Risk of Bleeding Among Cangrelor-Treated Patients Administered Upstream P2Y12 Inhibitor Therapy: The CAMEO Registry.

Background: Little is known about the bleeding risk associated with cangrelor use in patients with myocardial infarction (MI) who are exposed to an oral P2Y12 inhibitor before coronary angiography. Methods: Cangrelor in Acute MI: Effectiveness and Outcomes (CAMEO) is an observational registry studying platelet inhibition for patients with MI. Upstream oral P2Y12 inhibition was defined as receipt of an oral P2Y12 inhibitor within 24 hours before hospitalization or in-hospital before angiography. Among cangrelor-treated patients, we compared bleeding after cangrelor use through 7 days postdischarge between patients with and without upstream oral P2Y12 inhibitor exposure. Results: Among 1802 cangrelor-treated patients with MI, 385 (21.4%) received upstream oral P2Y12 inhibitor treatment. Of these, 101 patients (33.8%) started cangrelor within 1 hour, 103 (34.4%) between 1 and 3 hours, and 95 (31.8%), >3 hours after in-hospital oral P2Y12 inhibitor administration; the remaining received an oral P2Y12 inhibitor before hospitalization. There was no statistically significant difference in rates of bleeding among cangrelor-treated patients with and without upstream oral P2Y12 inhibitor exposure (6.5% vs 8.8%; adjusted odds ratio [OR], 0.62; 95% CI, 0.38-1.01). Bleeding was observed in 5.0%, 10.7%, and 3.2% of patients treated with cangrelor <1, 1 to 3, and >3 hours after the last oral PY12 inhibitor dose, respectively; bleeding rates were not statistically different between groups (1-3 hours vs <1 hour: adjusted OR, 2.70; 95% CI, 0.87-8.32; >3 hours vs <1 hour: adjusted OR, 0.65; 95% CI, 0.15-2.85). Conclusions: Bleeding risk was not observed to be significantly higher after cangrelor treatment in patients with and without upstream oral P2Y12 inhibitor exposure.

Contemporary Outcomes and Trends for the Transseptal Mitral Valve-in-Valve Procedure Using Balloon Expandable Transcatheter Valves in the United States.

BACKGROUND: Previous transcatheter valve therapy registry analyses of transcatheter mitral valve in valve (MViV) replacement of degenerated bioprosthesis reported early experience in the United States. Given recent increases in transseptal MViV volumes and introduction of the SAPIEN 3 Ultra valve, it is important to determine contemporary outcomes for patients undergoing transseptal SAPIEN 3/SAPIEN 3 Ultra MViV replacement. METHODS: The Society of Thoracic Surgeons (STS)/American College of Cardiology Transcatheter Valve Therapy Registry was used to extract data for all patients undergoing transseptal SAPIEN 3/SAPIEN 3 Ultra MViV from 2015 to September 2022. Primary efficacy outcome was 1-year all-cause mortality. Secondary end points included 30-day mortality, functional class, quality of life, and mitral valve performance. Primary safety outcomes were device success and in-hospital complications. RESULTS: A total of 4243 patients with a mean STS score of 9.2±7.7 underwent transseptal MViV at 455 sites. The rate of Mitral Valve Academic Research Consortium technical (96.6%) success was high, and procedural complications were low. All-cause in-hospital, 30-day, and 1-year mortality rates were 3.2%, 4.3%, and 13.4%, respectively. Significant improvements in New York Heart Association class (New York Heart Association I/II, 18% to 87%) and quality of life (Kansas City Cardiomyopathy Questionnaire score, 38 to 78) were noted at 1 year (P<0.0001 for both) after MViV. Upon stratifying by STS scores, it was observed that the low-risk group (STS<4) had a significantly lower in-hospital mortality rate of 0.4%, whereas the intermediate-risk group (STS, 4-8) had an in-hospital mortality rate of 1.9%. From 2015 to 2022, the number of transseptal MViV cases/year increased significantly, whereas procedure times, length of stay, and intensive care unit hours shortened significantly. At the same time, there was a significant trend toward reduced in-hospital (P=0.0005), 30-day (P=0.004), and 1-year mortality rates (P=0.01). CONCLUSIONS: This multicenter, prospective study reports excellent procedural outcomes, 1-year mortality rates, and a significant improvement in quality of life for patients undergoing transseptal MViV in the contemporary era. Patients in the low-risk and intermediate-risk STS score categories had significantly better outcomes compared with those in the high-risk category. MViV is a reasonable therapy for the majority of patients with degenerated bioprosthetic mitral valves, who are anatomical candidates.

