The somatic genomic landscape of glioblastoma.

We describe the landscape of somatic genomic alterations based on multidimensional and comprehensive characterization of more than 500 glioblastoma tumors (GBMs). We identify several novel mutated genes as well as complex rearrangements of signature receptors, including EGFR and PDGFRA. TERT promoter mutations are shown to correlate with elevated mRNA expression, supporting a role in telomerase reactivation. Correlative analyses confirm that the survival advantage of the proneural subtype is conferred by the G-CIMP phenotype, and MGMT DNA methylation may be a predictive biomarker for treatment response only in classical subtype GBM. Integrative analysis of genomic and proteomic profiles challenges the notion of therapeutic inhibition of a pathway as an alternative to inhibition of the target itself. These data will facilitate the discovery of therapeutic and diagnostic target candidates, the validation of research and clinical observations and the generation of unanticipated hypotheses that can advance our molecular understanding of this lethal cancer.

Clinical characteristics and outcomes of alcohol septal ablation in the era of transcatheter valve interventions.

BACKGROUND: The clinical efficacy and safety of alcohol septal ablation (ASA) for obstructive hypertrophic cardiomyopathy (HCM) have been well-established; however, less is known about outcomes in patients undergoing preemptive ASA before transcatheter mitral valve replacement (TMVR). AIMS: The goal of this study is to characterize the procedural characteristics and examine the clinical outcomes of ASA in both HCM and pre-TMVR. METHODS: This retrospective study compared procedural characteristics and outcomes in patient who underwent ASA for HCM and TMVR. RESULTS: In total, 137 patients were included, 86 in the HCM group and 51 in the TMVR group. The intraventricular septal thickness (mean 1.8 vs. 1.2 cm; p < 0.0001) and the pre-ASA LVOT gradient (73.6 vs. 33.8 mmHg; p ≤ 0.001) were higher in the HCM group vs the TMVR group. The mean volume of ethanol injected was higher (mean 2.4 vs. 1.7 cc; p < 0.0001). The average neo-left ventricular outflow tract area increased significantly after ASA in the patients undergoing TMVR (99.2 ± 83.37 mm2 vs. 196.5 ± 114.55 mm2; p = <0.0001). The HCM group had a greater reduction in the LVOT gradient after ASA vs the TMVR group (49.3 vs. 18 mmHg; p = 0.0040). The primary composite endpoint was higher in the TMVR group versus the HCM group (50.9% vs. 25.6%; p = 0.0404) and had a higher incidence of new permanent pacemaker (PPM) (25.5% vs. 18.6%; p = 0.3402). The TMVR group had a higher rate of all-cause mortality (9.8% vs. 1.2%; p = 0.0268). CONCLUSIONS: Preemptive ASA before TMVR was performed in patients with higher degree of clinical comorbidities, and correspondingly is associated with worse short-term clinical outcomes in comparison to ASA for HCM patients. ASA before TMVR enabled percutaneous mitral interventions in a small but significant minority of patients that would have otherwise been excluded. The degree of LVOT and neoLVOT area increase is significant and predictable.

Permutations in pacer wire implantation in patients evaluated for transcatheter tricuspid valve interventions.

Pacer wire induced tricuspid regurgitation is not well-understood. The mechanisms behind pacer wired induced tricuspid regurgitation have not been clearly defined. This clinical vignette sets to identify different technical mechanisms behind cardiac lead induced tricuspid regurgitation to help optimize cardiac lead implantation strategies for future device implantation.

3D print and multi-modality imaging guided transcatheter closure of multiple left ventricular pseudoaneurysms.

Left ventricular pseudoaneurysm (PSA) after surgical aortic valve replacement (AVR) is a known but uncommon complication. It is associated with risks such as thromboembolism and life-threatening rupture. Surgical repair has traditionally been utilized in low-risk patients but transcatheter closure has become a promising therapeutic option. This case report describes the utility of multimodality imaging in pre-, intra-, and post-procedural evaluation of transcatheter PSA closure and is among the first to demonstrate the utility of 3D print model.

Comparative differences of mitral valve-in-valve implantation: A new mitral bioprosthesis versus current mosaic and epic valves.

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.

