Electrocardiographic temporo-spatial assessment of depolarization and repolarization changes after epicardial arrhythmogenic substrate ablation in Brugada syndrome
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PROVIDER: S-EPMC10689926 | biostudies-literature | 2023 Sep
REPOSITORIES: biostudies-literature
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Project description:AimsTo evaluate the relationship between spatial heterogeneity of electrocardiographic repolarization and spatial heterogeneity of atrial depolarization with arrhythmic substrate represented by left ventricular fibrosis.Methods and resultsWe assessed the associations of T- and P-wave morphology parameters analysed from the standard 12-lead electrocardiograms with left ventricular fibrosis in 378 victims of unexpected sudden cardiac death (SCD) who underwent medico-legal autopsy. Based on autopsy findings, the SCD victims were categorized into four different groups according to different stages of severity of left ventricular fibrosis (substantial fibrosis, moderate patchy fibrosis, scattered mild fibrosis, no fibrosis). T-wave and P-wave area dispersion (TWAd: 0.0841 ± 0.496, 0.170 ± 0.492, 0.302 ± 404, 0.296 ± 0.476, P = 0.008; PWAd: 0.574 ± 0.384, 0.561 ± 0.367, 0.654 ± 0.281, 0.717 ± 0.257, P = 0.011, respectively; low values abnormal), non-dipolar components of T-wave and P-wave morphology (T_NonDipolarABS: 0.0496 ± 0.0377, 0.0571 ± 0.0487, 0.0432 ± 0.0476, 0.0380 ± 0.0377, P = 0.027; P_NonDipolarABS: 0.0132 ± 0.0164, 0.0130 ± 0.0135, 0.0092 ± 0.0117, 0.0069 ± 0.00472, P = 0.005, respectively, high values abnormal), T-wave morphology dispersion (TMD: 45.9 ± 28.3, 40.5 ± 25.8, 35.5 ± 24.9, 33.0 ± 24.6, P = 0.030, respectively, high values abnormal), and P-wave heterogeneity (PWH: 20.0 ± 9.44, 19.7 ± 8.87, 17.9 ± 9.78, 15.4 ± 4.60, P = 0.019, respectively, high values abnormal) differed significantly between the groups with different stages of left ventricular fibrosis. After adjustment with heart weight, T_NonDipolarABS [standardized β (sβ) = 0.131, P = 0.014], PWAd (sβ = -0.161, P = 0.003), P_NonDipolarABS (sβ = 0.174, P = 0.001), and PWH (sβ = 0.128, P = 0.015) retained independent association, and TWAd (sβ = -0.091, P = 0.074) and TMD (sβ = 0.097, P = 0.063) tended to retain their association with the degree of myocardial fibrosis.ConclusionOur findings suggest that abnormal values of T- and P-wave morphology are associated with arrhythmic substrate represented by ventricular fibrosis partly explaining the mechanism behind their prognostic significance.
| S-EPMC10062366 | biostudies-literature
Project description: Not available
| S-EPMC6007146 | biostudies-literature
Project description:The Brugada syndrome (BrS) is a cardiac arrhythmic disorder responsible for sudden cardiac death associated with the onset of ventricular arrhythmias, such as reentrant ventricular tachycardia and fibrillation. The mechanisms which lead to the onset of such electrical disorders in patients affected by BrS are not completely understood, yet. The aim of the present study is to investigate by means of numerical simulations the electrophysiological mechanisms at the basis of the morphology of electrocardiogram (ECG) and the onset of reentry associated with BrS. To this end, we consider the Bidomain equations coupled with the ten Tusscher-Panfilov membrane model, on an idealized wedge of human right ventricular tissue. The results have shown that: (1) epicardial dispersion of repolarization, generated by the coexistence of regions of early and late repolarization, due to different modulation of the [Formula: see text] current, produces ECG waveforms exhibiting qualitatively the typical BrS morphology, characterized by ST elevation and partially negative T-waves; (2) epicardial dispersion of repolarization promotes the onset of reentry during the implementation of the programmed stimulation protocol, because of the conduction block occurring when a premature beat reaches the border of late repolarizing regions; and (3) the modulation of the [Formula: see text] current affects the duration of reentry, which becomes sustained with a remarkable increase of [Formula: see text] in the subepicardial layers.
