Elevated T-wave alternans predicts nonsustained ventricular tachycardia in association with percutaneous coronary intervention in ST-segment elevation myocardial infarction (STEMI) patients.

INTRODUCTION: Successful reperfusion with primary percutaneous coronary intervention (PCI) can paradoxically elicit temporary vulnerability to ventricular arrhythmia. We examined whether T-wave alternans (TWA) level is correlated with nonsustained ventricular tachycardia (NSVT) incidence in association with PCI in patients with acute ST-segment elevation myocardial infarction (STEMI). METHODS AND RESULTS: We analyzed continuous 24-hour ambulatory electrocardiograms in 48 STEMI patients during and after successful primary PCI, achieving Thrombolysis in Myocardial Infarction (TIMI) grade 3 flow. TWA was measured using modified moving average method. Maximum TWA was elevated in patients with (N = 22) compared to without (N = 26) NSVT (75.1 ± 6.3 vs 49.9 ± 3.6 µV, P < 0.005) during the 22-hour monitoring period. TWA ≥ 60µV predicted NSVT with sensitivity of 77%; specificity, 73%; positive predictive value, 71%; and negative predictive value, 79%. Area under receiver operator characteristic curve (AUC) was 0.87 for maximum TWA in predicting NSVT. By comparison, ST-segment levels did not differ in patients with versus without NSVT and were not predictive (AUC = 0.52). TWA was elevated prior to PCI and remained elevated at 30 minutes after balloon inflation despite restoration of TIMI grade 3 flow in all patients, declining by 22 hours (P < 0.05). Maximum ST-segment levels decreased from before PCI to 30 minutes after balloon inflation. TWA is regionally specific, with higher values prior to PCI in precordial lead V5 than in V1 for left coronary lesions. CONCLUSIONS: TWA may be useful in identifying individuals at heightened risk for arrhythmia in association with primary PCI and can potentially signal time-dependent changes in arrhythmia vulnerability.

Patterns of ectopy leading to increased risk of fatal or near-fatal cardiac arrhythmia in patients with depressed left ventricular function after an acute myocardial infarction.

AIMS: To identify potential new markers for assessing the risk of sudden arrhythmic events based on a method that captures features of premature ventricular complexes (PVCs) in relation to sinus RR intervals in Holter recordings (heartprint). METHODS AND RESULTS: Holter recordings obtained 6 weeks after acute myocardial infarction from 227 patients with reduced ventricular function (left ventricular ejection fraction ≤ 40%) were used to produce heartprints. Measured indices were: PVCs per hour, standard deviation of coupling interval (SDCI), and the number of occurrences of the most prevalent form of PVCs (SNIB). Predictive values, survival analysis, and Cox regression with adjustment for clinical variables were performed based on primary endpoint, defined as an electrocardiogram-documented fatal or near-fatal arrhythmic event, death from any cause, and cardiac death. High ectopy (PVCs per hour ≥10) was a predictor of all endpoints. Repeating forms of PVCs (SNIB ≥ 83) was a predictor of primary endpoint, hazard ratio = 3.5 (1.3-9.5), and all-cause death, hazard ratio = 2.8 (1.1-7.3), but not cardiac death. SDCI ≤ 80 ms was a predictor of all-cause death and cardiac death, but not of primary endpoint. CONCLUSION: High ectopy, prevalence of repeating forms of PVCs, and low coupling interval variability are potentially useful risk markers of fatal or near-fatal arrhythmias after myocardial infarction.

Intracardiac QT integral on far-field ICD electrogram predicts sustained ventricular tachyarrhythmias in ICD patients.

