OBJECTIVE: To test the hypothesis that in recipients of primary prophylactic implantable cardioverter-defibrillators (ICDs), the non-planarity of ECG vector loops predicts (a) deaths despite ICD protection and (b) appropriate ICD shocks. METHODS: Digital pre-implant ECGs were collected in 1948 ICD recipients: 21.4% females, median age 65 years, 61.5% ischaemic heart disease (IHD). QRS and T wave three-dimensional loops were constructed using singular value decomposition that allowed to measure the vector loop planarity. The non-planarity, that is, the twist of the three-dimensional loops out of a single plane, was related to all-cause mortality (n=294; 15.3% females; 68.7% IHD) and appropriate ICD shocks (n=162; 10.5% females; 87.7% IHD) during 5-year follow-up after device implantation. Using multivariable Cox regression, the predictive power of QRS and T wave non-planarity was compared with that of age, heart rate, left ventricular ejection fraction, QRS duration, spatial QRS-T angle, QTc interval and T-peak to T-end interval. RESULTS: QRS non-planarity was significantly (p<0.001) associated with follow-up deaths despite ICD protection with HR of 1.339 (95% CI 1.165 to 1.540) but was only univariably associated with appropriate ICD shocks. Non-planarity of the T wave loop was the only ECG-derived index significantly (p<0.001) associated with appropriate ICD shocks with multivariable Cox regression HR of 1.364 (1.180 to 1.576) but was not associated with follow-up mortality. CONCLUSIONS: The analysed data suggest that QRS and T wave non-planarity might offer distinction between patients who are at greater risk of death despite ICD protection and those who are likely to use the defibrillator protection.

• MeSH
• Defibrillators, Implantable * adverse effects   MeSH
• Electrocardiography methods   MeSH
• Ventricular Function, Left MeSH
• Myocardial Ischemia * complications   MeSH
• Humans MeSH
• Death, Sudden, Cardiac etiology   prevention & control   MeSH
• Coronary Artery Disease * complications   MeSH
• Risk Factors MeSH
• Aged MeSH
• Arrhythmias, Cardiac diagnosis   therapy   etiology   MeSH
• Stroke Volume MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

Three-dimensional angle between the QRS complex and T wave vectors is a known powerful cardiovascular risk predictor. Nevertheless, several physiological properties of the angle are unknown or poorly understood. These include, among others, intra-subject profiles and stability of the angle relationship to heart rate, characteristics of angle/heart-rate hysteresis, and the changes of these characteristics with different modes of QRS-T angle calculation. These characteristics were investigated in long-term 12-lead Holter recordings of 523 healthy volunteers (259 females). Three different algorithmic methods for the angle computation were based on maximal vector magnitude of QRS and T wave loops, areas under the QRS complex and T wave curvatures in orthogonal leads, and weighted integration of all QRS and T wave vectors moving around the respective 3-dimensional loops. These methods were applied to orthogonal leads derived either by a uniform conversion matrix or by singular value decomposition (SVD) of the original 12-lead ECG, giving 6 possible ways of expressing the angle. Heart rate hysteresis was assessed using the exponential decay models. All these methods were used to measure the angle in 659,313 representative waveforms of individual 10-s ECG samples and in 7,350,733 individual beats contained in the same 10-s samples. With all measurement methods, the measured angles fitted second-degree polynomial regressions to the underlying heart rate. Independent of the measurement method, the angles were found significantly narrower in females (p < 0.00001) with the differences to males between 10o and 20o, suggesting that in future risk-assessment studies, different angle dichotomies are needed for both sexes. The integrative method combined with SVD leads showed the highest intra-subject reproducibility (p < 0.00001). No reproducible delay between heart rate changes and QRS-T angle changes was found. This was interpreted as a suggestion that the measurement of QRS-T angle might offer direct assessment of cardiac autonomic responsiveness at the ventricular level.

• Publication type
• Journal Article MeSH

Aims: Increased spatial angle between QRS complex and T wave loop orientations has repeatedly been shown to predict cardiac risk. However, there is no consensus on the methods for the calculation of the angle. This study compared the reproducibility and predictive power of three most common ways of QRS-T angle assessment. Methods and results: Electrocardiograms of 352 healthy subjects, 941 survivors of acute myocardial infarction (MI), and 605 patients recorded prior to the implantation of automatic defibrillator [implantable cardioverter defibrillator (ICD)] were used to obtain QRS-T angle measurements by the maximum R to T (MRT), area R to T (ART), and total cosine R to T (TCRT) methods. The results were compared in terms of physiologic reproducibility and power to predict mortality in the cardiac patients during 5-year follow-up. Maximum R to T results were significantly less reproducible compared to the other two methods. Among both survivors of acute MI and ICD recipients, TCRT method was statistically significantly more powerful in predicting mortality during follow-up. Among the acute MI survivors, increased spatial QRS-T angle (TCRT assessment) was particularly powerful in predicting sudden cardiac death with the area under the receiver operator characteristic of 78% (90% confidence interval 63-90%). Among the ICD recipients, TCRT also predicted mortality significantly among patients with prolonged QRS complex duration when the spatial orientation of the QRS complex is poorly defined. Conclusion: The TCRT method for the assessment of spatial QRS-T angle appears to offer important advantages in comparison to other methods of measurement. This approach should be included in future clinical studies of the QRS-T angle. The TCRT method might also be a reasonable candidate for the standardization of the QRS-T angle assessment.

