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Re-operative aortic arch operations (REDO) following previous cardiac surgery are challenging procedures associated with significant morbidity and mortality. We investigated post-operative outcomes for patients undergoing REDO and identified risk-factors for mortality in a contemporary series. From 1/2005-6/2018, 365 consecutive patients at an academic center underwent REDO: 257 HEMIARCH and 108 COMPLETE arch (45 stage I elephant trunk, 63 total arch) replacements. Outcomes included mortality and major adverse events. Long-term survival was determined with Kaplan-Meier analysis, and risk-factors for mortality were assessed with Cox proportional hazards regression. Operative mortality for the entire cohort was 6.8%, and rates of stroke, cardiac arrest, and renal failure were 6.0%, 7.4%, and 10.4%. Compared to HEMIARCH, COMPLETE patients had an increased incidence of renal failure requiring dialysis (15.7% vs 8.2%, p = 0.031) and re-exploration for bleeding or delayed chest closure (19.4% vs. 11.7%, p = 0.051). Although operative mortality was similar in both cohorts, long-term follow-up mortality (38.0% vs 26.8%, p = 0.047) was higher among COMPLETE vs. HEMIARCH. Predictors of overall mortality among all-comers undergoing REDO included older age, low body surface area, endocarditis, ejection fraction30%, emergent status of operation, extended cardiopulmonary bypass duration, intra-aortic balloon pump use, and a more extensive arch operation. Previous aortic surgery was not a risk-factor for mortality. Among all-comers undergoing REDO, survival was 81.4% at 1 year, 66.7% at 5 years, and 56.4% at 10 years of follow-up. While early postoperative outcomes are similar among HEMIARCH and COMPLETE, a more extensive arch-replacement is an independent risk-factor for overall mortality in REDO. Using appropriate clinical indications in the current era, REDO remains a viable option for selected patients.

Background Luminal narrowing, suspected secondary to thrombus, occurs within stent grafts at an unclear incidence after thoracic endovascular aortic repair (TEVAR). The significance of this phenomenon has not been determined, nor have the risk factors for development of intragraft luminal narrowing. Small graft diameter is hypothesized to be a risk factor for the development of ingraft stenosis. Methods A retrospective analysis was performed of a multicenter healthcare system including all patients who underwent TEVAR between July 2011 and July 2019 with at least 1 year of subsequently available surveillance contrast-enhanced computed tomography imaging. Standard demographic, preoperative, intraoperative, and postoperative variables were collected. Measurements were obtained via direct off-line images from computed tomography scans. Patent intragraft diameters were compared with baseline and interval change values were normalized to time to follow-up. The primary outcome measure was annual rate of intragraft luminal narrowing. Results There were 208 patients who met the inclusion criteria (94 women, 114 men) with a median follow-up of 822 days. The mean annual rate of percent intragraft diameter reduction was 10.5 ± 7.7% for women and 7.6 ± 5.6% for men (P = .0026). Multivariate analysis demonstrated female gender (P = .0283), preoperative diagnosis of hypertension (P = .0449), and need for coverage of the left subclavian artery (P = .0328) were all significant predictors of intragraft luminal narrowing. Small aortic diameters were not found to be associated independently with ingraft luminal narrowing nor was the concomitant use of antiplatelet or anticoagulation medications. Significant amounts of ingraft luminal narrowing, defined as a greater than 20% intragraft diameter decrease, were associated with an increased need for any reintervention, including for malperfusion, endoleak, and symptomatic aneurysm (P = .0249). Kaplan-Meier estimates demonstrated a significant gender-associated difference in high rates of intragraft luminal narrowing (P = .00189). Conclusions In this analysis, female gender is shown to be a significant nonmodifiable risk factor for intragraft luminal narrowing after TEVAR. The development of this phenomenon is not benign; as such, these findings were associated with an increased need for reintervention. This finding may be attributable to differences in aortic compliance or gender-associated differences in coagulation pathways and merits further investigation. Surveillance after thoracic stent grafting must account for patient-specific variations in complication risk.

Figure created with BioRender.com. OBJECTIVES Outcomes beyond 10 years for David V valve-sparing aortic root replacement (VSARR) in bicuspid aortic valve (BAV) patients have yet to be explored. We investigated long-term outcomes after BAV VSARR compared to VSARR for tricuspid aortic valve (TAV) patients. METHODS A total of 677 patients with BAV (n = 171) and TAV (n = 506) underwent VSARR between 2005 and 2020 from 2 aortic centres, excluding those with dissection, endocarditis, stenosis or prior aortic valve (AV) surgery. Multivariable Cox regression compared adjusted survival over a 12-year period. Fine and Gray competing risk regression compared risk and cumulative incidence of reoperation/reintervention. Propensity score matching created balanced groups, and landmark analysis isolated outcomes beginning 4 years postoperatively. Finally, longitudinal mixed modelling assessed AV deterioration on echocardiogram. RESULTS No difference was observed in 12-year survival of BAV versus TAV (propensity score matching 92.0% vs 89.9%, P = 0.97; multivariable hazard ratio 0.76, 95% confidence interval 0.34–1.69, P = 0.51). Adjusted 12-year cumulative incidence and risk of AV and/or proximal aorta reoperation/reintervention were not observed to be different (15.7% BAV vs 5.7% TAV, P = 0.37; subdistribution hazard ratio 1.54, 95% confidence interval 0.60–3.94, P = 0.36); however, landmark analysis showed increased incidence of late reoperation/reintervention in BAV versus TAV (11.7% vs 0.0%, P = 0.04). BAV was not associated with AV deterioration over time (BAV coefficient ± standard error: 0 ± 0.30, P = 1). CONCLUSIONS VSARR for BAV patients has excellent 12-year survival and low reoperation/reintervention rates, which were not observed to be different from TAV patients. However, higher incidence of reoperation/reintervention was observed in the late years after BAV VSARR. Our study provides key information for surgical consultation of patients with bicuspid aortopathy.

Background Left ventricular (LV) wall thickening occurs in patients following thoracic endovascular aortic repair (TEVAR). Clinical consequences of cardiovascular (CV) remodeling may be more significant younger patients with longer anticipated life spans. Risk factors for CV remodeling following TEVAR are unknown but may be related to graft size. Methods A retrospective analysis was performed of a multicenter healthcare system including patients aged ≤60 who underwent TEVAR between 2011 and 2019 with at least 1 year follow-up computed tomography angiography imaging available. Standard perioperative variables, native aortic diameter, and stent graft specifications were collected. Graft oversizing was calculated by dividing proximal graft diameter by proximal aortic diameter on preoperative imaging. Posterior LV wall thickness was measured at baseline and interval increases were normalized to time-to-follow-up. Primary outcome was annual rate of posterior LV wall thickening. Results One hundred one patients met inclusion criteria with a mean (SD) follow-up time of 1270 (693) days. Overall mean (SD) rate of LV wall thickness change was 0.534 (0.750) mm per year. Mean (SD) absolute LV wall thickness at most recent follow-up was 10.97 (2.85) mm for men, 9.69 (2.03) mm for women. Multivariate analysis demonstrated that higher rates of LV wall thickening were associated with narrower graft diameters (P = 0.0311). Greater absolute LV wall thickness at follow-up was associated with narrower grafts (P= 0.0155) and greater graft oversizing (P= 0.0376). Logistic regression demonstrated individuals who met criteria for LV hypertrophy were more likely to have narrower stent-grafts (P= 0.00798) and greater graft oversizing (P= 0.0315). Conclusions LV wall thickening occurred to a greater degree in individuals with narrower stent-grafts and higher rates of graft oversizing. This has significant implications for long-term cardiovascular health in younger patients may undergo TEVAR for atypical indications. Particular attention should be paid to long-term effects of stent-graft oversizing when selecting grafts in such populations.