BACKGROUND: Prediction of sustained ventricular tachycardia (VT)/ventricular fibrillation (VF) could help to guide preventive interventions in at-risk patients. The QRST integral (∫QT) reflects intrinsic repolarization properties. OBJECTIVE: The objective of this study was to determine whether intracardiac ∫QT predicts VT/VF in the next few months in patients with implantable cardioverter defibrillators (ICDs). METHODS: Far-field (FF) and near-field (NF) right ventricular intracardiac electrograms (EGMs) were recorded via telemetry in 46 patients with structural heart disease and ICDs implanted for secondary prevention of sudden cardiac death. Epochs of 4.9 ± 0.4 minutes during sinus rhythm (mean heart rate 70.9 ± 15.2 beats/min) and ventricular pacing at 105 beats/min were analyzed. Mean ∫QT was calculated on FF and NF EGMs as the algebraic sum of areas under the QRST curve and adjusted by mean heart rate. Patients were followed up for at least 3 months. True VT/VF events treated by the ICD served as the end point. RESULTS: During a mean follow-up of 4.6 months, 22 patients (48%) were treated for VT/VF. Unadjusted and adjusted by heart rate, FF EGM ∫QT in sinus rhythm was a significant predictor of VT/VF (unadjusted ∫QT hazard ratio 1.007; 95% confidence interval 1.002 to 1.0013; P = .007; adjusted ∫QT hazard ratio 1.68; 95% confidence interval 1.19 to 2.36; P = .002). The highest quartile of intracardiac ∫QT predicted VT/VF (log-rank test P = .042) and identified patients at risk with a specificity of 86% and positive predictive value of 73%. CONCLUSION: Increased intracardiac FF EGM ∫QT predicts VT/VF in patients with structural heart disease and secondary prevention ICDs.

Short-term variability of repolarization predicts ventricular tachycardia and sudden cardiac death in patients with structural heart disease: a comparison with QT variability index.

BACKGROUND: Monitoring arrhythmic risk may improve management of patients with implantable cardioverter-defibrillators (ICD) and prevent ICD shocks. Changes in repolarization duration between subsequent beats quantified as short-term variability (STV) is associated with ventricular arrhythmias in several animal models. OBJECTIVE: We evaluated STV of QT from right ventricular intracardiac ICD electrograms in patients with structural heart disease and compared its predictive value with the QT variability index (QTVI). METHODS: In 233 patients, STV over 60 beats for QT and RR intervals and their ratio was calculated (STV(QT), STV(RR), STV(Ratio), respectively). QTVI was derived from mean and SD of QT and heart rate. Follow-up duration was 26 ± 15 months. Predictive value was determined for sudden arrhythmic death (SAD) defined as sudden cardiac death or fast ventricular tachycardia/fibrillation [CL < 240 ms]. RESULTS: In univariate analysis, STV(Ratio), but not STV(QT) or STV(RR), was predictive of SAD. Hazard ratios for highest quartile STV(Ratio) and QTVI were comparable (STV(Ratio): 1.9, 95% confidence interval [CI] 1.1 to 3.3, P = .038, QTVI: 2.2, 95% CI 1.2 to 3.8, P = .010). In a multivariate model, highest quartile STV(Ratio) was predictive of SAD after adjustment for New York Heart Association class, history of ischemia, ICD indication, and use of class I antiarrhythmics (hazard ratio 1.8, 95% CI 1.0 to 3.4, P < .050). A combined criterion of highest quartile for both STV(Ratio) and QTVI identified patients at highest risk (hazard ratio 2.4, 95% CI 1.3 to 4.3, P = .005, positive predictive value 38%, negative predictive value 82%). CONCLUSION: STV(Ratio) from ICD electrograms is predictive of SAD. Predictive value is similar for order-based STV(Ratio) and distribution-based QTVI, but the combination of both parameters can further improve results.

Intracardiac electrogram T-wave alternans/variability increases before spontaneous ventricular tachyarrhythmias in implantable cardioverter-defibrillator patients: a prospective, multi-center study.

