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1.
Eur Heart J Open ; 4(3): oeae044, 2024 May.
Article in English | MEDLINE | ID: mdl-38933428

ABSTRACT

Aims: Pulmonary vein isolation (PVI) represents the gold standard in the treatment of atrial fibrillation (AF) and the use of single-shot techniques, such as cryoballoon ablation (CBA) and pulsed field ablation (PFA) using a pentaspline catheter, has gained prominence. Recent studies hypothesize that PFA might be superior to CBA, although procedural efficacy and safety data are inconsistent. A meta-analysis was conducted to compare both energy sources for the treatment of AF. Methods and results: A structured systematic database search and meta-analysis were performed on studies investigating outcomes, periprocedural complications, and/or procedural parameters of AF patients treated by either CBA or PFA. Eleven studies reporting data from 3805 patients were included. Pulmonary vein isolation by PFA was associated with a significantly lower recurrence of atrial fibrillation/atrial tachycardia [odds ratio (OR) = 0.73, 95% confidence interval (CI) = 0.54-0.98, I2 = 20%] and fewer periprocedural complications (OR = 0.62, 95% CI = 0.40-0.96, I2 = 6%) compared to CBA. The lower complication rate following PFA was mainly driven by fewer phrenic nerve injuries (OR = 0.19, 95% CI = 0.08-0.43, I2 = 0%). However, there were more cases of cardiac tamponades after PFA (OR = 2.56, 95% CI = 1.01-6.49, I2 = 0%). Additionally, using PFA for PVI was associated with shorter total procedure times [mean difference (MD) = -9.68, 95% CI = -14.92 to -4.43 min, I2 = 92%] and lower radiation exposure (MD = -148.07, 95% CI = -276.50 to -19.64 µGy·mI2 = 7%). Conclusion: Our results suggest that PFA for PVI, compared to CBA, enables shorter procedure times with lower arrhythmia recurrence and a reduced risk of periprocedural complications. Randomized controlled trials need to confirm our findings.

2.
Europace ; 25(6)2023 06 02.
Article in English | MEDLINE | ID: mdl-37306316

ABSTRACT

AIMS: To investigate the association of iatrogenic cardiac tamponades as a complication of invasive electrophysiology procedures (EPs) and mortality as well as serious cardiovascular events in a nationwide patient cohort during long-term follow-up. METHODS: From the Swedish Catheter Ablation Registry between 2005 and 2019, a total of 58 770 invasive EPs in 44 497 patients were analysed. From this, all patients with periprocedural cardiac tamponades related to invasive EPs were identified (n = 200; tamponade group) and matched (1:2 ratio) to a control group (n = 400). Over a follow-up of 5 years, the composite primary endpoint-death from any cause, acute myocardial infarction, transitory ischaemic attack (TIA)/stroke, and hospitalization for heart failure-revealed no statistically significant association with cardiac tamponade [hazard ratio (HR) 1.22 (95% CI, 0.79-1.88)]. All single components of the primary endpoint as well as cardiovascular death revealed no statistically significant association with cardiac tamponade. Cardiac tamponade was associated with a significantly higher risk with hospitalization for pericarditis [HR 20.67 (95% CI, 6.32-67.60)]. CONCLUSION: In this nationwide cohort of patients undergoing invasive EPs, iatrogenic cardiac tamponade was associated with an increased risk of hospitalization for pericarditis during the first months after the index procedure. In the long-term, however, cardiac tamponade revealed no significant association with mortality or other serious cardiovascular events.


Subject(s)
Cardiac Tamponade , Pericarditis , Humans , Cardiac Tamponade/epidemiology , Cardiac Tamponade/etiology , Pericarditis/diagnosis , Pericarditis/epidemiology , Pericarditis/etiology , Cardiac Electrophysiology , Hospitalization , Iatrogenic Disease
3.
J Interv Card Electrophysiol ; 66(3): 577-584, 2023 Apr.
Article in English | MEDLINE | ID: mdl-36085243

