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To study the safety and efficacy of AngioVac for left-sided transcatheter vacuum-assisted mass extraction (TVME).The AngioVac system is approved for right-sided TVME and has emerged as an effective and safe alternative for open surgical treatment. The use of the AngioVac device for aspiration of left-sided TVME has been limited.Consecutive patients from two Michigan centers who underwent left-sided TVME were included. Data on patient demographics, procedural information, in-hospital and follow-up events were collected through electronic medical records review. Technical success was defined as aspirating of 70%-100% of the material.Ten patients (mean age 58.3 [±17.3] years, 50% male) were included. Indications for TMVE were in large for recurrent embolic events. All patients underwent bilateral cerebro-embolic protection using the Sentinel device. The total mean procedure time was 192.5 (±47.5) min of which the meantime for active aspiration (bypass time) was 9.3 (±4.2) min. The circuit configuration was: arteriovenous (AV) in four cases and arterioarterial (AA) in six cases. Successful aspiration was achieved in 80% of cases. No complications were reported (range follow-up 1-16 months).Our small case series demonstrates the feasibility and safety of the AngioVac system in left-sided mass extraction. Larger trials are needed to further demonstrate its effectiveness and safety and potentially apply for on-label use.

Genetics of recurrent PDX

Purpose:Glioblastoma is the most frequent and lethal primary brain tumor. Development of novel therapies relies on the availability of relevant preclinical models. We have established a panel of 96 glioblastoma patient-derived xenografts (PDX) and undertaken its genomic and phenotypic characterization.Experimental Design:PDXs were established from glioblastoma, IDH-wildtype (n = 93), glioblastoma, IDH-mutant (n = 2), diffuse midline glioma, H3 K27M-mutant (n = 1), and both primary (n = 60) and recurrent (n = 34) tumors. Tumor growth rates, histopathology, and treatment response were characterized. Integrated molecular profiling was performed by whole-exome sequencing (WES, n = 83), RNA-sequencing (n = 68), and genome-wide methylation profiling (n = 76). WES data from 24 patient tumors was compared with derivative models.Results:PDXs recapitulate many key phenotypic and molecular features of patient tumors. Orthotopic PDXs show characteristic tumor morphology and invasion patterns, but largely lack microvascular proliferation and necrosis. PDXs capture common and rare molecular drivers, including alterations of TERT, EGFR, PTEN, TP53, BRAF, and IDH1, most at frequencies comparable with human glioblastoma. However, PDGFRA amplification was absent. RNA-sequencing and genome-wide methylation profiling demonstrated broad representation of glioblastoma molecular subtypes. MGMT promoter methylation correlated with increased survival in response to temozolomide. WES of 24 matched patient tumors showed preservation of most genetic driver alterations, including EGFR amplification. However, in four patient–PDX pairs, driver alterations were gained or lost on engraftment, consistent with clonal selection.Conclusions:Our PDX panel captures the molecular heterogeneity of glioblastoma and recapitulates many salient genetic and phenotypic features. All models and genomic data are openly available to investigators.

Figures S1-S8, Supplementary Methods, Supplementary Bibliography

Objectives To determine the safety and efficacy of the conveyor cardiovascular system (CCS) to facilitate the delivery of large profile transcatheter valve devices. Background Transcatheter valve devices rely on force provided by the operator to be delivered to their intended position. This delivery may be challenging in a variety of anatomic scenarios. The ability to provide steering from the tip of the device by forming an arterial venous loop may help overcome these challenges. Methods Between May, 2019 and October, 2020, five patients were recruited for delivery of transcatheter valve devices with the CCS. These patients were deemed by the operators to have challenging anatomy which could make conventional valve delivery difficult or impossible. These patients were recruited as part of an FDA approved early feasibility study or through an institutional review board approved compassionate use protocol. Results Three patients underwent transcatheter mitral valve replacement with a SAPIEN-3 valve. One patient each underwent transcatheter aortic valve (TAVR) implantation with a SAPIEN 3 and 1 patient underwent TAVR implantation with a Lotus valve. All patients underwent successful implantation of the valve and removal of the CCS and valve delivery systems. There was no more than trivial mitral regurgitation post procedure in any patient and there was no more than trivial paravavular leak. There were no major in-hospital complications. Conclusions The CCS facilitates the delivery of large profile transcatheter valve devices in challenging anatomic scenarios. Further studies are needed with additional valve technologies.

