Concomitant Tricuspid Repair in Patients with Degenerative Mitral Regurgitation.

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.).

Prospective Study of Risk Factors for Postoperative Atrial Fibrillation After Cardiac Surgery.

INTRODUCTION: To examine risk factors for new-onset postoperative atrial fibrillation (POAF) after cardiac surgery. METHODS: Patients enrolled in the Cardiothoracic Surgical Trials Network multicenter, randomized trial of rate control versus rhythm control for POAF were included. Predictors of POAF were determined using multivariable logistic regression. RESULTS: Among the 2104 patients who were enrolled preoperatively, 695 developed POAF (33.0%). Rates of POAF were 28.1% after isolated coronary artery bypass grafting (CABG), 33.7% after isolated valve repair or replacement, and 47.3% after CABG plus valve repair or replacement. Baseline characteristics associated with an increased risk of POAF identified on multivariable analysis included older age (odds ratio [OR] 1.57; 95% confidence interval [CI] 1.42-1.73, per 10 y), White race or non-Hispanic ethnicity (OR 1.52; CI: 1.11-2.07), history of heart failure (OR 1.55; CI: 1.16-2.08), and history of hypothyroidism (OR 1.42; CI 1.04-1.94). The type of cardiac procedure was associated with an increased risk of POAF with both isolated valve repair or replacement (OR 1.33, CI 1.08-1.64) and combined CABG plus valve repair or replacement (OR 1.64, CI 1.24-2.17) having increased risk of POAF compared to isolated CABG. No preoperative cardiac medication was associated with POAF. CONCLUSIONS: In this prospective cohort of patients, older age, a history of hypothyroidism, a history of heart failure, and valve repair or replacement, with or without CABG, and White non-Hispanic race were associated with an increased risk of POAF.

Tricuspid Valve Academic Research Consortium Definitions for Tricuspid Regurgitation and Trial Endpoints.

Interest in the pathophysiology, etiology, management, and outcomes of patients with tricuspid regurgitation (TR) has grown in the wake of multiple natural history studies showing progressively worse outcomes associated with increasing TR severity, even after adjusting for multiple comorbidities. Historically, isolated tricuspid valve surgery has been associated with high in-hospital mortality rates, leading to the development of transcatheter treatment options. The aim of this first Tricuspid Valve Academic Research Consortium document is to standardize definitions of disease etiology and severity, as well as endpoints for trials that aim to address the gaps in our knowledge related to identification and management of patients with TR. Standardizing endpoints for trials should provide consistency and enable meaningful comparisons between clinical trials. A second Tricuspid Valve Academic Research Consortium document will focus on further defining trial endpoints and will discuss trial design options.

Coronary Artery Bypass Surgery Among Medicare Beneficiaries in Health Professional Shortage Areas.

OBJECTIVE: Health professional shortage areas (HPSAs) 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). BACKGROUND: The aim was to compare postoperative surgical outcomes of high-complexity surgery in beneficiaries living in HPSA versus non-HPSA designated areas. METHODS: This study is a retrospective cohort review of Medicare beneficiaries who underwent CABG between 2014 and 2018. The authors 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 (eg, age, sex, comorbidities, surgery year) and hospital characteristics (eg, 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. RESULTS: Of the 370,532 Medicare beneficiaries who underwent CABG, 30,881 (8.3%) lived in a HPSA. Beneficiaries in HPSAs were found to experience comparable 30-day mortality (3.50% vs. 3.65%, P <0.001), complication (32.67% vs. 33.54%, P <0.001), reoperation (1.58% vs. 1.66%, P <0.001), and readmission (14.72% vs. 14.86%, P <0.001) rates. Beneficiaries experienced greater mean travel times (91.2 vs. 64.0 minutes, P <0.001) and mean travel distances (85.0 vs. 59.3 miles, P <0.001). CONCLUSIONS: Medicare beneficiaries living in designated HPSA experienced comparable surgical outcomes after CABG 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.

Preemptive alcohol septal ablation prior to transcatheter mitral valve replacement.

