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Abdominal Aortic Aneurysms (AAA) remain a clinically devastating disease with no effective medical treatment therapy. AAAs are characterized by immune cell infiltration, smooth muscle cell apoptosis, and extracellular matrix degradation. Interleukin-1 (IL-1) has been shown to play role in AAA associated inflammation through immune cell recruitment and activation, endothelial dysfunction, production of reactive oxygen species (ROS), and regulation of transcription factors of additional inflammatory mediators. In this review, we will discuss the principles of IL-1 signaling, its role in AAA specific inflammation, and regulators of IL-1 signaling. Additionally, we will discuss the influence of genetic and pharmacological inhibitors of IL-1 on experimental AAAs. Evidence suggests that IL-1 may prove to be a potential therapeutic target in the management of AAA disease.

Interleukin-1 (IL-1) signaling has an established role as a cytokine signaling pathway important for progression of abdominal aortic aneurysms (AAAs). While the IL-1β ligand and IL-1R1 have been previously investigated, the role of the IL-1α ligand in AAAs remains unknown. In this study, we sought to examine the role of IL-1α in AAAs using genetic and pharmacologic approaches.Eight-week-old wild-type (WT) or IL-1α knock-out (KO) male and female mice (n = 10-16/group) underwent experimental AAA and were harvested 14 days following surgery to assess AAA size and characteristics. In separate studies, 8-week-old WT mice were treated with an inhibitor to IL-1α during AAA formation and harvested 14 days following surgery. Finally, WT and IL-1α KO mice were administered Anakinra, an IL-R1 inhibitor, during AAA formation to determine the effect of inhibiting IL-1R1 when IL-1α is knocked out.Male and female IL-1α KO mice had larger AAAs compared to WT AAAs (male: 153% vs. 89.2%, P = 0.0001; female: 86.6% vs. 63.5%, P = 0.02). IL-1α KO mice had greater elastin breakage (P = 0.01), increased levels of macrophage staining (P = 0.0045), and greater pro-metallo proteinase 2 (P = 0.02). Pharmacologic inhibition of WT male mice with an IL-1α neutralizing antibody resulted in larger AAAs (133.1% vs. 77.0%, P 0.001). Finally, treatment of IL-1α KO male mice with Anakinra decreased AAA formation compared with vehicle control AAAs (Anakinra + IL-1α KO: 47.7% vs. WT: 147.1%; P = 0.0001).IL-1α disruption using either genetic or pharmacologic approaches worsens AAAs.

Background: Aging enhances most chronic diseases but its impact on human aortic tissue in health and in thoracic aortic aneurysms (TAA) remains unclear. Methods: We employed a human aortic biorepository of healthy specimens (n=17) and those that underwent surgical repair for TAA (n=20). First, we performed proteomics comparing aortas of healthy donors to aneurysmal specimens, in young (ie, Results: Proteomics revealed that aging transformed the aorta both quantitatively and qualitatively from health to TAA. Whereas young aortas exhibited an enrichment of immunologic processes, older aortas exhibited an enrichment of metabolic processes. Immunoblotting revealed that the expression of Parkin directly correlated to subject age in health but inversely to subject age in TAA. In TAA, but not in health, phosphorylation of STING and the expression of IFN-β was impacted by aging regardless of whether subjects had bicuspid or tricuspid valves. In subjects with bicuspid valves and TAAs, TLR9 expression positively correlated with subject age. Interestingly, whereas phosphorylation of STING was inversely correlated with subject age, IFN-β positively correlated with subject age. Conclusions: Aging transforms the human aortic proteome from health to TAA, leading to a differential regulation of biological processes. Our results suggest that the development of therapies to mitigate vascular diseases including TAA may need to be modified depending on subject age.

