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1.
Article in English | MEDLINE | ID: mdl-38761295

ABSTRACT

BACKGROUND: Data about necessity of performing transesophageal echocardiography (TOE) prior to every catheter ablation (CA) of atrial fibrillation (AF) is scarce. We aimed to evaluate the safety of an individualized risk-based approach to TOE with respect to thromboembolic cerebrovascular events (CVE) in patients undergoing CA for AF or left atrial tachycardia (AT). METHODS: We performed a retrospective clinical study based on our institutional registry database. Patients undergoing CA for AF or left-sided AT following initial AF ablation at two participating centers were enrolled. Prior to the procedure, patients were scheduled for TOE only if they had a history of thromboembolic stroke, left atrial appendage (LAA) thrombus, or inappropriate anticoagulation regimen in the previous 3 to 4 weeks. The incidence of periprocedural cerebrovascular thromboembolic events was assessed. RESULTS: We analyzed 1155 patients (median age 70 years, 54.8% male, 48.1% had persistent AF/AT). In 261 patients, a TOE was performed; in 2 patients (0.7%), an LAA thrombus was detected, which led to cancellation of the catheter ablation; in 894 patients, the TOE was omitted. Of the 1153 (0.35%) patients who underwent ablation, 4 (0.35%) experienced a CVE (one TIA and three strokes). The rate of CVE in our study does not exceed that reported in most multicenter trials. The low event rates limited statistical analysis of possible risk factors for CVE. In all 4 patients with CVE, post-CVE imaging showed the absence of LAA thrombus. CONCLUSIONS: An individualized selective approach to TOE before catheter ablation of AF or left AT showed a very low risk of overt intraprocedural thromboembolic events for the population in our study. A further randomized controlled study is needed to determine whether TOE prior to catheter ablation without ICE could be omitted in patients with uninterrupted OAC without previous thromboembolic events or a history of left atrial thrombus.

2.
Europace ; 26(5)2024 May 02.
Article in English | MEDLINE | ID: mdl-38647070

ABSTRACT

AIMS: Simplified ablation technologies for pulmonary vein isolation (PVI) are increasingly performed worldwide. One of the most common complications following PVI are vascular access-related complications. Lately, venous closure systems (VCSs) were introduced into clinical practice, aiming to reduce the time of bed rest, to increase the patients' comfort, and to reduce vascular access-related complications. The aim of the present study is to compare the safety and efficacy of using a VCS to achieve haemostasis following single-shot PVI to the actual standard of care [figure-of-eight suture and manual compression (MC)]. METHODS AND RESULTS: This is a prospective, multicentre, randomized, controlled, open-label trial performed at three German centres. Patients were randomized 1:1 to undergo haemostasis either by means of VCS (VCS group) or of a figure-of-eight suture and MC (F8 group). The primary efficacy endpoint was the time to ambulation, while the primary safety endpoint was the incidence of major periprocedural adverse events until hospital discharge. A total of 125 patients were randomized. The baseline characteristics were similar between the groups. The VCS group showed a shorter time to ambulation [109.0 (82.0, 160.0) vs. 269.0 (243.8, 340.5) min; P < 0.001], shorter time to haemostasis [1 (1, 2) vs. 5 (2, 10) min; P < 0.001], and shorter time to discharge eligibility [270 (270, 270) vs. 340 (300, 458) min; P < 0.001]. No major vascular access-related complication was reported in either group. A trend towards a lower incidence of minor vascular access-related complications on the day of procedure was observed in the VCS group [7 (11.1%) vs. 15 (24.2%); P = 0.063] as compared to the control group. CONCLUSION: Following AF ablation, the use of a VCS results in a significantly shorter time to ambulation, time to haemostasis, and time to discharge eligibility. No major vascular access-related complications were identified. The use of MC and a figure-of-eight suture showed a trend towards a higher incidence of minor vascular access-related complications.


Subject(s)
Atrial Fibrillation , Catheter Ablation , Pulmonary Veins , Suture Techniques , Humans , Atrial Fibrillation/surgery , Female , Male , Middle Aged , Catheter Ablation/adverse effects , Catheter Ablation/methods , Prospective Studies , Pulmonary Veins/surgery , Suture Techniques/adverse effects , Aged , Treatment Outcome , Germany , Time Factors , Vascular Closure Devices , Early Ambulation , Hemostatic Techniques/instrumentation
3.
Eur Heart J Case Rep ; 8(2): ytae048, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38332919

ABSTRACT

Background: In patients with a total cavopulmonary connection in Fontan circulation, the access to the common atrium (CA) during a catheter ablation can be challenging, even in the presence of fenestration in an intra-atrial lateral tunnel (IALT). In our department, the fenestration is typically marked with metal clips (MCs). To the best of our knowledge, there is no previous report of balloonoplasty of clipped fenestration. Case summary: A 19-year-old male with hypoplastic left heart syndrome (HLHS) was scheduled for catheter ablation of recurrent atrial tachycardia. He was diagnosed with HLHS prenatally and underwent a stepwise surgical palliation. Fontan circulation was completed with the creation of a fenestrated IALT. The fenestration was marked by four MCs. During the ablation procedure, the passage of the steerable sheath with mapping catheter to the CA was prevented by a small fenestration size and rigidness of the edges of the fenestration caused by the MCs. Multiple attempts to dilate the fenestration using a peripheric angioplasty balloon failed. Only angioplasty with the 'balloon-against-dilator' technique was finally successful. Activation map showed a counterclockwise atrial flutter in the CA; successful ablation was performed. Discussion: We present a case of challenging access to the CA through a clipped fenestration in a polytetrafluoroethylene baffle for atrial tachycardia ablation. Even though a tunnel fenestration in Fontan patients facilitates access to the CA, the passage of a steerable introducer with a mapping catheter may be challenging due to diameter mismatch and the rigidity of its edges caused by MCs. The balloon-against-dilator technique might be helpful when conventional balloon angioplasty fails.