BACKGROUND: Alcohol septal ablation (ASA) has been shown to increase the neo-left ventricular outflow tract (LVOT) area before transcatheter mitral valve replacement (TMVR) but there is little literature on its success and use with dedicated devices. AIMS: To describe our experience with preemptive ASA to increase the predicted neo-LVOT area and its utility with both dedicated TMVR devices and balloon-expandable valves. METHODS: All patients who underwent ASA for TMVR candidacy in our center between May 2018 and October 2022 and had computed tomography (CT) scans done before and after ASA were included. Each CT was assessed for the minimum predicted neo-LVOT area at end-systole, using a virtual valve of the desired TMVR device for each patient. The primary outcome was an increase in the predicted neo-LVOT area after ASA that was deemed sufficient for safe implantation of the desired TMVR device. The secondary outcome was the absence of acute LVOT obstruction after TMVR. RESULTS: A total of 12 patients underwent ASA and all but 1 (n = 11, 91.6%) achieved the primary outcome of having sufficient predicted neo-LVOT area to proceed with TMVR. The mean increase in neo-LVOT area after ASA was 126 ± 64 mm2 (median 119.5, interquartile range: 65.0-163.5 mm2 ). Two patients (16.7%) required a permanent pacemaker after ASA. Nine patients went on and underwent TMVR with their respective devices and none had LVOT obstruction after the procedure. Among the remaining three patients, one had insufficient neo-LVOT clearance after ASA, one had unrelated mortality before TMVR, and one had advanced heart failure before TMVR. CONCLUSION: In appropriately selected patients and at centers experienced with ASA, preemptive ASA can achieve sufficient neo-LVOT clearance for TMVR with a variety of devices in approximately 90% of patients.

Pulmonary Hypertension and Operative Risk in Mitral Valve and Coronary Surgery.

INTRODUCTION: Pulmonary hypertension (PHT) is a known risk factor for coronary artery bypass grafting (CABG), though less well understood for valve operations. We hypothesized PHT is associated with lower risk during mitral valve operations compared to CABG. METHODS: Patients undergoing isolated mitral valve or CABG operations (2011-2019) in a regional Society of Thoracic Surgeons (STS) database were stratified by pulmonary artery systolic pressure (PASP). The association of PASP by procedure type was assessed by hierarchical regression modeling, adjusting for STS predicted risk scores. RESULTS: Of the 2542 mitral and 11,059 CABG patients, the mitral population had higher mean STS risk of mortality (3.6% versus 2.4%, P < 0.0001) and median PASP (42 mmHg versus 32 mmHg, P < 0.0001). PASP was independently associated with operative mortality and major morbidity in both mitral and CABG patients. However, for mitral patients a 10-mmHg increase in PASP was associated with lower odds of morbidity (odds ratio: 1.06 versus 1.13), mortality (odds ratio: 1.11 versus 1.18) and intensive care unit time (4.3 versus 7.6 h) compared with CABG patients (interaction terms P < 0.0001). Among mitral patients, median PASP was higher in stenotic versus regurgitant disease (57 mmHg versus 40 mmHg, P < 0.0001). However, there was no differential association of PASP on morbidity or mortality (interaction terms P > 0.05). CONCLUSIONS: Although mitral surgery patients tend to have higher preoperative pulmonary artery pressures, PHT was associated with a lower risk for mitral outcomes compared with CABG. Further research on the management and optimization of patients with PHT perioperatively is needed to improve care for these patients.

Aging Alters the Aortic Proteome in Health and Thoracic Aortic Aneurysm.

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, <60 years of age) and old (ie, ≥60 years of age) subjects. Second, we measured proteins, via immunoblotting, involved in mitophagy (ie, Parkin) and also mitochondrial-induced inflammatory pathways, specifically TLR (toll-like receptor) 9, STING (stimulator of interferon genes), and IFN (interferon)-ß. 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-ß 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-ß 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.

Impact of baseline renal dysfunction on cardiac outcomes and end-stage renal disease in heart failure patients with mitral regurgitation: the COAPT trial.

