Search

Background: Action potential duration alternans (APDA) can vary regionally in magnitude and phase. The influence of APDA heterogeneity on T-wave alternans (TWA) has not been defined.Objective: Our objectives were: (1) to determine how APDA affects the magnitude and spatial distribution of TWA, and (2) to optimize electrocardiographic (ECG) lead configuration accordingly to improve TWA detection.Methods: Global, regional, and discordant APDA were simulated in a 257-node heart model. Using a forward solution, body surface potentials were derived at 300 points on the thorax and TWA was computed at each point. In 22 patients with cardiomyopathy (left ventricular ejection fraction 28% +/- 6%), TWA was measured from a 114-electrode body surface map using the spectral method during atrial pacing at 110 beats/min.Results: An increase in global APDA from 4 to 12 ms resulted in an increase in maximum TWA from 10 to 30 microV. TWA magnitude varied with the size and location of the alternating myocardium, but was largest with discordant APDA compared with regional or global APDA. Irrespective of the location or phase of APDA, TWA was largest over the precordium and correlated with T-wave amplitude in the simulation (R(2) = 0.56 +/- 0.24, P <.01) and clinical study (R(2) = 0.45 +/- 0.23, P <.02). A novel lead configuration (12 precordial leads + limb leads) significantly improved maximum TWA detection compared with the conventional 12-lead ECG+ Frank lead configuration.Conclusion: TWA magnitude is dependent on the interaction of concordant and discordant alternating sources within the heart. Maximum TWA consistently localizes to the precordium and a novel lead configuration using 12 precordial leads improves TWA quantification. [ABSTRACT FROM AUTHOR]