Objective To determine the rate and clinical outcomes of post-TAVR VSD. Background Transcatheter aortic valve replacement (TAVR) is a safe and established procedure for patients with severe symptomatic aortic stenosis. Ventricular septal defect (VSD) is a rare complication of TAVR. The rate of post-TAVR VSD and patient outcomes are not well known. Methods A retrospective record review of VSD cases occurring after all TAVRs performed between January 2012 and September 2020 at one urban US tertiary hospital. VSD rate and early- and long-term outcomes were analyzed. Computed tomography images taken before TAVR and transthoracic echocardiograms done before and after each procedure were analyzed. Results Of the 1908 patients who underwent TAVR in the study period, 7 patients (0.37%) had post-procedure VSD. The average patient age was 77 ± 11 years with average society of thoracic surgeons short-term risk score of 6%. All 7 implanted valves were balloon-expandable. Of the 7 TAVR procedures, 5 were performed on a native tricuspid valve, 1 was performed on a native bicuspid valve, and 1 was done as a "valve-in-valve" procedure on a prior surgical bioprosthetic valve. All VSDs were small and restrictive in nature. Right heart failure in a patient with preexisting right ventricular dysfunction occurred in 1 (13%) patient who died. The remaining 6 patients (86%) were discharged. All 6 patients (86%) were alive and stable at 1 year follow-up, reporting improvement in symptoms (NYHA class I-II), with no evidence of right ventricular dysfunction. Conclusion VSD is a rare complication of TAVR. Hemodynamic and clinical sequelae in majority of the patients in this study did not result in mortality. Proper imaging techniques and appropriate pre-procedure planning are needed to decrease the incidence of VSD formation post-TAVR.

Background Cerebrovascular events that occur during structural and interventional procedures are a well known risk which is associated with increased mortality. The FDA has approved the use of the Sentinel device in TAVR . Hereby we report on our experience on the safety and efficacy of using Sentinel in a patient population undergoing non-TAVR transcatheter procedures. Methods Retrospective analysis of a single center experience with using the Sentinel device for non-TAVR transcatheter procedures. Results We identified 33 patients (average age was 73.8 years, 36.7% females, and 30% with history of a prior stroke) felt to be at high risk for cerebroembolic events that underwent Sentinel device placement. Sentinel placement was successful in all patients. Examples of high risk features included high atheroma burden in the aortic arch, left sided valve vegetations, intra-cardiac thrombi and severe left sided valve calcifications/thrombi. No patients developed periprocedural stroke or vascular complications. Conclusion Overall, the use of Sentinel for non-TAVR indications appears feasible and safe. The use of cerebral protection devices should be studied further in non-TAVR patients to establish its role and its benefits, especially with expanding the number of non-TAVR transcatheter interventions.

We hereby report a case of severe shock from left ventricular outflow tract obstruction following transcatheter aortic valve replacement that did not respond to medical therapy and had to be treated with emergent alcohol septal ablation (ASA). Emergent ASA should be considered for bail-out treatment for these refractory cases. (Level of Difficulty: Advanced.), Central Illustration

BACKGROUND As transcatheter aortic valve replacement (TAVR) procedures increase, more data is available on the development of conduction abnormalities requiring permanent pacemaker (PPM) implantation post-TAVR. Mechanistically, new pacemaker implantation and incidence of associated tricuspid regurgitation (TR) post-TAVR is not well understood. Studies have evaluated the predictability of patient anatomy towards risk for needing permanent pacemaker (PPM) post-TAVR; however, little has been reported on new PPM and TR in patients post-TAVR. METHODS This retrospective study identified patients at our health system who underwent PPM following TAVR from January 2014 to June 2018. Data from both TAVR and PPM procedures as well as patient demographics were collected. Echocardiographic data before TAVR, between TAVR and PPM placement, and the most recent echocardiogram at the time of chart review were analyzed. RESULTS Of 796 patients who underwent TAVR between January 2014 and June 2018, 89 patients (11%) subsequently required PPM. Out of the 89 patients who required PPM implantation, 82 patients had pre-TAVR and 2-year post-TAVR echocardiographic imaging data. At baseline, 22% (18/82) of patients had at least moderate TR. At 2-year post-TAVR echocardiographic imaging follow-up; 27% (22/82) of patients had at least moderate TR. Subgroup analysis was performed according to the TAVR valve size implanted. In patients who received a TAVR device

