Cardiac repolarization
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INTRODUCTION: A variable proportion of non-responders to cardiac resynchronization therapy (CRT) warrants the search for new approaches to optimize the position of the left ventricular (LV) lead and the CRT device programming. CineECG is a novel ECG modality proposed for the spatial visualization and quantification of myocardial depolarization and repolarization sequences. OBJECTIVE: The present study aimed to evaluate CineECG-derived parameters in different pacing modes and to test their associations with acute hemodynamic responses in CRT patients. METHODS AND RESULTS: CineECG was used to construct the average electrical path within the cardiac anatomy from the 12-lead ECG. CineECG and LV dP/dt max were tested in 15 patients with nonischemic dilated cardiomyopathy and left bundle branch block (QRS: 170 ± 17 ms; LVEF: 26 ± 5.5%) under pacing protocols with different LV lead localizations. The CineECG-derived path directions were computed for the QRS and ST-T intervals for the anteroposterior (Xh), interventricular (Yh), and apicobasal (Zh) axes. In a multivariate linear regression analysis with adjustment for the pacing protocol type, the ST-T path direction Yh was independently associated with the increase in dP/dt max during CRT, [regression coefficient 639.4 (95% confidence interval: 187.9-1090.9), p = 0.006]. In ROC curve analysis, the ST-T path direction Yh was associated with the achievement of a 10% increase in dP/dt max (AUC: 0.779, p = 0.002) with the optimal cut-off > 0.084 (left-to-right direction) with sensitivity 0.67 and specificity 0.92. CONCLUSION: The acute hemodynamic response in CRT patients was associated with specific CineECG repolarization sequence parameters, warranting their further testing as potential predictors of clinical outcomes.
- Klíčová slova
- cardiac resynchronization therapy, heart failure, hemodynamics, multipoint pacing, multisite pacing, repolarization,
- MeSH
- elektrokardiografie * MeSH
- hemodynamika MeSH
- kontrakce myokardu MeSH
- lidé středního věku MeSH
- lidé MeSH
- prospektivní studie MeSH
- prostředky srdeční resynchronizační terapie * MeSH
- senioři MeSH
- srdeční resynchronizační terapie * metody MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
OBJECTIVE: Sepsis has been defined as the systemic host response to infection with an overwhelming systemic production of both proinflammatory and anti-inflammatory mediators. Continuous hemofiltration has been suggested as possible therapeutic option that may remove the inflammatory mediators. However, hemodialysis and hemofiltration were reported to influence cardiac electrophysiologic parameters and to increase the arrhythmogenic risk. We hypothesize that sepsis affects electrophysiologic properties of the pig heart and that the effects of sepsis are modified by hemofiltration. DESIGN: Laboratory animal experiments. SETTING: Animal research laboratory at university medical school. SUBJECTS: Forty domestic pigs of either gender. INTERVENTIONS: In anesthetized, mechanically ventilated, and instrumented pigs sepsis was induced by fecal peritonitis and continued for 22 hours. Conventional or high-volume hemofiltration was applied for the last 10 hours of this period. MEASUREMENTS AND MAIN RESULTS: Electrocardiogram was recorded before and 22 hours after induction of peritonitis. RR, QT, and QTc intervals were significantly shortened by sepsis. The plasma levels of interleukin-6 and tumor necrosis factor-alpha were increased in sepsis. High-volume hemofiltration blunted the sepsis-induced increase in tumor necrosis factor-alpha. Action potentials were recorded in isolated ventricular tissues obtained at the end of in vivo experiments. Action potential durations were significantly shortened in septic preparations at all stimulation cycle lengths tested. Both conventional and high-volume hemofiltrations lead to further shortening of action potential durations measured afterward in vitro. This action potential duration shortening was reversed by septic hemofiltrates obtained previously by conventional or high-volume hemofiltration. Tumor necrosis factor-alpha (500 ng/L) had no effect on action potential durations in vitro. CONCLUSIONS: In a clinically relevant porcine model of hyperdynamic septic shock, both sepsis and continuous hemofiltration shortened duration of cardiac repolarization. The continuous hemofiltration was not associated with an increased prevalence of ventricular arrhythmias. Tumor necrosis factor-alpha or interleukin-6 did not contribute to the observed changes in action potential durations.
