Exercise-Induced QRS Prolongation in Brugada Syndrome: Implications for Improving Disease Phenotyping and Diagnosis.

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 V6) 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 V6). QRSd in recovery was longer in BrS compared with controls (90 ± 12 ms vs 82 ± 11 ms in V6; 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 V6 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.

P-Wave Duration/Amplitude Ratio Quantifies Atrial Low-Voltage Area and Predicts Atrial Arrhythmia Recurrence After Pulmonary Vein Isolation.

BACKGROUND: Atrial low-voltage areas (LVAs) in patients with atrial fibrillation increase the risk of atrial arrhythmia (AA) recurrence after pulmonary vein isolation (PVI). Contemporary LVA prediction scores (DR-FLASH, APPLE) do not include P-wave metrics. We aimed to evaluate the utility of P-wave duration/amplitude ratio (PWR) in quantifying LVA and predicting AA recurrence after PVI. METHODS: In 65 patients undergoing first-time PVI, 12-lead ECGs were recorded during sinus rhythm. PWR was calculated as the ratio between the longest P-wave duration and P-wave amplitude in lead I. High-resolution biatrial voltage maps were collected and LVAs included bipolar electrogram amplitudes < 0.5 mV or < 1.0 mV. An LVA quantification model was created with the use of clinical variables and PWR, and then validated in a separate cohort of 24 patients. Seventy-eight patients were followed for 12 months to evaluate AA recurrence. RESULTS: PWR strongly correlated with left atrial (LA) (< 0.5 mV: r = 0.60; < 1.0 mV: r = 0.68; P < 0.001) and biatrial LVA (< 0.5 mV: r = 0.63; < 1.0 mV: r = 0.70; P < 0.001). Addition of PWR to clinical variables improved model quantification of LA LVA at the < 0.5 mV (adjusted R2 = 0.59 to 0.68) and < 1.0 mV (adjusted R2 = 0.59 to 0.74) cutoffs. In the validation cohort, PWR model-predicted LVA correlated strongly with measured LVA (< 0.5 mV: r = 0.78; < 1.0 mV: r = 0.81; P < 0.001). PWR model was superior to DR-FLASH (area under the receiver operating characteristic curve [AUC] 0.90 vs 0.78; P = 0.030) and APPLE (AUC 0.90 vs 0.67; P = 0.003) at detecting LA LVA and similar at predicting AA recurrence after PVI (AUC 0.67 vs 0.65 and 0.60). CONCLUSION: Our novel PWR model accurately quantifies LVA and predicts AA recurrence after PVI. PWR model-predicted LVA may help guide patient selection for PVI.

Unipolar electrogram-based voltage mapping with far-field cancellation to improve detection of abnormal atrial substrate during atrial fibrillation.

INTRODUCTION: An important substrate for atrial fibrillation (AF) is fibrotic atrial myopathy. Identifying low voltage, myopathic regions during AF using traditional bipolar voltage mapping is limited by the directional dependency of wave propagation. Our objective was to evaluate directionally independent unipolar voltage mapping, but with far-field cancellation, to identify low-voltage regions during AF. METHODS: In 12 patients undergoing pulmonary vein isolation for AF, high-resolution voltage mapping was performed in the left atrium during sinus rhythm and AF using a roving 20-pole circular catheter. Bipolar electrograms (EGMs) (Bi) < 0.5 mV in sinus rhythm identified low-voltage regions. During AF, bipolar voltage and unipolar voltage maps were created, the latter with (uni-res) and without (uni-orig) far-field cancellation using a novel, validated least-squares algorithm. RESULTS: Uni-res voltage was ~25% lower than uni-orig for both low voltage and normal atrial regions. Far-field EGM had a dominant frequency (DF) of 4.5-6.0 Hz, and its removal resulted in a lower DF for uni-orig compared with uni-res (5.1 ± 1.5 vs. 4.8 ± 1.5 Hz; p < .001). Compared with Bi, uni-res had a significantly greater area under the receiver operator curve (0.80 vs. 0.77; p < .05), specificity (86% vs. 76%; p < .001), and positive predictive value (43% vs. 30%; p < .001) for detecting low-voltage during AF. Similar improvements in specificity and positive predictive value were evident for uni-res versus uni-orig. CONCLUSION: Far-field EGM can be reliably removed from uni-orig using our novel, least-squares algorithm. Compared with Bi and uni-orig, uni-res is more accurate in detecting low-voltage regions during AF. This approach may improve substrate mapping and ablation during AF, and merits further study.