Acute Efficacy of a Traditional Chinese Medicine for Treatment of Frequent Premature Ventricular Contractions in Patients with Concomitant Sinus Bradycardia: Results from a Double-Blind, Placebo-Controlled, Multicentre, Randomized Clinical Trial.

Pharmacological antiarrhythmic therapy such as beta-blockers in patients with frequent premature ventricular contractions (PVCs) and concomitant bradycardia is challenging. A traditional Chinese medicine, Shensong Yangxin (SSYX), has been effective in treatment of frequent PVCs and sinus bradycardia (SB) in separate patient cohorts. This double-blind, placebo-controlled, multicentre, randomized clinical trial investigates the acute efficacy of SSYX in reducing PVCs burden in patients with concomitant SB. Patients with symptomatic, frequent PVCs, and SB, defined as mean heart rate (MHR) of 45 to 59 beats per min (bpm), were recruited at 33 medical centres in mainland China and randomly assigned by computer to either SSYX or matching placebo for eight weeks. Patients, investigators, and trial personnel were masked to treatment allocation. Primary endpoints were changes in PVCs burden and MHR as assessed by 24-hour Holter monitoring relative to baseline. Secondary efficacy endpoints were subjective symptom score, ECG, and biochemical parameters. Analysis was based on intention-to-treat principles. 333 patients were randomized, of which 166 received SSYX and 167 placebo. Baseline characteristics did not differ. SSYX reduced PVCs burden by 68.2% (p < 0.001) and increased MHR by 10.9% (p < 0.001) compared to 32.2% and 4.7%, respectively, in the placebo group. SSYX group experienced greater symptomatic improvement (p < 0.001). No differences in reported adverse events were seen (20 versus 23). SSYX is an effective antiarrhythmic therapy for symptomatic, frequent PVCs uniquely suited patients with concomitant SB. Clinical trial number was NCT01750775.

Electrophysiological Characteristics of Bundle Branch Reentry Ventricular Tachycardia in Patients Without Structural Heart Disease.

BACKGROUND: The distinct electrophysiological features of bundle branch reentry ventricular tachycardia (VT) in patients without structural heart disease have not been systemically characterized. METHODS: Nine patients (mean age, 29.6 years) with normal left ventricular function were enrolled. Bundle branch reentry VT with right and left bundle branch block (BBB) patterns was induced in 1 and 9 patients, respectively. The right bundle was attempted to record by a 6F decapolar or quadripolar catheter. Electroanatomic mapping of the left ventricle was performed in 6 patients. In all left BBB pattern VT, the mean VT cycle length was 329.3±89.1 ms, and the median HV interval during tachycardia was longer than that of baseline (78 [73-100] versus 71 [64.5-88] ms; P=0.11). RESULTS: The H-RB interval during VT was slightly shorter (P=0.14); however, the median RB-V interval was markedly longer than that during sinus rhythm (50 [29.5-83] versus 30 [8-51] ms; P=0.043]. In 6 patients with 3-dimensional mapping of the left ventricle, a slow anterograde or retrograde conduction over left HIS-Purkinje system with normal myocardial voltage was identified. In addition, Purkinje-related VTs (1.0±1.3 types) were also induced in 5 patients. Ablation was applied in distal left BB in patients with baseline left BBB and in one narrow QRS patient with sustained Purkinje-related VT, whereas right BB was targeted in other patients. During a mean follow-up of 31.4 months, frequent premature ventricular contractions occurred in one patient, and new VT developed in the other patient. CONCLUSIONS: Bundle branch reentry VT can occur in young patients with extensive conduction disturbances within HIS-Purkinje system. Ablation targeting at the distal left BB which bifurcates into left posterior and anterior fascicle can preserve the residual atrioventricular conduction, but intensive follow-up is needed.

Late cure of focal ventricular arrhythmias post-catheter ablation: electrophysiological characteristics and long-term outcome.