Repair of aortic root aneurysms with nonstenotic bicuspid valves (NS-BAVs) is achieved either with valve-sparing root replacement (VSRR) or conventional Bentall procedure (ROOT). Procedural and long-term outcomes comparing these 2 techniques are sparse and need investigation.From March 2004 to January 2019, 158 patients with an aortic root aneurysm and NS-BAV underwent VSRR (n = 78, 49.3%) or ROOT (n = 80, 50.6%). VSRR involved optional aortic valve repair (n = 47, 60%), and ROOT was performed with bioprosthetic (81.3%) or mechanical valve replacement (18.7%). Procedural and postoperative outcomes were obtained, and univariate and Kaplan-Meier analyses were performed.VSRR patients were younger (42.7 ± 12.0 years of age) than ROOT (54.8 ± 13.6 years of age) (P.001). Cardiopulmonary bypass (CPB) and cross-clamp duration were longer in VSRR (CPB: 228.0 ± 39.1 minutes; cross-clamp: 200.1 ± 36.2 minutes) compared with ROOT (CPB: 199.5 ± 55 minutes; cross-clamp: 170.3 ± 39.5 minutes) (P.001). Postoperative stroke, renal failure, pneumonia, and reoperation for bleeding were similar, but postoperative atrial and ventricular arrhythmias was lower in VSRR (15% vs 42%; P.001). Length of stay and 30-day mortality were similar. At discharge, none had greater than trivial aortic insufficiency. Long-term 10-year survival and incidence of moderate-severe aortic insufficiency, aortic stenosis, and reoperation were equivalent between groups.Surgery for aortopathy associated with NS-BAV is safe and effective with either VSRR or ROOT. Despite its complexity, VSRR should be considered in the surgical treatment of this population.

There are limited therapeutic options for patients with COVID-19-related acute respiratory distress syndrome (ARDS) with inflammation-mediated lung injury. Mesenchymal stromal cells offer promise as immunomodulatory agents.Evaluation of efficacy and safety of allogeneic mesenchymal cells in mechanically-ventilated patients with moderate or severe COVID-induced respiratory failure.Patients were randomized to two infusions of 2 million cells/kg or sham infusions, in addition to standard of care. We hypothesized that cell therapy would be superior to sham-control for the primary endpoint of 30-day mortality. The key secondary endpoint was ventilator-free survival within 60 days, accounting for deaths and withdrawals in a ranked analysis.At the third interim analysis, the Data and Safety Monitoring Board recommended that the trial halt enrollment as the pre-specified mortality reduction from 40% to 23% was unlikely to be achieved (n=222 out of planned 300). Thirty-day mortality was 37.5% (42/112) in cell recipients versus 42.7% (47/110) in control patients (RR 0.88;95% CI 0.64,1.21;p=0.43). There were no significant differences in days alive off ventilation within 60 days (median rank 117.3 [IQR:60.0,169.5] in cell patients and 102.0 [IQR:54.0,162.5] in controls; higher is better). Resolution or improvement of ARDS at 30-days was observed in 51/104 (49.0%) cell recipients and 46/106 (43.4%) of control patients (OR 1.36;95% CI 0.57, 3.21). There were no infusion-related toxicities and overall serious adverse events over 30 days were similar.Mesenchymal cells, while safe, did not improve 30-day survival or 60-day ventilator-free days in patients with moderate/severe COVID-related acute respiratory distress syndrome. Clinical trial registration available at www.gov, ID:NCT04371393. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Clinical outcomes of redo surgical aortic valve replacement (redo-SAVR) compared with valve-in-valve transcatheter aortic valve replacement (VIV-TAVR) are poorly understood. This study compared short- and midterm outcomes of patients undergoing isolated redo-SAVR vs VIV-TAVR after previous SAVR.A single-institutional review of the initial use of VIV-TAVR from 2012 to 2019 identified 273 patients undergoing VIV-TAVR (n = 187) or redo-SAVR (n = 86) after prior SAVR. Outcomes analysis included a univariate analysis and Kaplan-Meier survival analysis.The Society of Thoracic Surgeons predicted risk of mortality was higher for VIV-TAVR (6.3%; interquartile range [IQR], 3.6%-10.5%) vs redo-SAVR (4.2%; IQR, 2.4%-6.9%; P.01). VIV-TAVR patients (76 years; IQR, 67.5-82.5 years) were older than redo-SAVR patients (64 years; IQR, 54-72; P.01). Redo-SAVR and VIV-TAVR had similar early mortality (1.2% vs 1.6%, P = .92). Two redo-SAVR (2.3%) and 3 VIV-TAVR patients (1.6%) died 4.8 ± 0.5 years and 4.8 ± 1.5 months after discharge, respectively. Redo-SAVR had an increased stroke rate (7.0% vs 1.1%, P = .02). Postoperative mean valve gradients were similar between VIV-TAVR (14 mm Hg; IQR, 9-21 mm Hg) and redo-SAVR patients (12 mm Hg; IQR, 8-20 mm Hg; P = .08). Postprocedure transesophageal echocardiography showed at least mild aortic insufficiency for 24 VIV-TAVR patients (16%) and 2 redo-SAVR patients (2.9%) (P = .01). The cumulative incidence of aortic valve reintervention was 5.2% for the redo-SAVR patients and 28.5% for the VIV-TAVR patients (P = .07).After previous SAVR, redo-SAVR and VIV-TAVR can both be performed with acceptable operative results. Despite treating a high-risk patient population, we found redo-SAVR and VIV-TAVR both carry similar operative outcomes. Improved valve hemodynamics were observed in redo-SAVR patients compared with VIV-TAVR patients.

Background: Levels of plasma SARS-CoV-2 nucleocapsid (N) antigen may be an important biomarker in patients with COVID-19 and enhance our understanding of the pathogenesis of COVID-19. Objective: To evaluate whether levels of plasma antigen can predict short-term clinical outcomes and identify clinical and viral factors associated with plasma antigen levels in hospitalized patients with SARS-CoV-2. Design: Cross-sectional study of baseline plasma antigen level from 2540 participants enrolled in the TICO (Therapeutics for Inpatients With COVID-19) platform trial from August 2020 to November 2021, with additional data on day 5 outcome and time to discharge. Setting: 114 centers in 10 countries. Participants: Adults hospitalized for acute SARS-CoV-2 infection with 12 days or less of symptoms. Measurements: Baseline plasma viral N antigen level was measured at a central laboratory. Delta variant status was determined from baseline nasal swabs using reverse transcriptase polymerase chain reaction. Associations between baseline patient characteristics and viral factors and baseline plasma antigen levels were assessed using both unadjusted and multivariable modeling. Association between elevated baseline antigen level of 1000 ng/L or greater and outcomes, including worsening of ordinal pulmonary scale at day 5 and time to hospital discharge, were evaluated using logistic regression and Fine-Gray regression models, respectively. Results: Plasma antigen was below the level of quantification in 5% of participants at enrollment, and 1000 ng/L or greater in 57%. Baseline pulmonary severity of illness was strongly associated with plasma antigen level, with mean plasma antigen level 3.10-fold higher among those requiring noninvasive ventilation or high-flow nasal cannula compared with room air (95% CI, 2.22 to 4.34). Plasma antigen level was higher in those who lacked antispike antibodies (6.42 fold; CI, 5.37 to 7.66) and in those with the Delta variant (1.73 fold; CI, 1.41 to 2.13). Additional factors associated with higher baseline antigen level included male sex, shorter time since hospital admission, decreased days of remdesivir, and renal impairment. In contrast, race, ethnicity, body mass index, and immunocompromising conditions were not associated with plasma antigen levels. Plasma antigen level of 1000 ng/L or greater was associated with a markedly higher odds of worsened pulmonary status at day 5 (odds ratio, 5.06 [CI, 3.41 to 7.50]) and longer time to hospital discharge (median, 7 vs. 4 days; subhazard ratio, 0.51 [CI, 0.45 to 0.57]), with subhazard ratios similar across all levels of baseline pulmonary severity. Limitations: Plasma samples were drawn at enrollment, not hospital presentation. No point-of-care test to measure plasma antigen is currently available. Conclusion: Elevated plasma antigen is highly associated with both severity of pulmonary illness and clinically important patient outcomes. Multiple clinical and viral factors are associated with plasma antigen level at presentation. These data support a potential role of ongoing viral replication in the pathogenesis of SARS-CoV-2 in hospitalized patients.

