Steep repolarization time gradients in pig hearts cause distinct changes in composite electrocardiographic T-wave parameters.

BACKGROUND: The T wave of the electrocardiogram (ECG) reflects ventricular repolarization. Repolarization heterogeneity is associated with reentrant arrhythmias. Several T-wave markers (including QT interval) have been associated with ventricular arrhythmias, but studies linking such markers to underlying local repolarization time (RT) inhomogeneities are lacking. We aimed to investigate the relation of several T-wave markers to controlled drug-induced regional RT gradients in intact pig hearts. METHODS: Repolarization time gradients were created by regional infusion of dofetilide and pinacidil in four atrially paced porcine Langendorff-perfused hearts placed inside a torso tank. From the 12-lead ECG on the torso tank, the mean, maximum, and dispersion (max-min) of QTtime , JTtime , Tpeak-end , Twidth , TQratio , dV/dtmax , Tarea , Tamp , and T-upslope duration were determined, as well as upslope end difference between leads V1 and V6 . RESULTS: Temporal T-wave parameters Tpeak-end , Twidth, and TQratio show a significant and high correlation with RT gradient, best reflected by mean value. Tarea (mean, max and dispersion) and dV/dtmax dispersion show only a moderate significant correlation. T-upslope duration shows a significant correlation in particular for mean values. Mean, maximum, or dispersion of QTtime and V1 -V6 upslope end difference were not significantly correlated with RT gradient. CONCLUSION: Composite 12-lead ECG T-wave parameters Tpeak-end , Twidth , TQratio , upslope duration, and Tarea show a good correlation with underlying RT heterogeneity, whereas standard clinical metrics such as QTtime do not reflect local RT heterogeneity. The composite T-wave metrics may thus provide better insights in arrhythmia susceptibility than traditional QTtime metrics.

Adaptation of ventricular repolarization dispersion during heart rate increase in humans: A roller coaster process.

BACKGROUND: Regional differences in ventricular activation sequence and action potential duration and morphology result in dispersion in ventricular repolarization (VR). VR dispersion is a key factor in arrhythmogenesis. We studied the adaptation of global VR dispersion in humans during normal and abnormal ventricular activation, and the relation to the QT adaptation (hysteresis). METHODS: We measured global VR dispersion as T amplitude, T area, and ventricular gradient (VG), using continuous Frank vectorcardiography, in response to abrupt and sustained atrial (AP) or ventricular pacing (VP) aiming at 120 bpm, in 21 subjects with permanent pacemakers. RESULTS: Following pacing start, VR adaptation showed an initially rapid and complex tri-phasic pattern, most pronounced for T amplitude. There were major differences in the patterns of VR dispersion adaptation following abrupt AP vs VP, confirming that the adaptation pattern is activation dependent. In response to AP, an instantaneous decrease in VR dispersion occurred, followed by an increase and then a slow decrease, all at a lower level than baseline. In contrast, following VP there was an immediate increase to ~4× baseline in T amplitude and T area (but not in VG), with a subsequent biphasic adaptation lasting longer during VP than AP. The initial rapid changes occurred within the time for QT adaptation to reach steady-state. CONCLUSIONS: Our results corroborate and expand data from animal and invasive human studies, showing similarities of the adaptation pattern on different scales. The initial rapidly changing VR adaptation phase presumably reflects a window of increased vulnerability to arrhythmias.

The detection of T-wave variation linked to arrhythmic risk: an industry perspective.

Although the scientific literature contains ample descriptions of peculiar patterns of repolarization linked to arrhythmic risk, the objective quantification and classification of these patterns continues to be a challenge that impacts their widespread adoption in clinical practice. To advance the science, computerized algorithms spawned in the academic environment have been essential in order to find, extract and measure these patterns. However, outside the strict control of a core lab, these algorithms are exposed to poor quality signals and need to be effective in the presence of different forms of noise that can either obscure or mimic the T-wave variation (TWV) of interest. To provide a practical solution that can be verified and validated for the market, important tradeoffs need to be made that are based on an intimate understanding of the end-user as well as the key characteristics of either the signal or the noise that can be used by the signal processing engineer to best differentiate them. To illustrate this, two contemporary medical devices used for quantifying T-wave variation are presented, including the modified moving average (MMA) for the detection of T-wave Alternans (TWA) and the quantification of T-wave shape as inputs to the Morphology Combination Score (MCS) for the trending of drug-induced repolarization abnormalities.