Refractory right ventricular failure at the time of left ventricular assist device implantation requires treatment with supplemental mechanical circulatory support. However, the optimal strategy for support remains unknown.All patients undergoing first-time durable left ventricular assist device implantation with a contemporary device were selected from The Society of Thoracic Surgeons National Database (2011 to 2019). Patients requiring right ventricular assist device (RVAD) or venoarterial extracorporeal membrane oxygenation (VA-ECMO) were included in the analysis. Patients were stratified by RVAD or VA-ECMO and by timing of placement (intraoperative vs postoperative).In all, 18 423 left ventricular assist device implants were identified, of which 940 (5.1%) required RVAD (n = 750) or VA-ECMO (n = 190) support. Patients receiving an RVAD more frequently had preoperative inotrope requirement (76% vs 62%, P.01) and severe tricuspid regurgitation (20% vs 13%, P.01). The RVAD patients had lower rates of postoperative renal failure (40% vs 51%, P = .02) and limb ischemia (4% vs 13%, P.01), as well as significantly less operative mortality (41% vs 54%, P.01). After risk adjustment with propensity score analysis, support with VA-ECMO was associated with a higher risk of mortality (risk ratio 1.46; 95% confidence interval, 1.21 to 1.77; P.01) compared with patients receiving an RVAD. Importantly, institution of right ventricular support postoperatively was associated with higher mortality (1.43, P.01) compared with intraoperative initiation.Patients with severe right ventricular failure in the setting of durable left ventricular assist device implantation may benefit from the use of RVAD over VA-ECMO. Regardless of the type of support, initiation at the index operation was associated with improved outcomes.

BACKGROUND The association, if any, between the effective regurgitant orifice (EROA) to left ventricular end-diastolic volume (LVEDV) ratio and 1-year mortality is controversial in patients undergoing mitral transcatheter edge-to-edge repair (m-TEER) with the MitraClip™ system. The objective is to determine the association between EROA/LVEDV and 1-year mortality among patients undergoing m-TEER with MitraClip™. METHODS In patients with severe secondary (functional) mitral regurgitation (MR), we analyzed registry data from 11 centers using generalized linear models with the generalized estimating equations approach. RESULTS We studied 525 patients with secondary MR who underwent m-TEER in 11 centers. Most patients were male (63%) and were NYHA class III (61%) or IV (21%). MR was caused by ischemic cardiomyopathy in 51% of patients. EROA/LVEDV values varied widely with median=0.19 mm2/mL, interquartile range [0.12,0.28] mm2/mL, and 187 (36%) patients had values

BACKGROUND: Coronary artery bypass grafting (CABG) is the most common revascularization approach for the treatment of multi-vessel coronary artery disease. While the internal mammary artery is nearly universally used to bypass the left anterior descending coronary artery, autologous saphenous vein grafts (SVGs) are still the most frequently used conduits to grafts the remaining coronary artery targets Long-term failure of these grafts, however, continues to limit the benefits of surgery. DESIGN: The Cardiothoracic Surgical Trials Network trial of the safety and effectiveness of a Venous External Support (VEST) device is a randomized, multicenter, within-patient trial comparing VEST-supported versus unsupported saphenous vein grafts in patients undergoing CABG. Key inclusion criteria are the need for CABG with a planned internal mammary artery to the left anterior descending and two or more saphenous vein grafts to other coronary arteries. The primary efficacy endpoint of the trial is SVG intimal hyperplasia (plaque + media) area assessed by intravascular ultrasound at 12 months post randomization. Occluded grafts are accounted for in the analysis of the primary endpoint. Secondary confirmatory endpoints are lumen diameter uniformity and graft failure (>50% stenosis) assessed by coronary angiography at 12 months. The safety endpoints are the occurrence of major adverse cardiac and cerebrovascular events and hospitalization within 5 years from randomization. CONCLUSIONS: The results of the VEST trial will determine whether the VEST device can safely limit SVG intimal hyperplasia in patients undergoing CABG as treatment for coronary atherosclerotic disease.