| S-EPMC9931802 | biostudies-literature
Project description:Abstract Background Brugada Syndrome (BrS) is a cardiogenetic disease known for its association with sudden cardiac death (SCD) in individuals with structurally normal hearts. The prevalence of BrS is higher in males, who also face a greater risk of SCD. Its higher prevalence and worse outcome in male subjects may be due to testosterone effects on ion channels expression and function. The influence of testosterone on cardiac action potentials, both genomically and non-genomically, underscores its potential role in unmasking the syndrome and triggering life-threatening arrhythmias. Notably, testosterone replacement therapy (TRT), used for hypogonadism and gender reassignment, has been linked to BrS unmasking. The role of epicardial ablation in symptomatic BrS patients where hormonal therapy cannot be discontinued is unknown. Methods and results In this study we describe the first two cases of substrate mapping and ablation in BrS patients experiencing arrhythmic events while on TRT. In both cases, high-density epicardial mapping revealed abnormal areas of prolonged and fragmented electrograms in the right ventricular (RV) outflow tract and anterior wall. These abnormalities were completely abolished by radiofrequency ablation (RFA). After ablation, both patients showed a persistent normalization of the ECG and were free from ventricular arrhythmias at follow-up, despite ongoing TRT. Conclusion RFA can be considered as a therapeutic option in symptomatic BrS patients with a high-risk profile who cannot discontinue TRT, being essential for restoring their normal physiology or preserving their sexual identity. As testosterone use is increasing, further studies are warranted to define a standardized diagnostic and therapeutic strategy in this specific subset of BrS patients. Graphical Abstract Graphical Abstract
| S-EPMC10472325 | biostudies-literature
Project description: Not available
| S-EPMC10716613 | biostudies-literature
Project description:ObjectivesThis study sought to test the hypothesis that elimination of sites of abnormal repolarization, via epicardial RFA, suppresses the electrocardiographic and arrhythmic manifestations of BrS.BackgroundBrugada syndrome (BrS) is associated with ventricular tachycardia and ventricular fibrillation leading to sudden cardiac death. Nademanee et al. reported that radiofrequency ablation (RFA) of right ventricular outflow tract epicardium significantly reduced the electrocardiogram and arrhythmic manifestations of BrS. These authors concluded that low-voltage fractionated electrogram activity and late potentials are caused by conduction delay within the right ventricular outflow tract and that the ameliorative effect of RFA is caused by elimination of this substrate. Szel et al. recently demonstrated that the abnormal electrogram activity is associated with repolarization defects rather than depolarization or conduction defects.MethodsAction potentials (AP), electrograms, and pseudoelectrocardiogram were simultaneously recorded from coronary-perfused canine right ventricular wedge preparations. Two pharmacological models were used to mimic BrS genotype: combination of INa blocker ajmaline (1 to 10 μM) and IK-ATP agonist pinacidil (1 to 5 μM); or combination of Ito agonist NS5806 (4 to 10 μM) and ICa blocker verapamil (0.5 to 2 μM). After stable induction of abnormal electrograms and arrhythmic activity, the preparation was mapped and epicardial RFA was applied.ResultsFractionated low-voltage electrical activity was observed in right ventricular epicardium but not endocardium as a consequence of heterogeneities in the appearance of the second upstroke of the epicardial AP. Discrete late potentials developed as a result of delay of the second upstroke of the AP and of concealed phase 2 re-entry. Epicardial RFA of these abnormalities normalized Brugada pattern and abolished arrhythmic activity, regardless of the pharmacological model used.ConclusionsOur results suggest that epicardial RFA exerts its ameliorative effect in the setting of BrS by destroying the cells with the most prominent AP notch, thus eliminating sites of abnormal repolarization and the substrate for ventricular tachycardia ventricular fibrillation.
| S-EPMC5609479 | biostudies-literature
Project description:Background Dispersion and gradients in repolarization have been associated with life-threatening arrhythmias, but are difficult to quantify precisely from surface electrocardiography. The objective of this study was to evaluate electrocardiographic imaging (ECGI) to noninvasively detect repolarization-based abnormalities. Methods and Results Ex vivo data were obtained from Langendorff-perfused pig hearts (n=8) and a human donor heart. Unipolar electrograms were recorded simultaneously during sinus rhythm from an epicardial sock and the torso-shaped tank within which the heart was suspended. Regional repolarization heterogeneities were introduced through perfusion of dofetilide and pinacidil into separate perfusion beds. In vivo data included torso and epicardial potentials recorded simultaneously in anesthetized, closed-chest pigs (n=5), during sinus rhythm, and ventricular pacing. For both data sets, ECGI accurately reconstructed T-wave electrogram morphologies when compared with those recorded by the sock (ex vivo: correlation coefficient, 0.85 [0.52-0.96], in vivo: correlation coefficient, 0.86 [0.52-0.96]) and repolarization time maps (ex-vivo: correlation coefficient, 0.73 [0.63-0.83], in vivo: correlation coefficient, 0.76 [0.67-0.82]). ECGI-reconstructed repolarization time distributions were strongly correlated to those measured by the sock (both data sets, R2 ≥0.92). Although the position of the gradient was slightly shifted by 8.3 (0-13.9) mm, the mean, max, and SD between ECGI and recorded gradient values were highly correlated (R2=0.87, 0.75, and 0.86 respectively). There was no significant difference in ECGI accuracy between ex vivo and in vivo data. Conclusions ECGI reliably and accurately maps potentially critical repolarization abnormalities. This noninvasive approach allows imaging and quantifying individual parameters of abnormal repolarization-based substrates in patients with arrhythmogenesis, to improve diagnosis and risk stratification.