BACKGROUND: T-wave alternans (TWA) increases before ventricular tachycardia (VT) or fibrillation (VF), suggesting that it may warn of VT/VF in implantable cardioverter-defibrillator patients. Recently, we described a method for measuring alternans and nonalternans variability (TWA/V) from electrograms (EGMs) stored in implantable cardioverter-defibrillators before VT/VF. The goal of this prospective, multicenter study was to determine whether EGM TWA/V was greater before VT/VF than at baseline. METHODS AND RESULTS: We enrolled 63 implantable cardioverter-defibrillator patients. TWA/V was computed from stored EGMs before spontaneous VT/VF and from sequential windows of 8 pairs of beats using 4 different control recordings: baseline rhythm, rapid pacing at 105 bpm, segments of ambulatory Holter EGMs matched to the time of VT/VF episodes, and EGMs before spontaneous supraventricular tachycardia. During follow-up, 28 patients had 166 episodes of VT/VF. TWA/V was greater before VT/VF (62.9 ± 3.1 µV; n = 28) than during baseline rhythm (12.8 ± 1.8 µV; P < 0.0001; n = 62), during rapid pacing (14.5 ± 2.0 µV; P < 0.0001; n = 52), before supraventricular tachycardia (27.5 ± 6.1 µV; P < 0.0001; n = 9), or during time-matched ambulatory controls (12.3 ± 3.5 µV; P < 0.0001; n = 16). By logistic regression, the odds of VT/VF increased by a factor of 2.2 for each 10-µV increment in TWA/V (P < 0.0001). CONCLUSIONS: In implantable cardioverter-defibrillator patients, EGM TWA/V is greater before spontaneous VT/VF than in control recordings. Future implantable cardioverter-defibrillators that measure EGM TWA/V continuously may warn patients and initiate pacing therapies to prevent VT/VF.

Is surface ECG a useful surrogate for subcutaneous ECG?

BACKGROUND: Surface electrocardiograms (ECGs) have been used as surrogates for subcutaneous ECGs to optimize and evaluate subcutaneous devices, but differences between surface and subcutaneous ECGs remain poorly understood. This study evaluated the correspondence between surface and subcutaneous ECGs in Reveal Plus (Medtronic Inc., Minneapolis, MN, USA) patients during various maneuvers. METHODS: Surface electrodes were placed over the Reveal electrodes of 48 subjects (23 men, age 60 +/- 14.3 years, body mass index 27 +/- 4.9 kg/m(2), implant time 45 +/- 29 weeks). Surface and subcutaneous ECGs were recorded simultaneously for 30 seconds during rest, isometric myopotential noise (pushing palms together), and artifact-inducing maneuvers (repetitive displacement of device, chest thumping on device, arm flaps, handshake, hallwalk). RESULTS: During rest, subcutaneous and surface ECGs were highly correlated (R = 0.96), had similar R-wave amplitude (487 +/- 40 vs 507 +/- 49 microV, NS), and signal-to-noise ratio (SNR) (13.4 +/- 0.8 vs 13.5 +/- 0.7, NS). During myopotential noise, subcutaneous and surface ECGs were highly correlated (R = 0.91) and had similar SNR (10.0 +/- 0.6 vs 9.7 +/- 0.6, NS). During artifact-inducing maneuvers, subcutaneous and surface ECGs were less correlated (R = 0.82 displacement, 0.84 chest thumping, 0.93 arm flaps, 0.90 handshake, 0.92 hallwalk) with subcutaneous SNR significantly higher than surface (11.4 +/- 0.7 vs 9.9 +/- 0.7 displacement, 11.1 +/- 0.6 vs 8.4 +/- 0.6 chest thumping, 11.5 +/- 0.4 vs 10.3 +/- 0.5 arm flaps, 9.5 +/- 0.4 vs 8.4 +/- 0.4 handshake, 12.0 +/- 0.4 vs 10.0 +/- 0.4 hallwalk, P < 0.05). CONCLUSION: Surface ECGs are adequate surrogates for subcutaneous ECGs in situations free from motion artifacts but not in situations involving movement of the device, surface electrodes, or recording equipment. During artifact-inducing maneuvers, subcutaneous ECGs are of higher quality and less susceptible to artifacts than surface ECGs.