Item does not contain fulltext BACKGROUND: Acute kidney injury (AKI) after repair of type A acute aortic dissection (TAAAD) has been shown to affect both short- and long-term outcomes. This study aimed to validate the impact of postoperative AKI on in-hospital and long-term outcomes in a large population of dissection patients presenting to multinational aortic centers. Additionally, we assessed risk factors for AKI including surgical details. METHODS: Patients undergoing surgical repair for TAAAD enrolled in the International Registry of Acute Aortic Dissection database were evaluated to determine the incidence and risk factors for the development of AKI. RESULTS: A total of 3307 patients were identified. There were 761 (23%) patients with postoperative AKI (AKI group) vs 2546 patients without (77%, non-AKI group). The AKI group had a higher rate of in-hospital mortality (n = 193, 25.4% vs n = 122, 4.8% in the non-AKI group, P < .001). Additional postoperative complications were also more common in the AKI group including postoperative cerebrovascular accident, reexploration for bleeding, and prolonged ventilation. Independent baseline characteristics associated with AKI included a history of hypertension, diabetes, chronic kidney disease, evidence of malperfusion on presentation, distal extent of dissection to abdominal aorta, and longer cardiopulmonary bypass time. Kaplan-Meier survival curves revealed decreased 5-year survival among the AKI group (P < .001). CONCLUSIONS: AKI occurs commonly after TAAAD repair and is associated with a significantly increased risk of operative and long-term mortality. In this large study using the International Registry of Acute Aortic Dissection database, several factors were elucidated that may affect risk of AKI. 01 april 2023

Background Surgical reoperations for symptomatic aortic valve patient-prosthesis mismatch (PPM) are complex. The purpose of this research was to investigate the clinical and echocardiographic outcomes of patients who underwent reoperation for correction of symptomatic PPM after prior aortic valve replacement. Methods An institutional review identified 60 patients from 2004 to 2018 who underwent reoperative aortic valve replacement for PPM without structural valve degeneration. Univariate analyses were conducted to evaluate risk factors for perioperative mortality. Results Median patient age was 62.8 (interquartile range, 48.3-68.7) years, and mean body mass index was 29.2 ± 6.6 kg/m2. Thirty-nine (66%) patients underwent a first-time reoperation, and 18 (30.5%) underwent a second-time reoperation. The median interval between initial operation to reoperation for the treatment of PPM was 89 months. Thirty-four (56.7%) patients underwent aortic root replacement, while the remainder (43.3%) underwent aortic valve replacement. Additional procedures included replacement of the ascending aorta with or without aortic arch in 26 (43.3%) patients and coronary artery bypass grafting in 7 (12%) patients. Operative mortality and the rates of stroke and renal failure were 5.0%, 3.3%, and 5.0%, respectively. Echocardiographic follow-up was available in 64.9% of patients at a mean follow-up of 36.5 months. Preoperative mean pressure gradients were 32.1 ± 16.0 mm Hg and mean aortic valve area was 0.8 ± 0.3 cm2, and both improved to 6.6 ± 4.2 mm Hg and 2.3 ± 0.7 cm2 (P Conclusions Reoperative surgery for PPM is complex but may be performed with good outcomes and low mortality in experienced centers. These data provide excellent clinical and hemodynamic benchmarks for the treatment of PPM in the current era of valve-in-valve transcatheter aortic valve replacement.

OBJECTIVE: The David V valve-sparing root replacement (VSRR) is well-established for the treatment of AI and advanced root aortopathy. The impact of cusp repair in trileaflet aortic valve (TAV) patients, however, with preoperative moderate-severe AI and an eccentric jet is unclear. This study compares postoperative outcomes and the long-term cumulative incidence of recurrent AI >1+ and valve specific re-intervention in TAV patients with pre-operative AI >2+ based on jet centricity and cusp repair status. METHODS: Review of a single institutional database identified 309 consecutive patients undergoing VSRR from 2005–2018. Of these, 51 patients had a TAV with AI >2+: 25 concentric and 26 eccentric jets. Mean follow-up was 58 (SD=44) months. Echocardiographic parameters were compared between pre- and post-operative echocardiogram. Kaplan-Meier analysis and cumulative incidence were used to compare long-term survival, recurrence of AI >1+, and valve specific re-intervention. RESULTS: The mean age was 48 (SD=12) years and 84% were male. Differences in preoperative comorbidities or echocardiographic parameters between groups were not statistically significant. Concentric and eccentric patients underwent cusp repair at 48.0% vs. 57.7%, p=0.49. Postoperative outcomes were similar in concentric vs. eccentric undergoing cusp repair. On chest closure TEE, 98% of patients had AI < 1+, and no patients had AI >2+. Cumulative incidence for recurrence of AI >1+ and AVR were 0% for central and 4%, 9%, and 16% for eccentric at 3-, 5-, and 10-years and 0% for central and 5% for eccentric at 3-, 5-, and 10-years, respectively. Long-term mortality was similar regardless of jet centricity and cusp repair. CONCLUSIONS: In selected TAV patients with preoperative AI >2+, VSRR provides a durable repair regardless of jet centricity. The addition of cusp repair did not negatively impact recurrent AI >1+ or rates of valve related re-intervention.

BACKGROUND: We aimed to assess the efficacy and safety of two neutralising monoclonal antibody therapies (sotrovimab [Vir Biotechnology and GlaxoSmithKline] and BRII-196 plus BRII-198 [Brii Biosciences]) for adults admitted to hospital for COVID-19 (hereafter referred to as hospitalised) with COVID-19.METHODS: In this multinational, double-blind, randomised, placebo-controlled, clinical trial (Therapeutics for Inpatients with COVID-19 [TICO]), adults (aged ≥18 years) hospitalised with COVID-19 at 43 hospitals in the USA, Denmark, Switzerland, and Poland were recruited. Patients were eligible if they had laboratory-confirmed SARS-CoV-2 infection and COVID-19 symptoms for up to 12 days. Using a web-based application, participants were randomly assigned (2:1:2:1), stratified by trial site pharmacy, to sotrovimab 500 mg, matching placebo for sotrovimab, BRII-196 1000 mg plus BRII-198 1000 mg, or matching placebo for BRII-196 plus BRII-198, in addition to standard of care. Each study product was administered as a single dose given intravenously over 60 min. The concurrent placebo groups were pooled for analyses. The primary outcome was time to sustained clinical recovery, defined as discharge from the hospital to home and remaining at home for 14 consecutive days, up to day 90 after randomisation. Interim futility analyses were based on two seven-category ordinal outcome scales on day 5 that measured pulmonary status and extrapulmonary complications of COVID-19. The safety outcome was a composite of death, serious adverse events, incident organ failure, and serious coinfection up to day 90 after randomisation. Efficacy and safety outcomes were assessed in the modified intention-to-treat population, defined as all patients randomly assigned to treatment who started the study infusion. This study is registered with ClinicalTrials.gov, NCT04501978.FINDINGS: Between Dec 16, 2020, and March 1, 2021, 546 patients were enrolled and randomly assigned to sotrovimab (n=184), BRII-196 plus BRII-198 (n=183), or placebo (n=179), of whom 536 received part or all of their assigned study drug (sotrovimab n=182, BRII-196 plus BRII-198 n=176, or placebo n=178; median age of 60 years [IQR 50-72], 228 [43%] patients were female and 308 [57%] were male). At this point, enrolment was halted on the basis of the interim futility analysis. At day 5, neither the sotrovimab group nor the BRII-196 plus BRII-198 group had significantly higher odds of more favourable outcomes than the placebo group on either the pulmonary scale (adjusted odds ratio sotrovimab 1·07 [95% CI 0·74-1·56]; BRII-196 plus BRII-198 0·98 [95% CI 0·67-1·43]) or the pulmonary-plus complications scale (sotrovimab 1·08 [0·74-1·58]; BRII-196 plus BRII-198 1·00 [0·68-1·46]). By day 90, sustained clinical recovery was seen in 151 (85%) patients in the placebo group compared with 160 (88%) in the sotrovimab group (adjusted rate ratio 1·12 [95% CI 0·91-1·37]) and 155 (88%) in the BRII-196 plus BRII-198 group (1·08 [0·88-1·32]). The composite safety outcome up to day 90 was met by 48 (27%) patients in the placebo group, 42 (23%) in the sotrovimab group, and 45 (26%) in the BRII-196 plus BRII-198 group. 13 (7%) patients in the placebo group, 14 (8%) in the sotrovimab group, and 15 (9%) in the BRII-196 plus BRII-198 group died up to day 90.INTERPRETATION: Neither sotrovimab nor BRII-196 plus BRII-198 showed efficacy for improving clinical outcomes among adults hospitalised with COVID-19.FUNDING: US National Institutes of Health and Operation Warp Speed.

