WRN helicase is a synthetic lethal target in microsatellite unstable cancers.

Synthetic lethality-an interaction between two genetic events through which the co-occurrence of these two genetic events leads to cell death, but each event alone does not-can be exploited for cancer therapeutics1. DNA repair processes represent attractive synthetic lethal targets, because many cancers exhibit an impairment of a DNA repair pathway, which can lead to dependence on specific repair proteins2. The success of poly(ADP-ribose) polymerase 1 (PARP-1) inhibitors in cancers with deficiencies in homologous recombination highlights the potential of this approach3. Hypothesizing that other DNA repair defects would give rise to synthetic lethal relationships, we queried dependencies in cancers with microsatellite instability (MSI), which results from deficient DNA mismatch repair. Here we analysed data from large-scale silencing screens using CRISPR-Cas9-mediated knockout and RNA interference, and found that the RecQ DNA helicase WRN was selectively essential in MSI models in vitro and in vivo, yet dispensable in models of cancers that are microsatellite stable. Depletion of WRN induced double-stranded DNA breaks and promoted apoptosis and cell cycle arrest selectively in MSI models. MSI cancer models required the helicase activity of WRN, but not its exonuclease activity. These findings show that WRN is a synthetic lethal vulnerability and promising drug target for MSI cancers.

Utility of Thrombectomy in Nonagenarians: A Scoping Review.

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.

Multi-catheter cryotherapy for the treatment of resistant accessory pathways.

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.

Transvenous lead extraction: Experience of the Tandem approach.

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 ± 67 min, P < 0.01) but requiring more fluoroscopy (16.4 ± 10.9 vs. 10.8 ± 14.9 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.

Comparison of non-laser and laser transvenous lead extraction: a systematic review and meta-analysis.

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.

Occupational environment and ovarian cancer risk.

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.

Effect of esophageal cooling on ablation lesion formation in the left atrium: Insights from Ablation Index data in the IMPACT trial and clinical outcomes.

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.

Hourly variability in outflow tract ectopy as a predictor of its site of origin.

INTRODUCTION: Before ablation, predicting the site of origin (SOO) of outflow tract ventricular arrhythmia (OTVA), can inform patient consent and facilitate appropriate procedural planning. We set out to determine if OTVA variability can accurately predict SOO. METHODS: Consecutive patients with a clear SOO identified at OTVA ablation had their prior 24-h ambulatory ECGs retrospectively analysed (derivation cohort). Percentage ventricular ectopic (VE) burden, hourly VE values, episodes of trigeminy/bigeminy, and the variability in these parameters were evaluated for their ability to distinguish right from left-sided SOO. Effective parameters were then prospectively tested on a validation cohort of consecutive patients undergoing their first OTVA ablation. RESULTS: High VE variability (coefficient of variation ≥0.7) and the presence of any hour with <50 VE, were found to accurately predict RVOT SOO in a derivation cohort of 40 patients. In a validation cohort of 29 patients, the correct SOO was prospectively identified in 23/29 patients (79.3%) using CoV, and 26/29 patients (89.7%) using VE < 50. Including current ECG algorithms, VE < 50 had the highest Youden Index (78), the highest positive predictive value (95.0%) and the highest negative predictive value (77.8%). CONCLUSION: VE variability and the presence of a single hour where VE < 50 can be used to accurately predict SOO in patients with OTVA. Accuracy of these parameters compares favorably to existing ECG algorithms.

Cost-effectiveness of catheter ablation versus medical therapy for the treatment of atrial fibrillation in the United Kingdom.

INTRODUCTION: Research evidence has shown that catheter ablation is a safe and superior treatment for atrial fibrillation (AF) compared to medical therapy, but real-world practice has been slow to adopt an early interventional approach. This study aims to determine the cost effectiveness of catheter ablation compared to medical therapy from the perspective of the United Kingdom. METHODS: A patient-level Markov health-state transition model was used to conduct a cost-utility analysis. The population included patients previously treated for AF with medical therapy, including those with heart failure (HF), simulated over a lifetime horizon. Data sources included published literature on utilization and cardiovascular event rates in real world patients, a systematic literature review and meta-analysis of randomized controlled trials for AF recurrence, and publicly available government data/reports on costs. RESULTS: Catheter ablation resulted in a favorable incremental cost-effectiveness ratio (ICER) of £8614 per additional quality adjusted life years (QALY) gained when compared to medical therapy. More patients in the medical therapy group failed rhythm control at any point compared to catheter ablation (72% vs. 24%) and at a faster rate (median time to treatment failure: 3.8 vs. 10 years). Additionally, catheter ablation was estimated to be more cost-effective in patients with AF and HF (ICER = £6438) and remained cost-effective over all tested time horizons (10, 15, and 20 years), with the ICER ranging from £9047-£15 737 per QALY gained. CONCLUSION: Catheter ablation is a cost-effective treatment for atrial fibrillation, compared to medical therapy, from the perspective of the UK National Health Service.