Background Glioblastoma (GBM) has poor prognosis despite aggressive treatment. Dendritic cell (DC) vaccines are promising, but widespread clinical use has not been achieved, possibly reflecting manufacturing issues of antigen choice and DC potency. We previously optimized vaccine manufacture utilizing allogeneic human GBM tumor cell lysate and potent, mature autologous DCs. Here, we report a phase I study using this optimized DC vaccine in combination with standard therapy. Methods Following surgical resection and radiation with concurrent temozolomide (TMZ), newly diagnosed adult GBM patients received intradermal DC vaccines plus TMZ. Primary endpoints were safety and feasibility. Immune and treatment responses were recorded. Results Twenty-one patients were enrolled in this study. One progressed between leukapheresis and vaccine manufacture. Twenty patients received treatment per protocol. Vaccine doses (≥15) were generated following a single leukapheresis for each patient. No dose-limiting vaccine toxicities were encountered. One patient had symptomatic, histologically proven pseudoprogression. Median progression-free survival was 9.7 months. Median overall survival was 19 months. Overall survival was 25% at 2 years and 10% at 4 years. One patient remains progression-free 5 years after enrollment. Specific CD8 T-cell responses for the tumor-associated antigen gp100 were seen post-vaccination. Patients entered the trial with a leukocyte deficit compared to healthy donors which partly normalized over the course of therapy. Conclusions This vaccine platform is safe and highly feasible in combination with standard therapy for newly diagnosed patients. Imaging, histological, survival, and immunological data suggest a positive biological response to therapy that warrants further investigation.

OBJECTIVE Evaluate transcatheter mitral valve replacement (TMVR) valve-in-valve (VIV) outcomes in three different mitral bioprostheses (of comparable measured internal diameters) under stable hemodynamic and surgical conditions by bench, echocardiographic, computerized tomography (CT), and autopsy comparisons pre- and post-valve implantation in a porcine model under matched controlled conditions. BACKGROUND Impact of surgical bioprosthesis design on TMVR VIV procedures is unknown. METHODS Fifteen similar-sized Yorkshire pigs underwent pre-procedural CT screening. Twelve had consistent anatomic features and underwent implantation of mitral bioprostheses. Four valves from each of three manufacturers were implanted in randomized fashion: 27-mm Epic, 27-mm Mosaic, and 25-mm Mitris, followed by TMVR VIV with 26 Edwards Sapien3. Post-VIV, suprasternal TEE studies were performed to assess hemodynamic function, followed by a gated contrast CT. After euthanasia, animals underwent necropsy for anatomic evaluation. RESULTS All 12 animals had successful VIV implantation with no study deaths. The post vivMitris (3.77 ± 0.36)/(2.2 ± 0.25 mmHg) had the lowest peak/mean trans-mitral gradient and the vivEpic the highest (15.5 ± 2.55)/(7.09 ± 1.13 mmHg). All THVs (transcatheter heart valves) had greatest deformation within the center of the THV frame; with the smallest waist opening area in the vivEpic (329 ± 35.8 mm2 ) and greatest in the vivMitris (414 ± 33.12 mm2 ). Bioprosthetic frames without obvious radiopaque markers resulted in the most ventricular implantation of the THV's anteroseptal frame (Epic: -4.52 ± 0.76 mm), versus the most radiopaque bioprosthesis (Mitris: -1.18 ± 2.95 mm), and higher peak LVOT gradients (Epic: 4.82 ± 1.61 mmHg; Mitris: 2.91 ± 1.47 mmHg). CONCLUSIONS The current study demonstrates marked variations in hemodynamics, THV opening area, and anatomic dimensions among measured similarly sized mitral bioprostheses. These data suggest a critical need for understanding the potential impact of variations in bioprosthesis design on TMVR VIV clinical outcomes.

Background Transcatheter aortic valve replacement (TAVR) and balloon aortic valvuloplasty (BAV) are definitive and bridging therapies in patients with aortic stenosis. Data on utilization of mechanical circulatory support (MCS) in this population is scarce. This study sought to evaluate the clinical outcomes of the use of Impella (Abiomed, Danvers, MA) in patients undergoing TAVR or BAV at a tertiary-care center. Methods We reviewed all TAVRs and BAVs that required Impella from 2012 and 2020. Patient demographics, procedural outcomes, complications, and 30-day mortality were analyzed. Results A total of 1,965 TAVR and 715 BAV cases were performed in the study period. 30 TAVR and 94 BAV cases required an Impella. 65% of these cases were due to cardiogenic shock (CS) (100% of TAVR and 55% of BAV). 31% were performed in female patients. Transfemoral access was utilized in 98% of cases. Impella CP was used in 98% of cases, other types of MCS were used in 8.7% of cases. 32.2% of cases required MCS for more than 24 hours. In the TAVR population the indication for MCS was 46.6% profound hypotension post valve deployment requiring vasopressors, 16.6% cardiac arrest, 10% sustained ventricular arrhythmia, 10% cardiac tamponade [Office1] and 10% coronary occlusion. In the BAV group the indication was 44% high-risk PCI and 56% CS. The 30-day mortality in TAVR was 40% and 28% in BAV; from the BAV group in CS the mortality was 45%. VARC-2 vascular complications and bleeding complications were observed in 4.8% and 1.5%, respectively. 0.7% of the total cohort required conversion to open-heart surgery. Conclusions Impella support is required in a minority of TAVR or BAV cases. In those who require MCS with Impella for either BAV or TAVR, the total mortality remains high especially in those experiencing CS. Funding Acknowledgement Type of funding sources: None.