- MeSH
- akční potenciály MeSH
- elektrokardiografie MeSH
- hemodynamika MeSH
- hemofiltrace * MeSH
- interleukin-6 biosyntéza MeSH
- modely nemocí na zvířatech MeSH
- septický šok metabolismus patofyziologie terapie MeSH
- srdce - funkce komor MeSH
- srdce patofyziologie MeSH
- srdeční arytmie patofyziologie prevence a kontrola MeSH
- Sus scrofa MeSH
- TNF-alfa biosyntéza MeSH
- umělé dýchání MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- interleukin-6 MeSH
- TNF-alfa MeSH
BACKGROUND: Myocardial ischemic electrophysiological alterations are associated with the generation of reactive oxygen species. However, electrophysiological effects of antioxidants are unclear. Our objective was to determine the effects of the antioxidant echinochrome on ventricular repolarization in a feline model of 30-min ischemia. METHODS AND RESULTS: Activation-recovery intervals were measured from 64 ventricular electrograms recorded before and during the LAD ligation in untreated animals (controls, n=5) and animals given echinochrome (1mg/kg, n=5 and 2mg/kg, n=7). In controls, ischemia resulted in the increase of repolarization dispersion, QTc and Tpeak-Tend intervals and precordial T wave amplitude dispersion. Echinochrome attenuated the ischemic increase of repolarization dispersion. The increased dose of echinochrome abolished the ischemic ECG repolarization changes but did not modify the incidence of ventricular arrhythmias. CONCLUSION: Echinochrome modified ischemic alterations of repolarization dispersion that were associated with the changes of the body surface T wave amplitude dispersion and Tpeak-Tend interval.
- Klíčová slova
- Animal model, Antioxidant, Ischemia, Repolarization,
- MeSH
- akční potenciály účinky léků MeSH
- elektrokardiografie * MeSH
- ischemická choroba srdeční farmakoterapie MeSH
- kočky MeSH
- modely nemocí na zvířatech MeSH
- naftochinony farmakologie MeSH
- převodní systém srdeční účinky léků MeSH
- srdeční komory účinky léků MeSH
- zvířata MeSH
- Check Tag
- kočky MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- echinochrome A MeSH Prohlížeč
- naftochinony MeSH
BACKGROUND: The early repolarization (ER) pattern is associated with an increased risk of arrhythmogenic sudden death. However, strategies for risk stratification of patients with the ER pattern are not fully defined. OBJECTIVES: This study sought to determine the role of electrophysiology studies (EPS) in risk stratification of patients with ER syndrome. METHODS: In a multicenter study, 81 patients with ER syndrome (age 36 ± 13 years, 60 males) and aborted sudden death due to ventricular fibrillation (VF) were included. EPS were performed following the index VF episode using a standard protocol. Inducibility was defined by the provocation of sustained VF. Patients were followed up by serial implantable cardioverter-defibrillator interrogations. RESULTS: Despite a recent history of aborted sudden death, VF was inducible in only 18 of 81 (22%) patients. During follow-up of 7.0 ± 4.9 years, 6 of 18 (33%) patients with inducible VF during EPS experienced VF recurrences, whereas 21 of 63 (33%) patients who were noninducible experienced recurrent VF (p = 0.93). VF storm occurred in 3 patients from the inducible VF group and in 4 patients in the noninducible group. VF inducibility was not associated with maximum J-wave amplitude (VF inducible vs. VF noninducible; 0.23 ± 0.11 mV vs. 0.21 ± 0.11 mV; p = 0.42) or J-wave distribution (inferior, odds ratio [OR]: 0.96 [95% confidence interval (CI): 0.33 to 2.81]; p = 0.95; lateral, OR: 1.57 [95% CI: 0.35 to 7.04]; p = 0.56; inferior and lateral, OR: 0.83 [95% CI: 0.27 to 2.55]; p = 0.74), which have previously been demonstrated to predict outcome in patients with an ER pattern. CONCLUSIONS: Our findings indicate that current programmed stimulation protocols do not enhance risk stratification in ER syndrome.