Triple access transvenous lead extraction: Pull-through of a lead from subclavian to jugular access to facilitate extraction.

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.

Patient related outcomes of mechanical lead extraction techniques (PROMET) study: A comparison of two professions.

BACKGROUND: With an increasing number of cardiac implantable electronic devices (CIEDs), there has been a paralleled increase in demand for transvenous lead extraction (TLE). Cardiac surgeons (CS) and cardiologists perform TLE; however, data comparing the two groups of operators is scarce. OBJECTIVE: We compared the outcomes of TLE performed by cardiologists and CS from six European lead extraction units. METHOD: Data was collected retrospectively of 2205 patients who had 3849 leads extracted (PROMET) between 2005 and 2018. Patient demographics and procedural outcomes were compared between the CS and cardiologist groups, using propensity score matching. A multivariate regression analysis was also performed for variables associated with 30-day mortality. RESULTS: CS performed the majority of extractions (59.8%), of leads with longer dwell times (90 [57-129 interquartile range (IQR)] vs. 62 [31-102 IQR] months, CS vs. cardiologists, p < .001) and with pre-dominantly non-infectious indications (57.4% vs. 50.2%, CS vs. cardiologists, p < .001). CS achieved a higher complete success per lead than the cardiologists (98.1% vs. 95.7%, respectively, p < .01), with a higher number of minor complications (5.51% vs. 2.1%, p < .01) and similar number of major complications (0.47% vs. 1.3%, p = .12). Thirty-day mortality was similarly low in the CS and cardiologist groups (1.76% vs. 0.94%, p = .21). Unmatched data multivariate analysis revealed infection indication (OR 6.12 [1.9-20.3], p < .01), procedure duration (OR 1.01 [1.01-1.02], p < .01) and CS operator (OR 2.67, [1.12-6.37], p = .027) were associated with 30-day mortality. CONCLUSION: TLE by CS was performed with similar safety and higher efficacy compared to cardiologists in high and medium-volume lead extraction centers.

Multi-lead cephalic venous access and long-term performance of high-voltage leads.

BACKGROUND: Cardiac resynchronization therapy-defibrillator (CRT-D) implantation via the cephalic vein is feasible and safe. Recent evidence has suggested a higher implantable cardioverter-defibrillator (ICD) lead failure in multi-lead defibrillator therapy via the cephalic route. We evaluated the relationship between CRT-D implantation via the cephalic and ICD lead failure. METHODS: Data was collected from three CRT-D implanting centers between October 2008 and September 2017. In total 633 patients were included. Patient and lead characteristics with ICD lead failure were recorded. Comparison of "cephalic" (ICD lead via cephalic) versus "non-cephalic" (ICD lead via non-cephalic route) cohorts was performed. Kaplan-Meier survival and a Cox-regression analysis were applied to assess variables associated with lead failure. RESULTS: The cephalic and non-cephalic cohorts were equally male (81.9% vs. 78%; p = .26), similar in age (69.7 ± 11.5 vs. 68.7 ± 11.9; p = .33) and body mass index (BMI) (27.7 ± 5.1 vs. 27.1 ± 5.7; p = .33). Most ICD leads were implanted via the cephalic vein (73.5%) and patients had a mean of 2.9 ± 0.28 leads implanted via this route. The rate of ICD lead failure was low and statistically similar between both groups (0.36%/year vs. 0.13%/year; p = .12). Female gender was more common in the lead failure cohort than non-failure (55.6% vs. 17.9%, respectively; p = .004) as was hypertension (88.9% vs. 54.2%, respectively, p = .038). On multivariate Cox-regression, female sex (p = .008; HR, 7.12 [1.7-30.2]), and BMI (p = .047; HR, 1.12 [1.001-1.24]) were significantly associated with ICD lead failure. CONCLUSION: CRT-D implantation via the cephalic route is not significantly associated with premature ICD lead failure. Female gender and BMI are predictors of lead failure.