BACKGROUND: Tixagevimab-cilgavimab is a neutralising monoclonal antibody combination hypothesised to improve outcomes for patients hospitalised with COVID-19. We aimed to compare tixagevimab-cilgavimab versus placebo, in patients receiving remdesivir and other standard care.METHODS: In a randomised, double-blind, phase 3, placebo-controlled trial, adults with symptoms for up to 12 days and hospitalised for COVID-19 at 81 sites in the USA, Europe, Uganda, and Singapore were randomly assigned in a 1:1 ratio to receive intravenous tixagevimab 300 mg-cilgavimab 300 mg or placebo, in addition to remdesivir and other standard care. Patients were excluded if they had acute organ failure including receipt of invasive mechanical ventilation, extracorporeal membrane oxygenation, vasopressor therapy, mechanical circulatory support, or new renal replacement therapy. The study drug was prepared by an unmasked pharmacist; study participants, site study staff, investigators, and clinical providers were masked to study assignment. The primary outcome was time to sustained recovery up to day 90, defined as 14 consecutive days at home after hospital discharge, with co-primary analyses for the full cohort and for participants who were neutralising antibody-negative at baseline. Efficacy and safety analyses were done in the modified intention-to-treat population, defined as participants who received a complete or partial infusion of tixagevimab-cilgavimab or placebo. This study is registered with ClinicalTrials.gov, NCT04501978 and the participant follow-up is ongoing.FINDINGS: From Feb 10 to Sept 30, 2021, 1455 patients were randomly assigned and 1417 in the primary modified intention-to-treat population were infused with tixagevimab-cilgavimab (n=710) or placebo (n=707). The estimated cumulative incidence of sustained recovery was 89% for tixagevimab-cilgavimab and 86% for placebo group participants at day 90 in the full cohort (recovery rate ratio [RRR] 1·08 [95% CI 0·97-1·20]; p=0·21). Results were similar in the seronegative subgroup (RRR 1·14 [0·97-1·34]; p=0·13). Mortality was lower in the tixagevimab-cilgavimab group (61 [9%]) versus placebo group (86 [12%]; hazard ratio [HR] 0·70 [95% CI 0·50-0·97]; p=0·032). The composite safety outcome occurred in 178 (25%) tixagevimab-cilgavimab and 212 (30%) placebo group participants (HR 0·83 [0·68-1·01]; p=0·059). Serious adverse events occurred in 34 (5%) participants in the tixagevimab-cilgavimab group and 38 (5%) in the placebo group.INTERPRETATION: Among patients hospitalised with COVID-19 receiving remdesivir and other standard care, tixagevimab-cilgavimab did not improve the primary outcome of time to sustained recovery but was safe and mortality was lower.FUNDING: US National Institutes of Health (NIH) and Operation Warp Speed.

To compare transcatheter aortic valve replacement (TAVR) with surgical aortic valve replacement (SAVR) for patients in shock.There are minimal data on the clinical and echocardiographic outcomes for patients in shock that undergo TAVR and no data comparing these outcomes to similar patients undergoing SAVR.This is a single center, retrospective cohort study of patients having Society of Thoracic Surgeons (STS)-defined urgent or emergent AVR for aortic stenosis with clinical signs and symptoms of shock. Inclusion criteria were based on the Society of Cardiovascular AngiographyInterventions (SCAI) shock consensus statement and included: the need for inotropic or vasopressor agents, mechanical ventilation, continuous renal replacement therapy or newly initiated hemodialysis, and/or utilization of mechanical hemodynamic support. Clinical and echocardiographic outcomes for TAVR and SAVR were compared.Thirty-seven patients met the inclusion criteria for this study (17 TAVR, 20 SAVR). TAVR patients had a higher STS Predicted Risk of Mortality (PROM) score of 22.3% compared to 11.8% for SAVR patients (p = 0.001). No significant differences were found in baseline echocardiographic results. TAVR procedures required less procedure room time (185.9 min TAVR, 348.5 min SAVR, p 0.001) and fewer intraoperative packed red blood cell (pRBC) transfusions (0.2 units TAVR, 3.4 units SAVR, p 0.001). TAVR patients also had lower rates of prolonged postoperative ventilation compared to SAVR patients (38.5% TAVR, 75.0% SAVR, p = 0.047). TAVR and SAVR had similar rates of mortality at discharge (2 TAVR, 1 SAVR, p = 0.584), 30-days (2 TAVR, 1 SAVR, p = 0.584), and 1-year (8 TAVR, 5 SAVR, p = 0.149).Despite a higher risk TAVR group, patients in shock undergoing either TAVR or SAVR have similar 30-day mortality. At one year, SAVR patients have a numerically better, though not statistically significant, survival. These findings support the use of TAVR for patients in shock with aortic stenosis.

This Society for Vascular Surgery/Society of Thoracic Surgeons (SVS/STS) document illustrates and defines the overall nomenclature associated with type B aortic dissection. The contents describe a new classification system for practical use and reporting that includes the aortic arch. Chronicity of aortic dissection is also defined along with nomenclature in patients with prior aortic repair and other aortic pathologic processes, such as intramural hematoma and penetrating atherosclerotic ulcer. Complicated vs uncomplicated dissections are clearly defined with a new high-risk grouping that will undoubtedly grow in reporting and controversy. Follow-up criteria are also discussed with nomenclature for false lumen status in addition to measurement criteria and definitions of aortic remodeling. Overall, the document provides a facile framework of language that will allow more granular discussions and reporting of aortic dissection in the future.

