Long-term outcomes after recurrent acute thoracic aortic dissection: Insights from the International Registry of Aortic Dissection.

OBJECTIVE: With an aging population and advancements in imaging, recurrence of thoracic aortic dissection is becoming more common. METHODS: All patients enrolled in the International Registry of Aortic Dissection from 1996 to 2023 with type A and type B acute aortic dissection were identified. Among them, initial dissection and recurrent dissection were discerned. The study period was categorized into 3 eras: historic era, 1996 to 2005; middle era, 2006 to 2015; most recent era, 2016 to 2023. Propensity score matching was applied between initial dissection and recurrent dissection. Outcome of interests included long-term survival and cumulative incidence of major aortic events defined by the composite of reintervention, aortic rupture, and new dissection. RESULTS: The proportion of recurrent dissection increased from 5.9% in the historic era to 8.0% in the most recent era in the entire dissection cohort. In patients with type A dissection, propensity score matching between initial dissection and recurrent dissection yielded 326 matched pairs. Kaplan-Meier curves showed similar long-term survival between the 2 groups. However, the cumulative incidence of major aortic events was significantly higher in the recurrent dissection group (40.3% ± 6.2% vs 17.8% ± 5.1% at 4 years in the initial dissection group, P = .02). For type B dissection, 316 matched pairs were observed after propensity score matching. Long-term survival and the incidence of major aortic events were equivalent between the 2 groups. CONCLUSIONS: The case volume of recurrent dissection or the ability to detect recurrent dissection has increased over time. Acute type A recurrent dissection was associated with a higher risk of major aortic events than initial dissection. Further judicious follow-up may be crucial after type A recurrent dissection.

Comparison of open thoracoabdominal repair for chronic aortic dissections and aneurysms.

OBJECTIVE: Aortic dissection is common in patients undergoing open surgical repair of thoracoabdominal aortic aneurysms (TAAAs). Most often, dissection is chronic and is associated with progressive aortic dilatation. Because contemporary outcomes in chronic dissection are not clearly understood, we compared patient characteristics and outcomes after open TAAA repair between patients with chronic dissection and those with non-dissection aneurysm. METHODS: We retrospectively analyzed data from 3470 open TAAA repairs performed in a single practice. Operations were for non-dissection aneurysm in 2351 (67.8%) and chronic dissection in 1119 (32.2%). Outcomes included operative mortality and adverse events, a composite variable comprising operative death and persistent (present at discharge) stroke, paraplegia, paraparesis, and renal failure necessitating dialysis. Logistic regression identified predictors of operative mortality and adverse events. Time-to-event analyses examined survival, death, repair failure, subsequent progressive repair, and survival free of failure or subsequent repair. RESULTS: Compared with patients with non-dissection aneurysm, those with chronic dissection were younger, had fewer atherosclerotic risk factors, and were more likely to have heritable thoracic aortic disease and undergo extent II repair. The operative mortality rate was 8.5% (n = 296) overall and was higher in non-dissection aneurysm patients (n = 217; 9.2%) than in chronic dissection patients (n = 79; 7.1%; P = .03). Adverse events were less frequent (P = .01) in patients with chronic dissection (n = 145; 13.0%), 22 (2.0%) of whom had persistent paraplegia. Chronic dissection was not predictive of operative mortality (P = .5) or adverse events (P = .6). Operative mortality and adverse events, respectively, were independently predicted by emergency repair (odds ratio [OR], 3.46 and 2.87), chronic kidney disease (OR, 1.74 and 1.81), extent II TAAA repair (OR, 1.44 and 1.73), increasing age (OR, 1.04/year and 1.04/year), and increasing aortic cross-clamp time (OR, 1.02/minutes and 1.02/minutes). Patients with chronic dissection had lower 10-year unadjusted mortality (42% vs 69%) but more frequent repair failure (5% vs 3%) and subsequent repair for progressive aortic disease (11% vs 5%) than patients with non-dissection aneurysm (P < .001); these differences were no longer statistically significant after adjustment. CONCLUSIONS: Outcomes of open TAAA repair vary by aortic disease type. Emergency repairs and atherosclerotic diseases most commonly occur in patients with non-dissection aneurysm and independently predict operative mortality. Repair of chronic dissection is associated with low rates of adverse events, including operative mortality and persistent paraplegia, along with reasonable late survival and good durability. However, patients with chronic dissection tend to more commonly undergo subsequent repair to treat progressive aortic disease, which emphasizes the need for robust long-term imaging surveillance protocols.

