Noninvasive characterization of atrioventricular conduction in patients with atrial fibrillation.

The atrioventricular (AV) node plays a fundamental role in patients with atrial fibrillation (AF), acting as a filter to the numerous irregular atrial impulses which bombard the node. A phenomenological approach to better understand AV nodal electrophysiology is to analyze the ventricular response with respect to irregularity. In different cohorts of AF patients, such analysis has been performed with the aim to evaluate the association between ventricular response characteristics and long-term clinical outcome and to determine whether irregularity is affected by rate-control drugs. Another approach to studying AV nodal characteristics is to employ a mathematical model which accounts for the refractory periods of the two AV nodal pathways. With atrial fibrillatory rate and RR intervals as input, the model has been considered for analyzing data during (i) rest and head-up tilt test, (ii) tecadenoson and esmolol, and (iii) rate-control drugs. The present paper provides an overview of our recent work on the characterization and assessment of AV nodal conduction using these two approaches.

Variability of P-wave morphology predicts the outcome of circumferential pulmonary vein isolation in patients with recurrent atrial fibrillation.

INTRODUCTION: Severe atrial structural remodeling may reflect irreversible damage of the atrial tissue in patients with atrial fibrillation (AF) and is associated with changes of P-wave duration and morphology. Our aim was to study whether variability of P-wave morphology (PMV) is associated with outcome in patients with AF after circumferential PV isolation (CPVI). METHODS AND RESULTS: 70 consecutive patients (aged 60±9years, 46 men) undergoing CPVI due to symptomatic AF were studied. After cessation of antiarrhythmic therapy, standard 12-lead ECG during sinus rhythm was recorded for 10min at baseline and transformed to orthogonal leads. Beat-to-beat P-wave morphology was subsequently defined using a pre-defined classification algorithm. The most commonly observed P-wave morphology in a patient was defined as the dominant morphology. PMV was defined as the percentage of P waves with non-dominant morphology in the 10-min sample. At the end of follow-up, 53 of 70 patients had no arrhythmia recurrence. PMV was greater in patients without recurrence (19.5±17.1% vs. 8.2±6.7%, p<0.001). In the multivariate logistic regression model, PMV≥20% (upper tertile) was the only independent predictor of ablation success (OR=11.4, 95% CI 1.4-92.1, p=0.023). A PMV≥20% demonstrated a sensitivity of 41.5%, a specificity of 94.1%, a PPV of 96.7%, and an NPV of 34.0% for free of AF after CPVI. CONCLUSIONS: We report a significant association between increased PMV and 6-month CPVI success. PMV may help to identify patients with very high likelihood of freedom of AF 6-months after CPVI.

Non-invasive evaluation of the effect of metoprolol on the atrioventricular node during permanent atrial fibrillation.

AIMS: During atrial fibrillation (AF), conventional electrophysiological techniques for assessment of refractory period or conduction velocity of the atrioventricular (AV) node cannot be used. We aimed at evaluating changes in AV nodal properties during administration of metoprolol from electrocardiogram data, and to support our findings with simulated data based on results from an electrophysiological study. METHODS AND RESULTS: Sixty patients (age 71 ± 9 years, 42 men) with permanent AF were included in the RATe control in Atrial Fibrillation (RATAF) study. Two 15 min segments, during baseline and metoprolol administration, starting at 2 pm were analysed in this study. Atrial fibrillatory rate (AFR), heart rate (HR), and AV nodal parameters were assessed. The AV nodal parameters account for the probability of an impulse not taking the fast pathway, the absolute refractory periods of the slow and fast pathways (aRPs and aRPf), representing the functional refractory period, and their respective prolongation in refractory period. In addition, simulated RR series were generated that mimic metoprolol administration through prolonged AV conduction interval and AV node effective refractory period. During metoprolol administration, AFR and HR were significantly decreased and aRP was significantly prolonged in both pathways (aRPs: 337 ± 60 vs. 398 ± 79 ms, P < 0.01; aRPf: 430 ± 91 vs. 517 ± 100 ms, P < 0.01). Similar results were found for the simulated RR series, both aRPs and aRPf being prolonged with metoprolol (aRPs: 413 ± 33 vs. 437 ± 43 ms, P = 0.01; aRPf: 465 ± 40 vs. 502 ± 69 ms, P = 0.02). CONCLUSION: The AV nodal parameters reflect expected changes after metoprolol administration, i.e. a prolongation in functional refractory period. The simulations confirmed that aRPs and aRPf may serve as an estimate of the functional refractory period.

