Clinical outcomes of radiofrequency catheter ablation guided by intracardiac echocardiography for Chinese atrial fibrillation patients: a single-center, retrospective study.

Background: Intracardiac echocardiography (ICE) is a novel technology with certain advantages in treatment of atrial fibrillation (AF), yet there is limited research on the use of ICE in radiofrequency ablation for AF treatment in China. The aim of this study was to investigate the total fluoroscopy time and dose, safety, and effectiveness of ICE guided vs. traditional fluoroscopy (non-ICE) guided radiofrequency ablation for AF in China. Methods: We conducted a single-center retrospective analysis of patients who underwent ICE or traditional fluoroscopy-guided radiofrequency ablation for AF. The primary endpoint of this study was total fluoroscopy time, and the secondary endpoints included total fluoroscopy dose, acute surgery failure, transseptal puncture time, ablation time, total procedure time, and 6-month surgery success (no AF recurrence or atrial flutter). As an exploratory analysis, outcomes of interest by different types of AF were examined. Results: A total of 97 patients were included in the analysis. Forty-eight were in the ICE group and 49 were in the non-ICE group with comparable demographic and clinical characteristics at the baseline. None of patients experienced acute surgery failure with no major procedure-related complications occurred. The fluoroscopic time and dose were significantly lower in the ICE group compared to the non-ICE group (0.00 vs. 9.67±4.88 min, P<0.001; 0.00 vs. 77.10±44.28 mGy/cm2, P<0.001, respectively). There were no statistically significant differences in transseptal puncture time, ablation time and total procedure time between the two groups. There were two AF recurrences observed during the 6-month follow-up in each group (P>0.99). Conclusions: ICE significantly reduced the fluoroscopic time and dose for radiofrequency catheter ablation in AF patients. There were no significant differences in safety or effectiveness outcomes between the ICE and non-ICE groups.

Radiofrequency ablation using the ThermoCool SmartTouch Catheter guided by ablation index versus antiarrhythmic drugs in atrial fibrillation treatment in China: a cost-consequence analysis.

Aim: To evaluate the costs and consequences of two front-line atrial fibrillation (AF) treatments from Chinese healthcare system perspective: radiofrequency catheter ablation (RFCA) using ThermoCool SmartTouch Catheter guided by Ablation Index (STAI), in comparison to antiarrhythmic drugs (AADs). Patients & methods: We simulated clinical and economic consequences for AF patients initially receiving STAI or AADs using a short-term decision tree model leading to a 10-year long-term Markov model. The model projected both clinical consequences and costs associated with, among others, AF, heart failure (HF), strokes, and deaths due to AF or AF related complications. Data informing the models included combination of a local real-world study and published clinical studies. Results: STAI was advantageous versus AADs on all 4 main clinical outcomes evaluated; AF: 25.83% lower (12.84% vs 38.67%), HF: 2.22% lower (1.33% vs 3.55%), stroke or post stroke: 1.82% lower (10.00% vs 11.82%) and deaths due to AF or AF related complications: 0.64% lower (4.11% vs 4.75%). The average total cost per patient in STAI group was ¥16,682 lower (¥123,124 vs ¥139,806). The one-way sensitivity analysis indicated that the difference in total cost was most sensitive to annual AF recurrence probability in AADs-treated patients. Probabilistic sensitivity analysis indicated a 98.5% probability that RFCA treatment would result in cost savings by the end of the 10th year. Conclusion: Radiofrequency catheter ablation using SmartTouch catheter guided by Ablation Index was superior to AADs as the first-line AF treatment in Chinese setting with better clinical outcomes and at lower costs over a 10-year time horizon.

Bepotastine Sensitizes Ovarian Cancer to PARP Inhibitors through Suppressing NF-κB-Triggered SASP in Cancer-Associated Fibroblasts.