Noninvasive electrocardiographic imaging of arrhythmogenesis: insights from modeling and human studies.

BACKGROUND: Sudden cardiac death remains the leading cause of death, claiming more than 1000 lives per day in the United States alone. Noninvasive means to diagnose rhythm disorders of the heart have relied heavily on the 12-lead electrocardiogram and, to a lesser extent, on higher-resolution body-surface mapping. These lack sensitivity and specificity due to the smoothing effect of the torso volume conductor. In contrast, noninvasive electrocardiographic imaging (ECGI) reconstructs potentials, electrograms, and activation sequences directly on the heart surface from body-surface electrocardiograms and has been applied in animal as well as clinical studies. This presentation summarizes the application of ECGI for imaging epicardial arrhythmogenic substrates and associated properties, in particular, dispersion of myocardial repolarization, fractionated electrograms, and heterogeneous multipolar potential distributions. METHODS: Electrocardiographic imaging was evaluated in a canine model of temperature-induced dispersion of myocardial repolarization through localized warming and cooling and in 3 patients with preserved left ventricular ejection fraction (>or=50%) undergoing open heart surgery. Noninvasively reconstructed epicardial potentials, electrograms (and derived measures), as well as activation sequences were compared with their measured counterparts. RESULTS: Epicardial measures of dispersion of repolarization (activation recovery intervals [ARIs] and QRST integrals) accurately reflected the underlying repolarization properties: prolonged ARIs and increased QRST (warming), shortened ARIs and decreased QRST (cooling), and gradients of adjacent prolonged and shortened ARIs (increased and decreased QRST) during simultaneous warming and cooling. In open-heart surgery patients, ECGI reflected the underlying arrhythmogenic substrate by noninvasively reconstructing fractionated electrograms (cross-correlation with measured electrograms = 0.72 +/- 0.25), regions of heterogeneous multipolar potential distributions, and areas of slow conduction. CONCLUSION: These studies demonstrate that ECGI can capture and localize noninvasively important electrophysiologic properties of the heart. Its clinical significance lies in mapping arrhythmogenic substrates, evaluation and guidance of therapy, and risk stratification.

Electrocardiographic imaging of cardiac resynchronization therapy in heart failure: observation of variable electrophysiologic responses.

BACKGROUND: Cardiac resynchronization therapy (CRT) for congestive heart failure patients with delayed left ventricular (LV) conduction is clinically beneficial in approximately 70% of patients. Unresolved issues include patient selection, lead placement, and efficacy of LV pacing alone. Being an electrical approach, detailed electrical information during CRT is critical to resolving these issues. However, electrical data from patients have been limited because of the requirement for invasive mapping. OBJECTIVES: The purpose of this study was to provide observations and insights on the variable electrophysiologic responses of the heart to CRT using electrocardiographic imaging (ECGI). METHODS: ECGI is a novel modality for noninvasive epicardial mapping. ECGI was conducted in eight patients undergoing CRT during native rhythm and various pacing modes. RESULTS: In native rhythm (six patients), ventricular activation was heterogeneous, with latest activation in the lateral LV base in three patients and in the anterolateral, midlateral, or inferior LV in the remainder of patients. Anterior LV was susceptible to block and slow conduction. Right ventricular pacing improved electrical synchrony in two of six patients. LV pacing in three of four patients involved fusion with intrinsic excitation resulting in electrical resynchronization similar to biventricular pacing. Although generally electrical synchrony improved significantly with biventricular pacing, it was not always accompanied by clinical benefit. CONCLUSION: Results suggest that (1) when accompanied by fusion, LV pacing alone can be as effective as biventricular pacing for electrical resynchronization; (2) right ventricular pacing is not effective for resynchronization; and (3) efficacy of CRT depends strongly on the patient-specific electrophysiologic substrate.

Comparison of Laplacian and bipolar ECGs for R-wave detection during noise.