PURPOSE: Late cure after a previously failed ablation of ventricular arrhythmias (VAs) is a relatively common phenomenon. The present study sought to delineate the incidence and electrophysiological characteristics of late cure in idiopathic VA patients. METHODS: Totally, 45 idiopathic VA cases (mean age 44 ± 18 years, 27 males) either failed acutely or recurred within 12 h were enrolled in this study. Based on intensive clinical observations in the acute period, 19 (42%) patients demonstrated late cure in the first week after the procedure. RESULTS: The late cure patients had significantly better acute and cumulative ablation effects during the procedure than did those without a late cure. Additionally, they had a prediction that originated from the right ventricular outflow tract, aortic-mitral continuum, and left summit area relative to other sites (13/18 vs 6/27, p < 0.01). In a median follow-up of 24 [14, 46] months, 7/19 (37%) patients had their VAs recurred. The late cure group had significantly more patients cured at long-term follow-up than those without (12/19 vs 0/26, p < 0.01). A cutoff value of the "time to eliminate VAs" > 7.0 s was able to predict a long-term recurrence of the VAs with 62.5% sensitivity and 85.7% specificity. CONCLUSIONS: The late cure of VAs occurs in more than one third of patients who have a seemingly unsuccessful ablation session, which is clustered in the first week after the procedure. However, long-term recurrence of VAs occurred in 37% of the late cure patients, emphasizing the importance of long-term follow-up.

Idiopathic isolated fibrotic atrial cardiomyopathy underlies unexplained scar-related atrial tachycardia in younger patients.

Aims: Unexplained scar-related atrial tachycardia (AT) has been frequently encountered in clinical practice. We hypothesized that idiopathic, isolated fibrotic atrial cardiomyopathy (ACM) underlies this rhythm disorder. This study was aimed to characterize the underlying substrate and to explore the aetiology of this unexplained scar-related AT. Methods and results: Twenty-six (11 men, aged 46 ± 13 years) of 52 non-surgical scar-related AT patients identified by three-dimensional voltage mapping were enrolled in this prospective observational study. Multimodality image examinations (echocardiography, cardiac magnetic resonance, 99Tc single-photon emission computed tomography), ventricular voltage mapping, and intracardiac pressure curve recording ruled out ventricular involvement. Catheter ablation was acutely successful for all the patients, and pacemaker implantation was performed in seven patients who presented sinus node dysfunction or atrial standstill after termination of the AT. In three patients with multiple AT recurrences, the diseased areas of the right atrium were resected and dechannelled via mini-invasive surgical interventions. Histological examinations revealed profound fibrosis without amyloidosis or adipose deposition. Viral and familial investigations yielded negative results. Fibrosis progression over a median of 45 (5-109) months of follow-up manifested as atrial arrhythmia recurrence in seven patients and atrial lead non-capture due to newly developed atrial standstill in two patients. Two patients suffered four ischaemic stroke events before receiving anticoagulation treatment. Conclusion: Isolated, fibrotic ACM may underlie the idiopathic scar-related ATs. This novel cardiomyopathy has unique clinical characteristics with high morbidity including stroke and warrants specific therapeutic strategies. Further investigations are required to determine the aetiology and mechanism.

Prolonged Sinus Pauses upon Termination of Paroxysmal Atrial Fibrillation: Abnormal Right Atrial Electrophysiologic and Electroanatomic Findings.

The efficacy of pulmonary vein antral isolation for patients with prolonged sinus pauses (PSP) on termination of atrial fibrillation has been reported. We studied the right atrial (RA) electrophysiologic and electroanatomic characteristics in such patients. Forty patients underwent electroanatomic mapping of the RA: 13 had PSP (group A), 13 had no PSP (group B), and 14 had paroxysmal supraventricular tachycardia (control group C). Group A had longer P-wave durations in lead II than did groups B and C (115.5 ± 15.4 vs 99.5 ± 10.9 vs 96.5 ± 10.4 ms; P=0.001), and RA activation times (106.8 ± 13.8 vs 99 ± 8.7 vs 94.5 ± 9.1 s; P=0.02). Group A's PP intervals were longer during adenosine triphosphate testing before ablation (4.6 ± 2.3 vs 1.7 ± 0.6 vs 1.5 ± 1 s; P <0.001) and after ablation (4.7 ± 2.5 vs 2.2 ± 1.4 vs 1.6 ± 0.8 s; P <0.001), and group A had more complex electrograms (11.4% ± 5.4% vs 9.3% ± 1.6% vs 5.8% ± 1.6%; P <0.001). Compared with group C, group A had significantly longer corrected sinus node recovery times at a 400-ms pacing cycle length after ablation, larger RA volumes (100.1 ± 23.1 vs 83 ± 22.1 mL; P=0.04), and lower conduction velocities in the high posterior (0.87 ± 0.13 vs 1.02 ± 0.21 mm/ms; P=0.02) and high lateral RA (0.89 ± 0.2 vs 1.1 ± 0.35 mm/ms; P=0.04). We found that patients with PSP upon termination of atrial fibrillation have RA electrophysiologic and electroanatomic abnormalities that warrant post-ablation monitoring.