AIMS: Baseline renal dysfunction (RD) adversely impacts outcomes among patients with heart failure (HF) and severe secondary mitral regurgitation (MR). Heart failure and MR, in turn, accelerate progression to end-stage renal disease (ESRD), worsening prognosis. We sought to determine the impact of RD in HF patients with severe MR and the impact of transcatheter mitral valve repair (TMVr) on new-onset ESRD and the need for renal replacement therapy (RRT). METHODS AND RESULTS: The COAPT trial randomized 614 patients with HF and severe MR to MitraClip plus guideline-directed medical therapy (GDMT) vs. GDMT alone. Patients were stratified into three RD subgroups based on baseline estimated glomerular filtration rate (eGFR, mL/min/1.73 m2): none (≥60), moderate (30-60), and severe (<30). End-stage renal disease was defined as eGFR <15 mL/min/1.73 m2 or RRT. The 2-year rates of all-cause death or HF hospitalization (HFH), new-onset ESRD, and RRT according to RD and treatment were assessed. Baseline RD was present in 77.0% of patients, including 23.8% severe RD, 6.0% ESRD, and 5.2% RRT. Worse RD was associated with greater 2-year risk of death or HFH (none 45.3%; moderate 53.9%; severe 69.2%; P < 0.0001). MitraClip vs. GDMT alone improved outcomes regardless of RD (Pinteraction = 0.62) and reduced new-onset ESRD [2.9 vs. 8.1%, hazard ratio (HR) 0.34, 95% confidence interval (CI) 0.15-0.76, P = 0.008] and the need for new RRT (2.5 vs. 7.4%, HR 0.33, 95% CI 0.14-0.78, P = 0.011). CONCLUSION: Baseline RD was common in the HF patients with severe MR enrolled in COAPT and strongly predicted 2-year death and HFH. MitraClip treatment reduced new-onset ESRD and the need for RRT, contributing to the improved prognosis after TMVr.

Rationale and design of a randomized trial evaluating an external support device for saphenous vein coronary grafts.

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. METHODS: 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.

BAFF antagonism via the BAFF receptor 3 binding site attenuates BAFF 60-mer-induced classical NF-κB signaling and metabolic reprogramming of B cells.

Human recombinant B cell activating factor (BAFF) is secreted as 3-mers, which can associate to form 60-mers in culture supernatants. However, the presence of BAFF multimers in humans is still debated and it is incompletely understood how BAFF multimers activate the B cells. Here, we demonstrate that BAFF can exist as 60-mers or higher order multimers in human plasma. In vitro, BAFF 60-mer strongly induced the transcriptome of B cells which was partly attenuated by antagonism using a soluble fragment of BAFF receptor 3. Furthermore, compared to BAFF 3-mer, BAFF 60-mer strongly induced a transient classical and prolonged alternate NF-κB signaling, glucose oxidation by both aerobic glycolysis and oxidative phosphorylation, and succinate utilization by mitochondria. BAFF antagonism selectively attenuated classical NF-κB signaling and glucose oxidation. Altogether, our results suggest critical roles of BAFF 60-mer and its BAFF receptor 3 binding site in hyperactivation of B cells.

B Cell-Activating Factor Antagonism Attenuates the Growth of Experimental Abdominal Aortic Aneurysm.

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.

The role of surgery for secondary mitral regurgitation and heart failure in the era of transcatheter mitral valve therapies.