We report a novel percutaneous approach for the retrieval of a migrated balloon-expandable transcatheter aortic valve (TAVR) that: 1) minimizes interaction with the unstable valve; 2) stabilizes it on an arteriovenous rail; and 3) minimizes vascular trauma. A 90-year-old gentleman underwent

OBJECTIVES We sought to investigate the prognostic value of serum lactate on survival in patients postcardiac arrest. BACKGROUND Patients who experience cardiac arrest, in- or out-of-hospital, may have a poor outcome. Initial electrocardiograms may suggest ischemia as an underlying cause and urgent referral for catheterization occurs. It remains unclear which of these patients may suffer a poor outcome. METHODS We retrospectively reviewed all patients at our institution taken for urgent catheterization after cardiac arrest between January 2014 and September 2018. Three hundred and eighty four patients were referred urgently to the cath lab during this period, 50 with prior arrest. RESULTS Sixty six percent underwent coronary intervention. The mean age of the entire cohort was 57 years. Thirty four percent were female, 40% had a history of coronary artery disease, and 94% were intubated at the time of cardiac catheterization. Overall survival to discharge was 40%. Survival in patients who underwent coronary intervention compared with those who did not was similar (45.5 vs. 29.4%, p = .27). Mean lactate level in survivors versus nonsurvivors was 4.7 ± 3.8 and 9.8 ± 4.7 mmol/L, respectively (p

Background The optimal radiation dose for adult supratentorial low-grade glioma is unknown. The aim of this study was to provide a final update on oncologic and cognitive outcomes of high-dose versus low-dose radiation for low-grade glioma. Methods Between 1986 and 1994, 203 patients with supratentorial low-grade glioma were randomized (1:1) to 50.4 Gy in 28 fractions versus 64.8 Gy in 36 fractions after any degree of resection. Results For all patients, median overall survival (OS) was 8.4 years (95% CI: 7.2–10.8). Median progression-free survival (PFS) was 5.2 years (95% CI: 4.3–6.6). Median follow-up is 17.2 years for the 33 patients still alive. High-dose radiation did not improve 15-year OS (22.4%) versus low-dose radiation (24.9%, log-rank P = 0.978) or 15-year PFS (high dose, 15.2% vs low dose, 9.5%; P = 0.7142). OS was significantly better for patients with preoperative tumor diameter 27 and who underwent gross total resection. PFS was improved for patients with oligodendroglioma versus astrocytoma, preoperative tumor diameter 27. For patients who had normal MMSE at baseline, at 7 years only 1 patient (5%) had a clinically significant decrease in MMSE from the previous time point, with the remainder (95%) stable. None had decrease in MMSE at 10, 12, or 15 years. Conclusions Long-term follow-up indicates no benefit to high-dose over low-dose radiation for low-grade gliomas. Cognitive function appeared to be stable after radiation as measured by MMSE.

