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Oral anticoagulation therapy (OAC) is a mainstay for mitigating stroke and other embolic events in patients with atrial fibrillation (AF). Despite the demonstrated efficacy of OAC in reducing events, many patients are unable to tolerate OAC due to bleeding risks. Left atrial appendage occlusion (LAAO) devices were developed as implantable technologies to moderate stroke risk in patients with intolerance to OAC. Despite clinical data supporting near-comparable protection against thromboembolic events with OAC, device-related thrombus formation has emerged as a critical complication following LAAO that remains a potential limitation to the safety and efficacy of LAAO. Improved biocompatibility of LAAO devices with fluoropolymers, a well-established stent-coating technology used to reduce thrombus formation and promote endothelialization, may optimize outcomes after LAAO.
[Box: see text].
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BACKGROUND: Autonomic denervation is an ancillary phenomenon during thermal ablation of atrial fibrillation (AF), that may have synergistic effects on symptomatic improvement and long-term freedom from AF. Pulsed field ablation (PFA), a nonthermal ablation modality, was noninferior to thermal ablation in treating AF; however, PFA's relative myocardial selectivity may minimize autonomic effects. OBJECTIVES: This study sought to compare heart rate (HR) and heart rate variability (HRV) metrics as markers of autonomic function after ablation using PFA vs thermal ablation. METHODS: ADVENT (FARAPULSE ADVENT PIVOTAL Trial PFA System vs SOC Ablation for Paroxysmal Atrial Fibrillation) was a randomized pivotal study comparing PFA (pentaspline catheter) with thermal ablation (radiofrequency [RF] or cryoballoon [CB]) for treating paroxysmal AF. Baseline HR was acquired from a pre-ablation 12-lead electrocardiogram, whereas follow-up HRs, as well as HRV (standard deviation of all normal to normal RR intervals, standard deviation of 5-minute average RR intervals) metrics, were derived from 72-hour Holter monitors at 6 and 12 months. RESULTS: This study included 379 paroxysmal AF patients undergoing PFA (n = 194) or thermal ablation (n = 185; n = 102 RF, n = 83 CB) completing 6- and 12-month Holter monitoring. Compared with PFA, thermal patients had significantly greater increases in HR from baseline to 6 months (ΔHR; 10.1 vs 5.9 beats/min; P = 0.02) and 12 months (ΔHR; 8.8 vs 5.2 beats/min; P = 0.03). This increase in HR at 6 and 12 months was similar between CB and RF (P = 0.94 and 0.83, respectively). HRV, both standard deviation of all normal to normal RR intervals and standard deviation of 5-minute average RR intervals, were significantly lower at both 6 and 12 months after thermal ablation compared with PFA (P < 0.01). CONCLUSIONS: PFA's effect on the autonomic nervous system was attenuated compared with thermal ablation. Whether this affects long-term freedom from AF or symptomatic bradycardia/pauses after AF ablation requires further study.
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Fibrilação Atrial , Ablação por Cateter , Frequência Cardíaca , Fibrilação Atrial/cirurgia , Fibrilação Atrial/fisiopatologia , Fibrilação Atrial/terapia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Frequência Cardíaca/fisiologia , Ablação por Cateter/métodos , Idoso , Sistema Nervoso Autônomo/fisiopatologia , Criocirurgia/métodos , Eletrocardiografia Ambulatorial , Resultado do TratamentoRESUMO
BACKGROUND: Although expertise in left atrial appendage occlusion (LAAO) has grown, certain intricate anatomies may pose challenges, rendering them unsuitable for LAAO with the selected device. OBJECTIVE: This analysis aimed to characterize outcomes of patients with prior failed percutaneous LAAO procedures who underwent a subsequent attempt with an Amulet occluder in the EMERGE LAA postapproval study. METHODS: Patients enrolled in the National Cardiovascular Data Registry LAAO Registry who had an Amulet occluder implantation attempt between Food and Drug Administration approval (August 14, 2021) and June 30, 2023, were evaluated. A safety end point through 7 days or hospital discharge (whichever was later) and major adverse events through 45 days were reported. RESULTS: A total of 8591 patients underwent attempted Amulet occluder implantation, of whom 244 patients had prior failed LAAO. Implantation success was 88.9% and 96.2% in patients with prior failed LAAO and index LAAO, respectively (P < .001). The safety composite end point was low, occurring in 1.6% and 0.8% of patients with prior failed LAAO and index LAAO, respectively (P = .148). Any major adverse event through 45 days occurred in 7.4% and 6.3% of prior failed LAAO and index LAAO patient cohorts, respectively (P = .497); most adverse events were similar between the groups (P > .05). At 45 days, peridevice leak ≤3 mm was achieved in >90% of patients in either group. CONCLUSION: A high degree of implantation success with a low rate of adverse events can be achieved with the Amulet occluder. The findings imply that the dual occlusive mechanism Amulet occluder facilitates successful closure, even in challenging anatomic scenarios.
