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.

Circular RNA in colorectal cancer.

Circular RNA (circRNA) is a highly abundant type of single-stranded non-coding RNA. Novel research has discovered many roles of circRNA in colorectal cancer (CRC) including proliferation, metastasis and apoptosis. Furthermore, circRNAs also play a role in the development of drug resistance and have unique associations with tumour size, staging and overall survival in CRC that lend circRNAs the potential to serve as diagnostic and prognostic biomarkers. Among cancers worldwide, CRC ranks second in mortality and third in incidence. In order to have a better understanding of the influence of circRNA on CRC development and progression, this review summarizes the role of specific circRNAs in CRC and evaluates their potential value as therapeutic targets and biomarkers for CRC. We aim to provide insight in the development of therapy and clinical decision-making.

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.

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.

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.

Virtual Reality for Sedation During Atrial Fibrillation Ablation in Clinical Practice: Observational Study.

BACKGROUND: Connected devices are dramatically changing many aspects in health care. One such device, the virtual reality (VR) headset, has recently been shown to improve analgesia in a small sample of patients undergoing transcatheter aortic valve implantation. OBJECTIVE: We aimed to investigate the feasibility and effectiveness of VR in patients undergoing atrial fibrillation (AF) ablation under conscious sedation. METHODS: All patients who underwent an AF ablation with VR from March to May 2020 were included. Patients were compared to a consecutive cohort of patients who underwent AF ablation in the 3 months prior to the study. Primary efficacy was assessed by using a visual analog scale, summarizing the overall pain experienced during the ablation. RESULTS: The AF cryoablation procedure with VR was performed for 48 patients (mean age 63.0, SD 10.9 years; n=16, 33.3% females). No patient refused to use the device, although 14.6% (n=7) terminated the VR session prematurely. Preparation of the VR headset took on average 78 (SD 13) seconds. Compared to the control group, the mean perceived pain, assessed with the visual analog scale, was lower in the VR group (3.5 [SD 1.5] vs 4.3 [SD 1.6]; P=.004), and comfort was higher in the VR group (7.5 [SD 1.6] vs 6.8 [SD 1.7]; P=.03). On the other hand, morphine consumption was not different between the groups. Lastly, complications, as well as procedure and fluoroscopy duration, were not different between the two groups. CONCLUSIONS: We found that VR was associated with a reduction in the perception of pain in patients undergoing AF ablation under conscious sedation. Our findings demonstrate that VR can be easily incorporated into the standard ablation workflow.

Novel Aminoglycoside-Tolerant Phoenix Colony Variants of Pseudomonas aeruginosa.

Pseudomonas aeruginosa is an opportunistic bacterial pathogen and is known to produce biofilms. We previously showed the emergence of colony variants in the presence of tobramycin-loaded calcium sulfate beads. In this study, we characterized the variant colonies, which survived the antibiotic treatment, and identified three distinct phenotypes-classically resistant colonies, viable but nonculturable colonies (VBNC), and phoenix colonies. Phoenix colonies, described here for the first time, grow out of the zone of clearance of antibiotic-loaded beads from lawn biofilms while there are still very high concentrations of antibiotic present, suggesting an antibiotic-resistant phenotype. However, upon subculturing of these isolates, phoenix colonies return to wild-type levels of antibiotic susceptibility. Compared with the wild type, phoenix colonies are morphologically similar aside from a deficiency in green pigmentation. Phoenix colonies do not recapitulate the phenotype of any previously described mechanisms of resistance, tolerance, or persistence and, thus, form a novel group with their own phenotype. Growth under anaerobic conditions suggests that an alternative metabolism could lead to the formation of phoenix colonies. These findings suggest that phoenix colonies could emerge in response to antibiotic therapies and lead to recurrent or persistent infections, particularly within biofilms where microaerobic or anaerobic environments are present.

Exclusively cephalic venous access for cardiac resynchronisation: A prospective multi-centre evaluation.