Theoretical prediction of early afterdepolarization-evoked triggered activity formation initiating ventricular reentrant arrhythmias.

BACKGROUND AND OBJECTIVE: Excessive prolongation of QT interval on ECGs in patients with congenital/acquired long QT syndrome and heart failure is a sign suggesting the development of early afterdepolarization (EAD), an abnormal repolarization in the action potential of ventricular cardiomyocytes. The development of EAD has been believed to be a trigger for fatal tachyarrhythmia, which can be a risk for sudden cardiac death. The role of EAD in triggering ventricular tachycardia (VT) remains unclear. The aim of this study was to elucidate the mechanism of EAD-induced triggered activity formation that leads to the VT such as Torsades de Pointes. METHODS: We investigated the relationship between EAD and tachyarrhythmia initiation by constructing homogeneous myocardial sheet models consisting of the mid-myocardial cell version of a human ventricular myocyte model and performing simulations of excitation propagation. RESULTS: A solitary island-like (clustering) occurrence of EADs in the homogeneous myocardial sheet could induce a focal excitation wave. However, reentrant excitation, an entity of tachyarrhythmia, was not able to be triggered regardless of the EAD cluster size when the focal excitation wave formed a repolarization potential difference boundary consisting of only a convex surface. The discontinuous distribution of multiple EAD clusters in the ventricular tissue formed a specific repolarization heterogeneity due to the repolarization potential difference, the shape of which depended on EAD cluster size and placed intervals. We found that the triggered activity was formed in such a manner that the repolarization potential difference boundary included a concave surface. CONCLUSIONS: The formation of triggered activity that led to tachyarrhythmia required not only the occurrence of EAD onset-mediated focal excitation wave but also a repolarization heterogeneity-based specific repolarization potential difference boundary shape formed within the tissue.

Electric Field-Based Spatial Analysis of Noncontact Unipolar Electrograms to Map Regional Activation-Repolarization Intervals.

BACKGROUND: Spatial heterogeneity in repolarization plays an important role in generating and sustaining cardiac arrhythmias. Reliable determination of repolarization times remains challenging. OBJECTIVES: The goal of this study was to improve processing of densely sampled noncontact unipolar electrograms to yield reliable high-resolution activation and repolarization maps. METHODS: Endocardial noncontact unipolar electrograms were both simulated and recorded in pig left ventricle. Electrical activity on the endocardial surface was processed in terms of a pseudo-electric field. Activation and repolarization times were calculated by using an amplitude-weighted average on QRS and T waves (ie, the E-field method). This was compared vs the conventional Wyatt method on unipolar electrograms. Timing maps were validated against timing on endocardial action potentials in a simulation study. In vivo, activation and repolarization times determined by using this alternative E-field method were validated against simultaneously recorded endocardial monophasic action potentials (MAPs). RESULTS: Simulation showed that the E-field method provides viable measurements of local endocardial action potential activation and repolarization times. In vivo, correlation of E-field activation times with MAP activation times (rE = 0.76; P < 0.001) was similar to those of Wyatt (rWyatt = 0.80, P < 0.001; P[h1:rE > rWyatt] = 0.82); for repolarization times, correlation improved significantly (rE = 0.96, P < 0.001; rWyatt = 0.82, P < 0.001; P[h1:rE > rWyatt] < 0.00001). This resulted in improved correlations of activation-repolarization intervals to endocardial action potential duration on MAP (rE = 0.96, P < 0.001; rWyatt = 0.86, P < 0.001; P[h1:rE > rWyatt] < 0.00001). Spatial beat-to-beat variation of repolarization could only be calculated by using the E-field methodology and correlated well with the MAP beat-to-beat variation of repolarization (rE = 0.76; P = 0.001). CONCLUSIONS: The E-field method substantially enhances information from endocardial noncontact electrogram data, allowing for dense maps of activation and repolarization times and derived parameters.

Association between ventricular repolarization parameters and cardiovascular death in patients of the SWISS-AF cohort.

