Martina Šišáková

Subject-specific heart rate dependency of electrocardiographic QT, PQ, and QRS intervals

Although heart rate dependency of QT interval is well known, the relationship of other electrocardiogram (ECG) parameters to heart rate has been researched less intensively. This study investigated the heart rate dependencies of QT interval, PQ interval, and QRS width in 40 healthy subjects (18 women; mean age, 30.4 +/- 8.1 years). In each subject, 3 long-term (approximately 13 hours) 12-lead ECGs were obtained for 3 day-time periods with gaps of 2 to 3 weeks between repeated recordings. In each recording, approximately 230 ECG measurements of QT interval, PQ interval, and QRS width were made, each preceded by stable heart rate. For each recording, linear regression slopes of QT/RR, PQ/RR, and QRS/RR relationships were obtained. Intrasubject SDs of individual values were compared with intersubject SDs of intrasubject means to test the individuality of the relationships. The intrasubject means of the slope values were also compared between sexes. The individual SDs of the QT/RR regression slopes were 0.0116 +/- 0.0065, whereas the population SD of intrasubject means was 0.0245 (P = 3.6 x 10(-15)). For the PQ/RR slopes and QRS/RR slopes, these values were 0.0085 +/- 0.0050 vs 0.0314 (P = 7.9 x 10(-28)) and 0.00189 +/- 0.00157 vs 0.00550 (P = 2.6 x 10(-17)), respectively. The QT/RR slopes were steeper in women than in men (0.194 +/- 0.019 vs 0.168 +/- 0.022, 0.0005), whereas the QRS/RR slopes were, on average, negative in women while positive in men (-0.00138 +/- 0.0045 vs 0.00335 +/- 0.0054, P = .005). There were no sex differences in the PQ/RR slopes (0.054 +/- 0.032 in women vs 0.055 +/- 0.031 in men, P = .95). Thus, not only the heart rate dependency of QT interval but also the rate dependencies of PQ interval and of QRS width show high intrasubject stability with substantial intersubject differences.

The homozygous KCNQ1 gene mutation associated with recessive Romano-Ward syndrome.

In a 7‐year‐old boy with normal hearing suffering from repeated syncope an extremely prolonged QTc interval (up to 700 ms) was found. The mother was completely asymptomatic and the father had an intermittently borderline QTc interval (maximum 470 ms) but no symptoms. In the proband a mutation analysis of KCNQ1 gene revealed a homozygous 1893insC mutation. The parents were heterozygous for this mutation. There was no consanguineous marriage in the family. The clinical relevance of these findings is that apparently normal individuals may have a latent reduction of repolarizing currents, a “reduced repolarization reserve,” because they are carriers of latent ion channel genes mutations.

Dynamic properties of selected repolarization descriptors.

A number of morphological indices have been proposed to characterize electrocardiographic patterns of ventricular repolarization mostly studying spatial and temporal patterns of T waves. Comparisons between different clinical populations exist but data on the suitability of the T-wave descriptors to characterize and quantify physiologic regulations of ventricular repolarization are lacking. To initiate such investigations, a study was conducted comparing the influence of provoked heart rate changes on the duration of QT interval, the roundness of T wave loop expressed by the relative T wave area, and on the 3-dimensional QRS-T angle. A population of 40 healthy subjects (18 women, mean age 30.4 ± 8.1 years) was studied. In each subject, provocative tests involving changes from strict supine to unsupported sitting and to unsupported standing positions were repeated twice during each of 3 separate monitoring days. Continuous 12-lead electrocardiograms were obtained during the provocative tests. The speed of the adaptation of the repolarization descriptors to heart rate changes was characterized by λ parameters of previously published exponential decay model of R-R interval related hysteresis. The comparisons showed that the adaptation of QT interval to heart rate changes was much slower than that of the investigated T-wave morphological descriptors: the mean (SD) values of λ parameters were 5.01 ± 1.13, 12.72 ± 8.66, and 12.90 ± 11.37 for QT interval, QRS-T angle, and relative T-wave area, respectively (P < .001 for the difference between QT interval and both morphological descriptors). The study suggests that the different numerical quantifiers of vertricular repolarization that may be derived from standard electrocardiographic tracings likely represent separate and distinct physiologic entities.

The role of computerized diagnostic proposals in the interpretation of the 12-lead electrocardiogram by cardiology and non-cardiology fellows

