Impact of prior coronary artery bypass grafting and coronary lesion complexity on outcomes of transcatheter aortic valve replacement for severe aortic stenosis.

OBJECTIVE: To investigate the impact of prior coronary artery bypass grafting (CABG) and coronary lesion complexity on transcatheter aortic valve replacement (TAVR) outcomes for aortic stenosis. METHODS: Clinical outcomes of TAVR were retrospectively compared between patients with and without prior CABG, and between patients with prior CABG and without coronary artery disease (CAD). The impact of the CABG SYNTAX score was also evaluated in patients with prior CABG. RESULTS: The study included 1042 patients with a median age and follow-up of 82 years and 25 (range: 0-72) months, respectively. Of these, 175 patients had a history of CABG, while 401 were free of CAD. Patients with prior CABG were more likely to be male and had higher rates of diabetes, peripheral artery disease and atrial fibrillation compared with patients without prior CABG. After 2 : 1 propensity score matching, all-cause mortality (P = 0.17) and the composite of all-cause mortality, stroke and coronary intervention (P = 0.16) were similar between patients with (n = 166) and without (n = 304) prior CABG. A 1 : 1 propensity score-matched analysis, however, showed lower rates of all-cause mortality (P = 0.04) and the composite outcome (P = 0.04) in patients with prior CABG (n = 134) compared with patients without CAD (n = 134). The median CABG SYNTAX score was 16 (interquartile range: 9.0-23), which was not associated with better/worse clinical outcomes in patients with prior CABG. CONCLUSION: Prior CABG may positively affect mid-term TAVR outcomes for aortic stenosis compared with no CAD when adjusted for other comorbidities. The CABG SYNTAX score did not influence the prognosis after TAVR.

Impact of coronary artery disease and revascularization on outcomes of transcatheter aortic valve replacement for severe aortic stenosis.

BACKGROUND/PURPOSE: To evaluate the impact of coronary artery disease (CAD), percutaneous coronary intervention (PCI), and coronary lesion complexity on outcomes of transcatheter aortic valve replacement (TAVR) for aortic stenosis. METHODS/MATERIALS: This retrospective study included 1042 patients divided into two groups by the presence or absence of CAD (SYNTAX score 0, no history of revascularization). Propensity score matching was used to compare the two groups. The effect of PCI, SYNTAX score, and residual SYNTAX score was also analyzed. RESULTS: The median age of the cohort was 82 years, and 641 patients had CAD. After propensity score matching, 346 pairs were analyzed. During 5 years of follow-up (median: 25, range 0-72 months), the rate of coronary intervention was significantly higher in CAD patients (p = 0.018). However, all-cause mortality, composite of all-cause mortality, stroke, and coronary intervention, and overt bleeding defined by VARC-3 were comparable. After stratification, in patients with creatinine ≥1.5 mg/dl, CAD was associated with a worse composite outcome (p = 0.016). Neither PCI nor SYNTAX score was associated with all-cause mortality in CAD patients. Similarly, residual SYNTAX score showed no association with mortality in patients undergoing PCI (all p values >0.7). PCI did not reach a significant difference in overt bleeding in CAD patients (adjusted p = 0.06). CONCLUSIONS: Despite a higher incidence of coronary interventions, major clinical outcomes were similar between patients with and without CAD after TAVR. In patients with chronic kidney disease, CAD may be associated with an adverse composite outcome. Neither PCI nor SYNTAX/residual SYNTAX score influenced all-cause mortality.

Clinical utility of plasma Aß42/40 ratio by LC-MS/MS in Alzheimer's disease assessment.

Introduction: Plasma Aß42/40 ratio can help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear. Methods: Aß42/40 ratio was measured by LC-MS/MS for 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and for 6,192 consecutive clinical specimens submitted for Aß42/40 testing. Results: High diagnostic sensitivity and negative predictive value (NPV) for Aß-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aß42/40 values for individuals with positive vs. negative Aß-PET results. Assuming a moderate prevalence of Aß-PET positivity, a cutpoint was identified with 99% NPV, which could help predict that AD is likely not the cause of patients' cognitive impairment and help reduce PET evaluation by about 40%. Conclusion: High-throughput plasma Aß42/40 LC-MS/MS assays can help identify patients with low likelihood of AD pathology, which can reduce PET evaluations, allowing for cost savings.