• MeSH
• Action Potentials * MeSH
• Defibrillators, Implantable MeSH
• Adult MeSH
• Electric Countershock instrumentation   MeSH
• Electrocardiography * standards   MeSH
• Risk Assessment MeSH
• Myocardial Infarction diagnosis   mortality   physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Death, Sudden, Cardiac epidemiology   MeSH
• Predictive Value of Tests MeSH
• Prognosis MeSH
• Reproducibility of Results MeSH
• Risk Factors MeSH
• Aged MeSH
• Arrhythmias, Cardiac diagnosis   mortality   physiopathology   surgery   MeSH
• Heart Rate * MeSH
• Case-Control Studies MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

Human-secreted Ly-6/uPAR-related protein-2 (SLURP-2) regulates the growth and differentiation of epithelial cells. Previously, the auto/paracrine activity of SLURP-2 was considered to be mediated via its interaction with the α3β2 subtype of the nicotinic acetylcholine receptors (nAChRs). Here, we describe the structure and pharmacology of a recombinant analogue of SLURP-2. Nuclear magnetic resonance spectroscopy revealed a 'three-finger' fold of SLURP-2 with a conserved β-structural core and three protruding loops. Affinity purification using cortical extracts revealed that SLURP-2 could interact with the α3, α4, α5, α7, β2, and β4 nAChR subunits, revealing its broader pharmacological profile. SLURP-2 inhibits acetylcholine-evoked currents at α4β2 and α3β2-nAChRs (IC50 ~0.17 and >3 μM, respectively) expressed in Xenopus oocytes. In contrast, at α7-nAChRs, SLURP-2 significantly enhances acetylcholine-evoked currents at concentrations <1 μM but induces inhibition at higher concentrations. SLURP-2 allosterically interacts with human M1 and M3 muscarinic acetylcholine receptors (mAChRs) that are overexpressed in CHO cells. SLURP-2 was found to promote the proliferation of human oral keratinocytes via interactions with α3β2-nAChRs, while it inhibited cell growth via α7-nAChRs. SLURP-2/mAChRs interactions are also probably involved in the control of keratinocyte growth. Computer modeling revealed possible SLURP-2 binding to the 'classical' orthosteric agonist/antagonist binding sites at α7 and α3β2-nAChRs.

• MeSH
• alpha7 Nicotinic Acetylcholine Receptor metabolism   MeSH
• Cell Line MeSH
• PC12 Cells MeSH
• CHO Cells MeSH
• Cricetulus MeSH
• Adult MeSH
• Epilepsy, Temporal Lobe pathology   MeSH
• Evoked Potentials physiology   MeSH
• GPI-Linked Proteins metabolism   MeSH
• Keratinocytes metabolism   MeSH
• Rats MeSH
• Middle Aged MeSH
• Humans MeSH
• Receptors, Nicotinic metabolism   MeSH
• Nuclear Magnetic Resonance, Biomolecular MeSH
• Oocytes metabolism   MeSH
• Computer Simulation MeSH
• Cell Proliferation physiology   MeSH
• Receptors, Muscarinic metabolism   MeSH
• Protein Binding physiology   MeSH
• Binding Sites physiology   MeSH
• Xenopus MeSH
• Animals MeSH
• Check Tag
• Adult MeSH
• Rats MeSH
• Middle Aged MeSH
• Humans MeSH
• Female MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH

• MeSH
• Lasers MeSH
• Publication type
• Meeting Abstract MeSH
• Collected Work MeSH