Catheter Ablation of Nonparoxysmal Atrial Fibrillation Using Electrophysiologically Guided Substrate Modification During Sinus Rhythm After Pulmonary Vein Isolation.

BACKGROUND: The high incidence of postprocedural atrial tachycardia reduces the absolute arrhythmia-free success rate of extensive ablation strategies to treat nonparoxysmal atrial fibrillation (NPAF). We hypothesized that a strategy of targeting low-voltage zones and sites with abnormal electrograms during sinus rhythm (SR-AEs) in the left atrium after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation in patients with NPAF is superior. METHODS AND RESULTS: A total of 86 consecutive patients with NPAF were enrolled in study group. After circumferential pulmonary vein isolation, cavotricuspid isthmus ablation and cardioversion to SR, high-density mapping of left atrium was performed. Areas with low-voltage zone and SR-AE were targeted for further homogenization and elimination, respectively; 78 consecutive sex- and age-matched patients with NPAF who were treated with the stepwise approach served as the historical control group. In the study group, 92% (79/86) were successfully cardioverted after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation. Among the patients converted to SR, 70% (55/79) had low-voltage zone and SR-AE and received additional ablation, whereas in 30% (24/79) without SR-AE or low-voltage zone, no further ablation was performed. During a follow-up period of >30 months, the Kaplan-Meier estimated probability to maintain SR at 24 months was 69.8% versus 51.3%. And after a single procedure, 3.5% (3/86) developed postprocedural atrial tachycardia in study group, compared with 30% (24/78) in control group (P=0.0003). CONCLUSIONS: A strategy of selective electrophysiologically guided atrial substrate modification in SR after circumferential pulmonary vein isolation and cavotricuspid isthmus ablation is clinically more effective than the stepwise approach for NPAF ablation. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT01716143.

Non-contact mapping-guided ablation of ventricular arrhythmias originating from the pulmonary artery.

AIMS: To identify unique electrophysiological characteristics of pulmonary artery (PA) ventricular arrhythmias (VA) and determine long-term clinical outcomes following non-contact mapping (NCM)-guided ablation. METHODS AND RESULTS: The NCM array was deployed in consecutive patients undergoing clinically indicated ablation of outflow tract (OT) VA with left bundle branch block morphology, inferior axis and the precordial lead transition zone ≥ V3. Activation, pace and NCM mapping parameters, and electrocardiogram analysis of PA VA patients were compared with 50 patients with right ventricular OT (RVOT) or aortic coronary cusps (ACC) foci. Of 170 consecutive patients, 20 (12%) patients (8 male, 39.7 ± 12.8 years old) with PA VA were identified. Electrocardiogram morphologies of PA ventricular tachycardia (VT) (located 10.8 ± 15.1 mm above the PV) were indistinguishable from RVOT VT, particularly those arising from the septal RVOT. Pulmonary artery VT can be mapped and ablated by targeting the site of earliest activation on NCM maps, with success rates of 90% after a single procedure, without anti-arrhythmics and mean follow-up of >5 years. Pace-mapping in the PA is complicated by frequent inability to capture (P < 0.01). Small far-field atrial potentials and smaller ventricular electrograms were more frequently recorded at successful sites of ablation in the PA (P < 0.05). CONCLUSION: Non-contact mapping is a useful technique to map PA VT and ablation at sites of earliest activation above the pulmonary valve is associated with excellent long-term clinical success.

Catheter Ablation of Fascicular Ventricular Tachycardia: Long-Term Clinical Outcomes and Mechanisms of Recurrence.