Despite the rapid adoption of transcatheter aortic replacement (TAVR), surgical TAVR valve explantation (TAVR-explant) and the clinical impact of explanted TAVR device type are not well described.TAVR-explant from 2016 to 2019 was queried using the Society of Thoracic Surgeons (STS) National Database. A total of 483 patients with documented explanted valve type, consisting of 330 (68%) patients with balloon-expandable and 153 (32%) patients with self-expandable devices, were identified. The primary outcome was 30-day mortality. The secondary outcome was the need for any simultaneous procedures with TAVR-explant.The mean age was 72.8 years, 38% of the patients were female, and 51% demonstrated New York Heart Association functional class III to IV symptoms. During TAVR-explant, 63% of patients required other simultaneous procedures, including aortic repair (27%), mitral procedures (22%), coronary artery bypass grafting (15%), and tricuspid procedures (7%). Patients with a self-expandable device underwent more frequent ascending aortic replacement (22% vs 9%; P.001) than those with a balloon-expandable device, whereas the aortic root replacement rate was similar (19% vs 24%; P = .22). The overall 30-day mortality was 18% without differences in the mortality or other major complications between the groups. Of the 157 patients with isolated surgical aortic valve replacement and available STS predicted risk of mortality score, the observed-to-expected (O/E) mortality ratio was 2.2.The TAVR-explant outcomes were comparable between patients with balloon-expandable devices and patients with self-expandable devices, whereas ascending aortic replacement was observed more frequently in patients with self-expandable devices. Younger patients undergoing TAVR should be informed of the future TAVR-explant risk that may accompany a higher O/E ratio and frequent morbid concurrent procedures.

Tricuspid regurgitation is common in patients with severe degenerative mitral regurgitation. However, the evidence base is insufficient to inform a decision about whether to perform tricuspid-valve repair during mitral-valve surgery in patients who have moderate tricuspid regurgitation or less-than-moderate regurgitation with annular dilatation.We randomly assigned 401 patients who were undergoing mitral-valve surgery for degenerative mitral regurgitation to receive a procedure with or without tricuspid annuloplasty (TA). The primary 2-year end point was a composite of reoperation for tricuspid regurgitation, progression of tricuspid regurgitation by two grades from baseline or the presence of severe tricuspid regurgitation, or death.Patients who underwent mitral-valve surgery plus TA had fewer primary-end-point events than those who underwent mitral-valve surgery alone (3.9% vs. 10.2%) (relative risk, 0.37; 95% confidence interval [CI], 0.16 to 0.86; P = 0.02). Two-year mortality was 3.2% in the surgery-plus-TA group and 4.5% in the surgery-alone group (relative risk, 0.69; 95% CI, 0.25 to 1.88). The 2-year prevalence of progression of tricuspid regurgitation was lower in the surgery-plus-TA group than in the surgery-alone group (0.6% vs. 6.1%; relative risk, 0.09; 95% CI, 0.01 to 0.69). The frequencies of major adverse cardiac and cerebrovascular events, functional status, and quality of life were similar in the two groups at 2 years, although the incidence of permanent pacemaker implantation was higher in the surgery-plus-TA group than in the surgery-alone group (14.1% vs. 2.5%; rate ratio, 5.75; 95% CI, 2.27 to 14.60).Among patients undergoing mitral-valve surgery, those who also received TA had a lower incidence of a primary-end-point event than those who underwent mitral-valve surgery alone at 2 years, a reduction that was driven by less frequent progression to severe tricuspid regurgitation. Tricuspid repair resulted in more frequent permanent pacemaker implantation. Whether reduced progression of tricuspid regurgitation results in long-term clinical benefit can be determined only with longer follow-up. (Funded by the National Heart, Lung, and Blood Institute and the German Center for Cardiovascular Research; ClinicalTrials.gov number, NCT02675244.).

