The Spatial Ventricular Gradient is Associated with Inducibility of Ventricular Arrhythmias During Electrophysiology Study.

BACKGROUND: Myocardial electrical heterogeneity is critical for normal cardiac electromechanical function, but abnormal/excessive electrical heterogeneity is proarrhythmic. The spatial ventricular gradient (SVG), a vectorcardiographic measure of electrical heterogeneity, has been associated with arrhythmic events over long-term follow-up, but its relationship with short-term inducibility of ventricular arrhythmias (VAs) is unclear. OBJECTIVE: Determine associations between SVG and inducible VAs during electrophysiology study (EPS). METHODS: Retrospective study of adults without prior sustained VA, cardiac arrest, or implantable cardioverter-defibrillator (ICD), who underwent ventricular stimulation for evaluation of syncope, non-sustained VT, and/or risk-stratification prior to primary prevention ICD implantation. 12-lead ECGs were converted into vectorcardiograms and SVG magnitude (SVGmag) and direction (azimuth and elevation) were calculated. Odds of inducible VA were regressed using logistic models. RESULTS: Among 143 patients (median age 66, 80% male, median LVEF 47%, 52% myocardial infarction), 34 (23.8%) had inducible VAs. Inducible patients had lower median LVEF (38 vs 50%, p<0.0001), smaller SVGmag (29.5 vs 39.4mV*ms, p=0.0099), and smaller cosine SVG azimuth (cosSVGaz) (0.64 vs 0.89, p=0.0007). When LVEF, SVGmag, and cosSVGaz were dichotomized at their medians, there was a 39-fold increase in adjusted odds (p=0.002) between patients with all low LVEF, SVGmag, and cosSVGaz (65% inducible), compared to patients with all high LVEF, SVGmag, and cosSVGaz (4% [n=1] inducible). After multivariable adjustment, SVGmag, cosSVGaz, and sex, but not LVEF or other characteristics, remained associated with inducible VAs. CONCLUSION: Assessment of electrical heterogeneity via SVG, which reflects abnormal electrophysiological substrate, adds to LVEF and identifies patients at high and low risk of inducible VA at EPS.

P-wave alternans rebound following pulmonary vein isolation predicts atrial arrhythmia recurrence.

INTRODUCTION: Numerous P-wave indices have been explored as biomarkers to assess atrial fibrillation (AF) risk and the impact of therapy with variable success. OBJECTIVE: We investigated the utility of P-wave alternans (PWA) to track the effects of pulmonary vein isolation (PVI) and to predict atrial arrhythmia recurrence. METHODS: This medical records study included patients who underwent PVI for AF ablation at our institution, along with 20 control subjects without AF or overt cardiovascular disease. PWA was assessed using novel artificial intelligence-enabled modified moving average (AI-MMA) algorithms. PWA was monitored from the 12-lead ECG at ~1 h before and ~16 h after PVI (n = 45) and at the 4- to 17-week clinically indicated follow-up visit (n = 30). The arrhythmia follow-up period was 955 ± 112 days. RESULTS: PVI acutely reduced PWA by 48%-63% (p < .05) to control ranges in leads II, III, aVF, the leads with the greatest sensitivity in monitoring PWA. Pre-ablation PWA was ~6 µV and decreased to ~3 µV following ablation. Patients who exhibited a rebound in PWA to pre-ablation levels at 4- to 17-week follow-up (p < .01) experienced recurrent atrial arrhythmias, whereas patients whose PWA remained reduced (p = .85) did not, resulting in a significant difference (p < .001) at follow-up. The AUC for PWA's prediction of first recurrence of atrial arrhythmia was 0.81 (p < .01) with 88% sensitivity and 82% specificity. Kaplan-Meier analysis estimated atrial arrhythmia-free survival (p < .01) with an adjusted hazard ratio of 3.4 (95% CI: 1.47-5.24, p < .02). CONCLUSION: A rebound in PWA to pre-ablation levels detected by AI-MMA in the 12-lead ECG at standard clinical follow-up predicts atrial arrhythmia recurrence.

The Use of Local Activation Timing Histogram in Ablation of Focal and Re-Entrant Atrial Tachycardias.

