Clinical Manifestations, Outcomes, and Mortality Risk Factors of Atrial-Esophageal Fistula: A Systematic Review.

INTRODUCTION: Atrial-esophageal fistula (AEF) is a rare but life-threatening complication of catheter ablation. The clinical presentation and mortality risk factors of AEF have not been fully elucidated. The aim of this study was to systematically review the clinical characteristics and prognosis of AEF. METHODS: PubMed was searched from inception to October 2020 following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement protocol. RESULTS: A total of 190 AEF patients were included. The mean age was 59.29 ± 11.67 years, 74.21% occurred in males, and 81.58% underwent radiofrequency ablation. AEF occurred within 30 days after ablation in 80.82% of patients and occurred later in patients presenting with neurological symptoms compared with other symptoms (median of onset time: 27.5 days vs. 16 days, p < 0.001). Clinical presentation included fever (81.58%) and neurological symptoms (80.53%). Chest computed tomography (abnormal rate of 91.24%) was the preferred diagnostic test, followed by magnetic resonance imaging of the brain (abnormal rate of 90.91%). Repeated testing improved diagnostic evaluation sensitivity. Distinctive imaging results included free air in the mediastinum (incidence rate of 81.73%) and air embolism of the brain (incidence rate of 57.53%). The overall mortality was 63.16%, with worse nonsurgical treatment outcomes compared with outcomes of surgical treatment (94.19% vs. 33.71%, p < 0.001). Conservative or stent intervention was an independent risk factor for mortality. Age (adjusted odds ratio, 1.063, p = 0.004), presentation with neurological symptoms (adjusted odds ratio, 5.706, p = 0.017), and presentation with gastrointestinal bleeds (adjusted odds ratio, 3.009, p = 0.045) were also predictors of mortality. CONCLUSIONS: AEF is a fatal ablation complication. AEF can be diagnosed using a combination of a clinical history of ablation, infection, or neurological symptoms and an abnormal chest CT. Our analysis supports that surgical treatment reduces the mortality rate.

Feasibility and safety of left atrial appendage occlusion guided by procedural fluoroscopy only: A pilot study.

BACKGROUND: Left atrial appendage occlusion (LAAO) is usually performed via the guidance of procedural transesophageal echocardiography (TEE) companied by general anesthesia (GA). OBJECTIVE: To investigate the feasibility and safety of LAAO guided by procedural fluoroscopy only. METHODS: The patients eligible for LAAO were enrolled into the current study and received implantation of either Watchman device or LAmbre device. The procedure was carried out with procedural fluoroscopy only and no companied GA; the position, shape, and leakage of the device were assessed by contrast angiography. TEE was performed after 3-month follow-up to evaluate the thrombosis, and leakage of device. RESULTS: Ninety-seven patients with atrial fibrillation (AF) with either Watchman device (n = 49) or LAmbre device (n = 48) were consecutively enrolled. Watchman device group was of lower CHA2 DS2 -VASc and HAS-BLED scores compared with LAmbre device groups (p < .05); the two groups had similar distributions of other baseline characteristics (p > .05), including procedural success rate (98.0% vs. 97.9%), mean procedure time, mean fluoroscopy time, total radiation dose, contrast medium dose, percentage of peri-device leakage. Pericardial effusions requiring intervention occurred in two of the Watchman group. TEE follow-up found no patient with residual leakage ≥5 mm at 3 months and no device related thrombosis (DRT). During the 22.0 ± 11.1 months follow-up, two patients experienced ischemic stroke. CONCLUSIONS: LAAO with the procedural imaging of fluoroscopy only exhibited the promising results of efficacy and safety. A prospective randomized multicenter study would be required to verify the observations in this study.

Atrioesophageal fistula post atrial fibrillation ablation: A multicenter study from China.

BACKGROUND AND OBJECTIVE: Atrioesophageal fistula (AEF) is a rare but devastating complication with high mortality post atrial fibrillation (AF) ablation. The purpose of current study was to determine the epidemiology, clinical features, pathogenesis, and management of AEF after AF ablation. METHODS AND RESULTS: Patients with diagnosed AEF were included and retrospectively analyzed according to the registry of 11 centers in China from January 2010 to December 2019. A total of 16 AEF cases were identified from 44 794 patients who received a left atrial ablation procedure (0.035% per procedure). The interval from procedure to clinical onset of AEF averaged 18.3 days (3-39 days). The fever ranked the most common symptom, occurred in 14 of the 16 cases, followed by neurological deficits (n = 11), chest pain (n = 5), and hematemesis (n = 4). Patients undergoing surgical repair had a better prognosis compared to those receiving nonsurgical management ([4 of 8] 50.0% vs [8 of 8] 100%, P < .05) with an overall mortality rate of 75.0%. CONCLUSION: AEF is highly characterized by varied manifestations. Early diagnosis and urgent surgical repair are vital to those patients and associated with improved survival rates.