Body surface Laplacian mapping localizes cardiac activity and provides more detailed distributions compared to body surface potential mapping. Systematic comparison of the performance of bipolar and Laplacian ECGs during noise has not been performed. To determine whether Laplacian ECGs (2.5 cm diameter concentric rings) can reduce noise (myopotential and motion artifacts) and improve signal to noise ratio (SNR) compared to bipolar (4 cm spacing) ECGs, Laplacian and bipolar ECGs were recorded from the anterior (precordial V3) and lateral (precordial V6) chest regions in 25 patients undergoing posture changes and in-office exercises. Mean peak-to-peak (Vpp), root mean square noise (Noise(rms)) and SNR were computed across all activities and patients. Sensing performance using an R-wave detector with an auto-adjusting exponentially decaying threshold was assessed. Across all maneuvers, mean Vpp was larger for the bipolar ECG compared to the Laplacian ECG on the anterior (0.65 +/- 0.07 vs. 0.14 +/- 0.07 mV, p<0.05) and lateral (0.65 +/- 0.07 vs. 0.05 +/- 0.07 mV, p<0.05) regions. Laplacian ECGs resulted in least Noise(rms) compared to bipolar ECGs (anterior: 0.02 +/- 0.01 vs. 0.05 +/- 0.01, p<0.05; lateral: 0.01 +/- 0.01 vs. 0.07 +/- 0.01, p<0.05). Bipolar and Laplacian SNRs were comparable on the anterior chest (14.05 +/- 0.95 vs. 13.49 +/- 0.95, p=NS). On the lateral chest, bipolar SNR was larger than Laplacian SNR (13.78 +/- 0.95 vs. 8.67 +/- 0.96, p<0.05). Laplacian SNR on the anterior chest was larger compared to the lateral chest, confirming that Laplacian ECGs are sensitive to mapping location. Sensing performance showed that bipolar ECGs resulted in marginally superior sensing accuracy compared to Laplacian ECGs. In conclusion, Laplacian ECGs offer no advantage in SNR compared with standard bipolar ECGs.

Noninvasive electrocardiographic imaging (ECGI): comparison to intraoperative mapping in patients.

OBJECTIVES/BACKGROUND: Cardiac arrhythmias are a leading cause of death and disability. Electrocardiographic imaging (ECGI) is a noninvasive imaging modality that reconstructs potentials, electrograms, and isochrones on the epicardial surface from body surface measurements. We previously demonstrated in animal experiments through comparison with simultaneously measured epicardial data the high accuracy of ECGI in imaging cardiac electrical events. Here, images obtained by noninvasive ECGI are compared to invasive direct epicardial mapping in open heart surgery patients. METHODS: Three patients were studied during sinus rhythm and right ventricular endocardial and epicardial pacing (total of five datasets). Body surface potentials were acquired preoperatively or postoperatively using a 224-electrode vest. Heart-torso geometry was determined preoperatively using computed tomography. Intraoperative mapping was performed with two 100-electrode epicardial patches. RESULTS: Noninvasive potential maps captured epicardial breakthrough sites and reflected general activation and repolarization patterns, localized pacing sites to approximately 1 cm and distinguished between epicardial and endocardial origin of activation. Noninvasively reconstructed electrogram morphologies correlated moderately with their invasive counterparts (cross correlation = 0.72 +/- 0.25 [sinus rhythm], 0.67 +/- 0.23 [endocardial pacing], 0.71 +/- 0.21 [epicardial pacing]). Noninvasive isochrones captured the sites of earliest activation, areas of slow conduction, and the general excitation pattern. CONCLUSIONS: Despite limitations due to nonsimultaneous acquisition of the surgical and noninvasive data under different conditions, the study demonstrates that ECGI can capture important features of cardiac electrical excitation in humans noninvasively during a single beat. It also shows that general excitation patterns and electrogram morphologies are largely preserved in open chest conditions.

Comparative effects of single- and linear triple-site rapid bipolar pacing on atrial activation in canine models.