Background: Heterogeneous ventricular activation can provide the substrate for ventricular arrhythmias (VA), but its manifestation on the electrocardiogram (ECG) as a risk stratifier is not well-defined., Objective: To characterize the spatiotemporal features of QRS peaks that best predict VA in patients with cardiomyopathy (CM) using machine learning (ML)., Methods: Prospectively enrolled CM patients with prophylactic defibrillators (n=95) underwent digital, high-resolution ECG recordings during intrinsic rhythm and ventricular pacing at 100 to 120 beats/min. Intra QRS peaks in the signal-averaged precordial leads were identified and their characteristics (amplitude, width, and timing within the QRS) were transformed into 4-bin histograms. Random forest models of these characteristics in each lead alongside clinical data were trained on 76 patients and tested on 19 patients with cross-validation to determine the features that predicted VA., Results: Patients were followed up for 45 (22-48) months, and 21% had VA. The individual machine learning (ML) models determined (area under the receiver operating characteristic curve [AUROC]) intrinsic QRS peak amplitude (0.88), width (0.78), and location (0.84) to all predict VA. In a combined model including all QRS peak characteristics, peaks with amplitude < 31 μV in V1, a width of 4 to 8 ms in V1, and location in the final quarter of the QRS of V1 were most predictive. Neither clinical data nor QRS peak characteristics assessed during ventricular pacing improved VA prediction when combined with intrinsic QRS peak characteristics., Conclusions: Arrhythmogenic QRS fragmentation is characterized by narrow, low-amplitude peaks in the terminal QRS of lead V1. These features alone without clinical variables or ventricular pacing are sufficient to accurately risk stratify CM patients., Competing Interests: Disclosure Adrian Suszko and Vijay Chauhan are co-authors of patent US11298069B2 owned by University Health Network, Canada for QRS peak detection to risk stratify patient for ventricular arrhythmia, (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Abnormal ventricular activation at rest is reported in Brugada syndrome (BrS)., Objectives: The aim of this study was to evaluate the usefulness of dynamic changes in ventricular activation during exercise to improve disease phenotyping and diagnosis of BrS., Methods: Digital 12-lead electrocardiograms during stress testing were analyzed retrospectively at baseline, peak exercise, and recovery in 53 patients with BrS and 52 controls. Biventricular activation was assessed from QRS duration (QRSd), whereas right ventricular activation was assessed from S wave duration in the lateral leads (I and V 6 ) and terminal R wave duration in aVR. Exercise-induced changes in QRS parameters to predict a positive procainamide response were assessed in separate test and validation cohorts with suspected BrS., Results: Baseline electrocardiogram parameters were similar between BrS and controls. QRSd shortened with exercise in all controls but prolonged in all BrS (-6.1 ± 6.0 ms vs 7.1 ± 6.5 ms [P < 0.001] in V 6 ). QRSd in recovery was longer in BrS compared with controls (90 ± 12 ms vs 82 ± 11 ms in V 6 ; P = 0.002). Both groups demonstrated exercise-induced S duration prolongation in V6, with greater prolongation in BrS (8.2 ± 14.3 ms vs 1.2 ± 12.4 ms; P < 0.001). Any exercise-induced QRSd prolongation in V 6 differentiated those with a positive vs negative procainamide response with 100% sensitivity and 95% specificity in the test cohort, and 87% sensitivity and 93% specificity in the validation cohort., Conclusions: Exercise-induced QRSd prolongation is ubiquitous in BrS primarily owing to delayed right ventricular activation. This electrocardiogram phenotype predicts a positive procainamide response and may provide a noninvasive screening tool to aid in the diagnosis of BrS before drug challenge., Competing Interests: Funding Support and Author Disclosures Dr Chakraborty is supported by George Mine Traveling Fellowship from the Canadian Heart Rhythm Society. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background Patients with hypertrophic cardiomyopathy (HCM) are at risk of ventricular arrhythmia (VA) attributed to abnormal electrical activation arising from myocardial fibrosis and myocyte disarray. We sought to quantify intra-QRS peaks (QRSp) in high-resolution ECGs as a measure of abnormal activation to predict late VA in patients with HCM. Methods and Results Prospectively enrolled patients with HCM (n=143, age 53±14 years) with prophylactic implantable cardioverter-defibrillators had 3-minute, high-resolution (1024 Hz), digital 12-lead ECGs recorded during intrinsic rhythm. For each precordial lead, QRSp was defined as the total number of peaks detected in the QRS complex that deviated from a smoothing filtered version of the QRS. The VA end point was appropriate implantable cardioverter-defibrillator therapy during 5-year prospective follow-up. After 5 years, 21 (16%) patients had VA. Patients who were VA positive had greater QRSp (6.0 [4.0-7.0] versus 4.0 [2.0-5.0]; P <0.01) and lower left ventricular ejection fraction (57±11 versus 62±9; P =0.038) compared with patients who were VA negative, but had similar established HCM risk metrics. Receiver operating characteristic analysis revealed that QRSp discriminated VA (area under the curve=0.76; P <0.001), with a QRSp ≥4 achieving 91% sensitivity and 39% specificity. The annual VA rate was greater in patients with QRSp ≥4 versus QRSp <4 (4.4% versus 0.98%; P =0.012). In multivariable Cox regression, age <50 years (hazard ratio [HR], 2.53; P =0.009) and QRSp (HR per QRS peak, 1.41; P =0.009) predicted VA after adjusting for established HCM risk metrics. In patients aged <50 years, the annual VA rate was 0.0% for QRSp <4 compared with 6.9% for QRSp ≥4 ( P =0.012). Conclusions QRSp predicted VA in patients with HCM who were eligible for an implantable cardioverter-defibrillator after adjusting for established HCM risk metrics, such that each additional QRS peak increases VA risk by 40%. QRSp <4 was associated with a <1% annual VA risk in all patients, and no VA risk among those aged <50 years. This novel ECG metric may improve patient selection for prophylactic implantable cardioverter-defibrillator therapy by identifying those with low VA risk. These findings require further validation in a lower risk HCM cohort. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02560844.