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Importance: Left atrial appendage elimination may improve catheter ablation outcomes for atrial fibrillation. Objective: To assess the safety and effectiveness of percutaneous left atrial appendage ligation adjunctive to catheter pulmonary vein isolation for nonparoxysmal atrial fibrillation. Design, Setting, and Participants: This multicenter, prospective, open-label, randomized clinical trial evaluated the safety and effectiveness of percutaneous left atrial appendage ligation adjunctive to planned pulmonary vein isolation for nonparoxysmal atrial fibrillation present for less than 3 years. Eligible patients were randomized in a 2:1 ratio to undergo left atrial appendage ligation and pulmonary vein isolation or pulmonary vein isolation alone. Use of a 2:1 randomization ratio was intended to provide more device experience and safety data. Patients were enrolled from October 2015 to December 2019 at 53 US sites, with the final follow-up visit on April 21, 2021. Interventions: Left atrial appendage ligation plus pulmonary vein isolation compared with pulmonary vein isolation alone. Main Outcomes and Measures: A bayesian adaptive analysis was used for primary end points. Primary effectiveness was freedom from documented atrial arrythmias of greater than 30 seconds duration 12 months after undergoing pulmonary vein isolation. Rhythm was assessed by Holter monitoring at 6 and 12 months after pulmonary vein isolation, symptomatic event monitoring, or any electrocardiographic tracing obtained through 12 months after pulmonary vein isolation. Primary safety was a composite of predefined serious adverse events compared with a prespecified 10% performance goal 30 days after the procedure. Left atrial appendage closure was evaluated through 12 months after pulmonary vein isolation. Results: Overall, 404 patients were randomized to undergo left atrial appendage ligation plus pulmonary vein isolation and 206 were randomized to undergo pulmonary vein isolation alone. Primary effectiveness was 64.3% with left atrial appendage ligation and pulmonary vein isolation and 59.9% with pulmonary vein isolation only (difference, 4.3% [bayesian 95% credible interval, -4.2% to 13.2%]; posterior superiority probability, 0.835), which did not meet the statistical criterion to establish superiority (0.977). Primary safety was met, with a 30-day serious adverse event rate of 3.4% (bayesian 95% credible interval, 2.0% to 5.0%; posterior probability, 1.0) which was less than the prespecified threshold of 10%. At 12 months after pulmonary vein isolation, complete left atrial appendage closure (0 mm residual communication) was observed in 84% of patients and less than or equal to 5 mm residual communication was observed in 99% of patients. Conclusions and Relevance: Percutaneous left atrial appendage ligation adjunctive to pulmonary vein isolation did not meet prespecified efficacy criteria for freedom from atrial arrhythmias at 12 months compared with pulmonary vein isolation alone for patients with nonparoxysmal atrial fibrillation, but met prespecified safety criteria and demonstrated high rates of closure at 12 months. Trial Registration: ClinicalTrials.gov Identifier: NCT02513797.
