Sleep oscillations related to memory consolidation during aromatases inhibitors for breast cancer.

Aromatase inhibitors (AIs) are associated with sleep difficulties in breast cancer (BC) patients. Sleep is known to favor memory consolidation through the occurrence of specific oscillations, i.e., slow waves (SW) and sleep spindles, allowing a dialogue between prefrontal cortex and the hippocampus. Interestingly, neuroimaging studies in BC patients have consistently shown structural and functional modifications in these two brain regions. With the aim to evaluate sleep oscillations related to memory consolidation during AIs, we collected polysomnography data in BC patients treated (AI+, n = 17) or not (AI-, n = 17) with AIs compared to healthy controls (HC, n = 21). None of the patients had received chemotherapy and radiotherapy was finished since at least 6 months, that limit the confounding effects of other treatments than AIs. Fast and slow spindles were detected during sleep stage 2 at centro-parietal and frontal electrodes respectively. SW were detected at frontal electrodes during stage 3. Here, we show lower frontal SW densities in AI + patients compared to HC. These results concord with previous reports about frontal cortical alterations in cancer following AIs administration. Moreover, AI + patients tended to have lower spindle density at C4 electrode. Regression analyses showed that, in both patient groups, spindle density at C4 electrode explained a large variance of memory performances. Slow spindle characteristics did not differ between groups and sleep oscillations characteristics of AI- patients did not differ significantly from those of both AI + patients and HC. Overall, our results add to the compelling evidence of the systemic effects of AIs previously reported in animals, with deleterious effects on cortical activity during sleep and associated memory consolidation in the current study. There is thus a need to further investigate sleep modifications during AIs administration. Longitudinal studies are needed to confirm these findings and investigation in other cancers on this topic should be conducted.

Long-term Follow-up with MRI Scans After Enucleation of Peripheral Nerve Schwannomas: Results from a Single-center Case Series.

BACKGROUND: Enucleation is a surgical technique to resect peripheral nerve schwannomas. The procedure has a low risk for postoperative deficit, but a small chance for recurrence, because tumor cells may remain inside the pseudocapsule that is left after resection. Magnetic resonance imaging (MRI) scans are frequently performed after surgery to investigate potential residual tumor, but currently there is little information in the literature on the value of follow-up with MRI. MATERIAL AND METHODS: All patients who underwent enucleation of a peripheral nerve schwannoma between October 2013 and June 2022 were included. Postoperative MRI scans (gadolinium-enhanced) made at different time points after the surgery were re-examined for residual enhancement. Patients with residual enhancement were contacted to inform whether symptoms had recurred. RESULTS: A total of 75 schwannoma enucleations in 74 patients were included. The first postoperative MRI scan, performed 3 months after the surgery, showed no residual enhancement in 50 patients. In the remaining 24 patients, another MRI scan was made 1 year after the surgery, which still showed a possible remnant in 11 patients. On the third MRI scan, performed 2 years after enucleation, there were 7 suspected cases (9%). None of these patients had clinical symptoms at a mean postoperative follow-up of 5 years. CONCLUSIONS: Our data show that the value of postoperative MRI scans after enucleation of peripheral nerve schwannomas is limited, because residual enhancement in the beginning can be non-specific and the small percentage of patients, that persistently had a potential remnant, were all asymptomatic.

Preclinical characterization of the absorption and disposition of the brain penetrant PI3K/mTOR inhibitor paxalisib and prediction of its pharmacokinetics and efficacy in human.

Glioblastoma multiforme (GBM) is the most common primary brain tumour in adults. Available treatments have not markedly improved patient survival in the last twenty years. However, genomic investigations have showed that the PI3K pathway is frequently altered in this glioma, making it a potential therapeutic target.Paxalisib is a brain penetrant PI3K/mTOR inhibitor (mouse Kp,uu 0.31) specifically developed for the treatment of GBM. We characterised the preclinical pharmacokinetics and efficacy of paxalisib and predicted its pharmacokinetics and efficacious dose in humans.Plasma protein binding of paxalisib was low, with the fraction unbound ranging from 0.25 to 0.43 across species. The hepatic clearance of paxalisib was predicted to be low in mice, rats, dogs and humans, and high in monkeys, from hepatocytes incubations. The plasma clearance was low in mice, moderate in rats and high in dogs and monkeys. Oral bioavailability ranged from 6% in monkeys to 76% in rats.The parameters estimated from the pharmacokinetic/pharmacodynamic modelling of the efficacy in the subcutaneous U87 xenograft model combined with the human pharmacokinetics profile predicted by PBPK modelling suggested that a dose of 56 mg may be efficacious in humans. Paxalisib is currently tested in Phase III clinical trials.