BACKGROUND: In a randomized, placebo-controlled, clinical trial, bamlanivimab, a SARS-CoV-2-neutralizing monoclonal antibody, given in combination with remdesivir, did not improve outcomes among hospitalized patients with COVID-19 based on an early futility assessment.OBJECTIVE: To evaluate the a priori hypothesis that bamlanivimab has greater benefit in patients without detectable levels of endogenous neutralizing antibody (nAb) at study entry than in those with antibodies, especially if viral levels are high.DESIGN: Randomized, placebo-controlled trial. (ClinicalTrials.gov: NCT04501978).SETTING: Multicenter trial.PATIENTS: Hospitalized patients with COVID-19 without end-organ failure.INTERVENTION: Bamlanivimab (7000 mg) or placebo.MEASUREMENTS: Antibody, antigen, and viral RNA levels were centrally measured on stored specimens collected at baseline. Patients were followed for 90 days for sustained recovery (defined as discharge to home and remaining home for 14 consecutive days) and a composite safety outcome (death, serious adverse events, organ failure, or serious infections).RESULTS: Among 314 participants (163 receiving bamlanivimab and 151 placebo), the median time to sustained recovery was 19 days and did not differ between the bamlanivimab and placebo groups (subhazard ratio [sHR], 0.99 [95% CI, 0.79 to 1.22]; sHR > 1 favors bamlanivimab). At entry, 50% evidenced production of anti-spike nAbs; 50% had SARS-CoV-2 nucleocapsid plasma antigen levels of at least 1000 ng/L. Among those without and with nAbs at study entry, the sHRs were 1.24 (CI, 0.90 to 1.70) and 0.74 (CI, 0.54 to 1.00), respectively (nominal P for interaction = 0.018). The sHR (bamlanivimab vs. placebo) was also more than 1 for those with plasma antigen or nasal viral RNA levels above median level at entry and was greatest for those without antibodies and with elevated levels of antigen (sHR, 1.48 [CI, 0.99 to 2.23]) or viral RNA (sHR, 1.89 [CI, 1.23 to 2.91]). Hazard ratios for the composite safety outcome (LIMITATION: Subgroup analysis of a trial prematurely stopped because of futility; small sample size; multiple subgroups analyzed.CONCLUSION: Efficacy and safety of bamlanivimab may differ depending on whether an endogenous nAb response has been mounted. The limited sample size of the study does not allow firm conclusions based on these findings, and further independent trials are required that assess other types of passive immune therapies in the same patient setting.PRIMARY FUNDING SOURCE: U.S. government Operation Warp Speed and National Institute of Allergy and Infectious Diseases.

Objective Acute type A dissection with mesenteric malperfusion is a rare but lethal variant of aortic dissection. This study examines outcomes from various treatment algorithms. Methods A review from 2003 to 2017 of the Emory Aortic Database identified 34 patients who presented with acute type A dissection with mesenteric malperfusion. Outcomes from 4 different treatment strategies were analyzed: ascending aortic/arch replacement followed by laparotomy (n = 13), axillary-bifemoral artery bypass followed by ascending/arch replacement (n = 3); ascending/arch and concomitant antegrade thoracic endovascular aortic repair (TEVAR) (n = 5), and TEVAR followed by delayed ascending/arch replacement (TEVAR-1st) (n = 13). Results The mean age of all patients was 53 ± 13 years and was equivalent among the groups. The incidence of concomitant renal and ileofemoral malperfusion was 52% and 41%, and the initial serum lactate level was 4.3 ± 2.1 mmol/L. Overall mortality was 55.8%. In the ascending aortic/arch replacement followed by laparotomy group, 77% of patients had postoperative bowel necrosis or intractable acidosis and the mortality was 69.2%. All patients in the axillary-bifemoral artery bypass followed by ascending/arch replacement group survived, but 66% required postoperative dialysis. In the ascending/arch and concomitant antegrade/TEVAR group, the mortality was 80% secondary to persistent postoperative bowel necrosis or intractable acidosis. Three patients in the TEVAR-1st group died before aortic replacement. In the 10 patients who underwent TEVAR followed by delayed aortic replacement, the mortality was 30%. There were no cases of postoperative bowel necrosis or intractable acidosis in the TEVAR-1st group. Conclusions The TEVAR-1st strategy delays central aortic replacement until end-organ ischemia has resolved. This novel paradigm serves as a bridge to decision, and may improve survival compared with conventional treatment strategies in acute type A dissection with mesenteric malperfusion.

Historically, optimal medical therapy (OMT) has been the primary therapy for acute uncomplicated type B aortic dissection (auTBAD). However, recent data suggest that OMT provides poor long-term results, and aortic remodeling induced by thoracic endovascular aortic repair (TEVAR) may improve survival. This study compares adverse events and survival among auTBAD patients receiving either TEVAR or OMT. A retrospective analysis identified 146 consecutive auTBAD patients presenting to a single institution between 1/2012 and 10/2020. Patients were divided into 2 groups based upon whether they received TEVAR (n = 50) or OMT (n = 96) at index hospitalization. Major morbidity and survival were compared between groups. 67.1% of patients presented with a Debakey IIIB dissection with maximum thoracic aortic diameter of 4.3 ± 1.0 cm. Over follow-up, 35% of OMT patients failed medical therapy and underwent intervention (n = 23 TEVAR, n = 11 open). An additional 13 died for an all-cause failure rate of 49%. The composite incidence of renal failure, stroke, spinal cord ischemia, and retrograde type A dissections was similar between groups (TEVAR:6.0% vs OMT:4.2%). In-hospital mortality was 0%. Kaplan-Meier analysis demonstrated a trend towards improved survival among the TEVAR group at 1 and 3 years but no difference in overall survival (HR:0.30, 95% CI:0.08-1.08, P = 0.066). Five-year survival was 91% with TEVAR and 82% with OMT. Complete false lumen thrombosis was achieved in 72.1% with TEVAR and 20.0% with OMT (P0.001). In experienced centers, there is equivalent early mortality in the treatment of auTBAD with TEVAR compared to OMT. TEVAR provides superior aortic remodeling to OMT in auTBAD, which may translate into improved long-term survival.

Objectives This study sought to test safety and exploratory effectiveness of a dedicated transcaval closure device (TCD). Background Transcaval access enables delivery of large-caliber devices to the aorta in patients ineligible for transfemoral arterial access. Closure of aortocaval fistulae using off-label nitinol cardiac occluders has been shown to be safe, but persistent aortocaval fistulae at exit from the catheterization lab and bleeding complications were common in a prospective study. Methods Preclinical testing of the TCD was performed in 24 Yorkshire swine, including 10 under good laboratory practice conditions. Subsequently, subjects undergoing transcatheter aortic valve replacement for symptomatic severe aortic stenosis, ineligible for transfemoral arterial access, were enrolled in a U.S. Food and Drug Administration–approved early feasibility study of the TCD (Transmural Systems, Andover, Massachusetts). Independently adjudicated endpoints included technical, device, and procedural success, incorporating in-hospital and 30-day clinical and imaging follow-up. Results Transcaval access and closure in swine confirmed that at 30 days, TCDs were almost entirely endothelialized. Subsequently, 12 subjects were enrolled in the early feasibility study. Transcaval access, transcatheter aortic valve replacement, and aortocaval fistula closure was successful in all 12 subjects. The primary endpoint of technical success was met in 100% of subjects. Complete closure of the transcaval access tract was achieved in 75% of subjects at exit from the catheterization lab and in 100% of subjects at 30 days. There were zero modified Valve Academic Research Consortium-2 major vascular complications and zero Valve Academic Research Consortium-2 life-threatening or major bleeding complications related to transcaval access or the TCD. Conclusions The TCD achieved complete closure of the transcaval access tract in most subjects at exit from the catheterization lab and essentially eliminated transcaval-related bleeding. Dedicated devices for transcaval access and closure could enable more widespread adoption of transcaval techniques without fear of bleeding complications. (Transmural Systems Transcaval Closure Device for Transcaval Access Ports During Transcatheter Aortic Valve Replacement; NCT03432494).

The circulation management strategies and operative techniques that are essential for the successful surgical repair of acute type A intramural hematoma (ATAIMH) are similar to those utilized for acute type A aortic dissection. This article reviews the neuroprotection strategies and arterial cannulation sites used in the treatment of patients with ATAIMH.

