrocardiogram and continuous blood pressure monitoring was obtained. Statistical descriptors of heart rate and blood pressure, spectral descriptors of their modulation, and baroreflex index giving the proportion between simultaneous heart rate and blood pressure changes were obtained from each test. Although the exercise programme was not extensive enough to be detected in changes of the baseline heart rate, the minimum RR interval during the Valsalva manoeuvre prolonged significantly with exercise in the active group. The mean arterial diastolic pressure decreased significantly. High frequency components of RR interval modulations decreased in supine controlled respiration and increased in standing controlled respiration and a trend towards an increase of both high frequency and low frequency components of diastolic arterial pressure modulations was noted with exercise. Baroreflex index assessed from Valsalva manoeuvre increased significantly. The study suggests that a selected set of non-invasive autonomic tests is sensitive enough to depict moderate improvement in cardiovascular fitness and that a multivariate assessment of cardiovascular fitness based on these tests might be applicable to monitoring chronic cardiac patients subjected to different clinical management modes.

Research paper thumbnail of Computed quadripolar electrocardiographic leads for prediction of ventricular tachycardia

We present an excerpt from a continuous 15-lead electrocardiogram (standard 12 leads without lead... more We present an excerpt from a continuous 15-lead electrocardiogram (standard 12 leads without lead V 3 plus leads V 1 and V 2 from the third and the second intercostal space, 12.5 mm/s, 1 mV/cm) acquired during a negative diagnostic ajmaline test for the Brugada syndrome in a 43-year-old man with congenital long QT syndrome carrying the SCN5A-E1784K mutation. Fifteen seconds after the end of ajmaline administration (1 mg/kg for 5 minutes) and following marked QRS prolongation from 103 ms at baseline to 170 ms, the patient developed ventricular bigeminy with right bundle branch block morphology (likely originating from the left ventricle; and , top panel), which 1 minute and 30 seconds later degenerated into sustained polymorphic ventricular tachycardia (VT; , bottom panel).

Research paper thumbnail of Clinical utility of computed electrocardiographic leads

The standard 12-lead electrocardiogram (ECG) is only one of the possible ways to present the volt... more The standard 12-lead electrocardiogram (ECG) is only one of the possible ways to present the voltage differences between the nine recording electrodes. Other "non-conventional" leads may be constructed by physically connecting two or more electrodes in a different manner or by computation from the digital 12-lead ECG. Examples include bipolar or multipolar precordial leads and bipolar chest leads (between one precordial and one limb electrode). Such leads can remove or decrease noise originating from a limb cable/electrode that is present in the unipolar precordial leads. They can be diagnostically useful in Brugada syndrome and can display QRS fractionation that is not visible in the respective unipolar precordial or limb leads. Multipolar precordial leads sometimes display potentially useful information that is not visible in the respective unipolar leads and in bipolar leads computed from them. In conclusion, these computed ECG leads represent a potentially useful supplement to the conventional 12-lead ECG.

Research paper thumbnail of Prognostic value of corrected QT-interval prolongation in patients with unstable angina pectoris

American Journal of Cardiology, 2003

Research paper thumbnail of Inhibition of Atrial Electrical Activity by Ventricular Pacing Mediated by Vagal Stimulation

Pace-pacing and Clinical Electrophysiology, 1995

In the absence of retrograde (VA) conduction, ventricular pacing does not exert any appreciable e... more In the absence of retrograde (VA) conduction, ventricular pacing does not exert any appreciable effect upon atrial electrical activity. We report three patients (2 with complete AV block and 1 with preserved AV conduction) in which, during EP study, no VA conduction was present and, in spite of that, excessive suppression (for more than 15 secs in the first patient) of sinus (atrial) electrical activity during RV pacing was observed. The sinus node suppression was reproducible in two patients. In all patients the suppression phenomenon was not observed after intravenous administration of atropine, which suggests that it was mediated by enhanced vagal tone.

Research paper thumbnail of The Morphology of the Electrocardiogram

Research paper thumbnail of Comparison between ventricular gradient and a new descriptor of the wavefront direction of ventricular activation and recovery

Clinical Cardiology, 2002

Background: Total R T cosine (TCRT) is a new descriptor of repolarization heterogeneity that quan... more 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) [°] 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). VGM 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 non-redundant 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.

Research paper thumbnail of Precision of QT Interval Measurement by Advanced Electrocardiographic Equipment

Pace-pacing and Clinical Electrophysiology, 2006

The costs of clinical investigations of drug-induced QT interval prolongation are mainly related ... more 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.

