BackgroundThe impact of off-pump coronary artery bypass grafting (OPCAB) on great saphenous vein (GSV) harvest-site wound complications and graft integrity remains uncertain in the contemporary era. We compared harvest-site morbidity, early angiographic outcomes, and long-term clinical events between OPCAB and conventional on-pump coronary artery bypass grafting (CABG).MethodsThis single-center retrospective study included 394 patients who underwent isolated CABG with available pre- and postoperative coronary angiography between 2005 and 2017. Propensity score matching according to pump usage yielded 157 matched pairs [on-pump CABG, n = 157; OPCAB, n = 157]. The primary endpoint was GSV harvest-site wound complications. Secondary endpoints included early graft occlusion or saphenous vein graft (SVG) stenosis, reintervention, perioperative outcomes, and major adverse cardiac and cerebrovascular events (MACCE).ResultsAfter matching, baseline characteristics were comparable, although the on-pump group had more distal anastomoses. Leg wound complications were rare and similar between groups (1.3% vs. 0.6%, p = 1.00). Early graft occlusion (9.6% vs. 10.3%, p = 0.553) and SVG occlusion (5.7% vs. 4.5%, p = 0.798) did not differ significantly. SVG stenosis severity and reintervention rates were comparable. OPCAB was associated with shorter operative time, fewer red blood cell transfusions (49.7% vs. 64.3%, p = 0.012), shorter intensive care unit stay, and reduced hospital stay. Thirty-day mortality and 12-month MACCE rates (12.1% in both groups) were similar. Long-term MACCE-free survival up to 10 years showed no significant difference.ConclusionOPCAB did not reduce GSV harvest-site complications compared with on-pump CABG. Early graft integrity and long-term clinical outcomes were comparable, although OPCAB improved perioperative resource utilization.

Preemptive thoracic endovascular aortic repair (TEVAR) has been used increasingly for uncomplicated type B aortic dissection (TBAD); however, its optimal indications remain controversial, particularly when the proximal landing zone involves the aortic arch. We evaluated the long-term outcomes of aortic arch preemptive TEVAR for uncomplicated TBAD. Between July 2004 and January 2026, 473 patients with acute TBAD were treated at our institution and affiliated hospitals, 351 of whom completed initial medical therapy (follow-up, 1–241 months). Preemptive TEVAR was performed in 52 patients and 299 were managed medically. The subjects of this study were 41 patients who underwent preemptive TEVAR with a proximal landing zone in Zone 2 or 3. We compared the outcomes and aortic morphology on serial computed tomography (CT) of these 41 patients with those of 41 propensity-matched patients who did not undergo TEVAR. Before matching, the TEVAR group had a higher prevalence of patent false lumen and a larger false lumen diameter. Freedom from aortic adverse events was higher in the TEVAR group during long-term follow-up, although the difference was not significant (P = 0.065). There were no aortic-related deaths after TEVAR, and CT demonstrated favorable aortic remodeling. Aortic arch preemptive TEVAR was associated with favorable aortic remodeling and a trend toward improved long-term aortic outcomes.

We report a rare, life-saving endovascular intervention in a patient with acute type B aortic dissection (TBAD) complicated by severe lower limb ischemia due to dynamic obstruction. A 67-year-old woman, previously diagnosed with uncomplicated Stanford type B dissection with a thrombosed false lumen, suddenly developed bilateral leg pain and absent distal pulses on day 12. CT revealed a new entry tear in the descending aorta, leading to false lumen reperfusion and collapse of the true lumen at the abdominal aorta and both common iliac arteries. As appropriate thoracic endovascular aortic repair and endovascular aortic repair devices were not immediately available, emergency repair was performed using four self-expanding bare-metal stents via bilateral femoral access. This achieved prompt true lumen re-expansion and restoration of distal pulses. Post-procedure imaging confirmed improved perfusion. Although extra-anatomical bypass is often considered, complete collapse of the abdominal true lumen made it unlikely to be effective. This case demonstrates that widely available bare-metal stents offer a practical and effective emergency option for restoring distal perfusion when standard devices are not accessible. Importantly, this approach should be regarded as palliative for limb salvage rather than definitive treatment of the entry tear.