4.
Eur J Med Chem ; 208: 112768, 2020 Dec 15.
Article in English | MEDLINE | ID: mdl-32932211

ABSTRACT

4-Nitroso-3-trifluoromethyl-5-alkyl[(het)aryl]pyrazoles were synthesized via one-pot nitrosation of 1,3-diketones or their lithium salts followed by treatment of hydrazines. Reduction of nitroso-derivatives made it possible to obtain 4-amino-3-trifluoromethylpyrazoles chlorides. According to computer-aided calculations, all synthesized compounds are expected to have acceptable ADME profile for drug design. Tuberculostatic, antibacterial, antimycotic, antioxidant and cytotoxic activities of the compounds were evaluated in vitro, while their analgesic and anti-inflammatory action was tested in vivo along with acute toxicity studies. N-Unsubstituted 4-nitrosopyrazoles were the most effective tuberculostatics (MIC to 0.36 µg/ml) and antibacterial agents against Streptococcus pyogenes (MIC to 7.8 µg/ml), Staphylococcus aureus,S. aureus MRSA and Neisseria gonorrhoeae (MIC to 15.6 µg/ml). 4-Nitroso-1-methyl-5-phenylpyrazole had the pronounced antimycotic action against a wide range of fungi (Trichophytonrubrum, T. tonsurans, T. violaceum, T. interdigitale, Epidermophytonfloccosum, Microsporumcanis with MIC 0.38-12.5 µg/ml). N-Unsubstituted 4-aminopyrazoles shown high radical-scavenging activity in ABTS test, ORAC/AAPH and oxidative erythrocyte hemolysis assays. 1-Methyl-5-phenyl-3-trifluoromethylpyrazol-4-aminium chloride revealed potential anticancer activity against HeLa cells (SI > 1351). The pronounced analgesic activity was found for 4-nitroso- and 4-aminopyrazoles having phenyl fragment at the position 5 in "hot plate" test. The most of the obtained pyrazoles had a moderate acute toxicity.


Subject(s)
Nitroso Compounds/pharmacology , Pyrazoles/pharmacology , Animals , Bacteria/drug effects , Drug Screening Assays, Antitumor , Epidermophyton/drug effects , HeLa Cells , Humans , Mice , Microbial Sensitivity Tests , Molecular Structure , Nitroso Compounds/chemical synthesis , Nitroso Compounds/pharmacokinetics , Nitroso Compounds/toxicity , Pyrazoles/chemical synthesis , Pyrazoles/pharmacokinetics , Pyrazoles/toxicity , Rats, Sprague-Dawley , Structure-Activity Relationship , Trichophyton/drug effects
5.
Med Chem ; 15(5): 521-536, 2019.
Article in English | MEDLINE | ID: mdl-30398121

ABSTRACT

BACKGROUND: Formally belonging to the non-steroidal anti-inflammatory drug class pyrazolones have long been used in medical practices. OBJECTIVE: Our goal is to synthesize N-methylated 1-aryl-3-polyfluoroalkylpyrazolones as fluorinated analogs of antipyrine, their isomeric O-methylated derivatives resembling celecoxib structure and evaluate biological activities of obtained compounds. METHODS: In vitro (permeability) and in vivo (anti-inflammatory and analgesic activities, acute toxicity, hyperalgesia, antipyretic activity, "open field" test) experiments. To suggest the mechanism of biological activity, molecular docking of the synthesized compounds was carried out into the tyrosine site of COX-1/2. RESULTS: We developed the convenient methods for regioselective methylation of 1-aryl-3- polyfluoroalkylpyrazol-5-ols leading to the synthesis N-methylpyrazolones and O-methylpyrazoles as antipyrine and celecoxib analogs respectively. For the first time, the biological properties of new derivatives were investigated in vitro and in vivo. CONCLUSION: The trifluoromethyl antipyrine represents a valuable starting point in design of the lead series for discovery new antipyretic analgesics with anti-inflammatory properties.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Antipyrine/analogs & derivatives , Antipyrine/pharmacology , Fluorocarbons/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Antipyretics/chemical synthesis , Antipyretics/chemistry , Antipyretics/pharmacology , Antipyretics/toxicity , Antipyrine/chemical synthesis , Antipyrine/toxicity , Catalytic Domain , Cyclooxygenase 1/chemistry , Cyclooxygenase 1/metabolism , Cyclooxygenase 2/chemistry , Cyclooxygenase 2/metabolism , Female , Fluorocarbons/chemical synthesis , Fluorocarbons/chemistry , Fluorocarbons/toxicity , Male , Membrane Proteins/chemistry , Membrane Proteins/metabolism , Molecular Docking Simulation , Rats, Sprague-Dawley
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