LCZ696 Ameliorates Oxidative Stress and Pressure Overload-Induced Pathological Cardiac Remodeling by Regulating the Sirt3/MnSOD Pathway.

AIMS: We aimed to investigate whether LCZ696 protects against pathological cardiac hypertrophy by regulating the Sirt3/MnSOD pathway. METHODS: In vivo, we established a transverse aortic constriction animal model to establish pressure overload-induced heart failure. Subsequently, the mice were given LCZ696 by oral gavage for 4 weeks. After that, the mice underwent transthoracic echocardiography before they were sacrificed. In vitro, we introduced phenylephrine to prime neonatal rat cardiomyocytes and small-interfering RNA to knock down Sirt3 expression. RESULTS: Pathological hypertrophic stimuli caused cardiac hypertrophy and fibrosis and reduced the expression levels of Sirt3 and MnSOD. LCZ696 alleviated the accumulation of oxidative reactive oxygen species (ROS) and cardiomyocyte apoptosis. Furthermore, Sirt3 deficiency abolished the protective effect of LCZ696 on cardiomyocyte hypertrophy, indicating that LCZ696 induced the upregulation of MnSOD and phosphorylation of AMPK through a Sirt3-dependent pathway. CONCLUSIONS: LCZ696 may mitigate myocardium oxidative stress and apoptosis in pressure overload-induced heart failure by regulating the Sirt3/MnSOD pathway.

Comparison of transthoracic echocardiography with computed tomography in evaluation of pulmonary veins.

BACKGROUND: Transesophageal echocardiography may be used to assess pulmonary veins for atrial fibrillation ablation. No study focused on the role of transthoracic echocardiography (TTE) in evaluating the diameter and anatomy of pulmonary veins. METHODS: Among 142 atrial fibrillation patients (57.7% men; mean age, 60.5) hospitalised for catheter ablation, we assessed pulmonary veins and compared the measurements by TTE with cardiac computed tomography (CT) before ablation. Among 17 patients who had follow-up examinations, the second measurements were also studied. RESULTS: TTE identified and determined the diameters of 140 (98.6%) right and 140 (98.6%) left superior PVs, and 136 (95.7%) right and 135 (95.1%) left inferior PVs. A separate middle PV ostia was identified in 14 out of the 22 patients (63.6%) for the right side and in 2 out of 4 (50.0%) for the left side. The PV diameters before ablation assessed by CT vs. TTE were 17.96 vs. 18.07 mm for right superior, 15.92 vs. 15.51 mm for right inferior, 18.54 vs. 18.42 mm for left superior, and 15.56 vs. 15.45 mm for left inferior vein. The paired differences between the assessments of CT and TTE were not significant (P ≥ 0.31) except for the right inferior vein with a CT-minus-TTE difference of 0.41 mm (P = 0.018). The follow-up PV diameters by both CT (P ≥ 0.069) and TTE (P ≥ 0.093) were not different from baseline measurements in the 17 patients who had follow-up measurements. CONCLUSIONS: With a better understanding of PV anatomy in TTE imaging, assessing PV diameters by non-invasive TTE is feasible. However, the clear identification of anatomic variation might still be challenging.

A Practical Method for Ablation Catheter Reintroduction into the Left Atrium via Prior Transseptal Puncture, without Radiation.

BACKGROUND: We evaluated the feasibility and safety of reintroducing an ablation catheter (ABL) into the left atrium (LA) through a previously punctured interatrial septum under guidance of the show-catheter image-track function of the CARTO 3 3-dimensional (3D) electroanatomic mapping system. METHODS: One hundred consecutive paroxysmal or persistent drug-refractory atrial fibrillation (AF) patients (men: 55; mean age, 64.7 ± 12.1 years) who had undergone 2 fluoroscopy-guided transseptal punctures and anatomical LA reconstruction under CARTO 3-guidance, and required ABL reinsertion into the LA during mapping or ablation, were included. They were randomized 1:1 to the show-catheter (reintroduction under the CARTO 3 show-catheter image-track function) or fluoroscopy group (reintroduction under conventional fluoroscopy). RESULTS: Although the reconstructed 3D anatomy map was displaced in 21/100 patients (21.0%), the ABL was successfully reintroduced in all patients. In the show-catheter and fluoroscopy groups, model displacement incidence (18% versus 24%), tachyarrhythmias (46.0% versus 52.0%), complications (2% versus 4%), and number of ABLs reintroduced into the LA (3.3 ± 0.8 versus 3.1 ± 0.9) were similar (all P > .05). The show-catheter group displayed shorter ABL reintroduction time (9.5 ± 5.5 s versus 156.4 ± 35.5 s, P < .01), ABL reintroduction X-ray exposure time (0 s versus 39.3 ± 13.8 s, P < .01), and total X-ray exposure time (4.1 ± 1.4 min versus 4.7 ± 0.8, P < .05). CONCLUSION: During AF ablation, the catheter can be safely reintroduced into the LA, without additional fluoroscopy, under guidance of the CARTO 3 show-catheter image track function.