TWEAK/Fn14 mediates atrial-derived HL-1 myocytes hypertrophy via JAK2/STAT3 signalling pathway.

Atrial myocyte hypertrophy is one of the most important substrates in the development of atrial fibrillation (AF). The TWEAK/Fn14 axis is a positive regulator of cardiac hypertrophy in cardiomyopathy. This study therefore investigated the effects of Fn14 on atrial hypertrophy and underlying cellular mechanisms using HL-1 atrial myocytes. In patients with AF, Fn14 protein levels were higher in atrial myocytes from atrial appendages, and expression of TWEAK was increased in peripheral blood mononuclear cells, while TWEAK serum levels were decreased. In vitro, Fn14 expression was up-regulated in response to TWEAK treatment in HL-1 atrial myocytes. TWEAK increased the expression of ANP and Troponin T, and Fn14 knockdown counteracted the effect. Inhibition of JAK2, STAT3 by specific siRNA attenuated TWEAK-induced HL-1 atrial myocytes hypertrophy. In conclusion, TWEAK/Fn14 axis mediates HL-1 atrial myocytes hypertrophy partly through activation of the JAK2/STAT3 pathway.

Interaction between nitric oxide signaling and gap junctions during ischemic preconditioning: Importance of S-nitrosylation vs. protein kinase G activation.

Much effort has been dedicated to exploring the mechanisms of IPC, and the GJ is one of the proposed targets of IPC. Several lines of evidence have indicated that NO affects GJ permeability regulation and expression of connexin isoforms. NO-induced stimulation of the sGC-cGMP pathway and the subsequent PKG activation could lead directly to connexin phosphorylation and GJ coupling modification. Additionally, because NO-induced cardioprotection against I/R injury beyond the cGMP/PKG-dependent pathway has been reported in isolated cardiomyocytes, it has been posited that NO-mediated GJ coupling might be independent from the activation of the NO-induced cGMP/PKG pathway during IPC. S-nitrosylation by NO exerts a major influence in IPC-induced cardioprotection. It has been suggested that NO-mediated cardioprotection during IPC was not dependent on sGC/cGMP/PKG but on SNO signaling. We need more researches to prove that which signaling pathway (S-nitrosylation or protein kinase G activation) is the major one modulating GJ coupling during IPC. The aim of review article is to discuss the possible signaling pathways of NO in regulating GJ during IPC.

Plumbagin Mediates Cardioprotection Against Myocardial Ischemia/Reperfusion Injury Through Nrf-2 Signaling.

BACKGROUND Plumbagin is a potent antioxidant with anti-inflammatory and anti-carcinogenic action. Myocardial ischemia/reperfusion injury results in organ damage through oxidative stress and inflammatory mechanisms. In this study, we analyzed the potential role of plumbagin against myocardial I/R injury in Wistar rats. MATERIAL AND METHODS Oxidative stress was measured through ROS, lipid peroxide content, and antioxidant enzyme activities. The expression of redox signaling and inflammatory proteins was analyzed through Western blotting. Inflammatory cytokine expressions were determined through ELISA. RESULTS Oxidative stress status was reduced by plumbagin by decreasing ROS and lipid peroxide levels in rats with myocardial I/R (MI/R) injury. Plumbagin regulated redox imbalance induced by I/R injury by modulating the transcription factors NF-κB and Nrf-2. Further, downstream targets of NF-κB (COX-2, iNOS) and Nrf-2 (HO-1, NQO1 and GST) expression were significantly downregulated by plumbagin treatment. Pro-inflammatory cytokine expressions were significantly abrogated by plumbagin treatment. CONCLUSIONS This study shows the protective role of plumbagin against myocardial I/R injury by regulating antioxidant and inflammatory mechanisms.

Role of group I metabotropic glutamate receptors, mGluR1/mGluR5, in connexin43 phosphorylation and inhibition of gap junctional intercellular communication in H9c2 cardiomyoblast cells.