Improved Hemodynamics With Self-Expanding Compared to Balloon-Expandable Transcatheter Aortic Valve Implantation in Small Annulus Patients: A Propensity-Matched Analysis.

Patients with small aortic annuli (SAAs) pose a challenge in patients who underwent aortic valve replacement because of the potential for prosthesis-patient mismatch (PPM). This study aimed to compare the clinical and hemodynamic outcomes of self-expandable valve (SEV) versus balloon-expandable valve (BEV) transcatheter aortic valve implantation (TAVI) in patients with severe aortic stenosis and SAAs. All patients who underwent TAVI for severe native aortic stenosis with an SAA between January 2018 and December 2022 were retrospectively included in the study from a single center. Propensity score matching was performed to balance the baseline characteristics. Bioprosthesis valve dysfunction was based on modified Valve Academic Research Consortium 3 criteria. A total of 1,170 TAVI procedures were performed between 2018 and 2022. After applying the exclusion criteria, 332 patients reported an SAA at computed tomography scan, and the matching created 109 balanced pairs. Echocardiographic data at discharge showed higher mean transvalvular gradients (p <0.001), higher grades of mitral regurgitation (p = 0.029), and lower ejection fraction (p <0.043) in BEVs than SEVs. At follow-up, significant differences favoring the SEV group regarding bioprosthesis valve dysfunction were observed (p = 0.002), especially in terms of severe PPM (p = 0.046) and at least moderate structural valve deterioration (p = 0.040). In conclusion, TAVI in patients with SAAs using a BEV was associated with lower valve areas, higher mean pressure gradients, and PPM (including severe) than a SEV. Short- and midterm all-cause and cardiac-related mortality did not differ between the 2 groups. Future randomized studies with extended follow-ups are warranted to validate these outcomes.

New plasma LC-MS/MS assays for the quantitation of beta-amyloid peptides and identification of apolipoprotein E proteoforms for Alzheimer's disease risk assessment.

Early detection of Alzheimer's disease (AD) represents an unmet clinical need. Beta-amyloid (Aß) plays an important role in AD pathology, and the Aß42/40 peptide ratio is a good indicator for amyloid deposition. In addition, variants of the apolipoprotein E (APOE) gene are associated with variable AD risk. Here, we describe the development and validation of high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays for plasma Aß40 and Aß42 quantitation, as well as apolipoprotein E (ApoE) proteotype determination as a surrogate for APOE genotype. Aß40 and Aß42 were simultaneously immunoprecipitated from plasma, proteolytically digested, and quantitated by LC-MS/MS. ApoE proteotype status was qualitatively assessed by targeting tryptic peptides from the ApoE2, ApoE3, and ApoE4 proteoforms. Both assays were validated according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. Within-run precision was 1.8%-4.2% (Aß40), 1.9%-7.2% (Aß42), and 2.6%-8.3% (Aß42/40 ratio). Between-run precision was 3.5%-5.9% (Aß40), 3.8%-8.0% (Aß42), and 3.3%-8.7% (Aß42/40 ratio). Both Aß40 and Aß42 were linear from 10 to 2500 pg/mL. Identified ApoE proteotypes had 100% concordance with APOE genotypes. We have developed a precise, accurate, and sensitive high-throughput LC-MS/MS assay for plasma Aß40, Aß42, and proteoforms of ApoE.

Direct aortic cannulation versus femoral arterial cannulation for early outcomes in acute type A aortic dissection: A study-level meta-analysis.