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Apêndice Atrial , Fibrilação Atrial , Compostos Organotiofosforados , Veias Pulmonares , Humanos , Apêndice Atrial/cirurgia , Fibrilação Atrial/cirurgia , Teorema de Bayes , Estudos Prospectivos , Veias Pulmonares/cirurgia , Ablação por Cateter , CateterismoRESUMO
BACKGROUND AND AIMS: There is growing interest in the functional ecology of poikilohydric non-vascular photoautotrophs (NVPs), including 'cryptogamic' bryophytes and lichens. These organisms are structurally important in many ecosystems, contributing substantially to ecosystem function and services, while also being sensitive to climate change. Previous research has quantified the climate change response of poikilohydric NVPs using predictive bioclimatic models with standard climate variables including precipitation totals and temperature averages. This study aimed for an improved functional understanding of their climate change response based on their growth rate sensitivity to moisture and light. METHODS: We conducted a 24-month experiment to monitor lichen hydration and growth. We accounted for two well-known features in the ecology of poikilohydric NVPs, and exemplified here for a structurally dominant lichen epiphyte, Lobaria pulmonaria: (1) sensitivity to multiple sources of atmospheric moisture including rain, condensed dew-formation and water vapour; and (2) growth determined by the amount of time hydrated in the light, driving photosynthesis, referred to as the Iwet hypothesis. KEY RESULTS: First, we found that even within an oceanic high-rainfall environment, lichen hydration was better explained by vapour pressure deficit than precipitation totals. Second, growth at a monthly resolution was positively related to the amount of time spent hydrated in the light, and negatively related to the amount of time spent hydrated in the dark. CONCLUSIONS: Using multimodel averaging to project growth models for an ensemble of future climate change scenarios, we demonstrated reduced net growth for L. pulmonaria by the late 21st century, explained by extended climate dryness and lichen desiccation for periods when there is otherwise sufficient light to drive photosynthesis. The results further emphasize a key issue of photoperiodism when constructing functionally relevant models to understand the risk of climate change, especially for poikilohydric NVPs.
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Mudança Climática , Líquens , Fotossíntese , Líquens/fisiologia , Líquens/crescimento & desenvolvimento , Líquens/efeitos da radiação , Fotossíntese/fisiologia , Água/fisiologia , Luz , Ecossistema , ChuvaRESUMO
BACKGROUND: Left atrial appendage (LAA) occluder embolization is an infrequent but serious complication. OBJECTIVES: We aim to describe timing, management and clinical outcomes of device embolization in a multi-center registry. METHODS: Patient characteristics, imaging findings and procedure and follow-up data were collected retrospectively. Device embolizations were categorized according to 1) timing 2) management and 3) clinical outcomes. RESULTS: Sixty-seven centers contributed data. Device embolization occurred in 108 patients. In 70.4 % of cases, it happened within the first 24 h of the procedure. The device was purposefully left in the LA and the aorta in two (1.9 %) patients, an initial percutaneous retrieval was attempted in 81 (75.0 %) and surgery without prior percutaneous retrieval attempt was performed in 23 (21.3 %) patients. Two patients died before a retrieval attempt could be made. In 28/81 (34.6 %) patients with an initial percutaneous retrieval attempt a second, additional attempt was performed, which was associated with a high mortality (death in patients with one attempt: 2.9 % vs. second attempt: 21.4 %, p < 0.001). The primary outcome (bailout surgery, cardiogenic shock, stroke, TIA, and/or death) occurred in 47 (43.5 %) patients. Other major complications related to device embolization occurred in 21 (19.4 %) patients. CONCLUSIONS: The majority of device embolizations after LAA closure occurs early. A percutaneous approach is often the preferred method for a first rescue attempt. Major adverse event rates, including death, are high particularly if the first retrieval attempt was unsuccessful. CONDENSED ABSTRACT: This dedicated multicenter registry examined timing, management, and clinical outcome of device embolization. Early embolization (70.4 %) was most frequent. As a first rescue attempt, percutaneous retrieval was preferred in 75.0 %, followed by surgical removal (21.3 %). In patients with a second retrieval attempt a higher mortality (death first attempt: 2.9 % vs. death second attempt: 24.1 %, p < 0.001) was observed. Mortality (10.2 %) and the major complication rate after device embolization were high.