BACKGROUND: The effect of the ventricular repolarization heterogeneity has not been systematically assessed in patients with atrial fibrillation (AF). Aim of this study is to assess ventricular repolarization heterogeneity as predictor of cardiovascular (CV) death and/or other CV events in patients with AF. METHODS: From the multicenter prospective Swiss-AF (Swiss Atrial Fibrillation) Cohort Study, we enrolled 1711 patients who were in sinus rhythm (995) or AF (716). Resting ECG recordings of 5-min duration were obtained at baseline. Parameters assessing ventricular repolarization were computed (QTc, Tpeak-Tend, J-Tpeak and V-index). RESULTS: During AF, the V-index was found repeatable (no differences when computed over the whole recording, on the first 2.5-min and on the last 2.5-min segments). During a mean follow-up time of 2.6 ± 1.0 years, 90 patients died for CV reasons. In bivariate Cox regression analysis (adjusted for age only), the V-index was associated with an increased risk of CV death, both in the subgroup of patients in sinus rhythm (SR) as well as those in AF. In multivariate analysis adjusted for clinical risk factors and medications, both prolonged QTc and V-index were independently associated with an increased risk of CV death (QTc: hazard ratio [HR] 2.78, 95% CI 1.79-4.32, p < 0.001; V-index: HR 1.73, 95% CI 1.12-2.69, p = 0.014). CONCLUSIONS: QTc and V-index, measured in a single 5-min ECG recording, were independent predictors of CV death in a cohort of patients with AF and might be a valuable tool for further risk stratification to guide patient management. Clinical Trial Identifier Swiss-AF study: NCT02105844.

Early Life Trauma Is Associated With Increased Microvolt T-Wave Alternans During Mental Stress Challenge: A Substudy of Mental Stress Ischemia: Prognosis and Genetic Influences.

Background Early life trauma has been associated with increased cardiovascular risk, but the arrhythmic implications are unclear. We hypothesized that in patients with coronary artery disease, early life trauma predicts increased arrhythmic risk during mental stress, measured by elevated microvolt T-wave alternans (TWA), a measure of repolarization heterogeneity and sudden cardiac death risk. Methods and Results In a cohort with stable coronary artery disease (NCT04123197), we examined early life trauma with the Early Trauma Inventory Self Report-Short Form. Participants underwent a laboratory-based mental stress speech task with Holter monitoring, as well as a structured psychiatric interview. We measured TWA during rest, mental stress, and recovery with ambulatory electrocardiographic monitoring. We adjusted for sociodemographic factors, cardiac history, psychiatric comorbidity, and hemodynamic stress reactivity with multivariable linear regression models. We examined 320 participants with noise- and arrhythmia-free ECGs. The mean (SD) age was 63.8 (8.7) years, 27% were women, and 27% reported significant childhood trauma (Early Trauma Inventory Self Report-Short Form ≥10). High childhood trauma was associated with a multivariable-adjusted 17% increase in TWA (P=0.04) during stress, and each unit increase in the Early Trauma Inventory Self Report-Short Form total score was associated with a 1.7% higher stress TWA (P=0.02). The largest effect sizes were found with the emotional trauma subtype. Conclusions In a cohort with stable coronary artery disease, early life trauma, and in particular emotional trauma, is associated with increased TWA, a marker of increased arrhythmic risk, during mental stress. This association suggests that early trauma exposures may affect long-term sudden cardiac death risk during emotional triggers, although more studies are warranted.

Ventricular repolarization heterogeneity in patients with COVID-19: Original data, systematic review, and meta-analysis.

BACKGROUND: Coronavirus disease-2019 (COVID-19) has been associated with an increased risk of acute cardiac events. However, the effect of COVID-19 on repolarization heterogeneity is not yet established. In this study, we evaluated electrocardiogram (ECG) markers of repolarization heterogeneity in patients hospitalized with COVID-19. In addition, we performed a systematic review and meta-analysis of the published studies. METHODS: QT dispersion (QTd), the interval between T wave peak to T wave end (TpTe), TpTe/QT (with and without correction), QRS width, and the index of cardio-electrophysiological balance (iCEB) were calculated in 101 hospitalized COVID-19 patients and it was compared with 101 non-COVID-19 matched controls. A systematic review was performed in four databases and meta-analysis was conducted using Stata software. RESULTS: Tp-Te, TpTe/QT, QRS width, and iCEB were significantly increased in COVID-19 patients compared with controls (TpTe = 82.89 vs. 75.33 ms (ms), p-value = .005; TpTe/QT = 0.217 vs. 0.203 ms, p-value = .026). After a meta-analysis of 679 COVID-19 cases and 526 controls from 9 studies, TpTe interval, TpTe/QT, and TpTe/QTc ratios were significantly increased in COVID-19 patients. Meta-regression analysis moderated by age, gender, diabetes mellitus, hypertension, and smoking reduced the heterogeneity. QTd showed no significant correlation with COVID-19. CONCLUSION: COVID-19 adversely influences the ECG markers of transmural heterogeneity of repolarization. Studies evaluating the predictive value of these ECG markers are warranted to determine their clinical utility.