PURPOSE: To investigate the impact of direct aortic cannulation (DAC) versus femoral arterial cannulation (FAC) on clinical outcomes of surgery for acute type A aortic dissection. METHODS: PubMed/MEDLINE, Scopus, and Cochrane Central Register of Controlled Trials were searched until August 25, 2023, to conduct a meta-analysis. Primary endpoints of the study were operative mortality and postoperative stroke. Secondary endpoints were cardiopulmonary bypass time, myocardial ischemic time, hypothermic circulatory arrest time, temporary neurological dysfunction (TND), combined stroke and TND, re-exploration for bleeding, and need for renal replacement therapy. A random-effect model was used to estimate the pooled effect size, and a leave-one-out method was used for the primary endpoints for sensitivity analysis. RESULTS: 15 studies met our eligibility criteria, including a total of 7941 samples. Operative mortality was significantly lower in the DAC group with a pooled odds ratio (OR) of 0.72 [95% confidence interval (CI): 0.61-0.85)]. Incidence of postoperative stroke was also lower in the DAC group with a pooled OR of 0.79 (95% CI: 0.66-0.94). However, after excluding one study with the greatest weight, the difference became nonsignificant. DAC was also associated with a lower incidence of postoperative TND, and re-exploration for bleeding with a pooled OR of 0.52 (95% CI: 0.37-0.73), and 0.60 (95% CI: 0.47-0.77), respectively. CONCLUSIONS: This meta-analysis showed that patients who underwent ATAAD repair with DAC had a lower incidence of operative mortality, postoperative stroke, TND, and re-exploration for bleeding compared to those who underwent FAC.

Impact of mitral stenosis on early and late outcomes of transcatheter aortic valve replacement for aortic stenosis: a single-center analysis.

OBJECTIVES: To assess the impact of concomitant mitral stenosis (MS) on early and late outcomes of transcatheter aortic valve replacement (TAVR) for aortic stenosis. METHODS: This study involved 952 patients undergoing TAVR for severe tricuspid aortic stenosis. The patients were classified into 3 groups: without MS, with progressive MS, and severe MS (mitral valve area ≤ 1.5 cm2). Clinical outcomes between these groups were compared. RESULTS: The median age of the overall cohort was 82 years, and patients in the progressive (n = 49) and severe (n = 24) MS groups were more likely to be female than those in the no-MS group (n = 879). Periprocedural mortality rate was lowest in the no-MS group (1.8%) compared with the progressive (4.1%) and severe (4.2%) MS groups, which were not significantly different (P = .20). During 5 years of follow-up (median: 27, range: 0-72 months), there was no significant difference in all-cause mortality (log-rank P = .99), a composite of all-cause mortality or rehospitalization for heart failure (log-rank P = .84), or cardiovascular death (log-rank P = .57) between groups. Although crude analysis showed a significant difference in rehospitalization for heart failure in the severe MS group compared with the no-MS group (P = .049), the difference was not significant in the multivariate analysis (adjusted hazard ratio: 1.36 [95% CI, 0.66-2.80], P = .41). CONCLUSIONS: TAVR can be safely performed in patients with severe tricuspid aortic stenosis and concomitant MS, with early and mid-term outcomes comparable to those in patients without MS.

Aortic versus axillary cannulation in acute type A aortic dissection repair: A meta-analysis.

BACKGROUND: Research comparing the effectiveness of central aortic cannulation to axillary artery cannulation in repairing acute type A aortic dissection is limited and controversial. This meta-analysis aimed to compare early outcomes of central aortic cannulation versus axillary artery cannulation for surgery for acute aortic dissection type A. METHODS: A comprehensive systematic search was conducted across PubMed/MEDLINE, Scopus, and the Cochrane Central Register of Controlled Trials up to September 1, 2023. The primary endpoints were operative mortality and incidence of postoperative stroke. Secondary endpoints encompassed cardiopulmonary bypass time, myocardial ischemic time, hypothermic circulatory arrest time, postoperative temporary neurological dysfunction, combination of stroke and temporary neurological dysfunction, as well as the need for reexploration for bleeding, renal replacement therapy, and tracheotomy. A random-effect model was utilized to calculate the pooled effect size. RESULTS: Eleven studies met our eligibility criteria, enrolling a total of 7204 patients (2760 underwent aortic cannulation and 4444 underwent axillary cannulation). The operative mortality and incidence of postoperative stroke did not show statistical differences between the two groups, with a pooled odds ratio of 1.07 (95% confidence interval: 0.73-1.55) and 1.17 (0.95-1.42), respectively. Similarly, none of the secondary endpoints exhibited significant statistical differences between the two groups. CONCLUSIONS: Aortic cannulation can be a viable alternative to axillary artery cannulation for repair of acute aortic dissection type A, as both approaches present similar early clinical outcomes.

Clinical and Echocardiographic Outcomes of Patients Undergoing Transcatheter Edge-to-Edge Repair for Functional vs Degenerative Mitral Valve Regurgitation.

