Rationale: There are limited therapeutic options for patients with coronavirus disease (COVID-19)-related acute respiratory distress syndrome with inflammation-mediated lung injury. Mesenchymal stromal cells offer promise as immunomodulatory agents. Objectives: Evaluation of efficacy and safety of allogeneic mesenchymal cells in mechanically-ventilated patients with moderate or severe COVID-19-induced respiratory failure. Methods: Patients were randomized to two infusions of 2 million cells/kg or sham infusions, in addition to the 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. Measurements and Main Results: At the third interim analysis, the data and safety monitoring board recommended that the trial halt enrollment as the prespecified 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 (relative risk [RR], 0.88; 95% confidence interval, 0.64-1.21; P= 0.43). There were no significant differences in days alive off ventilation within 60 days (median rank, 117.3 [interquartile range, 60.0-169.5] in cell patients and 102.0 [interquartile range, 54.0-162.5] in control subjects; higher is better). Resolution or improvement of acute respiratory distress syndrome at 30 days was observed in 51/104 (49.0%) cell recipients and 46/106 (43.4%) control patients (odds ratio, 1.36; 95% confidence interval, 0.57-3.21). There were no infusion-related toxicities and overall serious adverse events over 30 days were similar. Conclusions: Mesenchymal cells, while safe, did not improve 30-day survival or 60-day ventilator-free days in patients with moderate and/or severe COVID-19-related acute respiratory distress syndrome.

Background: 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). Methods: From 2005 to 2019, 111 patients (65 TAVs, 46 BAVs) with >2+ 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. Results: 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). Conclusions: In patients presenting for valve-sparing root replacement with >2+ 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.

The David V valve-sparing root replacement (VSRR) is well-established for the treatment of aortic insufficiency (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 outcomes in TAV patients with pre-operative AI >2+ based on jet centricity and cusp repair status. Review of a single institutional database identified 309 consecutive patients undergoing VSRR from 2005 to 2018. Of these, 51 patients had TAV with AI >2+: 25 concentric and 26 eccentric jets. Mean follow-up was 58 (SD = 44) months. Echocardiographic parameters were compared pre- and post-operatively. Kaplan-Meier analysis, longitudinal mixed modeling, and cumulative incidence were used to compare long-term survival, recurrence of AI >1+, and valve specific re-intervention, respectively. The mean age was 48 (SD = 12) years and 84% were male. Differences in preoperative comorbidities and echocardiographic parameters between groups were not statistically significant. Postoperative outcomes were similar in concentric vs. eccentric and cusp vs. no cusp repair. Recurrence of AI>1+ was minimal and unrelated to jet centricity (concentric = 1, eccentric = 3) and cusp repair (no cusp repair = 1, cusp repair = 3) long-term. Aortic valve replacement cumulative incidence was 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. In appropriately selected TAV patients with preoperative AI >2+, current results suggest VSRR provides a durable repair regardless of jet centricity or the need for cusp repair based on low rates of reintervention reported.

Background: The advent of transcatheter aortic valve replacement (TAVR) has directly impacted the lifelong management of patients with aortic valve disease. The U.S. Food and Drug Administration has approved TAVR for all surgical risk: prohibitive (2011), high (2012), intermediate (2016), and low (2019). Since then, TAVR volumes are increasing and surgical aortic valve replacements (SAVR) are decreasing. This study sought to evaluate trends in isolated SAVR in the pre- and post-TAVR eras. Methods: From January 2000 to June 2020, 3,861 isolated SAVRs were performed at a single academic quaternary care institution which participated in the early trials of TAVR beginning in 2007. A formal structural heart center was established in 2012 when TAVR became commercially available. Patients were divided into the pre-TAVR era (2000–2011, n = 2,426) and post-TAVR era (2012–2020, n = 1,435). Data from the institutional Society of Thoracic Surgeons National Database was analyzed. Results: The median age was 66 years, similar between groups. The post-TAVR group had a statistically higher rate of diabetes, hypertension, dyslipidemia, heart failure, more reoperative SAVR, and lower STS Predicted Risk of Mortality (PROM) (2.0% vs. 2.5%, p < 0.0001). There were more urgent/emergent/salvage SAVRs (38% vs. 24%) and fewer elective SAVRs (63% vs. 76%), (p < 0.0001) in the post-TAVR group. More bioprosthetic valves were implanted in the post-TAVR group (85% vs. 74%, p < 0.0001). Larger aortic valves were implanted (25 vs. 23 mm, p < 0.0001) and more annular enlargements were performed (5.9% vs. 1.6%, p < 0.0001) in the post-TAVR era. Postoperatively, the post-TAVR group had less blood product transfusion (49% vs. 58%, p < 0.0001), renal failure (1.4% vs. 4.3%, p < 0.0001), pneumonia (2.3% vs. 3.8%, p = 0.01), shorter lengths of stay, and lower in-hospital mortality (1.5% vs. 3.3%, p = 0.0007). Conclusion: The approval of TAVR changed the landscape of aortic valve disease management. At a quaternary academic cardiac surgery center with a well-established structural heart program, patients undergoing isolated SAVR in the post-TAVR era had lower STS PROM, more implantation of bioprosthetic valves, utilization of larger valves, annular enlargement, and lower in-hospital mortality. Isolated SAVR continues to be performed in the TAVR era with excellent outcomes. SAVR remains an essential tool in the lifetime management of aortic valve disease.