ABSTRACT

BACKGROUND: To study the association between timing and success of electrical cardioversion (ECV) for the treatment of early recurrences (ERs) of atrial fibrillation post pulmonary vein isolation (PVI) on long-term rhythm outcome. METHODS: Data of 133 patients ablated for paroxysmal or persistent atrial fibrillation receiving ECV for ERs, i.e., atrial tachyarrhythmia recurrences within 90 days post ablation were analyzed. During 1-year follow-up, patients were screened for late recurrences (LRs), i.e., recurrences after the blanking period. RESULTS: In 114 patients (85.7%), ECV was successful compared to 19 patients (14.3%) with failed ECV. A higher body mass index (odds ratio (OR) 1.19 (95% CI 1.02-1.39), p = 0.029), a lower left ventricular ejection fraction (OR 1.07 (95% CI 0.99-1.15), p = 0.079), and performance of ECV > 7 days from ER onset (OR 2.99 (95% CI 1.01-8.87), p = 0.048) remained independently associated with ECV failure. During 1-year follow-up, the rate of LR was significantly higher among patients with failed ECV as compared to patients with successful ECV (hazard ratio (HR) 3.00 (95% CI, 1.79-5.03), p < 0.001). Patients with ECV performed > 7 days from ER onset had a significantly higher risk of developing LR as compared to patients with ECV performed within ≤ 7 days from ER onset (HR 1.73 (95% CI 1.15-2.62), p = 0.009). Performance of ECV > 7 days from ER onset (HR 1.76 (95% CI 1.16-2.67), p = 0.008) and failed ECV (HR 3.32 (95% CI 1.96-5.64), p < 0.001) remained independently associated with LR. CONCLUSIONS: A failed ECV and performance of ECV > 7 days from ER onset were independently associated with LR.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Humans , Electric Countershock/adverse effects , Pulmonary Veins/surgery , Stroke Volume , Ventricular Function, Left , Recurrence , Treatment Outcome
4.
Eur J Heart Fail ; 24(9): 1636-1646, 2022 09.
Article in English | MEDLINE | ID: mdl-35779270

ABSTRACT

AIMS: To investigate the association between catheter ablation for atrial fibrillation (AF) and mortality as well as hospitalization for heart failure (HF) in patients with HF across the ejection fraction (EF) spectrum. METHODS AND RESULTS: Patients with first-time catheter ablation for AF (ablation group) compared to only medical treated AF patients (no ablation group) were identified from the Swedish Heart Failure Registry between 2005 and 2019. The primary outcome (all-cause mortality/first HF hospitalization) was assessed by Cox regression models in a 1:2 propensity score (PS) matched cohort and pre-specified EF subgroups (preserved EF [≥50%], mildly reduced EF [40-49%], reduced EF [<40%]) of this cohort. A total of 452 patients in the ablation group and 43 766 patients in the no ablation group were identified. After PS matching, 434 patients in the ablation group were compared to 868 patients in the no ablation group. Over a median follow-up of 2.6 years (0.0-14.1 years), catheter ablation was associated with a lower risk of the primary outcome (all-cause mortality/first HF hospitalization) (hazard ratio [HR] 0.78, 95% confidence interval [CI] 0.65-0.94). Results were consistent across all EF subgroups. In HF with preserved EF (HFpEF), catheter ablation was also associated with a lower risk of recurrent HF hospitalization (incidence rate ratio 0.17, 95% CI 0.07-0.42). CONCLUSION: In HF patients across the EF spectrum, catheter ablation for AF was associated with lower risk of the primary outcome (all-cause mortality/first HF hospitalization). This study supports catheter ablation as a treatment option for AF in HF patients, including those with HFpEF.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Heart Failure , Ventricular Dysfunction, Left , Atrial Fibrillation/complications , Atrial Fibrillation/epidemiology , Atrial Fibrillation/surgery , Humans , Registries , Stroke Volume , Sweden/epidemiology , Ventricular Dysfunction, Left/complications
6.
J Cardiovasc Electrophysiol ; 32(11): 2971-2978, 2021 11.
Article in English | MEDLINE | ID: mdl-34535930

