Bergapten inhibits NLRP3 inflammasome activation and pyroptosis via promoting mitophagy.

Inhibition of NLRP3 inflammasome activation produces potent therapeutic effects in a wide array of inflammatory diseases. Bergapten (BeG), a furocoumarin phytohormone present in many herbal medicines and fruits, exibits anti-inflammatory activity. In this study we characterized the therapeutic potential of BeG against bacterial infection and inflammation-related disorders, and elucidated the underlying mechanisms. We showed that pre-treatment with BeG (20 µM) effectively inhibited NLRP3 inflammasome activation in both lipopolysaccharides (LPS)-primed J774A.1 cells and bone marrow-derived macrophages (BMDMs), evidenced by attenuated cleaved caspase-1 and mature IL-1ß release, as well as reduced ASC speck formation and subsequent gasdermin D (GSDMD)-mediated pyroptosis. Transcriptome analysis revealed that BeG regulated the expression of genes involved in mitochondrial and reactive oxygen species (ROS) metabolism in BMDMs. Moreover, BeG treatment reversed the diminished mitochondrial activity and ROS production after NLRP3 activation, and elevated the expression of LC3-II and enhanced the co-localization of LC3 with mitochondria. Treatment with 3-methyladenine (3-MA, 5 mM) reversed the inhibitory effects of BeG on IL-1ß, cleaved caspase-1 and LDH release, GSDMD-N formation as well as ROS production. In mouse model of Escherichia coli-induced sepsis and mouse model of Citrobacter rodentium-induced intestinal inflammation, pre-treatment with BeG (50 mg/kg) significantly ameliorated tissue inflammation and injury. In conclusion, BeG inhibits NLRP3 inflammasome activation and pyroptosis by promoting mitophagy and maintaining mitochondrial homeostasis. These results suggest BeG as a promising drug candidate for the treatment of bacterial infection and inflammation-related disorders.

Ventricular tachycardia originating from the His bundle: A case report.

BACKGROUND: Ventricular tachycardia (VT) commonly occurs among patients with heart failure and can even cause sudden cardiac death. VT originating from the His bundle branch has been rarely reported. We present the case of a patient with VT from the His bundle branch. CASE SUMMARY: A 58-year-old female complained of paroxysmal palpitations and dizziness for approximately 6 mo. She had a history of fatty liver and cholecystitis, and carotid atherosclerosis could not be excluded from the ultrasound results. An evaluation of the electrocardiogram obtained after admission showed spontaneous conversion between two different morphologies. The possible electrophysiologic mechanism suggested that the dual-source VT originated from the same source, the His bundle branch. Finally, the His bundle branch was ablated, and a dual-chamber pacemaker was inserted into the patient's heart. No further VT occurred during the 3-year follow-up after hospital discharge. CONCLUSION: The diagnosis of VT originating from the His bundle is rare and difficult to establish. The results of this study showed VT originating from the His bundle based on a careful evaluation of the electrocardiogram, and the diagnosis was confirmed by an intracardiac electrophysiologic examination.

Effect of pulmonary vein isolation on atrial fibrillation recurrence after accessory pathway ablation in patients with Wolff-Parkinson-White syndrome.

BACKGROUND: Although successful ablation of the accessory pathway (AP) eliminates atrial fibrillation (AF) in some of patients with Wolff-Parkinson-White (WPW) syndrome and paroxysmal AF, in other patients it can recur. HYPOTHESIS: Whether adding pulmonary vein isolation (PVI) after successful AP ablation effectively prevents AF recurrence in patients with WPW syndrome is unknown. METHODS: We retrospectively studied 160 patients (102 men, 58 women; mean age, 46 ± 14 years) with WPW syndrome and paroxysmal AF who underwent AP ablation, namely 103 (64.4%) undergoing only AP ablation (AP group) and 57 (35.6%) undergoing AP ablation plus PVI (AP + PVI group). Advanced interatrial block (IAB) was defined as a P-wave duration of >120 ms and biphasic (±) morphology in the inferior leads, using 12-lead electrocardiography (ECG). RESULTS: During the mean follow-up period of 30.9 ± 9.2 months (range, 3-36 months), 22 patients (13.8%) developed AF recurrence. The recurrence rate did not differ in patients in the AP + PVI group and AP group (15.5% vs 10.5%, respectively; P = .373). Univariable and multivariable Cox regression analyses showed that PVI was not associated with the risk of AF recurrence (hazard ratio, 0.66; 95% confidence interval, 0.26-1.68; P = .380). In WPW patients with advanced IAB, the recurrence rate was lower in patients in the AP + PVI group vs the AP group (90% vs 33.3%, respectively; P = .032). CONCLUSIONS: PVI after successful AP ablation significantly reduced the AF recurrence rate in WPW patients with advanced IAB. Screening of a resting 12-lead ECG immediately after AP ablation helps identify patients in whom PVI is beneficial.