Group I metabotropic glutamate receptors, mGluR1 and mGluR5, are associated with sympathetic nerve activity. Sympathetic nerve stimulation exerts a crucial effect on modulating phosphorylation status and distribution of connexin43 (Cx43) in rat heart. Hence, mGluR1 and mGluR5 have an indirect effect on regulating the function of gap junction channels, which is affected by the availability of Cx43 protein. Additionally, it has been demonstrated that mGluR1/5 are present in ventricular myocardium in particular intercalated disks where Cx43 is the principal component of ventricular gap junction channels. We, therefore, hypothesized that mGluR1/5 might regulate Cx43 phosphorylation and gap junctional intercellular communication (GJIC) directly, independent of sympathetic nerve stimulation. After documenting the presence of mGluR1 and mGluR5 in H9c2 cardiomyoblast cells, addition of the selective mGluR1/5 agonist (S)-3,5-dihydroxyphenylglycine hydrate (DHPG) induced Cx43 phosphorylation and GJIC inhibition in both concentration- and time-dependent manner. The effects of DHPG were abolished by the mGluR1 antagonist LY367385 and the specific inhibitor of MEK1, PD98059 which also reduced phosphorylation of extracellular-signal-regulated protein kinase 1/2 (ERK1/2); but not by the mGluR5 antagonist 6-methyl-2-(phenylethynyl) pyridine hydrochloride or the selective inhibitor of protein kinase C (PKC). In conclusion, in H9c2 cardiomyoblast cells mGluR1 increases Cx43 phosphorylation level and suppresses GJIC involving ERK1/2 but not PKC.

Association between serum uric acid and mortality in a Chinese population of hypertensive patients.

OBJECTIVES: To investigate the association between serum uric acid and mortality in a Chinese population of hypertensive patients. METHODS AND RESULTS: A total of 2757 Chinese hypertensive patients from department of cardiology of several hospitals in Shanghai in China were followed up for about six years in this prospective study. Mortality was recorded and related factors were evaluated. Hyperuricemia was diagnosed by serum uric acid levels of >420 µmol/L in males or >357 µmol/L in females. A total of 2585 hypertensive patients with complete data were included in the final statistical analysis. Totally 709 deaths (27.4%) occurred during the six-year follow-up, of which 475 deaths were attributable to cardiovascular disease (CVD). All-cause and CVD mortality of hypertensive patients with hyperuricemia was significantly higher than that of patients without hyperuricemia. The Cox regression analysis indicated that hazards ratios (HRs) of hyperuricemia for all-cause and CVD mortality were 1.206 (95% CI: 1.002-1.453) and 1.085 (95% CI: 1.002-1.271) respectively. All-cause and CVD mortality of hypertensive patients was significantly increased (both p < 0.05) when uric acid levels increased. HRs of uric acid levels >536 µmol/L to all-cause and CVD mortality of hypertensive patients were 2.115 (95% CI: 1.596-2.801) and 1.861 (95% CI: 1.296-2.673), respectively, compared with those of uric acid levels ≤357 µmol/L. CONCLUSIONS: The data from this cohort study indicate that hyperuricemia can predict increased all-cause and CVD mortality in hypertensive patients.

Dynamic alterations of connexin43, matrix metalloproteinase-2 and tissue inhibitor of matrix metalloproteinase-2 during ventricular fibrillation in canine.

The aim of this study is to investigate the dynamic alterations of cardiac connexin 43 (Cx43), matrix metalloproteinase-2 (MMP-2) and tissue inhibitor of metalloproteinase-2 (TIMP-2) in the setting of different ventricular fibrillation (VF) duration. In this study, thirty-two dogs were randomly divided into sham control group, 8-min VF group, 12-min VF group, and 30-min VF group. Cx43 and phosphorylated Cx43 (p-Cx43) in tissues were detected by western blot and immunofluorescence analysis. MMP-2 and TIMP-2 were detected by western blot and immunohistochemistry analysis. The results showed that Cx43 levels in three VF groups were significantly decreased compared with sham control group. p-Cx43 levels in 12-min and 30-min VF groups were significantly reduced compared with sham control group. The ratio of p-Cx43/Cx43 was also decreased in VF groups. Compared with sham controls, no significant difference was observed between the sham control group and 8-min VF group in MMP-2 level, but MMP-2 level increased in 12-min and 30-min VF groups. The ratios of MMP-2/TIMP-2 were higher in VF groups, and were correlated with the duration of VF. A remarkable correlation was observed between the ratio of p-Cx43/Cx43 and MMP-2/TIMP-2 (r = -0.93, P < 0.01). In conclusion, the alteration of Cx43 and/or p-Cx43 levels and the imbalance of MMP-2 and TIMP-2 may contribute to the initiation and/or persistence of VF. Maneuvers managed to modulate Cx43 level or normalize the balance of MMP-2/TIMP-2 are promising to ameliorate prognosis of VF.