BACKGROUND: Activation mapping is often used to differentiate focal from re-entrant arrhythmias. This can be challenging but is critical to ablation success. The local activation time (LAT) histogram, which depicts point distribution over isochronal segments, may help characterize arrhythmia mechanisms and identify an optimal ablation strategy. OBJECTIVES: This study aimed to investigate features of the LAT histogram associated with the focal vs re-entrant mechanism of atrial tachycardias (ATs) and the use of the LAT histogram in the identification of target ablation sites. METHODS: We retrospectively evaluated cases of focal and re-entrant ATs performed at a single academic tertiary care center for which activation mapping was performed using CARTO 3 version 7 software (Biosense Webster). Baseline patient, arrhythmia, and procedural characteristics as well as LAT histogram features were evaluated for each case. LAT histogram-guided ablation targets were also compared against actual ablation sites. RESULTS: Among 52 ATs assessed, 17 were focal, and 35 were re-entrant. Tachycardia cycle length was significantly shorter in re-entrant than in focal ATs (288.2 milliseconds [Q1-Q3: 250-306.5 milliseconds] vs 370 milliseconds [Q1-Q3: 285-400 milliseconds], respectively; P = 0.006). LAT histograms contained more "valleys" in re-entrant than in focal ATs (3 [Q1-Q3: 2-4] vs 1 [Q1-Q3: 1-1]; P < 0.001). No focal ATs contained >2 and no re-entrant ATs contained <1 LAT valley(s). All successful ablation sites correlated with LAT histogram-suggested sites. CONCLUSIONS: LAT histograms can help distinguish focal from re-entrant Ats and identify effective ablation sites.

Procedural Adaptations to Avoid Haemodynamic Instability During Catheter Ablation of Scar-related Ventricular Tachycardia.

Classically, catheter ablation for scar-related ventricular tachycardia (VT) relied upon activation and entrainment mapping of induced VT. Advances in post-MI therapies have led to VTs that are faster and haemodynamically less stable, because of more heterogeneous myocardial fibrosis patterns. The PAINESD score is one means of identifying patients at highest risk for haemodynamic decompensation during attempted VT induction, who may, therefore, benefit from alternative ablation strategies. One strategy is to use temporary mechanical circulatory support, although this warrants formal assessment of cost-effectiveness. A second strategy is to minimise or avoid VT induction altogether by employing a family of 'substrate'-based approaches aimed at identifying VT isthmuses during sinus or paced rhythm. Substrate mapping techniques are diverse, and focus on the timing, morphology and amplitude of local ventricular electrograms - sometimes aided by advanced non-invasive cardiac imaging modalities. In this review, the evolution of VT ablation over time is discussed, with an emphasis on procedural adaptations to the challenge of haemodynamic instability.

Correlation Between Functional Substrate Mapping and Cardiac Computed Tomography-Derived Wall Thinning for Ventricular Tachycardia Ablation.

BACKGROUND: Functional substrate mapping during baseline rhythm can identify arrhythmogenic tissue during ventricular tachycardia (VT) ablation. Wall thinning and wall thickness channels (WTCs) derived from computed tomography angiography have been shown to correlate with low voltage and VT isthmuses. The correlation between functional substrate mapping, wall thinning, and WTCs in patients with infarct- or non-infarct-related cardiomyopathies (ICM and NICM, respectively) has not been previously described. OBJECTIVES: The purpose of this study was to correlate cardiac CTA-derived myocardial wall thinning with functional VT substrate mapping using isochronal late activation mapping. METHODS: In 34 patients with ICM or NICM undergoing VT ablation who had a preprocedure computed tomography angiography, myocardial wall thinning was segmented in layers of 1 to 5 mm. Areas of wall thinning and WTCs were then spatially correlated with deceleration zones (DZs) from registered left ventricular endocardial isochronal late activation maps. RESULTS: In 21 ICM patients and 13 NICM patients, ICM patients had greater surfaces areas of wall thinning (P < 0.001). In ICM patients, 94.1% of primary DZs were located on areas of wall thinning, compared to 20% of DZs in NICM patients overall but 50% if there was any wall thinning present. Fifty-nine percent of DZs in ICM patients and 56% of DZs in NICM patients were located near WTCs. The positive predictive value for WTC in localizing DZs was 22.5% and 37.8% in ICM and NICM patients, respectively. CONCLUSIONS: Wall thinning is highly sensitive for functional substrate in ICM patients. WTCs had modest sensitivity for functional substrate but low positive predictive value for identifying DZs in ICM and NICM patients. These findings suggest that wall thinning may facilitate more efficient mapping in ICM patients, but WTCs are insufficient to localize wavefront discontinuities.

Individuals with chronic epilepsy have elevated P-wave heterogeneity comparable to patients with atrial fibrillation.