Advanced interatrial block predicts recurrence of atrial fibrillation after accessory pathway ablation in patients with Wolff-Parkinson-White syndrome.

BACKGROUND: Paroxysmal atrial fibrillation (AF) frequently occurs in patients with Wolff-Parkinson-White (WPW) syndrome. Although successful ablation of the accessory pathway (AP) eliminates paroxysmal AF in some patients, in other patients it can recur. HYPOTHESIS: We investigated the clinical utility of advanced interatrial block (IAB) for predicting the risk of AF recurrence in patients with verified paroxysmal AF and WPW syndrome after successful AP ablation. METHODS: This retrospective study included 103 patients (70 men, 33 women; mean age, 44 ± 16 years) with WPW syndrome who had paroxysmal AF. A resting 12-lead electrocardiogram was performed immediately after successful AP ablation to evaluate the presence of advanced IAB, which was defined as a P-wave duration of >120 ms and biphasic [±] morphology in the inferior leads. RESULTS: During the mean follow-up period of 30.9 ± 20.0 months (range, 2-71 months), 16 patients (15.5%) developed AF recurrence. Patients with advanced IAB had significantly reduced event-free survival from AF (P < .001). Cox regression analysis with adjustment for the left atrial diameter and CHA2 DS2 -VASc score identified advanced IAB (hazard ratio, 9.18; 95% confidence interval [CI], 2.30-36.72; P = .002) and age > 50 years (hazard ratio, 12.64; 95% CI, 1.33-119.75; P = .027) as independent predictors of AF recurrence. CONCLUSIONS: Advanced IAB was an independent predictor of AF recurrence after successful AP ablation in patients with WPW syndrome.

Association Between CHADS2 Score and the Development of Interatrial Block.

Interatrial block (IAB) is associated with a multitude of medical conditions. The aim of this retrospective study was to investigate whether CHADS2 (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke) score is positively associated with the development of IAB. A total of 1072 patients (men, 555; women, 517; mean age, 61 ± 14 years) were included in the study. P-wave duration was measured manually using a caliper. IAB was defined as a P-wave duration of ≥ 120 ms on a 12-lead electrocardiogram. CHADS2 scores were calculated retrospectively. Among the 1072 patients, the prevalence of IAB was 36.1% (387/1072). In multivariate analysis, increased CHADS2 score (odds ratio [OR], 1.810; 95% confidence interval [CI], 1.577-2.077; P < 0.001), coronary artery disease (OR, 1.536; 95% CI, 1.065-2.216; P = 0.022), and increased left atrial diameter (OR, 1.039; 95% CI, 1.008-1.071; P = 0.013) were independently associated with IAB. The percentages of patients with IAB among those with a CHADS2 score of 0, 1, 2, 3, 4, 5, and 6 were 20.6%, 33.0%, 45.0%, 55.9%, 61.9%, 77.8%, and 100%, respectively (P < 0.001). There was a greater percentage of patients with a CHADS2 score of ≥ 2 with IAB compared with a CHADS2 score of < 2 (26.5% vsrsus 52.0%; P < 0.001). In receiver operating curve (ROC) analysis, CHADS2 score (area under the curve, 0.670; 95% CI, 0.636-0.704; P < 0.001) was predictive of IAB. In conclusion, CHADS2 score was significantly associated with the development of IAB in this study population.

CHADS2 and CHA2DS2-VASc Scores Predict the Risk of Ischemic Stroke Outcome in Patients with Interatrial Block without Atrial Fibrillation.