BACKGROUND:Secondary aortoduodenal fistula (SADF) is a rare but life-threatening complication after abdominal aortic surgery, characterized by catastrophic hemorrhage and persistent infection. Emergency endovascular aortic repair (EVAR) is increasingly performed initially as a less invasive approach for rapid hemostasis in patients presenting with hemorrhagic shock; however, it does not eliminate the underlying source of infection. Although definitive open surgery to remove the infectious source remains essential, the optimal timing has not been established due to the rarity of this condition. Therefore, we evaluated emergency EVAR as an initial hemostatic strategy and the association between timing of definitive surgery and clinical outcomes. METHODS:We retrospectively reviewed six consecutive patients with SADF treated at our institution from 2016 to 2025. Emergency EVAR was performed in patients presenting with hemorrhagic shock, followed by definitive surgery. Until 2021, definitive surgery was performed electively after stabilization of the patient's general condition, whereas since 2022, it has been performed as early as clinically feasible. RESULTS:Emergency EVAR was performed in five patients to achieve hemostasis, and none of the patients died before definitive surgery. During follow-up, four patients died of sepsis due to recurrent infection within 2 years after surgery. Longer intervals from diagnosis to definitive surgery were observed in these patients. CONCLUSION:Emergency EVAR was an effective life-saving strategy for initial hemostasis. However, unfavorable outcomes were associated with prolonged delays before definitive surgery, suggesting that earlier transition to definitive surgery for infection control may be related to overall outcomes.

Background:In acute type A aortic dissection (ATAAD), early surgical intervention is critical; however, prognostic determinants in geographically stable populations remain incompletely defined. We sought to identify key predictors of in-hospital mortality in a closed regional cohort. Methods:We retrospectively analyzed patients undergoing surgery for ATAAD between January 2022 and June 2025 at 3 tertiary centers in Yamagata Prefecture, Japan. Demographics, transport time, admission to surgery interval, preoperative status, and operative variables were evaluated. Independent predictors of mortality were assessed by Cox proportional hazards modeling. Results:Of 164 patients (mean age, 66.3 ± 11.9 years; 50% male), surgical mortality was 8.5% and in-hospital mortality was 10.4%. Nonsurvivors more frequently presented with preoperative shock (41% vs 12%; P < .001) and malperfusion (35% vs 15%; P = .05). In multivariable analysis, preoperative shock was the sole independent predictor of mortality (hazard ratio, 9.12; 95% CI, 2.88-28.8; P < .001), whereas transport time and operative complexity were not significant. Conclusions:In a geographically isolated, consistently managed cohort, preoperative shock was the dominant determinant of in-hospital mortality in ATAAD. These findings emphasize the importance of early recognition and stabilization before surgery rather than transport speed alone.