BACKGROUND: Small series has shown that cardiac resynchronisation therapy (CRT) can be achieved in a majority of patients using exclusively cephalic venous access. We sought to determine whether this method is suitable for widespread use. METHODS: A group of 19 operators including 11 trainees in three pacing centres attempted to use cephalic access alone for all CRT device implants over a period of 8 years. The access route for each lead, the procedure outcome, duration, and complications were collected prospectively. Data were also collected for 105 consecutive CRT device implants performed by experienced operators not using the exclusively cephalic method. RESULTS: A new implantation of a CRT device using exclusively cephalic venous access was attempted in 1091 patients (73.6% male, aged 73 ± 12 years). Implantation was achieved using cephalic venous access alone in 801 cases (73.4%) and using a combination of cephalic and other access in a further 180 (16.5%). Cephalic access was used for 2468 of 3132 leads implanted (78.8%). Compared to a non-cephalic reference group, complications occurred less frequently (69/1091 vs 12/105; P = .0468), and there were no pneumothoraces with cephalic implants. Procedure and fluoroscopy duration were shorter (procedure duration 118 ± 45 vs 144 ± 39 minutes, P < .0001; fluoroscopy duration 15.7 ± 12.9 vs 22.8 ± 12.2 minutes, P < .0001). CONCLUSIONS: CRT devices can be implanted using cephalic access alone in a substantial majority of cases. This approach is safe and efficient.

Isolating the entire pulmonary venous component versus isolating the pulmonary veins for persistent atrial fibrillation: A propensity-matched analysis.

BACKGROUND: The outcomes of pulmonary vein isolation (PVI) for persistent atrial fibrillation (AF) are suboptimal. The entire pulmonary venous component (PV-Comp), consisting of the pulmonary veins, their antra, and the area between the antra, provides triggers and substrate for AF. PV-Comp isolation is an alternative strategy for persistent AF ablation. METHODS: Among 328 patients with persistent AF who underwent a first radiofrequency ablation procedure, 200 patients (PVI, n = 100; PV-Comp isolation, n = 100) were selected by propensity score matching. Both groups were followed up for 1 year. RESULTS: At 6- and 12-month follow-up, atrial tachyarrhythmia (AF/atrial tachycardia) recurred in 41 and 61 patients in PVI group and 22 (P = .006) and 33 patients (P < .001) in PV-Comp isolation group, respectively. PV-Comp isolation was associated with longer mean time to recurrence (PVI: 8 months, PV-Comp isolation: 10 months, log-rank P < .001) and a lower probability of recurrence (odds ratio [OR] = 0.32; 95% confidence of interval [CI] = 0.18-0.56, P < .001), with no increase in procedural complications (PVI: 5 of 100, PV-Comp isolation: 6 of 100, P = .76). Procedure duration was longer in PV-Comp isolation group (PVI: 186 ± 42 min, PV-Comp isolation: 238 ± 44 min, P < .001), as well as fluoroscopy time (PVI: 22 ± 16 min, PV-Comp isolation: 31 ± 21 min, P = .001). CONCLUSION: PV-Comp isolation for persistent AF reduced atrial tachyarrhythmia recurrence up to 1 year compared with PVI alone. While procedure and fluoroscopy time increased, there was no difference in procedural complications.

Proof of concept study of a novel pacemapping algorithm as a basis to guide ablation of ventricular arrhythmias.

Aims: To determine if a software algorithm can use an individualized distance-morphology difference model, built from three initial pacemaps, to prospectively locate the exit site (ES) of ventricular arrhythmias (VA). Methods and results: Consecutive patients undergoing ablation of VA from a single centre were recruited. During mapping, three initial pacing points were collected in the chamber of interest and the navigation algorithm applied to predict the ES, which was corroborated by conventional mapping techniques. Thirty-two patients underwent ES prediction over 35 procedures. Structural heart disease was present in 16 (7 ischaemic cardiomyopathy, 9 non-ischaemic cardiomyopathy), median ejection fraction 45% [Interquartile range (IQR) 26]. The remainder had normal hearts. The navigation algorithm was applied to 46 VA (24 left ventricle, 11 right ventricular outflow tract, 5 left ventricular outflow tract, 4 right ventricle, 2 epicardial) and successfully located the site of best pacemap match in 45 within a median area of 196.5 mm2 (IQR 161.3, range 46.6-1288.2 mm2). Conclusions: In a diverse population of patients with and without structural heart disease, the ES of VA can be accurately and reliably identified to within a clinically useful target area using a simple software navigation algorithm based on pacemapping.