ABSTRACT

AIM: Data on ablation for atypical recurrent atrioventricular nodal reentry tachycardia (AVNRT) and long-term follow-up are generally sparse. Furthermore, the rate of recurrence and safety of cryoablation for atypical AVNRT has not been established. We compared patients cryoablated for atypical AVNRT and typical AVNRT during long-term follow-up. METHODS: All patients (n = 2612) who underwent catheter ablation for AVNRT at the Karolinska University Hospital between January 2009 and August 2019 were analyzed. A total of 91 patients undergoing first-time cryoablation for atypical AVNRT were included. A control group with first-time cryoablation for typical AVNRT was matched in a 1:1 ratio. Patients were followed-up for recurrences for a median of 5.0 years (interquartile range: 3.1-7.5 years). RESULTS: After 5 years, AVNRT recurrence occurred in 10 patients (11.0%) in the atypical AVNRT group and in 8 patients (8.8%) in the typical AVNRT group (hazard ratio: 1.31 [95% confidence interval: 0.52-3.32]; p = 0.568). The duration of the index procedure was significantly longer for atypical compared to typical AVNRT ablation (132.1 ± 49.2 min vs. 110.1 ± 38.8 min; p = 0.001). Transient AV blocks occurred in a similar fashion in the atypical compared to typical group (11 [12.1%] vs. 4 [4.9%]; p = 0.103). However, no ablation induced persistent AV block developed in either group. CONCLUSION: Cryoablation for atypical AVNRT showed similar rate of recurrences and safety compared to typical AVNRT during long-term follow-up.


Subject(s)
Catheter Ablation , Cryosurgery , Tachycardia, Atrioventricular Nodal Reentry , Cryosurgery/adverse effects , Humans , Recurrence , Risk Factors , Tachycardia, Atrioventricular Nodal Reentry/surgery , Treatment Outcome
7.
J Cardiovasc Electrophysiol ; 32(11): 2953-2960, 2021 11.
Article in English | MEDLINE | ID: mdl-34535936

ABSTRACT

AIMS: This study evaluates the incidence of procedural complications related to catheter ablation of atrial fibrillation (AF) to assess the potential feasibility and safety of same-day discharge in a large cohort. METHODS: We performed an analysis of prospectively collected data of complications of all patients staying overnight after undergoing AF ablation between 2001 and 2020 at a tertiary center. Using medical records, we analyzed complications occurring intraprocedurally until 6 h postablation and between 6 h postablation and discharge the day after the ablation procedure. RESULTS: In 5414 AF ablations, we identified a total of 108 (2.0%) major complications occurring intraprocedural or before discharge. Most major complications occurred intraprocedurally or within 6 h after the procedure (n = 96, 1.8%). Twelve (0.2%) major complications occurred between 6 h Postablation and discharge. The most common of these major complications were congestive heart failure (n = 6) and transient ischemic attack (TIA, n = 4). During this time span, 61 (1.1%) minor complications occurred. Factors independently associated with major complications intraprocedurally and until discharge were body mass index (BMI) ≥ 30 kg/m2 (p = .009), significant valvular disease (p = .001), cardiomyopathy (p < .001), prior stroke or TIA (p = .014), first-time procedure versus repeat procedure (p = .013), cryoablation versus radiofrequency (p < .001), and procedure duration (p < .001). CONCLUSION: After AF ablation, very few complications occurred between 6 h postprocedure and discharge the next day. Therefore, same-day discharge is a safe option for a majority of patients.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Atrial Fibrillation/surgery , Catheter Ablation/adverse effects , Humans , Incidence , Patient Discharge , Treatment Outcome
8.
J Interv Card Electrophysiol ; 62(1): 75-81, 2021 Oct.
Article in English | MEDLINE | ID: mdl-32959177

ABSTRACT

PURPOSE: Implantation of a subcutaneous implantable cardioverter-defibrillator (S-ICD) has become an alternative option when a conventional transvenous approach is not suitable. The myocardial damage caused by S-ICD implantation appears to be minimal despite mandatory defibrillation threshold (DFT) testing. However, there has not been a direct comparison with the traditional transvenous placement of a single-chamber ICD (VVI-ICD). The aim of this study was to determine the extent of myocardial damage by analysing the changes in serum levels of cardiac enzymes after S-ICD implantation in comparison with VVI-ICD. METHODS: In 43 patients who received an S-ICD system, differences in serum levels of high-sensitive troponin T (ΔhsTnT) and creatine kinase total (ΔCK) and muscle brain fraction (ΔCK-MB) were acquired by blood sampling before and the day after implantation. The control group consisted of 43 patients from the TropShock study who had received a transvenous VVI-ICD without DFT. RESULTS: After S-ICD implantation and testing procedure, ΔhsTnT (0.000 ng/ml, IQR - 0.003-0.002 ng/ml) was significantly lower than after conventional VVI-ICD implantation (0.018 ng/ml, IQR 0.004-0.032 ng/ml; p < 0.001). There was no significant difference in CK (ΔCKS-ICD 85.0 U/I, IQR 30.5-225.8 U/I vs ΔCKVVI-ICD 69.5 U/I, IQR 22.9-172.3 U/I; p = 0.357), but there was a significant difference in CK-MB (ΔCK-MBS-ICD of - 0.60, IQR - 2.60-1.0 vs ΔCK-MBVVI-ICD 1.0, IQR - 1.08-3.18; p = 0.030). CONCLUSION: S-ICD implantation causes less myocardial damage than VVI-ICD implantation evidenced by ΔhsTnT and ΔCK-MB.