Invasive Assessment of Coronary Artery Disease in Clonal Hematopoiesis of Indeterminate Potential.

BACKGROUND: Clonal hematopoiesis of indeterminate potential (CHIP) occurs due to acquired mutations in bone marrow progenitor cells. CHIP confers a 2-fold risk of atherosclerotic cardiovascular disease. However, there are limited data regarding specific cardiovascular phenotypes. The purpose of this study was to define the coronary artery disease phenotype of the CHIP population-based on coronary angiography. METHODS: We recruited 1142 patients from the Vanderbilt University Medical Center cardiac catheterization laboratory and performed DNA sequencing to determine CHIP status. Multivariable logistic regression models and proportional odds models were used to assess the association between CHIP status and angiography phenotypes. RESULTS: We found that 18.4% of patients undergoing coronary angiography had a CHIP mutation. Those with CHIP had a higher risk of having obstructive left main (odds ratio, 2.44 [95% CI, 1.40-4.27]; P=0.0018) and left anterior descending (odds ratio, 1.59 [1.12-2.24]; P=0.0092) coronary artery disease compared with non-CHIP carriers. We additionally found that a specific CHIP mutation, ten eleven translocase 2 (TET2), has a larger effect size on left main stenosis compared with other CHIP mutations. CONCLUSIONS: This is the first invasive assessment of coronary artery disease in CHIP and offers a description of a specific atherosclerotic phenotype in CHIP wherein there is an increased risk of obstructive left main and left anterior descending artery stenosis, especially among TET2 mutation carriers. This serves as a basis for understanding enhanced morbidity and mortality in CHIP.

Transcatheter Edge-to-Edge Repair in 5,000 Patients With Secondary Mitral Regurgitation: COAPT Post-Approval Study.

BACKGROUND: Real-world applicability of the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation) randomized controlled trial (RCT) has been debated because of careful patient selection and the contrasting results of the MITRA-FR (Multicentre Study of Percutaneous Mitral Valve Repair MitraClip Device in Patients with Severe Secondary Mitral Regurgitation) RCT. OBJECTIVES: The COAPT-PAS (COAPT Post-Approval Study) was initiated to assess the safety and effectiveness of the MitraClip in patients with secondary mitral regurgitation (SMR). METHODS: COAPT-PAS is a prospective, single-arm, observational study of 5,000 consecutive patients with SMR treated with the MitraClip at 406 U.S. centers participating in the TVT (Transcatheter Valve Therapy) registry from 2019 to 2020. The 1-year outcomes from the COAPT-PAS full cohort and the COAPT-like and MITRA-FR-like subgroups who met RCT inclusion/exclusion criteria are reported. RESULTS: Patients in the COAPT-PAS had more comorbidities, more severe HF and functional limitations, and less guideline-directed medical therapy than those in the COAPT or MITRA-FR RCTs. Patients in the COAPT-PAS full cohort and the COAPT-like (n = 991) and MITRA-FR-like (n = 917) subgroups achieved a 97.7% MitraClip implant rate, a similar and durable reduction of mitral regurgitation to ≤2+ at 1 year (90.7%, 89.7%, and 86.6%, respectively), a large improvement in quality of life at 1 year (Kansas City Cardiomyopathy Questionnaire +29 COAPT-PAS, +27 COAPT-like, and +33 MITRA-FR-like), faster procedure times, similar or lower clinical event rates compared with the RCTs' MitraClip arms, and lower clinical event rates than the RCTs' guideline-directed medical therapy only arms. One-year heart failure hospitalizations was 18.9% in COAPT-PAS, 19.7% in COAPT-like compared with 24.9% in COAPT-RCT, and 28.7% in COAPT-PAS-MITRA-FR-like compared with 47.4% in MITRA-FR-RCT. CONCLUSIONS: This large, contemporary, real-world study reinforces the safety and effectiveness of the MitraClip System in patients with SMR, including those who met the COAPT or MITRA-FR RCT inclusion/exclusion criteria and patients excluded from the RCTs.

Modeling Antiretrovial Treatment to Mitigate HIV in the Brain: Impact of the Blood-Brain Barrier.