Therapy-induced senescence (TIS) is common in tumor cells treated with PARP inhibitors (PARPis) and can serve as a promising target for improving PARPi efficacy. However, whether stromal components within the tumor microenvironment undergo TIS caused by PARPis and contribute to consequential treatment failure remain unclear. We previously revealed that PARPis triggered a senescence-like secretory phenotype in stromal fibroblasts. Here, we further explored PARPi-induced senescence in the stroma, its contribution to PARPi resistance, and opportunities to leverage stromal TIS for improved PARPi sensitivity. In this study, we demonstrated that tumor tissues from patients treated with neoadjuvant PARPis showed a significant senescence-like phenotype in the stroma. Moreover, PARPi-induced senescent cancer-associated fibroblasts (CAFs) displayed a senescence-associated secretory phenotype (SASP) profile that was sufficient to induce tumor resistance to PARPis in both homologous recombination-deficient (HRD) and -proficient ovarian cancer cells. Using the GLAD4U database, we found that bepotastine, an approved H1-antihistamine, inhibited the SASP of PARPi-primed CAFs at clinical serum concentrations. We further demonstrated that bepotastine attenuated fibroblast-facilitated tumor resistance to PARPis in three-dimensional organotypic cultures and HRD-positive patient-derived xenograft models. Mechanistically, bepotastine suppressed PARPi-triggered SASP by inhibiting NF-κB signaling independent of the histamine H1 receptor. Taken together, our results highlight the importance of stromal TIS and SASP in PARPi resistance, and targeting SASP with bepotastine may be a promising therapeutic option for improving PARPi sensitivity in ovarian cancer.

Arrhythmogenesis of surgical atrial incisions and lesions in Maze procedure: insights from high-resolution mapping of atrial tachycardias.

BACKGROUND: Atrial tachycardias (ATs) frequently develop after a surgical Maze procedure. We aimed to elucidate the electrophysiologic mechanisms and their arrhythmogenic substrates of these ATs. METHODS AND RESULTS: We retrospectively reviewed 20 patients (14 females, mean age of 55.5 ± 8.6 years) with post-Maze ATs who underwent high-resolution mapping at three institutions. The slow conduction areas, reentry circuits, voltage signals, complex electrograms, and their correlation with the surgical incisions and lesions placed in the surgical Maze procedures were analyzed. Thirty-six ATs with a mean cycle length of 260.0 ± 67.6 ms were mapped in these patients. Among them, 22 (61.1%) were anatomical macro-reentrant ATs (AMAT), 12 (33.3%) non-AMATs (localized ATs), and 2 (5.6%) focal ATs, respectively. Epicardial conduction bridges were observed in 6/20 (30.0%) patients and 7/36 (19.4%) ATs. Different arrhythmogenic substrates were identified in these ATs, including slow conduction regions within the previous lesion areas or between the incisions and anatomical structures, the prolonged activation pathways caused by the short lesions connecting the tricuspid annulus, and the circuits around the long incisions and/or lesions. CONCLUSIONS: Reentry is the main mechanism of the post-Maze ATs. The pro-arrhythmic substrates are most likely caused by surgical incisions and lesions. The slow conduction regions and the protected channels yielded from these areas are the major arrhythmogenic factors.

Sacubitril/Valsartan Can Reduce Atrial Fibrillation Recurrence After Catheter Ablation in Patients with Persistent Atrial Fibrillation.

PURPOSE: This study compared the effectiveness of sacubitril/valsartan (SV) vs. valsartan (V) for treating persistent atrial fibrillation (AF) after radio-frequency catheter ablation (RFCA). METHODS: Patients with persistent AF who received RFCA were randomly assigned to the SV or V treatment group with the intervention lasting for 12 months. The primary outcome included any atrial arrhythmia episode lasting ≥ 30 s after a 3-month blanking period. The secondary outcome included any atrial arrhythmia episode lasting ≥ 24 h or requiring cardioversion after a 3-month blanking period. The H2FPEF score was used to assess the possibility of patients suffering from heart failure with preserved ejection fraction. RESULTS: A total of 143 patients with persistent AF who received RFCA were randomized for the study, with 5 patients failing to follow-up. Among them, 29 (42%) out of 69 patients receiving V and 15 (21.7%) out of 69 patients receiving SV reached the primary endpoint (P < 0.001). A total of 26 (37.7%) out of 69 patients receiving V and 7 (10.1%) out of 69 patients receiving SV reached the secondary endpoint (P < 0.001). A decrease in the H2FPEF score after a 1-year follow-up seemed to be related to the recurrence of AF (OR, 0.065; 95% CI: 0.018-0.238, P < 0.001). CONCLUSIONS: SV can decrease AF recurrence after catheter ablation in patients with persistent AF at the 1-year follow-up. The mechanism for this process may be related to the reduction in the H2FPEF score in patients with preserved ejection fraction heart failure.