Background Current surveillance recommendations after thoracic endovascular aortic repair (TEVAR) include contrast-enhanced computed tomography (CT) scans at 1-, 2-, 6-, and 12-month intervals, with annual scans thereafter. Patient compliance with such schedules remains inconsistent for all etiologies of aortic disease. It remains unclear which boundaries prevent compliance and whether compliance is associated with improved aorta-specific outcomes. Methods A retrospective analysis was performed of a multicenter health-care system's electronic medical records to include all patients who underwent TEVAR from July 1, 2011 to April 1, 2016. Patients were assigned a compliance score of 0 through 4 based on the number of images received at the recommended time intervals. Whether patients underwent any postoperative imaging within 1 year of discharge was also recorded. Patients who died within 12 months of discharge were excluded. Aorta-specific complications included postoperative sac expansion, rupture, or need for additional aortic intervention. Results A total of 262 patients were included; of whom, 203 (77.5%) received at least one postoperative contrast-enhanced CT scan. Race, insurance status, and distance to hospital were not associated with 12-month compliance or compliance score (all P > 0.05). Regarding 12-month compliance, 76.2% of aneurysm patients, 81.6% of dissection patients, 72.2% of transection patients, and 72.2% of penetrating aortic ulcer patients underwent at least 1 CT scan within the first year (all P > 0.05). There were no differences in compliance score based on indication for repair. The overall aorta-related complication rate was 34.7%. TEVAR for dissection was associated with increased long-term aorta-specific complications (49.5%, P Conclusions In this large, multihospital analysis of TEVAR outcomes, there was no difference in compliance among patients undergoing TEVAR for major indications, but patients with dissection who required TEVAR had a significant difference in aorta-specific complication rates. TEVAR for dissection should be subject to stricter surveillance guidelines than TEVAR for other indications.

BACKGROUND: Left ventricular outflow tract (LVOT) obstruction is a leading cause of mortality and exclusion from transcatheter mitral valve replacement (TMVR). Intentional laceration of the anterior mitral valve leaflet to prevent LVOT obstruction (LAMPOON) is a transcatheter mimic of surgical chord-sparing leaflet resection. OBJECTIVES: The purpose of this prospective multicenter trial was to study LAMPOON with transseptal (Edwards Lifesciences, Irvine, California) TMVR in annuloplasty rings or native mitral annular calcification (MAC). METHODS: Subjects at high or extreme surgical risk and prohibitive risk of LVOT obstruction from TMVR were included. Eligibility was modified midtrial to exclude subjects with threatened LVOT obstruction from a Sapien 3 valve fabric skirt. The primary endpoint was procedure survival with successful LAMPOON, with successful TMVR, without reintervention, and with LVOT gradient

Patients undergoing aortic arch replacement are at high risk for neurologic injury. This study compared two different established neuroprotective strategies in patients undergoing elective transverse hemiarch replacement.Twenty patients undergoing hemiarch replacement were prospectively randomized to receive deep hypothermic circulatory arrest with retrograde cerebral perfusion (DHCA+RCP) or moderate hypothermic circulatory arrest with antegrade cerebral perfusion (MHCA+ACP). All patients received neurologist-adjudicated examinations and magnetic resonance imaging before discharge. The primary end point was a composite of stroke, transient ischemic attack, and magnetic resonance imaging-adjudicated injury. Secondary end points were transient neurologic dysfunction, and the National Institutes of Health Stroke Scale, and neurocognitive scores.Randomization resulted in 11 DHCA+RCP patients and 9 MHCA+ACP patients. There was no difference in cardiopulmonary bypass, cross-clamp, or circulatory arrest times. MHCA+ACP patients underwent circulatory arrest at significantly warmer temperatures (26.3° ± 1.8°C) than DHCA+RCP patients (19.9° ± 0.1°C, p0.0001). There were no deaths or renal failure in either group. There was 1 stroke in each group. National Institute of Health stroke scale scores and neurocognitive test results were equivalent. Diffusion-weighted magnetic resonance imaging demonstrated lesions in 100% (9 of 9) of MHCA+ACP patients compared with 45% (5 of 11) of DHCA+RCP patients (p0.01). MHCA+ACP patients had a significantly higher number of lesions than DHCA+RCP patients (p0.01). The primary end point was achieved in 100% of MHCA+ACP patients compared with 45% of DHCA+RCP patients (p0.01).Although there was no significant difference in clinically evident neurologic injury, this pilot study suggests that MHCA+ACP may be associated with a higher incidence of radiographic neurologic injury than DHCA+RCP in patients undergoing elective hemiarch replacement.

Objectives The authors investigated 1-year outcomes after transcaval access and closure for transcatheter aortic valve replacement (TAVR), using commercially available nitinol cardiac occluders off-label. Background Transcaval access is a fully percutaneous nonfemoral artery route for TAVR. The intermediate-term fate of transcaval access tracts is not known. Methods The authors performed a prospective, multicenter, independently adjudicated trial of transcaval access, using Amplatzer nitinol cardiac occluders (Abbott Vascular, Minneapolis, Minnesota), among subjects without traditional transthoracic (transapical or transaortic) access options. One-year clinical follow-up included core laboratory analysis of serial abdominal computed tomography (CT). Results 100 subjects were enrolled. Twelve-month mortality was 29%. After discharge, there were no vascular complications of transcaval access. Among 83 evaluable CT scans after 12 months, 77 of fistulas (93%) were proven occluded, and only 1 was proven patent. Fistula patency was not associated with overall survival (p = 0.37), nor with heart failure admissions (15% if patent vs. 23% if occluded; p = 0.30). There were no cases of occluder fracture or migration or visceral injury. Conclusions Results are reassuring 1 year after transcaval TAVR and closure using permeable nitinol occluders off-label. There were no late major vascular complications. CT demonstrated spontaneous closure of almost all fistulas. Results may be different in a lower-risk cohort, with increased operator experience, and using a dedicated transcaval closure device. (Transcaval Access for Transcatheter Aortic Valve Replacement in People With No Good Options for Aortic Access; NCT02280824)

Background Standard therapy for aortic root dilation in the setting of bicuspid aortic valves remains use of a composite valve conduit. The long-term durability of valve-sparing root replacement (VSRR) in bicuspid aortopathy is presently unclear. In this study, the midterm results of performing VSRR in the setting of a bicuspid valve was analyzed. Methods A single institutional database identified 280 patients who underwent VSRR from 2005 to 2016. Outcomes were analyzed in 60 consecutive patients undergoing a VSRR in the setting of a bicuspid aortic valve with aortic insufficiency (AI). Patients were followed prospectively and had annual echocardiograms. Results The average age in this series was 42 ± 11 years. Eighty percent were men and 33% had New York Heart Association class III to IV symptoms. More than 2+ AI was present in 42% of patients preoperatively. The incidence of operative death, stroke, and renal failure was 0%. Mean follow-up was 39 ± 30 months. At latest follow-up, 62% of patients had zero AI and 87% of patients had 2+ AI was 97% and freedom from AVR was 96%. Preoperative AI was not found to be a significant risk factor for postoperative >2+ AI (p = 0.61) or AVR (p = 0.61). Conclusions VSRR can be safely and effectively performed in young patients with bicuspid valve anatomy regardless of degree of preoperative AI. Valve function is durable and the incidence of valve-related complications is low. VSRR is an attractive and potentially superior option to conventional root replacement in appropriately selected patients with bicuspid aortopathy.

Valve-sparing aortic root replacement (VSRR) is an established treatment for aortic root pathology for trileaflet valves. The safety and durability of VSRR in bicuspid aortopathy is unclear. In this study, outcomes of performing VSRR in the setting of bicuspid and trileaflet valves were compared.An institutional database identified 294 patients who underwent VSRR from 2005 to 2017. Of these, 225 had trileaflet valves and 69 had bicuspid valves. Patients were followed prospectively and had annual postoperative echocardiograms. Propensity-matched comparisons were made between trileaflet and bicuspid valve patients.The average patient age for trileaflet valves was 46.0 ± 13.5 versus 42.7 ± 12.2 years for bicuspid patients (p = 0.07). There was a higher presence of preoperative2+ aortic insufficiency (AI) present in bicuspid patients (63.8%) compared with trileaflet patients (31.1%) (p0.01). Mean follow-up was 39 months and was 98% complete. At 5 years, the cumulative incidence of2+ AI and aortic valve replacement (AVR) was 2.0% and 4.3% in trileaflet patients and 7.7% (p = 0.75) and 7.7% (p = 0.81) in bicuspid patients. Preoperative2+ AI was not predictive of2+ postoperative AI (p = 0.62) nor AVR (p = 0.49). Five-year survival was no different between groups (trileaflet: 98%, bicuspid: 84%, p = 0.24).VSRR can be safely and effectively performed in patients with trileaflet and bicuspid valves. Operative outcomes and valve function were equivalent in bicuspid and trileaflet patients in midterm follow-up. Performance of VSRR is a viable term option in the setting bicuspid aortic valve aortopathy.