Long-term Survival in Breast Cancer Patients Is Associated with Contralateral Parenchymal Enhancement at MRI: Outcomes of the SELECT Study.

Background Several single-center studies found that high contralateral parenchymal enhancement (CPE) at breast MRI was associated with improved long-term survival in patients with estrogen receptor (ER)-positive and human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Due to varying sample sizes, population characteristics, and follow-up times, consensus of the association is currently lacking. Purpose To confirm whether CPE is associated with long-term survival in a large multicenter retrospective cohort, and to investigate if CPE is associated with endocrine therapy effectiveness. Materials and Methods This multicenter observational cohort included women with unilateral ER-positive HER2-negative breast cancer (tumor size ≤50 mm and ≤three positive lymph nodes) who underwent MRI from January 2005 to December 2010. Overall survival (OS), recurrence-free survival (RFS), and distant RFS (DRFS) were assessed. Kaplan-Meier analysis was performed to investigate differences in absolute risk after 10 years, stratified according to CPE tertile. Multivariable Cox proportional hazards regression analysis was performed to investigate whether CPE was associated with prognosis and endocrine therapy effectiveness. Results Overall, 1432 women (median age, 54 years [IQR, 47-63 years]) were included from 10 centers. Differences in absolute OS after 10 years were stratified according to CPE tertile as follows: 88.5% (95% CI: 88.1, 89.1) in tertile 1, 85.8% (95% CI: 85.2, 86.3) in tertile 2, and 85.9% (95% CI: 85.4, 86.4) in tertile 3. CPE was independently associated with OS, with a hazard ratio (HR) of 1.17 (95% CI: 1.0, 1.36; P = .047), but was not associated with RFS (HR, 1.11; P = .16) or DRFS (HR, 1.11; P = .19). The effect of endocrine therapy on survival could not be accurately assessed; therefore, the association between endocrine therapy efficacy and CPE could not reliably be estimated. Conclusion High contralateral parenchymal enhancement was associated with a marginally decreased overall survival in patients with estrogen receptor-positive and human epidermal growth factor receptor 2-negative breast cancer, but was not associated with recurrence-free survival (RFS) or distant RFS. Published under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Honda and Iima in this issue.

Feasibility of Assessing Cryoballoon Pulmonary Vein Occlusion With Saline Injection and a Novel Mapping System.

Thirty-eight patients had assessment of pulmonary vein occlusion with the dielectric mapping system and injection of saline as an alternative to contrast. Contrast injection was required to ascertain pulmonary vein occlusion in 31.6% (12 of 38) of subjects and 17.4% (27 of 155) of veins. No contrast was required in the last 13 subjects. In this single center study, a novel mapping-guided cryoablation approach appeared to minimize the use of contrast in pulmonary vein isolation for the treatment of atrial fibrillation.

Factors associated with enrolment in clinical trials among women with early-stage breast cancer.