Multi-catheter cryotherapy compared with radiofrequency ablation in long-standing persistent atrial fibrillation: a randomized clinical trial.

AIMS: Restoring sinus rhythm (SR) by ablation alone is an endpoint used in radiofrequency (RF) ablation for long-standing persistent atrial fibrillation (AF) but not with cryotherapy. The simultaneous use of two cryotherapy catheters can improve ablation efficiency; we compared this with RF ablation in chronic persistent AF aiming for termination to SR by ablation alone. METHODS AND RESULTS: Consecutive patients undergoing their first ablation for persistent AF of >6 months duration were screened. A total of 100 participants were randomized 1:1 to multi-catheter cryotherapy or RF. For cryotherapy, a 28-mm Arctic Front Advance was used in tandem with focal cryoablation catheters. Open-irrigated, non-force sensing catheters were used in the RF group with a 3D mapping system. Pulmonary vein (PV) isolation and non-PV triggers were targeted. Participants were followed up at 6 and 12 months, then yearly. Acute PVI was achieved in all cases. More patients in the multi-catheter cryotherapy group were restored to SR by ablation alone, with a shorter procedure duration. Sinus rhythm continued to the last available follow-up in 16/49 patients (33%) in the multi-catheter at 3.0 ± 1.6 years post-ablation and in 12/50 patients (24%) in the RF group at 4.0 ± 1.2 years post-ablation. The yearly rate of arrhythmia recurrence was similar. CONCLUSION: Multi-catheter cryotherapy can restore SR by ablation alone in more cases and more quickly than RF ablation. Long-term success is difficult to achieve by either methods and is similar with both.

Randomized comparison of oesophageal protection with a temperature control device: results of the IMPACT study.

AIMS: Thermal injury to the oesophagus is an important cause of life-threatening complication after ablation for atrial fibrillation (AF). Thermal protection of the oesophageal lumen by infusing cold liquid reduces thermal injury to a limited extent. We tested the ability of a more powerful method of oesophageal temperature control to reduce the incidence of thermal injury. METHODS AND RESULTS: A single-centre, prospective, double-blinded randomized trial was used to investigate the ability of the ensoETM device to protect the oesophagus from thermal injury. This device was compared in a 1:1 randomization with a control group of standard practice utilizing a single-point temperature probe. In the protected group, the device maintained the luminal temperature at 4°C during radiofrequency (RF) ablation for AF under general anaesthesia. Endoscopic examination was performed at 7 days post-ablation and oesophageal injury was scored. The patient and the endoscopist were blinded to the randomization. We recruited 188 patients, of whom 120 underwent endoscopy. Thermal injury to the mucosa was significantly more common in the control group than in those receiving oesophageal protection (12/60 vs. 2/60; P = 0.008), with a trend toward reduction in gastroparesis (6/60 vs. 2/60, P = 0.27). There was no difference between groups in the duration of RF or in the force applied (P value range= 0.2-0.9). Procedure duration and fluoroscopy duration were similar (P = 0.97, P = 0.91, respectively). CONCLUSION: Thermal protection of the oesophagus significantly reduces ablation-related thermal injury compared with standard care. This method of oesophageal protection is safe and does not compromise the efficacy or efficiency of the ablation procedure.

Prevalence of bradyarrhythmias needing pacing in COVID-19.

BACKGROUND: The Sars-Cov-2 infection is a multisystem illness that can affect the cardiovascular system. Tachyarrhythmias have been reported but the prevalence of bradyarrhythmia is unclear. Cases have been described of transient high-degree atrioventricular (AV) block in COVID-19 that were managed conservatively. METHOD: A database of all patients requiring temporary or permanent pacing in two linked cardiac centers was used to compare the number of procedures required during the first year of the pandemic compared to the corresponding period a year earlier. The database was cross-referenced with a database of all patients testing positive for Sars-Cov-2 infection in both institutions to identify patients who required temporary or permanent pacing during COVID-19. RESULTS: The number of novel pacemaker implants was lower during the COVID-19 pandemic than the same period the previous year (540 vs. 629, respectively), with a similar proportion of high-degree AV block (38.3% vs. 33.2%, respectively, p = .069). Four patients with the Sars-Cov-2 infection had a pacemaker implanted for high-degree AV block, two for sinus node dysfunction. Of this cohort of six patients, two succumbed to the COVID-19 illness and one from non-COVID sepsis. Device interrogation demonstrated a sustained pacing requirement in all cases. CONCLUSION: High-degree AV block remained unaltered in prevalence during the COVID-19 pandemic. There was no evidence of transient high-degree AV block in patients with the Sars-Cov-2 infection. Our experience suggests that all clinically significant bradyarrhythmia should be treated by pacing according to usual protocols regardless of the COVID status.