• Conspectus
• Optika
• NML Fields
• fyzika, biofyzika
• technika

Abnormální heterogenita elektrických procesů v myokardu zvyšuje riziko maligních arytmií. Cílem studie bylo posoudit změny homogenity repolarizace u pacientů po akutním infarktu myokardu (IM) pomocí nových parametrů získaných z dlouhodobých 12svodových záznamů EKG. Metody: Soubor tvořilo 200 pacientů (45 žen, 155 mužů), kterým byl 48-72 hod po prodělaném IM pořízen 12svodový holterovský záznam (SEER MC, GE Medical) v režimu 10 min vleže. Ze získaných záznamů byly experimentálním softwarem hodnoceny parametry "celkový kosinus R : T" (total cosine R to T - TCRT) a "reziduum T vlny" (T wave residuum - TWR). Výsledky byly korelovány s vývojem Q kmitu a ejekční frakcí (EF) levé komory. Výsledky: Dle typu IM (Q vs nonQ) byly získány následující hodnoty: TCRT: 0,17 +- 0,61 vs 0,16 +- 0,49, p = 0,52, absolutní TWR: 21 200 +- 21 700 vs 25 700 +- 29 300, p = 0,3, relativní TWR: 0,0012 +- 0,0017 vs 0,0017 +- 0,0026, p = 0,28. Dle EF levé komory (<= 40 % vs > 40 %) pak TCRT: -0,03 +- 0,66 vs 0,25 +- 0,54, p = 0,01, absolutní TWR: 29 700 +- 32 400 vs 21 300 +- 21 500, p = 0,14, relativní TWR: 0,0021 +- 0,0047 vs 0,0013 +- 0,0021, p = 0,48. Závěry: TCRT představuje robustní měření prostorového úhlu mezi smyčkou komplexu QRS a smyčkou T vlny a je ve vztahu k EF levé komory. Výsledky TWR mohou naznačovat, že tento parametr je nezávislý na EF, potvrzení však vyžaduje další analýzu na větším souboru.

Abnormal heterogeneity of myocardial electrophysiologic processes increases the risk of malignant arrhythmias. The aim of the studywas to assess changes ofrepolarization homogeneity in patients after acute myocardial infarction (MI) using morphological parameters obtained from long-term 12-lead electrocardiographic recordings. METHODS: In the group of 200 patients (45 females, 155 males) a long-term (10 minutes supine) 12-lead electrocardiographic recording (SEER MC, GE Medical) was performed 48-72 hours after acute myocardial infarction. The following parameters were calculated using experimental software: total cosine R to T (TCRT) and Twave residuum (TWR). The results were correlated with Q wave evolution and left ventricular ejection fraction (LVEF). RESULTS: Distinguishing the MI type (Q vs nonQ) the following values were obtained: TCRT: 0.17 +/- 0.61 vs 0.16 +/- 0.49, p = 0.52, absolute TWR: 21,200 +/- 21,700 vs 25,700 +/- 29,300, p = 0.3, relative TWR: 0.0012 +/- 0.0017 vs 0.0017 +/- 0.0026, p = 0.28. Stratification according to LVEF (< or = 40% vs > 40%) led to: TCRT: -0.03 +/- 0.66 vs 0.25 +/- 0.54, p = 0.01, absolute TWR: 29,700 +/- 32,400 vs 21,300 +/- 21,500, p = 0.14, relative TWR: 0.0021 +/- 0.0047 vs 0.0013 +/- 0.0021, p = 0.48. CONCLUSION: TCRT is a robust measurement of the spatial angle between the QRS complex and T wave loops which is related to LVEF. The results concerning TWR might indicate that this parameter is independent of LVEF, which needs to be confirmed in further analyses in a larger population.

• MeSH
• Electrophysiologic Techniques, Cardiac MeSH
• Electrocardiography, Ambulatory MeSH
• Ventricular Function, Left MeSH
• Myocardial Infarction physiopathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Stroke Volume MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Aged MeSH
• Female MeSH