Nonuniform conduction may cause block and/or delay, thereby providing a substrate for the onset and maintenance of reentrant atrial arrhythmias. We tested the hypothesis that linear triple-site, bipolar, rapid pacing (LTSBRP) of the right atrium generates more uniform wave-front propagation compared with single-site, bipolar, rapid pacing (SSBRP), thereby reducing and/or eliminating conduction block and delay that is otherwise present. Five dogs with pericarditis and three normal dogs were studied. Three plunge-wire electrode pairs were placed 5-7 mm apart in both perpendicular and parallel configurations at the superior aspect of the crista terminalis and were used to pace at 200- and 300-ms cycle lengths for < or =6 s. During pacing, 380 electrograms were recorded simultaneously from electrode arrays placed epicardially on the atria, which produced activation sequence maps for each pacing episode. Local conduction-velocity vectors were computed for each site during each episode. Histograms of absolute velocity vector angles from the x-axis (of the crista terminalis) were plotted to assess uniformity of wave-front propagation, and the magnitude of each vector was computed to assess the local speed. LTSBRP showed 1) more uniform linear activation wave fronts compared with SSBRP, 2) velocity vectors with a more uniform magnitude and direction compared with SSBRP, 3) a predominant absolute velocity vector angle vs. a scattered angle distribution with SSBRP, and 4) shorter right atrial activation time and faster mean epicardial speed than SSBRP for each pacing cycle length. LTSBRP created a more uniform wave-front propagation with less or no conduction block and/or delay compared with SSBRP.

Noninvasive electrocardiographic imaging for cardiac electrophysiology and arrhythmia.

Over 7 million people worldwide die annually from erratic heart rhythms (cardiac arrhythmias), and many more are disabled. Yet there is no imaging modality to identify patients at risk, provide accurate diagnosis and guide therapy. Standard diagnostic techniques such as the electrocardiogram (ECG) provide only low-resolution projections of cardiac electrical activity on the body surface. Here we demonstrate the successful application in humans of a new imaging modality called electrocardiographic imaging (ECGI), which noninvasively images cardiac electrical activity in the heart. In ECGI, a multielectrode vest records 224 body-surface electrocardiograms; electrical potentials, electrograms and isochrones are then reconstructed on the heart's surface using geometrical information from computed tomography (CT) and a mathematical algorithm. We provide examples of ECGI application during atrial and ventricular activation and ventricular repolarization in (i) normal heart (ii) heart with a conduction disorder (right bundle branch block) (iii) focal activation initiated by right or left ventricular pacing, and (iv) atrial flutter.

Heart-surface reconstruction and ECG electrodes localization using fluoroscopy, epipolar geometry and stereovision: application to noninvasive imaging of cardiac electrical activity.

To date there is no imaging modality for cardiac arrhythmias which remain the leading cause of sudden death in the United States (> 300000/yr.). Electrocardiographic imaging (ECGI), a noninvasive modality that images cardiac arrhythmias from body surface potentials, requires the geometrical relationship between the heart surface and the positions of body surface ECG electrodes. A photographic method was validated in a mannequin and used to determine the three-dimensional coordinates of body surface ECG electrodes to within 1 mm of their actual positions. Since fluoroscopy is available in the cardiac electrophysiology (EP) laboratory where diagnosis and treatment of cardiac arrhythmias is conducted, a fluoroscopic method to determine the heart surface geometry was developed based on projective geometry, epipolar geometry, point reconstruction, b-spline interpolation and visualization. Fluoroscopy-reconstructed hearts in a phantom and a human subject were validated using high-resolution computed tomography (CT) imaging. The mean absolute distance error for the fluoroscopy-reconstructed heart relative to the CT heart was 4 mm (phantom) and 10 mm (human). In the human, ECGI images of normal cardiac electrical activity on the fluoroscopy-reconstructed heart showed close correlation with those obtained on the CT heart. Results demonstrate the feasibility of this approach for clinical noninvasive imaging of cardiac arrhythmias in the interventional EP laboratory.