Bezold-Jarisch-Like Reflex During Radiofrequency Ablation of the Pulmonary Vein Tissues in Patients with Paroxysmal Focal Atrial Fibrillation

Pulmonary Vein Ablation-Induced Bradycardia. Introduction: Information is lacking about the occurrence of radiation-related proarrhythmic events during application of radiofrequency (RF) energy at (he pulmonary veins in patients with paroxysmal focal atrial fibrillation. The purpose of this study was to assess the theoretical risk of reflex bradycardia and hypotension response during RF ablation of these regions rich in endocardial nerve terminals.
Methods and Results: Among the 40 consecutive patients (29 men, 11 women; mean age 65 ± 12 years) with clinically documented frequent attacks of paroxysmal atrial fibrillation who underwent superior pulmonary vein ablation for left local atrial fibrillation, 6 patients (15%) developed bradycardia-hypotension syndrome during energy delivery. A single atrial fibrillation trigger focus in the left or right superior pulmonary vein was found in 3 and 1 patients, respectively. Two patients had two trigger foci originating from the orifice or proximal part of both superior pulmonary veins. After RF current was applied for a period of 14 ± 10 seconds, 2 patients developed functional rhythm and sinus bradycardia, another 2 patients had profound sinus bradycardia, I patient had two episodes of sudden onset of complete AV block with resultant 9.5-second a systole, and I patient showed profound sinus bradycardia, transient AV block, and an K-second asystole due to sinus arrest. Blood pressure fell when any substantial bradyarrhythmias occurred. All 6 patients were free of rhythm disturbances during The postablation follow-up period (mean 8 ± 2 months).
Conclusion: RF catheter ablation of the pulmonary vein tissues could evoke a variety of profound bradycardia-hypotension responses. The Bezold-Jarisch-like reflex might be the underlying mechanism.     

Long‐Term Outcome of Catheter Ablation in Patients with Atrial Fibrillation Originating from Nonpulmonary Vein Ectopy

Long‐Term Outcome of NPV AF Ablation . Introduction: Data regarding the long‐term outcome of catheter ablation in patients with nonpulmonary vein (NPV) ectopy initiating atrial fibrillation (AF) are limited. We aimed to evaluate the long‐term result of patients with AF who had NPV triggers and underwent catheter ablation. Methods and Results: The study included 660 consecutive patients (age 54 ± 11 years old, 477 males) who had undergone catheter ablation for AF. Group 1 consisted of 132 patients with AF initiating from the NPV, and group 2 consisted of 528 patients with AF initiating from pulmonary vein (PV) triggers only. Patients from Group 1 were younger than those from Group 2 (51 ± 12 years old vs 54 ± 11 years old, P = 0.001) and were more likely to be females (34.4% vs 25.8%, P = 0.049). The incidences of nonparoxysmal AF (36.4% vs 16.3%, P < 0.001) and right atrial (RA) enlargement (31.3% vs 19%, P = 0.004) were higher, and the biatrial substrates were worse in Group 1 than those in Group 2 (left atrial voltage 1.5 ± 0.7 mV vs 1.9 ± 0.7 mV, P < 0.001, RA voltage 1.6 ± 0.5 mV vs 1.8 ± 0.6 mV, P = 0.014). During a follow‐up period of 46 ± 23 months, there was a higher AF recurrence rate in Group 1 than in Group 2 (57.6% vs 38.8%, P < 0.001). The independent predictors of AF recurrence were NPV trigger (P < 0.001, HR 2, 95% CI 1.4–2.85), nonparoxysmal AF (P = 0.021, HR 1.55, 95% CI 1.07–2.24), larger left atrial diameter (P = 0.002, HR 1.04, 95% CI 1.02–1.07) and worse left atrial substrate (P = 0.028, HR 1.3, 95% CI 1.03–1.64). Conclusion: Compared to AF originating from the PV alone, AF originating from the NPV ectopy showed a worse outcome. (J Cardiovasc Electrophysiol, Vol. 24, pp. 250‐258, March 2013)     

Optimal dose for stroke thrombolysis in Asians: low dose may have similar safety and efficacy as standard dose