Cyclin-Dependent Kinase Inhibitors Function as Potential Immune Regulators via Inducing Pyroptosis in Triple Negative Breast Cancer.

Background: Immunotherapy is the most promising treatment in triple-negative breast cancer (TNBC), and its efficiency is largely dependent on the intra-tumoral immune cells infiltrations. Thus, novel ways to assist immunotherapy by increasing immune cell infiltrations were highly desirable. Methods: To find key immune-related genes and discover novel immune-evoking molecules, gene expression profiles of TNBC were downloaded from Gene Expression Omnibus (GEO). Single-sample gene set enrichment analysis (ssGSEA) and Weighted Gene Co-expression Network Analysis (WGCNA) were conducted to identified hub genes. The CMap database was used subsequently to predicate potential drugs that can modulate the overall hub gene expression network. In vitro experiments were conducted to assess the anti-tumor activity and the pyroptosis phenotypes induced by GW-8510. Results: Gene expression profiles of 198 TNBC patients were downloaded from GEO dataset GSE76124, and ssGSEA was used to divide them into Immune Cell Proficiency (ICP) group and Immune Cell Deficiency (ICD) group. Hub differential expressed gene modules between two groups were identified by WGCNA and then annotated by Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. A cyclin-dependent kinase (CDK) 2 inhibitor, GW-8510 was then identified by the CMap database and further investigated. Treatment with GW-8510 resulted in potent inhibition of TNBC cell lines. More importantly, in vitro and in vivo studies confirmed that GW-8510 and other CDK inhibitors (Dinaciclib, and Palbociclib) can induce pyroptosis by activating caspase-3 and GSDME, which might be the mechanism for their immune regulation potentials. Conclusion: GW-8510, as well as other CDK inhibitors, might serve as potential immune regulators and pyroptosis promotors in TNBC.

Effectiveness and Safety of Niraparib as Neoadjuvant Therapy in Advanced Ovarian Cancer With Homologous Recombination Deficiency (NANT): Study Protocol for a Prospective, Multicenter, Exploratory, Phase 2, Single-Arm Study.

Background: Ovarian cancer (OC) is a heterogeneous gynecological malignancy with a poor prognosis as the majority of patients are diagnosed at an advanced stage. Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) is recommended for patients who cannot achieve optimal cytoreduction or cannot endure primary debulking surgery (PDS). As there is an increased risk of chemoresistance for platinum-based NACT, it is important to investigate an alternative option. A Poly (ADP-ribose) polymerase inhibitor (PARPi), niraparib, has shown high anti-tumor activity, especially in homologous recombination deficiency (HRD) positive patients with OC. Thus, niraparib as a neoadjuvant treatment agent may help improve surgery accessibility and create survival benefits. Methods: This multicenter, prospective, single-arm, open-label, phase II study plans to recruit 53 patients (aged 18-75 years) with newly diagnosed HRD positive, unresectable (Fagotti score ≥ 8 or upper abdominal computed tomography [CT] score ≥ 3) International Federation of Gynecology and Obstetrics (FIGO) stage III-IV OC. The HRD status was detected by next-generation sequencing and HRD positive patients will be counseled for study participation. Enrolled patients will receive niraparib capsules QD (200mg or 300mg per day) for two cycles (4 weeks/cycle). After neoadjuvant niraparib treatment, patients exhibiting complete response (CR), partial response (PR), or stable disease (SD) will undergo tumor reduction surgery and subsequent standard carboplatin/paclitaxel-based chemotherapy. The primary objectives include the objective response rate (ORR) and R0 resection rate. The rate of treatment interruption/termination and progression-free survival (PFS) will be secondary objectives. The study uses Simon's optimal two-stage design (24 and 21 patients for the first and second stage respectively). The data manager will record all adverse events (AEs). Discussion: This is the first prospective study to evaluate the effectiveness and safety of niraparib in neoadjuvant treatment for advanced OC. The result of this study will provide a solid base for further expanding the clinical applications of the PAPRi and exploring more therapeutic possibilities for patients with HRD positive advanced OC. Clinical Trial Registration: https://clinicaltrials.gov/, identifier NCT04507841.

TAGLN mediated stiffness-regulated ovarian cancer progression via RhoA/ROCK pathway.

