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BACKGROUND AND AIMS: Catheter ablation is superior to pharmacological therapy in controlling atrial fibrillation (AF). There are few data on the long-term outcome of AF ablation in octogenarian patients. This analysis aims to evaluate the outcome of AF ablation in octogenarians vs. younger patients. METHODS: In this retrospective study in 13 centres in the UK, France, and Switzerland, the long-term outcomes of 473 consecutive octogenarian patients undergoing ablation for AF were compared to 473 matched younger controls (median age 81.3 [80.0, 83.0] vs. 64.4 [56.5, 70.7] years, 54.3% vs. 35.1% females; p-value for both < 0.001). The primary endpoint was the recurrence of atrial arrhythmia after a blanking period of 90 days within 365 days of follow-up. RESULTS: Acute ablation success as defined as isolation of all pulmonary veins was achieved in 97% of octogenarians. Octogenarians experienced more procedural complications (11.4% vs 7.0%, p = 0.018). The median follow-up time was 281 [106, 365] days vs. 354 [220, 365] days for octogenarians vs. non-octogenarians (p < 0.001). Among octogenarians, 27.7% (131 patients) experienced a recurrence of atrial arrhythmia, in contrast to 23.5% (111 patients) in the younger group (odds ratio 1.49; 95% confidence interval 1.16-1.92; p = 0.002). In a multivariable regression model including gender, previous AF ablation, vascular disease, chronic kidney disease, CHA2DS2-VASc score, left atrial dilatation, and indwelling cardiac implantable electronic device, age above 80 remained an independent predictor of recurrence of arrhythmia. CONCLUSION: Ablation for AF is effective in octogenarians, but is associated with slightly higher procedural complication rate and recurrence of atrial arrhythmia than in younger patients.
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Proactive esophageal cooling for the purpose of reducing the likelihood of ablation-related esophageal injury resulting from radiofrequency (RF) cardiac ablation procedures is increasingly being used and has been Food and Drug Administration cleared as a protective strategy during left atrial RF ablation for the treatment of atrial fibrillation. In this review, we examine the evidence supporting the use of proactive esophageal cooling and the potential mechanisms of action that reduce the likelihood of atrioesophageal fistula (AEF) formation. Although the pathophysiology behind AEF formation after thermal injury from RF ablation is not well studied, a robust literature on fistula formation in other conditions (eg, Crohn disease, cancer, and trauma) exists and the relationship to AEF formation is investigated in this review. Likewise, we examine the abundant data in the surgical literature on burn and thermal injury progression as well as the acute and chronic mitigating effects of cooling. We discuss the relationship of these data and maladaptive healing mechanisms to the well-recognized postablation pathophysiological effects after RF ablation. Finally, we review additional important considerations such as patient selection, clinical workflow, and implementation strategies for proactive esophageal cooling.
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BACKGROUND: Mechanical thrombectomy represents a mainstay of management for acute ischemic stroke in the setting of large vessel occlusion. However, there are no clinical practice guidelines defining the role of thrombectomy at the extremes of age. In this scoping review, we aimed to summarize the existing medical and neurosurgical literature pertaining to mechanical thrombectomy in nonagenarians. The PubMed database was queried using the following terms and relevant citations assessed: "thrombectomy nonagenarian," "thrombectomy age 90," "stroke nonagenarian," and "ischemic stroke thrombectomy." Common measurable outcomes, including mortality, modified Rankin scale (mRS) score, and thrombolysis in cerebral infarction (TICI) scale score, were utilized to compare results. SUMMARY: Thrombectomy was shown to improve functional outcomes in all eight of the studies included in the analysis. Mortality was assessed in only two reported studies, and thrombectomy was shown to provide a mortality benefit in 1 study among patients for whom first-pass reperfusion was achieved. Other outcomes of reported interest included greater early neurologic recovery at discharge and improved functional outcomes at 90 days among nonagenarians who underwent thrombectomy as compared to those who received thrombolytic therapy alone. Nonagenarians with good functional status at baseline were the most likely to have favorable outcomes. KEY MESSAGES: Mechanical thrombectomy improves outcomes among nonagenarians presenting with acute ischemic stroke due to large vessel occlusion. Further large-scale prospective studies are warranted to optimize patient selection and develop clinical practice guidelines specific to this important patient demographic.