Research paper thumbnail of Assessment of Noise in Digital Electrocardiograms

Pace-pacing and Clinical Electrophysiology, 2002

Technically related noise in 12-lead ECGs recorded with ambulatory recorders has never been syste... more 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 &amp;amp;amp;amp;amp;amp;amp;amp;quot;residuum&amp;amp;amp;amp;amp;amp;amp;amp;quot; 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 &amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.003 and p &amp;amp;amp;amp;amp;amp;amp;amp;lt; 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.

Research paper thumbnail of Individual Patterns of QT/RR Relationship

Cardiac Electrophysiology Review, 2002

In clinical practice, an imprecision introduced by ad hoc selected heart rate correction formula ... more In clinical practice, an imprecision introduced by ad hoc selected heart rate correction formula of the QTinterval is unlikely to lead to erroneous conclusions if all borderline cases are carefully considered. On thecontrary, in clinical investigations (e.g., studies of drug effects) the over- or undercorrection of QTcmay 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 universallysuccessful because the QT/RR relationship is different between different subjects and a formula that correctsthe 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 substantialinter-subject variability but also a high intra-subject stability. Thus, in precise investigations, individualQT/RR relationship should be first established in each subject and subsequently translated into individualheart rate correction formula.

Research paper thumbnail of Comparison of Different Methods for Manual P Wave Duration Measurement in 12Lead Electrocardiograms

Pace-pacing and Clinical Electrophysiology, 1999

To determine whether different methods for the manual measurement of P wave duration are mutually... more To determine whether different methods for the manual measurement of P wave duration are mutually consistent, we evaluated the intraobserver and interobserver errors of P wave measurements obtained in three different ways: (1) by cursor on a high resolution computer screen (on screen), (2) by calipers and a magnifying glass (on paper), and (3) by a high resolution digitizing board (on board). The agreement between the methods was assessed in 30 normal subjects and 30 patients with a history of atrial fibrillation. The maximum P wave duration (P maximum), the minimum P wave duration (P minimum), mean P wave duration (P mean), P wave dispersion (P dispersion = P maximum - P minimum), and the standard deviation of the P wave duration in all measured leads (P SD) were calculated from a 12-lead electrocardiogram in each subject. Only P maximum, P mean, and P dispersion were significantly higher in patients than in controls with all three methods. Intraobserver and interobserver relative errors were significantly different among the three methods; the lowest errors were associated with the on-screen measurement. The agreement between the three different methods was acceptable for P maximum, P mean, and P SD and rather poor for P minimum and P dispersion in both groups. The differences of the measurement by different methods did not consistently differ between the two groups. Hence, the on-screen measurements are consistent with other manual methods and provide more stable results. Manual measurement of ECG patterns should be preferably performed with digital ECG recordings displayed on a high resolution computer screen.

Research paper thumbnail of Mental stress and sudden cardiac death: asymmetric midbrain activity as a linking mechanism

Patients with specific neurological, psychiatric or cardiovascular conditions are at enhanced ris... more 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 H 2 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 rightlateralized 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.

Research paper thumbnail of Brugada-Like Changes in the Peripheral Leads during Diagnostic Ajmaline Test in Patients with Suspected Brugada Syndrome

Pace-pacing and Clinical Electrophysiology, 2009

Background: Although cases of Brugada-type electrocardiographic (ECG) pattern in peripheral (limb... more Background: Although cases of Brugada-type electrocardiographic (ECG) pattern in peripheral (limb) leads have been reported (“atypical” Brugada syndrome [BS]), their incidence in patients investigated for BS is unknown.Methods: We retrospectively analyzed an ECG database collected during ajmaline test in 143 patients (89 men) with suspected BS. In 42 patients, 12-lead ECGs were recorded, whereas in 101 patients, leads V1–V3 from the third intercostal space were also recorded. The presence of types 1, 2, and 3 Brugada pattern in each limb and precordial lead was noted and the PR, QRS, and QTc intervals were calculated.Results: There were 114 (79.7%) negative and 29 (20.3%) positive tests. Type 1 pattern developed in ≥1 limb lead in six patients (4.2%) (3/29 with positive tests, 10.3%); all of them were male, symptomatic, and/or with family history of BS or sudden cardiac death. Their pre- and posttest QRS were significantly longer compared with the rest with positive (n = 26) or negative (n = 111) test (pretest: 129 ± 31 ms vs 101 ± 11 ms and 97 ± 12 ms, P < 0.001; posttest: 175 ± 44 ms vs 134 ± 14 ms and 131 ± 19 ms, P < 0.001). The posttest QTc was longer in patients with peripheral changes compared with the rest (507 ± 47 ms vs 453 ± 22 ms and 447 ± 24 ms, P < 0.001). The pretest QTc and pre- and posttest heart rate and PR intervals were not significantly different between the three groups.Conclusions: Type 1 Brugada pattern in the peripheral leads was observed in 4.2% of patients during ajmaline test (10.3% of positive tests) and was associated with longer QRS and greater QTc prolongation compared with the rest of the patients.