Subject(s)
Defibrillators, Implantable , Troponin T , Creatine Kinase, MB Form , Electric Countershock , Humans , Registries
9.
Clin Res Cardiol ; 110(6): 851-860, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33184675

ABSTRACT

PURPOSE: Cather ablation is known to influence the autonomic nervous system. This study sought to investigate the association of sinus heart rate pre-/post-ablation and recurrences in patients with atrial fibrillation undergoing pulmonary vein isolation (PVI). METHODS: Between January 2012 and December 2017, data of 482 patients undergoing their first PVI were included. Sinus heart rate was recorded before (PRE), directly post-ablation (POST) and 3 months post-ablation (3 M). All patients were screened for atrial tachyarrhythmia recurrences during the one-year follow-up. RESULTS: In the total study cohort, the mean resting sinus heart rate at PRE [mean 57.9 bpm (95% CI 57.1-58.7 bpm)] increased by over 10 bpm to POST [mean 69.4 bpm (95% CI 68.5-70.3 bpm); p < 0.001] followed by a slight decrease at 3 M [mean 67.3 bpm (95% CI 66.4-68.2 bpm)] but still remaining higher compared to PRE (p < 0.001). This pattern was observed in patients with and without recurrences at POST and 3 M (both p < 0.001 compared to PRE). However, at 3 M the mean sinus heart rate was significantly lower in patients with compared to patients without recurrences (p = 0.031). In this regard, patients with a heart rate change < 11 bpm (PRE to 3 M) or, as an alternative parameter, patients with a heart rate < 60 bpm at 3 M had a significantly higher risk of recurrences compared to the remaining patients (Hazard ratio (HR) 1.82 (95% CI 1.32-2.49), p < 0.001 and HR 1.64 (95% CI 1.20-2.25), p = 0.002, respectively). CONCLUSION: Our study confirms the impact of PVI on cardiac autonomic function with a significant sinus heart rate increase post-ablation. Patients with a sinus heart rate change < 11 bpm (PRE to 3 M) are at higher risk for recurrences during one-year post-PVI.


Subject(s)
Atrial Fibrillation/physiopathology , Catheter Ablation/methods , Heart Conduction System/physiopathology , Heart Rate/physiology , Atrial Fibrillation/surgery , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Period , Pulmonary Veins/surgery , Recurrence , Retrospective Studies , Time Factors , Treatment Outcome
10.
Europace ; 22(10): 1547-1557, 2020 10 01.
Article in English | MEDLINE | ID: mdl-32772100

ABSTRACT

AIMS: Iatrogenic cardiac tamponades are a rare but dreaded complication of invasive electrophysiology procedures (EPs). Their long-term impact on clinical outcomes is unknown. This study analysed the risk of death or serious cardiovascular events in patients suffering from EP-related cardiac tamponade requiring pericardiocentesis during long-term follow-up. METHODS AND RESULTS: Out of 19 997 invasive EPs at the Karolinska University Hospital between January 1998 and September 2018, all patients with EP-related periprocedural cardiac tamponade were identified (n = 60) and matched (1:3 ratio) to a control group (n = 180). After a follow-up of 5 years, the composite primary endpoint - death from any cause, acute myocardial infarction, transitory ischaemic attack (TIA)/stroke, and hospitalization for heart failure - occurred in significantly more patients in the tamponade than in the control group [12 patients (20.0%) vs. 19 patients (10.6%); hazard ratio (HR) 2.53 (95% confidence interval, CI 1.15-5.58); P = 0.021]. This was mainly driven by a higher incidence of TIA/stroke in the tamponade than in the control group [HR 3.75 (95% CI 1.01-13.97); P = 0.049]. Death from any cause, acute myocardial infarction, and hospitalization for heart failure did not show a significant difference between the groups. Hospitalization for pericarditis occurred in significantly more patients in the tamponade than in the control group [HR 36.0 (95% CI 4.68-276.86); P = 0.001]. CONCLUSION: Patients with EP-related cardiac tamponade are at higher risk for cerebrovascular events during the first 2 weeks and hospitalization for pericarditis during the first months after index procedure. Despite the increased risk for early complications tamponade patients have a good long-term prognosis without increased risk for mortality or other serious cardiovascular events.