AIM: To evaluate the role of CHADS2 and CHA2DS2-VASc scores in predicting the risk of ischemic stroke or transient ischemic attack (TIA) outcomes in patients with interatrial block (IAB) without a history of atrial fibrillation (AF). METHODS: A retrospective study was conducted, including 1,046 non-anticoagulated inpatients (612 males, 434 females; mean age: 63±10 years) with IAB and without AF. IAB was defined as P-wave duration ＞120 ms using a 12-lead electrocardiogram. CHADS2 and CHA2DS2-VASc scores were retrospectively calculated. The primary outcomes evaluated were ischemic stroke or TIA. RESULTS: During the mean follow-up period of 4.9±0.7 years, 55 (5.3%) patients had an ischemic stroke or TIA. Receiver operating characteristic (ROC) curve analysis showed that the CHADS2 score [area under the curve (AUC), 0.638; 95% confidence interval (CI), 0.562-0.715; P=0.001] and the CHA2DS2-VASc score (AUC, 0.671; 95% CI, 0.599-0.744; P＜0.001) were predictive of ischemic strokes or TIA. Cut-off point analysis showed that a CHADS2 score ≥3 (sensitivity=0.455 and specificity=0.747) and a CHA2DS2-VASc score ≥4 (sensitivity=0.564 and specificity=0.700) provided the highest predictive value for ischemic stroke or TIA. The multivariate Cox regression analysis showed that CHADS2 [hazard ratio (HR), 1.442; 95% CI, 1.171-1.774; P=0.001] and CHA2DS2-VASc (HR, 1.420; 95% CI, 1.203-1.677; P＜0.001) scores were independently associated with ischemic stroke or TIA following adjustment for smoking, left atrial diameter, antiplatelet agents, angiotensin inhibitors, and statins. CONCLUSIONS: CHADS2 and CHA2DS2-VASc scores may be predictors of risk of ischemic stroke or TIA in patients with IAB without AF.

Usefulness of a Combination of Interatrial Block and a High CHADS2 Score to Predict New Onset Atrial Fibrillation.

Interatrial block (IAB) is associated with an increased risk of atrial fibrillation (AF). The aim of this retrospective study was to investigate the association of a combination of IAB and the CHADS2 score, an AF-related risk score for ischemic stroke, with new onset AF in patients in sinus rhythm. A total of 1,571 patients (803 males, 768 females; mean age: 58 ± 16 years) were included in this study. IAB was defined as a P-wave duration > 120 ms in the 12-lead electrocardiogram, and a high CHADS2 score as ≥ 2 points. During the mean follow-up period of 4.8 ± 0.7 years, new onset AF occurred in 122 patients (16.1 per 1,000 patient-years). The incidence of new onset AF was 4.0 per 1,000 patient-years in patients with no IAB and a low CHADS2 score, and 44.0 per 1,000 patient-years in patients with IAB and a high CHADS2 score. In multivariate Cox regression analysis, the hazard ratio for IAB and a high CHADS2 score compared with no IAB and a low CHADS2 score was 12.18 (95% confidence interval: 6.22-23.87, P < 0.001), after adjustment for age, sex, coronary artery disease, valvular heart disease, smoking, medications, and echocardiographic parameters. In conclusion, IAB and a high CHADS2 score independently and synergistically predict new onset AF in patients in sinus rhythm, indicating an approximately 12-fold higher risk in patients with both IAB and a high CHADS2 score. Patients meeting these criteria should have more aggressive early intervention to prevent AF.

Efficacy of catheter ablation for atrial fibrillation in patients with a permanent pacemaker for atrioventricular block.

Catheter ablation has been established to be an effective therapy for drug-refractory paroxysmal AF and is recommended as the treatment of choice for many patients, including those with a permanent pacemaker (PM). However, the clinical efficacy of catheter ablation of paroxysmal AF in patients with a permanent PM for atrioventricular block (AVB) is not clear. Twenty-nine patients with a permanent PM for AVB (AVB + PM group), and 145 age- and gender-matched control patients (on a 1:5 basis) without AVB and without a permanent PM (no-AVB + no-PM group), were included in this study. Atrial fibrillation (AF) recurrence was defined as the occurrence of confirmed atrial tachyarrhythmia lasting more than 30 seconds beyond 3 months after catheter ablation in the absence of any antiarrhythmic treatment. During a mean follow-up period of 14.2 ± 8.6 months (range, 3-30 months), 54 patients (31.0%) developed recurrence of AF. The recurrence rate was higher in the AVB + PM group than in the no-AVB + no-PM group (48.3% versus 27.6%, P = 0.005). Cox regression analysis with adjustment for age, valvular heart disease, AVB and a PM together, left atrial (LA) diameter and PV isolation identified LA diameter (hazard ratio 1.054, 95% confidence interval 1.001-1.110, P = 0.047) and AVB and a PM together (hazard ratio 2.095, 95% confidence interval 1.109-3.960, P = 0.023) as two independent predictors of recurrence of AF. Patients with a permanent PM for AVB were at an increased risk of recurrence of AF after catheter ablation.