Research paper thumbnail of Sample Size, Power Calculations, and Their Implications for the Cost of Thorough Studies of Drug Induced QT Interval Prolongation

Pace-pacing and Clinical Electrophysiology, 2004

Regulatory authorities require new drugs to be investigated using a so-called &amp;amp;amp;am... more Regulatory authorities require new drugs to be investigated using a so-called &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;thorough QT/QTc study&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;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).

Research paper thumbnail of The heart vector, the regional information in the electrocardiogram, and QT dispersion

American Journal of Cardiology, 2002

Research paper thumbnail of Increased QT dispersion in patients with Prinzmetal's variant angina and cardiac arrest

We sought to compare QT dispersion in patients presenting with Prinzmetal's variant angina compli... more We sought to compare QT dispersion in patients presenting with Prinzmetal's variant angina complicated by cardiac arrest or syncope and patients with uncomplicated variant angina. Background: Despite the usually benign course of treated Prinzmetal's variant angina, a proportion of vasospastic angina patients develop ventricular arrhythmias and sudden death in association with coronary spasm. Increased QT dispersion has been suggested to increase susceptibility to ventricular arrhythmias in patients with coronary artery spasm. Methods: We studied 25 consecutive patients (mean age 58 years; 14 men) with classical Prinzmetal's variant angina and documented coronary artery spasm. None of the patients had coronary artery stenoses #40%. Five patients had suffered a documented cardiac arrest, two had recurrent syncope and 18 had no arrhythmic events or syncopal episodes. In all patients QT dispersion (QT maximum2QT minimum in every ECG lead) was measured on the baseline 12-lead electrocardiogram at study entry using a digitising board. Results: Mean (6S.D.) QT dispersion of study patients was 62.3619.5 ms. QT dispersion in patients with cardiac arrest and syncope (79.4617.3 ms) was significantly higher compared to patients with no such events (56.3616.9 ms), (95% CI 7.5-38.8, P50.005). No significant clinical, biochemical or angiographic differences were found between patients with and those without cardiac arrest or syncope. Conclusion: QT dispersion is increased in patients with Prinzmetal's variant angina complicated by cardiac arrest and syncope compared to patients without such events. Increased QT dispersion may be both a substrate for sudden cardiac death and a marker of risk in patients with Prinzmetal's variant angina.

Research paper thumbnail of QT Interval and QT Dispersion Measured with the Threshold Method Depend on Threshold Level

Pace-pacing and Clinical Electrophysiology, 1998

Various computerized methods with multiple parameter options for measurements of the QT interval ... more Various computerized methods with multiple parameter options for measurements of the QT interval now are available. The optimum parameter setting for most algorithms is not known. This study evaluated the influence of the threshold level applied on the T wave differential on the QT interval and its dispersion measured in normal and abnormal electrocardiograms (ECGs). Seven hundred sixty ECGs recorded in 76 normal subjects and 630 in 63 patients with hypertrophic cardiomyopathy (HCM) (10 consecutive recordings in each individual) were analyzed. In each lead of each ECG, the QT interval was measured by the threshold method applied to the first differential of the T wave. The threshold level was varied between 5% and 30% of the T wave maximum in 1% steps, resulting in 26 different choices of QT measurements. With each choice the maximum QTc and the QT dispersion (QTd, standard deviation of the QT in all 12 leads) were obtained for each recording. The maximum QTc was significantly longer in HCM patients than in normal subjects (P < 0.001) at all threshold levels except between 5% and 7%. The QTd was significantly greater in HCM patients at all threshold levels. The QTc and QTd changed significantly with the threshold level. The maximum QTc varied up to 60 ms in normal subjects and up to 70 ms in HCM patients, depending on the threshold level. Thus, the QT intervai and its dispersion measured with the threshold method applied to the first T wave differential depended significantly on the threshold level in both normal and diseased hearts. All programmable options of available automatic instruments should be examined carefully before any study, and all algorithmic details should be systematically presented.

Research paper thumbnail of Significance of QRS prolongation during diagnostic ajmaline test in patients with suspected Brugada syndrome

Heart Rhythm, 2009

BACKGROUND Current consensus documents on Brugada syndrome recommend the diagnostic intravenous a... more BACKGROUND Current consensus documents on Brugada syndrome recommend the diagnostic intravenous administration of a Na-channel blocker to be stopped when the QRS prolongs to Ն130% of baseline, presumably because of increased arrhythmic risk.

