BACKGROUND: Oral anticoagulation (OAC) has been considered the standard of care for stroke prophylaxis for patients with nonvalvular atrial fibrillation; however, many individuals are unable or unwilling to take long-term OAC. The safety and efficacy of percutaneous left atrial appendage closure (LAAC) have been controversial, and new trial data have recently emerged. We therefore sought to perform an updated meta-analysis of randomized clinical trials (RCTs) comparing OAC to percutaneous LAAC, focusing on individual clinical endpoints. METHODS: We performed a systematic search of the MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials from January 2000 through December 2021 for all RCTs comparing percutaneous LAAC to OAC in patients with nonvalvular atrial fibrillation. Fixed and random effects meta-analyses of hazard ratios (HRs) were performed using the longest follow-up duration available by intention-to-treat. The prespecified primary endpoint was all-cause mortality. RESULTS: Three RCTs enrolling 1516 patients were identified. The weighted mean follow-up was 54.7 months. LAAC was associated with a reduced risk of all-cause mortality (HR 0.76; 95% confidence interval [CI], 0.59-0.96; p = 0.023), hemorrhagic stroke (HR 0.24; 95% CI, 0.09-0.61; p = 0.003), and major nonprocedural bleeding (HR 0.52; 95% CI, 0.37-0.74; p < 0.001). There was no significant difference between LAAC and OAC for any other endpoints. CONCLUSIONS: The available evidence from RCTs suggests LAAC therapy is associated with reduced long-term risk of death compared with OAC. This may be driven by reductions in hemorrhagic stroke and major nonprocedural bleeding. There were no significant differences in the risk of all stroke. Further large-scale clinical trials are needed to validate these findings.
- Klíčová slova
- Atrial fibrillation, Left atrial appendage closure, Meta-analysis, Stroke,
- Publikační typ
- časopisecké články MeSH
Incomplete endothelialization of intracoronary stents has been associated with stent thrombosis and recurrent symptoms, whereas prolonged use of dual antiplatelet therapy increases bleeding-related adverse events. Facilitated endothelialization has the potential to improve clinical outcomes in patients who are unable to tolerate dual antiplatelet therapy. The objective of this study was to demonstrate the feasibility of magnetic cell capture to rapidly endothelialize intracoronary stents in a large animal model. A novel stent was developed from a magnetizable duplex stainless steel (2205 SS). Polylactic-co-glycolic acid and magnetite (Fe3O4) were used to synthesize biodegradable superparamagnetic iron oxide nanoparticles, and these were used to label autologous blood outgrowth endothelial cells. Magnetic 2205 SS and nonmagnetic 316L SS control stents were implanted in the coronary arteries of pigs (n = 11), followed by intracoronary delivery of magnetically labeled cells to 2205 SS stents. In this study, we show extensive endothelialization of magnetic 2205 SS stents (median 98.4% cell coverage) within 3 days, whereas the control 316L SS stents exhibited significantly less coverage (median 48.9% cell coverage, p < 0.0001). This demonstrates the ability of intracoronary delivery of magnetic nanoparticle labeled autologous endothelial cells to improve endothelialization of magnetized coronary stents within 3 days of implantation.
- Klíčová slova
- cell-targeting, endothelialization, magnetic stent, nanotechnology,
- MeSH
- endoteliální buňky cytologie účinky léků ultrastruktura MeSH
- fenotyp MeSH
- kovy chemie MeSH
- nanočástice chemie ultrastruktura MeSH
- nerezavějící ocel farmakologie MeSH
- prasata MeSH
- stenty * MeSH
- zvířata MeSH
- Check Tag
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Názvy látek
- kovy MeSH
- nerezavějící ocel MeSH
BACKGROUND: The PROTECT AF (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation) trial demonstrated that left atrial appendage closure (LAAC) with the Watchman device (Boston Scientific, St. Paul, Minnesota) was equivalent to warfarin for preventing stroke in atrial fibrillation, but had a high rate of complications. In a second randomized trial, PREVAIL (Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy), the complication rate was low. The warfarin cohort experienced an unexpectedly low ischemic stroke rate, rendering the efficacy endpoints inconclusive. However, these outcomes were based on relatively few patients followed for a relatively short time. OBJECTIVES: The final results of the PREVAIL trial, both alone and as part of a patient-level meta-analysis with the PROTECT AF trial, are reported with patients in both trials followed for 5 years. METHODS: PREVAIL and PROTECT AF are prospective randomized clinical trials with patients randomized 2:1 to LAAC or warfarin; together, they enrolled 1,114 patients for 4,343 patient-years. Analyses are by intention-to-treat, and rates are events per 100 patient-years. RESULTS: For the PREVAIL trial, the first composite coprimary endpoint of stroke, systemic embolism (SE), or cardiovascular/unexplained death did not achieve noninferiority (posterior probability for noninferiority = 88.4%), whereas the second coprimary endpoint of post-procedure ischemic stroke/SE