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Apêndice Atrial , Fibrilação Atrial , Cateterismo Cardíaco , Remoção de Dispositivo , Sistema de Registros , Humanos , Masculino , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/fisiopatologia , Feminino , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Fatores de Tempo , Idoso de 80 Anos ou mais , Fatores de Risco , Cateterismo Cardíaco/efeitos adversos , Cateterismo Cardíaco/instrumentação , Cateterismo Cardíaco/mortalidade , Fibrilação Atrial/terapia , Fibrilação Atrial/mortalidade , Remoção de Dispositivo/efeitos adversos , Embolia/etiologia , Embolia/mortalidade , Pessoa de Meia-Idade , Dispositivo para Oclusão Septal , Oclusão do Apêndice Atrial EsquerdoRESUMO
BACKGROUND: Recurrence after atrial fibrillation (AF) ablation remains common. We evaluated the association between recurrence and levels of biomarkers of cardiac remodeling, and their ability to improve recurrence prediction when added to a clinical prediction model. METHODS AND RESULTS: Blood samples collected before de novo catheter ablation were analyzed. Levels of bone morphogenetic protein-10, angiopoietin-2, fibroblast growth factor-23, insulin-like growth factor-binding protein-7, myosin-binding protein C3, growth differentiation factor-15, interleukin-6, N-terminal pro-brain natriuretic peptide, and high-sensitivity troponin T were measured. Recurrence was defined as ≥30 seconds of an atrial arrhythmia 3 to 12 months postablation. Multivariable logistic regression was performed using biomarker levels along with clinical covariates: APPLE score (Age >65 years, Persistent AF, imPaired eGFR [<60 ml/min/1.73m2], LA diameter ≥43 mm, EF <50%; which includes age, left atrial diameter, left ventricular ejection fraction, persistent atrial fibrillation, and estimated glomerular filtration rate), preablation rhythm, sex, height, body mass index, presence of an implanted continuous monitor, year of ablation, and additional linear ablation. A total of 1873 participants were included. A multivariable logistic regression showed an association between recurrence and levels of angiopoietin-2 (odds ratio, 1.08 [95% CI, 1.02-1.15], P=0.007) and interleukin-6 (odds ratio, 1.02 [95% CI, 1.003-1.03]; P=0.02). The area under the receiver operating characteristic curve of a model that only contained clinical predictors was 0.711. The addition of any of the 9 studied biomarkers to the predictive model did not result in a statistically significant improvement in the area under the receiver operating characteristic curve. CONCLUSIONS: Higher angiopoietin-2 and interleukin-6 levels were associated with recurrence after atrial fibrillation ablation in multivariable modeling. However, the addition of biomarkers to a clinical prediction model did not significantly improve recurrence prediction.
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Fibrilação Atrial , Remodelamento Atrial , Ablação por Cateter , Humanos , Idoso , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Angiopoietina-2 , Interleucina-6 , Modelos Estatísticos , Volume Sistólico , Remodelação Ventricular , Fatores de Risco , Prognóstico , Recidiva , Função Ventricular Esquerda , Biomarcadores , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Resultado do TratamentoRESUMO
BACKGROUND: The Food and Drug Administration approved the Amulet occluder (Abbott) after demonstrating safety and effectiveness in the Amulet IDE (AMPLATZER Amulet LAA Occluder) trial. OBJECTIVES: The aim of the EMERGE Left Atrial Appendage study is to evaluate early postapproval outcomes of the Amulet occluder in the United States using data from the National Cardiovascular Data Registry Left Atrial Appendage Occlusion Registry. METHODS: Patients with a commercial Amulet occluder implant attempt between Food and Drug Administration approval (August 14, 2021) and December 31, 2022, were included. The safety composite endpoint included all-cause death, ischemic stroke, systemic embolism, or device/procedure-related events requiring open cardiac surgery or endovascular intervention between device implantation and 7 days or hospital discharge (whichever is later). Major adverse events through 45 days were also reported and stratified by operator experience (early [<10 cases], moderate [10-29 cases], and high [30+ cases]). RESULTS: A total of 5,499 patients underwent attempted Amulet occluder implantation. Implant success was 95.8%, and complete closure was 97.2% post-left atrial appendage occlusion and 87.1% at 45 days. A safety composite endpoint event occurred in 0.76% patients. Any major adverse event occurred in 2.9% and 5.7% of patients in-hospital and through 45 days, respectively, driven by major bleeding and pericardial effusion (PE) requiring intervention. PE requiring surgery or percutaneous intervention decreased significantly with increasing experience both in-hospital (early vs high operator experience 1.8% vs 1.1%; P = 0.006) and at 45 days (2.3% vs 1.5%; P = 0.012). CONCLUSIONS: The EMERGE Left Atrial Appendage study demonstrates favorable safety and effectiveness of the Amulet occluder in the real-world setting. More experienced operators had improved implant success and fewer PEs, suggesting a learning curve effect implanting this dual occlusive mechanism device.