BACKGROUND: Fascicular ventricular tachycardia (FVT) is a common form of sustained idiopathic left ventricular tachycardia with an Asian preponderance. This study aimed to prospectively investigate long-term clinical outcomes of patients undergoing ablation of FVT and identify predictors of arrhythmia recurrence. METHODS AND RESULTS: Consecutive patients undergoing FVT ablation at a single tertiary center were enrolled. Activation mapping was performed to identify the earliest presystolic Purkinje potential during FVT that was targeted by radiofrequency ablation. Follow-up with clinic visits, ECG, and Holter monitoring was performed at least every 6 months. A total of 120 consecutive patients (mean age, 29.3±12.7 years; 82% men; all patients with normal ejection fraction) were enrolled. FVT involved left posterior fascicle and left anterior fascicle in 118 and 2 subjects, respectively. VT was noninducible in 3 patients, and ablation was acutely successful in 117 patients. With a median follow-up of 55.7 months, VT of a similar ECG morphology recurred in 17 patients, and repeat procedure confirmed FVT recurrence involving the same fascicle. Shorter VT cycle length was the only significant predictor of FVT recurrence (P=0.03). Six other patients developed new-onset upper septal FVT that was successfully ablated. CONCLUSIONS: Ablation of FVT guided by activation mapping is associated with a single procedural success rate without the use of antiarrhythmic drugs of 80.3%. Arrhythmia recurrences after an initially successful ablation were caused by recurrent FVT involving the same fascicle in two thirds of patients or new onset of upper septal FVT in the remainder.

Idiopathic accelerated idioventricular rhythm or ventricular tachycardia originating from the right bundle branch: unusual type of ventricular arrhythmia.

BACKGROUND: Accelerated idioventricular rhythm (AIVR) or ventricular tachycardia (VT) originating from the right bundle branch (RBB) is rare and published clinical data on such arrhythmia are scarce. In this study, we will describe the clinical manifestations, diagnosis, and management of a cohort of patients with this novel arrhythmia. METHODS AND RESULTS: Eight patients (5 men; median age, 25 years) with RBB-AIVR/VT were consecutively enrolled in the study. Pharmacological testing, exercise treadmill testing, electrophysiological study, and catheter ablation were performed in the study patients, and ECG features were characterized. All RBB-AIVR/VTs were of typical left bundle-branch block morphology with atrioventricular dissociation. The arrhythmias, which demonstrated chronotropic variability, were often isorhythmic with sinus rhythm and were accelerated by physical exercise, stress, and intravenous isoprenaline infusion. The rate of RBB-AIVR/VT varied from 45 to 200 beats per minute. Two patients experienced syncope, and 3 had impaired left ventricular function. Metoprolol was proven to be the most effective drug to decelerate the arrhythmia rate and relieve symptoms. Electrophysiology study was performed in 5 patients and the earliest activation with a sharp RBB potential was localized in the mid or distal RBB area. Catheter ablation terminated the arrhythmia with subsequent RBB block morphology during sinus rhythm. During follow-up, patients' symptoms were controlled with normalization of left ventricular function either on metoprolol or by catheter ablation. CONCLUSIONS: RBB-AIVR/VT is an unusual type of ventricular arrhythmia. It can result in significant symptoms and depressed ventricular function and can be successfully treated with catheter ablation.

Mapping of focal atrial tachycardia with an uninterpretable activation map after extensive atrial ablation: tricks and tips.

BACKGROUND: Atrial tachycardias (ATs) after extensive ablation are increasingly common and challenging arrhythmias. The prolonged intra-atrial conduction time (IACT) during ATs in the milieu may complicate the mapping of focal ATs. In this present study, we aim to characterize the electrophysiological features of ATs in this unique setting and to delineate an effective mapping strategy further. METHODS AND RESULTS: In total, 13 patients (average age, 59±7 years) in a cohort of 80 patients referred for AT ablation were selected for the study. The patients all demonstrated an undistinguishable map not ready to be interpreted the 3-dimensional mapping. A total of 13 ATs were mapped with mean tachycardia cycle length of 296±70 ms. Two activation patterns were identified, which were referred to as pseudo-macroreentry and chaotic activation. The former was a focal AT originating from the vicinity of an area of conduction block with the IACT less than the window of interest duration (4 cases; IACT/window of interest ratio range, 0.93-0.98). The latter refers to a focal AT exhibiting a disorderly color mapping display with IACT exceeding the window of interest duration (9 cases; IACT/window of interest ratio range, 1.02-1.29). The IACT was determined after resetting the annotation. All ATs were successfully eliminated at the originating site. CONCLUSIONS: We delineated a series of focal ATs in the setting of a significantly prolonged IACT encountered in patients after previous extensive ablation. Two activation patterns were identified, which may help facilitate the mapping of focal ATs in this setting.

Tachycardiomyopathy complicated by focal atrial tachycardia: incidence, risk factors, and long-term outcome.