Outcomes after bioprosthetic versus mechanical mitral valve replacement for infective endocarditis in the United States.

Objective: In patients who underwent mitral valve replacement for infectious endocarditis, we evaluated the association of prosthesis choice with readmission rates and causes (the primary outcomes), as well as with in-hospital mortality, cost, and length of stay (the secondary outcomes). Methods: Patients with infectious endocarditis who underwent isolated mitral valve replacement from January 2016 to December 2018 were identified in the United States Nationwide Readmissions Database and stratified by valve type. Propensity score matching was used to compare adjusted outcomes. Results: A weighted total of 4206 patients with infectious endocarditis underwent bioprosthetic mitral valve replacement (n = 3132) and mechanical mitral valve replacement (n = 1074) during the study period. Patients in the bioprosthetic mitral valve replacement group were older than those in the mechanical mitral valve replacement group (median 57 vs 46 y, P < .001). After propensity matching, the bioprosthetic mitral valve replacement group (n = 1068) had similar in-hospital mortality, length of stay, and costs compared with the mechanical mitral valve replacement group (n = 1056). Overall, 90-day readmission rates were high (28.9%) and comparable for bioprosthetic mitral valve replacement (30.5%) and mechanical mitral valve replacement (27.5%, P = .4). Likewise, there was no difference in readmissions over a calendar year by prosthesis type. Readmissions for infection and bleeding were common for both bioprosthetic mitral valve replacement and mechanical mitral valve replacement groups. Conclusions: Outcomes and readmission rates were similar for mechanical mitral valve replacement and bioprosthetic mitral valve replacement in infectious endocarditis, suggesting that valve choice should not be determined by endocarditis status. Additionally, strategies to mitigate readmission for infection and bleeding are needed for both groups.

Unplanned readmissions, community socioeconomic factors, and their effects on long-term survival after complex thoracic aortic surgery.

OBJECTIVE: We evaluated community socioeconomic factors in patients who had unplanned readmission after undergoing proximal aortic surgery (ascending aorta, aortic root, or arch). METHODS: Unplanned readmissions for any reason within 60 days of the index procedure were reviewed by race, acuity at presentation, and gender. We also evaluated 3 community socioeconomic factors: poverty, household income, and education. Kaplan-Meier survival curves were used to assess long-term survival differences by group (race, acuity, and gender). RESULTS: Among 2339 patients who underwent proximal aortic surgery during the 20-year study period and were discharged alive, our team identified 146 (6.2%) unplanned readmissions. Compared with White patients, Black patients lived in areas characterized by more widespread poverty (20.8% vs 11.1%; P = .0003), lower income ($42,776 vs $65,193; P = .0007), and fewer residents with a high school diploma (73.7% vs 90.1%; P < .0001). Compared with patients whose index operation was elective, patients who had urgent or emergency index procedures lived in areas with lower income ($54,425 vs $64,846; P = .01) and fewer residents with a high school diploma (81.1% vs 89.2%; P = .005). Community socioeconomic factors did not differ by gender. Four- and 6-year survival estimates were 63.1% and 63.1% for Black patients versus 89.1% and 83.0% for White patients (P = .0009). No significant differences by acuity or gender were found. CONCLUSIONS: Among readmitted patients, Black patients and patients who had emergency surgery had less favorable community socioeconomic factors and poorer long-term survival. Earlier and more frequent follow-up in these patients should be considered. Developing off-campus clinics and specific postdischarge measures targeting these patients is important.

Development of a Sensor Technology to Objectively Measure Dexterity for Cardiac Surgical Proficiency.