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BACKGROUND: Most breastfeeding individuals take at least one prescription drug, yet limited data from lactation studies are available to inform the safety of these drugs during breastfeeding. As a result, healthcare providers (HCPs) rely on available information about safety of drugs used during pregnancy or on personal experiences to inform prescribing/counseling decisions for breastfeeding individuals. To improve risk communication regarding drugs used during lactation, the U.S. Food and Drug Administration published the Pregnancy and Lactation Labeling Rule (PLLR) in 2015, which added a narrative summary of available risk information to the lactation section of Prescribing Information (PI). Prior studies on labeling in PLLR format revealed that although HCPs found these details valuable, they regarded the narrative as too long to support decision-making during patient encounters. OBJECTIVE: This qualitative study's objective was to assess the utility of adding a concise summary to the Lactation subsection of PI to complement the narrative and succinctly communicate to busy HCPs a drug's risks when used during lactation. The concise summary consisted of a bolded headline, bulleted descriptions of available study findings and potential adverse reactions, and recommendations for risk mitigation. METHODS: Twenty-five online focus groups were conducted with five segments of HCPs to obtain their feedback on the concise summary and discuss their prescribing/counseling decisions for four fictitious prescription drugs including one vaccine. RESULTS: HCPs utilized the concise summary to make initial prescribing/counseling decisions. Many also used the labeling narrative for a comprehensive benefit-risk assessment. CONCLUSION: The findings indicate a need to continue to improve communication about safety of drugs used during lactation, and that the concise summary may help facilitate this communication. The study also highlights the need to educate HCPs about PI limitations when clinical data are lacking and the need to encourage clinical studies to be conducted to support actionable recommendations about use of prescription drugs during lactation.
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Lactação , Medicamentos sob Prescrição , Gravidez , Feminino , Humanos , Aleitamento Materno , Medicamentos sob Prescrição/efeitos adversos , Grupos Focais , Pessoal de SaúdeRESUMO
Coupling red blood cell (RBC) supply to O2 demand is an intricate process requiring O2 sensing, generation of a stimulus, and signal transduction that alters upstream arteriolar tone. Although actively debated, this process has been theorized to be induced by hypoxia and to involve activation of endothelial inwardly rectifying K+ channels (KIR) 2.1 by elevated extracellular K+ to trigger conducted hyperpolarization via connexin40 (Cx40) gap junctions to upstream resistors. This concept was tested in resting healthy skeletal muscle of Cx40-/- and endothelial KIR2.1-/- mice using state-of-the-art live animal imaging where the local tissue O2 environment was manipulated using a custom gas chamber. Second-by-second capillary RBC flow responses were recorded as O2 was altered. A stepwise drop in PO2 at the muscle surface increased RBC supply in capillaries of control animals while elevated O2 elicited the opposite response; capillaries were confirmed to express Cx40. The RBC flow responses were rapid and tightly coupled to O2; computer simulations did not support hypoxia as a driving factor. In contrast, RBC flow responses were significantly diminished in Cx40-/- mice. Endothelial KIR2.1-/- mice, on the other hand, reacted normally to O2 changes, even when the O2 challenge was targeted to a smaller area of tissue with fewer capillaries. Conclusively, microvascular O2 responses depend on coordinated electrical signaling via Cx40 gap junctions, and endothelial KIR2.1 channels do not initiate the event. These findings reconceptualize the paradigm of blood flow regulation in skeletal muscle and how O2 triggers this process in capillaries independent of extracellular K+.
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Capilares , Oxigênio , Animais , Camundongos , Capilares/fisiologia , Proteína alfa-5 de Junções Comunicantes/metabolismo , Junções Comunicantes/metabolismo , Hipóxia/metabolismo , Músculo Esquelético/metabolismo , Oxigênio/metabolismoAssuntos
Apêndice Atrial , Fibrilação Atrial , Dispositivo para Oclusão Septal , Acidente Vascular Cerebral , Doenças Vasculares , Humanos , Apêndice Atrial/diagnóstico por imagem , Resultado do Tratamento , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/terapia , Cateterismo Cardíaco/efeitos adversos , Ecocardiografia TransesofagianaRESUMO
BACKGROUND: The Amulet (Abbott) left atrial appendage occluder investigational device exemption trial is the largest randomized trial evaluating the safety and effectiveness of the Amulet left atrial appendage occluder compared with the Watchman 2.5 device (Boston Scientific) through 5 years. OBJECTIVES: This analysis evaluated the device effect on 3-year outcomes in the Amulet investigational device exemption trial. METHODS: The medication regimen and key clinical outcomes were reported through 3 years including: 1) the composite of ischemic stroke or systemic embolism (SE); 2) the composite of all strokes, SE, or cardiovascular (CV) death; 3) major bleeding; and 4) all-cause death and CV death. RESULTS: A total of 1,878 patients at 108 sites were randomized. A significantly higher percentage of patients were free of oral anticoagulation usage at 3 years with Amulet (96.2%) vs Watchman (92.5%) (P < 0.01). Clinical outcomes were comparable for the composite of ischemic stroke or SE (5.0% vs 4.6%; P = 0.69); the composite of all strokes, SE, or CV death (11.1% vs 12.7%; P = 0.31); major bleeding (16.1% vs 14.7%; P = 0.46); all-cause death (14.6% vs 17.9%; P = 0.08); and CV death (6.6% vs 8.5%; P = 0.14) for Amulet and Watchman, respectively. Through 3 years, device factors (device-related thrombus or peridevice leak ≥3 mm) preceded ischemic stroke events and CV deaths more frequently in Watchman compared with Amulet patients. CONCLUSIONS: The Amulet occluder demonstrated continued safety and effectiveness with over 96% free of oral anticoagulation usage through 3 years in a high-risk population compared to the Watchman device. (AMPLATZER Amulet LAA Occluder Trial [Amulet IDE]; NCT02879448).