The Role of Angle in the Evaluation of Ablation Accuracy in Pulmonary Vein Isolation Navigated by Image Integration.

BACKGROUND: The conventional index for ablation accuracy is to compare the distance between mapping points with and without treatment by using image integration. We attempted to quantitatively evaluate the role of angle as an index in the ablation accuracy in patients with atrial fibrillation (AF). METHODS: A total of 48 patients with AF were included in the present study. Virtual fluoroscopy planes were predicted by pulmonary vein (PV) angiography, and the standard image planes were defined on the basis of the computed tomography images. Ablations were performed, guided by image integration; and the ablation planes were defined by the actual ablation rings. The predicted angle (distance) was defined as the angle (distance) between the fluoroscopy (predicted) plane and image (standard) plane, whereas the actual angle (distance) was defined as the angle (distance) between the ablation (actual) planes and the image (standard) planes. RESULTS: We found that all actual angles were significantly smaller than the predicted angles (P <.05), but only the actual distances in the left PV, right inferior PV, right superior PV, and right PV were significantly smaller; the distances in the left inferior PV and left superior PV were not significantly different (P >.05). CONCLUSION: Our finding indicates that both the angle and the distance can be significantly reduced by navigation with image integration, but that the angle exhibited better sensitivity than the conventional index of distance. We suggest that the angle should be considered as a new index for ablation accuracy.

Comparison of circumferential pulmonary vein anatomy mapping guided by 3D mapping versus a mesh mapping catheter.

OBJECTIVE: Catheter-based pulmonary vein isolation (PVI) is an established therapy for paroxysmal atrial fibrillation. The high-density mesh mapper (HDMM) guides circumferential PV-atrium isolation without the 3D electroanatomic mapping. This study aims to compare circumferential pulmonary vein (CPV) anatomy mapping between guiding by a 3D mapping system and the HDMM. METHODS: Forty-four consecutive patients with paroxysmal atrial fibrillation were scheduled for a first procedure for PVI. A CPV ostial anatomy map guided by HDMM was set up in the CARTO system while the operator was blinded to the CARTO screen. Then CARTO-guided ipsilateral PV maps were obtained and PVI was performed. This established another set of CPV ostial anatomy maps. The differences between the two mapping images were compared and analyzed. RESULTS: All 176 PVs in 44 patients could be mapped by both HDMM and CARTO. About 44.9% of the PV ostial anatomies were generally similar between the two different map images. The average point-to-point straight distance between the HDMM-guided map and the CARTO-guided map was 6.2 ± 1.4 mm. The area of the circumferential right PV (CRPV) in the HDMM map was larger than that in the CARTO map (P = 0.013). After a mean follow-up of 18.3 ± 4.3 months (6-24 months), 72.7% of patients (32/44) were free of atrial arrhythmia without anti-arrhythmic drugs (AADs). CONCLUSION: Compared to the CARTO-guided CPV anatomy image, a highly similar figure could be achieved by mapping guided by the HDMM. (Clinical trial.gov number, ChiCTR-TNRC-11001390.).

Lysophosphatidic acid increases the electrophysiological instability of adult rabbit ventricular myocardium by augmenting L-type calcium current.