BACKGROUND: Technical skill is essential for good outcomes in cardiac surgery. However, no objective methods exist to measure dexterity while performing surgery. The purpose of this study was to validate sensor-based hand motion analysis (HMA) of technical dexterity while performing a graft anastomosis within a validated simulator. METHODS: Surgeons at various training levels performed an anastomosis while wearing flexible sensors (BioStamp nPoint, MC10 Inc) with integrated accelerometers and gyroscopes on each hand to quantify HMA kinematics. Groups were stratified as experts (n = 8) or novices (n = 18). The quality of the completed anastomosis was scored using the 10 Point Microsurgical Anastomosis Rating Scale (MARS10). HMA parameters were compared between groups and correlated with quality. Logistic regression was used to develop a predictive model from HMA parameters to distinguish experts from novices. RESULTS: Experts were faster (11 ± 6 minutes vs 21 ± 9 minutes; P = .012) and used fewer movements in both dominant (340 ± 166 moves vs 699 ± 284 moves; P = .003) and nondominant (359 ± 188 moves vs 567 ± 201 moves; P = .02) hands compared with novices. Experts' anastomoses were of higher quality compared with novices (9.0 ± 1.2 MARS10 vs 4.9 ± 3.2 MARS10; P = .002). Higher anastomosis quality correlated with 9 of 10 HMA parameters, including fewer and shorter movements of both hands (dominant, r = -0.65, r = -0.46; nondominant, r = -0.58, r = -0.39, respectively). CONCLUSIONS: Sensor-based HMA can distinguish technical dexterity differences between experts and novices, and correlates with quality. Objective quantification of hand dexterity may be a valuable adjunct to training and education in cardiac surgery training programs.

Outcomes After Extent I Thoracoabdominal Aortic Repair: Focus on Heritable Aortic Disease.

BACKGROUND: Crawford extent I thoracoabdominal aortic aneurysm (TAAA) repairs are increasingly performed by an endovascular approach, including in patients with heritable thoracic aortic disease (HTAD). We evaluated outcomes after open extent I TAAA repair in patients with and without HTAD. METHODS: This retrospective study included 992 patients (median age, 67 years; quartile 1-quartile 3, 57-73 years) who underwent extent I TAAA (1990-2022), stratified by the presence of HTAD (n = 177 [17.8%]). Patients with HTAD had genetic aortopathies or presented at age ≤50 years, and 35% (62 of 177) had Marfan syndrome. Logistic regression was used to identify predictors of operative death and adverse event, a composite of operative death and persistent (present at discharge) stroke, paraplegia, paraparesis, and renal failure necessitating dialysis. Long-term outcomes were analyzed with competing risks analysis. RESULTS: Patients with HTAD had lower rates of operative mortality (1.7% vs 7.0%, P = .01) and composite adverse event (2.8% vs 12.3%, P < .001) than non-HTAD patients. Most HTAD patients were discharged home (92.6% vs 76.9%, P < .001). Predictors of operative death were increasing age, aortic dissection, tobacco use, chronic symptoms, and rupture. Predictors for adverse event were increasing age, acute symptoms, chronic dissection, and rupture. Patients with HTAD had substantially better repair-failure-free survival (P < .001). CONCLUSIONS: Open extent I TAAA repair was effective in patients with HTAD, with low operative mortality and adverse event rates, better late survival, and excellent long-term durability, making a compelling argument for preferring open repair in these patients.

Racial disparities in thoracic aortic surgery: Myth or reality?