Background Thoracic aortic aneurysms (TAA) are a progressive disease characterized by inflammation, smooth muscle cell activation and matrix degradation. We hypothesized that mesenchymal stem cells (MSCs) can immunomodulate vascular inflammation and remodeling via altered microRNA (miRNAs) expression profile to attenuate TAA formation. Materials and methods C57BL/6 mice underwent topical elastase application to form descending TAAs. Mice were also treated with MSCs on days 1 and 5 and aortas were analyzed on day 14 for aortic diameter. Cytokine array was performed in aortic tissue and total RNA was tagged and hybridized for miRNAs microarray analysis. Immunohistochemistry was performed for elastin degradation and leukocyte infiltration. Results Treatment with MSCs significantly attenuated aortic diameter and TAA formation compared to untreated mice. MSC administration also attenuated T-cell, neutrophil and macrophage infiltration and prevented elastic degradation to mitigate vascular remodeling. MSC treatment also attenuated aortic inflammation by decreasing proinflammatory cytokines (CXCL13, IL-27, CXCL12 and RANTES) and upregulating anti-inflammatory interleukin-10 expression in aortic tissue of elastase-treated mice. TAA formation demonstrated activation of specific miRNAs that are associated with aortic inflammation and vascular remodeling. Our results also demonstrated that MSCs modulate a different set of miRNAs that are associated with decrease leukocyte infiltration and vascular inflammation to attenuate the aortic diameter and TAA formation. Conclusions These results indicate that MSCs immunomodulate specific miRNAs that are associated with modulating hallmarks of aortic inflammation and vascular remodeling of aortic aneurysms. Targeted therapies designed using MSCs and miRNAs have the potential to regulate the growth and development of TAAs.

B cell–activating factor (BAFF), part of a tumor necrosis factor family of cytokines, was recently identified as a regulator of atherosclerosis; however, its role in aortic aneurysm has not been determined. Here, the study examined the effect of selective BAFF antagonism using an anti-BAFF antibody (blocks binding of BAFF to receptors BAFF receptor 3, transmembrane activator and CAML interactor, and B-cell maturation antigen) and mBaffR-mFc (blocks binding of BAFF to BAFF receptor 3) on a murine model of abdominal aortic aneurysm (AAA). In a prevention strategy, the antagonists were injected before the induction of AAA, and in an intervention strategy, the antagonists were injected after the induction of AAA. Both strategies attenuated the formation of AAA. In the intervention group, BAFF antagonism depleted most of the mature B-cell subsets in spleen and circulation, leading to enhanced resolution of inflammation in AAA as indicated by decreased infiltration of B cells and proinflammatory macrophages and a reduced number of apoptotic cells. In AAA tissues, B cells and macrophages were found in close contact. In vitro, B cells, irrespective of treatment with BAFF, impaired the efferocytosis activity of macrophages, suggesting a direct innate role of B cells on macrophage function. Altogether, BAFF antagonism affects survival of the mature B cells, promotes resolution of inflammation in the aorta, and attenuates the growth of AAA in mice.

Objectives Two trials (Cardiovascular Outcomes Assessment of the MitraClip Percutaneous Therapy for Heart Failure Patients with Functional Mitral Regurgitation Trial and Percutaneous Repair with the MitraClip Device for Severe Functional/Secondary Mitral Regurgitation Trial) were published in 2018 evaluating the effectiveness and safety of transcatheter repair for patients with heart failure with significant functional mitral regurgitation, which yielded different results. This article reviews the strength of the evidence, differences in trial designs, ethical and implementation implications, and delineates future research needs to help guide the appropriate dissemination of transcatheter repair for functional patients with mitral regurgitation. Methods The National Heart, Lung, and Blood Institute convened a workshop of interdisciplinary experts to address these objectives. Results Transcatheter repair of functional mitral regurgitation can provide significant benefits in terms of heart failure hospitalizations, survival, and quality of life when appropriate heart failure candidates with moderate to severe or severe mitral regurgitation while on optimal guideline-directed medical therapy can be identified. Key ingredients for success are preoperative evaluation and management and postoperative care by an interdisciplinary heart team. Conclusions Given the discordance observed between trials, ongoing innovation in patient management, and potential expansion of indications for use, the evidence base must be expanded to optimize appropriate implementation of this complex therapy. This will require more complete capture of outcome data in real-world settings for all eligible candidates whether or not they receive this therapy. Inevitably, the indications for use of this therapy will expand, as will the devices and therapeutic approaches for this population, necessitating the study of comparative effectiveness through randomized trials or observational studies. Moreover, given the substantial variations in care delivery, conducting implementation research to delineate characteristics of the optimal care model would be of benefit.