BACKGROUND: Ovarian cancer (OC) progression is an unmet medical challenge. Since omental metastases were palpated harder than their primary counterparts during cytoreductive surgery of patients with epithelial ovarian cancer (EOC), we were inspired to investigate OC progression from the perspective of biomechanics. METHODS: Atomic Force Microscope (AFM) was used to measure the Young's modulus of tissues. The collagen-coated polyacrylamide hydrogel (PA gel) system was prepared to mimic the soft and stiff substrates in vitro. The effect of TAGLN was evaluated both in vitro and in vivo using transwell assay, immunofluorescence, western blot analysis and immunohistochemistry. RESULTS: We quantitatively confirmed that omental metastases were stiffer and more abundant in desmoplasia compared with paired primary tumors, and further demonstrated that matrix stiffness could notably regulate OC progression. Remarkably, TAGLN, encoding an actin cross-linking/gelling protein, was identified as a potent mechanosensitive gene that could form a regulation loop with Src activation reacting to environmental stiffness, thus mediating stiffness-regulated OC progression through regulating RhoA/ROCK pathway. CONCLUSIONS: These data demonstrate that targeting extra-cellular matrix (ECM) stiffness could probably hamper OC progression, and of note, targeting TAGLN might provide promising clinical therapeutic value for OC therapy.

PARP inhibitors promote stromal fibroblast activation by enhancing CCL5 autocrine signaling in ovarian cancer.

Cancer-associated fibroblasts (CAFs) play significant roles in drug resistance through different ways. Antitumor therapies, including molecular targeted interventions, not only effect tumor cells but also modulate the phenotype and characteristics of CAFs, which can in turn blunt the therapeutic response. Little is known about how stromal fibroblasts respond to poly (ADP-ribose) polymerase inhibitors (PARPis) in ovarian cancer (OC) and subsequent effects on tumor cells. This is a study to evaluate how CAFs react to PARPis and their potential influence on PARPi resistance in OC. We discovered that OC stromal fibroblasts exhibited intrinsic resistance to PARPis and were further activated after the administration of PARPis. PARPi-challenged fibroblasts displayed a specific secretory profile characterized by increased secretion of CCL5, MIP-3α, MCP3, CCL11, and ENA-78. Mechanistically, increased secretion of CCL5 through activation of the NF-κB signaling pathway was required for PARPi-induced stromal fibroblast activation in an autocrine manner. Moreover, neutralizing CCL5 partly reversed PARPi-induced fibroblast activation and boosted the tumor inhibitory effect of PARPis in both BRCA1/2-mutant and BRCA1/2-wild type xenograft models. Our study revealed that PARPis could maintain and improve stromal fibroblast activation involving CCL5 autocrine upregulation. Targeting CCL5 might offer a new treatment modality in overcoming the reality of PARPi resistance in OC.

Impact of Left Atrial Sphericity Index on the Outcome of Catheter Ablation for Atrial Fibrillation.

Left atrial sphericity index (LASI) is one significant geometric remodeling parameter to evaluate the prognosis of atrial fibrillation (AF). We aimed to determine whether transthoracic echocardiography (TTE)-derived LASI may help predict the outcomes following AF radiofrequency catheter ablation (RFCA). This prospective study enrolled 190 consecutive AF patients who underwent TTE 24 h before RFCA. LASI was calculated as the ratio of left atrial maximum volume to spherical volume. After 1-year follow-up, 56 patients (29.5%) relapsed. Multivariate Cox regression showed that LASI (hazard ratio = 1.48, 95% Cl 1.15-1.92, P = 0.003) was an independent predictor of AF recurrence. Stratifying patients into four subgroups with different LAVI showed that high LASI value indicated a high risk of recurrence, especially in patients with mildly and moderately enlarged atria (the recurrence rate was 0% vs. 26.3%, P = 0.049; 9.5% vs. 40.9%, P = 0.018, respectively). In conclusion, TTE-derived LASI may be useful to predict AF recurrence after RFCA.

Flutter Wave Morphology of Peri-Mitral Atrial Flutters Is Mainly Determined by Right Atrial Activation: Insights From High-Resolution Mapping.