The approach to the management of mitral valve (MV) disease and heart failure (HF) has dramatically changed over the last decades. It is well recognized that severe mitral regurgitation secondary to ischemic or non-ischemic cardiomyopathy is associated with an excess risk of mortality. Understanding the impact of the surgical treatment modality on mortality outcomes has been difficult due to the broad spectrum of secondary mitral regurgitation (SMR) phenotypes and lack of randomized surgical clinical trials. Over the last 30 years, surgeons have failed to provide compelling evidence to convince the medical community of the need to treat SMR in patients with severe HF. Therefore, the surgical treatment of SMR has never gained uniform acceptance as a significant option among patients suffering from SMR. Recent evidence from randomized trials in a non-surgical eligible patients treated with transcatheter therapies, has provided a new perspective on SMR treatment. Recently published European and American guidelines confirm the key role of percutaneous treatment of SMR and in parallel, these guidelines reinforce the role of mitral valve surgery in patients who require surgical revascularization. Complex mitral valve repair combining subvalvular apparatus repair along with annuloplasty seems to be a promising approach in selected patients in selected centers. Meanwhile, mitral valve replacement has become the preferred surgical strategy in most patients with advanced heart failure and severe LV remodeling or high risk of recurrent mitral regurgitation. In this comprehensive review, we aimed to discuss the role of mitral surgery for SMR in patients with heart failure in the contemporary era and to provide a practical approach for its surgical management.

Access to Left Ventricular Assist Device: Travel Time Does Not Tell The Whole Story.

BACKGROUND: Negative health effects of traveling longer distances for surgical services have been reported. Given the high complexity of multidisciplinary care required for management of Left Ventricular Assist Device (LVAD) implantation, only 4 of 18 centers in our state perform these operations. Given the limited access we hypothesized increased travel time would adversely affect postoperative outcomes and 30-d mortality. METHODS: A statewide Society of Thoracic Surgeons database was queried to identify patients undergoing Heartmate II/III and HVAD implantation, and 725 patients were identified. Travel time was calculated by zip code. Patients were stratified into regional and distant groups by the upper quartile of travel time (1-h). Preoperative variables and outcomes were compared between the groups. Multivariate analysis was performed to evaluate the impact of travel time in risk-adjusted models of 30-d mortality. RESULTS: Median patient travel time to their LVAD center in our state is 32 min (mean 53 ± 65 min, 46 ± 71 miles). Patients in the distant group (n = 191) had lower median incomes, higher self-pay status, higher rates of medical comorbid disease. Despite these differences there was no difference between the groups in ICU and/or hospital length of stay, readmission, postoperative complications, or 30-d mortality. Multivariate regression demonstrated insurance status, age, and prior surgery predicted 30-d mortality, but not travel time. CONCLUSIONS: Despite only four centers in the state performing LVAD implantation, travel time was strongly associated with preoperative risk, and socioeconomic status but not postoperative outcomes or 30-d mortality. Therefore, increasing access should focus on insurance, and patient characteristics not travel time.

Genetic and Pharmacological Disruption of Interleukin-1α Leads to Augmented Murine Aortic Aneurysm.

BACKGROUND: 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-1ß 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: IL-1α disruption using either genetic or pharmacologic approaches worsens AAAs.

Contemporary prevalence and outcomes of rheumatic mitral valve surgery.

OBJECTIVE: Rheumatic mitral valve disease is often viewed as a historic disease in North America with limited contemporary data. We hypothesized that rheumatic pathology remains common and has worse short-term outcomes and higher resource utilization compared to other mitral valve pathologies. METHOD: All patients undergoing mitral valve repair or replacement (2011-2019) were extracted from a regional Society of Thoracic Surgeons database. Resource utilization metrics included inflation-adjusted hospital costs. Patients were stratified by mitral valve pathology for univariate analysis. RESULT: Out of the 6625 mitral valve procedures, 835 (12.6%) were from rheumatic disease, a proportion that incrementally increased over time (+0.39% per year, p = .032). Among 19 hospitals, there was high variability in number of rheumatic mitral operations (median: 22, interquartile range [IQR]: 5-80) and rate of rheumatic repairs (median: 3%, IQR: 0%-6%). Rheumatic patients were younger (62 vs. 65, p < .0001), more often female (75% vs. 43%, p < .001) and with greater burden of heart failure, multi-valve disease, and lung disease, but less coronary disease. There were no differences in operative mortality (5.2% vs. 5.0%, p = .85) or major morbidity (22.2% vs. 21.8%, p = .83). However, resource utilization was higher for rheumatic patients, including more frequent transfusions (43% vs. 39%, p = .012), longer ICU (73 vs. 64 h, p < .0001) and postoperative length of stay (8 vs. 7 days, p < .0001). CONCLUSIONS: Rheumatic mitral disease accounts for a meaningful (12%) and rising percentage of mitral valve operations in the region, with high variability among hospitals. Rheumatic mitral surgery yielded similar short-term outcomes compared to nonrheumatic pathology, but required greater resource utilization.