OBJECTIVE: Focal atrial tachycardias (ATs) are known to have the potential to develop tachycardiomyopathy (TCM). The aim of the study was to investigate the incidence, risk factors, and long-term outcome of TCM patients complicated by focal ATs. METHODS AND RESULTS: A total of 237 patients undergoing electrophysiological studies were enrolled, among which 216 patients were diagnosed as focal ATs. In total, 18 patients (8.3%, 13 males) were identified to have TCM. The TCM patients were younger (29.8 ± 20.1 vs. 45.9 ± 17.3; P < 0.000) and were more frequently males (13/18 vs. 80/198; P = 0.014). The ATs were more likely to be persistent (11/18 vs. 32/198; P < 0.001). There was no difference between the 2 groups in terms of the tachycardia cycle length (392 milliseconds vs. 380 milliseconds; P = 0.56) and heart rate (144 bpm vs. 156 bpm; P = 0.15). The persistence and incidence of symptoms and prevalence of structural heart disease were comparable between the groups. In a multivariable analysis, the younger age and persistent nature were independently associated with TCM. In a 56 ± 21-month follow-up, all TCM patients had improved left ventricle ejection fraction after successful catheter ablation or medical therapy (43.9 ± 5.8% vs. 61.1 ± 3.5%; P ＜ 0.05). However, 1 patient suffered sudden cardiac death due to unauthorized withdrawal of the drug and progressive heart failure. CONCLUSIONS: The incidence of TCM in focal ATs patients was 8.3%. Younger age and persistent nature were the independent risk factors of TCM. Most TCM patients had a benign outcome; however, long-term risk of sudden death does exist.

LV dyssynchrony as assessed by phase analysis of gated SPECT myocardial perfusion imaging in patients with Wolff-Parkinson-White syndrome.

PURPOSE: The purpose of this study was to evaluate left ventricular (LV) mechanical dyssynchrony in patients with Wolff-Parkinson-White (WPW) syndrome pre- and post-radiofrequency catheter ablation (RFA) using phase analysis of gated single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI). METHODS: Forty-five WPW patients were enrolled and had gated SPECT MPI pre- and 2-3 days post-RFA. Electrophysiological study (EPS) was used to locate accessory pathways (APs) and categorize the patients according to the AP locations (septal, left and right free wall). Electrocardiography (ECG) was performed pre- and post-RFA to confirm successful elimination of the APs. Phase analysis of gated SPECT MPI was used to assess LV dyssynchrony pre- and post-RFA. RESULTS: Among the 45 patients, 3 had gating errors, and thus 42 had SPECT phase analysis. Twenty-two patients (52.4%) had baseline LV dyssynchrony. Baseline LV dyssynchrony was more prominent in the patients with septal APs than in the patients with left or right APs (p < 0.05). RFA improved LV synchrony in the entire cohort and in the patients with septal APs (p < 0.01). CONCLUSION: Phase analysis of gated SPECT MPI demonstrated that LV mechanical dyssynchrony can be present in patients with WPW syndrome. Septal APs result in the greatest degree of LV mechanical dyssynchrony and afford the most benefit after RFA. This study supports further investigation in the relationship between electrical and mechanical activation using EPS and phase analysis of gated SPECT MPI.

Transvenous phrenic nerve stimulation in patients with Cheyne-Stokes respiration and congestive heart failure: a safety and proof-of-concept study.

BACKGROUND: Cheyne-Stokes respiration (CSR), which often occurs in patients with congestive heart failure (CHF), may be a predictor for poor outcome. Phrenic nerve stimulation (PNS) may interrupt CSR in patients with CHF. We report the clinical use of transvenous PNS in patients with CHF and CSR. METHODS: Nineteen patients with CHF and CSR were enrolled. A single stimulation lead was placed at the junction between the superior vena cava and brachiocephalic vein or in the left-side pericardiophrenic vein. PNS stimulation was performed using Eupnea System device (RespiCardia Inc). Respiratory properties were assessed before and during PNS. PNS was assessed at a maximum of 10 mA. RESULTS: Successful stimulation capture was achieved in 16 patients. Failure to capture occurred in three patients because of dislocation of leads. No adverse events were seen under maximum normal stimulation parameters for an overnight study. When PNS was applied following a series of central sleep apneic events, a trend toward stabilization of breathing and heart rate as well as improvement in oxygen saturation was seen. Compared with pre-PNS, during PNS there was a significant decrease in apnea-hypopnea index (33.8 ± 9.3 vs 8.1 ± 2.3, P = .00), an increase in mean and minimal oxygen saturation as measured by pulse oximetry (89.7% ± 1.6% vs 94.3% ± 0.9% and 80.3% ± 3.7% vs 88.5% ± 3.3%, respectively, all P = .00) and end-tidal CO2 (38.0 ± 4.3 mm Hg vs 40.3 ± 3.1 mm Hg, P = .02), but no significant difference in sleep efficiency (74.6% ± 4.1% vs 73.7% ± 5.4%, P = .36). CONCLUSIONS: The preliminary results showed that in a small group of patients with CHF and CSR, 1 night of unilateral transvenous PNS improved indices of CSR and was not associated with adverse events.

