Dominant frequency increase rate predicts transition from paroxysmal to long-term persistent atrial fibrillation.

BACKGROUND: Little is known about the mechanisms underlying the transition from paroxysmal to persistent atrial fibrillation (AF). In an ovine model of long-standing persistent AF we tested the hypothesis that the rate of electric and structural remodeling, assessed by dominant frequency (DF) changes, determines the time at which AF becomes persistent. METHODS AND RESULTS: Self-sustained AF was induced by atrial tachypacing. Seven sheep were euthanized 11.5±2.3 days after the transition to persistent AF and without reversal to sinus rhythm; 7 sheep were euthanized after 341.3±16.7 days of long-standing persistent AF. Seven sham-operated animals were in sinus rhythm for 1 year. DF was monitored continuously in each group. Real-time polymerase chain reaction, Western blotting, patch clamping, and histological analyses were used to determine the changes in functional ion channel expression and structural remodeling. Atrial dilatation, mitral valve regurgitation, myocyte hypertrophy, and atrial fibrosis occurred progressively and became statistically significant after the transition to persistent AF, with no evidence for left ventricular dysfunction. DF increased progressively during the paroxysmal-to-persistent AF transition and stabilized when AF became persistent. Importantly, the rate of DF increase correlated strongly with the time to persistent AF. Significant action potential duration abbreviation, secondary to functional ion channel protein expression changes (CaV1.2, NaV1.5, and KV4.2 decrease; Kir2.3 increase), was already present at the transition and persisted for 1 year of follow up. CONCLUSIONS: In the sheep model of long-standing persistent AF, the rate of DF increase predicts the time at which AF stabilizes and becomes persistent, reflecting changes in action potential duration and densities of sodium, L-type calcium, and inward rectifier currents.

Characterization of myocardial scars: electrophysiological imaging correlates in a porcine infarct model.

BACKGROUND: Definition of myocardial scars as identified by electroanatomic mapping is integral to catheter ablation of ventricular tachycardia (VT). Myocardial imaging can also identify scars prior to ablation. However, the relationship between imaging and voltage mapping is not well characterized. OBJECTIVE: The purpose of this study was to verify the anatomic location and heterogeneity of scars as obtained by electroanatomic mapping with contrast-enhanced MRI (CeMRI) and histopathology, and to characterize the distribution of late potentials in a chronic porcine infarct model. METHODS: In vivo 3-dimensional cardiac CeMRI was performed in 5 infarcted porcine hearts. High-density electroanatomic mapping was used to generate epicardial and endocardial voltage maps. Scar surface area and position on CeMRI were then correlated with voltage maps. Locations of late potentials were subsequently identified. These were classified according to their duration and fractionation. All hearts underwent histopathological examination after mapping. RESULTS: The total dense scar surface area and location on CeMRI correlated to the total epicardial and endocardial surface scar on electroanatomic maps. Electroanatomic mapping (average of 1,532 ± 480 points per infarcted heart) showed that fractionated late potentials were more common in dense scars (<0.50 mV) as compared with border zone regions (0.51 to 1.5 mV), and were more commonly observed on the epicardium. CONCLUSION: In vivo, CeMRI can identify areas of transmural and nontransmural dense scars. Fractionated late diastolic potentials are more common on the epicardium than the endocardium in dense scar. These findings have implications for catheter ablation of VT and for targeting the delivery of future therapies to scarred regions.

Distribution of late potentials within infarct scars assessed by ultra high-density mapping.

BACKGROUND: Late potential (LP) electrograms represent areas of slow conduction and are often sites critical to reentrant tachycardia circuits. The distribution of LPs within infarct scar is not known. OBJECTIVE: The purpose of this study was to delineate infarct heterogeneity using ultra high-density mapping and to determine the location of LPs with respect to scar architecture. METHODS: Detailed endocardial (n = 21) and epicardial (n = 8) ultra high-density mapping was performed to delineate the substrate for ventricular tachycardia (VT) in 21 patients with ischemic cardiomyopathy. LP was defined as a low-voltage electrogram (< 1.5 mV) with distinct onset after the QRS. Very late potentials (vLPs) were classified as LPs with onset > 100 ms after the QRS. RESULTS: A mean of 787 ± 391 and 810 ± 375 points in the LV endocardium and epicardium were sampled. Multipolar mapping identified heterogeneous islets (HIs) with relatively preserved electrogram amplitudes (≥ 0.51 mv) within dense scar (8.5 ± 4.9/4.5 ± 2.6 HIs per endocardium/epicardium) in all patients. In maps on which putative VT isthmuses were identified (25/29), 57% of vLP were recorded in or adjacent to HI. An LP-targeted ablation strategy combined with pace mapping achieved acute success in all patients (complete success in 52% and partial success in 48%). After 15 ± 7 months, 65% of patients remained free of VT episodes. CONCLUSION: Ultra high-density mapping with a multipolar catheter facilitates the delineation of heterogeneous scar architecture at higher resolution. Electrograms within and adjacent to HIs have a higher incidence of vLP, and these sites are frequently critical to reentry. These findings have important implications for substrate-based ablation strategies.