Direct Oral Anticoagulants versus Vitamin K Antagonists in Cirrhotic Patients with Atrial Fibrillation: Update of Systematic Review and Meta-Analysis.

BACKGROUND: Prevention of ischemic stroke is an essential part of managing atrial fibrillation (AF). In recent years, direct oral anticoagulants (DOACs) have emerged as an alternative to vitamin K antagonists (VKAs). Little is understood regarding the efficacy and safety of DOACs in AF patients with liver cirrhosis (LC). OBJECTIVE: This meta-analysis is designed to evaluate the benefits and risks of DOACs compared to VKAs in AF patients with concomitant LC. METHODS: A thorough search was conducted in PubMed, Cochrane Library, Web of Science, Embase, Scopus, and CNKI databases up to February 2023. A total of seven clinical studies including 7551 patients were analyzed in this meta-analysis. All data analyses were performed using Review Manager software version 5.3. RESULTS: Regarding efficacy outcomes, DOACs had comparable clinical benefit in reducing ischemic stroke/systemic thromboembolism (HR=0.79, 95% CI [0.59, 1.06], p = 0.12) to VKAs. The incidence of all-cause death was similar between the DOACs and VKAs group (HR 0.94, 95% CI [0.69, 1.28], p = 0.69). Regarding safety outcomes, DOACs were associated with a significantly lower risk of major bleeding (HR 0.61, 95% CI [0.50, 0.75], p < 0.00001), intracranial hemorrhage (HR 0.55, 95% CI [0.31, 0.98], p = 0.04) and major gastrointestinal bleeding (HR 0.66, 95% CI [0.51, 0.85], p = 0.001) than VKAs. Additional subgroup analysis of advanced cirrhosis revealed that DOACs were associated with a significantly lower risk of major bleeding (HR 0.59, 95% CI [0.39, 0.89], p = 0.01) than VKAs. There were no significant differences between the DOACs and VKAs group concerning the incidence of ischemic stroke/systemic thromboembolism (HR 1.38, 95% CI [0.75, 2.55], p = 0.31) and major gastrointestinal bleeding (HR 0.65, 95% CI [0.41, 1.04], p = 0.08). CONCLUSION: DOACs are associated with more favorable safety outcomes and may be a feasible option of oral anticoagulant for individuals with atrial fibrillation and cirrhosis. Pending validation by randomized prospective studies, the findings of this study should be interpreted with caution.

Imbalance between tissue inhibitor of metalloproteinase 1 and matrix metalloproteinase 9 after cardiopulmonary resuscitation.

AIMS: This study aimed to determine whether (a) there was an imbalance between matrix metalloproteinase 9 (MMP-9) and tissue inhibitor of metalloproteinase 1 (TIMP-1) after cardiopulmonary resuscitation (CPR) in a canine model of prolonged ventricular fibrillation (VF); (b) with the duration of VF, the degree of the imbalance would be greater; and (c) there was a relationship between the level of MMP-9 or TIMP-1 and the cardiac function. METHODS AND RESULTS: Ventricular fibrillation was electrically induced in 24 dogs. The animals were randomly divided into 3 groups (sham control, n = 8; 8-minute VF, n = 8; 12-minute VF, n = 8). Echocardiographic measurement and hemodynamic variables were recorded before VF and after return of spontaneous circulation. Tissue inhibitor of metalloproteinase 1 (TIMP-1) and MMP-9 were analyzed by Western blot and immunohistochemistry. Compared with sham controls, dogs under VF and CPR showed significantly decreased level of TIMP-1 (P < .001), and with the duration of VF, the level of TIMP-1 declined (P < .01). The level of MMP-9 did not achieve statistical significance in the 3 groups (P > .05); however, they were higher in VF and longer duration VF groups. The ratios of TIMP-1/MMP-9 were lower in VF groups (P < .05). There was a negative correlation between TIMP-1 and left atrium dimension and left ventricular diastolic dimensions (r = -0.83 and r = -0.96, respectively; P < .01) and a positive correlation between TIMP-1 and left ventricular ejection fraction (r = 0.85; P < .01). CONCLUSIONS: There was an imbalance between TIMP-1 and MMP-9 after CPR. It may partly contribute to the postresuscitation cardiac dysfunction.