Aortic root replacement (ROOT) has been an established therapy, yet the impact of adding coronary artery bypass grafting (CABG) to ROOT (CABG-R) is unknown. The purpose of this research was to investigate the impact of CABG on the outcomes of ROOT.A retrospective review from 2004 to 2016 of patients undergoing nonemergent ROOT surgical procedure was performed. Cohorts were established based on the presence or absence of added CABG. A propensity-score weighted comparison of outcomes was then conducted.A total of 867 patients met inclusion criteria and were analyzed (711 ROOT [72.0%], 156 CABG-R [18.0%]). CABG-R patients were older and had higher proportions of previous valve operation, hypertension, endocarditis, immunosuppressive therapy, renal insufficiency, and redo operation (all p0.01). Indications for CABG included anatomy (n = 48, 30.8%), coronary artery disease (80, 51.3%), and ventricular failure (28, 17.9%). The permanent stroke rate was not significantly increased with the addition of CABG-R (p = 0.06). Thirty-day mortality was 5.5% for the entire cohort but was substantially higher in patients who underwent concomitant CABG (3.4% ROOT, 15.4% CABG-R). Mortality rates were highest among patients with acute ventricular failure and CABG (28.8%) compared with patients who underwent CABG for coronary artery disease (6.3%) or patients for anatomy (22.9%; p = 0.003).CABG-R results in increased postoperative morbidity or mortality compared with isolated ROOT. Outcomes, however, are influenced by the specific clinical indication. CABG for coronary artery disease was associated with similar outcomes compared with isolated ROOT. Patients undergoing unplanned CABG for acute ventricular failure had the worst outcomes, thus underscoring the importance of technical success during coronary reimplantation.

BACKGROUND: LY-CoV555, a neutralizing monoclonal antibody, has been associated with a decrease in viral load and the frequency of hospitalizations or emergency department visits among outpatients with coronavirus disease 2019 (Covid-19). Data are needed on the effect of this antibody in patients who are hospitalized with Covid-19.METHODS: In this platform trial of therapeutic agents, we randomly assigned hospitalized patients who had Covid-19 without end-organ failure in a 1:1 ratio to receive either LY-CoV555 or matching placebo. In addition, all the patients received high-quality supportive care as background therapy, including the antiviral drug remdesivir and, when indicated, supplemental oxygen and glucocorticoids. LY-CoV555 (at a dose of 7000 mg) or placebo was administered as a single intravenous infusion over a 1-hour period. The primary outcome was a sustained recovery during a 90-day period, as assessed in a time-to-event analysis. An interim futility assessment was performed on the basis of a seven-category ordinal scale for pulmonary function on day 5.RESULTS: On October 26, 2020, the data and safety monitoring board recommended stopping enrollment for futility after 314 patients (163 in the LY-CoV555 group and 151 in the placebo group) had undergone randomization and infusion. The median interval since the onset of symptoms was 7 days (interquartile range, 5 to 9). At day 5, a total of 81 patients (50%) in the LY-CoV555 group and 81 (54%) in the placebo group were in one of the two most favorable categories of the pulmonary outcome. Across the seven categories, the odds ratio of being in a more favorable category in the LY-CoV555 group than in the placebo group was 0.85 (95% confidence interval [CI], 0.56 to 1.29; P = 0.45). The percentage of patients with the primary safety outcome (a composite of death, serious adverse events, or clinical grade 3 or 4 adverse events through day 5) was similar in the LY-CoV555 group and the placebo group (19% and 14%, respectively; odds ratio, 1.56; 95% CI, 0.78 to 3.10; P = 0.20). The rate ratio for a sustained recovery was 1.06 (95% CI, 0.77 to 1.47).CONCLUSIONS: Monoclonal antibody LY-CoV555, when coadministered with remdesivir, did not demonstrate efficacy among hospitalized patients who had Covid-19 without end-organ failure. (Funded by Operation Warp Speed and others; TICO ClinicalTrials.gov number, NCT04501978.).

Introduction: There has been a recent trend towards the increased use of biologic valves at the time of surgical aortic valve replacement (SAVR) with an understanding there may be a potential need for future valve intervention. In this study, we compared the clinical outcomes of Redo-SAVR with valve-in-valve transcatheter aortic valve replacement (VIVTAVR) in patients with a prior history of SAVR. Methods: From 2012 to 2019, 263 patients underwent isolated aortic valve reintervention after prior SAVR: VIV-TAVR (n=187) or redo-SAVR (n=86). Multivariable analysis was performed to identify risk factors mortality and aortic reintervention. Sub-analyses were performed to compare VIV-TAVR patients to Redo-SAVR patients undergoing biologic valve explant and implant (Biologic) as well as VIV-TAVR and Redo-SAVR patients matched by STS Predicted Risk of Mortality (STS PROM). Results: Operative mortality for the Redo-SAVR and VIV-TAVR was 1.2% (1) and 1.6% (3) respectively (p=0.92). Redo-SAVR patients had an increased stroke rate (7.0% vs 1.1%, p=0.02) and longer postoperative length of stay (7 vs 2 days, p Conclusions: Aortic valve reintervention following prior SAVR is associated with outstanding clinical outcomes. Both Redo-SAVR and VIV-TAVR can be performed with lower than expected predicted mortality. Redo-SAVR was associated with increased morbidity compared to VIV-TAVR, but improved valve function and hemodynamics. Differences in long term valve durability and patient survival between these two therapies are yet to be determined.

BACKGROUND: Cerebral malperfusion and carotid artery dissection in patients with acute type A aortic dissections (TAAD) carry high morbidity and mortality. There are limited data on outcomes of concomitant carotid artery replacement with total arch replacement in the setting of a TAAD. METHODS: All patients with acute TAAD who underwent a total arch replacement (TAR) between 2007 and 2018 were included. Data were retrospectively collected from a prospectively maintained database. Baselines variables were compared, and Kaplan-Meier estimates were used for long term survival. Cox multivariable regression analysis was used to identify predictors of mortality. RESULTS: A total of 161 patients underwent TAR for acute TAAD. Of these, 111 underwent conventional total arch reconstruction, while 50 had a concomitant carotid artery replacement. Baseline characteristics were similar between both cohorts apart from the carotid replacement cohort having a higher rate of preoperative cerebral malperfusion (48% vs 10.81%; p

Experimental studies have shown that aortic wall tensile strengths in circumferential and longitudinal directions are different (i.e., anisotropic), and vary significantly among patients with aortic aneurysm. To assess aneurysm rupture and dissection risk, material failure metric of the aortic wall needs to be accurately defined and determined. Previously such risk assessment methods have largely relied on deterministic or isotropic failure metric. In this study, we develop a novel probabilistic and anisotropic failure metric for risk stratification of ascending thoracic aortic aneurysm (ATAA). To this end, uniaxial tensile tests were performed using aortic tissue samples of 84 ATAA patients, from which a joint probability distribution of the anisotropic wall strengths was obtained. Next, the anisotropic failure probability (FP) based on the Tsai−Hill (TH) failure criterion was derived. The novel FP metric, which incorporates uncertainty in the anisotropic failure properties, can be evaluated after the aortic wall stresses are computed from patient-specific biomechanical analysis. For method validation, “ground-truth” risks of additional 41 ATAA patients were numerically-reconstructed using corresponding CT images and tissue testing data. Performance of different risk stratification methods (e.g., with and without patient-specific hyperelastic properties) was compared using p-value and receiver operating characteristic (ROC) curve. The results show that: (1) the probabilistic FP metric outperforms the deterministic TH metric; and (2) patient-specific hyperelastic properties can help to improve the performance of probabilistic FP metric in ATAA risk stratification.