OBJECTIVE: Identification of epilepsy patients with elevated risk for atrial fibrillation (AF) is critical given the heightened morbidity and premature mortality associated with this arrhythmia. Epilepsy is a worldwide health problem affecting nearly 3.4 million people in the United States alone. The potential for increased risk for AF in patients with epilepsy is not well appreciated, despite recent evidence from a national survey of 1.4 million hospitalizations indicating that AF is the most common arrhythmia in people with epilepsy. METHODS: We analyzed inter-lead heterogeneity of P-wave morphology, a marker reflecting arrhythmogenic nonuniformities of activation/conduction in atrial tissue. The study groups consisted of 96 patients with epilepsy and 44 consecutive patients with AF in sinus rhythm before clinically indicated ablation. Individuals without cardiovascular or neurological conditions (n = 77) were also assessed. We calculated P-wave heterogeneity (PWH) by second central moment analysis of simultaneous beats from leads II, III, and aVR ("atrial dedicated leads") from standard 12-lead electrocardiography (ECG) recordings from admission day to the epilepsy monitoring unit (EMU). RESULTS: Female patients composed 62.5%, 59.6%, and 57.1% of the epilepsy, AF, and control subjects, respectively. The AF cohort was older (66 ± 1.1 years) than the epilepsy group (44 ± 1.8 years, p < .001). The level of PWH was greater in the epilepsy group than in the control group (67 ± 2.6 vs. 57 ± 2.5 µV, p = .046) and reached levels observed in AF patients (67 ± 2.6 vs. 68 ± 4.9 µV, p = .99). In multiple linear regression analysis, PWH levels in individuals with epilepsy were mainly correlated with the PR interval and could be related to sympathetic tone. Epilepsy remained associated with PWH after adjustments for cardiac risk factors, age, and sex. SIGNIFICANCE: Patients with chronic epilepsy have increased PWH comparable to levels observed in patients with AF, while being ~20 years younger, suggesting an acceleration in structural change and/or cardiac electrical instability. These observations are consistent with emerging evidence of an "epileptic heart" condition.

Reduction in atrial and ventricular electrical heterogeneity following pulmonary vein isolation in patients with atrial fibrillation.

BACKGROUND: Pulmonary vein isolation (PVI) modulates the intrinsic cardiac autonomic nervous system and reduces atrial fibrillation (AF) recurrence. METHODS: In this retrospective analysis, we investigated the impact of PVI on ECG interlead P-wave, R-wave, and T-wave heterogeneity (PWH, RWH, TWH) in 45 patients in sinus rhythm undergoing clinically indicated PVI for AF. We measured PWH as a marker of atrial electrical dispersion and AF susceptibility and RWH and TWH as markers of ventricular arrhythmia risk along with standard ECG measures. RESULTS: PVI acutely (16 ± 8.9 h) reduced PWH by 20.7% (from 31 ± 1.9 to 25 ± 1.6 µV, p < 0.001) and TWH by 27% (from 111 ± 7.8 to 81 ± 6.5 µV, p < 0.001). RWH was unchanged after PVI (p = 0.068). In a subgroup of 20 patients with longer follow-up (mean = 47 ± 3.7 days after PVI), PWH remained low (25 ± 1.7 µV, p = 0.01), but TWH partially returned to the pre-ablation level (to 93 ± 10.2, p = 0.16). In three individuals with early recurrence of atrial arrhythmia in the first 3 months after ablation, PWH increased acutely by 8.5%, while in patients without early recurrence, PWH decreased acutely by 22.3% (p = 0.048). PWH was superior to other contemporary P-wave metrics including P-wave axis, dispersion, and duration in predicting early AF recurrence. CONCLUSION: The rapid time course of decreased PWH and TWH after PVI suggests a beneficial influence likely mediated via ablation of the intrinsic cardiac nervous system. Acute responses of PWH and TWH to PVI suggest a favorable dual effect on atrial and ventricular electrical stability and could be used to track individual patients' electrical heterogeneity profile.

Wide Complex Tachycardia and Cardiac Arrest During Endoscopy.

A 59-year-old man presented for implantable cardioverter-defibrillator placement after a wide QRS complex tachycardia cardiac arrest at an outside hospital. In this case report, we discuss the differential diagnosis of this patient's tachyarrhythmia and the electrophysiological studies that established the diagnosis and guided management. (Level of Difficulty: Intermediate.).

Risk of QT Interval Prolongation Associated With Use of Hydroxychloroquine With or Without Concomitant Azithromycin Among Hospitalized Patients Testing Positive for Coronavirus Disease 2019 (COVID-19).