Analyzing the Role of Repolarization Gradients in Post-infarct Ventricular Tachycardia Dynamics Using Patient-Specific Computational Heart Models.

Aims: Disease-induced repolarization heterogeneity in infarcted myocardium contributes to VT arrhythmogenesis but how apicobasal and transmural (AB-TM) repolarization gradients additionally affect post-infarct VT dynamics is unknown. The goal of this study is to assess how AB-TM repolarization gradients impact post-infarct VT dynamics using patient-specific heart models. Method: 3D late gadolinium-enhanced cardiac magnetic resonance images were acquired from seven post-infarct patients. Models representing the patient-specific scar and infarct border zone distributions were reconstructed without (baseline) and with repolarization gradients along both the AB-TM axes. AB only and TM only models were created to assess the effects of each ventricular gradient on VT dynamics. VTs were induced in all models via rapid pacing. Results: Ten baseline VTs were induced. VT inducibility in AB-TM models was not significantly different from baseline (p>0.05). Reentry pathways in AB-TM models were different than baseline pathways due to alterations in the location of conduction block (p<0.05). VT exit sites in AB-TM models were different than baseline VT exit sites (p<0.05). VT inducibility of AB only and TM only models were not significantly different than that of baseline (p>0.05) or AB-TM models (p>0.05). Reentry pathways and VT exit sites in AB only and TM only models were different than in baseline (p<0.05). Lastly, repolarization gradients uncovered multiple VT morphologies with different reentrant pathways and exit sites within the same structural, conducting channels. Conclusion: VT inducibility was not impacted by the addition of AB-TM repolarization gradients, but the VT reentrant pathway and exit sites were greatly affected due to modulation of conduction block. Thus, during ablation procedures, physiological and pharmacological factors that impact the ventricular repolarization gradient might need to be considered when targeting the VTs.

Ex vivo Validation of Noninvasive Epicardial and Endocardial Repolarization Mapping.

Background: The detection and localization of electrophysiological substrates currently involve invasive cardiac mapping. Electrocardiographic imaging (ECGI) using the equivalent dipole layer (EDL) method allows the noninvasive estimation of endocardial and epicardial activation and repolarization times (AT and RT), but the RT validation is limited to in silico studies. We aimed to assess the temporal and spatial accuracy of the EDL method in reconstructing the RTs from the surface ECG under physiological circumstances and situations with artificially induced increased repolarization heterogeneity. Methods: In four Langendorff-perfused pig hearts, we simultaneously recorded unipolar electrograms from plunge needles and pseudo-ECGs from a volume-conducting container equipped with 61 electrodes. The RTs were computed from the ECGs during atrial and ventricular pacing and compared with those measured from the local unipolar electrograms. Regional RT prolongation (cooling) or shortening (pinacidil) was achieved by selective perfusion of the left anterior descending artery (LAD) region. Results: The differences between the computed and measured RTs were 19.0 ± 17.8 and 18.6 ± 13.7 ms for atrial and ventricular paced beats, respectively. The region of artificially delayed or shortened repolarization was correctly identified, with minimum/maximum RT roughly in the center of the region in three hearts. In one heart, the reconstructed region was shifted by ~2.5 cm. The total absolute difference between the measured and calculated RTs for all analyzed patterns in selectively perfused hearts (n = 5) was 39.6 ± 27.1 ms. Conclusion: The noninvasive ECG repolarization imaging using the EDL method of atrial and ventricular paced beats allows adequate quantitative reconstruction of regions of altered repolarization.