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Trombectomia , Humanos , Trombectomia/métodos , Idoso de 80 Anos ou mais , AVC Isquêmico/cirurgia , AVC Isquêmico/terapia , Resultado do TratamentoRESUMO
A patient with shocks from his ICD related to AF underwent redo ablation. The only identifiable target was the superior vena cava. This was isolated using ultra-low cryotherapy, eliminating episodes of AF.
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OBJECTIVE: To investigate the utility of simultaneous multi-catheter cryotherapy for the treatment of APs that were previously resistant to standard radiofrequency (RF) catheter ablation. BACKGROUND: Catheter ablation is established in the treatment of accessory pathways (AP), with high rates of permanent procedural success with a single attempt. However, there are still instances of acute procedural failure and AP recurrences with standard RF and cryotherapy methods. METHODS: Seven consecutive cases of pre-excitation syndromes with prior failed RF catheter ablation had the novel treatment. Cryotherapy was delivered using two 8 mm tip focal cryoablation catheters (Freezor® Max, Medtronic, Minneapolis, Minnesota, USA). RESULTS: Accessory pathway localisation was septal in 5 cases, left posterolateral in 1, right lateral in 1. In all cases, ablation of the AP was acutely successful with no procedural complications. Median procedure and fluoroscopy durations were 199 and 35 min, sequentially. Median Procedure duration fell significantly in the second half of series (174 min) compared to the first half (233 min, P = 0.05). One patient had evidence of a recurring AP conduction with pre-excitation at 5-week follow up. After a median follow up of 66.8+-6.5 months, 6 out of 7 patients remained asymptomatic and free of pre-excitation. CONCLUSION: Simultaneous multi-catheter cryotherapy is feasible, safe and can provide definitive cure of accessory pathways that were previously resistant to standard radiofrequency ablation. Further study is required in the assessment of this novel form of advanced cryotherapy to treat complex and resistant arrhythmias.
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AIMS: Transvenous lead extraction (TLE) is important in the management of cardiac implantable electronic devices but carries risk. It is most commonly completed from the superior access, often with 'bail-out' support via the femoral approach. Superior and inferior access may be used in tandem, which has been proposed as an advance in safety and efficacy. The aim of this study is to evaluate the safety and efficacy of the Tandem approach. METHOD: The 'Tandem' procedure entailed grasping of the targeted lead in the right atrium to provide countertraction as a rotational dissecting sheath was advanced over the lead from the subclavian access. Consecutive 'Tandem' procedures performed by a single operator between December 2020 and March 2023 in a single large-volume TLE centre were included and compared with the conventional superior approach (control) using 1:1 propensity score matching; patients were statistically matched for demographics. RESULTS: The Tandem in comparison with the conventional approach extracted leads of much greater dwell time (148.9 ± 79 vs. 108.6 ± 77 months, P < 0.01) in a shorter procedure duration (96 ± 36 vs. 127 ± 67â min, P < 0.01) but requiring more fluoroscopy (16.4 ± 10.9 vs. 10.8 ± 14.9â min, P < 0.01). The Tandem and control groups had similar clinical (100% vs. 94.7%, P = 0.07) and complete (94.8% vs. 92.8%, P = 0.42) success, with comparable minor (4% vs. 6.7%, P = 0.72) and major (0% vs. 4%, P = 0.25) complications; procedural (0% vs. 1.3%, P = 1) and 30-day (1.3% vs. 4%, P = 0.62) mortality were also similar. CONCLUSION: The Tandem procedure is as safe and effective as the conventional TLE. It can be applied to leads of a long dwell time with a potentially shorter procedure duration.
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Desfibriladores Implantáveis , Marca-Passo Artificial , Humanos , Desfibriladores Implantáveis/efeitos adversos , Marca-Passo Artificial/efeitos adversos , Remoção de Dispositivo/efeitos adversos , Remoção de Dispositivo/métodos , Fatores de Tempo , Fluoroscopia , Resultado do Tratamento , Estudos RetrospectivosRESUMO
Cardiac resynchronisation therapy (CRT) has become the cornerstone of heart failure (HF) treatment. Despite the obvious benefit from this therapy, an estimated 30% of CRT patients do not respond ("non-responders"). The cause of "non-response" is multi-factorial and includes suboptimal device settings. To optimise CRT settings, echocardiography has been considered the gold standard but has limitations: it is user dependent and consumes time and resources. CRT proprietary algorithms have been developed to perform device optimisation efficiently and with limited resources. In this review, we discuss CRT optimisation including the various adopted proprietary algorithms and conduction system pacing.