BACKGROUND/AIM To evaluate three mitral bioprostheses (of comparable measured internal diameters) under controlled, stable, hemodynamic and surgical conditions by bench, echocardiographic, computerized tomography and autopsy comparisons pre- and postvalve implantation. METHODS Fifteen similar-sized Yorkshire pigs underwent preprocedural computerized tomography anatomic screening. Of these, 12 had consistent anatomic features and underwent implantation of a mitral bioprosthesis via thoracotomy on cardiopulmonary bypass (CPB). Four valves from each of three manufacturers were implanted in randomized fashion: 27-mm Epic, 27-mm Mosaic, and 25-mm Mitris bioprostheses. After CPB, epicardial echocardiographic studies were performed to assess hemodynamic function and define any paravalvular leaks, followed by postoperative gated contrast computerized tomography. After euthanasia, animals underwent necropsy for anatomic evaluation. RESULTS All 12 animals had successful valve implantation with no study deaths. Postoperative echocardiographic trans-valve gradients varied among bioprosthesis manufacturers. The 25-mm Mitris (5.1 ± 2.7)/(2.6 ± 1.3 torr) had the lowest peak/mean gradient and the 27-mm Epic bioprosthesis had the highest (9.2 ± 3.7)/(4.6 ± 1.9 torr). Surgical valve opening area (SOA) varied with the 25-mm Mitris having the largest SOA (2.4 ± 0.15 cm2 ) followed by the 27-mm Mosaic (2.04 ± 0.23 cm2 ) and the 27-mm Epic (1.8 ± 0.27 cm2 ) valve. Bench device orthogonal internal diameter measurements did not match manufacturer device size labeling: 25-mm Mitris (23 × 23 mm), 27-mm Mosaic (23 × 22 mm), 27-mm Epic (21 × 21 mm). CONCLUSIONS Current advertisement/packaging of commercial surgical mitral valves is not uniform. This study demonstrates marked variations in hemodynamics, valve opening area and anatomic dimensions between similar sized mitral bioprostheses. These data suggest a critical need for standardization and close scientific evaluation of surgical mitral bioprostheses to ensure optimal clinical outcomes.

Background Transesophageal echocardiogram is currently the standard preprocedural imaging for left atrial appendage occlusion. This study aimed to assess the additive value of preprocedural computed tomography (CT) planning versus stand‐alone transesophageal echocardiogram imaging guidance to left atrial appendage occlusion. Methods and Results We retrospectively reviewed 485 Watchman implantations at a single center to compare the outcomes of using additional CT preprocedural planning (n=328, 67.6%) versus stand‐alone transesophageal echocardiogram guidance (n=157, 32.4%) for left atrial appendage occlusion. The primary end point was the rate of successful device implantation without major peri‐device leak (>5 mm). Secondary end points included major adverse events, total procedural time, delivery sheath and devices used, risk of major peri‐device leak and device‐related thrombus at follow‐up imaging. A single/anterior‐curve delivery sheath was used more commonly in those who underwent CT imaging (35.9% versus 18.8%; P P =0.02), a shorter procedural time (median, 45.5 minutes versus 51.0 minutes; P =0.03) and a less frequent change of device size (5.6% versus 12.1%; P =0.01), particularly device upsize (4% versus 9.4%; P =0.02). However, there was no significant difference in the risk of major adverse events (2.1% versus 1.9%; P =0.87). Only 1 significant peri‐device leak (0.2%) and 5 device‐related thrombi were detected in follow‐up (1.2%) with no intergroup difference. Conclusions Additional preprocedural planning using CT in Watchman implantation was associated with a higher successful device implantation rate, a shorter total procedural time, and a less frequent change of device sizes.

OBJECTIVES To compare in-hospital outcomes of bailout support to prophylactic support with percutaneous ventricular assist devices (pVAD) for high-risk nonemergent percutaneous coronary intervention (HRPCI). BACKGROUND Prophylactic support with pVAD for a HRPCI is used in patients felt to be at risk for hemodynamic collapse during PCI. An alternative strategy of bailout pVAD support in the event of hemodynamic collapse is also entertained. METHODS We compared the outcomes of patients entered in the cVAD database who underwent Impella Protected PCI (ProPCI group) with patients from the cVAD and USpella databases receiving bailout Impella support for hemodynamic collapse during HRPCI (Bailout group). RESULTS A total of 1,028 patients supported with Impella pVAD were entered into the cVAD database as of July 2019 and were included in this analysis. Of those 971 were in the ProPCI group and 57 in the Bailout group. Patients in the Bailout group were more often female (50.9%vs. 27.2%, p = .0002) with higher median baseline left ventricular ejection fraction (LVEF) (40%vs. 30%, p