Aberrant right subclavian artery (ARSA) is a rare anatomic variant in which the right subclavian artery originates distal to the left subclavian artery (LSA) and crosses the midline in a retroesophageal course before assuming its right subclavicular position. Patients with acute type B aortic dissection (ATBAD) and ARSA pose a unique challenge due to the absence of an appropriate proximal landing zone for thoracic endovascular aortic repair (TEVAR) without covering both subclavian arteries. In this case series, 2 different hybrid techniques of central 4-vessel arch reconstruction with TEVAR are described to treat 4 patients with complicated ATBAD and ARSA.

N/A

Proximal thoracic aortic reconstruction performed with or without hypothermic circulatory arrest (HCA) is an effective surgical strategy for aortic pathology. In this study, the clinical outcomes of patients undergoing reoperative proximal thoracic aortic surgery were evaluated. A retrospective review was performed for reoperative proximal aortic surgery from 2004 to date. Patient data were abstracted from the society of thoracic surgeons (STS) institutional database and patient charts. Univariate analysis was conducted on the HCA group in order to determine the impact of variables on in-hospital mortality. Kaplan–Meier survival estimates were calculated for long-term survival analysis. One hundred and twenty-two patients were included in the analysis. Twenty-seven (22.1%) were female, and the mean age was 53.8 years. Seventy-seven (63.1%) patients had an aortic root replacement, and 93 (76.2%) patients underwent aortic arch replacement. Circulatory arrest was performed in 92 (75.4%) patients. Operative mortality occurred in 14 patients (11.5%). Complications included re-exploration for haemorrhage (nine patients, 7.4%), stroke (four, 3.3%), renal failure (13, 10.7%) and major adverse events (18, 14.8%). Univariate and multivariate analyses of HCA patients showed cardiopulmonary bypass (CPB) time, preoperative renal failure and prior coronary revascularization as independent predictors of mortality. Reoperative proximal aortic surgery can be performed with acceptable morbidity and mortality. These data also suggest that HCA represents a safe operative strategy for this patient population.

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).

To date, transapical (TA) access has proven to be a safe and effective method of performing transcatheter aortic valve replacement (TAVR) for the treatment of patients with severe aortic stenosis. Current transcatheter mitral valve technologies are forthcoming, with the majority being performed via the TA access route. Current first generation devices will utilize >34F sheaths for deployment of the new mitral technology. It is quite feasible that novel apical access may potentially facilitate access and closure of this high-risk patient population. Although TA access has a <1% access-related complication rate, the ventricle can be quite difficult to manage when adverse consequences do occur (1,2). The TA technique has several advantages over transfemoral access, including: (I) a short distance to the aortic valve which enables precise control over the device facilitating accurate valve deployment; (II) avoidance of delivery device transit across the aortic arch which may reduce the risk of stroke; (III) no restriction on the sheath size of the delivery device. These characteristics make TA access the ideal platform for future transcatheter mitral valve interventions. Despite the aforementioned advantages, the increased utilization of TA access has been limited due to the need for a small anterolateral thoracotomy and the potential risk of hemorrhage when closing the apex with sutures. These two limitations have sparked the development of apical access and closure devices that could transform TA access into a more reproducible and percutaneous procedure. This article reviews the current status of these devices.

Objective Over the past decade, thoracic endovascular aortic repair (TEVAR) has increased as a treatment option for a variety of aortic pathologies. Despite this rise in the use of thoracic stent grafts, real-world outcomes from a robust, adjudicated, contemporary dataset have yet to be reported. Previous studies have shown peri-procedural mortality rates between 1.5%-9.5% and procedure-related stroke rates of 2.3%-8.2%. With advances in device engineering and increased physician experience, we hypothesized that the rates of these complications would be reduced in a more recent sample set. The purpose of this study was to determine current rates of mortality and stroke after TEVAR, identify risk factors that contribute to thirty-day mortality, and develop a simple scoring system that allows for risk stratification of patients undergoing TEVAR. Methods We examined the 30-day mortality rate following TEVAR using the 2013-2014 American College of Surgeons National Surgical Quality Improvement Program database. Patients undergoing TEVAR for all aortic pathology were identified using procedure codes. Bivariate analyses were performed to evaluate the association of pre-, intra- and post-operative variables with 30-day mortality, followed by multivariable logistic analysis using pre-operative variables only, with P<.10 as criteria for model entry. The predictive logistic model was internally validated by cross validation. Variables included in the multivariable model were used to develop a risk score. Results Eight hundred twenty-six patients were included. The thirty-day mortality and stroke rate were 7.63% (n=63) and 4.5% (n= 37), respectively. In regression analysis, mortality was independently associated with age ≥80 years (odds ratio [OR] 2.32, 95% confidence interval [CI] 1.25-4.31), emergency case (OR 2.61, 95% CI 1.39-4.90), ASA classification >3 (OR 2.89, 95% CI 1.34-6.24), transfusion >4 units in the 72 hours prior to surgery (OR 2.86, 95% CI 1.30-6.28), pre-operative creatinine ≥1.8 mg/dL (OR 2.07, 95% CI 1.05-4.08), and pre-operative white blood cell count ≥12 × 109/L (OR 2.65, 95% CI 1.41-4.96). Incorporating these factors, a six-point risk score was generated and demonstrated high predictability for overall thirty-day mortality. Conclusions Recent data from a national, retrospective dataset demonstrate that high perioperative mortality and stroke rates have persisted over the last decade. The risk score derived from this dataset is simple and convenient and serves as a prognostic tool in the pre-operative risk stratification of patients being evaluated for thoracic endovascular aortic repair.