Background and aim of study Mid and long-term data regarding the durability of bicuspid aortic valve sparing root replacement is not completely understood. In this study, our institutional experience is reviewed regarding this procedure with special attention to the operative technique. Methods From 2004 to 2019, 1241 patients underwent aortic root replacement and of these 79 patients underwent bicuspid aortic valve sparing root replacement. Early and late outcomes along with echocardiographic data were reviewed. Univariate analysis was used to identify risk factors for mortality. Results Median age at operation was 43 (inner quartile range: 34.5-50.5) years, with 17% (14) being female. Median follow up time was 4 (inner quartile range: 1-8) years with 359 years of total follow up. Early mortality was 2.5% (2). Overall 10-year freedom from aortic valve intervention was 95.6%. Risk factor analysis did not demonstrate preoperative root diameter, aortic diameter, or aortic insufficiency to be risk factors for mortality. Conclusion Bicuspid aortic valve sparing root replacement can be performed safely in the setting of aortic root pathology and valve insufficiency. With appropriate selection and excellent surgical technique, long-term durable valve function is observed without the need for repeat valve intervention.

Worse outcomes have been reported for women with type A acute aortic dissection (TAAD). We sought to determine sex-specific operative approaches and outcomes for TAAD in the current era.The Interventional Cohort (IVC) of the International Registry of Acute Aortic Dissection (IRAD) database was queried to explore sex differences in presentation, operative approach, and outcomes. Multivariable logistic regression was performed to identify adjusted outcomes in relation to sex.Women constituted approximately one-third (34.3%) of the 2823 patients and were significantly older than men (65.4 vs 58.6 years, P.001). Women were more likely to present with intramural hematoma, periaortic hematoma, or complete or partial false lumen thrombosis (all P.05) and more commonly had hypotension or coma (P = .001). Men underwent a greater proportion of Bentall, complete arch, and elephant trunk procedures (all P.01). In-hospital mortality during the study period was higher in women (16.7% vs 13.8%, P = .039). After adjustment, female sex trended towards higher in-hospital mortality overall (odds ratio, 1.40; P = .053) but not in the last decade of enrollment (odds ratio, 0.93; P = .807). Five-year mortality and reintervention rates were not significantly different between the sexes.In-hospital mortality remains higher among women with TAAD but demonstrates improvement in the last decade. Significant differences in presentation were noted in women, including older age, distinct imaging findings, and greater evidence of malperfusion. Although no distinctions in 5-year mortality or reintervention were observed, a tailored surgical approach should be considered to reduce sex disparities in early mortality rates for TAAD.

Objective The incidence and outcomes of patients with heparin-induced thrombocytopenia (HIT) are well defined for general cardiac surgical populations. The purpose of this study was to define the outcomes of patients with HIT in a population excluding patients who underwent coronary artery bypass grafting (CABG). Methods The local Society of Thoracic Surgeons cardiac surgical database was queried between January 2008 and May 2017 for patients who underwent either open valvular surgery or aortic surgery. Patients who underwent either isolated or combined CABG procedures were excluded. Cohorts were formed based on the presence or absence of postoperative HIT. Logistic regression models were built to determine the association between postoperative HIT and outcomes, adjusted for both preoperative and intraoperative variables. Results Of the total cohort (8,107 patients), 176 patients (2.2%) developed HIT after surgery. HIT patients experienced an increased incidence of morbidities postoperatively, including reoperation for bleeding, reoperation for cardiac and noncardiac etiologies, postoperative stroke, perioperative myocardial infarction, postoperative sternal infection, postoperative arrhythmia, new-onset renal failure, and dialysis (all with P < 0.01). The unadjusted 30-day mortality was 14.8% in HIT patients vs 4.9% in those without HIT ( P < 0.01). After risk adjustment, reoperation for noncardiac events, renal failure, new dialysis, postoperative stroke, arrhythmia, and sternal wound infection remained significantly elevated in patients who developed postoperative HIT. Conclusions Patients who developed HIT after non-CABG cardiac surgery experienced increased postoperative rates of morbidity and mortality. Early diagnosis and treatment remained mainstays of therapy. Early identification of patients at highest risk should prompt careful risk stratification when possible.

Valve-sparing root replacement is more challenging with eccentric aortic insufficiency due to cusp and root asymmetry, which may impact valve durability and survival. This study analyzed the effect of jet eccentricity on long-term outcomes in tricuspid aortic valves (TAVs) and bicuspid aortic valves (BAVs).From 2005 to 2019, 111 patients (65 TAVs, 46 BAVs) with2+ aortic insufficiency underwent valve-sparing root replacement at an academic center. Pre- and postoperative echocardiograms were analyzed. Of these, 32 patients presented with concentric jets (29 TAVs, 3 BAVs) and 71 with eccentric jets (28 TAVs, 43 BAVs). Median follow-up was 49 months (interquartile range, 12-93). Kaplan-Meier analysis and cumulative risk were used to compare long-term survival and valve-related reintervention.Mean patient age was 44 ± 12 years. Compared with TAV, more BAV patients presented with eccentric jets (93.5% vs 43.1%, P.001). All BAV patients received cusp repair compared with 52.3% of TAV patients (P.001). At 3, 5, and 10 years the cumulative risk of aortic valve replacement for TAV (4.7%, 6.4%, and 6.4%) versus BAV (5.8%, 7.8%, and 7.8%) patients (P = .87) and concentric (0%, 0%, and 0%) versus eccentric (6.4%, 9.4%, and 9.4%) jets (P = .98) was similar. Overall survival at 10 years was 71% for TAV and 97% for BAV (P = .19) and 86% for concentric and 79% for eccentric jets (P = .17).In patients presenting for valve-sparing root replacement with2+ aortic insufficiency the risk of valve-related reintervention long term was low after cusp repair in TAVs and BAVs. Current results suggest preoperative jet eccentricity does not impact long-term survival and valve durability.

BACKGROUND. Thoracic endovascular aortic repair (TEVAR) with endograft coverage from the left subclavian artery to the celiac artery has been hypothesized to increase spinal cord ischemia. This study analyzes the impact of extended coverage on adverse outcomes and aortic remodeling in patients with complicated acute type B aortic dissection (aTBAD). METHODS. From January 2012 to October 2018, 91 patients underwent TEVAR for aTBAD. Median follow-up was 3.1 (interquartile range, 1.2-4.9) years and was complete in 94% of patients. The extent of aortic endograft coverage was categorized as standard (n = 39) or extended (n = 52). Contrast-enhanced imaging scans were analyzed to determine length of coverage, maximum aortic diameters, and false lumen (FL) status. RESULTS. The mean age was 52.6 ± 13.9 years, and 66% were men. The most common indications for intervention were malperfusion (42%) and refractory pain (34%). Thirteen (14%) patients required a lumbar drain (preoperative: n = 3; postoperative: n = 10). Mean duration between scans was 2.0 ± 1.9 years. Length of aortic coverage was significantly longer in the extended group (241.7 ± 29.2 mm vs 180.8 ± 22.3 mm in the standard group; P < .001). In-hospital and overall mortality were 6% and 11%, respectively. There were no cases of paraplegia, and the incidence of spinal cord ischemia was 3%. After TEVAR, there was a higher incidence of FL obliteration or thrombosis at the distal descending thoracic aorta in the extended group (53% vs 16% in the standard group; P = .004). CONCLUSIONS. Extended TEVAR carries a low risk of spinal cord ischemia and improves FL remodeling of the descending thoracic aorta in patients with aTBAD. This strategy may decrease the need for reinterventions on the thoracic aorta in the chronic phase of TBAD.