[Types and risk factors of arrhythmia on young patients with acute coronary syndrome in Henan province].

OBJECTIVE: The types and risk factors of arrhythmia were analyzed on acute coronary syndrome (ACS) patients under the age of 44 years who were hospitalized in Henan province between September 2009 to June 2012. METHODS: Medical records of eligible patients were obtained from the information system of the First Affiliated Hospital of Zhengzhou University teleconsultation information center. Middle aged and elderly ACS patients who were hospitalized at the same period served as controls. Data on arrhythmia types, blood pressure, thyroid disease, respiratory sleep apnea syndrome, smoking history, history of alcohol consumption, eating habits, family history of early-onset arrhythmia, laboratory tests were analyzed. RESULTS: (1) Arrhythmia was detected in 110 out of young ACS patients (55%), which was significantly lower than that in the elderly ACS patients (71.05%, P < 0.01). (2) The top three arrhythmias in young ACS patients were: sinus tachycardia (30.50%), the premature ventricular contractions (19.00%), atrial flutter/atrial fibrillation (16.50%). Incidence of sinus tachycardia, atrial flutter/atrial fibrillation were significantly higher while incidence of ventricular tachycardia, ventricular fibrillation, paroxysmal supraventricular tachycardia were significantly lower in young ACS patients than in middle-aged ACS patients (all P < 0.05). The incidence of sinus tachycardia was higher while incidence of ventricular premature accelerated ventricular spontaneous cardiac rhythm, ventricular tachycardia, ventricular fibrillation, non-paroxysmal supraventricular tachycardia, atrial flutter/atrial fibrillation, paroxysmal supraventricular tachycardia, sinus bradycardia, nodal escape, atrioventricular block were significantly lower in young ACS patients than in elderly ACS patients (all P < 0.05). (3) Body mass index, incidence of smoking, coronary three-vessel disease, drinking, eating salty foods, thyroid dysfunction, sleep apnea were significantly higher in youth ACS patients with arrhythmia than in young ACS patients without arrhythmia (all P < 0. 05). (4) Logistic regression analysis found that number of diseased coronary vessels (OR = 24.293), smoking (OR = 1.112) and alcohol consumption (OR = 1.039) were independent risk factor for developing arrhythmia in young ACS patients from Henan province. CONCLUSIONS: The main types of arrhythmia are sinus tachycardia, premature ventricular contractions, atrial flutter/atrial fibrillation and the major risk factors related to the arrhythmia are number of diseased coronary vessels, smoking and alcohol consumption in young ACS patients from Henan province.

[Population characteristics and impact on heart rate variability, heart rate and blood pressure of passive smoking].

OBJECTIVE: To investigate the basic characteristics of passive smoking population, and the impact of passive smoking on heart rate variability, heart rate and blood pressure. METHODS: Eighty-six passive smokers [mean age: (52.4 ± 7.6) years] were recruited from patients and their relatives who visited cardiovascular outpatient department and excluded structural heart disease between June 2010 and June 2012, 80 normal subjects who were not exposed to smoking served as controls. Questionnaire survey, 24 hours ambulatory electrocardiogram examination and blood pressure measurement were performed in all recruited subjects. RESULTS: (1) Non-marriage rate [18.60% (16/86) vs. 3.75% (3/80), P < 0.01] was significantly higher while education level were significantly lower in passive smoking group than in control group. Passive smokers were more likely service industry workers [29.07% (25/86) vs. 15.00% (12/80), P < 0.05] and had longer daily working time [(7.56 ± 1.24) h vs. (6.02 ± 0.96) h, P < 0.01], and were less likely to be professional technology industry employers [20.93% (18/86) vs. 36.25% (29/80), P < 0.05] and managers [13.95% (12/86) vs. 38.75% (31/80), P < 0.01] compared to controls. The main place of passive smoking was workplace (67.44%, 58/86), entertainment venues (63.95%,55/86), restaurants (48.84%, 42/86). (2) Standard of the normal sinus RR intervals (SDNN), the normal consecutive sinus RR interval difference between the root-mean-square (rMSSD) and adjacent the difference between the RR interval>50 ms the number of share the percentage (PNN50) were significantly lower in passive smoking group than in the control group (all P < 0.05). Every 5 min average of the standard deviation of sinus RR cycle (SDNN index) and 24 h every 5 min sinus RR interval mean standard deviation (SDANN) were similar between the 2 groups (all P > 0.05). Ultra-low-frequency power (VLF), low frequency power (LF), high frequency power (HF) and LF/HF were significantly lower in passive smoking group than in the control group (all P < 0.01). (3) Heart rate and diastolic blood pressure were significantly higher in passive smoking group than in control group (all P < 0.05) while systolic blood pressure was similar between the 2 groups (P > 0.05). CONCLUSIONS: Marriage status, education level, profession and daily working time are independent determinants for passive smoking. Passive smoking mainly occurred in the workplace, entertainment venues and restaurants. Passive smoking is linked with reduced heart rate variability, increased 24 h average heart rate and diastolic blood pressure.