Prolonged QT predicts prognosis in COVID-19.

BACKGROUND: Coronavirus disease-2019 (COVID-19) causes severe illness and multi-organ dysfunction. An abnormal electrocardiogram is associated with poor outcome, and QT prolongation during the illness has been linked to pharmacological effects. This study sought to investigate the effects of the COVID-19 illness on the corrected QT interval (QTc). METHOD: For 293 consecutive patients admitted to our hospital via the emergency department for COVID-19 between 01/03/20 -18/05/20, demographic data, laboratory findings, admission electrocardiograph and clinical observations were compared in those who survived and those who died within 6 weeks. Hospital records were reviewed for prior electrocardiograms for comparison with those recorded on presentation with COVID-19. RESULTS: Patients who died were older than survivors (82 vs 69.8 years, p < 0.001), more likely to have cancer (22.3% vs 13.1%, p = 0.034), dementia (25.6% vs 10.7%, p = 0.034) and ischemic heart disease (27.8% vs 10.7%, p < 0.001). Deceased patients exhibited higher levels of C-reactive protein (244.6 mg/L vs 146.5 mg/L, p < 0.01), troponin (1982.4 ng/L vs 413.4 ng/L, p = 0.017), with a significantly longer QTc interval (461.1 ms vs 449.3 ms, p = 0.007). Pre-COVID electrocardiograms were located for 172 patients; the QTc recorded on presentation with COVID-19 was longer than the prior measurement in both groups, but was more prolonged in the deceased group (448.4 ms vs 472.9 ms, pre-COVID vs COVID, p < 0.01). Multivariate Cox-regression analysis revealed age, C-reactive protein and prolonged QTc of >455 ms (males) and >465 ms (females) (p = 0.028, HR 1.49 [1.04-2.13]), as predictors of mortality. QTc prolongation beyond these dichotomy limits was associated with increased mortality risk (p = 0.0027, HR 1.78 [1.2-2.6]). CONCLUSION: QTc prolongation occurs in COVID-19 illness and is associated with poor outcome.

Percutaneous management of lead-related cardiac perforation with limited use of computed tomography and cardiac surgery.

BACKGROUND: Cardiac implantable electronic device (CIED)-related perforation is uncommon but potentially lethal. Management typically includes the use of computed tomography (CT) scanning and often involves cardiac surgery. METHODS: Patients presenting to a single referral centre with CIED-related cardiac perforation between 2013 and 2019 were identified. Demographics, diagnostic modalities, the method of lead revision, and 30-day complications were examined. RESULTS: A total of 46 cases were identified; median time from implantation to diagnosis was 14 days (interquartile range = 4-50). Most were females (29/46, 63%), 9/46 (20%) had cancer, 18 patients (39%) used oral anticoagulants, and no patients had prior cardiac surgery. Active fixation was involved in 98% of cases; 9% involved an implantable cardioverter defibrillator lead. Thirty-seven leads perforated the right ventricle (apex: 24) and 9 punctured the right atrium (lateral wall: 5). Abnormal electrical parameters were noted in 95% of interrogated cases. Perforation was visualized in 41% and 6% of cases with chest X-ray (CXR) and transthoracic echocardiography, respectively. CXR revealed a perforation, gross lead displacement, or left-sided pleural effusion in 74% of cases. Pericardial effusion occurred in 26 patients (57%) of whom 11 (24%) developed tamponade, successfully drained percutaneously. Pre-extraction CT scan was performed in 19 patients but was essential in four cases. Transvenous lead revision (TLR) was successfully performed in all cases with original leads repositioned in six patients, without recourse to surgery. Thirty-day mortality and complications were low (0% and 26%, respectively). CONCLUSION: CT scanning provides incremental diagnostic value in a minority of CIED-related perforations. TLR is a safe and effective strategy.

Transvenous lead extraction: The influence of age on patient outcomes in the PROMET study cohort.

