Impedance rise of 500 Ω at <90 seconds with freeze time of 90 seconds resulted in 100% PVI. Impedance measurements from the nose of the balloon is a direct measure of ice formation on the balloon. It provides real-time feedback on the quality of the ablation and defines the cryoapplication termination time based on ice formation, limiting ice expansion to extracardiac tissues.
BackgroundA direct indicator of effective pulmonary vein isolation (PVI) based on early ice formation is presently lacking.ObjectiveThe initial impedance rise within 30 to 60 seconds (sec) of single cryoablation relating to ice on the distal surface of the cryoballoon could; predict effective PVI with early termination, the need for prolonging the cryoablation, or failure to achieve effective ablation.MethodsImpedance measurements were taken between two ring electrodes, at the anterior balloon surface and at the shaft behind the balloon. Ice covering the anterior ring leads to impedance rise. Single cryoablation (eight animals, 37 veins) was applied for 90 to 180 sec. Cryoapplication was terminated if the impedance reached ≥500 Ω. Impedance levels at ≤60 sec of cryoablation were divided into three groups based on the characteristics of the impedance rise. PVI was confirmed acutely and at 45 ± 9 days recovery by electrophysiology mapping and histopathology.ResultsAt 60 sec of freezing, an impedance rise of 34.1 ± 15.2 Ω (13‐50 Ω) and slope of the impedance rise (measured during 15‐30 sec of cryoapplication) less than 1 Ω/sec resulted in failed PVI. An impedance rise of 104.4 ± 31.5 Ω (76‐159 Ω) and slope of 2 Ω/sec resulted in 100% PVIs. An impedance rise of 130.9 ± 137.8 Ω (40‐590 Ω) and slope of 10 Ω/sec resulted in 100% PVIs with early termination at 90 sec.ConclusionThe efficacy of single cryoablation can be defined within 30 to 60 sec based on ice impedance. Three unique impedance profiles described in this investigation are associated with the uniformity and thickness of the ice buildup on the anterior surface of the balloon. One cryoablation with an adequate impedance rise is needed for successful outcomes.
Background: Atrial fibrillation (AF), the most common sustained cardiac arrhythmia, increases thromboembolic stroke risk five-fold. Although atrial hypocontractility contributes to stroke risk in AF, the molecular mechanisms reducing myofilament contractile function remain unknown. We tested the hypothesis that increased expression of PPP1R12C, the PP1 regulatory subunit targeting atrial myosin light chain 2 (MLC2a), causes hypophosphorylation of MLC2a and results in atrial hypocontractility. Methods: Right atrial appendage tissues were isolated from human AF patients versus sinus rhythm controls. Western blots, co-immunoprecipitation, and phosphorylation studies were performed to examine how the PP1c-PPP1R12C interaction causes MLC2a de-phosphorylation. In vitro studies of pharmacologic MRCK inhibitor (BDP5290) in atrial HL-1 cells were performed to evaluate PP1 holoenzyme activity on MLC2a. Cardiac-specific lentiviral PPP1R12C overexpression was performed in mice to evaluate atrial remodeling with atrial cell shortening assays, echocardiography, and AF inducibility with EP studies. Results: In human patients with AF, PPP1R12C expression was increased two-fold versus SR controls (P=2.0x10-2, n=12,12 in each group) with >40% reduction in MLC2a phosphorylation (P=1.4x10-6, n=12,12 in each group). PPP1R12C-PP1c binding and PPP1R12C-MLC2a binding were significantly increased in AF (P=2.9x10-2 and 6.7x10-3 respectively, n=8,8 in each group). In vitro studies utilizing drug BDP5290, which inhibits T560-PPP1R12C phosphorylation, demonstrated increased PPP1R12C binding with both PP1c and MLC2a, and dephosphorylation of MLC2a. Lenti-12C mice demonstrated a 150% increase in LA size versus controls (P=5.0x10-6, n=12,8,12), with reduced atrial strain and atrial ejection fraction. Pacing-induced AF in Lenti-12C mice was significantly higher than controls (P=1.8x10-2 and 4.1x10-2 respectively, n= 6,6,5). Conclusions: AF patients exhibit increased levels of PPP1R12C protein compared to controls. PPP1R12C overexpression in mice increases PP1c targeting to MLC2a and causes MLC2a dephosphorylation, which reduces atrial contractility and increases AF inducibility. These findings suggest that PP1 regulation of sarcomere function at MLC2a is a key determinant of atrial contractility in AF.
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