Objective:The use of preemptive thoracic endovascular aortic repair (TEVAR) has been expanding, especially in cases where aortic enlargement is an indication for surgical intervention. Current guidelines recommend treatment for chronic type B aortic dissection (TBAD) when aortic diameter increases by ≥5 mm over a 6-month period. However, the optimal window for preemptive TEVAR is the subacute phase (up to 3 months), creating a dilemma where intervention may be delayed beyond this window. This study investigates the short- and long-term outcomes of aggressive treatment for rapidly enlarging aneurysms. Subjects and methods:Between July 2004 and August 2024, 432 patients with acute Stanford type B aortic dissection were treated at two centers. Of these, 324 patients who completed acute best medical therapy (BMT) were included. Patients with rapid enlargement of aortic aneurysms who did not meet absolute surgical indications (aneurysm diameter <55 mm and <5 mm/month) were compared to those who continued BMT. Propensity score matching was performed between the BMT group (Group B, n = 83) and the aortic expansion group (Group E, n = 83). Results:Among the 324 eligible patients, 88 exhibited rapid aortic enlargement (≤5 mm in <6 months). Of these, 42 (48%) underwent surgical intervention: 12 (14%) received graft replacement, and 30 (34%) underwent TEVAR, with 28 (32%) receiving preemptive TEVAR. The BMT group continued without surgery, with 7 patients (3%) receiving graft replacement and 20 (8%) undergoing TEVAR. In Group E, aortic diameter significantly increased compared to Group B (0.4 ± 0.2 vs. 1.1 ± 0.2 mm, p < 0.001). The false lumen was thrombosed in all preemptive TEVAR patients (mean 3.2 ± 5.1 months). In addition, univariate Cox regression identified preemptive TEVAR as a significant protective factor against aorta-related events (HR: 0.03, 95% CI: 0.004-0.22, p < 0.001), highlighting its potential role in reducing adverse aortic outcomes. The aorta-related death-free survival rates at 1, 5, and 10 years were 99/99/99% vs. 99/93/88% for Groups B and E, respectively (p = 0.097). Seven deaths occurred in Group E, with six related to ruptured aortic aneurysms. Conclusion:Selective preemptive TEVAR for patients with rapid aortic enlargement in the subacute and chronic phases of TBAD showed favorable outcomes. Although no significant difference in aorta-related mortality was found, the higher incidence of rupture in untreated patients suggests that preemptive TEVAR may offer a benefit. Further research is needed to identify the patients most likely to benefit from early surgical intervention.

Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening condition for which early risk stratification and preventive strategies present critical challenges. Although genetic contributions are well established in high-risk populations, the clinical relevance of rare variants in the general population remains poorly understood. We aimed to explore the association between low-frequency homozygous minor allele genotypes in TAAD-related genes and TAAD-related mortality using a Japanese community-based cohort. We selected 14 single-nucleotide polymorphisms from genes with definitive or strong clinical validity for TAAD, based on the criterion that the frequency of individuals homozygous for the minor allele was less than 5

Background:The saphenous vein graft (SVG) remains a mainstay conduit for coronary artery bypass grafting (CABG) due to its accessibility and length. Although the no-touch technique may improve long-term patency, wound complications are a continuing concern. Since 2011, our institution has adopted endoscopic vein harvesting (EVH) as the standard approach. This study provides angiographic insights into graft quality and patency after EVH compared with open vein harvesting (OVH), with additional assessment of mid-term clinical outcomes. Methods:Among 471 patients who underwent CABG between 2005 and 2017, 307 were included in this study. Patients were divided into the EVH group (Group A, n = 134) and the OVH group (Group B, n = 173). Postoperative coronary angiography was used to evaluate SVG graft patency, anastomotic integrity, and graft body stenosis. Clinical outcomes including major adverse cardiac and cerebrovascular events (MACCE) and wound complications were also compared. Results:Angiographic assessment demonstrated comparable SVG patency between the EVH and OVH groups (93% vs. 94%), with similar rates of anastomotic stenosis (2.2% vs. 2.3%) and severe graft stenosis (≥90%; 1.5% vs. 1.2%). No significant differences were observed in 30-day mortality (1.5% vs. 3.5%), in-hospital mortality (1.5% vs. 2.1%), or postoperative stroke. Wound-related complications were rare, including wound dehiscence (1.5% vs. 2.3%) and infection (0.7% vs. 1.2%). MACCE-free survival rates at 1, 3, and 5 years were 97%, 94%, and 91% in the EVH group vs. 92%, 86%, and 76% in the OVH group, respectively (p = 0.070), showing a favorable trend in the EVH group. Conclusion:Detailed angiographic evaluation revealed that EVH did not compromise graft quality or patency compared with conventional OVH. The incidence of wound complications was very low, and early postoperative SVG-related events were favorable. These findings suggest that EVH is a safe and reliable harvesting technique, providing high-quality grafts with excellent angiographic integrity. Individualized selection of harvesting strategy remains important for optimizing surgical outcomes.