BACKGROUND: Peri-mitral atrial flutters frequently develop post-atrial fibrillation ablation or postcardiac surgery. The determinants of the flutter wave morphology on surface ECG have been less studied. METHODS: We retrospectively reviewed 24 patients with peri-mitral atrial flutters who underwent biatrial high-resolution mapping at 3 institutions with LUMIPOINT software. We analyzed the overlap between the right atrial (RA) activation time and flutter wave duration and compared the proportion of the endocardial area that was activated in both atria during the flutter wave duration. Biatrial activation patterns and interatrial conductions were also identified. RESULTS: The mean tachycardia cycle length was 264±60 ms, with RA activation time 155±45 ms (60.8±20.6% of the tachycardia cycle length), and the flutter wave duration 107±31 ms (41.6±11.7% of the tachycardia cycle length). The overlap between the RA activation time and the flutter wave duration was 102±29 ms, which takes 68.5±17.2% of the RA activation time and 95.7±9.1% of the flutter wave duration, respectively. Quantitative analysis also showed that during the flutter wave duration, more percentage of the endocardial area was activated in the RA than in the left atrium (73.0±12.7% versus 45.2±13.0%, P<0.001). We consistently observed that the RA anterior wall rightward activation corresponded to the positive component in V1 in both flutter patterns, and the RA downward activation corresponded to the positive component in the counterclockwise group or the upward activation corresponded to the negative component in the clockwise group in the inferior leads. The passive RA activation patterns were varied with spontaneous atrial scarring or previous linear ablation. CONCLUSIONS: ECG flutter wave morphology of peri-mitral atrial flutters is mainly dependent on RA activation patterns.

CHA2DS2-VASc and SAMe-TT2R2 scores as predictors of recurrence for nonvalvular atrial fibrillation patients on vitamin K antagonists after radiofrequency catheter ablation.

AIMS: Atrial fibrillation is the most common sustained arrhythmia in the general population, and circumferential pulmonary vein isolation has emerged as a cornerstone in the treatment of drug-resistant atrial fibrillation. However, there is a paucity of data regarding the CHA2DS2-VASc and SAMe-TT2R2 scores as predictors of outcomes among patients with nonvalvular atrial fibrillation on vitamin K antagonists after radiofrequency catheter ablation (RFCA). METHODS: The current prospective observational study enrolled 304 consecutive patients with atrial fibrillation who underwent RFCA. Warfarin was maintained for at least 3 months after RFCA. The 1-year atrial fibrillation recurrence rate was documented. RESULTS: Persistent atrial fibrillation (P = 0.003), heart failure (P < 0.001), an enlarged left atrium (P = 0.003), current smoking (P < 0.001), the CHA2DS2-VASc score (P = 0.001), and the SAMe-TT2R2 score (P < 0.001) were univariate associated with recurrent atrial fibrillation. Cutoff analysis showed that a CHA2DS2-VASc score at least 3 (areas under the curve = 0.612; 95% confidence interval 0.537-0.687) and a SAMe-TT2R2 score at least 5 (areas under the curve = 0.642, 95% confidence interval 0.575-0.708) had the highest predictive value for atrial fibrillation recurrence. Patients with a CHA2DS2-VASc score at least 3 (P < 0.001) and a SAMe-TT2R2 score at least 5 (P = 0.001) had a higher probability of experiencing atrial fibrillation recurrence after RFCA compared with patients with a CHA2DS2-VASc score less than 3 and a SAMe-TT2R2 score less than 5. CONCLUSION: CHA2DS2-VASc and SAMe-TT2R2 scores were associated with 1-year recurrence of atrial fibrillation in patients on vitamin K antagonists after RFCA. For CHA2DS2-VASc and SAMe-TT2R2 scores, a cutoff value of at least 3 and at least 5 had the highest predictive value for atrial fibrillation recurrence, respectively.

Noncoding RNAs in Atrial Fibrillation: Current Status and Prospect.

Atrial fibrillation (AF) is an important cause of cardiovascular morbidity and mortality. Current therapies for AF are ineffective, mainly due to incomplete understanding of the pathogenesis of AF. Atrial remodeling contributes to the occurrence and progression of AF, but molecular mechanisms underlying AF remain unclear. Noncoding RNAs, including microRNAs, long noncoding RNAs and circular RNAs, are now considered to play an important role in the pathophysiology of AF. In this review, we summarize recent evidence supporting the role of noncoding RNAs in AF and highlight their diagnostic and prognostic applications as potential biomarkers and therapeutic strategies.

Insight Into the Mechanism of Macroreentrant Atrial Tachycardia With Cycle Length Alternans Using Ultrahigh Density Mapping System.