Initial in-human experience with the conveyor cardiovascular system for the delivery of large profile transcatheter valve devices.

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.

Transcatheter vacuum-assisted left-sided mass extraction with the AngioVac system.

OBJECTIVES: To study the safety and efficacy of AngioVac for left-sided transcatheter vacuum-assisted mass extraction (TVME). BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Pacemaker following transcatheter aortic valve replacement and tricuspid regurgitation: A single-center experience.

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 < 29 mm in diameter in size, 25% (11/44) had worsening TR. In patients who received a TAVR device ≥ 29 mm in diameter, 37% (14/38) had worsening TR. CONCLUSION: We have demonstrated a patient population that may be predisposed to developing worsening TR and right heart function after TAVR and Pacemaker implantation.

The prognostic value of initial serum lactate for survival in postcardiac arrest patients undergoing cardiac catheterization.

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 < .05). When divided into tertiles by serum lactate (< 4.5, 4.5-9, 9 mmol/L), survival to discharge was 75, 29.4, and 17.6%, respectively (p < .05). Initial serum lactate and age were independent predictors of in-hospital mortality. CONCLUSIONS: In patients undergoing cardiac catheterization following cardiac arrest, routine measurement of serum lactate is a useful and available laboratory test that may help identify patients at risk for a poor outcome.

Outcomes of bailout percutaneous ventricular assist device versus prophylactic strategy in patients undergoing nonemergent percutaneous coronary intervention.

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 < .0001) and with lower prevalence of both heart failure (42.1%vs. 56.9%, p = .0385) and left main disease (40.0%vs. 56.1%, p = .0250) compared to the ProPCI group. Unadjusted and adjusted in-hospital mortality was significantly higher in the Bailout group (49.1%vs. 4.3%, and 57.8%vs. 4.4%, p < .0001 for both). CONCLUSIONS: In our study population, the bailout group was associated with significant increased mortality compared to ProPCI group. Female gender was more frequently observed in patients requiring bailout pVAD. Further investigation is warranted in order to generalize the findings of our study.

Short- and mid-term outcomes in percutaneous mitral valve replacement using balloon expandable valves.

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 <20% survival at 4 years. After adjusting for co-variates, MViV procedure was the strongest predictor of survival (HR 0.24 [95% CI 0.079-0.7]). CONCLUSION: TMVR is performed in at high-risk patients with attenuated long-term survival. MViV has the best success and survival rate, but long-term survival in MViR and ViMAC is guarded.

Comparison of a new bioprosthetic mitral valve to other commercially available devices under controlled conditions in a porcine model.

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.

Low and elevated B-type natriuretic peptide levels are associated with increased mortality in patients with preserved ejection fraction undergoing transcatheter aortic valve replacement: an analysis of the PARTNER II trial and registry.

AIMS: B-type natriuretic peptide (BNP) is a cardiac neurohormone that is secreted in response to ventricular volume expansion and pressure overload. There are conflicting data regarding the association between BNP levels and outcomes after transcatheter aortic valve replacement (TAVR). We therefore sought to assess the association between baseline BNP and adverse outcomes in patients with symptomatic, severe aortic stenosis (AS), and left ventricular ejection fraction (LVEF) ≥50%, undergoing TAVR in the PARTNER 2 Trial and Registry. METHODS AND RESULTS: A total of 1782 patients were included in the analysis, and BNP was evaluated both as a continuous log-transformed value and by a priori categories: low (<50 pg/mL), normal (≥50 and <100 pg/mL), moderately elevated (≥100 and <400 pg/mL), or markedly elevated (≥400 pg/mL). Clinical outcomes from discharge to 2 years were compared between patients according to their baseline BNP level, using Kaplan-Meier event rates and multivariable Cox proportional hazards regression models. After adjustment, spline curves revealed a non-linear association between log-transformed BNP and all-cause and cardiovascular mortality in which both the lowest and highest values were associated with increased mortality. Two-year all-cause mortality rates for those with low (n = 86), normal (n = 202), moderately elevated (n = 885), and markedly elevated (n = 609) baseline BNP were 20.0%, 9.8%, 17.7%, and 26.1%, respectively. In adjusted models, compared to a normal baseline BNP, low [adjusted hazard ratio (HR) 2.6, 95% confidence interval (CI) 1.3-5.0, P-value 0.005], moderately elevated (adjusted HR 1.6, 95% CI 1.0-2.6, P-value 0.06), and markedly elevated (adjusted HR 2.1, 95% CI 1.3-3.5, P-value 0.003) BNP were associated with increased all-cause mortality, driven by cardiovascular mortality. CONCLUSIONS: In a large cohort of patients with severe symptomatic AS and preserved LVEF undergoing TAVR, all-cause and cardiovascular mortality rates at 2 years were higher in patients with low and markedly elevated BNP levels. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/ unique identifier #NCT01314313, #NCT02184442, #NCT03222128, and #NCT03222141.