Background The role of preemptive thoracic endovascular aortic repair (TEVAR) in uncomplicated type B aortic dissection (TBAD) remains debated, and long-term outcome data from real-world cohorts are limited. We evaluated the safety and long-term effectiveness of risk stratification–guided preemptive TEVAR within a comprehensive aortic management strategy. Methods Among 473 consecutive patients with acute type B aortic dissection treated at multiple centers between 2004 and 2026, 351 patients who successfully completed acute-phase best medical therapy were included. Preemptive TEVAR was selectively performed in patients considered at high risk for late aortic events. Propensity score matching was performed using age, sex, hypertension, maximal aortic diameter in the early subacute phase, patent false lumen, and false lumen diameter in the early subacute phase, resulting in 52 matched pairs. Long-term aortic outcomes were evaluated using Kaplan–Meier analysis and Cox proportional hazards models. Results Patients undergoing preemptive TEVAR exhibited unfavorable aortic morphology during follow-up, including narrower true lumen and enlarged false lumen. After preemptive TEVAR, all patients achieved partial or complete false lumen thrombosis with favorable aortic remodeling, resulting in significant reduction of aortic diameter to levels comparable with the non-preemptive group at 12 months. In the propensity-matched cohort, freedom from aortic adverse events at 10 and 13 years was 95.7% and 82.0% in the preemptive TEVAR group versus 70.1% and 70.1% in the non-preemptive group (P=0.008). No aortic-related deaths occurred after preemptive TEVAR. Multivariable analysis identified age and narrow true lumen as independent predictors of aortic adverse events. Conclusions Risk stratification–guided preemptive TEVAR was safe and associated with durable aortic remodeling without excess late mortality in selected patients with uncomplicated TBAD. These findings suggest that a selective risk stratification–guided approach to preemptive TEVAR may contribute to favorable aortic remodeling; however, its impact on long-term clinical benefit remains uncertain.

OBJECTIVE:Endoscopic vein harvesting (EVH) has become a standard technique in coronary artery bypass grafting (CABG) due to its benefits in wound healing and recovery. However, EVH involves a learning curve, and concerns remain about graft quality with less experienced operators. Few studies have assessed graft failure patterns by anatomical location or used detailed postoperative angiography. This study evaluated the impact of EVH operator experience on saphenous vein graft (SVG) quality, focusing on early graft failure patterns such as anastomotic and graft body stenosis. METHODS:From 2005 to 2017, patients who underwent CABG with EVH at two institutions were analyzed. After propensity score matching, 60 patients each were assigned to novice (Group A) and experienced (Group B) EVH surgeon groups. Graft patency and major adverse cardiac and cerebrovascular events (MACCE) were compared during follow-up. RESULTS:Among 719 CABG patients, 173 underwent EVH and were included in the matched analysis. Early postoperative SVG occlusion occurred in three patients (5%) in Group A and six patients (10%) in Group B (P=0.355). SVG stenosis was observed in five (8.3%) and one (1.7%) patients, respectively (P=0.272). In-hospital and 30-day mortality were 1.7% (Group A) vs. 0% (Group B) (P=1.0). The one-, three-, and five-year MACCE-free survival rates were 96.4%, 90.7%, and 90.7% in Group A versus 96.0%, 91.3%, and 84.8% in Group B (P=0.175). CONCLUSIONS:No significant differences were found between novice and experienced EVH surgeons in graft occlusion, stenosis, or major adverse cardiac events. EVH can be safely performed by less experienced surgeons under appropriate supervision.