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AIMS: Transvenous lead extraction (TLE) is performed using non-laser and laser techniques with overall high efficacy and safety. Variation in outcomes between the two approaches does exist with limited comparative evidence in the literature. We sought to compare non-laser and laser TLE in a meta-analysis. METHODS AND RESULTS: We searched Medline, Embase, Scopus, ClinicalTrials.gov, and CENTRAL databases for TLE studies published between 1991 and 2021. From the included 68 studies, safety and efficacy data were carefully evaluated and extracted. Aggregated cases of outcomes were used to calculate odds ratio (OR), and pooled rates were synthesized from eligible studies to compare non-laser and laser techniques. Subgroup comparison of rotational tool and laser extraction was also performed. Non-laser in comparison with laser had lower procedural mortality (pooled rate 0% vs. 0.1%, P < 0.01), major complications (pooled rate 0.7% vs. 1.7%, P < 0.01), and superior vena cava (SVC) injury (pooled rate 0% vs. 0.5%, P < 0.001), with higher complete success (pooled rate 96.5% vs. 93.8%, P < 0.01). Non-laser comparatively to laser was more likely to achieve clinical [OR 2.16 (1.77-2.63), P < 0.01] and complete [OR 1.87 (1.69-2.08), P < 0.01] success, with a lower procedural mortality risk [OR 1.6 (1.02-2.5), P < 0.05]. In the subgroup analysis, rotational tool compared with laser achieved greater complete success (pooled rate 97.4% vs. 95%, P < 0.01) with lower SVC injury (pooled rate 0% vs. 0.7%, P < 0.01). CONCLUSION: Non-laser TLE is associated with a better safety and efficacy profile when compared with laser methods. There is a greater risk of SVC injury associated with laser sheath extraction.
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Desfibriladores Implantáveis , Marca-Passo Artificial , Humanos , Desfibriladores Implantáveis/efeitos adversos , Veia Cava Superior/cirurgia , Remoção de Dispositivo/efeitos adversos , Remoção de Dispositivo/métodos , Lasers , Cateterismo Cardíaco , Marca-Passo Artificial/efeitos adversos , Resultado do Tratamento , Estudos RetrospectivosRESUMO
OBJECTIVES: To investigate employment in an occupation or industry and specific occupational exposures in relation to ovarian cancer risk. METHODS: In a population-based case-control study conducted in Montreal, Canada (2011-2016), lifetime occupational histories were collected for 491 cases of ovarian cancer and 897 controls. An industrial hygienist coded the occupation and industry of each participant's job. Associations with ovarian cancer risk were estimated for each of several occupations and industries. Job codes were linked to the Canadian job-exposure matrix, thereby generating exposure histories to many agents. The relationship between exposure to each of the 29 most prevalent agents and ovarian cancer risk was assessed. Odds ratios and 95% confidence intervals (OR (95% CI)) for associations with ovarian cancer risk were estimated using logistic regression and controlling for multiple covariates. RESULTS: Elevated ORs (95% CI) were observed for employment ≥10 years as Accountants (2.05 (1.10 to 3.79)); Hairdressers, Barbers, Beauticians and Related Workers (3.22 (1.25 to 8.27)); Sewers and Embroiderers (1.85 (0.77 to 4.45)); and Salespeople, Shop Assistants and Demonstrators (1.45 (0.71 to 2.96)); and in the industries of Retail Trade (1.59 (1.05 to 2.39)) and Construction (2.79 (0.52 to 4.83)). Positive associations with ORs above 1.42 were seen for high cumulative exposure versus never exposure to 18 agents: cosmetic talc, ammonia, hydrogen peroxide, hair dust, synthetic fibres, polyester fibres, organic dyes and pigments, cellulose, formaldehyde, propellant gases, aliphatic alcohols, ethanol, isopropanol, fluorocarbons, alkanes (C5-C17), mononuclear aromatic hydrocarbons, polycyclic aromatic hydrocarbons from petroleum and bleaches. CONCLUSIONS: Certain occupations, industries and specific occupational exposures may be associated with ovarian cancer risk. Further research is needed to provide a more solid grounding for any inferences in this regard.