Background Unlike T-wave alternans (TWA), the relation between QRS alternans (QRSA) and ventricular arrhythmia (VA) risk has not been evaluated in hypertrophic cardiomyopathy (HCM). We assessed microvolt QRSA/TWA in relation to HCM risk factors and late VA outcomes in HCM. Methods and Results Prospectively enrolled patients with HCM (n=130) with prophylactic implantable cardioverter-defibrillators underwent digital 12-lead ECG recordings during ventricular pacing (100-120 beats/min). QRSA/TWA was quantified using the spectral method. Patients were categorized as QRSA+ and/or TWA+ if sustained alternans was present in ≥2 precordial leads. The VA end point was appropriate implantable cardioverter-defibrillator therapy over 5 years of follow-up. QRSA+ and TWA+ occurred together in 28% of patients and alone in 7% and 7% of patients, respectively. QRSA magnitude increased with pacing rate (1.9±0.6 versus 6.2±2.0 µV; P =0.006). Left ventricular thickness was greater in QRSA+ than in QRSA- patients (22±7 versus 20±6 mm; P =0.035). Over 5 years follow-up, 17% of patients had VA. The annual VA rate was greater in QRSA+ versus QRSA- patients (5.8% versus 2.0%; P =0.006), with the QRSA+/TWA- subgroup having the greatest rate (13.3% versus 2.6%; P <0.001). In those with <2 risk factors, QRSA- patients had a low annual VA rate compared QRSA+ patients (0.58% versus 7.1%; P =0.001). Separate Cox models revealed QRSA+ (hazard ratio [HR], 2.9 [95% CI, 1.2-7.0]; P =0.019) and QRSA+/TWA- (HR, 7.9 [95% CI, 2.9-21.7]; P <0.001) as the most significant VA predictors. TWA and HCM risk factors did not predict VA. Conclusions In HCM, microvolt QRSA is a novel, rate-dependent phenomenon that can exist without TWA and is associated with greater left ventricular thickness. QRSA increases VA risk 3-fold in all patients, whereas the absence of QRSA confers low VA risk in patients with <2 risk factors. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02560844.

Background: Although QRS duration (QRSd) is an important determinant of cardiac resynchronization therapy (CRT) response, non-responder rates remain high. QRS fragmentation can also reflect electrical dyssynchrony. We hypothesized that quantification of abnormal QRS peaks (QRSp) would predict CRT response., Methods: Forty-seven CRT patients (left ventricular ejection fraction = 23±7%) were prospectively studied. Digital 12-lead ECGs were recorded during native rhythm at baseline and 6 months post-CRT. For each precordial lead, QRSp was defined as the total number of peaks detected on the unfiltered QRS minus those detected on a smoothed moving average template QRS. CRT response was defined as >5% increase in left ventricular ejection fraction post-CRT., Results: Sixty-percent of patients responded to CRT. Baseline QRSd was similar in CRT responders and non-responders, and did not change post-CRT regardless of response. Baseline QRSp was greater in responders than non-responders (9.1±3.5 vs. 5.9±2.2, p = 0.001) and decreased in responders (9.2±3.6 vs. 7.9±2.8, p = 0.03) but increased in non-responders (5.5±2.3 vs. 7.5±2.8, p = 0.049) post-CRT. In multivariable analysis, QRSp was the only independent predictor of CRT response (Odds Ratio [95% Confidence Interval]: 1.5 [1.1-2.1], p = 0.01). ROC analysis revealed QRSp (area under curve = 0.80) to better discriminate response than QRSd (area under curve = 0.67). Compared to QRSd ≥150ms, QRSp ≥7 identified response with similar sensitivity but greater specificity (74 vs. 32%, p<0.05). Amongst patients with QRSd <150ms, more patients with QRSp ≥7 responded than those with QRSp <7 (75 vs. 0%, p<0.05)., Conclusions: Our novel automated QRSp metric independently predicts CRT response and decreases in responders. Electrical dyssynchrony assessed by QRSp may improve CRT selection and track structural remodeling, especially in those with QRSd <150ms., Competing Interests: The authors have declared that no competing interests exist.

Background: T wave alternans (TWA) is an electrocardiographic marker of heightened sudden death risk from ventricular tachyarrhythmias in patients with cardiomyopathy. TWA is evaluated from the 12-lead electrocardiogram, Frank lead, or Holter lead recordings, however these clinical lead configurations will not record TWA from adjacent regions of the body torso., Objective: We tested the hypothesis that changing heart rate or ventricular activation may alter the body surface distribution of TWA such that the clinical ECG leads fail to detect TWA in some patients; thereby producing a false-negative test., Methods: In 28 cardiomyopathy patients (left ventricular ejection fraction 28±6%), 114 unipolar electrograms were recorded across the body torso during incremental atrial pacing, followed by atrioventricular pacing at 100, 110 and 120bpm. TWA was measured from each unipolar electrogram using the spectral method. A clinically positive TWA test was defined as TWA magnitude (Valt) ≥1.9 uV with k ≥3 at ≤110bpm., Results: Maximum Valt (TWAmax) was greater from the body torso than clinical leads during atrial (p<0.005) and atrioventricular pacing (p<0.005). TWAmax was most prevalent in the right lower chest with atrial pacing 100 bpm and shifted to the left lower chest at 120 bpm. TWAmax was most prevalent in left lower chest with atrioventricular pacing at 100 bpm and shifted to the left upper chest at 120 bpm. Using the body torso as a gold standard, the false-negative rate for clinically positive TWA with clinical leads was 21% during atrial and 11% during atrioventricular pacing. Due to TWA signal migration outside the clinical leads, clinically positive TWA became false-negative when pacing mode was switched (atrial→atrioventricular pacing) in 21% of patients., Conclusions: The body surface distribution of TWA is modulated by heart rate and the sequence of ventricular activation in patients with cardiomyopathy, which can give rise to modest false-negative TWA signal detection using standard clinical leads., Competing Interests: The authors have declared that no competing interests exist.

