Background: Simultaneous atrial fibrillation (AF) catheter ablation and left atrial appendage closure (LAAC) is sometimes recommended for both rhythm control and stroke prevention. However, the advantages of intracardiac echocardiography (ICE) guidance for this combined procedure have been scarcely reported. To evaluate the clinical outcomes and safety of ICE guided LAAC within a zero-fluoroscopy catheter ablation procedure. Methods and Results:From April 2019 to April 2020, 56 patients with symptomatic AF underwent concomitant catheter ablation and LAAC. ICE with a multi-angled imaging protocol mimicking the TEE echo windows was used to guide LAAC. Successful radiofrequency catheter ablation and LAAC was achieved in all patients. Procedure-related adverse event rate was 3.6%. During the 12-month follow-up, 77.8% of patients became free of arrhythmia recurrences and oral anticoagulants were discontinued in 96.4% of patients. No ischemic stroke occurred despite two cases of device-related thrombosis versus an expected stroke rate of 4.8% based on the CHA2DS2-VASc score. The overall major bleeding events rate was 1.8%, which represented a relative reduction of 68% versus an expected bleeding rate of 5.7% based on the HAS-BLED score of the patient cohort. The incidence of iatrogenic atrial septal defect secondary to a single transseptal access dropped from 57.9% at 2 months to 4.2% at 12 months TEE follow-up. Conclusion:The combination of catheter ablation and LAAC under ICE guidance was safe and effective in AF patients with high stroke risk. ICE with our novel protocol was technically feasible for comprehensive and systematic assessment of device implantation.

Background and Purpose: The profibrotic and proinflammatory effects induced by doxorubicin (DOX) are key processes in the development of serious heart damage. The lack of effective drugs and the unclear mechanisms of their side effects limit the clinical treatment of DOX-induced cardiac injury. This study aimed to explore the protective role of LCZ696 and the potential mechanism of Toll-like receptor 2 (TLR2) in doxorubicin-induced cardiac failure. Experimental Approach: DOX (5 mg/kg/week, 3 times) was used to establish a chronic cardiomyopathy mouse model. Heart function tests, pathology examinations and molecular biology analyses were used to explore the effects of LCZ696 and TLR2 deficiency. H9C2 cells were used to verify the protective role and mechanism of LCZ696 in vitro. Key Results: The EF% declined, and the LVIDd, pro-fibrosis marker levels and NF-κB pathway-related inflammatory response increased in the chronic cardiomyopathy group induced by DOX. LCZ696 treatment and TLR2 deficiency reversed this heart damage in vivo. In H9C2 cells, pretreatment with LCZ696 and TLR2 knockdown suppressed the DOX-induced high expression of profibrotic and proinflammatory markers. Moreover, DOX notably increased the TLR2-MyD88 interaction in H9C2 cells, which was inhibited by LCZ696 pretreatment. Conclusion and Implications: LCZ696 prevents DOX-induced cardiac dilation failure, fibrosis and inflammation by reducing the formation of TLR2-MyD88 complexes. LZC696 may be a potential effective drug to treat DOX-induced heart failure.