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Doenças Profissionais , Exposição Ocupacional , Neoplasias Ovarianas , Humanos , Feminino , Estudos de Casos e Controles , Canadá/epidemiologia , Indústrias , Ocupações , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/etiologia , Exposição Ocupacional/efeitos adversos , Fatores de Risco , Doenças Profissionais/epidemiologia , Doenças Profissionais/etiologiaAssuntos
Apêndice Atrial , Fibrilação Atrial , Ablação por Cateter , Humanos , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Átrios do Coração/cirurgia , Átrios do Coração/fisiopatologia , Apêndice Atrial/cirurgia , Ablação por Cateter/efeitos adversosRESUMO
Systematic identification of signaling pathways required for the fitness of cancer cells will facilitate the development of new cancer therapies. We used gene essentiality measurements in 1,086 cancer cell lines to identify selective coessentiality modules and found that a ubiquitin ligase complex composed of UBA6, BIRC6, KCMF1, and UBR4 is required for the survival of a subset of epithelial tumors that exhibit a high degree of aneuploidy. Suppressing BIRC6 in cell lines that are dependent on this complex led to a substantial reduction in cell fitness in vitro and potent tumor regression in vivo. Mechanistically, BIRC6 suppression resulted in selective activation of the integrated stress response (ISR) by stabilization of the heme-regulated inhibitor, a direct ubiquitination target of the UBA6/BIRC6/KCMF1/UBR4 complex. These observations uncover a novel ubiquitination cascade that regulates ISR and highlight the potential of ISR activation as a new therapeutic strategy. SIGNIFICANCE: We describe the identification of a heretofore unrecognized ubiquitin ligase complex that prevents the aberrant activation of the ISR in a subset of cancer cells. This provides a novel insight on the regulation of ISR and exposes a therapeutic opportunity to selectively eliminate these cancer cells. See related commentary Leli and Koumenis, p. 535. This article is highlighted in the In This Issue feature, p. 517.
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Carcinoma , Humanos , Ubiquitinação , Linhagem Celular , Transdução de Sinais , UbiquitinasRESUMO
INTRODUCTION: The IMPACT study established the role of controlled esophageal cooling in preventing esophageal thermal injury during radiofrequency (RF) ablation for atrial fibrillation (AF). The effect of esophageal cooling on ablation lesion delivery and procedural and patient outcomes had not been previously studied. The objective was to determine the effect of esophageal cooling on the formation of RF lesions, the ability to achieve procedural endpoints, and clinical outcomes. METHODS: Participants in the IMPACT trial underwent AF ablation guided by Ablation Index (30 W at 350-400 AI posteriorly, 40 W at ≥450 AI anteriorly). A blinded 1:1 randomization assigned patients to the use of the ensoETM® device to keep esophageal temperature at 4°C during ablation or standard practice using a single-sensor temperature probe. Ablation parameters and clinical outcomes were analyzed. RESULTS: Procedural data from 188 patients were analyzed. Procedure and fluoroscopy times were similar, and all pulmonary veins were isolated. First-pass pulmonary vein isolation and reconnection at the end of the waiting period were similar in both randomized groups (51/64 vs. 51/68; p = 0.54 and 5/64 vs. 7/68; p = 0.76, respectively). Posterior wall isolation was also similar: 24/33 versus 27/38; p = 0.88. Ablation effect on tissue, measured in impedance drop, was no different between the two randomized groups: 8.6Ω (IQR: 6-11.8) versus 8.76Ω (IQR: 6-12.2; p = 0.25). Arrhythmia recurrence was similar after 12 months (21.1% vs. 24.1%; 95% CI: 0.38-1.84; HR: 0.83; p = 0.66). CONCLUSIONS: Esophageal cooling has been shown to be effective in reducing ablation-related thermal injury during RF ablation. This protection does not compromise standard procedural endpoints or clinical success at 12 months.
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Fibrilação Atrial , Ablação por Cateter , Veias Pulmonares , Humanos , Resultado do Tratamento , Átrios do Coração/cirurgia , Ablação por Cateter/métodos , Veias Pulmonares/cirurgia , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/cirurgia , Fibrilação Atrial/etiologia , RecidivaRESUMO
Injury to structures adjacent to the heart, particularly oesophageal injury, accounts for a large proportion of fatal and life-altering complications of ablation for persistent AF. Avoiding these complications dictates many aspects of the way ablation is performed. Because avoidance involves limiting energy delivery in areas of interest, fear of extracardiac injury can impede the ability of the operator to perform an effective procedure. New techniques are becoming available that may permit the operator to circumvent this dilemma and deliver effective ablation with less risk to adjacent structures. The authors review all methods available to avoid injury to extracardiac structures to put these developments in context.