Parameters of repolarization heterogeneity are associated with myocardial recovery in acute heart failure.

BACKGROUND: Heart failure (HF) with recovered ejection fraction (HFrecEF) is an increasingly recognized yet not well understood phenotype. Little is known about electrical parameters associated with myocardial recovery in acute systolic HF. METHODS: We identified a subset of 87 patients from a non-ischemic cardiomyopathy cohort with left ventricular ejection fraction (LVEF) < 40% during index HF hospitalization. HFrecEF was defined as follow-up LVEF ≥40% and ≥ 10% improvement from baseline. We analyzed baseline and follow up electrocardiograms (ECG) in this group for several electrical parameters known to reflect repolarization heterogeneity. RESULTS: Among 87 patients, 30 (34%) patients recovered in a median of 122 (IQR: 58-275) days after index hospitalization. Baseline demographics were similar among HFrecEF versus persistent HFrEF except for increased diabetes in the persistent HFrEF cohort. Patients with HFrecEF had baseline decreased QRST angle, decreased QT dispersion, and less negative signed JT area compared to persistent HFrEF. Patients with HFrecEF had greater decrease in QT dispersion and QTc duration, and greater increase in the signed JT and TpTe areas over time. Baseline QRST angle correlated with longitudinal and circumferential strain and myocardial systolic performance (MSP). Signed JT area correlated with increased baseline LVEF, smaller baseline LV dimensions, increased longitudinal and circumferential strain, and MSP. Signed TpTe correlated with increased longitudinal and circumferential strain, and MSP. CONCLUSIONS: Several conventional and novel ECG parameters that reflect repolarization heterogeneity may differentiate patients with acute HF who ultimately recover LVEF. These parameters are associated with baseline structural parameters and are dynamic during recovery.

Body Surface Mapping of Ventricular Repolarization Heterogeneity: An Ex-vivo Multiparameter Study.

BACKGROUND: Increased heterogeneity of ventricular repolarization is associated with life-threatening arrhythmia and sudden cardiac death (SCD). T-wave analysis through body surface potential mapping (BSPM) is a promising tool for risk stratification, but the clinical effectiveness of current electrocardiographic indices is still unclear, with limited experimental validation. This study aims to investigate performance of non-invasive state-of-the-art and novel T-wave markers for repolarization dispersion in an ex vivo model. METHODS: Langendorff-perfused pig hearts (N = 7) were suspended in a human-shaped 256-electrode torso tank. Tank potentials were recorded during sinus rhythm before and after introducing repolarization inhomogeneities through local perfusion with dofetilide and/or pinacidil. Drug-induced repolarization gradients were investigated from BSPMs at different experiment phases. Dispersion of electrical recovery was quantified by duration parameters, i.e., the time interval between the peak and the offset of T-wave (TPEAK-TEND) and QT interval, and variability over time and electrodes was also assessed. The degree of T-wave symmetry to the peak was quantified by the ratio between the terminal and initial portions of T-wave area (Asy). Morphological variability between left and right BSPM electrodes was measured by dynamic time warping (DTW). Finally, T-wave organization was assessed by the complexity of repolarization index (CR), i.e., the amount of energy non-preserved by the dominant eigenvector computed by principal component analysis (PCA), and the error between each multilead T-wave and its 3D PCA approximation (NMSE). Body surface indices were compared with global measures of epicardial dispersion of repolarization, and with local gradients between adjacent ventricular sites. RESULTS: After drug intervention, both regional and global repolarization heterogeneity were significantly enhanced. On the body surface, TPEAK-TEND was significantly prolonged and less stable in time in all experiments, while QT interval showed higher variability across the interventions in terms of duration and spatial dispersion. The rising slope of the repolarization profile was steeper, and T-waves were more asymmetric than at baseline. Interventricular shape dissimilarity was enhanced by repolarization gradients according to DTW. Organized T-wave patterns were associated with abnormal repolarization, and they were properly described by the first principal components. CONCLUSION: Repolarization heterogeneity significantly affects T-wave properties, and can be non-invasively captured by BSPM-based metrics.

T-Peak to T-End Improvements After Beta-Blocker Administration in Peripartum Cardiomyopathy Patients.