Background: Thoracic aortic aneurysm and dissection (TAAD) is a life-threatening condition for which early risk stratification and preventive strategies represent critical challenges in modern medicine. Although genetic contributions have been well-established in high-risk populations, the clinical relevance of rare variants in the general population remains poorly understood. This study aimed to investigate their clinical significance using a community-based cohort. Methods: We conducted a population-based survival analysis using the Yamagata Cohort, a prospective study in Japan. We selected 14 single-nucleotide polymorphisms from genes with definitive or strong clinical validity for TAAD, based on the criterion that the frequency of individuals homozygous for the minor allele was < 5%. Participants were categorized as carriers if they harbored homozygous rare variants, and as non-carriers otherwise. The primary outcome was TAAD-related mortality. Results: Among 24,478 participants, we analyzed 5,722 individuals with genome-wide genotyping data. The carrier group included 1,499 individuals, and the non-carrier group comprised 4,223 individuals. TAAD-related deaths occurred in 12 individuals (8 carriers vs 4 non-carriers). The carrier group showed significantly lower survival rates than the non-carrier group (P=0.0010). In the multivariable Cox model, carrier status was independently associated with increased TAAD-related mortality (hazard ratio, 2.27; 95% confidence interval, 1.24?4.14; P=0.0056). Conclusions: Rare homozygous variants in specific TAAD-related genes were significantly associated with TAAD-related mortality in this general Japanese population, despite the absence of prior pathogenic classification. These findings provide novel insights for pre-symptomatic risk stratification and a foundation for developing future preventive strategies in TAAD. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial This study is a prospective observational cohort study and was not registered as a clinical trial because it does not involve any interventional component. ### Funding Statement This research received no external funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study protocol was approved by the institutional review board of Yamagata University (Approval No. 2024-007). I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data underlying this study are derived from the Yamagata Cohort and cannot be made publicly available due to ethical and legal restrictions. Summary-level results are provided within the article and its supplementary material. Additional data may be available from the corresponding author upon reasonable request and subject to institutional ethics committee approval.

Objective: The saphenous-vein graft (SVG) is a key graft commonly used in coronary-artery bypass grafting (CABG), and its quality affects postoperative outcomes. endoscopic vein harvest (EVH) is an effective technique for wound healing and prevention of infection, but there is a learning curve, and there is no established assessment of how harvesting by a novice surgeon affects the patient's postoperative outcome. In this study, we investigated the effect of graft harvesting proficiency on the outcome of postoperative CABG patients. Methods: From 2005 to 2017, the patients who completed EVH were included in the analysis. Propensity score-matched EVH-experienced surgeon group and novice surgeon group, respectively, were compared for the graft patency and major adverse cardiac and cerebrovascular events (MACCE) extending into the remote phase. Results: A total of 719 patients underwent either isolated or combined CABG at the two institutions, and of those, the 173 patients with SVG harvested by EVH were divided into 60 Propensity score-matched groups, respectively. SVG occlusion in early postoperative period was 3 (5%) in group of novice surgeons (group A) and 6 (10%) in group of experienced surgeons (group B) (P=0.355). Similarly, there were 5 cases (8.3%) in group A and 1 case (1.7%) in group B for SVG stenosis (P = 0.272). Inpatient surgical mortality, 30-day mortality and 30-day in-hospital deaths were 1.7 % (Group A) vs 0 % (Group B) (P = 1.0). MACCE free rate of 1-, 3-, and 5-year was 96.4%/90.7%/90.7% vs. 96%/91.3%/84.8% (P = 0.175) (Group A vs. Group B), respectively. Conclusions: Among the patients undergoing CABG with EVH, a significant difference was not found between the surgeons of novice vein-graft harvesting and experienced in the risk of graft occlusion and major adverse cardiac events.