BACKGROUND: Atrial tachycardia (AT) with cycle length (CL) alternans is a rare phenomenon. We aimed to identify the characteristics and precise mechanism of this special category of ATs by using an ultrahigh density mapping system. METHODS: We identified 7 ATs with alternating CL in a total of 478 ATs from 2 institutions mapped with an ultrahigh density mapping system. Activation maps were performed for long CL (289±35 ms; mapping points, 21 520±11 103) and short CL (251±18 ms; mapping points,17 594±8059) separately. RESULTS: We classified ATs with CL alternans into 2 types. Type 1: There existed 2 potential loops with different routes. CL alternans resulted from an intermittently 2:1 conducting block within the channel of the smaller loop. Type 2: CL alternans resulted from different conduction velocity through 2 closely spaced gaps within preexisting linear lesions. Catheter ablation successfully terminated all the 7 ATs. CONCLUSIONS: Ultrahigh density mapping provides an opportunity to delineate the precise mechanism of AT with CL alternans. Intermittent conduction block or slowing of a channel was essential for the maintenance of AT.

Association between chymase gene polymorphisms and atrial fibrillation in Chinese Han population.

BACKGROUND: Chymase is the major angiotensin II (Ang II)-forming enzyme in cardiovascular tissue, with an important role in atrial remodeling. This study aimed to examine the association between chymase 1 gene (CMA1) polymorphisms and atrial fibrillation (AF) in a Chinese Han population. METHODS: This case-control study enrolled 126 patients with lone AF and 120 age- and sex-matched healthy controls, all from a Chinese Han population. Five CMA1 polymorphisms were genotyped. RESULTS: The CMA1 polymorphism rs1800875 (G-1903A) was associated with AF. The frequency of the GG genotype was significantly higher in AF patients compared with controls (p = 0.009). Haplotype analysis further demonstrated an increased risk of AF associated with the rs1800875-G haplotype (Hap8 TGTTG, odds ratio (OR) = 1.668, 95% CI 1.132-2.458, p = 0.009), and a decreased risk for the rs1800875-A haplotype (Hap5 TATTG, OR = 0.178, 95% CI 0.042-0.749, p = 0.008). CONCLUSIONS: CMA1 polymorphisms may be associated with AF, and the rs1800875 GG genotype might be a susceptibility factor for AF in the Chinese Han population.

Cross-talk between macrophages and atrial myocytes in atrial fibrillation.

Increased macrophage accumulation occurs in the atria of patients with atrial fibrillation (AF). However, the phenotype and functions of the macrophages in AF remain unclear. We investigated the macrophage-atrial myocyte interaction in AF patients and found that the increased macrophages were mainly pro-inflammatory macrophages (iNOS+, Arg1-). Tachypacing of HL-1 atrial myocytes also led to pro-inflammatory macrophage polarization. In addition, lipopolysaccharide (LPS)-stimulated pro-inflammatory macrophages-induced atrial electrical remodeling, evidenced by increased AF incidence and decreased atrial effective refractory period and L-type calcium currents (I Ca-L) in both canine and mouse AF models. Depletion of macrophages relieved LPS-induced atrial electrical remodeling, confirming the role of pro-inflammatory macrophages in the pathogenesis of AF. We also found that the effect of LPS-stimulated macrophages on atrial myocytes was mediated by secretion of interleukin 1 beta (IL-1ß), which inhibited atrial myocyte quaking protein (QKI) expression. IL-1ß knockout in macrophages restored the LPS-stimulated macrophage-induced inhibition of QKI and CACNA1C (α1C subunit of L-type calcium channel) in atrial myocytes. Meanwhile, QKI overexpression in atrial myocytes restored the LPS-stimulated macrophage-induced electrical remodeling through enhanced binding of QKI to CACNA1C mRNA, which upregulated the expression of CACNA1C as well as I Ca-L. In contrast, QKI knockout inhibited CACNA1C expression. Finally, using transcription factor activation profiling plate array and chromatin immunoprecipitation, we revealed that special AT-rich sequence binding protein 1 activated QKI transcription. Taken together, our study uncovered the functional interaction between macrophages and atrial myocytes in AF. AF induced pro-inflammatory macrophage polarization while pro-inflammatory macrophages exacerbated atrial electrical remodeling by secreting IL-1ß, further inhibiting QKI expression in atrial myocytes, which contributed to I Ca-L downregulation. Our study demonstrates a novel molecular mechanism underlying the pathogenesis and progression of AF and suggests that QKI is a potential therapeutic target.