To analyze clinical and echocardiographic outcomes after transcatheter edge-to-edge repair (TEER) with mitral valve clip device (MitraClip-TM) for functional vs degenerative mitral valve regurgitation (MR). All consecutive 185 patients undergoing TEER between January 2019 and March 2023 were included in the study. A propensity-adjusted analysis investigated differences among functional vs degenerative MR mechanism groups. Preoperatively, functional vs degenerative MR included 43 vs 142 patients, respectively. Mean ejection fraction (EF) values were 37% vs 57.8%, mean STS-PROM risk score was 7% vs 4% while patients with severe MR included 29 (67.4%) vs 129 (90.9%) patients, respectively. Postoperatively, functional MR patients experienced a higher incidence of prolonged postoperative length of stay (LOS), reduced creatinine clearance, and EF<50% compared to the degenerative MR group. Mean EF was 35.9% vs 56.2% (P < 0.0001) and 1 (2.3%) vs 16 (11.3%) patients had residual severe MR (P = 0.01) in functional vs degenerative MR groups, respectively. At 30-days follow-up, all-cause death incidence was 1 (2.3%) vs 3 (2.1%) patients in functional vs degenerative MR, respectively (P = 0.9). At a mean of 1.6-years follow-up, all-cause death (P = 0.01), major adverse cardiovascular and cerebrovascular events (MACCE) (P = 0.02), cardiac death (P = 0.01) and hazard ratio for all-cause death higher in functional vs degenerative MR group. Mean EF was 39.7% vs 56% (P < 0.001) while residual severe MR was 4 (9.3%) vs 34 (24.5%) (P = 0.1) in functional vs degenerative MR groups, respectively. TEER with MitraClip device showed a higher incidence of all-cause death, cardiac death, and MACCE at follow-up for functional compared to degenerative MR after TEER.

One-Year Outcomes From the CLASP IID Randomized Trial for Degenerative Mitral Regurgitation.

BACKGROUND: The CLASP IID (Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical) trial is the first randomized controlled trial comparing the PASCAL system and the MitraClip system in prohibitive risk patients with significant symptomatic degenerative mitral regurgitation (DMR). OBJECTIVES: The study sought to report primary and secondary endpoints and 1-year outcomes for the full cohort of the CLASP IID trial. METHODS: Prohibitive-risk patients with 3+/4+ DMR were randomized 2:1 (PASCAL:MitraClip). One-year assessments included secondary effectiveness endpoints (mitral regurgitation [MR] ≤2+ and MR ≤1+), and clinical, echocardiographic, functional, and quality-of-life outcomes. Primary safety (30-day composite major adverse events [MAE]) and effectiveness (6-month MR ≤2+) endpoints were assessed for the full cohort. RESULTS: Three hundred patients were randomized (PASCAL: n = 204; MitraClip: n = 96). At 1 year, differences in survival, freedom from heart failure hospitalization, and MAE were nonsignificant (P > 0.05 for all). Noninferiority of the PASCAL system compared with the MitraClip system persisted for the primary endpoints in the full cohort (For PASCAL vs MitraClip, the 30-day MAE rates were 4.6% vs 5.4% with a rate difference of -0.8% and 95% upper confidence bound of 4.6%. The 6-month MR≤2+ rates were 97.9% vs 95.7% with a rate difference of 2.2% and 95% lower confidence bound (LCB) of -2.5%, for, respectively). Noninferiority was met for the secondary effectiveness endpoints at 1 year (MR≤2+ rates for PASCAL vs MitraClip were 95.8% vs 93.8% with a rate difference of 2.1% and 95% LCB of -4.1%. The MR≤1+ rates were 77.1% vs 71.3% with a rate difference of 5.8% and 95% LCB of -5.3%, respectively). Significant improvements in functional classification and quality of life were sustained in both groups (P <0.05 for all vs baseline). CONCLUSIONS: The CLASP IID trial full cohort met primary and secondary noninferiority endpoints, and at 1 year, the PASCAL system demonstrated high survival, significant MR reduction, and sustained improvements in functional and quality-of-life outcomes. Results affirm the PASCAL system as a beneficial therapy for prohibitive-surgical-risk patients with significant symptomatic DMR.

1-Year Outcomes of Transcatheter Edge-to-Edge Repair in Anatomically Complex Degenerative Mitral Regurgitation Patients.

