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 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.

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.

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.

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.

Vertebral Tortuosity Is Associated With Increased Rate of Cardiovascular Events in Vascular Ehlers-Danlos Syndrome.

Background Arterial tortuosity is associated with adverse events in Marfan and Loeys-Dietz syndromes but remains understudied in Vascular Ehlers-Danlos syndrome. Methods and Results Subjects with a pathogenic COL3A1 variant diagnosed at age <50 years were included from 2 institutions and the GenTAC Registry (National Registry of Genetically Triggered Thoracic Aortic Aneurysms and Cardiovascular Conditions). Height-adjusted vertebral artery tortuosity index (VTI-h) using magnetic resonance or computed tomography angiography was calculated. Associations between VTI-h and outcomes of (1) cardiovascular events (arterial dissection/rupture, aneurysm requiring intervention, stroke), or (2) hollow organ collapse/rupture at age <50 years were evaluated using receiver operator curve analysis (using outcome by age 30 years) and mixed-effects Poisson regression for incidence rate ratios. Of 65 subjects (54% male), median VTI-h was 12 (interquartile range, 8-16). Variants were missense in 46%, splice site in 31%, and null/gene deletion in 14%. Thirty-two subjects (49%) had 59 events, including 28 dissections, 5 arterial ruptures, 4 aneurysms requiring intervention, 4 strokes, 11 hollow organ ruptures, and 7 pneumothoraces. Receiver operator curve analysis suggested optimal discrimination at VTI-h ≥15.5 for cardiovascular events (sensitivity 70%, specificity 76%) and no association with noncardiovascular events (area under the curve, 0.49 [95% CI, 0.22-0.78]). By multivariable analysis, older age was associated with increased cardiovascular event rate while VTI-h ≥15.5 was not (incidence rate ratios, 1.79 [95% CI, 0.76-4.24], P=0.185). However, VTI-h ≥15.5 was associated with events among those with high-risk variants <40 years (incidence rate ratios, 4.14 [95% CI, 1.13-15.10], P=0.032), suggesting effect modification by genotype and age. Conclusions Increased arterial tortuosity is associated with a higher incidence rate of cardiovascular events in Vascular Ehlers-Danlos syndrome. Vertebral tortuosity index may be a useful biomarker for prognosis when evaluated in conjunction with genotype and age.

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.

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.

Genome-wide association study of thoracic aortic aneurysm and dissection in the Million Veteran Program.

The current understanding of the genetic determinants of thoracic aortic aneurysms and dissections (TAAD) has largely been informed through studies of rare, Mendelian forms of disease. Here, we conducted a genome-wide association study (GWAS) of TAAD, testing ~25 million DNA sequence variants in 8,626 participants with and 453,043 participants without TAAD in the Million Veteran Program, with replication in an independent sample of 4,459 individuals with and 512,463 without TAAD from six cohorts. We identified 21 TAAD risk loci, 17 of which have not been previously reported. We leverage multiple downstream analytic methods to identify causal TAAD risk genes and cell types and provide human genetic evidence that TAAD is a non-atherosclerotic aortic disorder distinct from other forms of vascular disease. Our results demonstrate that the genetic architecture of TAAD mirrors that of other complex traits and that it is not solely inherited through protein-altering variants of large effect size.

Dispersion of National Institute of Health Funding to Departments of Surgery Is Contracting.

INTRODUCTION: NIH funding to departments of surgery reported as benchmark Blue Ridge Institute for Medical Research (BRIMR) rankings are unclear. METHODS: We analyzed inflation-adjusted BRIMR-reported NIH funding to departments of surgery and medicine between 2011 and 2021. RESULTS: NIH funding to departments of surgery and medicine both increased 40% from 2011 to 2021 ($325 million to $454 million; $3.8 billion to $5.3 billion, P < 0.001 for both). The number of BRIMR-ranked departments of surgery decreased 14% during this period while departments of medicine increased 5% (88 to 76 versus 111 to 116; P < 0.001). There was a greater increase in the total number of medicine PIs versus surgery PIs during this period (4377 to 5224 versus 557 to 649; P < 0.001). These trends translated to further concentration of NIH-funded PIs in medicine versus surgery departments (45 PIs/program versus 8.5 PIs/program; P < 0.001). NIH funding and PIs/program in 2021 were respectively 32 and 20 times greater for the top versus lowest 15 BRIMR-ranked surgery departments ($244 million versus $7.5 million [P < 0.01]; 20.5 versus 1.3 [P < 0.001]). Twelve (80%) of the top 15 surgery departments maintained this ranking over the 10-year study period. CONCLUSIONS: Although NIH funding to departments of surgery and medicine is growing at a similar rate, departments of medicine and top-funded surgery departments have greater funding and concentration of PIs/program versus surgery departments overall and lowest-funded surgery departments. Strategies used by top-performing departments to obtain and maintain funding may assist less well-funded departments in obtaining extramural research funding, thus broadening the access of surgeon-scientists to perform NIH-supported research.