Current research in Human Immunodeficiency Virus (HIV) focuses on eradicating virus reservoirs that prevent or dampen the effectiveness of antiretroviral treatment (ART). One such reservoir, the brain, reduces treatment efficacy via the blood-brain barrier (BBB), causing an obstacle to drug penetration into the brain. In this study, we develop a mathematical model to examine the impact of the BBB on ART effectiveness for mitigating brain HIV. A thorough analysis of the model allowed us to fully characterize the global threshold dynamics with the viral clearance and persistence in the brain for the basic reproduction number less than unity and greater than unity, respectively. Our model showed that the BBB has a significant role in inhibiting the effect of ART within the brain despite the effective viral load suppression in the plasma. The level of impact, however, depends on factors such as the CNS Penetration Effectiveness (CPE) score, the slope of the drug dose-response curves, the ART initiation timing, and the number of drugs in the ART protocol. These results suggest that reducing the plasma viral load to undetectable levels due to some drug regimen may not necessarily indicate undetectable levels of HIV in the brain. Thus, the effect of the BBB on viral suppression in the brain must be considered for developing proper treatment protocols against HIV infection.

Outcomes of transcatheter aortic valve replacement in patients with cardiogenic shock.

AIMS: The safety and efficacy of transcatheter aortic valve replacement (TAVR) with contemporary balloon expandable transcatheter valves in patients with cardiogenic shock (CS) remain largely unknown. In this study, the TAVRs performed for CS between June 2015 and September 2022 using SAPIEN 3 and SAPIEN 3 Ultra bioprosthesis from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were analysed. METHODS AND RESULTS: CS was defined as: (i) coding of CS within 24 h on Transcatheter Valve Therapy Registry form; and/or (ii) pre-procedural use of inotropes or mechanical circulatory support devices and/or (iii) cardiac arrest within 24 h prior to TAVR. The control group was comprised of all the other patients undergoing TAVR. Baseline characteristics, all-cause mortality, and major complications at 30-day and 1-year outcomes were reported. Landmark analysis was performed at 30 days post-TAVR. Cox-proportional multivariable analysis was performed to determine the predictors of all-cause mortality at 1 year. A total of 309 505 patients underwent TAVR with balloon-expandable valves during the study period. Of these, 5006 patients presented with CS prior to TAVR (1.6%). The mean Society of Thoracic Surgeons score was 10.76 ± 10.4. The valve was successfully implanted in 97.9% of patients. Technical success according to Valve Academic Research Consortium-3 criteria was 94.5%. In a propensity-matched analysis, CS was associated with higher in-hospital (9.9% vs. 2.7%), 30-day (12.9% vs. 4.9%), and 1-year (29.7% vs. 22.6%) mortality compared to the patients undergoing TAVR without CS. In the landmark analysis after 30 days, the risk of 1-year mortality was similar between the two groups [hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.95-1.21]. Patients who were alive at 1 year noted significant improvements in functional class (Class I/II 89%) and quality of life (ΔKCCQ score +50). In the multivariable analysis, older age (HR 1.02, 95% CI 1.02-1.03), peripheral artery disease (HR 1.25, 95% CI 1.06-1.47), prior implantation of an implantable cardioverter-defibrillator (HR 1.37, 95% CI 1.07-1.77), patients on dialysis (HR 2.07, 95% CI 1.69-2.53), immunocompromised status (HR 1.33, 95% CI 1.05-1.69), New York Heart Association class III/IV symptoms (HR 1.50, 95% CI 1.06-2.12), lower aortic valve mean gradient, lower albumin levels, lower haemoglobin levels, and lower Kansas City Cardiomyopathy Questionnaire scores were independently associated with 1-year mortality. CONCLUSION: This large observational real-world study demonstrates that the TAVR is a safe and effective treatment for aortic stenosis patients presenting with CS. Patients who survived the first 30 days after TAVR had similar mortality rates to those who were not in CS.

Transcatheter Tricuspid Interventions: Past, Present, and Future.