BACKGROUND Due to elevated surgical risk, transcatheter mitral valve replacement (TMVR) is used as an alternative for treating failed bioprosthetic valves, annuloplasty repairs and mitral annular calcification (MAC). We report the procedural and longitudinal outcomes for each subtype: Mitral valve-in-valve (MVIV), mitral valve-in-ring (MViR), and valve-in-MAC (ViMAC). METHODS Consecutive patients undergoing TMVR from October 2013 to December 2019 were assessed. Patients at high risk for left ventricular outflow tract obstruction had either alcohol septal ablation or intentional laceration of the anterior leaflet (LAMPOON). RESULTS Eight-eight patients underwent TMVR; 38 MViV, 31 MViR, and 19 ViMAC procedures were performed. The median Society of Thoracic Surgery 30-day predicted risk of mortality was 8.2% (IQR 5.2, 19.9) for all. Sapien 3 (78%) and transseptal access (98%) were utilized in most cases. All-cause in-hospital mortality, technical, and procedural success were 8%, 83%, and 66% respectively. Median follow up was 1.4 years (IQR 0.5-2.9 years) and overall survival was 40% at 4 years. Differential survival rates were observed with MViV doing the best, followed by MViR and ViMAC having a

In patients with challenging femoral vein anatomy, transcatheter patent foramen ovale (PFO) closure can be safely and effectively be done through the jugular veins guided by ICE from the arm. This novel technique can potentially save resources (anesthesia and TEE) and provide an option for patients without a femoral option.

Despite advances in cardiovascular care, managing cardiogenic shock caused by structural heart disease is challenging. Patients with cardiogenic shock are critically ill upon presentation and require early disease recognition and rapid escalation of care. Temporary mechanical circulatory support provides a higher level of care than current medical therapies such as vasopressors and inotropes. This review article focuses on the role of hemodynamic monitoring, mechanical circulatory support, and device selection in patients who present with cardiogenic shock due to structural heart disease. Early initiation of appropriate mechanical circulatory support may reduce morbidity and mortality.

Anal cancer is a relatively rare cancer with 660 cases diagnosed in 2000–2015 in Ireland (1). The current standard treatment is radical chemoradiotherapy (CRT). The aim of our study was to review the treatment and outcomes of patients with localised anal squamous cell carcinoma (SCC), who received radical treatment in our radiation oncology network between 2008 and 2014 inclusive. Data were collected retrospectively from ARIA® oncology information system and patient charts. Statistical analyses were performed using IBM® SPSS® statistical software version 25.0. Seventy-nine cases of anal SCC were identified. Mean age of patients at commencement of radiotherapy (RT) was 60.2 years (standard deviation: 13.1 years). The most common total RT dose was 50.4 Gy in 28 fractions (N = 58; 73.4%). Median follow-up was 5.6 years. Two (2.6%) patients had persistent disease, seventeen (21.8%) patients developed loco-regional recurrence and nine (11.5%) patients developed solid organ metastases, four of whom had complete treatment response at the primary site. Eight patients underwent salvage anal surgery following completion of RT. Median overall survival was 10.5 years (95% confidence interval (CI) 5.1–15.8 years), median loco-regional relapse-free survival was 10.4 years (95% CI 4.4–16.3 years) and median disease-free survival was 9.3 years (95% CI 6.3–12.2 years). Our study demonstrates that treatment for anal SCC and outcomes following definitive CRT in Ireland during the study period were comparable to international standards.

Severe symptomatic tricuspid regurgitation (TR) remains an undertreated disease. Multiple trans-catheter treatment options are currently under investigation. Transcatheter caval valve implantation (CAVI) has been utilized as a treatment option and aims at decreasing or eliminating the caval backflow that occurs in severe TR patients. Understanding challenges with this therapy is paramount. Hereby we present a CAVI case with resultant non-coaptation of valve leaflets in a patient with a prominent Eustachian ridge.

Introduction: Non-white patients have been reported to face barriers to left atrial appendage occlusion (LAAO). Hypothesis: We hypothesized that white vs. non-white patients would have disparate wait times for and post-procedural treatment course after LAAO. Methods: We identified consecutive patients undergoing LAAO (Watchman TM ) at our institution between November 2015 - March 2020. In white vs. non-white patients, we compared patient characteristics, indications for LAAO, procedural wait time from index event (IE) and cardiology encounter to LAAO procedure, complications, post-procedure anticoagulation regimen, and adherence to 45-day post-procedural transesophageal echocardiogram (TEE). Results: Of 109 consecutive patients receiving LAAO implants, 45% were white (n = 49). White patients were less likely to have prior cerebral vascular accident (14% vs. 43%, p=0.001), heart failure (18% vs. 48%, p=0.001), and end stage renal disease (0% vs. 20%, p Conclusions: Whites and non-whites had similar indications for LAAO, procedural wait time, risk of procedural complications, and adherence to post-procedural TEE, despite a higher burden of co-morbidities. White patients may be more likely to be discharged on oral anticoagulation.