Independent associations with early mortality after open repair of Crawford extent IV thoracoabdominal aortic aneurysms.

OBJECTIVE: We aimed to identify outcomes and factors that independently associate with early mortality after open repair of Crawford extent IV thoracoabdominal aortic aneurysms, defined as aneurysms confined to the segment below the diaphragm. METHODS: This retrospective analysis included 721 extent IV thoracoabdominal aortic aneurysm repairs performed in our institution from 1986 to 2021. Indications for repair were aneurysm without dissection in 627 cases (87.0%) and aortic dissection in 94 cases (13.0%). Overall, 466 patients (64.6%) were symptomatic preoperatively; 124 (17.2%) procedures were performed in patients with acute presentation, including 58 (8.0%) ruptured aneurysms. RESULTS: Operative death occurred after 49 (6.8%) repairs. Persistent renal failure necessitating dialysis occurred after 43 (6.0%) repairs. Binary logistic regression modeling revealed that previous extent II thoracoabdominal aortic aneurysm repair, chronic kidney disease, previous myocardial infarction, urgent or emergency repair, and longer crossclamp times during surgery were independently associated with operative mortality. Among early survivors (n = 672), competing risk analysis revealed that cumulative incidence of mortality and reintervention rates at 10 years were 74.8% (95% confidence interval, 71.4%-78.5%) and 3.3% (95% confidence interval, 2.2%-5.1%), respectively. CONCLUSIONS: Although patient comorbidities contributed to operative mortality, factors associated with the repair, such as urgent or emergency status, the duration of aortic crossclamping, and certain types of complex reoperation, also played prominent roles. Patients who survive the operation can expect a durable repair that usually is free from late reintervention. Expanding our collective knowledge regarding patients who undergo open repair of extent IV thoracoabdominal aortic aneurysms will enable clinicians to establish best practices and improve patient outcomes.

Midterm outcomes of aortic root surgery in patients with Marfan syndrome: A prospective, multicenter, comparative study.

OBJECTIVE: The objective of this study was to compare midterm outcomes of aortic valve-replacing root replacement (AVR) and aortic valve-sparing root replacement (AVS) operations in patients with Marfan syndrome. METHODS: Patients who met strict Ghent diagnostic criteria for Marfan syndrome and who underwent either AVR or AVS between March 1, 2005 and December 31, 2010 were enrolled in a 3-year follow-up prospective, multicenter, international registry study; the study was subsequently amended to include 20-year follow-up. Enrollees were followed clinically and echocardiographically. RESULTS: Of the 316 patients enrolled, 77 underwent AVR and 239 underwent AVS; 214 gave reconsent for 20-year follow-up. The median clinical follow-up time for surviving patients was 64 months (interquartile range, 42-66 months). Survival rates for the AVR and AVS groups were similar at 88.2% ± 4.4% and 95.0% ± 1.5%, respectively (P = .1). Propensity score-adjusted competing risk modeling showed associations between AVS and higher cumulative incidences of major adverse valve-related events, valve-related morbidity, combined structural valve deterioration and nonstructural valve dysfunction, and aortic regurgitation ≥2+ (all P < .01). No differences were found for reintervention (P = .7), bleeding (P = .2), embolism (P = .3), or valve-related mortality (P = .8). CONCLUSIONS: Five years postoperatively, major adverse valve-related events and valve-related morbidity were more frequent after AVS than after AVR procedures, primarily because of more frequent aortic valve dysfunction. No between-group differences were found in rates of survival, valve-related mortality, reintervention on the aortic valve, or bleeding. We plan to follow this homogenous cohort for 20 years after aortic root replacement.

Effect of sarcopenia on survival and spinal cord deficit outcomes after thoracoabdominal aortic aneurysm repair in patients 60 years of age and older.

OBJECTIVE: Sarcopenia (core muscle loss) has been used as a surrogate marker of frailty. We investigated whether sarcopenia would adversely affect survival after thoracoabdominal aortic aneurysm repair. METHODS: We retrospectively reviewed prospectively collected data from patients aged 60 years or older who underwent thoracoabdominal aortic aneurysm repairs from 2006 to 2016. Imaging was reviewed by 2 radiologists blinded to clinical outcomes. The total psoas index was derived from total psoas muscle cross-sectional area (cm2) at the mid-L4 level, normalized for height (m2). Patients were divided by sex-specific total psoas index values into sarcopenia (lower third) and nonsarcopenia (upper two-thirds) groups. Multivariable modeling identified operative mortality and spinal cord injury predictors. Unadjusted and adjusted survival curves were analyzed. RESULTS: Of 392 patients identified, those with sarcopenia (n = 131) were older than nonsarcopenic patients (n = 261) (70.0 years vs 68.0 years; P = .02) and more frequently presented with aortic rupture or required urgent/emergency operations. Operative mortality was comparable (sarcopenia 13.7% vs nonsarcopenia 10.0%; P = .3); sarcopenia was not associated with operative mortality in the multivariable model (odds ratio, 1.40; 95% confidence interval, 0.73-2.77; P = .3). Sarcopenic patients experienced more frequent delayed (13.0% vs 4.6%; P = .005) and persistent (10.7% vs 3.4%; P = .008) paraplegia. Sarcopenia independently predicted delayed paraplegia (odds ratio, 3.17; 95% confidence interval, 1.42-7.08; P = .005) and persistent paraplegia (odds ratio, 3.29; 95% confidence interval, 1.33-8.13; P = .01) in the multivariable model. Adjusted for preoperative/operative covariates, midterm survival was similar for sarcopenic and nonsarcopenic patients (P = .3). CONCLUSIONS: Sarcopenia did not influence early mortality or midterm survival after thoracoabdominal aortic aneurysm repair but was associated with greater risk for delayed and persistent paraplegia.