Subject(s)
Cardiac Tamponade , Catheter Ablation , Ischemic Attack, Transient , Cardiac Tamponade/diagnosis , Cardiac Tamponade/epidemiology , Cardiac Tamponade/etiology , Humans , Incidence , Pericardiocentesis/adverse effects , Treatment Outcome
11.
J Cardiovasc Electrophysiol ; 31(3): 674-681, 2020 03.
Article in English | MEDLINE | ID: mdl-31984563

ABSTRACT

AIMS: To investigate the significance of early recurrence (ER) of atrial tachyarrhythmias after pulmonary vein isolation (PVI) on the development of late recurrence (LR) and to redefine the blanking period during which an ER is considered nonspecific. METHODS: Data of 713 patients undergoing their first PVI for paroxysmal or persistent atrial fibrillation between January 2012 and December 2017 were included. All patients were followed-up for 12 months according to clinical and outpatient routine and were screened for any atrial tachyarrhythmia lasting >30 seconds occurring during the first 3 months postablation (ER) and after the 3 months blanking period (LR). RESULTS: Patients with ER compared to those without ER had significantly more LR (74.5% vs 16.5% vs, P < .001). The occurrence of ER during the first, second and third months showed increasing LR rates of 35.2%, 67.9%, and 94.8%, respectively (P < .001). Receiver operator characteristic analysis revealed a blanking period of 46 days with the highest sensitivity (68.1%) and specificity (96.5%). Later timing and longer time span of ER were independent predictors for LR in multivariable analysis. CONCLUSION: ER is a strong predictor for LR. Our study advocates a shortening of the post-PVI blanking period followed by a "gray zone" up to 3 months where individualized therapeutic decisions based on additional risk factors should be considered. We suggest that the ER time span might serve as such a predictor identifying patients at the highest risk for LR.


Subject(s)
Atrial Fibrillation/surgery , Catheter Ablation/adverse effects , Pulmonary Veins/surgery , Action Potentials , Aged , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Female , Heart Rate , Humans , Male , Middle Aged , Pulmonary Veins/physiopathology , Recurrence , Registries , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome
13.
J Interv Card Electrophysiol ; 56(3): 335-339, 2019 Dec.
Article in English | MEDLINE | ID: mdl-31617041

ABSTRACT

PURPOSE: To determine the current incidence of antitachycardia therapy suspension due to magnet reversion in patients with implantable cardioverter defibrillators (ICDs). METHODS: From March 2012 to September 2018, all St. Jude Medical ICD interrogations performed at the Deutsches Herzzentrum München were screened for stored events of antitachycardia therapy suspension caused by static magnetic fields (flux densities ≥ 1 mT as defined in St. Jude Medical ICDs) affecting the giant magnetoresistance (GMR) sensor. Intentional ICD deactivation or inappropriate magnet application in the hospital was classified as non-environmental electromagnetic interference (EMI) whereas in the case of any other stored magnet reversion, the event was classified as presumably environmental EMI. RESULTS: Data from 201 St. Jude Medical ICD patients (mean age 62 ± 24 years, 165 males/36 females) were included in the analysis. ICD interrogations occurred at a mean follow-up of 25.1 months ± 15.6 months and summed up to a total of 464 patient-years of follow-up. A total number of 43 magnet reversion events were detected in 21 patients. Thirty-two events in 13 patients were presumably related to environmental EMI sources. Suspension of antitachycardia therapy only occurred in a temporary fashion. None of the patients experienced any ventricular tachyarrhythmia during ICD inhibition. The incidence of antitachycardia therapy suspension due to magnet reversion related to presumably environmental EMI sources was 6.9% per patient and year. CONCLUSION: Although none of the patients experienced any harmful event, antitachycardia therapy suspension due to magnet reversion is a common issue. Patients should be well-educated about potential EMI sources as well as trained in handling them.


