Herpen, G. van

Common variants in 22 loci are associated with QRS duration and cardiac ventricular conduction (Article)

2010-12-01T00:00:00Z

The QRS interval, from the beginning of the Q wave to the end of the S wave on an electrocardiogram, reflects ventricular depolarization and conduction time and is a risk factor for mortality, sudden death and heart failure. We performed a genome-wide association meta-analysis in 40,407 individuals of European descent from 14 studies, with further genotyping in 7,170 additional Europeans, and we identified 22 loci associated with QRS duration (P < 5 × 10 -8). These loci map in or near genes in pathways with established roles in ventricular conduction such as sodium channels, transcription factors and calcium-handling proteins, but also point to previously unidentified biologic processes, such as kinase inhibitors and genes related to tumorigenesis. We demonstrate that SCN10A, a candidate gene at the most significantly associated locus in this study, is expressed in the mouse ventricular conduction system, and treatment with a selective SCN10A blocker prolongs QRS duration. These findings extend our current knowledge of ventricular depolarization and conduction.

Local Depolarization Abnormalities Are the Dominant Pathophysiologic Mechanism for Type 1 Electrocardiogram in Brugada Syndrome. A Study of Electrocardiograms, Vectorcardiograms, and Body Surface Potential Maps During Ajmaline Provocation (Article)

2010-02-23T00:00:00Z

Objectives: We sought to obtain new insights into the pathophysiologic basis of Brugada syndrome (BrS) by studying changes in various electrocardiographic depolarization and/or repolarization variables that occurred with the development of the signature type 1 BrS electrocardiogram (ECG) during ajmaline provocation testing. Background: BrS is associated with sudden cardiac death. Its pathophysiologic basis, although unresolved, is believed to reside in abnormal cardiac depolarization or abnormal repolarization. Methods: Ajmaline provocation was performed in 269 patients suspected of having BrS with simultaneous recording of ECGs, vectorcardiograms, and 62-lead body surface potential maps. Results: A type 1 ECG was elicited in 91 patients (BrS patients), 162 patients had a negative test result (controls), and 16 patients had an abnormal test result. Depolarization abnormalities were more prominent in BrS patients and were mapped to the right ventricle (RV) by longer right precordial filtered QRS complex durations (142 ± 23 ms vs. 125 ± 14 ms, p < 0.01) and right terminal conduction delay (60 ± 11 ms vs. 53 ± 9 ms, p < 0.01). Repolarization abnormalities remained concordant with depolarization abnormalities as indicated by steady low nondipolar content (12 ± 8% vs. 8 ± 4%, p = NS), lower spatial QRS-T integrals (33 ± 12 mV·ms vs. 40 ± 16 mV·ms, p < 0.05), similar spatial QRS-T angles (92 ± 39° vs. 87 ± 31°, p = NS), similar Tpeak-Tendinterval (143 ± 36 ms vs. 138 ± 25 ms, p = NS), and similar Tpeak-Tenddispersion (47 ± 37 ms vs. 45 ± 27 ms, p = NS). Conclusions: The type 1 BrS ECG is characterized predominantly by localized depolarization abnormalities, notably (terminal) conduction delay in the RV, as assessed with complementary noninvasive electrocardiographic techniques. We could not define a separate role for repolarization abnormalities but suggest that the typical signs of repolarization derangements seen on the ECG are secondary to these depolarization abnormalities.

IK1 modulates the U-wave: insights in a 100-year-old enigma (Article)

2009-03-01T00:00:00Z

Methodology of QT-interval measurement in the modular ECG analysis system (MEANS) (Article)

2009-01-01T00:00:00Z

Background: QT prolongation as can be induced by drugs, signals the risk of life-threatening arrhythmias. The methodology of QT measurement in the modular ECG analysis system (MEANS) is described. Methods: In the simultaneously recorded leads of the standard 12-lead electrocardiogram (ECG), the QRS complexes are detected by a spatial velocity function. They are typed as dominant or nondominant, and a representative complex per lead is obtained by averaging over the dominant complexes. QRS onset and T end are determined by a template technique, and QT is measured. MEANS performance was evaluated on the 125 ECGs of the common standards for quantitative electrocardiography (CSE) multilead database, of which the waveform boundaries have been released. Results: MEANS detected correctly all 1445 complexes of the CSE library, with one false-positive detection due to a sudden baseline jump. All dominant complexes were correctly typed. The average of the differences between MEANS and reference was less than 2 ms (=1 sample) for both QRS onset and T end, and 2.1 ms for QT duration. The standard deviation of the differences was 3.8, 8.4, and 10.4 ms, respectively. Conclusions: A standard deviation of 10.4 ms for QT measurement seems large when related to the regulatory requirement that a prolongation as small as 5 ms should be detected. However, QT variabilities as encountered in different individuals will be larger than when measured in one individual during pharmacological intervention. Finally, if the U wave is part of the total repolarization, then T and U form a continuum and the end of T becomes questionable.