Glioma Groups Based on 1p/19q, IDH, and TERT Promoter Mutations in Tumors.

BACKGROUND: The prediction of clinical behavior, response to therapy, and outcome of infiltrative glioma is challenging. On the basis of previous studies of tumor biology, we defined five glioma molecular groups with the use of three alterations: mutations in the TERT promoter, mutations in IDH, and codeletion of chromosome arms 1p and 19q (1p/19q codeletion). We tested the hypothesis that within groups based on these features, tumors would have similar clinical variables, acquired somatic alterations, and germline variants. METHODS: We scored tumors as negative or positive for each of these markers in 1087 gliomas and compared acquired alterations and patient characteristics among the five primary molecular groups. Using 11,590 controls, we assessed associations between these groups and known glioma germline variants. RESULTS: Among 615 grade II or III gliomas, 29% had all three alterations (i.e., were triple-positive), 5% had TERT and IDH mutations, 45% had only IDH mutations, 7% were triple-negative, and 10% had only TERT mutations; 5% had other combinations. Among 472 grade IV gliomas, less than 1% were triple-positive, 2% had TERT and IDH mutations, 7% had only IDH mutations, 17% were triple-negative, and 74% had only TERT mutations. The mean age at diagnosis was lowest (37 years) among patients who had gliomas with only IDH mutations and was highest (59 years) among patients who had gliomas with only TERT mutations. The molecular groups were independently associated with overall survival among patients with grade II or III gliomas but not among patients with grade IV gliomas. The molecular groups were associated with specific germline variants. CONCLUSIONS: Gliomas were classified into five principal groups on the basis of three tumor markers. The groups had different ages at onset, overall survival, and associations with germline variants, which implies that they are characterized by distinct mechanisms of pathogenesis. (Funded by the National Institutes of Health and others.).

Intermediate term hemodynamic effects of single inferior vena cava valve implant for the treatment of severe tricuspid regurgitation.

Severe tricuspid regurgitation (TR) remains a vastly undertreated disease, with sustained elevation of right atrial (RA) pressure directly resulting in chronic end-organ damage. Recently, bi-caval valve implantation has been shown to improve symptoms in patients with symptomatic TR who are at high risk for surgery. We present the first report of intermediate term hemodynamic effects of single inferior vena cava (IVC) valve implantation (CAVI) for treatment of severe TR. We performed CAVI on a 66-year-old female with severe TR, who suffered from repeat hospitalizations for treatment refractory NYHA class III-IV heart failure symptoms and had prohibitive operative risk. Pre-implantation right heart catheterization (RHC) revealed a mean RA pressure of 12 mm Hg, an IVC mean pressure of 13 mm Hg, with V-waves to 16 and 18 mm Hg in the RA and IVC respectively, and a cardiac output (CO) of 3.5 liters per minute (LPM). Postprocedure, mean IVC and RA pressures decreased to 11 and 10 mm Hg, respectively, with CO increasing to 5.1 LPM. At one month, symptoms improved to NYHA class II. At 9 months, mean RA pressure was 5 mm Hg with V-waves to 7 mm Hg and an improvement in CO to 6.3 LPM. CAVI appears to result in similar decreases in RA pressure at intermediate follow-up as compared to bi-caval valve implantation. The favorable hemodynamic effects were likely mediated by redirection of regurgitant blood flow away from the IVC thereby resulting in sustained reduction in right-sided pressures as well as an increase in CO. © 2017 Wiley Periodicals, Inc.