BACKGROUND: Clinical trials allow development of innovative treatments and ameliorate the quality of clinical care in oncology. Data show that only a minority of patients are enrolled in clinical trials. We assessed enrolment in clinical trials and its correlates among women with early breast cancer. METHODS: We included 9516 patients with stage I-III breast cancer from the multicenter, prospective CANTO study (NCT01993498), followed-up until year 4 (Y4) post-diagnosis. We assessed factors associated with enrolment using multivariable logistic regression. In exploratory, propensity score matched analyses, we used multiple linear regression to evaluate the relationship of enrolment in clinical trials with the European Organisation for Research and Treatment of Cancer Quality Of Life (QoL) questionnaire (EORTC QLQ-C30) Summary Score and described clinical outcomes (distant disease event, invasive disease event, and death by any cause) according to enrolment. RESULTS: Overall, 1716 patients (18%) were enrolled in a clinical trial until Y4 post-diagnosis of breast cancer. Socioeconomic factors were not associated with enrolment. Centres of intermediate volume were most likely to enrol patients in clinical trials [versus low volume, odds ratio 1.45 (95% confidence interval (CI) 1.08-1.95), P = 0.0124]. Among 2118 propensity score matched patients, enrolment was associated with better QoL at Y4 (adjusted mean difference versus not enrolled 1.37, 95% CI 0.03-2.71, P = 0.0458), and clinical outcomes (enrolled versus not enrolled, distant disease event 7.3% versus 10.1%, P = 0.0206; invasive disease event 8.2% versus 10.5%, P = 0.0732; death by any cause 2.8% versus 3.7%, P = 0.2707). CONCLUSIONS: In this large study, one in five patients enrolled on a clinical trial until Y4 after diagnosis of early breast cancer. Geographical and centre-related factors were significantly associated with enrolment in clinical trials. Inclusion in clinical trials seemed associated with improved QoL and clinical outcomes. Access to innovation for early-stage breast cancer patients should be encouraged and facilitated by overcoming organizational and geographical barriers to recruitment.

Accelerated Partial Breast Irradiation Using External Beam or Intraoperative Electron Radiation Therapy: 5-Year Oncological Outcomes of a Prospective Cohort Study.

PURPOSE: To evaluate the ipsilateral breast tumor recurrence (IBTR) after 2 accelerated partial breast irradiation (APBI) techniques (intraoperative electron radiation therapy [IOERT] and external beam APBI [EB-APBI]) in patients with early-stage breast cancer. METHODS AND MATERIALS: Between 2011 and 2016, women ≥60 years of age with breast carcinoma or Ductal Carcinoma In Situ (DCIS) of ≤30 mm and cN0 undergoing breast-conserving therapy were included in a 2-armed prospective multicenter cohort study. IOERT (1 × 23.3 Gy prescribed at the 100% isodose line) was applied in 1 hospital and EB-APBI (10 × 3.85 Gy daily) in 2 other hospitals. The primary endpoint was IBTR (all recurrences in the ipsilateral breast irrespective of localization) at 5 years after lumpectomy. A competing risk model was used to estimate the cumulative incidences of IBTR, which were compared using Fine and Gray's test. Secondary endpoints were locoregional recurrence rate, distant recurrence, disease-specific survival and overall survival. Univariate Cox regression models were estimated to identify risk factors for IBTR. Analyses were performed of the intention to treat (ITT) population (IOERT n = 305; EB-APBI n = 295), and sensitivity analyses were done of the per-protocol population (IOERT n = 270; EB-APBI n = 207). RESULTS: The median follow-up was 5.2 years (IOERT) and 5 years (EB-APBI). Cumulative incidence of IBTR in the ITT population at 5 years after lumpectomy was 10.6% (95% confidence interval, 7.0%-14.2%) after IOERT and 3.7% (95% confidence interval, 1.2%-5.9%) after EB-APBI (P = .002). The locoregional recurrence rate was significantly higher after IOERT than EB-APBI (12.1% vs 4.5%, P = .001). There were no differences between groups in other endpoints. Sensitivity analysis showed similar results. For both groups, no significant risk factors for IBTR were identified in the ITT population. In the per-protocol population, surgical margin status of the DCIS was the only significant risk factor for developing IBTR in both treatment groups. CONCLUSIONS: Ipsilateral breast tumor recurrences and locoregional recurrence rates were unexpectedly high in patients treated with IOERT, and acceptable in patients treated with EB-APBI.

Sleep macro- and microstructure in breast cancer survivors.

Complaints of sleep disturbance are prevalent among breast cancer (BC) patients and are predictors of quality of life. Still, electrophysiological measures of sleep are missing in patients, which prevents from understanding the pathophysiological consequences of cancer and its past treatments. Using polysomnography, sleep can be investigated in terms of macro- (e.g. awakenings, sleep stages) and micro- (i.e. cortical activity) structure. We aimed to characterize sleep complaints, and macro- and microstructure in 33 BC survivors untreated by chemotherapy and that had finished radiotherapy since at least 6 months (i.e. out of the acute effects of radiotherapy) compared to 21 healthy controls (HC). Compared to HC, BC patients had a larger number of awakenings (p = 0.008); and lower Delta power (p < 0.001), related to sleep deepening and homeostasis; greater both Alpha (p = 0.002) and Beta power (p < 0.001), related to arousal during deep sleep; and lower Theta power (p = 0.004), related to emotion regulation during dream sleep. Here we show that patients have increased cortical activity related to arousal and lower activity related to sleep homeostasis compared to controls. These results give additional insights in sleep pathophysiology of BC survivors and suggest sleep homeostasis disruption in non-advanced stages of BC.