Summary. Background: Although intravenous tissue‐type plasminogen activator (t‐PA) at a standard dose of 0.9 mg kg^?1 is effective for patients with acute ischemic stroke, concerns have been raised regarding Asians. Objectives: To compare the safety and efficacy between low and standard doses for stroke thrombolysis. Patients/Methods: Consecutive patients receiving t‐PA treatment were recruited according to the prespecified dosing policy from two medical centers in Taiwan: low dose (0.7 mg kg^?1) at National Cheng Kung University Hospital (NCKUH) from August 2006 to June 2009, or standard dose (0.9 mg kg^?1) at NCKUH from July 2009 to December 2010 and at Changhua Christian Hospital from May 2008 to December 2010. The primary safety outcome was the occurrence of symptomatic intracerebral hemorrhage (SICH). The secondary efficacy outcome was the proportion of patients with a modified Rankin Scale (mRS) grade of ≤ 1 at 3 months. Results: From August 2006 to December 2010, 261 patients were recruited, of whom 105 and 156 received low and standard doses, respectively. The occurrence of SICH was non‐significantly lower in the standard‐dose group than in the low‐dose group (2.6% vs. 4.8%, respectively; P = 0.34). The favorable outcome of mRS grade of ≤ 1 at 3 months was similar (38.4% and 41.1%, respectively; P = 0.676). A review of other case series of low vs. standard doses in Asians also showed similar safety and efficacy. Conclusion: Our study, as well as other case series on Asians, revealed that standard‐dose thrombolysis for acute ischemic stroke in an Asian population carries no increased risk of symptomatic intracerebral hemorrhage when compared with the low dose.     

Background ionizing radiation plays a minor role in the production of chromosome translocations in a control population

Purpose: To obtain a relationship between background chromosome translocation frequency and age with translocation frequency measured to a high statistical precision, and to identify the role of background ionizing radiation in the production of chromosome translocations in a control population. Materials and methods: Lymphocytes from 35 healthy control individuals (15 females and 20 males) were scored, using fluorescence in situ hybridization, for the presence of chromosomal translocations. Translocation frequencies were measured to a high statistical precision (s.d. 25% or less for each individual). These control subjects were of varying ages, ranging from 0 (cord blood) to 98 years. Results: In a total of 521,492 metaphases (203,754 genome equivalent cells) scored, an average of 5,822 genome equivalent cells per individual, 764 translocations were observed in the 35 individuals. The translocation frequencies ranged from 0 (for cord blood) to 0.0167 (for a 98 year old) translocations per cell. The average age and translocation frequency was 50 years and 0.004 translocations per cell, respectively. The best fit of the relationship between translocations and age was: Y = 7 x 10-4 + 6.9 x 10-6 A + 1.35 x 10-6 A2, which does not obey the linear relationship expected from chronic background radiation alone. The curvilinear relationship observed clearly shows that other endogenous and exogenous clastogens or clastogenic events, in addition to radiation, serve to generate chromosome translocations in control populations. Conclusion: The background translocation frequency in control individuals follows a curvilinear relationship with age. No significant variation was observed between individuals of the same age. Clastogenic processes of normal aging and physiological factors in additional to ionizing radiation play a major role in the production of chromosome translocations in a control population. Background radiation, however, appears to play a minor role in chromosome translocation production in control individuals living near sea level.     

Increasing expression of extracellular matrix metalloprotease inducer in renal cell carcinoma: Tissue microarray analysis of immunostaining score with clinicopathological parameters

AIM: Renal tumor cell invasion is responsible for both local tissue destruction and distant metastasis. Invasion is largely mediated by matrix metalloproteases that are thought to be induced by tumor cell-derived extracellular matrix metalloprotease inducer (EMMPRIN) in surrounding fibroblasts. We hypothesized that EMMPRIN and matrix metalloproteinase-9 (MMP-9) are over-expressed in renal cell carcinoma. METHODS: Immunohistochemical analysis of EMMPRIN and MMP-9 was performed in tissue microarrays of 79 renal cell carcinomas including 12 cases of chromophobe renal cell carcinoma (ChRCC), 53 cases of clear cell renal cell carcinoma (CRCC), 8 cases of papillary renal cell carcinoma (PRCC), and 6 cases of carcinoma of the collecting ducts of Bellini (CoRCC). RESULTS: All renal cell carcinomas showed significant immunohistochemical expression of EMMPRIN. The EMMPRIN score in ChRCC (321+/-21) was significantly higher than in other histological subtypes of RCC (166+/-19 for CRCC; 276+/-24 for PRCC; 98+/-17 for CoRCC). MMP-9 was mainly expressed in tumor stromal cells and not in non-cancerous fibrovascular regions. The percent positive staining of MMP-9 at the invasive front of tumor cells was significantly higher in CRCC than in ChRCC, PRCC, or CoRCC. Higher EMMPRIN scores in CRCC were associated with shorter survival time, and correlated with higher T staging and nuclear grading. CONCLUSIONS: Our findings demonstrate for the first time that EMMPRIN is over-expressed in renal cell carcinomas. Increased expression of EMMPRIN in tumor cells is associated with poor prognosis of patients with CRCC.     