The meaning of the Tp-Te interval and its diagnostic value (Article)

2008-11-01T00:00:00Z

Background: The interval between T peak (Tp) and T end (Te) has been proposed as a measure of transmural dispersion of repolarization, but experimental and clinical studies to validate Tp-Te have given conflicting results. We have investigated the meaning of Tp-Te and its diagnostic potential. Methods: We used a digital model of the left ventricular wall to simulate the effect of varying action potential durations on the timing of Tp and Te. Furthermore, we used the vectorcardiogram to explain the relationships between Tp locations in the precordial electrocardiogram leads. Results: Prolongation or ischemic shortening of action potentials in our model did not result in substantial Tp shifts. The phase relationships revealed by the vectorcardiogram showed that Tp-Te in the precordial leads is a derivative of T loop morphology. Conclusion: Tp-Te is the resultant of the global distribution of the repolarization process and is a surrogate diagnostic parameter.

Electrocardiographic criteria for left ventricular hypertrophy in children (Article)

2008-09-01T00:00:00Z

Previous studies to determine the sensitivity of the electrocardiogram (ECG) for left ventricular hypertrophy (LVH) in children had their imperfections: they were not done on an unselected hospital population, several criteria used in adults were not applied to children, and obsolete limits of normal for the ECG parameters were used. Furthermore, left ventricular mass (LVM) was taken as the reference standard for LVH, with no regard for other clinical evidence. The study population consisted of 832 children from whom a 12-lead ECG and an M-mode echocardiogram were taken on the same day. The validity of the ECG criteria was judged on the basis of an abnormal LVM index, either alone or in combination with other clinical evidence. The ECG criteria were based on recently established age-dependent normal limits. At 95% specificity, the ECG criteria have low sensitivities (<25%) when an elevated LVM index is taken as the reference for LVH. When clinical evidence is also taken into account, the sensitivity improved considerably (<43%). Sensitivities could be further improved when ECG parameters were combined. The sensitivity of the pediatric ECG in detecting LVH is low but depends strongly on the definition of the reference used for validation.

Intraindividual variability in electrocardiograms (Article)

2008-05-01T00:00:00Z

The electrocardiogram (ECG) can be affected by intraindividual variations from various sources that may confuse the diagnosis of the underlying cardiac condition and impair the accuracy of ECG interpretation. Intraindividual variability is a hindrance in serial ECG analysis, where ECGs of the same individual, but taken at different times, are compared. Two sources of intraindividual variability can be distinguished as follows: variability related to the technical circumstances during ECG recording (technical sources) and nonpathologic biologic variability (biological sources). Among the technical sources, variation in electrode positioning between recordings is the most confusing. Of the biological sources, respiratory variations are effective at any time scale, but the most important are age and weight that work on prolonged time scales. Technical problems are best prevented by rigorously sticking to a standard acquisition protocol. Criteria can be adapted to changing circumstances (age, weight), and by computer modeling, it may be possible to correct the ECG diagnosis for some sources of intraindividual variability.

Mirror image electrocardiograms and additional electrocardiographic leads: new wine in old wineskins? (Article)

2008-05-01T00:00:00Z

Background: Mirror image electrocardiograms (ECGs), obtained by inverting the original signals, and additional precordial leads have been proposed as means to improve ECG diagnosis. The theoretical backgrounds of these proposals are discussed. Methods: In 746 body surface potential maps, the mirror areas of the 6 precordial leads, V3R, and 2 more leads higher up and 1 lower down the thorax have been determined. The similarity between the original signal and its mirror image was expressed by a similarity index. This was done separately for QRS and ST-T; for the first and second parts of QRS; and for the categories normal, left ventricular hypertrophy, and infarct. Results: In general, high similarity scores were obtained. The mirror images of V1and V2are almost diametrically located on the back. Inverting these leads could render the V8and V9leads. The other mirror areas may deviate considerably from where generally expected. Conclusion: Mirror images can be obtained consistently from all locations, supporting the dipole representation of cardiac electrical activity. Neither mirror image ECGs nor additional chest leads contribute essentially to ECG diagnosis.