RTK-Dependent Inducible Degradation of Mutant PI3Kα Drives GDC-0077 (Inavolisib) Efficacy.

PIK3CA is one of the most frequently mutated oncogenes; the p110a protein it encodes plays a central role in tumor cell proliferation. Small-molecule inhibitors targeting the PI3K p110a catalytic subunit have entered clinical trials, with early-phase GDC-0077 studies showing antitumor activity and a manageable safety profile in patients with PIK3CA-mutant breast cancer. However, preclinical studies have shown that PI3K pathway inhibition releases negative feedback and activates receptor tyrosine kinase signaling, reengaging the pathway and attenuating drug activity. Here we discover that GDC-0077 and taselisib more potently inhibit mutant PI3K pathway signaling and cell viability through unique HER2-dependent mutant p110a degradation. Both are more effective than other PI3K inhibitors at maintaining prolonged pathway suppression. This study establishes a new strategy for identifying inhibitors that specifically target mutant tumors by selective degradation of the mutant oncoprotein and provide a strong rationale for pursuing PI3Kα degraders in patients with HER2-positive breast cancer. SIGNIFICANCE: The PI3K inhibitors GDC-0077 and taselisib have a unique mechanism of action; both inhibitors lead to degradation of mutant p110a protein. The inhibitors that have the ability to trigger specific degradation of mutant p110a without significant change in wild-type p110a protein may result in improved therapeutic index in PIK3CA-mutant tumors.See related commentary by Vanhaesebroeck et al., p. 20.This article is highlighted in the In This Issue feature, p. 1.

Pegasus, a small extracellular peptide enhancing short-range diffusion of Wingless.

Small Open Reading Frames (smORFs) coding for peptides of less than 100 amino-acids are an enigmatic and pervasive gene class, found in the tens of thousands in metazoan genomes. Here we reveal a short 80 amino-acid peptide (Pegasus) which enhances Wingless/Wnt1 protein short-range diffusion and signalling. During Drosophila wing development, Wingless has sequential functions, including late induction of proneural gene expression and wing margin development. Pegasus mutants produce wing margin defects and proneural expression loss similar to those of Wingless. Pegasus is secreted, and co-localizes and co-immunoprecipitates with Wingless, suggesting their physical interaction. Finally, measurements of fixed and in-vivo Wingless gradients support that Pegasus increases Wingless diffusion in order to enhance its signalling. Our results unveil a new element in Wingless signalling and clarify the patterning role of Wingless diffusion, while corroborating the link between small open reading frame peptides, and regulation of known proteins with membrane-related functions.

Tine-Based Leadless Pacemaker: Strategies for Safe Implantation in Unconventional Clinical Scenarios.

Leadless pacemakers (LPs) have emerged as a meaningful alternative to transvenous pacemakers for single-ventricular pacing. LPs eliminate many of lead- and pocket-associated complications observed with transvenous pacemakers. Owing to the lack of atrioventricular synchronous pacing until recently, the use of LP was generally reserved for those patients who either required minimal ventricular pacing or had permanent atrial fibrillation. The only commercially available LP is the Micra transcatheter pacing system (Micra-TPS, Medtronic Inc. Fridley, Minnesota), which requires insertion of a 27-F (outer diameter) introducer sheath in the femoral vein. The LP is delivered to the right ventricle using a 23-F delivery catheter. Owing to the need for a large-bore sheath, the pivotal studies for the Micra transcatheter pacing system excluded patients with indwelling inferior vena cava filters and included only a few patients with bioprosthetic or repaired tricuspid valve. Subsequent real-world experience has demonstrated the overall safety and feasibility of LP placement, and use in various unconventional clinical settings has been validated, albeit with specific precautions. Additionally, incorporation of adjunctive techniques and strategies can improve the safety of the procedure in routine clinical settings as well. The objective of this state-of-the-art review is to highlight the key procedural elements to facilitate safe and efficient implantation of LP in routine as well as in unique clinical settings.