Myocardial injury resulting from radiofrequency catheter ablation: comparison of circumferential pulmonary vein isolation and complex fractionated atrial electrograms ablation.

BACKGROUND: Radiofrequency catheter ablation (RFCA) necessarily produces an area of myocardial necrosis. However, the difference of the extent of myocardial injury between circumferential pulmonary vein isolation (CPVI) and complex fractionated atrial electrograms (CFAE) ablation in patients with atrial fibrillation (AF) has not been investigated before. METHODS: Twenty-nine consecutive male patients (n = 29) with either paroxysmal or persistent AF were selected for CPVI or CFAE ablation. The CPVI or CFAE ablation was performed with a three-dimensional electroanatomical mapping system (CARTO). Serum cardiac biomarkers, for example, cardiac troponin T (cTnT), aspartate transaminase (AST), lactate dehydrogenase (LDH), creatine kinase (CK), and creatine kinase myocardial bound (CKMB) were determined by the Elecsys STATE immunoassay. Cardiac structure and function were measured with echocardiography. RESULTS: Echocardiography showed that there was no significant difference of atrioventricular structure or function parameters between the CPVI group and the CFAE ablation group. Serum cTnT showed a significant increase in the CFAE ablation group over the CPVI group at 12 and 24 hours after the procedure (P < 0.05, respectively), and then it was reduced to a normal level after 48 hours. Serum AST showed a significant increase in the CFAE ablation group over the CPVI group at post-procedure, 4 and 12 hours after the procedure (P < 0.05, respectively), and then it reached to a normal level after 24 hours. There was no significant difference in LDH, CK, or CKMB levels between the CFAE ablation group and the CPVI group at any time point (P > 0.05). CONCLUSIONS: cTnT and AST other than LDH, total CK or CKMB activity significantly increased more in the CFAE ablation group than the CPVI group. However, the difference of the serum levels of cTnT, AST between two groups was temporary.

Puerarin inhibits iNOS, COX-2 and CRP expression via suppression of NF-κB activation in LPS-induced RAW264.7 macrophage cells.

Puerarin (7,4'-dihydroxy-8-C-glucosylisoflavone) is the most abundant isoflavone-C-glucoside extracted from Radix puerariae, and it has been used for various medicinal purposes in traditional oriental medicine for thousands of years. In the present study, the ability of the puerarin to modulate inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2) and C reactive protein (CRP) expression and induce changes in the nuclear factor κB (NF-κB) pathway in RAW264.7 macrophage cells was examined. The protein and mRNA levels of lipopolysaccharide (LPS)-induced iNOS, COX-2 and CRP were determined in RAW246.7 macrophage cells. Inhibitor κB (I-κB) phosphorylation and p65NF-κB expression in RAW246.7 macrophage cells were also detected under our experimental conditions. The results indicated that puerarin inhibited the expression of LPS-induced iNOS, COX-2 and CRP proteins and also suppressed their mRNAs from RT-PCR experiments in RAW264.7 cells. Subsequently, we determined that the inhibition of iNOS, COX-2 and CRP expression was due to a dose-dependent inhibition of phosphorylation and degradation of I-κB, which resulted in the reduction of p65NF-κB nuclear translocation. These data suggested that the effect of puerarin-mediated inhibition of LPS-induced iNOS, COX-2 and CRP expression is attributed to suppressed NF-κB activation at the transcriptional level.

Randomized comparison between pulmonary vein antral isolation versus complex fractionated electrogram ablation for paroxysmal atrial fibrillation.