OBJECTIVE: We examined the relationship between Black or White race and adverse outcomes in patients who underwent surgery of the ascending aorta, aortic root, or aortic arch at our center. METHODS: We analyzed 2335 consecutive patients who identified as Black (n = 217, 9.3%) or White (n = 2118, 90.7%) and underwent proximal aortic surgery. Patient zip codes were used to determine community socioeconomic (CSE) characteristics. The composite adverse outcome comprised mortality, persistent neurologic injury, and renal failure necessitating dialysis at discharge. We performed multivariable analysis, Kaplan-Meier analysis, and propensity score matching adjusted for CSE factors. RESULTS: Median follow-up time was 3.7 years. Compared with White patients, Black patients lived in areas characterized by a higher percentage living below poverty level, lower income, and lower education level (P < .0001). Black patients had higher rates of emergency presentation (P < .0001) and lower 5- and 10-year survival rates (P = .0002). Short-term outcomes were similar between groups, except for respiratory failure and length of stay (P < .0001), which were higher in the Black population. After propensity score matching adjusted for CSE factors, Black and White patients (n = 204 each) had similar short-term outcomes and 5- and 10-year survival rates (P = .30). Multivariable analysis stratified by race showed that CSE factors independently predicted adverse outcomes in Black but not White patients. CONCLUSIONS: This is among few studies that have analyzed the relationship between race and proximal aortic surgery. Although outcomes were similar between Black and White patients in our cohort after adjusting for CSE factors, unfavorable CSE factors predicted adverse outcomes in Black but not White patients. More patient-specific studies are needed.

Thoracoabdominal aortic aneurysm: a journey through the distal aorta.

The field of surgical aortic repair has advanced significantly over time, transitioning from aneurysm ligation to homografts, then to Dacron grafts, and now endovascular procedures. With new endovascular technologies emerging, they are likely to dominate the field of aortic surgery, but surgeons must exercise caution and not abandon their open-surgery skills. Open repair of thoracoabdominal aortic aneurysm surgery continues to be a durable operation. As the field continues to evolve, further research is needed to advance this complex surgical endeavor.

Surgical techniques/case videos-complex aortic case: top tips (TAAAR).

This complex case study describes the surgical approach for a patient with chronic aortic dissection and multiple comorbidities. The patient had multiple previous surgeries, including aortic repair. The surgical approach involved a thoracoabdominal aortic aneurysm repair with left heart bypass, spinal fluid drainage, selective visceral perfusion, and protection of the surviving kidney. A Dacron tube graft was used to replace the damaged area. Supplementary Information: The online version contains supplementary material available at 10.1007/s12055-023-01632-2.

Emergency and Compassionate Use of a Novel Ascending Endograft for Ascending and Arch Aortic Pathology.

PURPOSE: Patients with complicated ascending aortic pathology, including patients with acute type A aortic dissection may be at extreme risk for open repair. Thoracic endovascular aortic repair (TEVAR), infrequently used for the ascending aorta, may be considered an alternative in this setting. We describe early results for emergency and compassionate (E&C) use of a novel endograft, specifically designed for use to treat pathology of the ascending aorta. MATERIALS AND METHODS: This case series evaluated 19 patients (mean age, 68.84±13.12 years; 57.9% female) treated with ascending TEVAR for acute and chronic acute (4), subacute (1), or chronic (1) aortic dissection or pseudoaneurysm (13). Six of the 19 patients (31.5%) were treated under compassionate use and 13 patients (68.4%) were treated under the emergency use exemption. Ten patients (52.6%) received additional devices to extend treatment into the arch and descending aorta. RESULTS: Device delivery was achieved in all patients (100%). Thirty-day mortality and stroke occurred in 3 patients (15.8%) and in 1 patient (5.3%), respectively. In 1 patient (5.3%), with an Unanticipated Adverse Device Event, the aorta ruptured when the endograft eroded into the adventitial portion of dissection site at the posterior aspect of the ascending wall. Devices were explanted in 2 patients (10.5%), 353 and 610 days after the index procedure, respectively. Six patients had endoleaks (31.6%), including type I (n=2, 10.5%), type II endoleaks (n=3, 15.8%), and indeterminate endoleak (n=1, 5.3%). CONCLUSIONS: Delivery and deployment of a novel ascending thoracic stent graft with or without an additional branched arch extension is feasible in patients with complex anatomy and pathology, including acute aortic dissection and pseudoaneurysm. Additional experience with this novel device will further refine the patient population most suitable for endovascular ascending aortic repair for these pathologies. CLINICAL IMPACT: This study describes a novel stent graft specifically designed for treatment of ascending aortic pathology, including acute type A dissection. The patients described in this series constituted a group outside the formal US FDA sponsored clinical trial, and were those accepted as part of an emergency and compassionate use basis.