Antibody repertoire deep sequencing reveals antigen-independent selection in maturing B cells.

Antibody repertoires are known to be shaped by selection for antigen binding. Unexpectedly, we now show that selection also acts on a non-antigen-binding antibody region: the heavy-chain variable (VH)-encoded "elbow" between variable and constant domains. By sequencing 2.8 million recombined heavy-chain genes from immature and mature B-cell subsets in mice, we demonstrate a striking gradient in VH gene use as pre-B cells mature into follicular and then into marginal zone B cells. Cells whose antibodies use VH genes that encode a more flexible elbow are more likely to mature. This effect is distinct from, and exceeds in magnitude, previously described maturation-associated changes in heavy-chain complementarity determining region 3, a key antigen-binding region, which arise from junctional diversity rather than differential VH gene use. Thus, deep sequencing reveals a previously unidentified mode of B-cell selection.

Pre-emptive treatment of heart failure exacerbations in patients managed with the HeartLogic™ algorithm.

AIMS: Heart failure (HF) is a chronic disease affecting 64 million people worldwide and places a severe burden on society because of its mortality, numerous re-hospitalizations and associated costs. HeartLogic™ is an algorithm programmed into implanted devices incorporating several biometric parameters which aims to predict HF episodes. It provides an index which can be monitored remotely, allowing pre-emptive treatment of congestion to prevent acute decompensation. We aim to assess the impact and security of pre-emptive HF management, guided by the HeartLogic™ index. METHODS AND RESULTS: The HeartLogic™ France Cohort Study is an investigator-initiated, prospective, multi-centre, non-randomized study. Three hundred ten patients with a history of HF (left ventricular ejection fraction ≤40%; or at least one episode of clinical HF with elevated NT-proBNP ≥450 ng/L) and implanted with a cardioverter defibrillator enabling HeartLogic™ index calculation will be included across 10 French centres. The HeartLogic™ index will be monitored remotely for 12 months and in the event of a HeartLogic™ index ≥16, the local investigator will contact the patient for assessment and adjust HF treatment as necessary. The primary endpoint is unscheduled hospitalization for HF. Secondary endpoints are all-cause mortality, cardiovascular death, HF-related death, unscheduled hospitalizations for ventricular or atrial arrhythmia and HeartLogic™ index evolution over time. Blood samples will be collected for biobanking, and quality of life will be assessed. Finally, the safety of a HeartLogic™-triggered strategy for initiating or increasing diuretic therapy will be assessed. A blind and independent committee will adjudicate the events. CONCLUSIONS: The HeartLogic™ France Cohort Study will provide robust real-world data in a cohort of HF patients managed with the HeartLogic™ algorithm allowing pre-emptive treatment of heart failure exacerbations.

Skin burns associated with radiofrequency catheter ablation of cardiac arrhythmias.

Skin burns are a rare complication associated with radiofrequency catheter ablation of cardiac arrhythmias. Burns related to the indifferent electrode patch may be severe and result in significant comorbidity. We describe our experience of skin burns and discuss potential predisposing and possible causative factors.

Primary cutaneous plasmacytoma occurring after pacemaker implantation and recurring in scar tissue.

Primary cutaneous plasmacytomas are rare and little is known about their treatment and progression. We describe for the first time the predilection of primary cutaneous plasmacytoma to occur in a scar or sites of trauma. We report an 89-year-old man who presented with a slowly expanding asymptomatic mass over his pacemaker implantation, 1 year after insertion. Further investigation ruled out multiple myeloma and histology confirmed it to be a cutaneous plasmacytoma. This was treated successfully by local radiotherapy after extraction of the pacemaker and implantation of a new pacemaker on the opposite side. The patient subsequently developed an additional cutaneous plasmacytoma over the new pacemaker site, followed by the development of progressive multiple myeloma. Primary cutaneous plasmacytoma can show predilection for sites of trauma or surgery. Surgical excision of the plasmocytoma and local radiotherapy may be a reasonable strategy in the first initially after pacemaker removal.