Irena Andrsova

Mutation Analysis Ion Channel Genes Ventricular Fibrillation Survivors with Coronary Artery Disease

Background: Observations from population‐based studies demonstrated a strong genetic component of sudden cardiac death. The aim of this study was to test the hypothesis that ion channel genes mutations are more common in ventricular fibrillation (VF) survivors with coronary artery disease (CAD) compared to controls.

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.

Clinical Characteristics and Mutational Analysis of the RyR2 Gene in Seven Czech Families with Catecholaminergic Polymorphic Ventricular Tachycardia

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare hereditary arrhythmia. The onset of clinical symptoms usually occurs during childhood, and is typically related to exercise. The aim of our study was to describe the clinical characteristics of seven Czech families with CPVT and the results of mutational analysis of the RyR2 gene in these families.

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.

Hypersensitivity to material and environmental burden as a possible cause of late complications of cardiac implantable electronic devices

Abstract Aims To evaluate whether patients with late complications of pacemakers or implantable cardioverter-defibrillators have hypersensitivity reactions to some of the materials used in generators or in electrodes, or to environmental metal burden. Methods and results The cohort consisted of 20 men and 4 women (mean age: 62.3 ± 17.2 years) who had a history of late complications of implanted devices. The control group involved 25 men and 8 women (mean age: 64.6 ± 14.0 years) who had comparable devices, but no history of late complications. Lymphocyte transformation test was used to evaluate hypersensitivity to eight metal pollutants (antimony, manganese, mercury, molybdenum, nickel, platinum, tin, and titanium) selected by results of questionnaires on environmental burden, and by material analysis of generators and electrode surfaces. Exposures to metal pollutants were approximately the same in patients and in controls. Titanium alloy used in generators contained at least 99.32% of titanium and trace levels of other metals; higher levels of tin and platinum were detected in electrode surfaces. Hypersensitivity reactions to mercury and tin were significantly more frequent in patients than in controls (patients and controls: mercury: 68.2 and 31.1%, respectively; P = 0.022; tin: 25.0 and 3.2%, respectively; P = 0.035). In contrast, hypersensitivity to manganese was significantly more frequent in controls than in patients (patients and controls: 13.6 and 50.0%, respectively; P = 0.008). Conclusion Our findings suggest a possible relation between hypersensitivity to metals used in implantable devices or to environmental metal burden and the occurrence of their late complications.

Higher incidence of hypotension episodes in women during the sub-acute phase of ST elevation myocardial infarction and relationship to covariates

Objective The introduction of primary percutaneous coronary intervention (PPCI) has modified the profile of ST elevation myocardial infarction (STEMI) patients. Occurrence and prognostic significance of hypotension episodes are not known in PPCI treated STEMI patients. It is also not known whether and/or how the hypotension episodes correlate with the degree of myocardial damage and whether there are any sex differences. Methods Data of 293 consecutive STEMI patients (189 males) treated by PPCI and without cardiogenic shock were analyzed. Blood pressure was measured noninvasively. A hypotensive episode was defined as a systolic blood pressure below 90 mmHg over a period of at least 30 minutes. Results A hypotensive episode was observed in 92 patients (31.4%). Female sex was the strongest independent predictor of hypotension episodes (p < 0.0001), while there was no relationship to electrocardiographic STEMI localization. Hypotensive patients had significantly higher levels of troponin T and brain natriuretic peptide; hypotensive episodes were particularly frequent in women with increased troponin T. Treatment with angiotensin-converting enzyme inhibitor (ACEI), angiotensin receptor blocker (ARB) and betablockers was less frequent in hypotensive patients. After a mean 20-month follow-up, all-cause mortality did not differ between hypotensive patients and others. However, mortality in hypotensive patients who did not tolerate ACEI/ARB therapy was significantly higher compared to other hypotensive patients (p = 0.016). Conclusion Hypotension episodes are not uncommon in the sub-acute phase of contemporarily treated STEMI patients with a striking difference between sexes—female sex was the strongest independent predictor of hypotension episodes. Hypotensive episodes may lead to a delay in pharmacotherapy which influences prognosis. Higher incidence of hypotension in women could at least partially explain the sex-related differences in the use of cardiovascular pharmacotherapy which was repeatedly observed in various studies.