Aortic valve biologic protheses: A cohort comparison of premature valve failure.

BACKGROUND: Recent reports suggest an increased rate of early structural valve degeneration (SVD) in the Trifecta bioprosthesis (Abbott Cardiovascular). We sought to compare the intermediate-term outcomes of the Magna (Edwards Life Sciences) and Trifecta valves. METHODS: All surgical aortic valve replacements (SAVRs) with Trifecta or Magna/Magna Ease bioprostheses at an academic medical center were extracted from an institutional database. Patients who survived until after discharge (2011-2019) were included. The primary outcome was valve failure for any reason requiring reintervention or contributing to death, identified by reintervention or review of cause of death. Time to failure was estimated with Kaplan-Meier analysis and Cox Proportional Hazards Modeling. RESULTS: Out of 1444 patients, 521 (36%) underwent Trifecta and 923 (64%) underwent Magna implantation with a median follow-up of 27.6 months. Trifecta patients had larger median valve size (25 vs. 23 mm, p < .001) and lower median gradient (8.0 vs. 10.9 mmHg, p < .001). Trifecta patients had higher 48-month estimated failure rates (20.2 ± 7.6% vs. 2.6 ± 0.7%, p < .0001), with failure rates of 21.4 versus 9.2 failures per 1000 person-years (p < .001). After risk-adjustment, Trifecta patients had a 5.3 times hazard of failure (95% confidence interval: 2.78-12.34, p < .001) compared to Magna patients. Only Trifecta valves failed due to sudden aortic regurgitation, 8 out of 521 (1.5%). CONCLUSION: Despite lower postoperative mean gradients, the Trifecta bioprosthesis may have an increased risk of intermediate-term SVD. Further research is warranted to confirm the potential for sudden valve failure.

Meaningful Patient-centered Outcomes 1 Year Following Cardiac Surgery.

OBJECTIVE: To evaluate meaningful, patient-centered outcomes including alive-at-home status and patient-reported quality of life 1 year after cardiac surgery. BACKGROUND: Long-term patient-reported quality of life after cardiac surgery is not well understood. Current operative risk models and quality metrics focus on short-term outcomes. METHODS: In this combined retrospective/prospective study, cardiac surgery patients at an academic institution (2014-2015) were followed to obtain vital status, living location, and patient-reported outcomes (PROs) at 1 year using the NIH Patient-Reported Outcomes Measurement Information System (PROMIS). We assessed the impact of cardiac surgery, discharge location, and Society of Thoracic Surgeons perioperative predicted risk of morbidity or mortality on 1-year outcomes. RESULTS: A total of 782 patients were enrolled; 84.1% (658/782) were alive-at-home at 1 year. One-year PROMIS scores were global physical health (GPH) = 48.8 ±â€Š10.2, global mental health (GMH) = 51.2 ±â€Š9.6, and physical functioning (PF) = 45.5 ±â€Š10.2 (general population reference = 50 ±â€Š10). All 3 PROMIS domains at 1 year were significantly higher compared with preoperative scores (GPH: 41.7 ±â€Š8.5, GMH: 46.9 ±â€Š7.9, PF: 39.6 ±â€Š9.0; all P < 0.001). Eighty-two percent of patients discharged to a facility were alive-at-home at 1 year. These patients, however, had significantly lower 1-year scores (difference: GPH = -5.1, GMH = -5.1, PF = -7.9; all P < 0.001). Higher Society of Thoracic Surgeons perioperative predicted risk was associated with significantly lower PRO at 1 year (P < 0.001). CONCLUSIONS: Cardiac surgery results in improved PROMIS scores at 1 year, whereas discharge to a facility and increasing perioperative risk correlate with worse long-term PRO. One-year alive-at-home status and 1-year PRO are meaningful, patient-centered metrics that help define long-term quality and the benefit of cardiac surgery.