Perindopril for the prevention of atrial fibrillation recurrence after radiofrequency catheter ablation: One-year experience.

BACKGROUND: Recurrence of atrial fibrillation (AF) after ablation is still high. Perindopril plays an essential role in AF induction and maintenance. OBJECTIVE: We aimed to prove that perindopril (8 mg) could prevent recurrence after pulmonary vein isolation. METHODS: Patients with paroxysmal AF who received radiofrequency ablation were randomized to a 3-month course of perindopril 8 mg once daily (perindopril group) or placebo (placebo group). Angiotensin-II (Ang-II) therapy and standard transthoracic echocardiography were performed. All 256 patients with paroxysmal AF who received radiofrequency ablation were randomized. And we followed them for complete 1 year. The 3-month recurrence and the 1-year recurrence were compared between the 2 groups. RESULTS: The 3-month recurrence of AF was observed in 33 (26.19%) of 126 patients in the placebo group vs 19 (14.62%) of 130 patients who received perindopril 8 mg once daily (χ2, P = .021). One-year recurrence of AF was observed in 36 (28.5%) of 126 patients in the placebo group as compared with 21 (16.2%) of 130 patients who received perindopril after 1 year (P = .017). The κ value was 0.94 in the control group (P < .001) and 0.96 in the perindopril group (P < .001) between 3-month and 1-year recurrence. The Ang-II level was related to the left atrial distance with the reduction in AF recurrence (r = 0.17, P = .005 at 3 months; r = 0.25, P < .001 at 1 year). CONCLUSION: Perindopril is an effective and safe treatment for the prevention of AF recurrence after radiofrequency catheter ablation. This effect seems to be strongly associated with a significant decrease in Ang-II level and left atrial distance.

Paeoniflorin protects diabetic mice against myocardial ischemic injury via the transient receptor potential vanilloid 1/calcitonin gene-related peptide pathway.

BACKGROUND: Diabetes mellitus has multiple complications including neuropathy and increases cardiovascular events. Paeoniflorin (PF), a monoterpene glycoside, plays an essential role in neuroprotection and ischemic heart disease. In this study, we aimed to investigate the hypothesis that PF protects mice with diabetes mellitus against myocardial ischemic injury, and determine its associated mechanisms. RESULTS: Myocardial infarction (MI) was generated in the streptozotocin-mediated diabetic mice, which were pretreated with either vehicle or PF, respectively. Myocardial infarct size, myocardial enzyme, cardiac function, circulating calcitonin gene-related peptide (CGRP) concentration, histological analysis and the expression of associated molecules were determined and compared among different experimental groups. Compared to diabetic hearts pretreated with vehicle, hearts pretreated with PF exhibited less tissue damage and better CGRP concentration in serum when subjected to myocardial ischemia. Transient receptor potential vanilloid 1(TRPV1) gene knockout attenuated PF-mediated cardioprotection. Moreover, a specific Ca(2+)/calmodulin-dependent protein kinase (CaMK) inhibitor, KN-93, increased tissue damage and decreased CGRP activity in serum. Meanwhile, pretreated with PF increased the phosphorylation of cAMP response element binding protein (CREB). CONCLUSIONS: Taken together, these findings demonstrate that PF protects diabetic mice against MI at least partially via the TRPV1/CaMK/CREB/CGRP signaling pathway.

Uncommon presentation of postcardiac injury syndrome induced by radiofrequency catheter ablation for atrial fibrillation: Only pulmonary parenchymal inflammation.

Postcardiac injury syndrome (PCIS) is characterized by the appearance of pericardial, pleural, or pulmonary parenchymal inflammation following a cardiac operation. The autoimmune disorder is characterized by eosinophilia, pleuritic chest pain, pleural, and pericardial effusion. It is a troublesome complication, which may prolong hospital stay and lead to severe and life-threatening conditions. Recently, its incidence appears to be declining, owing to modern immunomodulatory drug therapies. Here we report an uncommon case of PCIS, which occurred following a pulmonary vein isolation for atrial fibrillation. The patient suffered from pulmonary parenchymal inflammation but no pleuropericarditis after the operation. We describe with detailed clinical information, laboratory, and imaging tests, treatment processes, and a favorable prognosis in the content. This case illustrates that even after initially uneventful radiofrequency catheter ablation, careful, long-term follow-up is necessary to recognize the potential development of postcardiac injury syndrome. .