Percutaneous approaches for retrieval of an embolized or malpositioned left atrial appendage closure device: A multicenter experience.

BACKGROUND: Experience with retrieval of a Watchman left atrial (LA) appendage (LAA) closure device (WD) is limited. An embolized or grossly malpositioned WD warrants retrieval to minimize the risk of thromboembolic complications and vascular occlusion. OBJECTIVE: The purpose of this study was to report approaches for percutaneous retrieval of a WD from multicenter experience. METHODS: Data on successful WD retrievals were obtained from high-volume operators. Data included clinical characteristics; structural characteristics of the LA and LAA; and procedural details of the deployment and retrieval procedure, type of retrieval (immediate: during the same procedure; delayed: during a separate procedure after the successful deployment), equipment used, complications, and postretrieval management. RESULTS: Ten successful percutaneous and 1 surgical retrievals comprised this study. Seven patients had immediate retrieval, while 4 had delayed retrieval. The median duration before delayed retrieval was 45 days (range 1-45 days). The median LAA diameter and size of a successfully deployed WD was 16 mm (range 14-24 mm) and 21 mm (range 21-30 mm), respectively. A WD was retrieved from the LA (n = 1), LAA (n = 2), left ventricle (n = 2), and aorta (n = 6). The reason for retrieval from the LAA was inadequate deployment, resulting in a significant peri-device leak. Retrieval from the LA or LAA was successfully performed using snares (n = 2) and a Raptor grasping device (n = 1). Retrieval from the left ventricle was achieved with a snare (n = 1) and surgery (n = 1). Retrieval from the aorta required snares (n = 5) and retrieval forceps (n = 1). Five patients were successfully reimplanted with a larger size WD. The only complication during percutaneous retrieval was a pseudoaneurysm. CONCLUSION: Retrieval of an embolized or malpositioned WD is feasible, and familiarity with snares and grasping tools can facilitate a successful removal.

Emergent Phenol Injection of Bilateral Stellate Ganglion for Management of Refractory Malignant Ventricular Arrhythmias.

BACKGROUND Management of incessant electrical storm is poorly defined. These 2 case studies demonstrate a simplified percutaneous approach to achieve stellate ganglion ablation (SGA) and to promptly control malignant ventricular arrhythmias. CASE REPORT This report describes 2 patients with deteriorating hemodynamics, progressive ventricular arrhythmias, and worsening heart failure, managed with emergent percutaneous fluoroscopically-guided bilateral SGA to achieve bilateral cardiac sympathetic denervation. While supine and intubated, the left and then right stellate ganglion were identified guided by anatomic landmarks. Using a 22-guage, 3.5-inch spinal needle, contrast dye was injected with appropriate outline of the stellate ganglion at the uncinate process of the C6 vertebra. Bupivacaine 0.5% was injected, followed by phenol 6%. Successful SGA was confirmed by intentional Horner's syndrome with bilateral eye lag. The procedures were completed in about 30 min without complications and there was a dramatic reduction in ventricular arrhythmias. CONCLUSIONS Emergent percutaneous bilateral SGA can be accomplished with a brief procedure resulting in management of electrical storm.

Implantation of subcutaneous defibrillator is feasible and safe with monitored anesthesia care.

BACKGROUND: The perioperative anesthesia care during subcutaneous implantable cardioverter-defibrillator (S-ICD) implantation is still evolving. OBJECTIVE: To assess the feasibility and safety of S-ICD implantation with monitored anesthesia care (MAC) versus general anesthesia (GA) in a tertiary care center. METHODS: This is a single-center retrospective study of patients undergoing S-ICD implantation between October 2012 and May 2019. Patients were categorized into MAC and GA group based on the mode of anesthesia. Procedural success without escalation to GA was the primary endpoint of the study, whereas intraprocedural hemodynamics, need of pharmacological support for hypotension and bradycardia, length of the procedure, stay in the post-anesthesia care unit, and postoperative pain were assessed as secondary endpoints. RESULTS: The study comprises 287 patients with MAC in 111 and GA in 176 patients. Compared to MAC, patients in GA group were younger and had a higher body mass index. All patients had successful S-ICD implantation. Only one patient (0.9%) in the MAC group was converted to GA. Despite a similar baseline heart rate (HR) and mean arterial blood pressure (MAP) in both groups, patients with GA had significantly lower HR and MAP during the procedure and more frequently required pharmacological hemodynamic support. Length of the procedure, stay in the postanesthesia care unit, and postoperative pain was similar in both groups. CONCLUSION: This retrospective experience suggests that implantation of S-ICD is feasible and safe with MAC. Use of GA is associated with more frequent administration of hemodynamic drugs during S-ICD implantation.