BACKGROUND: Favorable 6-month outcomes from the CLASP IID Registry (Edwards PASCAL transcatheter valve repair system pivotal clinical trial) demonstrated that mitral valve transcatheter edge-to-edge repair with the PASCAL transcatheter valve repair system is safe and beneficial for treating prohibitive surgical risk degenerative mitral regurgitation (DMR) patients with complex mitral valve anatomy. OBJECTIVES: The authors sought to assess 1-year safety, echocardiographic and clinical outcomes from the CLASP IID Registry. METHODS: Patients with 3+ or 4+ DMR who were at prohibitive surgical risk, had complex mitral valve anatomy based on the MitraClip Instructions for Use, and deemed suitable for treatment with the PASCAL system were enrolled prospectively. Safety, clinical, echocardiographic, functional, and quality-of-life outcomes were assessed at 1 year. Study oversight included a central screening committee, echocardiographic core laboratory, and clinical events committee. RESULTS: Ninety-eight patients were enrolled. One-year Kaplan-Meier (KM) estimates of freedom from composite major adverse events, all-cause mortality, and heart failure hospitalization were 83.5%, 89.3%, and 91.5%, respectively. Significant mitral regurgitation (MR) reduction was achieved at 1 year (P < 0.001 vs baseline) including 93.2% at MR ≤2+ and 57.6% at MR ≤1+ with improvements in related echocardiographic measures. NYHA functional class and Kansas City Cardiomyopathy Questionnaire score also improved significantly (P < 0.001 vs baseline). CONCLUSIONS: At 1 year, treatment with the PASCAL system demonstrated safety and significant MR reduction, with continued improvement in clinical, echocardiographic, functional, and quality-of-life outcomes, illustrating the value of the PASCAL system in the treatment of prohibitive surgical risk patients with 3+ or 4+ DMR and complex mitral valve anatomy.

Long-Term Outcomes of Sternal-Sparing Versus Sternotomy Approaches for Mitral Valve Repair: Meta-Analysis of Reconstructed Time-to-Event Data.

OBJECTIVE: Since there are concerns about the durability of mitral valve repair (MVRp) with minimally invasive techniques in patients with mitral regurgitation (MR), we aimed to evaluate the long-term outcomes of these sternal-sparing approaches when compared with conventional approaches with sternotomy in patients undergoing MVRp. METHODS: We performed a systematic review according to a preestablished protocol and performed a pooled analysis of Kaplan-Meier-derived reconstructed time-to-event data from studies with longer follow-up comparing sternal-sparing versus sternotomy approaches for MVRp. Our outcomes of interest were survival, freedom from recurrent MR, and freedom from reoperation. RESULTS: Eleven studies met our eligibility criteria comprising 7,596 patients with follow-up (sternal sparing, n = 4,246; sternotomy, n = 3,350). Patients who underwent sternal-sparing MVRp had a significantly lower risk of mortality over time compared with patients who underwent MVRp with sternotomy (hazard ratio [HR] = 0.29, 95% confidence interval [CI]: 0.23 to 0.36, P < 0.001) in the overall analysis. However, we found no statistically significant difference between the groups in the sensitivity analysis with adjusted populations (HR = 0.85, 95% CI: 0.63 to 1.15, P = 0.301). Regarding the outcomes freedom from recurrent MR and freedom from reoperation, we found no statistically significant differences between the groups in the follow-up in both overall and sensitivity analyses. CONCLUSIONS: In comparison with MVRp with sternotomy approaches, sternal-sparing MVRp was not associated with worse outcomes in terms of survival, recurrent MR, and reoperations over time.

Computed tomography-derived membranous septum length as predictor of conduction abnormalities and permanent pacemaker implantation after TAVI: A meta-analysis of observational studies.