Contemporary Midterm Outcomes After Primary Repair of Chronic Type A Aortic Dissection.

BACKGROUND: Without surgical repair, acute type A aortic dissection (TAAD) is usually fatal. However, some patients survive without an early operation and progress to the chronic phase. Contemporary outcomes of primary surgical repair of chronic TAAD are unclear, so we evaluated them at our single-practice service. METHODS: During 1990 to 2021, 205 patients underwent repair of TAAD in the chronic phase (>60 days after onset). The 2 relevant DeBakey classifications were nearly equally represented: type I, 52% (n = 107), and type II, 48% (n = 98). The median interval between dissection onset and repair was 7 months (interquartile range, 3-25 months). Kaplan-Meier and competing-risk analyses provided time-dependent outcomes. RESULTS: At the time of intervention, most patients (40%) had chronic symptoms. Type I patients were younger than type II patients; however, comorbidities were similar. Most patients (n = 183 [87%]) underwent hemiarch or total arch repair, although total arch replacement was more common in type I dissection (P < .001). There were 15 operative deaths (7%), and 7 strokes (3%) persisted to the time of death or discharge. No patient had persistent paraplegia. Median follow-up was 5 years (interquartile range, 2-11 years). The 5-year reoperation-free survival was 61% (95% CI, 54%-68%), and the incidence of reoperation was 3% (95% CI, 0.4%-5%). Patients with type I and type II dissection did not differ significantly in survival (P = .2). CONCLUSIONS: Durable repair can be achieved with reasonable operative risk. Treatment is individualized and is associated with low rates of persistent neurologic complications. Despite differing operative approaches by DeBakey type, early and late outcomes were similar.

Aortic Stress Activates an Adaptive Program in Thoracic Aortic Smooth Muscle Cells That Maintains Aortic Strength and Protects Against Aneurysm and Dissection in Mice.

BACKGROUND: When aortic cells are under stress, such as increased hemodynamic pressure, they adapt to the environment by modifying their functions, allowing the aorta to maintain its strength. To understand the regulation of this adaptive response, we examined transcriptomic and epigenomic programs in aortic smooth muscle cells (SMCs) during the adaptive response to AngII (angiotensin II) infusion and determined its importance in protecting against aortic aneurysm and dissection (AAD). METHODS: We performed single-cell RNA sequencing and single-cell sequencing assay for transposase-accessible chromatin (scATAC-seq) analyses in a mouse model of sporadic AAD induced by AngII infusion. We also examined the direct effects of YAP (yes-associated protein) on the SMC adaptive response in vitro. The role of YAP in AAD development was further evaluated in AngII-infused mice with SMC-specific Yap deletion. RESULTS: In wild-type mice, AngII infusion increased medial thickness in the thoracic aorta. Single-cell RNA sequencing analysis revealed an adaptive response in thoracic SMCs characterized by upregulated genes with roles in wound healing, elastin and collagen production, proliferation, migration, cytoskeleton organization, cell-matrix focal adhesion, and PI3K-PKB/Akt (phosphoinositide-3-kinase-protein kinase B/Akt) and TGF-ß (transforming growth factor beta) signaling. ScATAC-seq analysis showed increased chromatin accessibility at regulatory regions of adaptive genes and revealed the mechanical sensor YAP/transcriptional enhanced associate domains as a top candidate transcription complex driving the expression of these genes (eg, Lox, Col5a2, Tgfb2). In cultured human aortic SMCs, cyclic stretch activated YAP, which directly bound to adaptive gene regulatory regions (eg, Lox) and increased their transcript abundance. SMC-specific Yap deletion in mice compromised this adaptive response in SMCs, leading to an increased AAD incidence. CONCLUSIONS: Aortic stress triggers the systemic epigenetic induction of an adaptive response (eg, wound healing, proliferation, matrix organization) in thoracic aortic SMCs that depends on functional biomechanical signal transduction (eg, YAP signaling). Our study highlights the importance of the adaptive response in maintaining aortic homeostasis and preventing AAD in mice.