Design of a brain-penetrant CDK4/6 inhibitor for glioblastoma.

CDK4 and CDK6 are kinases with similar sequences that regulate cell cycle progression and are validated targets in the treatment of cancer. Glioblastoma is characterized by a high frequency of CDKN2A/CCND2/CDK4/CDK6 pathway dysregulation, making dual inhibition of CDK4 and CDK6 an attractive therapeutic approach for this disease. Abemaciclib, ribociclib, and palbociclib are approved CDK4/6 inhibitors for the treatment of HR+/HER2- breast cancer, but these drugs are not expected to show strong activity in brain tumors due to poor blood brain barrier penetration. Herein, we report the identification of a brain-penetrant CDK4/6 inhibitor derived from a literature molecule with low molecular weight and topological polar surface area (MW = 285 and TPSA = 66 Å2), but lacking the CDK2/1 selectivity profile due to the absence of a basic amine. Removal of a hydrogen bond donor via cyclization of the pyrazole allowed for the introduction of basic and semi-basic amines, while maintaining in many cases efflux ratios reasonable for a CNS program. Ultimately, a basic spiroazetidine (cpKa = 8.8) was identified that afforded acceptable selectivity over anti-target CDK1 while maintaining brain-penetration in vivo (mouse Kp,uu = 0.20-0.59). To probe the potency and selectivity, our lead compound was evaluated in a panel of glioblastoma cell lines. Potency comparable to abemaciclib was observed in Rb-wild type lines U87MG, DBTRG-05MG, A172, and T98G, while Rb-deficient cell lines SF539 and M059J exhibited a lack of sensitivity.

Targeting the PI3K/Akt/mTOR pathway with the pan-Akt inhibitor GDC-0068 in PIK3CA-mutant breast cancer brain metastases.

BACKGROUND: Activating mutations in the pathway of phosphatidylinositol-3 kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) occur in 43-70% of breast cancer brain metastasis patients. To date, the treatment of these patients presents an ongoing challenge, mainly because of the lack of targeted agents that are able to sufficiently penetrate the blood-brain barrier. GDC-0068 is a pan-Akt inhibitor that has shown to be effective in various preclinical tumor models as well as in clinical trials. The purpose of this study was to analyze the efficacy of GDC-0068 in a breast cancer brain metastases model. METHODS: In in vitro studies, antitumor activity of GDC-0068 was assessed in breast cancer cells of phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)-mutant and PIK3CA-wildtype breast cancer cell lines using cell viability and apoptosis assays, cell cycle analysis, and western blots. In vivo, the efficacy of GDC-0068 was analyzed in a PIK3CA-mutant breast cancer brain metastasis orthotopic xenograft mouse model and evaluated by repeated bioluminescent imaging and immunohistochemistry. RESULTS: GDC-0068 decreased cell viability, induced apoptosis, and inhibited phosphorylation of proline rich Akt substrate 40 kDa and p70 S6 kinase in a dose-dependent manner in PIK3CA-mutant breast cancer brain metastatic cell lines compared with PIK3CA-wildtype cell lines. In vivo, treatment with GDC-0068 notably inhibited the growth of PIK3CA-mutant tumors and resulted in a significant survival benefit compared with sham, whereas no effect was detected in a PIK3CA-wildtype model. CONCLUSIONS: This study suggests that the Akt inhibitor GDC-0068 may be an encouraging targeted treatment strategy for breast cancer brain metastasis patients with activating mutations in the PI3K pathway. These data provide a rationale to further evaluate the efficacy of GDC-0068 in patients with brain metastases.

Feasibility of concomitant vacuum-assisted removal of lead-related vegetations and cardiac implantable electronic device extraction.