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Randomised evidence supports an early rhythm control strategy as treatment for AF, and catheter ablation outperforms medical therapy in terms of effectiveness when studied as first- and second-line treatment. Despite evidence consistently showing that catheter ablation treatment is superior to medical therapy in most AF patients, only a small proportion receive ablation, in some cases after a prolonged trial of ineffective medical therapy. Health economics research in electrophysiology remains limited but is recognised as being important in influencing positive change to ensure early access to ablation services for all eligible patients. Such information has informed the updated recommendations from the recently published National Institute for Health and Care Excellence clinical guideline on the diagnosis and management of AF, but increased awareness is needed to drive real-world adoption and to ensure patients are quickly referred to specialists. In this article, economic evaluations of catheter ablation versus medical therapy are reviewed.
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Recent decades have seen a series of advances in percutaneous transvenous procedures for cardiac arrhythmias, including the implantation of leadless pacemakers. Many of these procedures require the insertion of large caliber sheaths in large veins, usually the femoral vein. Securing hemostasis efficiently and reliably at the access site is a key step to improving a procedure's safety profile. Traditionally, hemostasis was achieved by manual compression of venous access sites, but the trend toward larger sheaths and the increased use of uninterrupted anticoagulation has pushed the limits of this method. Achieving hemostasis by compression alone in these circumstances requires more attention and longer duration, leading to greater patient discomfort and prolonged immobility. In turn, manual compression may be more time-consuming for medical professionals and increase the number of occupied hospital beds. New approaches have been developed to facilitate early ambulation, decrease patient discomfort, and address the risk of access site complications. These approaches include vascular closure devices and subcutaneous suture techniques including figureof- eight and purse-string sutures. This article reviews the new approaches applied to achieve venous access site hemostasis in patients undergoing transvenous procedures for cardiac arrhythmias.
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Técnicas de Sutura , Suturas , Arritmias Cardíacas/cirurgia , Artéria Femoral/cirurgia , Hemostasia , Humanos , Resultado do TratamentoRESUMO
A 39-years old ventricular lead of a right-sided single-chamber pacemaker required extraction for infection. Angulation at the right subclavian-superior vena cava junction coupled with calcified fibrotic encapsulating tissue prevented advancement of a rotational dissecting sheath. To straighten the lead, it was pulled from the subclavian and out of the right internal jugular vein, whilst the Needle's-Eye Snare via the femoral access provided counter-traction. A 13-french rotational dissecting sheath was successfully advanced over the lead via the jugular access to complete the lead extraction without any complication.
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Marca-Passo Artificial , Veia Cava Superior , Humanos , Adulto , Remoção de Dispositivo , Veias Jugulares/cirurgia , Artéria FemoralRESUMO
OBJECTIVES: To evaluate disease-free survival (DFS) as a surrogate endpoint for overall survival (OS) using aggregate-level data from resectable esophageal or gastroesophageal junction cancer (EC/GEJC) trials assessing therapies in (neo)adjuvant and perioperative settings. METHODS: A systematic literature review was conducted to identify trials reporting OS and DFS, or compatible progression-free survival (PFS). Bivariate random-effects meta-analysis was used to estimate correlation between the treatment effects on DFS/PFS and OS, and weighted linear regression models assuming trial sample sizes as weights were used to estimate surrogacy equations. The primary analysis consisted of trials across all treatment settings, and secondary analysis consisted of trials only in the adjuvant setting. Leave-one-out cross-validation (LOOCV) was performed to measure the stability and predictive accuracy of the surrogacy equations while surrogate threshold effects (STE)-the minimum treatment effect on DFS/PFS that would translate into a positive OS benefit-were derived to measure their usefulness. RESULTS: The primary analysis included 26 trials. The estimated correlation coefficient between the hazard ratio (HR) of DFS/PFS (HRDFS/PFS) and HR of OS (HROS) was 0.83 (95% confidence interval [CI]: 0.70-0.90). The estimated surrogacy equation was log(HROS) = 0.80 × log(HRDFS/PFS) with a corresponding STE of 0.82. Reported HROS was within the 95% prediction interval of the predicted HROS from the model for more than 95% of the trials in the LOOCV, indicating a valid model. Secondary analysis included 7 trials with an estimated correlation coefficient of 0.76 (95% CI: 0.18-0.95). Through LOOCV, the surrogacy equation in the adjuvant setting was deemed valid. CONCLUSIONS: Our meta-analysis suggests that HRDFS/PFS -where DFS/PFS is defined as time from resection to disease recurrence (local, locoregional, or distant) or death-is correlated to HROS, and a valid and useful surrogate predictor for HROS in the neoadjuvant, perioperative, or adjuvant settings.