Background Patient prosthesis mismatch is associated with significant long-term morbidity and mortality after aortic valve replacement, but the role and outcomes of annular enlargement (AE) remain poorly defined. We hypothesized that increasing rates of AE may lead to improved outcomes for patients at risk for severe patient prosthesis mismatch. Methods Patients over age 65 years undergoing surgical aortic valve replacement with or without coronary artery bypass grafting from 2008-2016 in The Society of Thoracic Surgeons Adult Cardiac Surgery Database with matching Centers for Medicare & Medicaid Services data were included (n=189,268). Univariate, multivariate, and time-to-event analysis was used to evaluate the association between AE and early and late outcomes. Patients were stratified by projected degree of patient prosthesis mismatch based on calculated effective orifice area index. Results A total of 5412 (2.9%) patients underwent AE. The Society of Thoracic Surgeons Adult Cardiac Surgery Database–predicted mortality was similar between AE and non-AE groups (2.97% vs 2.99%, P = .052). Patients undergoing AE had higher risk-adjusted rates of 30-day complications and death (5.4% vs 3.4%, P Conclusions These data suggest that annular enlargement during surgical aortic valve replacement is associated with increased short-term risk in a Medicare population. Survival curves crossed after 3 years, which may portend a benefit in select patients. However, annular enlargement is still only performed in the minority of patients who are at risk for patient prosthesis mismatch.

Objectives The aim of this study was to determine clinical and echocardiographic characteristics, mechanisms of failure, and outcomes of mitral valve (MV) surgery after transcatheter edge-to-edge repair (TEER). Background Although >100,000 mitral TEER procedures have been performed worldwide, longitudinal data on MV surgery after TEER are lacking. Methods Data from the multicenter, international CUTTING-EDGE registry were retrospectively analyzed. Clinical and echocardiographic outcomes were evaluated. Median follow-up duration was 9.0 months (interquartile range [IQR]: 1.2-25.7 months) after MV surgery, and follow-up was 96.1% complete at 30 days and 81.1% complete at 1 year. Results From July 2009 to July 2020, 332 patients across 34 centers underwent MV surgery after TEER. The mean age was 73.8 ± 10.1 years, median Society of Thoracic Surgeons risk for MV repair at initial TEER was 4.0 (IQR: 2.3-7.3), and primary/mixed and secondary mitral regurgitation were present in 59.0% and 38.5%, respectively. The median interval from TEER to surgery was 3.5 months (IQR: 0.5-11.9 months), with overall median Society of Thoracic Surgeons risk of 4.8% for MV replacement (IQR: 2.8%-8.4%). The primary indication for surgery was recurrent mitral regurgitation (33.5%), and MV replacement and concomitant tricuspid surgery were performed in 92.5% and 42.2% of patients, respectively. The 30-day and 1-year mortality rates were 16.6% and 31.3%, respectively. On Kaplan-Meier analysis, the actuarial estimates of mortality were 24.1% at 1 year and 31.7% at 3 years after MV surgery. Conclusions In this first report of the CUTTING-EDGE registry, the mortality and morbidity risks of MV surgery after TEER were not negligible, and only

Transcatheter mitral valve replacement (TMVR) is a new therapy for treating symptomatic mitral regurgitation (MR) and stenosis. The proposed benefit of TMVR is the predictable, complete elimination of MR, which is less certain with transcatheter repair technologies such as TEER (transcatheter edge-to-edge repair). The potential benefit of MR elimination with TMVR needs to be rigorously evaluated against its risks which include relative procedural invasiveness, need for anticoagulation, and chronic structural valve deterioration. Randomized controlled trials (RCTs) are a powerful method for evaluating the safety and effectiveness of TMVR against current standard of care transcatheter therapies, such as TEER. RCTs not only help with the assessment of benefits and risks, but also with policies for determining operator or institutional requirements, resource utilization, and reimbursement. In this paper, the authors provide recommendations and considerations for designing pivotal RCTs for first-in-class TMVR devices.