Subject(s)
Defibrillators, Implantable , Electromagnetic Fields/adverse effects , Equipment Failure Analysis , Female , Humans , Male , Middle Aged , Risk Factors
14.
EuroIntervention ; 15(8): 700-706, 2019 Oct 20.
Article in English | MEDLINE | ID: mdl-30834895

ABSTRACT

AIMS: Clopidogrel is the P2Y12 inhibitor of choice in patients who undergo PCI and have an indication for oral anticoagulation (OAC). Prediction of the bleeding risk is of major interest in this population. The aim of this analysis was to investigate whether an enhanced platelet inhibition by clopidogrel measured by platelet function testing (PFT) with the Multiplate Analyzer is associated with an increased bleeding risk in patients on triple antithrombotic therapy. METHODS AND RESULTS: This investigation was performed in a cohort of 524 patients from the randomised ISAR-TRIPLE trial; 458 (87.4%) had PFT results available in the first 24 hours after PCI. Patients belonging to the lowest quintile according to PFT were considered as enhanced responders to clopidogrel. The primary endpoint was major bleeding according to TIMI criteria at nine months. The median of ADP-induced platelet aggregation in the whole population was 163 AU*min (107-241). Patients in the lowest quintile had values below 93 AU*min. These enhanced responders (92 patients) had a significantly higher risk of TIMI major bleeding (hazard ratio [HR] 3.13, 95% confidence interval [CI]: 1.38-7.09, p=0.01) and overall mortality (HR 3.42, 95% CI: 1.55-7.52, p=0.004) compared with the remaining patients (366 patients). No significant difference was observed for the secondary combined ischaemic endpoint (HR 1.27, 95% CI: 0.47-3.47, p=0.64). CONCLUSIONS: Enhanced platelet inhibition delivered by clopidogrel is associated with an increased risk for major bleeding and death in patients on OAC who undergo PCI. These results support the use of PFT to identify patients with an increased risk for bleeding.


Subject(s)
Anticoagulants/adverse effects , Clopidogrel/pharmacology , Drug-Eluting Stents , Hemorrhage/chemically induced , Percutaneous Coronary Intervention , Platelet Aggregation Inhibitors/adverse effects , Platelet Aggregation/drug effects , Anticoagulants/administration & dosage , Humans , Randomized Controlled Trials as Topic , Ticlopidine/adverse effects , Treatment Outcome
15.
Oncotarget ; 9(74): 33947-33960, 2018 Sep 21.
Article in English | MEDLINE | ID: mdl-30338037

ABSTRACT

Hepatitis B virus (HBV) infection is a prominent cause of hepatocellular carcinoma (HCC) but the underlying molecular mechanisms are complex and multiple pathways have been proposed such as the activation of the Wnt-/ß-catenin-signalling and dysregulation of E-cadherin/ß-catenin adherens junctions. This study aimed to identify mechanisms of how HBV infection and replication as well as HBV X protein (HBx) gene expression in the context of an HBV genome influence Wnt-/ß-catenin-signalling and formation of adherens junctions and to which extent HBx contributes to this. Regulation of E-cadherin/ß-catenin junctions and ß-catenin-signalling as well as the role of HBx were investigated using constructs transiently or stably inducing replication of HBV+/-HBx in hepatoma cell lines. In addition, HCC and adjacent non-tumorous tissue samples from HBV-infected HCC patients and drug interference in HBV-infected cells were studied. Although HBV did not alter overall expression levels of E-cadherin or ß-catenin, it diminished their cell surface localization resulting in nuclear translocation of ß-catenin and activation of its target genes. In addition, HBV gene expression increased the amount of phosphorylated c-Src kinase. Treatment with Src kinase inhibitor Dasatinib reduced HBV replication, prevented adherens junction disassembly and reduced ß-catenin-signalling, while Sorafenib only did so in cells with mutated ß-catenin. Interestingly, none of the HBV induced alterations required HBx. Thus, HBV stimulated ß-catenin-signalling and induced disassembly of adherens junctions independently of HBx through Src kinase activation. These pathways may contribute to hepatocellular carcinogenesis and seem to be more efficiently inhibited by Dasatinib than by Sorafenib.