Effect of ZP123, a gap junction modifier, on prolonged ventricular fibrillation in swine.

OBJECTIVES: It was the aim of this study to investigate the effect of ZP123 on prolonged ventricular fibrillation (VF) in swine. METHODS: VF was electrically induced in 20 pigs. The animals randomly received either ZP123 or saline control infusion before VF. After 8 min of untreated VF, cardiopulmonary resuscitation and biphasic defibrillation shocks were applied. VF mean frequency (VF(mf)) and mean amplitude (VF(ma)), hemodynamics, outcome of defibrillation and the rate of return of spontaneous circulation (ROSC) were analyzed. RESULTS: Compared with the control group, VF(mf) was higher but VF(ma) lower during the 8 min of VF in the drug group (11.8 ± 2.1 vs. 10.4 ± 2.0 Hz and 0.24 ± 0.10 vs. 0.31 ± 0.16 mV, respectively; p < 0.05). Hemodynamic variables in the 2 groups were comparable (p > 0.05). The defibrillation threshold was lower and the rate of successful defibrillation was higher in the drug group compared with the control group (92.2 ± 26.4 vs. 133.3 ± 28.9 J and 90 vs. 30%, respectively; p < 0.05). The rate of ROSC was not different between the 2 groups (40 vs. 30%; p > 0.05). CONCLUSION: In prolonged VF, ZP123 could decrease the defibrillation threshold and improve the rate of successful defibrillation. However, it could not improve the rate of ROSC - which may be due to its side effect of decreasing VF(ma).

[Changes in myocardial connexin 43 during ventricular fibrillation].

OBJECTIVE: To observe changes in connexin 43 (Cx43) after ventricular fibrillation (VF) and the effects of rotigaptide (ZP123) on Cx43. METHODS: Thirty domestic pigs were randomly assigned to three groups (10 in each group): sham group, model group and ZP123 group. VF was induced by an 80 V AC transthoracic shock for 5 seconds with the use of subcutaneous needles. Before the induction of VF, animals in ZP123 group were administered with ZP123 (1 µg/kg bolus+10 µg×kg(-1)×h(-1) dissolved in 50 ml normal saline and pumped for 15 minutes ). Those in model group received 50 ml normal saline pumped for 15 minutes. For pigs in sham group VF was not induced and no fluid was given. After 8 minutes of VF, animals were euthanized and myocardial tissues were harvested along the long axis of each left ventricular free wall. Immunofluorescence combined with laser scanning confocal microscope was used to detect the distribution of Cx43. Western blotting was used for quantitative determination of Cx43 protein expression. RESULTS: Immunofluorescence signals for Cx43 in sham group were strong and regularly distributed. In model group, Cx43 signals were weak and distributed in heterogeneity, while in ZP123 group, Cx43 signals were enhanced and their distribution were much more orderly. Compared with sham group, the percentage area and the optical densities (A value) of Cx43 fluorescence signals and Cx43 protein expression were significantly decreased in model group [the percentage area: (0.64±0.36)% vs.(1.27±0.19)%, A value: 15 201± 2 613 vs. 30 634±4 975, Cx43 protein expression: 0.72±0.08 vs. 0.97±0.07, all P<0.05]. The level of Cx43 expression in ZP 123 group [the percentage area (0.96±0.16)%, A value 22 100±4 404, Cx43 protein expression 0.82±0.04] was much higher than model group (all P<0.05). CONCLUSION: During VF, down-regulation of myocardial Cx43 expression occurred, which could be attenuated by administration of ZP123.

Initial defibrillation versus initial chest compression in a 4-minute ventricular fibrillation canine model of cardiac arrest.