INTRODUCTION: Circumferential pulmonary vein antral isolation (PVAI) and atrial complex fractionated electrograms (CFEs) are both ablative techniques for the treatment of paroxysmal atrial fibrillation (PAF). However, data on the comparative value of these 2 ablation strategies are very limited. METHODS AND RESULTS: We randomized 118 patients with drug-refractory PAF to receive PVAI ablation (n = 60) or CFE ablation (n = 58). For CFE group, spontaneous/induced AF was mapped using validated, automated software to guide ablation until all CFE areas were eliminated. For PVAI group, all 4 pulmonary vein antra were electrically isolated as confirmed by circular mapping catheter. Patients with spontaneous/inducible AF after the initial ablation procedure were crossed over to the other arms. After initial ablation procedure, AF persisted/inducible in 24/59 patients (41%), and 34/58 patients (59%) assigned to PVAI and CFE ablation, respectively (P = 0.05). Then 58 patients underwent PVAI + CFE ablation. After 22.6 ± 6.4 months, PVAI ablation group was more likely than CFE ablation group to achieve control of any AF/atrial tachycardia (AT) off drugs (43/60, 72% vs 33/58, 57%, P = 0.075) and lower recurrence rate of AT (11.9% vs 34.5%, P = 0.004). Patients who received CFE ablation alone (38%) had significantly lower overall success rate to achieve control of AF/AT off drugs compared with patients who received PVAI ablation (77%, P = 0.002) alone or PVAI + CFE ablation (69%, P = 0.008) due to higher recurrence rate of AT (50% vs 6% vs 13%, P < 0.01). CONCLUSIONS: CFE ablation in PAF patients was associated with higher occurrence rate of postprocedure AT compared with PVAI ablation, whereby making it less likely to be a sole ablation strategy for PAF patients.

Evaluation of the traditional Chinese Medicine Shensongyangxin capsule on treating premature ventricular contractions: a randomized, double-blind, controlled multicenter trial.

BACKGROUND: Premature ventricular contraction (PVC) is one of the most common kinds of arrhythmias for which the treatment falls into dilemma. Previous clinical application showed that the traditional Chinese Medicine Shensongyangxin (SSYX) capsule is efficacious for the treatment of PVCs. This randomized clinical trial aimed to further evaluate the efficacy and safety of SSYX capsule on treating PVC. METHODS: The subjects who had frequent PVCs with or without organic heart disease and normal cardiac function were enrolled in the study. The primary endpoint was the change of PVC numbers after eight-week medication with SSYX capsule. The secondary endpoints included change of clinical symptoms related to PVCs and the safety evaluation of SSYX capsule. Totally 188 PVC patients were randomly enrolled in the non-organic heart disease PVCs trial and orally took either SSYX capsules or analogues (three times per day, 4 capsules one time). A total of 671 PVCs patients were randomly enrolled in the organic heart disease PVCs trial, and orally took either SSYX capsules (three times per day, 4 capsules one time) or mexiletine tablet (three times per day, 150 mg one time). The PVCs were monitored and calculated with 24-hour Holter electrocardiogram. Routine blood, liver and kidney function were tested before and after medication with SSYX capsule. RESULTS: SSYX capsules significantly decreased the PVCs numbers and alleviated the related symptoms in patients with or without organic heart disease. In non-organic heart disease group, SSYX capsules and the placebos decreased the PVCs from 12,561.34 ± 9,777.93 to 4,806.87 ± 6,507.17, and 12,605.69 ± 8,736.34 to 10,364.94 ± 9,903.41, respectively. The total effective rate was 74.2% and 28.9% in SSYX and placebo groups (P < 0.001). In organic heart disease group, SSYX capsule and mexiletine decreased the PVCs from 8,641.01 ± 8,923.57 to 3,853.68 ± 7,096.42, 8,621.61 ± 8,367.74 to 5,648.29 ± 8,667.38, respectively. The total effective rate was 65.8% and 50.7% in SSYX and mexiletine groups (P < 0.001). In addition, SSYX capsule significantly alleviated PVCs-related symptoms such as palpitations, chest tightness, insomnia, fatigue, and night sweats. No adverse cardiac events were observed except some slight gastrointestinal side effects during the study. CONCLUSIONS: Compared with placebo or mexiletine, SSYX capsules have significant therapeutic efficacy in reducing PVCs numbers and alleviate PVCs-related symptoms.

Long-term clinical implication of the occurrence of dissociated pulmonary vein activities after circumferential left atrial ablation in patients with paroxysmal atrial fibrillation.