17.
Int J Cardiol ; 254: 146-150, 2018 03 01.
Article in English | MEDLINE | ID: mdl-29273240

ABSTRACT

BACKGROUND: The incidence of pulmonary vein stenosis (PVS) as complication after pulmonary vein isolation (PVI) for atrial fibrillation (AF) has decreased in the last decade. However, as PVI for AF is becoming more prevalent, the incidence remains considerable in absolute terms. The purpose of this meta-analysis is to investigate the optimal approach for management of PVS after PVI for AF. METHODS AND RESULTS: We searched electronic scientific databases for studies comparing plain balloon angioplasty (BA) versus stenting for PVS after PVI for AF. Aggregate data were pooled to perform a meta-analysis. The primary and secondary outcomes were restenosis requiring repeated intervention and procedure-related complications, respectively. A total of 4 studies, treating 315 PVS in 188 patients (BA, n=171 versus stent, n=144 PVS) were considered. After a median follow-up of 32months, the overall incidence of restenosis was 46%. A percutaneous therapy with BA was associated with a higher risk for restenosis requiring repeat intervention compared to stent (risk ratio - RR, 95% confidence interval [95% CI]=2.18 [1.64-2.89], p<0.001). Procedure-related complications were comparable between BA and stent (RR [95% CI]=0.96 [0.19-4.96], p=0.96). The time to diagnosis of PVS after PVI for AF did not modify the treatment effect for the primary outcome with BA versus stent (p for interaction=0.16). CONCLUSIONS: In patients presenting PVS after PVI for AF, a percutaneous therapy with BA is associated with higher risk for restenosis requiring repeat intervention as compared to stent. These percutaneous therapies display comparable safety.


Subject(s)
Angioplasty, Balloon/methods , Atrial Fibrillation/therapy , Catheterization, Peripheral/methods , Stenosis, Pulmonary Vein/therapy , Stents , Angioplasty, Balloon/standards , Atrial Fibrillation/diagnosis , Atrial Fibrillation/epidemiology , Catheterization, Peripheral/standards , Humans , Prospective Studies , Retrospective Studies , Stenosis, Pulmonary Vein/diagnosis , Stenosis, Pulmonary Vein/epidemiology , Treatment Outcome
18.
Cell Mol Gastroenterol Hepatol ; 4(3): 339-363, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28884137

ABSTRACT

BACKGROUND & AIMS: The human hepatitis B virus (HBV) is a major cause of chronic hepatitis and hepatocellular carcinoma, but molecular mechanisms driving liver disease and carcinogenesis are largely unknown. We therefore studied cellular pathways altered by HBV infection. METHODS: We performed gene expression profiling of primary human hepatocytes infected with HBV and proved the results in HBV-replicating cell lines and human liver tissue using real-time polymerase chain reaction and Western blotting. Activation of signal transducer and activator of transcription (STAT3) was examined in HBV-replicating human hepatocytes, HBV-replicating mice, and liver tissue from HBV-infected individuals using Western blotting, STAT3-luciferase reporter assay, and immunohistochemistry. The consequences of STAT3 activation on HBV infection and cell survival were studied by chemical inhibition of STAT3 phosphorylation and small interfering RNA-mediated knockdown of STAT3. RESULTS: Gene expression profiling of HBV-infected primary human hepatocytes detected no interferon response, while genes encoding for acute phase and antiapoptotic proteins were up-regulated. This gene regulation was confirmed in liver tissue samples of patients with chronic HBV infection and in HBV-related hepatocellular carcinoma. Pathway analysis revealed activation of STAT3 to be the major regulator. Interleukin-6-dependent and -independent activation of STAT3 was detected in HBV-replicating hepatocytes in cell culture and in vivo. Prevention of STAT3 activation by inhibition of Janus tyrosine kinases as well as small interfering RNA-mediated knockdown of STAT3-induced apoptosis and reduced HBV replication and gene expression. CONCLUSIONS: HBV activates STAT3 signaling in hepatocytes to foster its own replication but also to prevent apoptosis of infected cells. This very likely supports HBV-related carcinogenesis.