OBJECTIVE: Previous laboratory and clinical studies have demonstrated that chest compression preceding defibrillation in prolonged ventricular fibrillation (VF) increases the likelihood of successful cardiac resuscitation. The lower limit of VF duration when preshock chest compression provides no benefit has not been specifically studied. We aimed to study the effect of order of defibrillation and chest compression on defibrillation and cardiac resuscitation in a 4-minute VF canine model of cardiac arrest. DESIGN: Prospective, randomized animal study. SETTING: Key Laboratory of Cardiovascular Remodeling and Function Research and Department of Cardiology, QiLu Hospital. SUBJECTS: Twenty-four domestic dogs. INTERVENTIONS: VF was induced in anesthetized and ventilated canines. After 4 minutes of untreated VF, animals were randomly assigned to receive shock first or chest compression first. Animals in the shock-first group received an immediate single countershock of 360 J for <10 seconds, then 200 immediate compressions before pulse check or rhythm reanalysis. The ratio of compression to ventilation was 30:2. Interruptions to deliver rescue breaths were eliminated in this study. Animals in the chest compression-first group received 200 chest compressions before a single countershock; the other interventions were the same as for the shock-first group. End points were restoration of spontaneous circulation (ROSC), defined as spontaneous systolic arterial pressure >50 mm Hg, when epinephrine (0.02 mg/kg intravenously) was given, and resuscitation, defined as maintaining systolic arterial pressure >50 mm Hg at the 24-hour study end point. MEASUREMENTS AND MAIN RESULTS: In the shock-first group, all animals achieved ROSC, and ten of 12 survived at the 24-hour study end point. In the chest compression-first group, 11 of 12 animals achieved ROSC, and nine of 12 survived at the 24-hour study end point. CONCLUSIONS: In this 4-minute VF canine model of cardiac arrest, the order of initial defibrillation or initial chest compression does not affect cardiac resuscitation.

Correction: Role of Caveolin-1 in Atrial Fibrillation as an Anti-Fibrotic Signaling Molecule in Human Atrial Fibroblasts.

[This corrects the article DOI: 10.1371/journal.pone.0085144.].

Changes in connexin 43, metalloproteinase and tissue inhibitor of metalloproteinase during tachycardia-induced cardiomyopathy in dogs.

OBJECTIVE: To study changes in connexin, metalloproteinase and tissue inhibitor of metalloproteinase levels during tachycardia-induced cardiomyopathy (TIC). METHODS: Canine models of TIC were established by rapid right atrial pacing at 350-400 beats per min for 8 weeks in 11 dogs, six dogs acted as a sham operation group. Echocardiography, left ventricular pressure and its first derivation with time (positive and negative maximum, dp/dtmax, -dp/dtmax), and intracardiac electrograms were recorded before and after rapid pacing at 1, 4 and 8 weeks. Data were acquired in sinus rhythm. Ultrastructural changes in left ventricular tissue were observed by transmission electron microscope. Connexin 43 (Cx43) levels in the left ventricular myocardium were measured by confocal laser microscopy. The relative abundance of matrix metalloproteinase (MMP-2) and tissue inhibitor of metalloproteinase (TIMP-2) were studied by immunoblotting. RESULT AND CONCLUSIONS: (1) Ventricular dilatation and systolic dysfunction occurred after 1 week of rapid right atrial pacing. (2) There was structural damage to the myofibrils, mitochondria, and the sarcoplasmic reticulum with intercalated disk discontinuity. (3) Levels of Cx43 decreased significantly and gap junction remodelling occurred during TIC. (4) TIC may result from several mechanisms, such as ultrastructural changes or gap junction and matrix remodelling.

Effects of rotigaptide, a gap junction modifier, on defibrillation energy and resuscitation from cardiac arrest in rabbits.

The gap junction modifier Rotigaptide (ZP123), which promotes cellular coupling, was hypothesized to decrease defibrillation thresholds during prolonged ventricular fibrillation (VF). Thirty-two New Zealand white rabbits were randomized to receive saline (control, n = 16) or Rotigaptide (n = 16). Following 4 min of untreated VF, biphasic defibrillation shocks were applied through chest wall patches, starting either at 300 volts (V) (n = 16) or 500 V (n = 16), with 200 V increasing steps to 900 V in case of shock failure. Rotigaptide significantly decreased defibrillation voltage requirements (average cumulative voltage of all shocks: 1206 +/- 709 V in control group vs. 844 +/- 546 V in treated group, P = .002). Rotigaptide had no effect on heart rate, QRS duration, QT interval, ventricular effective refractory period, monophasic action potential duration or on connexin 43 density using immunofluorescence. Rotigaptide improves the ability to defibrillate after untreated VF.