Current approaches to spinal cord protection during open thoracoabdominal aortic aneurysm repair.

Spinal cord deficit (SCD) is a feared complication after thoracoabdominal aortic aneurysm repair. Vigilant management throughout the perioperative period is necessary to reduce the risk of SCD. Measures for preventing SCD during the intraoperative period include preoperative optimization and recognizing patients at a higher risk of SCD. In this manuscript, we discuss intraoperative adjuncts including utilization of cerebrospinal fluid drainage, left heart bypass, mild hypothermia, selective reimplantation of intercostal and lumbar arteries, and renal and visceral vessel perfusion. From the operative to the postoperative period, careful attention to avoiding hypotension and anemia is important. If SCD is recognized early, therapeutic intervention may be implemented to mitigate injury.

Outcomes of thoracoabdominal aortic aneurysm repair in patients with a previous myocardial infarction.

OBJECTIVE: Many patients undergoing thoracoabdominal aortic aneurysm (TAAA) repair have had a previous myocardial infarction (MI). To address the paucity of data regarding outcomes in such patients, we aimed to compare outcomes after open TAAA repair in patients with and without previous MI. METHODS: From 1986 to 2022, we performed 3737 consecutive open TAAA repairs. Of these, 706 (18.9%) were in patients with previous MI. We used multivariable logistic regression to identify predictors of operative death. Propensity score matching analyzed preoperative and select operative variables to create matched groups of patients with or without a previous MI (n = 704 pairs). Late survival was determined by Kaplan-Meier analysis and compared by log rank test. RESULTS: Overall, operative mortality was 8.5% and the adverse event rate was 15.2%; these were elevated in patients with MI (11.0% vs 7.9% [P = .01] and 18.0% vs 14.6% [P = .02], respectively). In the propensity score-matching cohort, the MI group had a greater rate of cardiac complications (32.4% vs 25.4%; P = .005) and delayed paraparesis (5.1% vs 2.4%; P = .1); however, there was no difference in operative mortality (11.1% vs 10.9%; P = 1) or adverse event rate (18.0% vs 16.8%; P = .6). Overall, previous MI was not independently associated with operative mortality in multivariable analysis (P = .1). The matched MI group trended toward poorer 10-year survival (29.8% ± 1.9% non-MI vs 25.0% ± 1.8% MI; P = .051). CONCLUSIONS: Although previous MI was not associated with early mortality after TAAA repair, patients with a previous MI had greater rates of cardiac complications and delayed paraparesis. Patients with a previous MI also trended toward poorer survival.

The severity of chronic obstructive pulmonary disease is associated with adverse outcomes after open thoracoabdominal aortic aneurysm repair.

OBJECTIVE: We assessed associations between outcomes after open thoracoabdominal aortic aneurysm (TAAA) repair and preoperative airflow limitation stratified by the Global Initiative for Chronic Obstructive Lung Disease (GOLD) spirometric classification of chronic obstructive pulmonary disease (COPD) severity. METHODS: Among 2368 open elective TAAA repairs in patients with spirometric data, 1735 patients had COPD and 633 did not. Those with COPD were stratified by preoperative respiratory dysfunction as GOLD 1 (forced expiratory volume in the first second of expiration [FEV1] ≥80% of predicted; n = 228), GOLD 2 (50% ≤ FEV1 < 80% of predicted; n = 1215), GOLD 3 (30% ≤ FEV1 < 50% of predicted; n = 260), or GOLD 4 (FEV1 < 30% of predicted; n = 32). Early outcomes included operative mortality and adverse events (operative death or persistent stroke, spinal cord deficit, or renal failure requiring dialysis); associations of outcomes were determined using logistic regression models. Kaplan-Meier analysis compared late survival by the log-rank test. RESULTS: Pulmonary complications occurred in 38.4% of patients with COPD versus 30.0% without COPD (P < .001). Operative mortality and adverse events were more frequent in patients with COPD than without COPD (7.9% vs 3.8% [P < .001] and 14.9% vs 9.8% [P = .001], respectively). Worsening GOLD severity was independently associated with operative death and adverse event. Survival was poorer in patients with COPD than in those without (61.9% ± 1.2% vs 73.6% ± 1.8% at 5 years; P < .001), particularly in patients with increasing GOLD severity (68.7% ± 3.2% vs 63.7% ± 1.4% vs 51.4% ± 3.2% vs 31.3% ± 8.2% at 5 years; P < .001). CONCLUSIONS: Patients with COPD are at elevated risk for operative death and adverse events. Staging by GOLD severity aids preoperative risk stratification. Patients with airflow limitations may benefit from optimization before TAAA repair.