did achieve noninferiority (posterior probability for noninferiority = 97.5%); the warfarin arm maintained an unusually low ischemic stroke rate (0.73%). In the meta-analysis, the composite endpoint was similar between groups (hazard ratio [HR]: 0.820; p = 0.27), as were all-stroke/SE (HR: 0.961; p = 0.87). The ischemic stroke/SE rate was numerically higher with LAAC, but this difference did not reach statistical significance (HR: 1.71; p = 0.080). However, differences in hemorrhagic stroke, disabling/fatal stroke, cardiovascular/unexplained death, all-cause death, and post-procedure bleeding favored LAAC (HR: 0.20; p = 0.0022; HR: 0.45; p = 0.03; HR: 0.59; p = 0.027; HR: 0.73; p = 0.035; HR: 0.48; p = 0.0003, respectively). CONCLUSIONS: These 5-year outcomes of the PREVAIL trial, combined with the 5-year outcomes of the PROTECT AF trial, demonstrate that LAAC with Watchman provides stroke prevention in nonvalvular atrial fibrillation comparable to warfarin, with additional reductions in major bleeding, particularly hemorrhagic stroke, and mortality. (WATCHMAN Left Atrial Appendage System for Embolic Protection in Patients With Atrial Fibrillation; NCT00129545; and Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation Versus Long Term Warfarin Therapy; NCT01182441).
- Klíčová slova
- Watchman *, atrial fibrillation *, left atrial appendage *, left atrial appendage closure *, oral anticoagulation *, stroke prevention *, warfarin *,
- MeSH
- časové faktory MeSH
- cévní mozková příhoda etiologie prevence a kontrola MeSH
- echokardiografie transezofageální MeSH
- fibrilace síní diagnóza chirurgie MeSH
- kardiochirurgické výkony metody MeSH
- lidé MeSH
- následné studie MeSH
- prospektivní studie MeSH
- senioři MeSH
- síňové ouško diagnostické zobrazování chirurgie MeSH
- výsledek terapie MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- randomizované kontrolované studie MeSH
OBJECTIVE: Pharmacotherapy for epilepsy is limited with 30% of patients refractory to this approach of suppressing seizures. Current surgical options are invasive and carry significant morbidities including infection, bleeding, and the potential for deleterious neurocognitive effects. As a result, there is a burgeoning need for innovation to develop safer and efficacious interventions. METHODS: Four distinct catheters (2 existing: Cardima catheter, Standard EPT Blazer catheter; 2 new prototypes: balloon catheter, basket catheters) were tested in 12 baboons (21-30 kg, 100% male). For each, we assessed whether or not the catheter was able to be maneuvered safely in various locations of the cerebral venous system, provide adequate cortical tissue contact to record signals, detect these signals as normal or abnormal, successfully stimulate the cortex, and capture the cortical tissue. Locations trialed included the petrosal sinus, straight sinus, vein of Galen, and occipital vein. Pacing cycle length and pacing thresholds varied among experiments. RESULTS: Successful mapping was conducted in all 12 baboons. The pacing cycle length varied from 75 ms to 650 ms depending on location of the cortex. Pacing threshold was recorded in 4/12 (33%) of the experiments; data is not available for the remaining 8/12 experiments. The threshold values ranged from 0.3 - 20 mAmps. Capture of cortical electrical activity was observed in 11/12 (91.7 %) experiments though the number of successful capture and stimulation attempts varied among experiments. The most reliable and consistent capture occurred with the use of our novel prototyped over-the-wire balloon catheter (9/12; 75%) and basket catheter (3/3; 100%). Necropsy and histology were performed post-experimentation, and only minimal complications were noted (Table 1). CONCLUSION: New electrode design can be maneuvered safely in the venous system, provide adequate cortical tissue contact to record signals, detect these signals as normal or abnormal, successfully stimulate the cortex, and capture cortical tissue. These novel devices merit further study in chronic baboons to establish long-term efficacy of continuous seizure recording.
- Klíčová slova
- Epilepsy, cerebral cortex, primates, venous pacing,
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Pharmacology frequently fails for the treatment of epilepsy. Although surgical techniques are effective, these procedures are highly invasive. We describe feasibility and efficacy of minimally invasive mapping and ablation for the treatment of epilepsy. METHODS: Mapping and radiofrequency ablations were performed via the venous system in eleven baboons and three dogs. RESULTS: Mapping in deep cerebral areas was obtained in all animals. High-frequency pacing was able to induce seizure activity of local cerebral tissue in 72% of our attempts. Cerebral activity could be seen during mapping. Ablative lesions were deployed at deep brain sites without steam pops or sudden impedance rise. Histologic analysis showed necrosis at the sites of ablation in all primates. CONCLUSION: Navigation through the cerebral venous system to map seizure activity is feasible. Radiofrequency energy can be delivered transvenously or transcortically to successfully ablate cortical tissue in this animal model using this innovative approach.
