Effects of catheter ablation of atrial fibrillation on the biomarker profile.

BACKGROUND: Following catheter ablation for atrial fibrillation (AF), there are dynamic changes in the atrial myocardium associated with damage to and necrosis of atrial tissue and other procedure related changes in rhythm and anticoagulation. Early time-dependent changes in biomarkers of necrosis, inflammation, and coagulation have been reported. This study examines mid-term (4-8 weeks post-ablation) changes in biomarkers and explores their ability to predict AF recurrence at one-year. METHODS: Twenty-seven patients (mean age 65.4 ± 9.7 years, 30% female) undergoing catheter ablation for AF had peripheral venous blood samples obtained at the time of ablation and 4-8 weeks later. All samples were processed to obtain plasma which was frozen for subsequent analysis. Coagulation studies were performed at the Northwestern Special Hemostasis Laboratory: VWF, ADAMTS13, PAI-1, D-dimer, and TAT complexes. A commercial lab analyzed samples for CRP, cystatin C, fibrinogen, galectin, IL-6, MMP-2, myoglobin, NT-proBNP, PAI-1, TIMP-1, TIMP-2, TPA, and VWF. RESULTS: Significant changes were noted with higher levels of ADAMTS13 (p < 0.0001), fibrinogen (p = 0.004), MMP-2 (p = 0.0002), TIMP-2 (p = 0.003), and TPA (p = 0.001) compared to lower levels of TAT (p < 0.0001) and NT-proBNP (p = 0.0001) at follow up post-ablation. One year after ablation, AF had recurred in 11/26 (42%) of patients. None of the biomarker changes predicted the 1-year outcome, and there was no significant association with the use of warfarin versus rivaroxaban. CONCLUSION: In patients undergoing catheter ablation for AF, there were significant changes in pre- vs post-ablation levels of multiple biomarkers. However, these changes were not associated with 1-year outcome of AF recurrence.

Bronchial effects of cryoballoon ablation for atrial fibrillation.

BACKGROUND: Damage to extracardiac structures, including the esophagus and phrenic nerve, is a known complication of cryoballoon ablation (CBA) during pulmonary vein (PV) isolation for atrial fibrillation (AF). Other adjacent structures, including the pulmonary bronchi and lung parenchyma, may be affected during CBA at the PV ostia. OBJECTIVE: The purpose of this study was to prospectively study the bronchial effects of CBA in humans undergoing CBA for PV isolation. METHODS: Ten patients undergoing CBA for AF under general anesthesia were enrolled in an institutional review board-approved prospective observational study. Real-time bronchoscopy was performed during cryoablation of PVs adjacent to pulmonary bronchi to monitor for thermal injury. Patients were followed for the development of respiratory complaints postprocedure. RESULTS: In 7 of 10 patients (70%) and in 13 of 22 freezes (59%), ice formation was visualized in the left mainstem bronchus during CBA in the left upper PV. Ice formation was not seen in the right mainstem bronchus during right upper PV CBA. The average time to ice formation was 89 seconds. There was no significant difference (P = -.45) in average minimum balloon temperature during freezes with ice formation (-48.5°C) and freezes without ice formation (-46.3°C). No patients went on to develop respiratory complications. CONCLUSION: Unrecognized ice formation occurs frequently in the left mainstem bronchus during CBA for AF. This information helps explain the source of cough and hemoptysis in some patients who undergo CBA. The long-term consequences of this novel finding and the implications for procedural safety are unknown.

Cardiac Monitoring for Atrial Fibrillation in Cryptogenic Stroke.

Despite an extensive initial evaluation, the cause of up to a third of ischemic strokes remains undetermined. The detection of atrial fibrillation (AF) in these patients with cryptogenic stroke is critical as the diagnosis of AF would warrant anticoagulation to reduce the risk of recurrent stroke. Observational studies and prospective randomized controlled trials have shown that a substantial proportion of patients with cryptogenic stroke have AF detected by post-stroke cardiac monitoring with higher AF detection rates observed with longer monitoring periods.

Effects on platelet function of a direct acting antagonist of coagulation factor Xa.

Because novel direct acting anticoagulants are being tested in the secondary prevention of cardiovascular events, we assessed potential effects of a direct acting antagonist of Factor Xa on platelet function. Blood from patients with known coronary artery disease who were treated with aspirin but no other antithrombotic agent was spiked in vitro with rivaroxaban alone or in combination with a direct acting P2Y12 antagonist (cangrelor). To limit cofounding effects of anticoagulants and to enable interaction between coagulation factors, blood was anticoagulated only with a specific inhibitor of Factor XIIa, corn trypsin inhibitor. Polymerization of fibrin was prevented with the peptide GPRP. Activation of platelets was determined with the use of flow cytometry in response to lipidated tissue factor, thrombin, the collagen mimetic convulxin, and adenosine diphosphate (ADP). Rivaroxaban inhibited the activation of platelets induced by tissue factor and to a lesser extent activation induced by thrombin, effects that were accentuated when combined with cangrelor. Rivaroxaban did not attenuate convulxin-induced activation of platelets; however, a limited but consistent attenuation of ADP-induced platelet activation was seen with blood anticoagulated with rivaroxaban. Effects of rivaroxaban on ADP-induced platelet activation were not mediated by thrombin, tissue factor, or platelet-leukocyte aggregation. In conclusion, rivaroxaban attenuated in vitro the activation of platelets mediated by thrombin. In light of the pivotal role of thrombin in platelet activation after rupture of an atherosclerotic plaque, rivaroxaban should attenuate platelet activation in vivo, an effect that is accentuated by combination with a P2Y12 antagonist.