Background: Cardiomyopathy patients are at risk of sudden death, typically from scar-related abnormalities of electrical activation that promote ventricular tachyarrhythmias. Abnormal intra-QRS peaks may provide a measure of altered activation. We hypothesized that quantification of such QRS peaks (QRSp) in high-resolution ECGs would predict arrhythmic events in implantable cardioverter-defibrillator (ICD)-eligible cardiomyopathy patients., Methods and Results: Ninety-nine patients with ischemic or non-ischemic dilated cardiomyopathy undergoing prophylactic ICD implantation were prospectively enrolled (age 62±11 years, left ventricular ejection fraction 27±7%). High-resolution (1024 Hz) digital 12-lead ECGs were recorded during intrinsic rhythm. QRSp was quantified for each precordial lead as the total number of low-amplitude deflections that deviated from their respective naive QRS template. The primary end point of arrhythmic events was defined as appropriate ICD therapy or sustained ventricular tachyarrhythmias. After a median follow-up of 24 (15-43) months, 20 (20%) patients had arrhythmic events. Both QRSp and QRS duration were greater in those with arrhythmic events (both P <0.001) and this was consistent for QRSp for both cardiomyopathy types. In a multivariable Cox regression model that included age, left ventricular ejection fraction, QRS duration, and QRSp, only QRSp was an independent predictor of arrhythmic events (hazard ratio, 2.1; P <0.001). Receiver operating characteristic analysis revealed that a QRSp ≥2.25 identified arrhythmic events with greater sensitivity (100% versus 70%, P <0.05) and negative predictive value (100% versus 89%, P <0.05) than QRS duration ≥120 ms., Conclusions: QRSp measured from high-resolution digital 12-lead ECGs independently predicts ventricular tachyarrhythmias in ICD-eligible cardiomyopathy patients. This novel QRS morphology index has the potential to improve sudden death risk stratification and patient selection for prophylactic ICD therapy., (© 2017 American Heart Association, Inc.)

Background: Nonsustained ventricular tachycardia (NSVT) detected by ambulatory Holter (Holter NSVT) is a major risk factor for sudden cardiac death in hypertrophic cardiomyopathy (HCM). We hypothesized that the prognostic utility of Holter NSVT in HCM would improve with prolonged monitoring and a higher heart rate cut-off for detection., Methods: We enrolled 60 patients (44 ± 14 years) with HCM, who had a prophylactic implantable cardioverter defibrillator (ICD). Positive Holter NSVT (prior to implant) was defined as ≥3 beats at ≥120 beats per minute (bpm). We assessed the prevalence of rapid NSVT (RNSVT) detected by their ICD within 12 months of its implant, defined as 4-16 beats at ≥150-200 bpm. The primary outcome was appropriate ICD therapy (antitachycardia pacing and shocks) for sustained ventricular arrhythmia (VA)., Results: Holter NSVT was detected in 34 patients. RNSVT occurred in 21 (35%) patients of whom five did not have Holter NSVT. Over a median follow-up of 61 (interquartile range 29, 129) months after ICD implant, nine patients had VA. RNSVT, but not Holter NSVT, was significantly associated with VA (hazard ratio 6.2, 95% confidence interval [1.3-30], P = 0.01) by multivariable Cox regression analysis that included conventional risk factors. Receiver operating characteristic analysis for RNSVT (area under curve 0.80, P = 0.005) showed that the occurrence of ≥2 episodes of RNSVT discriminated patients for VA optimally (sensitivity 78%, specificity 84%, positive predictive value 47%, negative predictive value 96%)., Conclusions: In this pilot study, RNSVT detected by continuous monitoring independently predicted VA in HCM and offered superior discrimination of VA risk compared to conventional risk factors, including Holter NSVT. Future studies are needed to validate these findings in a larger, unselected HCM cohort., (©2016 Wiley Periodicals, Inc.)