Study design and rationale of the heterotopic implantation of the Edwards-Sapien XT transcatheter valve in the inferior VEna cava for the treatment of severe tricuspid regurgitation (HOVER) trial.

BACKGROUND: Tricuspid regurgitation (TR) is an under treated disease. Although surgery for TR remains an effective therapy, many patients are considered to be at a high risk or otherwise inoperable. Caval valve implant (CAVI) offers an alternative to surgery in these patients. Trials assessing the safety and efficacy of caval valve implant are lacking. METHODS: The Heterotopic Implantation Of the Edwards-Sapien XT Transcatheter Valve in the Inferior VEna cava for the treatment of severe Tricuspid Regurgitation (HOVER) trial is an FDA approved, physician initiated, prospective, non-blinded (open label), non-randomized safety and feasibility study to determine the safety and efficacy of the heterotopic implantation of the Edwards-Sapien XT valve in the inferior vena cava for the treatment of severe TR in patients who are at high risk or inoperable. Patients with severe TR in the absence of severe pulmonary hypertension will be recruited. They will be evaluated by a multi-disciplinary team who will agree by consensus that the patients' symptoms are from TR. They will undergo imaging to assess the size of the inferior vena cava (IVC) to determine feasibility of the procedure. If patients meet the inclusion criteria and are free from exclusion criteria, after informed consent they will be eligible for enrollment in the study. A total of 30 patients will be enrolled. The primary objective of the study will be to demonstrate procedural success at 30-days and patient success at 1-year. CONCLUSION: Caval valve implant may present an alternative for patients who are at high risk or inoperable for tricuspid valve surgery (TVS) for TR. © 2016 Wiley Periodicals, Inc.

Long-term outcomes associated with the transaortic approach to transcatheter Aortic valve replacement.

OBJECTIVE: We investigated the long-term safety, efficacy and clinical outcomes associated with transaortic (TAO) transcatheter aortic valve replacement (TAVR) in the United States. BACKGROUND: We previously reported the technical feasibility and short-term safety of TAO TAVR. Compared to transapical (TAP) access, the TAO approach was associated with shorter median intensive care unit (ICU) length of stay (LOS) and more favorable technical learning curve. However, outcomes data beyond 30 days were lacking and the longer-term clinical consequences of this strategy were unknown. METHODS: Mortality outcomes at 1 year (and longer) of 44 consecutive patients who underwent TAO TAVR in our institution were compared with that of 76 consecutive patients who underwent TAP TAVR at our site. Risk-adjusted analysis was performed in propensity-matched patients (25 from each group) to account for baseline differences. RESULTS: TAO TAVR was associated with a trend towards lower all-cause mortality at 1 year compared to TAP TAVR (18% vs. 34%, P=0.09 in the overall sample; 12% vs. 40%, P=0.05 in the matched cohort). The higher probability of survival with TAO TAVR persisted after a median follow-up period of 23 months (hazard ratio [HR]=1.96, P=0.06 in the overall sample; HR=3.4, P=0.01 in the matched cohort). Cardiovascular mortality at 1 year was lower with TAO TAVR (2% vs. 22%, P=0.01 in the overall sample; 4% vs. 28%, P=0.05 in the matched cohort). ICU LOS (shorter in the TAO group) and implantation of second prosthetic valve (higher incidence in the TAP group) were independent predictors of long-term mortality. CONCLUSION: The outcomes associated with TAO TAVR compare favorably with TAP TAVR. Our results appear to corroborate the long-term safety and efficacy of the TAO approach in TAVR patients with inadequate iliofemoral access.

Brain Tumor Epidemiology - A Hub within Multidisciplinary Neuro-oncology. Report on the 15th Brain Tumor Epidemiology Consortium (BTEC) Annual Meeting, Vienna, 2014.