Management of the left subclavian artery during aortic arch replacement using a frozen elephant trunk approach: a review.

The frozen elephant trunk (FET) technique for total aortic arch replacement extends repair into the proximal portion of the descending thoracic aorta. Several techniques and modifications of total arch replacement have been described in the literature, and many of these iterations are related to facilitating the distal anastomosis while preserving flow to the left subclavian artery (LSCA), as well as maintaining posterior circulation of the brain via the vertebral artery, by reducing the circulatory arrest time during reconstruction. Because of the LSCA's posterior and deep anatomic location in the chest, particularly in obese patients, this revascularization is often challenging; additional concerns regarding LSCA revascularization include patients with large aortic arch aneurysms, those with dissected or calcified arteries, and reoperation. A careful plan for reconstruction is necessary. Whether revascularization is performed preoperative, intraoperative, or postoperatively, every effort should be made to include the left subclavian artery as part of the operational approach. Revascularization techniques include reimplantation as part of the island patch or direct anastomosis, stenting, bypass, transposition or a hybrid approach. The importance of maintaining circulation of the LSCA cannot be overstated. Preserving flow to the spinal cord via collaterals minimizes the risk of cord injury during FET procedure. In patients with a patent left internal mammary artery bypass, left arm arteriovenous fistula for hemodialysis, dominant circulation, or direct aortic origin of the left vertebral artery, revascularization is necessary as well. In the case of initial sacrifice, arm claudication or steal syndrome usually dictates delayed extra-anatomic revascularization in the postoperative period.

Outcomes of aortic root replacement in patients with Marfan syndrome: the role of valve-sparing and valve-replacing approaches.

Background: Marfan syndrome (MFS) is a heritable thoracic aortic disease with pervasive cardiovascular effects, including commonly, a dilated aortic root. Traditionally, the root is replaced using a mechanical composite valve graft (CVG); however, this valve-replacing (VR) approach necessitates a lifelong regimen of anticoagulation with a potential for late bleeding complications. In time, valve-sparing (VS) approaches were developed. Today, several options for aortic root replacement (ARR) exist; each has advantages and disadvantages that helps inform choice. The Aortic Valve Operative Outcomes in Marfan Patients (AVOMP) is a multi-center international registry to analyze clinical outcomes of ARR in MFS patients using either VR or VS techniques to better elucidate choice. We summarize outcomes of AVOMP and present our own experience. Methods: We performed 223 consecutive elective ARR [1991-2023] in patients with MFS; 15 such repairs were included in AVOMP. Repairs included 113 (51%) using a mechanical CVG, 62 (28%) using a VS approach, and 48 (22%) using a bioprosthetic root. Many patients underwent aortic arch repair (30% to 54% by type). Results: The median patient age was 38 [29-52] years. In comparing VS and VR groups, patients were similar in age and rates of major comorbidities and symptoms. Patients with VR repair had a more complex aortic history. The rate of redo sternotomy was 24% (n=54). Operative death was uncommon [4% overall (10/223); ranging from 2% to 8% by type], and stroke was rare [1/223 (<1%)]. Late survival and reoperation differed by operative approach; survival was improved in patients who underwent VS repair. Conclusions: We found that repair in patients with MFS undergoing ARR resulted in low operative risk. Our late results were similar to those of AVOMP in that patients undergoing VS repair tended to experience greater rates of valvular-structural deterioration, although this did not appear to impact survival.