- Klíčová slova
- early repolarization, sudden cardiac death, ventricular fibrillation,
- MeSH
- časové faktory MeSH
- dospělí MeSH
- elektrokardiografie metody MeSH
- fibrilace komor komplikace diagnóza patofyziologie MeSH
- incidence MeSH
- lidé MeSH
- míra přežití trendy MeSH
- náhlá srdeční smrt epidemiologie etiologie prevence a kontrola MeSH
- následné studie MeSH
- prediktivní hodnota testů MeSH
- převodní systém srdeční patofyziologie MeSH
- prognóza MeSH
- retrospektivní studie MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Evropa epidemiologie MeSH
BACKGROUND: Cardiac repolarization is assessed by the QT interval on the surface electrocardiogram and varies with the heart rate. Standard QT corrections (QTc) do not account for the lag in QT change following a change in heart rate (QT hysteresis). Our group has developed and tested a transfer function (TRF) model to assess the effectiveness of a dynamic model of QT/RR coupling in eliminating hysteresis. METHODS: We studied three groups: group I, healthy volunteers (n = 23, 41 ± 17 years); group II, hypertensive patients (n = 25, 45 ± 11 years); and group III, patients in a predominately paced rhythm (n = 5, 75 ± 6 years). To vary the heart rate, either exercise bicycling in the supine position (groups I and II) or manipulation of the pacemaker parameters (group III) was done. We then compared a dynamic TRF model with a model based on weighted averages of previous RR intervals. Two parameters were tested: root mean square (RMS) of the error signal between measured and computed QT and the elimination of hysteretic loops. RESULTS: TRF-based measurements eliminated hysteresis in 22/23 (95%) group I patients, 21/25 (84%) group II patients, and 4/5 (80%) group III patients. When hysteresis elimination was not complete, the QT drift that followed RR intervals was different before and after bicycling (100 ms). In these patients, the corresponding QT interval did not significantly change during this period. The TRF model was found superior to the other tested models with respect to both analyzed parameters (RMS and hysteresis elimination). CONCLUSION: The TRF model limited QT hysteresis in healthy, hypertensive, and pacemaker-dependent patients. In addition, an important finding of QT drift in patients with hypertension was identified. With further study in these and other diseased states, the TRF model may improve our ability to measure accurately cardiac repolarization and to determine arrhythmia risk.
- MeSH
- dospělí MeSH
- elektrokardiografie * MeSH
- hodnocení rizik MeSH
- hypertenze diagnóza patofyziologie MeSH
- kardiostimulace umělá metody MeSH
- kardiostimulátor * MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- modely kardiovaskulární MeSH
- následné studie MeSH
- převodní systém srdeční patofyziologie MeSH
- referenční hodnoty MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- srdeční frekvence fyziologie MeSH
- syndrom dlouhého QT diagnóza terapie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
The aim was to investigate effects of continuous hemofiltration (CHF) and of coupled plasma filtration adsorption (CPFA) on electrophysiological properties of the septic heart. Sepsis was induced in anesthetized pigs by fecal peritonitis and continued for 22 h either without intervention (control sepsis) or with intervention (CHF or CPFA) applied for the last 10 h of this period. Electrocardiograms were recorded at baseline, before induction of peritonitis, and 22 h later, at the end of in vivo experiment. In vitro, action potentials were recorded in right ventricular trabeculae. RR, QT, and QTc (QT corrected for heart rate) intervals were shortened by sepsis. Action potential durations (APDs) were shortened by CHF, but not by CPFA, compared with control sepsis. Continuous hemofiltration prolonged APD. Coupled plasma filtration adsorption filtrate did not exert any effect on APD. Plasma separated during CPFA prolonged APD. Continuous hemofiltration shortened cardiac repolarization, and this effect was reversed by the hemofiltrate. In contrast, neither CPFA nor the CPFA filtrate influenced APD. The data indicate that some inflammatory mediators able to delay cardiac repolarization were removed from plasma to hemofiltrate by CHF but not by CPFA.
- MeSH
- akční potenciály MeSH
- elektrofyziologie MeSH
- hemodynamika MeSH
- hemofiltrace * MeSH
- peritonitida komplikace patofyziologie MeSH
- prasata MeSH
- septický šok metabolismus patofyziologie terapie MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.