Effects of 17β-Estradiol on Tachycardia-Induced Changes of Atrial Refractoriness and Cisapride-Induced Ventricular Arrhythmia

INTRODUCTION: Gender difference is known to be associated with the occurrence of arrhythmia. However, the effects of female sex hormone on atrial electrophysiology, and on the occurrence of torsades de pointes (TdP) induced by cisapride have been unclear. METHODS AND RESULTS: Two experiments were included in this study. In experiment 1, effective refractory periods (ERPs) from five epicardial atrial sites were measured before and after rapid atrial pacing at 800 beats/min for 30 minutes in dogs with pretreatment of verapamil (n = 10), 17beta-estradiol (n = 10), or without pretreatment (n = 10, control group). In experiment 2, limb-lead ECG and monophasic action potentials in the left and right ventricles were recorded before and after each dose of cisapride (2 to 6 mg/kg) during different ventricular rates in dogs with (n = 9) and without (n = 14) concomitant administration of 17beta-estradiol (0.3 microg/kg). After 17beta-estradiol administration, there were greater atrial ERPs in the study dogs than in the control group. The atrial ERPs were shortened significantly after rapid atrial pacing, but the degree was greater in the control group than in the dogs pretreated with verapamil or 17beta-estradiol. Moreover, the recovery of atrial ERPs was faster in dogs pretreated with verapamil or 17beta-estradiol than in the control group. In experiment 2, cisapride prolonged the QT interval and biventricular APD90 and induced early afterdepolarizations (EADs) in a dose-dependent manner. However, dogs receiving cisapride combined with 17beta-estradiol had a greater increase of ventricular repolarization and a higher incidence of EADs than those receiving cisapride only. Moreover, dogs receiving cisapride combined with 17beta-estradiol (3/9, 33%) had a greater incidence of TdP than those receiving cisapride only (0/14, 0%, P < 0.05). CONCLUSIONS: 17beta-estradiol has a significant effect on atrial electrophysiology, which may be related to the prevention of atrial fibrillation. However, the high incidence of TdP in dogs receiving cisapride combined with 17beta-estradiol suggests that the female sex hormone is an important risk factor of cisapride-induced proarrhythmia.     

Relationship between fatty liver, alanine aminotransferase, HBsAg and hepatitis C virus

A community health survey of 923 residents aged 30 years or more was performed in Putai Township of Taiwan. To elucidate the relationships between hepatitis C virus (HCV) and surrogate tests for non-A, non-B hepatitis in hyperendemic areas of hepatitis B virus (HBV) serum levels of alanine aminotransferase (ALT), triglycerides, cholesterol, hepatitis B surface antigen (HBsAg) and antibody to HCV (anti-HCV) were examined. Glucose tolerance tests and the history of diabetes treatment were used to define the diabetes status. Fatty liver was diagnosed by sonography. The prevalence of anti-HCV was 2.6% (95% confidence interval, 1.6-3.6%). Elevated ALT and fatty liver were significantly associated with anti-HCV in univariate analysis. Anti-HCV was not an associated factor for fatty liver after adjusting for serum triglycerides and cholesterol, sex, body mass index and diabetes status through multiple logistic regression. However elevated ALT was still associated with anti-HCV after adjusting for serum triglycerides, sex, body mass index, HBsAg and age through multiple linear regression. The anti-HCV prevalence was similar between HBsAg-positive and negative subjects. Aggregation of HCV infection was found among spouses. It was concluded that elevated ALT and intimate contact with HCV carriers might be associated factors for HCV infection, and that HBV infection and fatty liver were not related to HCV infection in Taiwan.