The Brain Tumor Epidemiology Consortium (BTEC) is an open scientific forum, which fosters the development of multi-center, international and inter-disciplinary collaborations. BTEC aims to develop a better understanding of the etiology, outcomes, and prevention of brain tumors (http://epi.grants.cancer.gov/btec/). The 15th annual Brain Tumor Epidemiology Consortium Meeting, hosted by the Austrian Societies of Neuropathology and Neuro-oncology, was held on September 9 - 11, 2014 in Vienna, Austria. The meeting focused on the central role of brain tumor epidemiology within multidisciplinary neuro-oncology. Knowledge of disease incidence, outcomes, as well as risk factors is fundamental to all fields involved in research and treatment of patients with brain tumors; thus, epidemiology constitutes an important link between disciplines, indeed the very hub. This was reflected by the scientific program, which included various sessions linking brain tumor epidemiology with clinical neuro-oncology, tissue-based research, and cancer registration. Renowned experts from Europe and the United States contributed their personal perspectives stimulating further group discussions. Several concrete action plans evolved for the group to move forward until next year's meeting, which will be held at the Mayo Clinic at Rochester, MN, USA.

Clinical outcomes with on-label and off-label use of the transcatheter heart valve in the United States.

OBJECTIVE: We explored the efficacy, safety, and clinical consequences of on-label and off-label transcatheter aortic valve replacement (TAVR) in the real-world setting. BACKGROUND: The transcatheter heart valve (THV) was initially approved only for transfemoral (TF) delivery (on-label use) during TAVR in inoperable patients with severe aortic stenosis (AS). Because of lack of alternative options in TAVR-eligible patients with inadequate TF access, other routes have been utilized for THV implantation (off-label use), outcomes of which were previously unknown. METHODS: Consecutive patients with severe inoperable AS who underwent clinical TAVR at our site were enrolled in a prospective database. Fifty subjects underwent TF-TAVR (on-label group), while non-TF routes were utilized in 60 subjects (off-label group). Procedural events, 30-day clinical outcomes, and 1-year all-cause mortality data were analyzed. RESULTS: Technical device success was similar between on-label and off-label groups (88% vs. 87%, respectively; P = 0.92), as was the incidence of procedural complications and 30-day clinical events. The on-label group had lower 1-year all-cause death rate (12%) compared to the off-label group (32%; P = 0.02). The 1-year all-cause mortality in the off-label group was comparable to published clinical trial and registry data on TAVR, and appeared lower than historical outcomes with conservative medical therapy. CONCLUSION: On-label use of the THV in the real-world setting was associated with favorable survival outcomes compared to off-label TAVR and historical data. Off-label use of the THV appeared to be safe and effective when used in select patients with inoperable AS who are not eligible for TAVR via TF approach.

Impact of CMS coverage decision on access to transcatheter aortic valve replacement.

OBJECTIVES: To assess the impact of the Centers for Medicare and Medicaid Services (CMS) national coverage determination (NCD) on access for patients with aortic stenosis (AS) with transcatheter aortic valve replacement (TAVR) in a tertiary care center. BACKGROUND: TAVR has given hope to patients with AS who are deemed inoperable. The effects of the NCD on access to patients with AS has not been evaluated. MATERIALS AND METHODS: A total of 94 inoperable AS patients were evaluated and treated from December 2011 through June of 2012 with TAVR. Patients who underwent transfemoral (TF) vs. non-TF access were compared. The CMS NCD was released on May 1, 2012 and on July 1, 2012, the nontransfemoral access program was put on hold due to lack of reimbursement. RESULTS: Patients in the TF (n = 33) and non-TF access (n = 61) groups were similar in age (85.2 ± 6.3 vs. 84.8 ± 6.6 P = 0.74) and STS mortality (9.38 ± 5.33 vs. 7.91 ± 3.69, P = 0.074). The iliofemoral arteries were larger diameter in the TF group (7.72 ± 1.49 vs. 6.21 ± 1.78, P < 0.001) and males (7.39 ± 1.81 vs. 6.1 ± 1.61 P < 0.001). More women underwent valve implantation via non-TF access (73 vs. 23%, P = 0.03). After the NCD, 21 patients who previously qualified for non-TF TAVR would not be reimbursed by CMS. Four died soon after. CONCLUSIONS: After the NCD, the proportion of inoperable patients with severe AS that can be treated with TAVR was greatly reduced due the lack of reimbursement for TAVR via non-TF access. This effect is particularly pronounced in women. © 2014 Wiley Periodicals, Inc.