PURPOSE Non-white patients are underrepresented in left atrial appendage occlusion (LAAO) trials, and racial disparities in LAAO periprocedural management are unknown. METHODS We assessed sociodemographics and comorbidities of consecutive patients at our institution undergoing LAAO between 2015 and 2020, then in adjusted analyses, compared procedural wait time, procedural complications, and post-procedure oral anticoagulation (OAC) use in whites versus non-whites. RESULTS Among 109 patients undergoing LAAO (45% white), whites had lower CHA2 DS2 VASc scores, on average, than non-whites (4.0 vs. 4.8, p = .006). There was no difference in median time from index event (IE) or initial outpatient cardiology encounter to LAAO procedure (whites 10.5 vs. non-whites 13.7 months, p = .9; 1.9 vs. 1.8 months, p = .6, respectively), and there was no difference in procedural complications (whites 4% vs. non-whites 5%, p = .33). After adjusting for CHA2 DS2 VASc score, OAC use at discharge tended to be higher in whites (OR 2.4, 95% CI [0.9-6.0], p = .07). When restricting the analysis to those with prior gastrointestinal (GI) bleed, adjusting for CHA2 DS2 VASc score and GI bleed severity, whites had a nearly five-fold odds of being discharged on OAC (OR 4.6, 95% CI [1-21.8], p = 0.05). The association between race and discharge OAC was not mediated through income category (total mediation effect 19% 95% CI [-.04-0.11], p = .38). CONCLUSION Despite an increased prevalence of comorbidities amongst non-whites, wait time for LAAO and procedural complications were similar in whites versus non-whites. Among those with prior GI bleed, whites were nearly five-fold more likely to be discharged on OAC than non-whites, independent of income.

Importance Among those with aortic stenosis, natriuretic peptide levels can provide risk stratification, predict symptom onset, and aid decisions regarding the timing of valve replacement. Less is known about the prognostic significance and potential clinical utility of natriuretic peptide levels measured after valve replacement. Objective To determine the associations of elevated B-type natriuretic peptide (BNP) levels after transcatheter aortic valve replacement (TAVR) and change in BNP levels between follow-up time points with risk of subsequent clinical outcomes. Design, Setting, and Participants In this cohort study, patients with severe symptomatic aortic stenosis at intermediate, high, or prohibitive surgical risk for aortic valve replacement who underwent TAVR from the PARTNER IIA cohort, PARTNER IIB cohort, SAPIEN 3 intermediate-risk registry, and SAPIEN 3 high-risk registry were included. B-type natriuretic peptide levels were obtained at baseline and discharge as well as 30 days and 1 year after TAVR. For each measurement, a BNP ratio was calculated using measured BNP level divided by the upper limit of normal for the assay used. Outcomes were evaluated in landmark analyses out to 2 years. Data were collected from April 2011 to January 2019. Main Outcomes and Measures All-cause death, cardiovascular death, rehospitalization, and the combined end point of cardiovascular death or rehospitalization. Results Among 3391 included patients, 1969 (58.1%) were male, and the mean (SD) age was 82 (7.5) years. Most patients had a BNP ratio greater than 1 at each follow-up time point, including 2820 of 3256 (86.6%) at baseline, 2652 of 2995 (88.5%) at discharge, 1779 of 2209 (80.5%) at 30 days, and 1799 of 2391 (75.2%) at 1 year. After adjustment, every 1-point increase in BNP ratio at 30 days (approximately equivalent to an increase of 100 pg/mL in BNP) was associated with an increased hazard of all-cause death (adjusted hazard ratio [aHR], 1.11; 95% CI, 1.07-1.15), cardiovascular death (aHR, 1.16; 95% CI, 1.11-1.21), and rehospitalization (aHR, 1.08; 95% CI, 1.03-1.14) between 30 days and 2 years. Among those with a BNP ratio of 2 or more at discharge, after adjustment, every 1-point decrease in BNP ratio between discharge and 30 days was associated with a decreased hazard of all-cause death (aHR, 0.92; 95% CI, 0.88-0.96) between 30 days and 2 years. Conclusions and Relevance Elevated BNP levels after TAVR was independently associated with increased subsequent mortality and rehospitalizations. Further studies to determine how best to mitigate this risk are warranted.