BACKGROUND: Cardiac implantable electronic device (CIED) therapy contributes to an improvement in morbidity and mortality across all patient demographics. Patient age is a recognized risk factor for unfavorable outcomes in invasive procedures. This is the largest series of non-laser transvenous lead extraction (TLE) evaluating the association between patient age and procedure outcomes. METHODS: Data of 2205 (3849 leads) patients was collected retrospectively from six European TLE centers between January 2005-December 2018 in the PROMET study. Of these, 153 patients with 319 leads were excluded for incomplete data. A comparison of outcomes was performed between the age groups young [< 50 years], young intermediate [50-69 years], older intermediate [70-79 years], and octogenarian [≥80 years]. RESULTS: Infection was most common indication for TLE in the octogenarian cohort, less common in the younger population (60.1% vs. 33.2%, respectively, p < .01). High-voltage leads were extracted most frequently from young patients, less frequently from octogenarians (31.6% vs. 10%, p < .001), while the opposite was evident for pacemaker leads (p < .001). Rotational sheath use was equally prevalent across all patient groups (p = .79). Minor and major complications across all the age groups were statistically similar, as was procedural success; the 30-day mortality was most significant in the octogenarian and least in the young patients (4.9% vs. 0.4%, p = .005). Propensity matching multivariate analysis found systemic infection, lead dwell time, and patient age (p = .013, OR 1.064 [1.013-1.116]) increased risk of 30-day mortality. CONCLUSION: TLE is safe and effective across all age groups. 30-day mortality risk is significantly higher in the older patients.

Electrophysiology in the time of coronavirus: coping with the great wave.

AIMS: To chart the effect of the COVID-19 pandemic on the activity of interventional electrophysiology services in affected regions. METHODS AND RESULTS: We reviewed the electrophysiology laboratory records in three affected cities: Wenzhou in China, Milan in Italy, and London in the UK. We inspected catheter lab records and interviewed electrophysiologists in each centre to gather information on the impact of the pandemic on working patterns and on the health of staff members and patients. There was a striking decline in interventional electrophysiology activity in each of the centres. The decline occurred within a week of the recognition of widespread community transmission of the virus in each region and shows a striking correlation with the national figures for new diagnoses of COVID-19 in each case. During the period of restriction, workflow dropped to <5% of normal, consisting of emergency cases only. In two of three centres, electrophysiologists were redeployed to perform emergency work outside electrophysiology. Among the centres studied, only Wenzhou has seen a recovery from the restrictions in activity. Following an intense nationwide programme of public health interventions, local transmission of COVID-19 ceased to be detectable after 18 February allowing the electrophysiology service to resume with a strict testing regime for all patients. CONCLUSION: Interventional electrophysiology is vulnerable to closure in times of great social difficulty including the COVID-19 pandemic. Intense public health intervention can permit suppression of local disease transmission allowing resumption of some normal activity with stringent precautions.

Left atrial appendage isolation during ablation in the interatrial septum: Rapid recognition by continuous monitoring of appendage electrograms.

Extensive atrial ablation in the setting of atrial fibrillation (AF) and atrial tachycardia (AT) can affect interatrial connections. A 76-year-old man with a history of tachycardia-induced cardiomyopathy and nine ablation procedures for AF/AT over 15 years presented with highly symptomatic recurrent AT. Previous ablation lesions included pulmonary vein isolation, left atrial posterior wall isolation, mitral isthmus line, cavotricuspid isthmus line, and the ablation of areas of fractionated electrograms. Electroanatomical mapping found the pulmonary veins and the left atrial posterior wall to be silent, as was the posterior interatrial septum and the mitral isthmus area. Activation mapping showed progression of electrograms in the left atrial appendage (LAA) from the septal aspect posteriorly, and in the coronary sinus from proximal to distal; implying the existence of a septal circuit, where extensive fractionation was noted. This was targeted, while monitoring conduction into the LAA using a multielectrode catheter. Ablation led to prompt termination of tachycardia and simultaneous LAA isolation. Immediate cessation of ablation led to recovery of conduction into LAA. Additional lesions in the interatrial septum were required to render the tachycardia noninducible, accompanied by temporary isolation of LAA. The ablation lesion sets employed while ablating AF and left AT can block many interatrial pathways, rendering conduction dependent on muscle bundles in the interatrial septum and, therefore, vulnerable to block by lesions in this area. LAA isolation has been associated with high incidence of LAA thrombus formation and stroke despite oral anticoagulation. Continuous observation of LAA electrograms during ablation can help to avoid this complication.