Use of dabigatran vs. warfarin with low-molecular-weight heparin bridging in catheter ablation for atrial fibrillation patients with a low CHADS2 score.

The purpose of the present study was to compare the efficacy and safety of dabigatran and interrupted warfarin with low-molecular-weight heparin bridging in non-valvular atrial fibrillation (AF) catheter ablation. Previously, there has been concerns that bridging therapy increases bleeding events without the benefit of stroke prevention. It has been suggested that bridging therapy should be considered only for patients at high-risk of thrombosis. Nevertheless, bridging therapy in AF patients with a low CHADS2 score may be safe and effective. The authors performed a prospective, observational study that included consecutive 240 patients undergoing AF ablation in P.R. China. A total of 139 patients received 110 mg dabigatran twice daily and 101 patients took dose-adjusted warfarin that had been bridged with low-molecular-weight heparin. The mean patient age was 55.48 years with 72.1% being men and 74.2% having paroxysmal AF. One thromboembolic complication occurred in the dabigatran group compared to none in the warfarin group. Both the groups presented a similar major bleeding rate, total bleeding rate, and bleeding and thromboembolic complications. In patients undergoing AF ablation, the risk of bleeding or thromboembolic complications was similar for both dabigatran and interrupted warfarin with bridging therapy. Bridging therapy appeared to be safe and effective for the low-risk population.

Effect of levocarnitine on TIMP-1, ICAM-1 expression of rats with coronary heart disease and its myocardial protection effect.

OBJECTIVE: To study the effect of levocarnitine (L-CN) on tissue inhibitor of metalloproteinase-1 (TIMP-1) and intercellular adhesion molecule-1 (ICAM-1) expression of rats with coronary heart disease and evaluate the protective effect of L-CN on myocardial cells. METHODS: High-fat diet feeding and intraperitoneal injection of pituitrin was performed on rats in model group and CHD Model of rats was built. Rats with successful model-building were selected and divided into L-CN group and Ctrl group randomly. Rats in L-CN group were given L-CN treatment, with intraperitoneal injection of 200 mg·kg(-1)·d(-1) and successive administration for 3 d. Rats in Ctrl group were given equal volumes of normal saline. Blood was collected from carotid artery at different time and expression quantity of creatine kinase-MB (CK-MB) and Troponin Ⅰ (TnⅠ) in serum was detected. Rats in each group were put to death and were separated to obtain the myocardial tissue. Real-time PCR and Western Blotting hybridization were performed to detect the TIMP-1, ICAM-1 expression in myocardial tissue in each group. Statistical analysis was employed to explore the expression changes of TIMP-1 and ICAM-1, and ELISA test was used to analyze the expression changes of myocardial necrosis marker-CK-MB and TnⅠto learn the effect of L-CN and its myocardial protective effect. RESULTS: The total cholesterol, triglyceride and blood glucose levels of rats in model group were significantly higher than that in control group, which indicated that due to high-fat diet feeding, blood lipid of rats in model group was obviously higher than that in control group. In myocardial tissue of rats in model group, TIMP-1 level significantly reduced and ICAM-1 level significantly increased (P < 0.01). In model group, after L-CN treatment, TIMP-1 level had double increase, while ICAM-1 level had 43% of decrease in L-CN group compared with Ctrl group. After L-CN intervention treatment, CK-MB and TnⅠ content in L-CN group relatively reduced compared with Ctrl group. The difference among groups was obvious (P < 0.01). CONCLUSIONS: L-CN could increase the TIMP-1 expression level and inhibit the ICAM-1 expression level. L-CN has a certain myocardial protective effect.

Acute Myocardial Infarction in a Young Man with Hyperhomocysteinemia and Pulmonary Tuberculosis.

Acute myocardial infarction, hyperhomocysteinemia and pulmonary tuberculosis (PTB) are rare in individuals under the age of 30 years. We herein report the case of a 27-year-old man who presented with intermittent chest pain, elevated homosysteine level, and PTB. The patient was treated successfully with a combination of medications and percutaneous coronary intervention. This uncommon case highlights that homocysteine, folate and B vitamins levels should be regularly evaluated, and that chest X-rays or thoracic computed tomography should be ordered routinely to exclude PTB in patients under the age of 30 years who present acute myocardial infarction and lack the traditional risk factors.