Time-directed extubation (fast-track) protocols may decrease length of stay and cost but data on operating room (OR) extubation is limited. The objective of this study was to compare the outcomes of extubation in the OR versus fast-track extubation within 6 hours of leaving the operating room. Patients undergoing nonemergent STS index cases (2011-2021) who were extubated within 6 hours were identified from a regional STS quality collaborative. Patients were stratified by extubation in the OR versus fast track. Propensity score matching (1:n) was performed to balance baseline differences. Of the 24,962 patients, 498 were extubated in the OR. After matching, 487 OR extubation cases and 899 fast track cases were well balanced. The rate of reintubation was higher for patients extubated in the OR [21/487 (4.3%) vs 16/899 (1.8%), P = 0.008] as was the incidence of reoperation for bleeding [12/487 (2.5%) vs 8/899 (0.9%), P = 0.03]. There was no significant difference in the rate of any reoperation [16/487 (3.3%) vs 15/899 (1.6%), P = 0.06] or operative mortality [4/487 (0.8%) vs 6/899 (0.6%), P = 0.7]. OR extubation was associated with shorter hospital length of stay (5.6 vs 6.2 days, P0.001) and lower total cost of admission ($29,602 vs $31,565 P0.001). OR extubation is associated with a higher postoperative risk of reintubation and reoperation due to bleeding, but lower resource utilization.Future research exploring predictors of extubation readiness may be required prior to widespread adoption of this practice.

Health Professional Shortage Areas (HPSA) were created by the Health Resources and Services Administration to identify communities with a shortage of clinical providers. For medical conditions, these designations are associated with worse outcomes. However, far less is known about patients undergoing high complexity surgical procedures, such as coronary artery bypass grafting (CABG).To compare post-operative surgical outcomes of high complexity surgery in beneficiaries living in HPSA versus non-HPSA designated areas.This study is a retrospective cohort review of Medicare beneficiaries who underwent CABG between 2014-2018. We compared risk-adjusted 30-day mortality, complication, reoperation, and readmission rates for beneficiaries living in a designated HPSA versus non-HPSA using a multivariable logistic regression model accounting for patient (e.g., age, sex, comorbidities, surgery year) and hospital characteristics (e.g., patient-to-nurse ratio, teaching status). Patient travel burden was measured based on the time and distance required to travel from the beneficiary's home zip code to the hospital zip code.Of the 370,532 Medicare beneficiaries who underwent CABG, 30,881 (8.3%) lived in a Health Professional Shortage Area. Beneficiaries in HPSAs were found to experience comparable 30-day mortality (3.50% vs. 3.65%, P0.001), complication (32.67% vs. 33.54%, P0.001), reoperation (1.58% vs. 1.66%, P0.001), and readmission (14.72% vs. 14.86%, P0.001) rates. Beneficiaries experienced greater mean travel times (91.2 minutes vs. 64.0 minutes, P0.001) and mean travel distances (85.0 miles vs. 59.3 miles, P0.001).Medicare beneficiaries living in designated Health Professional Shortage Areas experienced comparable surgical outcomes after coronary artery bypass graft surgery but a significantly greater travel burden. The greater travel burden experienced by patients living in designated shortage areas to obtain comparable surgical care for complex procedures demonstrates important tradeoffs between access and quality.

Objective: The need for concomitant tricuspid surgery during mitral valve surgery is associated with higher operative risk. We hypothesized that concomitant tricuspid surgery through a minimally invasive thoracotomy (MICS) is associated with noninferior risk compared with a sternotomy. Methods: All patients undergoing mitral valve surgery at a single institution (2010 to 2020) were evaluated. After excluding endocarditis, emergent operations, and concomitant aortic valve or coronary artery bypass grafting procedures, patients were stratified by MICS versus sternotomy. Multivariable logistic regression assessed the risk-adjusted association between concomitant tricuspid valve procedure and Society of Thoracic Surgeons major morbidity or mortality. An interaction term evaluated the impact of approach on concomitant tricuspid surgery. Results: A total of 772 patients underwent mitral valve surgery, including 138 (17.9%) with concomitant tricuspid valve operation. Of the total cohort, 243 patients (31.5%) underwent the MICS approach. Concomitant tricuspid operation was performed in 104 sternotomy patients (19.7%) compared with 34 MICS patients (14.0%, P = 0.056). After risk adjustment, patients who underwent concomitant tricuspid valve surgery via sternotomy had nearly 2 times greater odds of morbidity and mortality relative to those undergoing isolated mitral surgery via sternotomy (adjOR = 1.86, P = 0.049), while patients who underwent concomitant tricuspid surgery via the MICS approach had no increased risk of the composite outcome (adjOR = 0.66, P = 0.543), relative to isolated mitral surgery via MICS approach. Conclusions: Concomitant tricuspid surgery at the time of mitral valve surgery carries additional risk in a broad patient population. A minimally invasive approach appears to be safe for selected patients requiring concomitant tricuspid valve surgery.