- MeSH
- celogenomová asociační studie metody MeSH
- dospělí MeSH
- elektrokardiografie metody MeSH
- genetická predispozice k nemoci MeSH
- genotyp MeSH
- jednonukleotidový polymorfismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- myokard metabolismus MeSH
- náhlá srdeční smrt etiologie MeSH
- senioři MeSH
- srdeční arytmie genetika metabolismus MeSH
- srdeční komory metabolismus MeSH
- syndrom dlouhého QT genetika metabolismus MeSH
- vápníková signalizace genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- metaanalýza MeSH
Effects of ectopic pacing on left ventricular repolarization were studied in six anesthetized open-chest chickens. In each animal, unipolar electrograms were acquired from as many as 98 sites with 14 plunge needles (seven transmural locations between epicardium and endocardium in each needle). Activation-recovery intervals (ARIs), corrected to the cycle length, were used for estimating repolarization. At baseline, the nonuniform ARI distribution in the left ventricle resulted in the apicobasal differences being greater than the transmural gradient. Nonuniform ARI prolongation caused by ectopic pacing resulted in decreasing the transmural repolarization gradient and increasing the differences in the apex-to-base direction. The basal, but not apical transmural differences contributed to the total left ventricular transmural gradient. The total left ventricular apicobasal gradient was contributed by the apicobasal differences in mid-myocardial and subendocardial layers more than in subepicardial ones. Thus, in in situ chicken hearts, the transmural and apicobasal ARI gradients exist within the left ventricle with the shortest ARIs in the basal subepicardium and the longest ARIs in the subendocardium of the apical and middle parts of the left ventricle. Apicobasal compared to transmural heterogeneity of local repolarization properties contributes more to the total left ventricular repolarization gradient.
- MeSH
- akční potenciály MeSH
- časové faktory MeSH
- elektrokardiografie MeSH
- endokard fyziologie MeSH
- funkce levé komory srdeční * MeSH
- kardiostimulace umělá * MeSH
- kur domácí MeSH
- perikard fyziologie MeSH
- převodní systém srdeční fyziologie MeSH
- srdeční frekvence * MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The role of a border zone in arrhythmogenesis is not fully understood. In this study we evaluated independent contributions of action potential duration (APD) and dispersion of repolarization (DOR) across the normal/ischemic border to the development of ventricular tachycardia and/or fibrillation (VT/VF). Ischemia-reperfusion episodes were induced in anesthetized rats by transient coronary occlusion. Unipolar electrograms were recorded from ischemic and perfused areas using a 64-lead array to obtain activation times (ATs), repolarization times (RTs), activation-repolarization intervals (ARIs, a surrogate for APD) and dispersion of repolarization (DOR, as a difference between the earliest and latest RTs). Pinacidil (0.3 mg/kg) and glibenclamide (2 mg/kg) were applied to reduce DOR and to clamp APD at a lower and upper levels, respectively. In the control animals, APD shortened in the ischemic zone, DOR increased to 9 ± 3 ms, and VT/VF developed at reperfusion (6 out of 10). Pre-occlusion application of glibenclamide prolonged APD in the ischemic and perfused zones, decreased DOR to 5 ± 2 ms and did not affect VT/VF development (4 out of 11). Post-occlusion infusion of pinacidil shortened APD in the perfused zone, decreased DOR to 6 ± 3 ms and VT/VF incidence (2 out of 11). Extrasystolic burden at reperfusion was associated with VT/VF incidence in logistic regression analysis (β = 1.182, 95%CI 1.008 - 1.386, p = 0.04) and was lesser (p < 0.01) in the pinacidil group as compared to the control and glibenclamide groups. In conclusion, the results of this study suggest that the APDs in the perfused zone were a superior arrhythmogenic factor in respect to DOR in the present ischemia-reperfusion model.
- MeSH
- akční potenciály MeSH
- fibrilace komor MeSH
- komorová tachykardie * MeSH
- krysa rodu Rattus MeSH
- reperfuze MeSH
- srdce MeSH
- srdeční arytmie * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Cardiac repolarization is prolonged in diabetes mellitus (DM), however the distribution of repolarization durations in diabetic hearts is unknown. We estimated the ventricular repolarization pattern and its relation to the ECG phenomena in diabetic mice. Potential mapping was performed on the anterior ventricular surface in healthy (n=18) and alloxan-induced diabetic (n=12) mice with the 64-electrode array. Activation times, end of repolarization times, and activation-recovery intervals (ARIs) were recorded along with limb lead ECGs. ARIs were shorter in the left as compared to right ventricular leads (P<0.05). The global dispersion of repolarization, interventricular and apicobasal repolarization gradients were greater in DM than in healthy animals (P<0.03). The increased dispersion of repolarization and apicobasal repolarization gradient in DM correlated with the prolonged QTc and Tpeak-Tend intervals, respectively. The increased ventricular repolarization heterogeneity corresponded to the electrocardiographic markers was demonstrated in DM.
- MeSH
- akční potenciály MeSH
- alloxan farmakologie MeSH
- diabetes mellitus patofyziologie MeSH
- elektrokardiografie MeSH
- experimentální diabetes mellitus patofyziologie MeSH
- myši MeSH
- srdce - funkce komor fyziologie MeSH
- srdeční komory metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- alloxan MeSH