[Effect of the smoking cessation services in the out-patient department for patients with coronary heart disease].

OBJECTIVE: To evaluate the effects and clinical prognosis of out-patient department-based smoking cessation services for coronary heart disease (CHD) patients. METHODS: A total of 140 smoking patients diagnosed with coronary heart disease in our cardiovascular department were randomly divided into the intensive smoking cessation clinic follow-up group (intervention group, patients were informed on the importance and methods to quit smoking at the first visit and reminded for that at months interval for 6 months, n = 70) and the conventional treatment group (control group, n = 70). After 6 months, the smoking status, cardiovascular event rates, drug usage, out-patient medical costs and quality of life were compared between the two groups. RESULTS: Age, gender, concomitant diseases, drug usage were similar between the two groups at baseline (all P > 0.05). After 6 months, smoking quit rate [34.2% (24/70) vs. 5.7% (4/70), P < 0.01], drug use rates: lipid-lowering drugs [95.3% (67/70) vs. 80.4% (56/70)], ß blockers [82.4% (57/70) vs. 41.3% (28/70)], and ACEI/ARB [61.4% (43/70) vs. 34.4% (24/70)] were significantly higher in the intervention group than in the control group, while total cardiovascular event rates [21.4% (15/70) vs. 47.1% (33/70), P < 0.01] and out-patient medical costs (3789.3 RMB vs. 4984.2 RMB, P < 0.01) were significantly lower in the intervention group than in the control group. The quality of life scores derived from MYO health survey questionnaire was significantly higher in the intervention group than in the control group (P < 0.01). The top three reasons responsible for continuous smoking for all patients failed to quit smoking were: (1) others smoked more than me and still alive and healthy [90.3% (56/62)]; (2) smoking helped me to keep relaxed and reduce trouble in daily work and life [70.9% (44/62)]; (3) smoking was essential while chatting and drinking with friends [66.1% (41/62)]. The overall satisfactory rate to this smoking cessation program was 42.8% and the satisfactory rate was up to 50.0% by patients. CONCLUSIONS: Intensive outpatient smoking cessation follow-up program can significantly improve the smoking cessation rates, the guideline drug use rate and the quality of life while reduce medical costs for coronary heart disease patients.

[Electrophysiological characteristics of peri-cingulum atrial tachycardia and its treatment with radiofrequency ablation].

OBJECTIVE: To analyze the characteristics of atrial tachycardia originating from the atrioventricular cingulum. METHOD: The electrophysiological mechanism, ablation site graph and nerve distribution of 16 cases of atrial tachycardia originating from the atrioventricular cingulum or adjacent atrial muscle which were proved by electrophysiological monitoring and radiofrequency ablation. RESULTS: Atrial tachycardia from peri-cingulum represented 23.2% of atrial tachycardia treated by radiofrequency ablation during the same period. The ratio of left to right atrioventricular cingulum was 3:16. There was no difference of the surface ECG characteristics and electrophysiological mechanism between the atrial tachycardia originating from atrioventricular cingulum and that from other positions. Both A and V components were recorded at all the successful ablation sites. The ratio of amplitude of A to V was between 2:3 and 6:1. Atrial potential in the target site was 20-46 (38.6 +/- 6.7) ms earlier than P'wave in surface ECG. The success rate of ablation was 87.5% and the recurrent rate 7.1%. CONCLUSIONS: Peri-cingulum atrial tachycardia accounts for a certain proportion in all atrial tachycardia. The exciting sites originating from right cingulum are more common than those from left cingulum. Its electrophysiological mechanism has no difference from other positions. Cingulum mapping and ablation have important practical meanings.