BACKGROUND: Many studies have shown that T-peak to T-end (TPTE) interval was associated with sudden cardiac events. Peripartum cardiomyopathy (PPCM) causes reversible left ventricle systolic dysfunction which may deteriorate into sudden cardiac death. This study aimed to evaluate beta-blocker as an antiarrhythmic agent to improve TPTE interval as a prognostic value of sudden cardiac death. METHODS: A cohort experimental prospective study was performed. The PPCM was diagnosed from the emergency ward. A total of 54 cases were identified from 2014 to 2016. Thirty-four patients were followed up for further analysis. Electrocardiograms were conducted in all the patients, and TPTE interval was measured. After a follow-up of 6 months of beta-blocker treatment, the echocardiography and TPTE interval were measured again to obtain the repolarization heterogeneity. RESULTS: The mean age of subjects was 32 ± 6.4 years. The mean left ventricular ejection fraction (LVEF) was 32.24±6.3%. The mean TPTE interval was 123.7 ± 28.2 ms. After 6 months of beta-blocker administration, the mean LVEF was 58.26±4.4% and the mean TPTE was 98.7 ± 39.5 ms. The paired t-test showed a significant difference between TPTE interval pre- and post-administration of beta-blocker (P value < 0.001). CONCLUSIONS: There is an improvement of TPTE in PPCM patients after 6 months of beta-blocker administration. Administration of beta-blocker in PPCM patients is expected to prevent sudden cardiac death in PPCM populations.

Wavelength and Fibrosis Affect Phase Singularity Locations During Atrial Fibrillation.

The mechanisms underlying atrial fibrillation (AF), the most common sustained cardiac rhythm disturbance, remain elusive. Atrial fibrosis plays an important role in the development of AF and rotor dynamics. Both electrical wavelength (WL) and the degree of atrial fibrosis change as AF progresses. However, their combined effect on rotor core location remains unknown. The aim of this study was to analyze the effects of WL change on rotor core location in both fibrotic and non-fibrotic atria. Three patient specific fibrosis distributions (total fibrosis content: 16.6, 22.8, and 19.2%) obtained from clinical imaging data of persistent AF patients were incorporated in a bilayer atrial computational model. Fibrotic effects were modeled as myocyte-fibroblast coupling + conductivity remodeling; structural remodeling; ionic current changes + conductivity remodeling; and combinations of these methods. To change WL, action potential duration (APD) was varied from 120 to 240ms, representing the range of clinically observed AF cycle length, by modifying the inward rectifier potassium current (IK1) conductance between 80 and 140% of the original value. Phase singularities (PSs) were computed to identify rotor core locations. Our results show that IK1 conductance variation resulted in a decrease of APD and WL across the atria. For large WL in the absence of fibrosis, PSs anchored to regions with high APD gradient at the center of the left atrium (LA) anterior wall and near the junctions of the inferior pulmonary veins (PVs) with the LA. Decreasing the WL induced more PSs, whose distribution became less clustered. With fibrosis, PS locations depended on the fibrosis distribution and the fibrosis implementation method. The proportion of PSs in fibrotic areas and along the borders varied with both WL and fibrosis modeling method: for patient one, this was 4.2-14.9% as IK1 varied for the structural remodeling representation, but 12.3-88.4% using the combination of structural remodeling with myocyte-fibroblast coupling. The degree and distribution of fibrosis and the choice of implementation technique had a larger effect on PS locations than the WL variation. Thus, distinguishing the fibrotic mechanisms present in a patient is important for interpreting clinical fibrosis maps to create personalized models.

Repolarization heterogeneity in patients with cardiac resynchronization therapy and its relation to ventricular tachyarrhythmias.