19.
Europace ; 19(3): 378-384, 2017 Mar 01.
Article in English | MEDLINE | ID: mdl-27702864

ABSTRACT

AIMS: Radiofrequency (RF) ablation represents a standard of care for pulmonary vein isolation in patients with drug-refractory paroxysmal atrial fibrillation (AF). In this setting, cryoballoon (CB) ablation has emerged as alternative therapy. However, the efficacy and safety of CB vs. RF ablation in patients with paroxysmal AF remain a matter of debate. METHODS AND RESULTS: We searched electronic scientific databases for studies of CB vs. RF ablation in patients with paroxysmal AF. Aggregate data were pooled to perform a meta-analysis. The primary efficacy and safety outcomes were the recurrence of any atrial arrhythmia and procedure-related complications, respectively. A total of 6473 participants from 10 studies (CB, n = 2232 vs. RF, n = 4241) were studied. After a median follow-up of 16 months, the risk of any atrial arrhythmia recurrence (risk ratio, RR 95% confidence interval [95% CI] = 1.01 [0.90-1.14], P = 0.83) and procedure-related complications (RR [95% CI] = 0.92 [0.66-1.28], P = 0.61) were comparable between CB vs. RF ablation. Cryoballoon ablation led to a higher risk of persistent phrenic nerve palsy (RR [95% CI] = 13.60 [3.87-47.81], P < 0.01) and a lower risk of cardiac tamponade (RR [95% CI] = 0.48 [0.25-0.89], P = 0.02) compared with RF ablation. There was a trend of statistically significant interaction between the type of CB and the duration of ablation (P for interaction = 0.09). CONCLUSION: In patients with paroxysmal AF, ablation therapy with CB is associated with efficacy and safety comparable to that of RF. Second-generation CB catheters seem to reduce procedure duration. Further studies are warranted to disclose the impact of second-generation CB catheters compared with RF for ablation of paroxysmal AF.


Subject(s)
Atrial Fibrillation/surgery , Cardiac Catheters , Catheter Ablation , Cryosurgery/instrumentation , Pulmonary Veins/surgery , Atrial Fibrillation/diagnosis , Atrial Fibrillation/physiopathology , Catheter Ablation/adverse effects , Chi-Square Distribution , Cryosurgery/adverse effects , Equipment Design , Female , Humans , Male , Middle Aged , Observational Studies as Topic , Odds Ratio , Pulmonary Veins/physiopathology , Randomized Controlled Trials as Topic , Recurrence , Risk Factors , Time Factors , Treatment Outcome
20.
Clin Res Cardiol ; 105(8): 657-665, 2016 Aug.
Article in English | MEDLINE | ID: mdl-26825328

ABSTRACT

PURPOSE: Electromagnetic interference (EMI) with implantable cardioverter defibrillators (ICDs) can cause oversensing and subsequently inappropriate ICD therapies. We retrospectively investigated the current incidence and clinical relevance of oversensing related EMI in a large cohort of ICD patients. METHODS: From January 2005 to April 2013, all ICD interrogations performed at our institution were analyzed for the occurrence of oversensing related EMI. EMI episodes were classified as clinically significant, potentially significant or of minor significance. To identify risk factors for EMI, we also analyzed different lead models in our cohort (integrated vs true bipolar leads). RESULTS: Data of 2940 ICD patients (mean age 63 ± 16 years, 2322 male patients, 7772 patient-years) were retrospectively analyzed for the occurrence of EMI. During the observation period, a total of 145 (hospital environment n = 97, non-hospital environment n = 48) episodes occurred and resulted in an overall EMI incidence, i.e. event rate, of 1.87 % per patient per year. Focusing on clinically significant or potentially significant episodes, the EMI incidence was 0.27 % per patient per year. Cox proportional hazards regression analysis did not reveal a statistically significant higher hazard of oversensing for patients with integrated bipolar leads compared to patients with true bipolar leads (HR = 2.21; 95 % CI 0.90-5.39; p = 0.083). CONCLUSIONS: Our data demonstrate that EMI continues to occur in everyday life. Patients should be well informed about the potential sources and risks of EMI but they need not be overly concerned since the risk of EMI-especially in a non-hospital environment-is low.


Subject(s)
Arrhythmias, Cardiac/therapy , Defibrillators, Implantable , Electric Countershock/instrumentation , Electromagnetic Fields/adverse effects , Environmental Exposure/adverse effects , Prosthesis Failure , Aged , Arrhythmias, Cardiac/diagnosis , Arrhythmias, Cardiac/physiopathology , Electrophysiologic Techniques, Cardiac , Female , Humans , Male , Materials Testing , Middle Aged , Proportional Hazards Models , Prosthesis Design , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors
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