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Apêndice Atrial , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Apêndice Atrial/diagnóstico por imagem , Resultado do Tratamento , Acidente Vascular Cerebral/etiologia , AnticoagulantesRESUMO
BACKGROUND: Catheter-based pulmonary vein isolation is an effective treatment for paroxysmal atrial fibrillation. Pulsed field ablation, which delivers microsecond high-voltage electrical fields, may limit damage to tissues outside the myocardium. The efficacy and safety of pulsed field ablation as compared with conventional thermal ablation are not known. METHODS: In this randomized, single-blind, noninferiority trial, we assigned patients with drug-refractory paroxysmal atrial fibrillation in a 1:1 ratio to undergo pulsed field ablation or conventional radiofrequency or cryoballoon ablation. The primary efficacy end point was freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation. The primary safety end point included acute and chronic device- and procedure-related serious adverse events. RESULTS: A total of 305 patients were assigned to undergo pulsed field ablation, and 302 were assigned to undergo thermal ablation. At 1 year, the primary efficacy end point was met (i.e., no events occurred) in 204 patients (estimated probability, 73.3%) who underwent pulsed field ablation and 194 patients (estimated probability, 71.3%) who underwent thermal ablation (between-group difference, 2.0 percentage points; 95% Bayesian credible interval, -5.2 to 9.2; posterior probability of noninferiority, >0.999). Primary safety end-point events occurred in 6 patients (estimated incidence, 2.1%) who underwent pulsed field ablation and 4 patients (estimated incidence, 1.5%) who underwent thermal ablation (between-group difference, 0.6 percentage points; 95% Bayesian credible interval, -1.5 to 2.8; posterior probability of noninferiority, >0.999). CONCLUSIONS: Among patients with paroxysmal atrial fibrillation receiving a catheter-based therapy, pulsed field ablation was noninferior to conventional thermal ablation with respect to freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation and with respect to device- and procedure-related serious adverse events at 1 year. (Funded by Farapulse-Boston Scientific; ADVENT ClinicalTrials.gov number, NCT04612244.).
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Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Fibrilação Atrial/classificação , Fibrilação Atrial/cirurgia , Teorema de Bayes , Ablação por Cateter/efeitos adversos , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , Recidiva , Método Simples-Cego , Taquicardia/etiologia , Resultado do TratamentoRESUMO
AIMS: Incomplete left atrial appendage occlusion (LAAO) due to peri-device leak (PDL) is a limitation of the therapy. The Amulet IDE trial is the largest randomized head-to-head trial comparing the Amulet and Watchman 2.5 LAAO devices with fundamentally different designs. The predictors and mechanistic factors impacting differences in PDLs within the Amulet IDE trial are assessed in the current analysis. METHODS AND RESULTS: An independent core lab analysed all images for the presence or absence of severe PDL (>5â mm). The incidence, mechanistic factors, predictors using propensity score-matched controls, and evolution of severe PDLs through 18 months were assessed. Of the 1878 patients randomized in the trial, the Amulet occluder had significantly fewer severe PDLs than the Watchman device at 45 days (1.1 vs. 3.2%, P < 0.001) and 12 months (0.1 vs. 1.1%, P < 0.001). Off-axis deployment or missed lobes were leading mechanistic PDL factors in each device group. Larger left atrial appendage (LAA) dimensions including orifice diameter, landing zone diameter, and depth predicted severe PDL with the Watchman device, with no significant anatomical limitations noted with the Amulet occluder. Procedural and device implant predictors were found with the Amulet occluder attributed to the learning curve with the device. A majority of Watchman device severe PDLs did not resolve over time through 18 months. CONCLUSION: The dual-occlusive Amplatzer Amulet LAA occluder provided improved LAA closure compared with the Watchman 2.5 device. Predictors and temporal observations of severe PDLs were identified in the Amulet IDE trial. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov Unique identifier NCT02879448.