Research paper thumbnail of Individual Patterns of Dynamic QT/RR Relationship in Survivors of Acute Myocardial Infarction and Their Relationship to Antiarrhythmic Efficacy of Amiodarone

Journal of Cardiovascular Electrophysiology, 2004

Postinfarction QT/RR Dynamics. Introduction: Amiodarone is an effective antiarrhythmic drug, but ... more Postinfarction QT/RR Dynamics. 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.

Research paper thumbnail of Diagnostic utility of bipolar precordial leads during ajmaline testing for suspected Brugada syndrome

Heart Rhythm, 2010

Leads V(1) and V(2) recorded from the standard position (fourth intercostal space) have insuffici... more Leads V(1) and V(2) recorded from the standard position (fourth intercostal space) have insufficient sensitivity to detect the diagnostic type 1 Brugada ECG pattern. The purpose of this study was to compare the sensitivity of bipolar leads with a positive pole at V(2) and a negative pole at V(4) or V(5) with that of the standard unipolar lead V(2) for detection of the type 1 Brugada pattern. We analyzed digital 15-lead ECGs (12 standard leads plus leads V(1) to V(3) recorded from the third intercostal space [V(1h) to V(3h)]) acquired during diagnostic ajmaline testing in 128 patients (80 men, age 37 +/- 15 years) with suspected Brugada syndrome and standard 12-lead ECGs recorded in 229 healthy subjects (111 men, age 33 +/- 4 years). Bipolar leads between V(2) (positive pole) and V(4) or V(5) (leads V(2-4), V(2-5)) were derived by subtracting leads V(4) and V(5) from V(2). All ECGs were examined for the presence of type 1 Brugada pattern. During 21 (16.4%) positive ajmaline tests, type 1 pattern was observed in lead V(2h) during 20 tests (95.2%) and in V(2) during 10 tests (47.6%). Type 1 pattern appeared in lead V(2-4) or V(2-5) in all tests when it was present in V(2) and in seven tests during which it was observed in lead V(2h) but not V(2) (17 tests [81%]). Type 1-like pattern was observed in lead V(2-4) or V(2-5) during two nonpositive tests (1.9%) and in one healthy subject (0.4%). Bipolar leads V(2-4) and V(2-5) are more sensitive than lead V(2) for detection of the type 1 Brugada pattern.

Research paper thumbnail of Effect of moderate physical exercise on noninvasive cardiac autonomic tests in healthy volunteers

International Journal of Cardiology, 1999

In addition to the assessment of extreme cardiovascular reserve, new methodology is needed which ... more In addition to the assessment of extreme cardiovascular reserve, new methodology is needed which is sensitive enough to detect subtle improvement in cardiovascular fitness in cardiac patients. This study modelled subtle clinical improvement by a moderate physical activity programme in healthy volunteers and investigated whether the improved fitness is detectable by non-invasive tests of cardiac autonomic status. Twenty healthy volunteers (ten women, mean age 39.6+/-7.8 years) were divided into two groups of five women and five men in each. One group (the active group) was subjected to a moderate physical training programme for 6 months. The other group (the passive group) served as controls and continued with a predominantly sedentary lifestyle. Twice before commencing the exercise programme and regularly afterwards, subjects were investigated by a series of non-invasive autonomic tests including controlled respiration, active postural change, isometric handgrip, and Valsalva manoeuvre. A continuous three lead semi-orthogonal electrocardiogram and continuous blood pressure monitoring was obtained. Statistical descriptors of heart rate and blood pressure, spectral descriptors of their modulation, and baroreflex index giving the proportion between simultaneous heart rate and blood pressure changes were obtained from each test. Although the exercise programme was not extensive enough to be detected in changes of the baseline heart rate, the minimum RR interval during the Valsalva manoeuvre prolonged significantly with exercise in the active group. The mean arterial diastolic pressure decreased significantly. High frequency components of RR interval modulations decreased in supine controlled respiration and increased in standing controlled respiration and a trend towards an increase of both high frequency and low frequency components of diastolic arterial pressure modulations was noted with exercise. Baroreflex index assessed from Valsalva manoeuvre increased significantly. The study suggests that a selected set of non-invasive autonomic tests is sensitive enough to depict moderate improvement in cardiovascular fitness and that a multivariate assessment of cardiovascular fitness based on these tests might be applicable to monitoring chronic cardiac patients subjected to different clinical management modes.