Lysophosphatidic acid (LPA) has diverse actions on the cardiovascular system and is widely reported to modulate multiple ion currents in some cell types. However, little is known about its electrophysiological effects on cardiac myocytes. This study investigated whether LPA has electrophysiological effects on isolated rabbit myocardial preparations. The results indicate that LPA prolongs action potential duration at 90% repolarization (APD(90)) in a concentration- and frequency-dependent manner in isolated rabbit ventricular myocytes. The application of extracellular LPA significantly increases the coefficient of APD(90) variability. LPA increased L-type calcium current (I(Ca,L)) density without altering its activation or deactivation properties. In contrast, LPA has no effect on two other ventricular repolarizing currents, the transient outward potassium current (I(to)) and the delayed rectifier potassium current (I(K)). In arterially perfused rabbit left ventricular wedge preparations, the monophasic action potential duration, QT interval, and Tpeak-end are prolonged by LPA. LPA treatment also significantly increases the incidence of ventricular tachycardia induced by S(1)S(2) stimulation. Notably, the effects of LPA on action potentials and I(Ca,L) are PTX-sensitive, suggesting LPA action requires a G(i)-type G protein. In conclusion, LPA prolongs APD and increases electrophysiological instability in isolated rabbit myocardial preparations by increasing I(Ca,L) in a G(i) protein-dependent manner.

Lysophosphatidic acid as a potential trigger of atrial fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia in clinical practice, but its pathogenesis is incompletely understood. Current evidences have highlighted the progression of atrial fibrosis and electrophysiological remodeling in AF development. Lysophosphatidic acid (LPA), the simplest phospholipid, is associated with fibrotic disease and promotes proliferation of a wide variety of fibroblast. It was demonstrated that LPA stimulation in many cell types such as human endothelial cells, human renal fibroblasts, and myoblasts, significantly upregulates connective tissue growth factor (CTGF) expression, which acts as a downstream signaling effector for transforming growth factor-ß1 (TGF-ß1) to drive fibrosis. We hypothesized that LPA could also evoke growth factor-like responses to atrial fibroblast, and subsequently induce atrial fibrosis to trigger AF. LPA is also verified to involve in numerous electrophysiological activities in non-myocardiocytes. So LPA is a possible cause of AF by initiating fibrosis response and altering electrophysiological properties in atrium. If the hypothesis is confirmed, LPA will act as a new target for AF treatment and administration of LPA receptor blockers may be applied in the prophylaxis of AF.

[Incidence, risk factors and management of pericardial effusion post radiofrequency catheter ablation in patients with atrial fibrillations].

OBJECTIVE: Pericardial effusion (PE) is a major complication of atrial fibrillation ablation (AFB). We analyzed the incidence, risk factors and managements of PE post AFB (radiofrequency catheter ablation). METHODS: A total of 156 consecutive patients with AF [male 108, paroxysmal AF 114, (57.6 +/- 11.3) years], who underwent AFB guided by a three-dimensional mapping system (CARTO or CARTO-Merge, Biosense-Webster Inc., Diamond Bar, California) and a circular mapping catheter (Lasso, Biosense-Webster Inc., Diamond Bar, California), were included in this study. The ablation strategy included circumferential pulmonary veins isolation (CPVI), linear ablation and/or complex fractionated atrial electrograms (CFAEs) ablation. Electrophysiological data and vital signs of patients were recorded by a multiple physiological recorder (Prucka, GE Medical Systems) during ablation. Ablation process, sites, duration and other related factors were also recorded. Echocardiography and other examinations were performed for diagnosing and monitoring PE. RESULTS: CPVI were achieved in all 156 patients. Incidence of PE was 10.3% (16/156) post AFB. One patient developed acute cardiac tamponade and emergency drainage of the pericardial effusion was performed through a median sternotomy and patient recovered without complications during the 18 months follow-up. The rest 15 PE patients with small PE received outpatient care and no invasive treatment was needed and PE disappeared after 3 months in 6 patients and after 6 months in 9 patients. Univariate analysis showed that the composition of gender (P < 0.01), ablation in coronary sinus (CS, P = 0.026), ablation of CFAEs (P = 0.037) and superior vena cava (SVC, P = 0.041) were risk factors for PE. Logistic regression analysis showed that female gender [beta = 3.594, exp (b) = 36.4, 95% confidence interval (CI): 4.2 - 312.1, P = 0.001] and ablation in CS [beta = 2.419, exp (b) = 11.2, 95% CI: 1.0 - 124.6, P = 0.049] were independent risk factors for PE post AFB. CONCLUSIONS: PE is a common complication of AFB, female gender and ablation in CS were independent risk factors for PE. Most PE patients experienced spontaneous recovery but emergency treatment was needed for patient with cardiac tamponade.