BACKGROUND: Permanent pacemaker implantation (PPI) after transcatheter aortic valve implantation (TAVI) is associated with higher risk of mortality and rehospitalization for heart failure. Efforts to prevent conduction abnormalities (CA) requiring PPI after TAVI should be made. The membranous septum (MS) length and its interaction with implantation depth (ID-ΔMSID) could provide useful information about the risk of CA/PPI following TAVI. OBJECTIVES: To identify MS length and ΔMSID as predictors of CA/PPI following TAVI. METHODS: Study-level meta-analysis of studies published by September 30, 2022. RESULTS: Eighteen studies met our eligibility including 5740 patients. Shorter MS length was associated with a significantly higher risk of CA/PPI (per 1 mm decrease: odds ratio [OR] 1.60, 95% confidence interval [CI] 1.28-1.99, p < 0.001). Similarly, lower ΔMSID was associated with a significantly higher risk of CA/PPI (per 1 mm decrease: OR 1.75, 95% CI 1.32-2.31, p < 0.001). Meta-regression analyses revealed a statistically significant modulation of the effect of shorter MS length and lower ΔMSID on the outcome (CA/PPI) by balloon postdilatation (positive regression coefficients with p < 0.001); with increasing use of balloon postdilatation, the effect of shorter MS length and lower ΔMSID on the outcome increased. MS length and ΔMSID demonstrated excellent discriminative abilities, with diagnostic ORs equaling 9.49 (95% CI 4.73-19.06), and 7.19 (95% CI 3.31-15.60), respectively. CONCLUSION: Considering that short MS length and low ΔMSID are associated with higher risk of CA and PPI, we should include measurement of MS length in the pre-TAVI planning with MDCT and try to establish optimal ID values before the procedure to avoid CA/PPI.

Transcatheter Edge-to-Edge Repair in Patients With Anatomically Complex Degenerative Mitral Regurgitation.

BACKGROUND: Mitral valve transcatheter edge-to-edge repair is safe and effective in treating degenerative mitral regurgitation (DMR) patients at prohibitive surgical risk, but outcomes in complex mitral valve anatomy patients vary. OBJECTIVES: The PASCAL IID registry assessed safety, echocardiographic, and clinical outcomes with the PASCAL system in prohibitive risk patients with significant symptomatic DMR and complex mitral valve anatomy. METHODS: Patients in the prospective, multicenter, single-arm registry had 3+ or 4+ DMR, were at prohibitive surgical risk, presented with complex anatomic features based on the MitraClip instructions for use, and were deemed suitable for the PASCAL system by a central screening committee. Enrolled patients were treated with the PASCAL system. Safety, effectiveness, and functional and quality-of-life outcomes were assessed. Study oversight also included an echocardiographic core laboratory and clinical events committee. RESULTS: The study enrolled 98 patients (37.2% ≥2 independent significant jets, 15.0% severe bileaflet/multi scallop prolapse, 13.3% mitral valve orifice area <4.0 cm2, and 10.6% large flail gap and/or large flail width). The implant success rate was 92.9%. The 30-day composite major adverse event rate was 11.2%. At 6 months, 92.4% patients achieved MR ≤2+ and 56.1% achieved MR ≤1+ (P < 0.001 vs baseline). The Kaplan-Meier estimates for survival, freedom from major adverse events, and heart failure hospitalization at 6 months were 93.7%, 85.6%, and 92.6%, respectively. Patients experienced significant symptomatic improvement compared with baseline (P < 0.001). CONCLUSIONS: The outcomes of the PASCAL IID registry establish the PASCAL system as a useful therapy for prohibitive surgical risk DMR patients with complex mitral valve anatomy. (PASCAL IID Registry within the Edwards PASCAL TrAnScatheter Valve RePair System Pivotal Clinical Trial [CLASP IID] NCT03706833).

Alternative Application Technique for the MANTA Vascular Closure Device for Percutaneous Large-Bore Arterial Access Closure: The Fluoroscopic DOT Technique.