| S-EPMC8200734 | biostudies-literature
Project description:AimsThe long-QT syndrome (LQTS) represents a leading cause of sudden cardiac death (SCD). The aim of this study was to assess the presence of an underlying electroanatomical arrhythmogenic substrate in high-risk LQTS patients.Methods and resultsThe present study enrolled 11 consecutive LQTS patients who had experienced frequent implantable cardioverter-defibrillator (ICD discharges triggered by ventricular fibrillation (VF). We acquired electroanatomical biventricular maps of both endo and epicardial regions for all patients and analyzed electrograms sampled from several myocardial regions. Abnormal electrical activities were targeted and eliminated by the means of radiofrequency catheter ablation. VF episodes caused a median of four ICD discharges in eleven patients (6 male, 54.5%; mean age 44.0 ± 7.8 years, range 22-53) prior to our mapping and ablation procedures. The average QTc interval was 500.0 ± 30.2 ms. Endo-epicardial biventricular maps displayed abnormally fragmented, low-voltage (0.9 ± 0.2 mV) and prolonged electrograms (89.9 ± 24.1 ms) exclusively localized in the right ventricular epicardium. We found electrical abnormalities extending over a mean epicardial area of 15.7 ± 3.1 cm2. Catheter ablation of the abnormal epicardial area completely suppressed malignant arrhythmias over a mean 12 months of follow-up (median VF episodes before vs. after ablation, 4 vs. 0; P = 0.003). After the procedure, the QTc interval measured in a 12-lead ECG analysis shortened to a mean of 461.8 ± 23.6 ms (P = 0.004).ConclusionThis study reveals that, among high-risk LQTS patients, regions localized in the epicardium of the right ventricle harbour structural electrophysiological abnormalities. Elimination of these abnormal electrical activities successfully prevented malignant ventricular arrhythmia recurrences.
| S-EPMC10062343 | biostudies-literature
Project description:The solution of the inverse problem of electrocardiology allows the reconstruction of the spatial distribution of the electrical activity of the heart from the body surface electrocardiogram (electrocardiographic imaging, ECGI). ECGI using the equivalent dipole layer (EDL) model has shown to be accurate for cardiac activation times. However, validation of this method to determine repolarization times is lacking. In the present study, we determined the accuracy of the EDL model in reconstructing cardiac repolarization times, and assessed the robustness of the method under less ideal conditions (addition of noise and errors in tissue conductivity). A monodomain model was used to determine the transmembrane potentials in three different excitation-repolarization patterns (sinus beat and ventricular ectopic beats) as the gold standard. These were used to calculate the body surface ECGs using a finite element model. The resulting body surface electrograms (ECGs) were used as input for the EDL-based inverse reconstruction of repolarization times. The reconstructed repolarization times correlated well (COR > 0.85) with the gold standard, with almost no decrease in correlation after adding errors in tissue conductivity of the model or noise to the body surface ECG. Therefore, ECGI using the EDL model allows adequate reconstruction of cardiac repolarization times. Graphical abstract Validation of electrocardiographic imaging for repolarization using forward calculated body surface ECGs from simulated activation-repolarization sequences.
| S-EPMC7340677 | biostudies-literature
Project description:A prominent J wave is encountered in a number of life-threatening cardiac arrhythmia syndromes, including the Brugada syndrome and early repolarization syndromes. Brugada syndrome and early repolarization syndromes differ with respect to the magnitude and lead location of abnormal J waves and are thought to represent a continuous spectrum of phenotypic expression termed J-wave syndromes. Despite two decades of intensive research, risk stratification and the approach to therapy of these 2 inherited cardiac arrhythmia syndromes are still undergoing rapid evolution. Our objective in this review is to provide an integrated synopsis of the clinical characteristics, risk stratifiers, and molecular, ionic, cellular, and genetic mechanisms underlying these 2 fascinating syndromes that have captured the interest and attention of the cardiology community in recent years.
| S-EPMC4737709 | biostudies-literature