IMPORTANCE: Administration of hydroxychloroquine with or without azithromycin for the treatment of coronavirus disease 2019 (COVID-19)-associated pneumonia carries increased risk of corrected QT (QTc) prolongation and cardiac arrhythmias. OBJECTIVE: To characterize the risk and degree of QT prolongation in patients with COVID-19 in association with their use of hydroxychloroquine with or without concomitant azithromycin. DESIGN, SETTING, AND PARTICIPANTS: This was a cohort study performed at an academic tertiary care center in Boston, Massachusetts, of patients hospitalized with at least 1 positive COVID-19 nasopharyngeal polymerase chain reaction test result and clinical findings consistent with pneumonia who received at least 1 day of hydroxychloroquine from March 1, 2020, through April 7, 2020. MAIN OUTCOMES AND MEASURES: Change in QT interval after receiving hydroxychloroquine with or without azithromycin; occurrence of other potential adverse drug events. RESULTS: Among 90 patients given hydroxychloroquine, 53 received concomitant azithromycin; 44 (48.9%) were female, and the mean (SD) body mass index was 31.5 (6.6). Hypertension (in 48 patients [53.3%]) and diabetes mellitus (in 26 patients [28.9%]) were the most common comorbid conditions. The overall median (interquartile range) baseline QTc was 455 (430-474) milliseconds (hydroxychloroquine, 473 [454-487] milliseconds vs hydroxychloroquine and azithromycin, 442 [427-461] milliseconds; P < .001). Those receiving concomitant azithromycin had a greater median (interquartile range) change in QT interval (23 [10-40] milliseconds) compared with those receiving hydroxychloroquine alone (5.5 [-15.5 to 34.25] milliseconds; P = .03). Seven patients (19%) who received hydroxychloroquine monotherapy developed prolonged QTc of 500 milliseconds or more, and 3 patients (8%) had a change in QTc of 60 milliseconds or more. Of those who received concomitant azithromycin, 11 of 53 (21%) had prolonged QTc of 500 milliseconds or more and 7 of 53 (13 %) had a change in QTc of 60 milliseconds or more. The likelihood of prolonged QTc was greater in those who received concomitant loop diuretics (adjusted odds ratio, 3.38 [95% CI, 1.03-11.08]) or had a baseline QTc of 450 milliseconds or more (adjusted odds ratio, 7.11 [95% CI, 1.75-28.87]). Ten patients had hydroxychloroquine discontinued early because of potential adverse drug events, including intractable nausea, hypoglycemia, and 1 case of torsades de pointes. CONCLUSIONS AND RELEVANCE: In this cohort study, patients who received hydroxychloroquine for the treatment of pneumonia associated with COVID-19 were at high risk of QTc prolongation, and concurrent treatment with azithromycin was associated with greater changes in QTc. Clinicians should carefully weigh risks and benefits if considering hydroxychloroquine and azithromycin, with close monitoring of QTc and concomitant medication usage.

Global longitudinal strain from resting echocardiogram is associated with long-term adverse cardiac outcomes in patients with suspected coronary artery disease.

PURPOSE: Measuring myocardial strain using two-dimensional speckle tracking echocardiography has emerged as a new tool to identify subclinical ventricular dysfunction. Abnormal strain has been shown to have superior sensitivity compared with dobutamine stress echocardiography for viability assessment; however, there is a paucity of data regarding the prediction of long-term major adverse cardiac events. We compared the prognostic ability of both global longitudinal strain (GLS) from resting echocardiograms to regional wall motion score index (WMSI) from stress echocardiograms in their ability to predict long-term major adverse cardiac events. METHODS: Patients referred for stress echocardiography, who also underwent coronary angiography within 3 months of stress echo (n=122), were enrolled. Patients with reduced ejection fractions (<40%) were excluded. Patients were followed for a median of 3.4 years for major adverse cardiac events, readmissions and repeat cardiac testing. RESULTS: Patients with abnormal GLS (GLS <16.8%) from the resting echocardiogram obtained as part of the exercise echocardiogram experienced a significantly shorter time to major adverse cardiac events (p=0.026), first cardiovascular hospitalization and repeat cardiac testing (p=0.0011) compared to those with normal GLS. Abnormal GLS appears to be a better predictor than abnormal WMSI in predicting major adverse cardiac events (p=0.174) and time to first cardiovascular hospitalization or repeat cardiac testing (p=0.0093). CONCLUSION: GLS may be a better predictor of long-term major adverse cardiac events, readmissions and repeat cardiac testing than WMSI in patients undergoing stress echocardiography.