BACKGROUND: The incidence and clinical implication of dissociated pulmonary vein (PV) electrical activities after circumferential antrum PV ablation for paroxysmal atrial fibrillation (AF) remains unclear. METHODS AND RESULTS: A total of 196 patients with symptomatic paroxysmal AF who underwent circumferential antrum PV ablation were prospectively studied. Dissociated PV electrical activities were observed in 101 patients (Group 1), but absent in the remaining 95 patients (Group 2). There were no significant differences in the baseline clinical characteristics between them, except that Group 2 had a higher prevalence of hypertension (30 vs. 44%, P = 0.04). After 21.8 ± 7.9 months of follow-up, 148 had no recurrence of AF after the initial procedure. AF recurrence rate was significantly higher in Group 2 than in Group 1 (P = 0.023). Relapse of PV conduction was the major cause of AF recurrence in both groups (16/16 vs. 19/23, P = 0.08), and the overall procedural success rate after the redo ablation procedure was similar in the 2 groups (90 vs. 86%, P = 0.44). However, the total number of patients with non-PV foci was significantly higher in Group 2 than in Group 1 (12/95 vs. 2/101, P < 0.01). CONCLUSIONS: Dissociated PV electrical activities might identify a subgroup of patients with relatively higher initial procedural success with circumferential PV antrum ablation.

Improvement of heart function in postinfarct heart failure swine models after hepatocyte growth factor gene transfer: comparison of low-, medium- and high-dose groups.

Despite advances in surgical and reperfusion therapy, there is no effective therapy currently exists to prevent the progressive decline in cardiac function following myocardial infarction. Hepatocyte growth factor has potent angiogenic and anti-apoptotic activities. The aim of this study was to investigate the therapeutic effect and dose-effect relationship on postinfarction heart failure with different doses of adenovirus-mediated human hepatocyte growth factor (Ad(5)-HGF) transference in swine models. Totally twenty swine were randomly divided into four groups: (a) control group (null- Ad(5), 1 ml); (b) low-dose group (1 x 10(9) Pfu/ml Ad(5)-HGF, 1 ml); (c) medium-dose group (5 x 10(9) Pfu/ml Ad(5)-HGF, 1 ml); (d) high-dose group (1 x 10(10) Pfu/ml Ad(5)-HGF, 1 ml). Four weeks after left anterior descending coronary artery (LAD) ligation, different doses of Ad(5)-HGF were transferred in three therapeutic groups via right coronary artery. Four and seven weeks after LAD ligation, gate cardiac perfusion imaging was performed to evaluate cardiac perfusion and left ventricular ejection fraction (LVEF). Seven weeks after surgery, the apoptotic index of cardiocyte was observed by TUNEL, the expression of Bcl-2, Bax, alpha-SMA and Factor VIII in the border zones were evaluated by immunohistochemistry, respectively. Four weeks after myocardial infarction, no significant difference was observed among four groups. Three weeks after Ad(5)-HGF transfer, the improvement of cardiac perfusion and LVEF was obviously observed, especially after 1 x 10(10) Pfu Ad(5)-HGF transfer. TUNEL assay showed that 5 x 10(9) Pfu and 1 x 10(10) Pfu Ad(5)-HGF treatment had a obvious reduction in the apoptotic index compared with the null-Ad(5) group, especially after 1 x 10(10) Pfu Ad(5)-HGF treatment. The expression of Bcl-2 protein was increased and the expression of Bax protein was inhibited in the 5 x 10(9) Pfu and 1 x 10(10) Pfu Ad(5)-HGF groups compared with the null-Ad(5) group. The vessel density of Factor VIII(+) and alpha-SMA(+) was increased in Ad(5)-HGF groups compared with the null-Ad(5) group. There were no significant differences in angiogenesis, reducing apoptosis and ameliorating heart function between the 1 x 10(9) Pfu Ad(5)-HGF group and the null-Ad(5) group. Although no statistical difference was observed between 1 x 10(10) Pfu and 5 x 10(9) Pfu Ad(5)-HGF groups, the cardiac protective effects of 1 x 10(10) Pfu Ad(5)-HGF treatment were greater than 5 x 10(9) Pfu Ad(5)-HGF treatment. Different doses of Ad5-HGF injected via noninfarct-related artery could induce angiogenesis, reduce apoptosis and ameliorate heart function, and the cardiac protective effects of 1 x 10(10) Pfu Ad5-HGF is of most significance.