- Klíčová slova
- Catheter ablation, Cerebral cortex, Epilepsy, Radiofrequency, Venous system,
- MeSH
- epilepsie patologie patofyziologie chirurgie MeSH
- katetrizační ablace škodlivé účinky přístrojové vybavení metody MeSH
- magnetické pole MeSH
- mapování mozku MeSH
- miniinvazivní chirurgické výkony škodlivé účinky přístrojové vybavení metody MeSH
- modely nemocí na zvířatech MeSH
- mozková kůra krevní zásobení patologie patofyziologie chirurgie MeSH
- neurochirurgické výkony škodlivé účinky přístrojové vybavení metody MeSH
- Papio MeSH
- psi MeSH
- studie proveditelnosti MeSH
- zvířata MeSH
- Check Tag
- psi MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: To evaluate the benefit of statistical SPECT processing over traditional subtraction methods, we compared ictal-interictal SPECT analyzed by statistical parametric mapping (SPM) (ISAS), statistical ictal SPECT coregistered to MRI (STATISCOM), and subtraction ictal-interictal SPECT coregistered with MRI (SISCOM) in patients with MRI-negative focal temporal lobe epilepsy (nTLE) and extratemporal lobe epilepsy (nETLE). METHODS: We retrospectively identified 49 consecutive cases of drug-resistant focal epilepsy that had a negative preoperative MRI and underwent interictal and ictal SPECT prior to resective epilepsy surgery. Interictal and ictal SPECT scans were analyzed using SISCOM, ISAS, and STATISCOM to create hyperperfusion and hypoperfusion maps for each patient. Reviewers blinded to clinical data and the SPECT analysis method marked the site of probable seizure origin and indicated their confidence in the localization. RESULTS: In nTLE and nETLE, the hyperperfusions detected by STATISCOM (71% nTLE, 57% nETLE) and ISAS (67% nTLE, 53% nETLE) were more often colocalized with surgery resection site compared to SISCOM (38% nTLE, 36% nETLE). In nTLE, localization of the hyperperfusion to the region of surgery was associated with an excellent outcome for STATISCOM (p = 0.005) and ISAS (p = 0.027), but not in SISCOM (p = 0.071). This association was not present in nETLE for any method. CONCLUSION: In an unselected group of patients with normal MRI and focal epilepsy, SPM-based methods of SPECT processing showed better localization of SPECT hyperperfusion to surgical resection site and higher interobserver agreement compared to SISCOM. These results show the benefit of statistical SPECT processing methods and further highlight the challenge of nETLE.
- MeSH
- dospělí MeSH
- elektroencefalografie MeSH
- epilepsie * diagnostické zobrazování patologie chirurgie MeSH
- jednofotonová emisní výpočetní tomografie * MeSH
- lidé středního věku MeSH
- lidé MeSH
- magnetická rezonanční tomografie * MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mozek diagnostické zobrazování patologie patofyziologie MeSH
- retrospektivní studie MeSH
- výsledek terapie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Over 50% of ST-segment elevation myocardial infarction (STEMI) patients suffer multi-vessel coronary artery disease, which is known to be associated with worse prognosis. Treatment strategies used in clinical practice vary from acute multi-vessel percutaneous coronary intervention (PCI), through staged PCI procedures to a conservative approach with primary PCI of only the infarct-related artery (IRA) and subsequent medical therapy unless recurrent ischaemia occurs. Each approach has advantages and disadvantages. This review paper summarizes the international experience and authors' opinion on this clinically important question. Multi-vessel disease in STEMI is not a single entity and thus the treatment approach should be individualized. However, the following general rules can be proposed till future large randomized trials prove otherwise: (i) Single-vessel acute PCI should be the default strategy (to treat only the IRA during the acute phase of STEMI). (ii) Acute multi-vessel PCI can be justified only in exceptional patients with multiple critical (>90%) and potentially unstable lesions. (iii) Significant lesions of the non-infarct arteries should be treated either medically or by staged revascularization procedures-both options are currently acceptable.
- MeSH
- balónková koronární angioplastika metody mortalita MeSH
- infarkt myokardu komplikace mortalita terapie MeSH
- Kaplanův-Meierův odhad MeSH
- koronární bypass metody mortalita MeSH
- lidé MeSH
- mortalita v nemocnicích MeSH
- nemoci koronárních tepen komplikace mortalita terapie MeSH
- výsledek terapie MeSH
- zátěžový test MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