Characteristics and outcomes of surgically ineligible patients with multivessel disease treated with percutaneous coronary intervention.

OBJECTIVES: In this study we evaluated the clinical characteristics and outcomes of surgically ineligible patients with coronary artery disease (CAD) who underwent multivessel percutaneous coronary intervention (PCI). BACKGROUND: Patients with multivessel CAD who are surgically ineligible and undergo PCI are not well represented in large trials. METHODS: Out of 1,061 consecutive patients who underwent a non-emergent PCI for unprotected left main or multivessel CAD at the University of Virginia Medical Center, 137 patients were determined to be surgically ineligible for coronary artery bypass graft (CABG) surgery by a heart team. The clinical characteristics and reasons for surgical ineligibility were collected. The coronary angiograms were reviewed and the SYNTAX score calculated. The Society of Thoracic Surgeons (STS) score was calculated. Outcomes were determined at 30 days and 1-year. RESULTS: The mean age of the cohort was 71 and 59% were women. Hypertension, hyperlipidemia, tobacco abuse, and diabetes were common comorbidities. The average SYNTAX score was 22. The most commonly cited reasons for surgical ineligibility were advanced age, frailty, severe lung disease, ejection fraction ≤ 30% and STS score ≥ 8%. Outcomes at 30 days were excellent and better than those predicted by STS for surgery. Frailty and STS score predicted one-year outcomes. CONCLUSIONS: Patients undergoing PCI for multivessel disease who are surgically ineligible have multiple risk factors and comorbidities. Frailty, lung disease, poor left ventricular function, and high STS score represent common reasons for surgical ineligibility. Frailty and the STS score better predict one-year outcomes after PCI compared to the SYNTAX score.

Sex-Based Differences Among Experimental Swine Abdominal Aortic aneurysms.

BACKGROUND: Female sex protects against abdominal aortic aneurysms (AAAs); however, the mechanisms behind these sex-based differences remain unknown. The purpose of this study was to explore the role of sex and sex hormones in AAA formation among swine. MATERIALS AND METHODS: Using a previous validated model, infrarenal AAA were surgically created in uncastrated male (n = 8), female (n = 5), and castrated male (n = 4) swine. Aortic dilation was measured on postoperative day 28 during the terminal procedure and compared to initial aortic diameter measured during the index procedure. Tissue was analyzed for immunohistochemistry, cytokine array, gelatin zymography, serum 17ß-estradiol, and testosterone assay. RESULTS: Uncastrated males had significantly larger maximal aortic dilation compared to castrated males (113.5% ± 11.4% versus 38.1% ± 4.5%, P = 0.0012). Females had significantly higher mean aortic dilation compared to castrated males (96.2% ± 7.5% versus 38.1% ± 4.5%, P = 0.0004). Aortic diameters between females and uncastrated males were not significantly different on day 28. Female swine had significantly higher concentrations of 17ß-estradiol compared with uncastrated males (1590 ± 873.3 ng/mL versus 95.2 ± 2.3 ng/mL, P = 0.047), with no significant difference between females and castrated males. Uncastrated male AAA demonstrated significantly more elastin degradation compared with female and castrated males (P = 0.01 and <0 .01, respectively). No differences existed for T-cells or smooth muscle cells between groups. Multiple proinflammatory cytokines were elevated within uncastrated male aortic walls compared to females and castrated males. CONCLUSIONS: Sex hormones, specifically 17ß-estradiol and testosterone, influence experimental swine AAA formation as demonstrated by increased aneurysm size, collagen turnover, and elastolysis in uncastrated males in processes reflective of human disease.

Mesenchymal Stem Cells Alter MicroRNA Expression and Attenuate Thoracic Aortic Aneurysm Formation.

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.