Tricuspid regurgitation (TR) etiologies include primary valve pathology or secondary (functional) regurgitation from increased hemodynamic pressure or volume on the right side of the heart. Patients with severe TR have a worse prognosis independent of all other variables. Surgical treatment for TR has mostly been limited to patients undergoing concomitant left-sided cardiac surgery. The results and durability of surgical repair or replacement are not well defined. For patients with significant and symptomatic TR, transcatheter techniques would be beneficial, but these techniques and devices have been slow to develop. Much of the delay is a result of neglect and challenges in defining the symptoms associated with TR. In addition, the anatomic and physiological aspects of the tricuspid valve apparatus present unique challenges. Several devices and techniques are in various phases of clinical investigation. This review highlights the current landscape of transcatheter tricuspid interventions and future opportunities. It is imminent that these therapies become commercially available and widely adopted to have a significant positive impact on millions of patients that have been neglected.

Ventricular Remodeling and Outcomes After Mitral Transcatheter Edge-to-Edge Repair in Heart Failure: The COAPT Trial.

BACKGROUND: The relationship between left ventricular (LV) remodeling and clinical outcomes after treatment of severe mitral regurgitation (MR) in heart failure (HF) has not been examined. OBJECTIVES: The aim of this study was to evaluate the association between LV reverse remodeling and subsequent outcomes and assess whether transcatheter edge-to-edge repair (TEER) and residual MR are associated with LV remodeling in the COAPT (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation) trial. METHODS: Patients with HF and severe MR who remained symptomatic on guideline-directed medical therapy (GDMT) were randomized to TEER plus GDMT or GDMT alone. Baseline and 6-month core laboratory measurements of LV end-diastolic volume index and LV end-systolic volume index were examined. Change in LV volumes from baseline to 6 months and clinical outcomes from 6 months to 2 years were evaluated using multivariable regression. RESULTS: The analytical cohort comprised 348 patients (190 treated with TEER, 158 treated with GDMT alone). A decrease in LV end-diastolic volume index at 6 months was associated with reduced cardiovascular death between 6 months and 2 years (adjusted HR: 0.90 per 10 mL/m2 decrease; 95% CI: 0.81-1.00; P = 0.04), with consistent results in both treatment groups (Pinteraction = 0.26). Directionally similar but nonsignificant relationships were present for all-cause death and HF hospitalization and between reduced LV end-systolic volume index and all outcomes. Neither treatment group nor MR severity at 30 days was associated with LV remodeling at 6 or 12 months. The treatment benefits of TEER were not significant regardless of the degree of LV remodeling at 6 months. CONCLUSIONS: In patients with HF and severe MR, LV reverse remodeling at 6 months was associated with subsequently improved 2-year outcomes but was not affected by TEER or the extent of residual MR. (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients With Functional Mitral Regurgitation [The COAPT Trial] and COAPT CAS [COAPT]; NCT01626079).

No-Implant Interatrial Shunt for HFpEF: 6-Month Outcomes From Multicenter Pilot Feasibility Studies.

BACKGROUND: Most approaches to the creation of an interatrial shunt require placement of a permanent implant to maintain patency. OBJECTIVES: The goal of this study was to investigate the safety and efficacy of a no-implant interatrial shunt for patients with heart failure with preserved ejection fraction (HFpEF) and heart failure with mildly reduced ejection fraction (HFmrEF). METHODS: This was a multicenter, uncontrolled study of patients with HFpEF/HFmrEF and NYHA functional class ≥II, ejection fraction >40%, and pulmonary capillary wedge pressure (PCWP) during supine exercise ≥25 mm Hg with PCWP-to-right atrial gradient ≥5 mm Hg. Follow-up was through 6 months with imaging to assess shunt durability. RESULTS: A total of 28 patients were enrolled: mean age was 68 ± 9 years, and 68% were female. Baseline resting and peak exercise PCWP were 19 ± 7 mm Hg and 40 ± 11 mm Hg, respectively. All procedures displayed technical success with confirmation of left-to-right flow (shunt diameter 7.1 ± 0.9 mm). At 1 month, peak exercise PCWP decreased 5.4 ± 9.6 mm Hg (P = 0.011) with no change in right atrial pressure. There were no serious device or procedure-related adverse events through 6 months. Mean 6-minute walk distance increased 101 ± 71 meters (P < 0.001); Kansas City Cardiomyopathy Questionnaire Overall Summary Score increased 26 ± 19 points (P < 0.001); N-terminal pro-B-type natriuretic peptide decreased 372 ± 857 pg/mL (P = 0.018); and shunt patency was confirmed with unchanged diameter. CONCLUSIONS: In these feasibility studies of a no-implant interatrial shunt, HFpEF/HFmrEF shunts exhibited stability with favorable safety and early efficacy signals. The results show promise toward this new approach for treating patients with HFpEF/HFmrEF and an appropriate hemodynamic profile. (Evaluation of the Safety and Feasibility of a Percutaneously Created Interatrial Shunt to Alleviate Heart Failure Symptoms in Patients With Chronic Heart Failure and Preserved or Mid-Range Left Ventricular Ejection Fraction [ALLEVIATE-HF-1]; NCT04583527; Evaluation of the Safety and Effectiveness of a Percutaneously Created Interatrial Shunt to Alleviate Heart Failure Symptoms in Patients With Chronic Heart Failure and Preserved or Mid-Range Left Ventricular Ejection Fraction [ALLEVIATE-HF-2]; NCT04838353).