BACKGROUND: Vascular complications are a cause of increased morbidity and mortality when performing percutaneous procedures requiring large-bore arterial access. MANTA vascular closure device (VCD) is currently the only large-bore VCD using an intraluminal foot plate and an extraluminal collagen plug. The traditional depth locator approach might be compromised in; emergent cases without the required measurements, cases of hematoma formation, or other patient, procedure, or operator-specific variables. Furthermore, this technique can be used for postclosure in cases without the required measurement of depth. We describe vascular outcomes using fluoroscopy (fluoroscopic DOT technique) rather than traditional depth locator approach for vascular closure with the MANTA VCD. METHODS: Fifty patients who underwent transcatheter aortic valve implantation (TAVI) were retrospectively analyzed using fluoroscopic DOT technique with 18F MANTA VCD between May and August 2021. All patients >18 years of age who qualified for transfemoral TAVI were included. Access was obtained with ultrasound guidance with vessel diameter of at least > 6 mm and free from anterior vessel wall calcification. Patient related factors and primary outcomes of access site bleeding and acute flow-limited limb ischemia requiring intervention were prospectively analyzed. Furthermore, 1 patient who failed hemostasis with suture-mediated VCD had successful hemostasis with fluoroscopic DOT technique as dry postclosure after balloon aortic valvuloplasty. RESULTS: In total, 50 patients were analyzed with a mean age of 81 years and majority were male (56%). Majority had comorbidities of hypertension (88%) and hyperlipidemia (94%), 24% had peripheral arterial disease, 38% coronary artery disease, and 58% were former smokers. Importantly, 40% were obese with an average body mass index (BMI) of 29 kg/m2. There were no bleeding or ischemic limb complications post MANTA VCD deployment using the fluoroscopic DOT technique. Furthermore, none of the patients required peripheral intervention from index procedure to 1 month post verified during their 1-month post TAVR follow-up. CONCLUSION: Fluoroscopic DOT technique using the MANTA VCD is highly reproducible and allows hemostasis in a predictable manner for procedures requiring large-bore arterial access in the absence of MANTA depth measurement.

Clinical utility of plasma Aß42/40 ratio by LC-MS/MS in Alzheimer's disease assessment.

INTRODUCTION: Plasma Aß42/40 ratio can be used to help predict amyloid PET status, but its clinical utility in Alzheimer's disease (AD) assessment is unclear. METHODS: Aß42/40 ratio was measured by LC-MS/MS in 250 specimens with associated amyloid PET imaging, diagnosis, and demographic data, and 6,192 consecutive clinical specimens submitted for Aß42/40 testing. RESULTS: High diagnostic sensitivity and negative predictive value (NPV) for Aß-PET positivity were observed, consistent with the clinical performance of other plasma LC-MS/MS assays, but with greater separation between Aß42/40 values for individuals with positive vs negative Aß-PET results. Assuming a moderate prevalence of Aß-PET positivity, a cutpoint was identified with 99% NPV, which could help predict that AD is likely not the cause of patients' cognitive impairment and help reduce PET evaluation by about 40%. DISCUSSION: Using high-throughput plasma Aß42/40 LC-MS/MS assays can help reduce PET evaluations in patients with low likelihood of AD pathology, allowing for cost savings.

Randomized Comparison of Transcatheter Edge-to-Edge Repair for Degenerative Mitral Regurgitation in Prohibitive Surgical Risk Patients.

BACKGROUND: Severe symptomatic degenerative mitral regurgitation (DMR) has a poor prognosis in the absence of treatment, and new transcatheter options are emerging. OBJECTIVES: The CLASP IID (Edwards PASCAL Transcatheter Valve Repair System Pivotal Clinical Trial) randomized trial (NCT03706833) is the first to evaluate the safety and effectiveness of the PASCAL system compared with the MitraClip system in patients with significant symptomatic DMR. This report presents the primary safety and effectiveness endpoints for the trial. METHODS: Patients with 3+ or 4+ DMR at prohibitive surgical risk were assessed by a central screening committee and randomized 2:1 (PASCAL:MitraClip). Study oversight also included an echocardiography core laboratory and a clinical events committee. The primary safety endpoint was the composite major adverse event rate at 30 days. The primary effectiveness endpoint was the proportion of patients with mitral regurgitation (MR) ≤2+ at 6 months. RESULTS: A prespecified interim analysis in 180 patients demonstrated noninferiority of the PASCAL system vs the MitraClip system for the primary safety and effectiveness endpoints of major adverse event rate (3.4% vs 4.8%) and MR ≤2+ (96.5% vs 96.8%), respectively. Functional and quality-of-life outcomes significantly improved in both groups (P < 0.05). The proportion of patients with MR ≤1+ was durable in the PASCAL group from discharge to 6 months (PASCAL, 87.2% and 83.7% [P = 0.317 vs discharge]; MitraClip, 88.5% and 71.2% [P = 0.003 vs discharge]). CONCLUSIONS: The CLASP IID trial demonstrated safety and effectiveness of the PASCAL system and met noninferiority endpoints, expanding transcatheter treatment options for prohibitive surgical risk patients with significant symptomatic DMR.