Transcatheter tricuspid valve replacement (TTVR) is rapidly emerging as a therapeutic option amongst patients with secondary tricuspid regurgitation. Historical data from surgical tricuspid valve replacement (TVR) studies may serve as a benchmark for the development of TTVR trials.The aim of the study was to investigate the early and late outcomes following isolated surgical TVR.Multiple electronic databases were searched to identify studies on isolated surgical TVR. The prespecified primary endpoint was operative mortality; secondary endpoints were early and late outcomes. Overall estimates of proportions and incidence rates with 95% confidence intervals (CI) were calculated using random-effects models. Multiple sensitivity analyses accounting for baseline characteristics, country and the operative period were applied. Results: A total of 35 studies (5,316 patients) were included in this meta-analysis. The operative period ranged from 1974 to 2019. The overall rate of operative mortality was 12% (95% CI: 9-15), with higher mortality for patients who were operated on before 1995, who had prior cardiac surgeries, or who had liver disease. The most frequent clinical events were pacemaker implantation (10% [95% CI: 6-16]), bleeding (12% [95% CI: 8-17]), acute kidney injury (15% [95% CI: 9-24]) and respiratory complications (15% [95% CI: 12-20]). At follow-up analysis of the bioprosthetic TVR, there was an incidence rate per 100 person-years of 6 (95% CI: 2-13) for death and 8 (95% CI: 5-13) for recurrence of significant tricuspid regurgitation.This meta-analysis provides an overview of the historical clinical outcomes following isolated surgical TVR. These findings can support the development of future clinical trials in the tricuspid space by providing thresholds for clinical outcomes.

Background Alpha-gal syndrome is a tick-acquired disease caused by immunoglobulin E (IgE) to the oligosaccharide galactose-alpha-1,3-galactose (alpha-gal), causing allergic reactions to meat and products sourced from nonprimate mammals. As heparin is porcine-derived, we hypothesized that patients with alpha-gal syndrome who received high-dose heparin for cardiac surgery would have increased risk of anaphylaxis. Methods All cardiac surgery patients at an academic medical center from 2007 to 2019 were cross-referenced with research and clinical databases for the alpha-gal IgE blood test. Clinical data were obtained through the institutional Society of Thoracic Surgeons Adult Cardiac Database and chart review. Patients were stratified by development of an allergic reaction for univariate statistical analysis. Results Of the 8819 patients, 17 (0.19%) had a positive alpha-gal test before cardiac surgery. Of these 17 patients, 4 (24%) had a severe allergic reaction. The median alpha-gal titer was significantly higher in patients with a reaction (75 [interquartile range, 61-96] IU/mL vs 8 [interquartile range, 3-18] IU/mL; P = .006). There were no differences in median heparin loading dose, total dose, or maximum activated clotting time (all P > .05). In a subgroup of 8 patients with recent alpha-gal IgE level, 4 (50%) developed an allergic reaction. Conclusions Although alpha-gal is rare in patients undergoing cardiac surgery, there is up to a 50% risk of serious allergic reaction to heparin for cardiopulmonary bypass. Higher preoperative alpha-gal titers may confer a higher risk of severe allergic reaction. For patients with a clinical suspicion of alpha-gal syndrome, we recommend prescreening with IgE levels and premedicating before receiving high doses of intravenous heparin.