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Apêndice Atrial , Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Dispositivo para Oclusão Septal , Acidente Vascular Cerebral , Humanos , Apêndice Atrial/diagnóstico por imagem , Apêndice Atrial/cirurgia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/complicações , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Resultado do Tratamento , Dispositivo para Oclusão Septal/efeitos adversos , Cateterismo Cardíaco/efeitos adversos , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: Experimental evidence suggests genetic variation in 4q25/PITX2 modulates pulmonary vein (PV) myocardial sleeve length. Although PV sleeves are the main target of atrial fibrillation (AF) ablation, little is known about the association between different PV sleeve characteristics with ablation outcomes. OBJECTIVES: This study sought to evaluate the association between clinical and genetic (4q25) risk factors with PV sleeve length in humans, and to evaluate the association between PV sleeve length and recurrence after AF ablation. METHODS: In a prospective, observational study of patients undergoing de novo AF ablation, PV sleeve length was measured using electroanatomic voltage mapping before ablation. The sentinel 4q25 AF susceptibility single nucleotide polymorphism, rs2200733, was genotyped. The primary analysis tested the association between clinical and genetic (4q25) risk factors with PV sleeve length using a multivariable linear regression model. Covariates included age, sex, body mass index, height, and persistent AF. The association between PV sleeve length and atrial arrhythmia recurrence (>30 seconds) was tested using a multivariable Cox proportional hazards model. RESULTS: Between 2014 and 2019, 197 participants were enrolled (median age 63 years [IQR: 55 to 70 years], 133 male [67.5%]). In multivariable modeling, men were found to have PV sleeves 2.94 mm longer than women (95% CI: 0.99-4.90 mm; P < 0.001). Sixty participants (30.5%) had one 4q25 risk allele and 6 (3.1%) had 2 alleles. There was no association between 4q25 genotype and PV sleeve length. Forty-six participants (23.4%) experienced arrhythmia recurrence within 3 to 12 months, but there was no association between recurrence and PV sleeve length. CONCLUSIONS: Common genetic variation at 4q25 was not associated with PV sleeve length and PV sleeve length was not associated with ablation outcomes. Men did have longer PV sleeves than women, but more research is needed to define the potential clinical significance of this observation.
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Fibrilação Atrial , Veias Pulmonares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fibrilação Atrial/genética , Fibrilação Atrial/cirurgia , Genótipo , Estudos Prospectivos , Veias Pulmonares/cirurgia , Fatores de Risco , Idoso , Proteína Homeobox PITX2RESUMO
Excess nitrogen is a pollutant and global problem that harms ecosystems and can severely affect human health. Pollutant nitrogen is becoming more widespread and intensifying in the tropics. There is thus a requirement to develop nitrogen biomonitoring for spatial mapping and trend analysis of tropical biodiversity and ecosystems. In temperate and boreal zones, multiple bioindicators for nitrogen pollution have been developed, with lichen epiphytes among the most sensitive and widely applied. However, the state of our current knowledge on bioindicators is geographically biased, with extensive research effort focused on bioindicators in the temperate and boreal zones. The development of lichen bioindicators in the tropics is further weakened by incomplete taxonomic and ecological knowledge. In this study we performed a literature review and meta-analysis, attempting to identify characteristics of lichens that offer transferability of bioindication into tropical regions. This transferability must overcome the different species pools between source information - drawing on extensive research effort in the temperate and boreal zone - and tropical ecosystems. Focussing on ammonia concentration as the nitrogen pollutant, we identify a set of morphological traits and taxonomic relationships that cause lichen epiphytes to be more sensitive, or more resistant to this excess nitrogen. We perform an independent test of our bioindicator scheme and offer recommendations for its application and future research in the tropics.