Epigenetic Induction of Smooth Muscle Cell Phenotypic Alterations in Aortic Aneurysms and Dissections.

BACKGROUND: Smooth muscle cell (SMC) phenotypic switching has been increasingly detected in aortic aneurysm and dissection (AAD) tissues. However, the diverse SMC phenotypes in AAD tissues and the mechanisms driving SMC phenotypic alterations remain to be identified. METHODS: We examined the transcriptomic and epigenomic dynamics of aortic SMC phenotypic changes in mice with angiotensin II-induced AAD by using single-cell RNA sequencing and single-cell sequencing assay for transposase-accessible chromatin. SMC phenotypic alteration in aortas from patients with ascending thoracic AAD was examined by using single-cell RNA sequencing analysis. RESULTS: Single-cell RNA sequencing analysis revealed that aortic stress induced the transition of SMCs from a primary contractile phenotype to proliferative, extracellular matrix-producing, and inflammatory phenotypes. Lineage tracing showed the complete transformation of SMCs to fibroblasts and macrophages. Single-cell sequencing assay for transposase-accessible chromatin analysis indicated that these phenotypic alterations were controlled by chromatin remodeling marked by the reduced chromatin accessibility of contractile genes and the induced chromatin accessibility of genes involved in proliferation, extracellular matrix, and inflammation. IRF3 (interferon regulatory factor 3), a proinflammatory transcription factor activated by cytosolic DNA, was identified as a key driver of the transition of aortic SMCs from a contractile phenotype to an inflammatory phenotype. In cultured SMCs, cytosolic DNA signaled through its sensor STING (stimulator of interferon genes)-TBK1 (tank-binding kinase 1) to activate IRF3, which bound and recruited EZH2 (enhancer of zeste homolog 2) to contractile genes to induce repressive H3K27me3 modification and gene suppression. In contrast, double-stranded DNA-STING-IRF3 signaling induced inflammatory gene expression in SMCs. In Sting-/- mice, the aortic stress-induced transition of SMCs into an inflammatory phenotype was prevented, and SMC populations were preserved. Finally, profound SMC phenotypic alterations toward diverse directions were detected in human ascending thoracic AAD tissues. CONCLUSIONS: Our study reveals the dynamic epigenetic induction of SMC phenotypic alterations in AAD. DNA damage and cytosolic leakage drive SMCs from a contractile phenotype to an inflammatory phenotype.

Long-term outcomes of valve-sparing aortic root versus composite aortic valve graft replacement for aortic root aneurysm: Meta-analysis of reconstructed time-to-event data.

BACKGROUND: We aimed to evaluate the long-term outcomes of valve-sparing aortic root replacement (VSARR) versus composite aortic valve graft replacement (CAVGR) for aortic root aneurysms. METHODS: Meta-analysis of Kaplan-Meier-derived time-to-event data from studies with follow-up including propensity-score matching or propensity-score adjustment. RESULTS: Six studies met our eligibility criteria, comprising 3215 patients (1770 patients treated with VSARR and 1445 patients with CAVGR). We observed a statistically significant difference for overall survival favoring VSARR (HR 0.63, 95%CI 0.49-0.82, P â€‹= â€‹0.001), but no statistically significant difference in the risk of reoperation (HR 0.77, 95%CI 0.51-1.14, P â€‹= â€‹0.187) in the overall follow-up. Landmark analyses revealed that, in the first 10 years after the procedure, reoperation rates were comparable between VSARR and CAVGR (HR 0.96, 95%CI 0.62-1.48, p â€‹= â€‹0.861), but the results beyond 10 years showed improved rates of freedom from reoperation in patients undergoing VSARR (HR 0.10, 95%CI 0.01-0.78; p â€‹= â€‹0.027). CONCLUSION: VSARR seems to confer better long-term survival and lower risk of reoperation in the follow-up of patients treated for aortic root aneurysm when compared with CAVGR.