Optimizing the 12-lead electrocardiogram: a data driven approach to locating alternative recording sites (Article)

2007-05-01T00:00:00Z

Background: Despite its widespread use, the limitations of the 12-lead electrocardiogram (ECG) are undisputed. The main deficiency is that just a small area of the precordium is interrogated and for some abnormalities information may be transmitted to a region of the body surface where information is not recorded. In this study, we attempted to optimize the 12-lead ECG by using a data-driven approach to suggest alternate recording sites. Methods: A sequential lead selection algorithm was applied to a set of 744 body surface potential maps (BSPMs), consisting of recordings from subjects with myocardial infarction, left ventricular hypertrophy, and no apparent disease. A number of scenarios were investigated in which pairs of precordial leads were repositioned; these pairs were V3and V5, V4and V5, and V4and V6. The algorithm was also used to find optimal positions for all 6 precordial leads. Result: Through estimation of entire surface potential distributions it was found that each of the scenarios, with 2 leads repositioned, captured more information than the standard 12-lead ECG. The scenario with V4and V6repositioned performed best with a root mean square error of 22.3 microvolts and a correlation coefficient of 0.967. This configuration also fared favorably when compared to the scenario where all 6 precordial leads were repositioned as optimizing all 6 leads offered no significant improvement. Conclusion: This study demonstrated the use of a lead selection algorithm in enhancing the 12-lead ECG. The results also indicated that repositioning just 2 precordial leads can provide the same level of information capture as that observed when all precordial leads are optimally placed.

Dynamic changes of the TU complex in the electrocardiogram (Article)

2007-01-01T00:00:00Z

Abstract: The dynamicity of the repolarization process is reflected in the beat-to-beat variation of the TU complex. In short term (≤5 minutes) recordings this variability is measured on a beat by beat basis. The recordings were obtained from 86 healthy subjects and 13 patients with the long QT syndrome. No effect of preceding RR on T or U amplitude could be demonstrated, although these amplitudes show a substantial intraindividual variation. Peak T and U do show a (weak) correlation. Patients with the long QT syndrome have an instability of the repolarization process which is expressed in substantial variation in QT duration and the appearance of TU wavelets well beyond the classical end of T wave.

QT dispersion as an attribute of T-loop morphology (Article)

1999-01-01T00:00:00Z

BACKGROUND: The suggestion that increased QT dispersion (QTD) is due to increased differences in local action potential durations within the myocardium is wanting. An alternative explanation was sought by relating QTD to vectorcardiographic T-loop morphology. METHODS AND RESULTS: The T loop is characterized by its amplitude and width (defined as the spatial angle between the mean vectors of the first and second halves of the loop). We reasoned that small, wide ("pathological") T loops produce larger QTD than large, narrow ("normal") loops. To quantify the relationship between QTD and T-loop morphology, we used a program for automated analysis of ECGs and a database of 1220 standard simultaneous 12-lead ECGs. For each ECG, QT durations, QTD, and T-loop parameters were computed. T-loop amplitude and width were dichotomized, with 250 microV (small versus large amplitudes) and 30 degrees (narrow versus wide loops) taken as thresholds. Over all 1220 ECGs, QTDs were smallest for large, narrow T loops (54.2+/-27.1 ms) and largest for small, wide loops (69. 5+/-33.5 ms; P<0.001). CONCLUSIONS: QTD is an attribute of T-loop morphology, as expressed by T-loop amplitude and width.

Measurement error as a source of QT dispersion: a computerised analysis (Article)

1998-01-01T00:00:00Z

OBJECTIVE: To establish a general method to estimate the measuring error in QT dispersion (QTD) determination, and to assess this error using a computer program for automated measurement of QTD. SUBJECTS: Measurements were done on 1220 standard simultaneous 12 lead electrocardiograms. DESIGN: The computer program was validated against two observers on a random subset of 100 electrocardiograms. Simple laws of physics require that at least five of the six extremity leads have the same QT duration. This allows the direct assessment of the error in measuring QTD derived from five extremity leads (QTD5). It also enables ST-T amplitude dependent distributions of measurement error in determining QT duration to be established. These QT error distributions were then used to estimate the error in measuring QTD from all 12 leads (QTD12). MAIN OUTCOME MEASURES: Mean and standard deviation of error in measuring QTD duration, QTD5, and QTD12. RESULTS: Performance of the program was comparable to that of observers. Errors in measuring QT duration (measured QT minus reference QT) fell from a mean (SD) of 6.9 (17.1) ms for ST-T amplitudes < 50 microV to -1.4 (6.3) ms for amplitudes > 350 microV. Measurement errors of QTD5 and QTD12 were 20.4 (11.5) ms and 29.4 (14.9) ms. CONCLUSIONS: The fact that no QTD can exist between five of the six extremity leads provides a means of estimating QTD measurement error. Measuring error of QT duration is dependent on ST-T amplitude. QTD measurement error is large compared with typical QTD values reported.