Assuntos
Poluentes Ambientais , Líquens , Humanos , Biomarcadores Ambientais , Ecossistema , Nitrogênio/análise , Monitoramento Ambiental , Poluentes Ambientais/análiseRESUMO
BACKGROUND: Cardiac implantable electronic device (CIED) infection has a high mortality. Previous investigations showed reduced postoperative infections using skin preparation with chlorhexidine, preoperative intravenous antibiotics, and a TYRX-a antibacterial envelope. The additional benefit of antibiotic pocket wash and postoperative antibiotics has not been systematically studied. METHODS: The ENVELOPE trial (A Randomized trial of Stand-Alone Use of the Antimicrobial Envelope in High-Risk Cardiac Device Patients) was a prospective, multicenter, randomized, controlled trial enrolling patients undergoing CIED procedures with ≥2 risk factors for infection. The control arm received standard chlorhexidine skin preparation, intravenous antibiotics, and the TYRX-a antibiotic envelope. The study arm received pocket wash (500 mL antibiotic solution) and postoperative antibiotics for 3 days along with the prophylactic control measures. The primary end point was CIED infection and system removal at 6 months. RESULTS: One thousand ten subjects (505 per arm) were enrolled and randomized. Patients were seen in person for a wound check with digital photo 2 weeks postimplant and at 3 and 6 months. CIED infection rate was low in both groups (1.0% control arm and 1.2% study arm, P=0.74). In the 11 subjects with infection and system removal, the time to study end point was 107±92 days with a PADIT (Prevention of Arrhythmia Device Infection Trial) score of 7.4 and a 64% 1-year mortality. Prior history of CIED infection independently predicted CIED system removal at 6 months in all subjects (odds ratio, 9.77, P=0.004). Of 11 infections requiring system removal, 5 were in the setting of pocket hematoma. CONCLUSIONS: The use of antibiotic pocket irrigation and postoperative oral antibiotics provides no additional benefit to the prophylactic measures of chlorhexidine skin preparation, preoperative intravenous antibiotics, and an antibiotic envelope in reducing CIED infection. Postoperative hematoma is a major risk factor for infection, driven by the use of antiplatelet and anticoagulant medications. The strongest predictor of CIED removal at 6 months, regardless of intervention, was prior CIED infection. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02809131.
Assuntos
Desfibriladores Implantáveis , Cardiopatias , Marca-Passo Artificial , Infecções Relacionadas à Prótese , Humanos , Desfibriladores Implantáveis/efeitos adversos , Estudos Prospectivos , Clorexidina , Antibacterianos/uso terapêutico , Cardiopatias/complicações , Hematoma/etiologia , Infecções Relacionadas à Prótese/diagnóstico , Infecções Relacionadas à Prótese/epidemiologia , Infecções Relacionadas à Prótese/prevenção & controle , Marca-Passo Artificial/efeitos adversosRESUMO
The nation's opioid overdose deaths reached an all-time high in 2021. The majority of deaths are due to synthetic opioids represented by fentanyl. Naloxone, which is an FDA-approved reversal agent, antagonizes opioids through competitive binding at the mu-opioid receptor (mOR). Thus, knowledge of opioid's residence time is important for assessing the effectiveness of naloxone. Here we estimated the residence times of 15 fentanyl and 4 morphine analogs using metadynamics, and compared them with the most recent measurement of the opioid kinetic, dissociation, and naloxone inhibitory constants (Mann, Li et al, Clin. Pharmacol. Therapeut. 2022). Importantly, the microscopic simulations offered a glimpse at the common binding mechanism and molecular determinants of dissociation kinetics for fentanyl analogs. The insights inspired us to develop a machine learning (ML) approach to analyze the kinetic impact of fentanyl's substituents based on the interactions with mOR residues. This proof-of-concept approach is general; for example, it may be used to tune ligand residence times in computer-aided drug discovery.
RESUMO
The nation's opioid overdose deaths reached an all-time high in 2021. The majority of deaths are due to synthetic opioids represented by fentanyl. Naloxone, which is a FDA-approved reversal agent, antagonizes opioids through competitive binding at the µ-opioid receptor (mOR). Thus, knowledge of the opioid's residence time is important for assessing the effectiveness of naloxone. Here, we estimated the residence times (τ) of 15 fentanyl and 4 morphine analogs using metadynamics and compared them with the most recent measurement of the opioid kinetic, dissociation, and naloxone inhibitory constants (Mann et al. Clin. Pharmacol. Therapeut. 2022, 120, 1020-1232). Importantly, the microscopic simulations offered a glimpse at the common binding mechanism and molecular determinants of dissociation kinetics for fentanyl analogs. The insights inspired us to develop a machine learning approach to analyze the kinetic impact of fentanyl's substituents based on the interactions with mOR residues. This proof-of-concept approach is general; for example, it may be used to tune ligand residence times in computer-aided drug discovery.