Východisko. V návaznosti na výsledky našich recentních studií, které zjistily zvýšení QT disperze (QTd) u skupiny těhotných, bylymatematickými postupy hledánymožné geometrické příčiny tohoto nálezu, zejména, zda pozorované změny mohou být důsledkem rotace případně posunu srdce. Metody a výsledky. Byl vytvořen model elektrického pole srdečního, které bylo studováno jako pole časově proměnného dipólu v homogenním prostorovém vodiči. Z experimentálně získaných vektorkardiografických záznamů, reprezentujících časový průběh srdečního dipólu, byly pomocí modelu vypočteny povrchové elektrokardiogramy. Ověření adekvátnosti modelu bylo provedeno srovnáním takto rekonstruovaných elekrokardiogramů s empirickými daty. Pro zjištění vlivu rotace byla originální empirická VKG data kontrolní skupiny transformována ve shodě s předpokládanými či zjištěnými změnami v důsledku těhotenství, proveden výpočet povrchových elektrokardiogramů a ty porovnány s empiricky získanými kardiogramy skupiny těhotných. Závěry. Na základě uvedených výsledků lze odvodit několik závěrů: 1) Na QT disperzi se nutně podílí složka způsobená čistě geometrickými vztahy mezi orientací srdečního vektoru terminální fáze repolarizace a směrem os konkrétního svodového systému. Takto vzniklá disperze má typický výskyt na povrchu hrudníku – minima trvání QT se nacházejí v rovině kolmé na osu svodu terminálního vektoru. 2) Při stanovení trvání repolarizace z klasických hrudních svodů existují v rámci fyziologické variability sklonu elektrické osy orientace terminálního vektoru, z nichž u některých zmíněné minimum trvání QT bude a u jiných nebude zachyceno. Hodnota zjištěné QT disperze mezi těmito dvěma extrémy pak bude významně různá. 3) U horizontálního sklonu srdce bude mít EKG signál ve velké většině svodů systému povrchového mapování vyšší voltáž oproti svodům s vertikálnějším sklonem srdeční osy v důsledku menšího úhlu mezi osami terminálního vektoru a většinou svodů. Tato skutečnost bude přispívat k přesnějšímu odečtu konce vlny T a stanovení trvání QT intervalu, obvykle s menší hodnotou QTd. 4) Změna srdečního pole odpovídající změněné poloze srdce (rotace) sama o sobě nevede ke změně QTd, pokud je tato hodnocena z EKG záznamů z celého hrudníku. Naopak, horizontalizace srdce spíše přispívá ke stanovení nižších hodnot QTd, jak je uvedeno výše. 5) QT disperze zjištěná u souboru těhotných ve vysokém stupni těhotenství je spíše než důsledkem geometrických změn zapříčiněná změnou morfologie T smyčky, která byla u souboru těhotných pozorována. Dalším možným vysvětlením pozorované disperze je nedipolární charakter změn elektrického pole během těhotenství. Naše výsledky svědčí pro hypotézu, že nález QT disperze je v podstatné míře důsledkem rozdílných geometrických poměrů (srdce, hrudníku a detekčního systému) a takto nutně subjektem možných chyb díky ne zcela standardizovanému způsobu měření. Vyvinuté prostředí umožňuje další, podrobnější studium problematiky elektrického pole srdečního.

Background. In concurrence of our recent findings of the elevation of QT dispersion (QTd) in the group of pregnant women, mathematical approaches were developed aimed to give possible geometrical explanation whether the observed changes result from the rotation or from the changed position of the heart. Methods and Results. Mathematical model of the cardiac electrical field approximated as a time variable dipole in a homogenous spatial conductor was developed. From the experimental vectocardiographic records, representing time course of the cardiac dipole, body surface potential maps were calculated on the basis of the model. To validate the adequacy of the model, the reconstructed electrocardiograms were compared with the empiric data. To determine the effects of rotation, original empiric VCG data of the control group were transformed accordingly the hypothetic pregnancy related changes. Calculated surface electrocardiograms were then compared with empiric cardiograms of the pregnant women. Conclusions. Based on the results, several conclusions can be drawn: 1) QT dispersion is associated also with the geometrical relations between the direction of cardiac vector during the terminal phase of repolarization and the direction of axes in the given system of leads. The dispersion then has its typical occurrence at the thoracic surface – minimums of the QT duration are found in the plane perpendicular to the axis of the terminal vector lead. 2) When the duration of repolarization is estimated from the classic thoracic leads within the phisiological variations of terminal–depolarization vector orientations, can exist that in some cases the minimum of QT interval is and in others it is not recorded by the lead system. Value of QT dispersion between these two extremes will be significantly different. 3) In case of the horizontal declination of the heart, the ECG signal in most of the leads of the body surface mapping has a higher voltage than in case of vertical declination due to a smaller angle between axes of the terminal vector and most of the leads. Such factwill contribute tomore accurate reading of the T wave end and to the estimation of QT interval, usually with smaller value of QTd. 4) The change of the cardiac electrical field corresponding to the changed position of the heart (rotation) does not result by itself in QTd changes, if it is evaluated from the records from the whole thorax. Obversely, horizontalization of the heart contributes more to the evaluation of lower QTd values, as it is given above. 5) More then the result of geometrical changes, QT dispersion found in the group women in high level of pregnancy is an effect of changes in the T loop morphology, which was observed in this group. Another possible explanation of the observed dispersion is the non-dipolar character of the electrical field changes during pregnancy.

• MeSH
• Electrophysiologic Techniques, Cardiac MeSH
• Electrocardiography MeSH
• Computer Simulation MeSH
• Long QT Syndrome MeSH

• MeSH
• Physical Phenomena MeSH
• Magnetic Resonance Imaging MeSH

• Conspectus
• Patologie. Klinická medicína
• NML Fields
• radiologie, nukleární medicína a zobrazovací metody
• NML Publication type
• kolektivní monografie

• MeSH
• Physiological Phenomena MeSH
• Publication type
• Textbook MeSH

• Conspectus
• Fyziologie člověka a srovnávací fyziologie
• NML Fields
• fyziologie