In silico cardiac risk assessment in patients with long QT syndrome: type 1: clinical predictability of cardiac models.

OBJECTIVES: The study was designed to assess the ability of computer-simulated electrocardiography parameters to predict clinical outcomes and to risk-stratify patients with long QT syndrome type 1 (LQT1). BACKGROUND: Although attempts have been made to correlate mutation-specific ion channel dysfunction with patient phenotype in long QT syndrome, these have been largely unsuccessful. Systems-level computational models can be used to predict consequences of complex changes in channel function to the overall heart rhythm. METHODS: A total of 633 LQT1-genotyped subjects with 34 mutations from multinational long QT syndrome registries were studied. Cellular electrophysiology function was determined for the mutations and introduced in a 1-dimensional transmural electrocardiography computer model. The mutation effect on transmural repolarization was determined for each mutation and related to the risk for cardiac events (syncope, aborted cardiac arrest, and sudden cardiac death) among patients. RESULTS: Multivariate analysis showed that mutation-specific transmural repolarization prolongation (TRP) was associated with an increased risk for cardiac events (35% per 10-ms increment [p < 0.0001]; ≥upper quartile hazard ratio: 2.80 [p < 0.0001]) and life-threatening events (aborted cardiac arrest/sudden cardiac death: 27% per 10-ms increment [p = 0.03]; ≥upper quartile hazard ratio: 2.24 [p = 0.002]) independently of patients' individual QT interval corrected for heart rate (QTc). Subgroup analysis showed that among patients with mild to moderate QTc duration (<500 ms), the risk associated with TRP was maintained (36% per 10 ms [p < 0.0001]), whereas the patient's individual QTc was not associated with a significant risk increase after adjustment for TRP. CONCLUSIONS: These findings suggest that simulated repolarization can be used to predict clinical outcomes and to improve risk stratification in patients with LQT1, with a more pronounced effect among patients with a lower-range QTc, in whom a patient's individual QTc may provide less incremental prognostic information.

Interatrial conduction can be accurately determined using standard 12-lead electrocardiography: validation of P-wave morphology using electroanatomic mapping in man.

BACKGROUND: Different P-wave morphologies during sinus rhythm as displayed on standard ECGs have been postulated to correspond to differences in interatrial conduction. OBJECTIVE: The purpose of this study was to evaluate the hypothesis by comparing P-wave morphologies using left atrial activation maps. METHODS: Twenty-eight patients (mean age 49 +/- 9 years) admitted for ablation of paroxysmal atrial fibrillation were studied. Electroanatomic mapping of left atrial activation was performed at baseline during sinus rhythm with simultaneous recording of standard 12-lead ECG. Unfiltered signal-averaged P waves were analyzed to determine orthogonal P-wave morphology. The morphology was subsequently classified into one of three predefined types. All analyses were blinded. RESULTS: The primary left atrial breakthrough site was the fossa ovalis in 8 patients, Bachmann bundle in 18, and coronary sinus in 2. Type 1 P-wave morphology was observed in 9 patients, type 2 in 17, and type 3 in 2. Seven of eight patients with fossa ovalis breakthrough had type 1 P-wave morphology, 16 of 18 patients with Bachmann bundle breakthrough had type 2 morphology, and both patients with coronary sinus breakthrough had type 3 P-wave morphology. Overall, P-wave morphology criteria correctly identified the site of left atrial breakthrough in 25 (89%) of 28 patients. CONCLUSION: In the vast majority of patients, P-wave morphology derived from standard 12-lead ECG can be used to correctly identify the left atrial breakthrough site and the corresponding route of interatrial conduction.