BACKGROUND: Cardiac resynchronization therapy (CRT) has been shown to induce left ventricular reverse remodeling, but little is known about its influence on ventricular repolarization. OBJECTIVE: The purpose of this study was to evaluate changes in ventricular repolarization of native conduction after CRT and its relation to ventricular tachycardia (VT) and ventricular fibrillation (VF) during long-term follow-up. METHODS: We prospectively included 64 patients with heart failure treated with CRT. QT interval, TpTe, and TpTe/QT ratio were analyzed from 20-minute high-resolution ECGs that were recorded at baseline and 1, 3, 6, 9, and 12 months after CRT implantation. CRT was temporary inhibited during follow-up to record intrinsic ECG. Patients with a decrease of left ventricular end-systolic volume ≥15% at 12-month follow-up (mid-term follow-up) were considered as responders. Occurrences of VT/VF during follow-up were noted. RESULTS: Significant increase of repolarization heterogeneity in the first months after implantation was observed (P <.05) but then declined during 12 months of follow-up. Patients with VT/VF during long-term follow-up had higher repolarization heterogeneity at mid-term follow-up than patients without VT/VF (TpTe/QT ratio: 0.263 [0.204-0.278] vs 0.225 [0.204-0.239]; P = .045). Echocardiographic response at mid-term follow-up did not significantly influence the rate of VT/VF (log-rank P = .252). In multivariate Cox regression analysis, only high repolarization heterogeneity at mid-term follow-up (TpTe/QT ratio >0.260) was independently associated with high risk of VT/VF (hazard ratio 4.29; 95% confidence interval 1.40-13.15; P = .011). CONCLUSION: CRT induces time-dependent changes in repolarization parameters in the first year after implantation. High repolarization heterogeneity at mid-term follow-up was associated with higher rate of VT/VF during long-term follow-up.

Unmasking atrial repolarization to assess alternans, spatiotemporal heterogeneity, and susceptibility to atrial fibrillation.

BACKGROUND: Detection of atrial repolarization waves free of far-field signal contamination by ventricular activation would allow investigation of atrial electrophysiology and factors that influence susceptibility to atrial tachycardia and atrial fibrillation (AF). OBJECTIVE: The purpose of this study was to identify means for high-resolution intracardiac recording of atrial repolarization (Ta) waves using standard clinical electrocatheters and to assess fundamental electrophysiologic properties relevant to AF risk. METHODS: In alpha-chloralose anesthetized Yorkshire pigs, we studied effects of vagus nerve stimulation (VNS) on PTa and QT intervals and effects of acute atrial ischemia or administration of intrapericardial acetylcholine followed by intravenous epinephrine on susceptibility to AF. RESULTS: Electrocatheters with closely spaced (1-mm) electrode pairs yielded high-resolution tracings of atrial repolarization waves. These recordings permitted detection of differential effects of right or left VNS, which shortened atrial PTa interval by 30% vs. 21% (P <.01) and lengthened QT interval by 1.5% vs. 9%, respectively (P < .05). During atrial ischemia, STa segments were elevated 3.4-fold (P < .01), and the threshold for inducing AF was reduced 3.1-fold (P = .004). Ischemia amplified atrial T-wave alternans (TWAa) and spatiotemporal heterogeneity (TWHa) by 23- and 13-fold, respectively, in inverse correlation to AF threshold (r = 0.74, P <.01; r = 0.61, P = .03). TWAa and TWHa increased by 4.5- and 2-fold shortly before autonomically triggered atrial premature beats and AF. CONCLUSION: This study used standard electrocatheters to demonstrate that TWAa and TWHa analysis provides means to assess vulnerability to AF without provocative electrical stimuli. These parameters could be evaluated in the clinical electrophysiology laboratory to determine risk for this prevalent arrhythmia and efficacy of contemporary and new agents.

The proarrhythmic effect of cardiac resynchronization therapy: an issue that should be borne in mind.

The demonstrated benefits of cardiac resynchronization therapy (CRT) in reducing mortality and hospitalizations for heart failure, improving NYHA functional class and inducing reverse remodeling have led to its increasing use in clinical practice. However, its potential contribution to complex ventricular arrhythmias is controversial.We present the case of a female patient with valvular heart failure and severe systolic dysfunction, in NYHA class III and under optimal medical therapy, without previous documented ventricular arrhythmias. After implantation of a CRT defibrillator, she suffered an arrhythmic storm with multiple episodes of monomorphic ventricular tachycardia (VT), requiring 12 shocks. Subsequently, a pattern of ventricular bigeminy was observed, as well as reproducible VT runs induced by biventricular pacing. Since no other vein of the coronary sinus system was accessible, it was decided to implant an epicardial lead to stimulate the left ventricle, positioned in the left ventricular mid-lateral wall. No arrhythmias were detected in the following six months. This case highlights the possible proarrhythmic effect of biventricular pacing with a left ventricular lead positioned in the coronary sinus venous system.