BACKGROUND: Cardiac implantable electronic device (CIED) infections associated with large, mobile vegetation adds to the complexity of lead extraction and is associated with significant patient morbidity and mortality. OBJECTIVE: To show the feasibility of concomitant cardiovascular implantable electronic device extraction and vacuum-assisted removal of lead-related vegetations. METHODS: This is a single-center retrospective case series of consecutive patients with persistent bacteremia, sepsis, or endocarditis despite medical therapy who have vegetations >2 cm and subsequently underwent immediate CIED lead extraction after debulking with vacuum-assisted suction. RESULTS: Eight patients underwent successful removal of 17 leads immediately after debulking of vegetations with vacuum-assisted device suction. Debulking procedure was not successful in 1 patient due to inability to direct the vacuum suction device into proper position. There were no intraprocedure complications related to the vacuum-assisted debulking. One patient required open sternotomy for tear of the coronary sinus ostium related to extraction of a left ventricular pacing electrode. There was no mortality within 30 days of the procedure. CONCLUSIONS: Based upon these clinical results, it is feasible for patients with infected CIED systems that have large right-sided vegetations to undergo vacuum-assisted debulking then immediately followed by percutaneous CIED removal in whom surgical removal is considered high risk.

Adenosine triphosphate/adenosine guided pulmonary vein isolation does not improve the outcomes of ablation: a meta-analysis of randomized controlled trials.

BACKGROUND: Successful pulmonary vein isolation (PVI) is the most reliable predictor of success after ablation in patients with atrial fibrillation (AF). Adenosine triphosphate (ATP) unmasks the dormant conduction and can be used to improve the effectiveness of PVI. The impact of ATP guided PVI on clinical outcomes is discordant in various randomized controlled trials (RCTs). OBJECTIVES: To delineate the incremental benefit of ATP during PVI in patients with AF through a meta-analysis. METHODS AND RESULTS: Database searches through January 2017 identified 5 RCTs (enrolling 2839 patients) comparing ATP guided PVI versus standard PVI (non-ATP). Four trials exclusively studied paroxysmal AF while one trial included both paroxysmal and non-paroxysmal AF patients. Baseline characteristics, dose of adenosine and ablation strategies were clearly identified among all the trials. The risk ratio (RR) for AF episodes lasting >30 s after 3-month blanking period was calculated with random effects meta-analysis and showed no difference at a median follow up of 12 months [RR: 1.02, 95 % Confidence interval (CI): 0.85 to 1.25; p = 0.82]. Similarly, the number of repeat ablation was similar in both groups [RR: 1.02, 95 % CI: 0.63, 1.56; p = 0.98]. CONCLUSIONS: ATP guided PVI does not decrease the recurrence of AF or the need for repeat ablation at 12 months.

Techniques for successful early retrieval of the Micra transcatheter pacing system: A worldwide experience.

BACKGROUND: Experience with retrieval of the Micra transcatheter pacing system (TPS) is limited because of its relatively newer technology. Although abandonment of the TPS at end of life is recommended, certain situations such as endovascular infection or device embolization warrant retrieval. OBJECTIVE: The purpose of this study was to report the worldwide experience with successful retrieval of the Micra TPS. METHODS: A list of all successful retrievals of the currently available leadless pacemakers (LPs) was obtained from the manufacturer of Micra TPS. Pertinent details of retrieval, such as indication, days postimplantation, equipment used, complications, and postretrieval management, were obtained from the database collected by the manufacturer. Other procedural details were obtained directly from the operators at each participating site. RESULTS: Data from the manufacturer consisted of 40 successful retrievals of the Micra TPS. Operators for 29 retrievals (73%) provided the consent and procedural details. Of the 29 retrievals, 11 patients underwent retrieval during the initial procedure (immediate retrieval); the other 18 patients underwent retrieval during a separate procedure (delayed retrieval). Median duration before delayed retrieval was 46 days (range 1-95 days). The most common reason for immediate retrieval was elevated pacing threshold after tether removal. The most common reasons for delayed retrieval included elevated pacing threshold at follow-up, endovascular infection, and need for transvenous device. Mean procedure duration was 63.11 ± 56 minutes. All retrievals involved snaring via a Micra TPS delivery catheter or steerable sheath. No serious complications occurred during the reported retrievals. CONCLUSION: Early retrieval of the Micra TPS is feasible and safe.