Scar delineation with late gadolinium-enhanced MRI can direct VT substrate mapping and ablation, but imaging is poor and relatively contraindicated in the majority of patients with ICDs. We present a case of scar definition using late iodine-enhanced multidetector CT in a patient with ischemic cardiomyopathy and multiple ICD shocks for VT. CT images were acquired using a novel intracoronary contrast delivery protocol which provided high-resolution subendocardial scar visualization. The segmented scar images were subsequently imported into an electroanatomic mapping platform to guide successful VT ablation., (© 2012 Wiley Periodicals, Inc.)

Background: Bipolar voltage mapping has a role in defining endocardial-based scar in postinfarct patients undergoing ventricular tachycardia catheter ablation. The utility of bipolar and unipolar voltages in characterizing scar has not been evaluated in patients with nonischemic cardiomyopathy., Objective: To relate left ventricular (LV) endocardial bipolar and unipolar voltages in these patients to scar transmurality (endocardial vs nonendocardial) and composition (homogeneous core vs heterogeneous gray)., Methods: Ten consecutive cardiomyopathy patients undergoing endocardial LV tachycardia ablation were included (age 48 ± 14 years; left ventricular ejection fraction 43% ± 15%). Preablation late gadolinium-enhanced magnetic resonance imaging was used to quantify core and gray scar by using signal-intensity thresholding. Electroanatomic LV endocardial mapping provided bipolar and unipolar voltages. Electroanatomic maps and late gadolinium-enhanced magnetic resonance imaging were rigidly registered in order to relate voltage to scar (registration error 3.6 ± 2.9 mm)., Results: Bipolar voltage was lower in endocardial core than in no scar (P <.001). Unipolar voltage was lower in endocardial core and nonendocardial core than in no scar (P <.001). Endocardial and nonendocardial gray scar had an effect similar to that of core in reducing bipolar and unipolar voltages (P <.001). The mass of healthy myocardium and endocardial core scar independently predicted bipolar and unipolar voltages using general estimating equation modeling. With receiver operating characteristic curve analysis, bipolar voltage >1.9 mV and unipolar voltage <6.7 mV had a high negative predictive value (91%) for detecting nonendocardial scar from either endocardial scar or no scar., Conclusions: In patients with nonischemic cardiomyopathy, LV endocardial bipolar voltage is dependent on endocardial core and gray scar, while the unipolar voltage is influenced by core and gray scar across the LV wall as defined by late gadolinium-enhanced magnetic resonance imaging., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The arrhythmogenic substrate in survivors of unexplained cardiac arrest (UCA) has not been defined., Objectives: To test the hypothesis that patients with UCA have latent repolarization abnormalities, in particular T-wave alternans (TWA), which may be unmasked with epinephrine (EPI) challenge., Methods: We prospectively studied 10 UCA survivors (46 ± 9 years) and 11 first-degree relatives (FDRs) of sudden death victims (37 ± 14 years). Patients with UCA underwent standard clinical testing, which was normal. FDRs had normal clinical history and testing. All subjects underwent an EPI infusion (0.05, 0.1, and 0.2 μg/(kg·min), 5 minutes each dose) while recording continuous digital 12-lead electrocardiograms. Corrected QT interval and QT variability index were evaluated at each EPI dose. TWA magnitude (V(alt)) was assessed at each dose by using the spectral method. Positive (+) TWA at each dose was defined as V(alt) > 0 with k ≥ 3 in 1 or more 128-beat segment in ≥2 electrocardiogram leads. A novel metric, TWA burden, reflecting V(alt) integrated over time (s), was also evaluated for each EPI dose., Results: There was no difference between UCA survivors and FDRs with respect to heart rate, QT, corrected QT interval, or QT variability index at baseline or during EPI. At baseline, +TWA was similar between UCA survivors and FDRs (10% vs 0%; P = NS). During EPI, +TWA was more prevalent in UCA survivors than in FDRs (80% vs 18%; P = .009). TWA burden was greater in UCA survivors than in FDRs during EPI 0.1 (P = .039) and EPI 0.2 μg/(kg·min) (P = .009)., Conclusions: UCA survivors are more likely to demonstrate latent TWA compared with FDRs, which becomes manifest with EPI. This novel finding provides evidence for an arrhythmogenic substrate in UCA survivors., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)