Impact of Transcatheter Mitral Valve Repair Availability on Volume and Outcomes of Surgical Repair.

BACKGROUND: The impact of transcatheter edge-to-edge repair (TEER) on national surgical mitral valve repair (MVr) volume and outcomes is unknown. OBJECTIVES: This study aims to assess the impact of TEER availability on MVr volumes and outcomes for degenerative mitral regurgitation. METHODS: MVr volume, 30-day and 5-year outcomes, including mortality, heart failure rehospitalization and mitral valve reintervention, were obtained from the Society of Thoracic Surgeons database linked with Medicare administrative claims and were compared within TEER centers before and after the first institutional TEER procedure. A difference-in-difference approach comparing parallel trends in coronary artery bypass grafting outcomes was used to account for temporal improvements in perioperative care. RESULTS: From July 2011 through December 2018, 13,959 patients underwent MVr at 278 institutions, which became TEER-capable during the study period. There was no significant change in median annualized institutional MVr volume before (32 [IQR: 17-54]) vs after (29 [IQR: 16-54]) the first TEER (P = 0.06). However, higher-risk (Society of Thoracic Surgeons predicted risk of mortality ≥2%) MVr procedures declined over the study period (P < 0.001 for trend). The introduction of TEER was associated with reduced risk-adjusted odds of mortality after MVr at 30 days (adjusted OR: 0.73; 95% CI: 0.54-0.99) and over 5 years (adjusted HR: 0.75; 95% CI: 0.66-0.86). These improvements in 30-day and 5-year mortality were significantly greater than equivalent trends in coronary artery bypass grafting. CONCLUSIONS: The introduction of TEER has not significantly changed overall MVr case volumes for degenerative mitral regurgitation but is associated with a decrease in higher-risk surgical operations and improved 30-day and 5-year outcomes within institutions adopting the technology.

Association of Transcatheter Aortic Valve Replacement Reimbursement, New Technology Add-on Payment, and Procedure Volumes With Embolic Protection Device Use.

Importance: In the setting of uncertain efficacy and additional, unreimbursed cost, use of an embolic protection device (EPD) during transcatheter aortic valve replacement (TAVR) has had variable uptake. The Centers for Medicare & Medicaid Services (CMS) instituted a new technology add-on payment to cover EPD use in October 2018. Objective: To evaluate the association between CMS TAVR reimbursement rates and EPD use. Design, Setting, and Participants: This cohort study used the Society for Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy registry to identify patients who underwent TAVR between January 2018 and September 2019. Analysis took place between July 2020 and February 2022. Main Outcomes and Measures: The association between EPD use and CMS reimbursement was assessed using multivariable logistic regression models adjusted for patient characteristics (model 1) and patient/hospital (annualized TAVR volume and teaching status) characteristics (model 2). Results: Among 511 institutions, CMS reimbursement for TAVR ranged from $28 062 to $111 280 with a median (IQR) of $45 884 ($40 331-$53 627). Among 84 353 patients (median [IQR] age, 81.0 [75.0-86.0] years; 46 247 male individuals [54.8%]; 3958 [4.7%] of Hispanic or Latino ethnicity; 78 170 White individuals [92.7%]) treated at the sites, 6012 (7.1%) underwent TAVR with EPD. Patient characteristics associated with EPD use included prior stroke (adjusted odds ratio [aOR], 1.13 [95% CI, 1.00-1.27]; P = .048), female sex (aOR, 0.85 [95% CI, 0.78-0.93]; P < .001), hemodialysis (aOR, 0.52 [95% CI, 0.40-0.68]; P < .001), and shock (aOR, 0.62 [95% CI, 0.41-0.94]; P = .03). Higher CMS reimbursement up to $50 000 per TAVR was associated with greater likelihood of EPD use in model 1 (per $1000; aOR, 1.08 [95% CI, 1.01-1.16]; P = .02). However, this association was no longer apparent after adjusting for site characteristics (model 2; aOR, 1.03 [95% CI, 0.96-1.11]; P = .38). Higher TAVR volume was associated with increased EPD use (per 25 TAVRs; aOR, 1.15 [95% CI, 1.09-1.21]; P < .001). There was no significant change in the odds of EPD uptake before vs after institution of the CMS new technology add-on payment across tertiles of CMS TAVR reimbursement (Wald χ2 = 3.59; P = .17). Conclusions and Relevance: EPD use during TAVR remains infrequent and is associated with multiple patient and site characteristics. While CMS reimbursement varies significantly across institutions, TAVR case volume, rather than CMS TAVR reimbursement or the CMS new technology add-on payment, appears to be the predominant factor associated with EPD use. Ongoing work is needed to understand the economic drivers that contribute to the association between procedural volume and EPD use.