INTRODUCTION Most contemporary 12-lead electrocardiogram (ECG) devices offer computerized diagnostic proposals. The reliability of these automated diagnoses is limited. It has been suggested that incorrect computer advice can influence physician decision-making. This study analyzed the role of diagnostic proposals in the decision process by a group of fellows of cardiology and other internal medicine subspecialties. MATERIALS AND METHODS A set of 100 clinical 12-lead ECG tracings was selected covering both normal cases and common abnormalities. A team of 15 junior Cardiology Fellows and 15 Non-Cardiology Fellows interpreted the ECGs in 3 phases: without any diagnostic proposal, with a single diagnostic proposal (half of them intentionally incorrect), and with four diagnostic proposals (only one of them being correct) for each ECG. Self-rated confidence of each interpretation was collected. RESULTS Availability of diagnostic proposals significantly increased the diagnostic accuracy (p<0.001). Nevertheless, in case of a single proposal (either correct or incorrect) the increase of accuracy was present in interpretations with correct diagnostic proposals, while the accuracy was substantially reduced with incorrect proposals. Confidence levels poorly correlated with interpretation scores (rho≈2, p<0.001). Logistic regression showed that an interpreter is most likely to be correct when the ECG offers a correct diagnostic proposal (OR=10.87) or multiple proposals (OR=4.43). CONCLUSION Diagnostic proposals affect the diagnostic accuracy of ECG interpretations. The accuracy is significantly influenced especially when a single diagnostic proposal (either correct or incorrect) is provided. The study suggests that the presentation of multiple computerized diagnoses is likely to improve the diagnostic accuracy of interpreters.

Clinical characteristics of 30 Czech families with long QT syndrome and KCNQ1 and KCNH2 gene mutations: importance of exercise testing

BACKGROUND Classic symptoms of long QT syndrome (LQTS) include prolongation of QT interval on electrocardiograph, syncope, and cardiac arrest due to a distinctive form of polymorphic ventricular tachycardia, known as Torsade de Pointes. We assessed occurrence of LQTS signs in individuals from 30 Czech families with mutations in KCNQ1 and KCNH2 genes. METHODS AND RESULTS One hundred five individuals from 30 Czech families with LQTS were genotyped for KCNQ1 and KCNH2. The occurrence of typical LQTS signs (pathologic prolongation of QT interval; syncope; cardiac arrest; Torsade de Pointes) was clinically assessed by exercise test with QT interval analysis. Family history of sudden cardiac death was taken. Statistical analysis was performed to determine correlation of clinical results and mutation status. KCNQ1 gene mutations were found in 23 families, and KCNH2 gene mutations in eight families. Only 46 (70%) of the 66 mutation carriers had at least two of the typical LQTS signs. The others were minimally or asymptomatic. From 39 noncarrier individuals, only 1 fulfilled the clinical criteria of LQTS diagnosis, another 4 had an intermediate probability of diagnosis. The exercise test had 92% sensitivity and 93% specificity for LQTS diagnosis. CONCLUSIONS Incidence of classical signs of LQTS was not high in Czech carriers of KCNQ1 and KCNH2 mutations. Therefore, proper diagnosis relies on detection of symptoms at presentation. The exercise test may be beneficial owing to its high sensitivity and specificity for LQTS diagnosis.

Pilot study of sex differences in QTc intervals of heart transplant recipients

BACKGROUND Repolarization processes in female and male are different. This study provided pilot data on automatic measurements of QT intervals in heart transplant (HT) recipients stratified according to the sex of the recipient and the donor. METHODS AND RESULTS The following groups were analyzed: Group A-20 males with male heart, group B-14 females with male heart, group C-13 females with female heart, group D-11 males with female heart, group E-20 healthy males, and group F-20 healthy females. Twelve-lead electrocardiograms were digitally captured during autonomic provocative test of five postural 8-minute stages-supine, unsupported sitting, supine, unsupported standing, and supine. Fridericia formula was used for heart rate correction together with a generic correction for QT/RR hysteresis. Neither female nor male HT recipients exhibit any differences in QTc interval duration related to the sex of the donor. There was, however, a trend towards longer QTc intervals in female HT recipients compared to male HT recipients irrespective of the sex of the donor. The QTc differences between healthy control females and males were highly statistically significant proving the assay sensitivity of the study. CONCLUSION The available pilot data suggest that in HT patients, the sex of the donor has little influence on the QTc interval of the transplanted heart.

Effect of atorvastatin on dynamic parameters of myocardial repolarization in healthy subjects

BACKGROUND Antiarrhythmic properties of statins were suggested as a part of their pleiotropic effects. The aim of the present study was to evaluate the effects of atorvastatin on myocardial repolarization as manifested on surface electrocardiograms (ECGs) in healthy subjects. METHODS AND RESULTS Forty young healthy volunteers (20 men, 20 women) underwent a single-dose double-blind 3-way crossover study of 20 and 80 mg of atorvastatin and placebo. Long-term 13-hour 12-lead ECGs were obtained in each subject and each study period starting 15 minutes before drug administration. Each study period contained 18 time-points of 5-minute durations when the subjects were in resting supine positions. Digital ECG recordings were analyzed automatically, and the results were completed blindly before statistical analyses. Dynamic parameters of myocardial repolarization and T-wave morphology descriptors were evaluated. Although some trends were observed, no significant drug-related changes in any of investigated ECG repolarization descriptors were found. CONCLUSION In comparison with placebo, single doses of atorvastatin had no effect on repolarization heterogeneity in healthy subjects. The observation confirms safe profile of the drug with limited proarrhythmic potential.