A paucity of randomized phase III clinical trials in primary central nervous system lymphoma (PCNSL) has resulted in no uniform consensus on the optimal strategy for consolidation and conditioning regimens for autologous stem cell transplant (ASCT). The past 2 decades have witnessed a preference for thiotepa (TT)-based conditioning regimens due to superior central nervous system penetration. We retrospectively evaluated outcomes of patients with PCNSL who underwent ASCT at Mayo Clinic, Rochester over the past 2 decades, and the impact of TT-based conditioning regimens. Fifty-six patients underwent transplant for PCNSL, with 25 and 31 patients receiving BEAM (non-thiotepa) and carmustine (BCNU)/TT-based conditioning, respectively. All patients received high-dose methotrexate-based induction therapy. While the BCNU/TT group had higher risk disease features such as high International Extranodal Lymphoma Study Group prognostic score, elevated cerebrospinal fluid protein, and older patient population, there was no significant difference at 2 years post-transplant in progression-free survival (BEAM 68.0% [46.1% to 82.5%] versus BCNU/TT, 65.5% [45.2% to 79.8%], P = .99) or overall survival (OS) (84.0% [62.8% to 93.7%] in the BEAM group versus 81.6% [61.3% to 91.9%] in the BCNU/TT group, P = .95). Disease response status before transplant significantly affected the outcomes as those in complete remission had an OS at 2 years post-transplant of 94.7% (68.1% to 99.2%) in the BEAM group and 90.5% (67.0% to 97.5%) in the BCNU/TT group compared with those in partial response, 57.1% (17.2% to 83.7%) in BCNU/TT group and 50.0% (11.1% to 80.4%) in the BEAM group, respectively (P.0001). Our retrospective cohort adds to the currently available literature and identifies the disease status before transplant as a significant factor affecting survival.

The tricuspid valve is a highly complex structure, with variability in the number of leaflets and scallops. The mechanism of regurgitation is multifactorial in etiology, a mix of functional and degenerative tricuspid regurgitation. Iatrogenic tricuspid regurgitation is becoming more common secondary to pacemaker wire impingement of leaflet function and coaptation. Echocardiographic imaging of the tricuspid valve is particularly challenging given its anatomic location and other interfering structures, including pacemaker wires. Preprocedural planning and intraprocedural guidance for transcatheter intervention relies on a comprehensive understanding of tricuspid anatomy and the use of 3-dimensional transesophageal echocardiography. The incorporation of computed tomography and cardiac magnetic resonance imaging likely will provide increasing accuracy and optimization of procedural success.

The use of the Watchman left atrial appendage occlusion device (Boston Scientific Inc.) is becoming increasingly frequent in patients with atrial fibrillation. Cardiac computed tomography (CT) for device sizing pre-procedure can help facilitate more accurate device selection compared with transesophageal echo (TEE) alone. CT can also help identify minor lobes and trabeculations that may not be apparent on TEE. We report a series of three cases to highlight the utility of a novel application of CT-TEE fusion imaging to provide procedural guidance during Watchman implant and to assess for peri-device leak post-implant.

Purpose: Glioblastoma is the most frequent and lethal primary brain tumor. Development of novel therapies relies on the availability of relevant preclinical models. We have established a panel of 96 glioblastoma patient-derived xenografts (PDX) and undertaken its genomic and phenotypic characterization. Experimental Design: PDXs were established from glioblastoma, IDH-wildtype (n = 93), glioblastoma, IDH-mutant (n = 2), diffuse midline glioma, H3 K27M-mutant (n = 1), and both primary (n = 60) and recurrent (n = 34) tumors. Tumor growth rates, histopathology, and treatment response were characterized. Integrated molecular profiling was performed by whole-exome sequencing (WES, n = 83), RNA-sequencing (n = 68), and genome-wide methylation profiling (n = 76). WES data from 24 patient tumors was compared with derivative models. Results: PDXs recapitulate many key phenotypic and molecular features of patient tumors. Orthotopic PDXs show characteristic tumor morphology and invasion patterns, but largely lack microvascular proliferation and necrosis. PDXs capture common and rare molecular drivers, including alterations of TERT, EGFR, PTEN, TP53, BRAF, and IDH1, most at frequencies comparable with human glioblastoma. However, PDGFRA amplification was absent. RNA-sequencing and genome-wide methylation profiling demonstrated broad representation of glioblastoma molecular subtypes. MGMT promoter methylation correlated with increased survival in response to temozolomide. WES of 24 matched patient tumors showed preservation of most genetic driver alterations, including EGFR amplification. However, in four patient–PDX pairs, driver alterations were gained or lost on engraftment, consistent with clonal selection. Conclusions: Our PDX panel captures the molecular heterogeneity of glioblastoma and recapitulates many salient genetic and phenotypic features. All models and genomic data are openly available to investigators.