Heat inactivation of clinical COVID-19 samples on an industrial scale for low risk and efficient high-throughput qRT-PCR diagnostic testing.

We report the development of a large scale process for heat inactivation of clinical COVID-19 samples prior to laboratory processing for detection of SARS-CoV-2 by RT-qPCR. With more than 266 million confirmed cases, over 5.26 million deaths already recorded at the time of writing, COVID-19 continues to spread in many parts of the world. Consequently, mass testing for SARS-CoV-2 will remain at the forefront of the COVID-19 response and prevention for the near future. Due to biosafety considerations the standard testing process requires a significant amount of manual handling of patient samples within calibrated microbiological safety cabinets. This makes the process expensive, effects operator ergonomics and restricts testing to higher containment level laboratories. We have successfully modified the process by using industrial catering ovens for bulk heat inactivation of oropharyngeal/nasopharyngeal swab samples within their secondary containment packaging before processing in the lab to enable all subsequent activities to be performed in the open laboratory. As part of a validation process, we tested greater than 1200 clinical COVID-19 samples and showed less than 1 Cq loss in RT-qPCR test sensitivity. We also demonstrate the bulk heat inactivation protocol inactivates a murine surrogate of human SARS-CoV-2. Using bulk heat inactivation, the assay is no longer reliant on containment level 2 facilities and practices, which reduces cost, improves operator safety and ergonomics and makes the process scalable. In addition, heating as the sole method of virus inactivation is ideally suited to streamlined and more rapid workflows such as 'direct to PCR' assays that do not involve RNA extraction or chemical neutralisation methods.

Trends in utilization, outcomes, and readmissions after transcatheter mitral valve replacement.

BACKGROUND: There is a paucity of real-world data regarding the temporal trends and outcomes of trans-septal transcatheter mitral valve replacement (TS-TMVR) in the United States (US). METHODS: We queried the Nationwide Readmissions Database (October 2015 to December 2018) for patients undergoing TS-TMVR procedures. We reported the temporal trends in the utilization, in-hospital outcomes and 30-day readmissions after TS-TMVR. The main study outcome was in-hospital mortality. RESULTS: There was an increase in the number of TS-TMVR procedures over time (48 in 2015 vs. 978 in 2018, Ptrend < 0.001), with a notable increase in the proportion of women (Ptrend  = 0.04) and the prevalence of diabetes (Ptrend  = 0.03). There was an increase in the number of centers performing TS-TMVR (21 in 2015 vs. 164 in 2018, Ptrend < 0.001). The overall in-hospital mortality was 7.2% with no change over time (6.3% in 2015 vs. to 5.2% in 2018, Ptrend  = 0.67). There was no change in the frequency of in-hospital complications after TS-TMVR; however, the median length of stay has decreased over time. The overall 30-day readmission rate was 17.8%, with no change during the study years. The most frequent cause for 30-day readmission after TS-TMVR was acute heart failure followed by bleeding and infection-related complications. Prior coagulopathy and small-sized hospitals were independently associated with higher in-hospital mortality and 30-day readmissions. CONCLUSION: This nationwide observational analysis of real-world data showed an increase in the number of TS-TMVR procedures over time, which is now performed at a greater number of centers. There was no change in the rate of in-hospital mortality, complications or 30-day readmissions; but a significant reduction in the length of hospital stay over time was noted. As the number of TS-TMVR continue to expand, these data provide a perspective on the early experience with this procedure.

Feasibility of a No-Implant Approach to Interatrial Shunts: Preclinical and Early Clinical Studies.

Background: Heart failure with preserved ejection fraction represents a major unmet clinical need with limited treatment options. Recent device therapies under investigation have focused on decompression of the left atrium through an implantable interatrial shunt. Although these devices have shown favorable safety and efficacy signals, an implant is required to maintain shunt patency, which may increase the patient risk profile and complicate subsequent interventions requiring transseptal access. Methods: The Alleviant System is a no-implant approach to creating an interatrial shunt using radiofrequency energy to securely capture, excise, and extract a precise disk of tissue from the interatrial septum. Acute preclinical studies in healthy swine (n = 5) demonstrated the feasibility of the Alleviant System to repeatably create a 7 mm interatrial orifice with minimal collateral thermal effect and minimal platelet and fibrin deposition observed histologically. Results: Chronic animal studies (n = 9) were carried out to 30- and 60-day time points and exhibited sustained shunt patency with histology demonstrating completely healed margins, endothelialization, and no trauma to adjacent atrial tissue. Preliminary clinical safety and feasibility were validated in a first-in-human study in patients with heart failure with preserved ejection fraction (n = 15). All patients demonstrated shunt patency by transesophageal echocardiographic imaging at 1, 3, and 6 months, as well as cardiac computed tomography imaging at 6-month follow-up timepoints. Conclusions: Combined, these data support the safety and feasibility of a novel no-implant approach to creating an interatrial shunt using the Alleviant System. Continued follow-up and subsequent clinical studies are currently ongoing.

Transcatheter Aortic Valve Replacement and Surgical Aortic Valve Replacement Outcomes in Left Ventricular Assist Device Patients with Aortic Insufficiency.

Background: Worsening aortic insufficiency (AI) is a known sequela of prolonged continuous-flow left ventricular assist device (LVAD) support with a significant impact on patient outcomes. While medical treatment may relieve symptoms, it is unlikely to halt progression. Surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) are among non-medical interventions available to address post-LVAD AI. Limited data are available on outcomes with either SAVR or TAVR for the management of post-LVAD AI. Methods: The National Inpatient Sample data collected for hospital admissions between the years 2015 and 2018 for patients with pre-existing continuous-flow LVAD undergoing TAVR or SAVR for AI were queried. The primary outcome of interest was a composite of in-hospital mortality, stroke, transient ischaemic attack, MI, pacemaker implantation, need for open aortic valve surgery, vascular complications and cardiac tamponade. Results: Patients undergoing TAVR were more likely to receive their procedure during an elective admission (57.1 versus 30%, p=0.002), and a significantly higher prevalence of comorbidities, as assessed by the Elixhauser Comorbidity Index, was observed in the SAVR group (29 versus 18; p=0.0001). We observed a significantly higher prevalence of the primary composite outcome in patients undergoing SAVR (30%) compared with TAVR (14.3%; p=0.001). Upon multivariable analysis adjusting for the type of admission and Elixhauser Comorbidity Index, TAVR was associated with significantly lower odds of the composite outcome (odds ratio 0.243; 95% CI [0.06-0.97]; p=0.045). Conclusion: In this nationally representative cohort of LVAD patients with post-implant AI, it was observed that TAVR was associated with a lower risk of adverse short-term outcomes compared with SAVR.

Successful Orbital Atherectomy of Left Main Bifurcation Lesion Using Microcatheter Protection of Nonatherectomy Wire.

-Optimal PCI may be challenging with calcified left main bifurcation lesions-Orbital atherectomy is a common strategy for lesion optimization-Side branch occlusion is a feared complication of orbital atherectomy-Utilizing microcatheter wire protection can minimize occlusion risk with orbital atherectomy.

Corrigendum to "Successful Orbital Atherectomy of Left Main Bifurcation Lesion Using Microcatheter Protection of Nonatherectomy Wire".

[This corrects the article DOI: 10.1016/j.jscai.2021.100007.].