Background:Elevated matrix metalloproteinase-12 (MMP-12) levels have been shown to be elevated in patients with aortic dissection (AD) and aortic aneurysm (AA). However, whether MMP-12 is associated with AD and AA has not been conclusively examined. The aim of this study was to clarify the role of MMP-12 in AD and AA formation and to verify the correlation between MMP-12 and AD and AA development at the gene level via Mendelian randomization (MR) analysis. Methods:The data for analyzing MMP-12 gene mutations were obtained from the Integrative Epidemiology Unit (IEU) OpenGWAS database, which includes data from 21,758 European residents. Data on the genetic variation of AD and AA were retrieved from the FinnGen database. In the forward MR analysis, we evaluated the causal effect of MMP-12 on AD and AA. Subsequently, the causal association of AD and AA with MMP-12 was investigated in the reverse MR study. The inverse-variance weighting (IVW) method was the principal statistical technique used in this study. Results:In the forward MR analysis, the IVW results showed that serum MMP-12 levels were positively related to an increased risk of AD [odds ratio (OR) =1.301; 95% confidence interval (CI): 1.002-1.697; P=0.048] and AA (OR =1.121; 95% CI: 1.007-1.248; P=0.04). For the reverse MR studies, no genetic relationships were observed between AD or AA and MMP-12 levels, nor was any heterogeneity or pleiotropy. Conclusions:There was a correlation between serum MMP-12 and the risk of AD and AA. MMP-12 may be a potential therapeutic target for AD and AA.

Background: Thoracic aortic aneurysms and dissections (TAAD) are primarily associated with acquired factors. However, 20% of cases exhibit familial clustering, indicating a genetic contribution. Although multiple causative genes have been identified, there may be as yet unknown etiologic variants, and it remains to be determined how these may affect prognosis. Research Questions: To explore the possibility that the discovery of minor alleles with new pathological significance may lead to early detection and personalized preventive aortic therapy based on individual risk profiles. Whether the presence of rare single nucleotide polymorphisms (SNPs) in TAAD-related genes established in a prospective regional cohort affects long-term outcome and may be an independent risk factor for TAAD-related mortality. Methods: The Yamagata cohort is a longitudinal study of 25000 residents who participated in community health screenings. Of 5948 individuals with whole-genome data, 5722 with complete baseline information were analyzed (median age: 65 years; 45.9% male; smoking history: 32.4%; hypertension: 43.5%; diabetes mellitus: 19.2%; dyslipidemia: 50.7%; obesity: 27.7%). Based on the Japanese Circulation Society guidelines, SNPs in genes categorized as Strong/Definitive for TAAD association were comprehensively screened. Individuals harboring homozygous minor alleles with <5% frequency in the cohort were defined as the carrier group and compared to the non-carrier group. Results: Fourteen SNPs were identified, all located in regions related to smooth muscle contraction or TGF-β signaling. None had previously been reported as pathogenic. There were 1499 carriers and 4223 non-carriers. Median follow-up duration was 4984 days. TAAD-related deaths occurred in 8 individuals (0.53%) in the carrier group and 4 individuals (0.09%) in the non-carrier group. Kaplan-Meier analysis revealed a significantly higher mortality risk in the carrier group (P = 0.001). Multivariate Cox proportional hazards analysis demonstrated that SNP carriage was an independent risk factor for TAAD-related death (HR = 2.27, 95% CI: 1.24-4.14, P = 0.0056). Conclusion: Carriage of rare SNPs not previously reported as pathogenic was significantly associated with TAAD-related death, suggesting the existence of novel genetic risk factors. These findings support the importance of further variant discovery and the potential utility of early genetic screening to facilitate pre-symptomatic therapeutic intervention.

Background:Uncomplicated Stanford type B aortic dissection (TBAD) is associated with aortic complications in the subacute or chronic phase, but it is still unclear in which patients these complications occur. The objective of this study was to identify the ideal imaging parameter predictive of the risk of aorta-related complications in patients with uncomplicated TBAD. Methods:A retrospective study was conducted using prospectively collected data from patients with uncomplicated TBAD at two local hospitals in Japan. Computed tomography (CT) images were analyzed serially, and their association with "aorta-related complication" during follow-up was assessed. Results:During a mean follow-up of 3.5 years, 53 out of 213 patients with uncomplicated TBAD experienced the aorta-related complications, among which 50 (23.5%) were aortic enlargement. Receiver operating characteristic curve analysis revealed that a low true lumen area ratio (TLAR) (<2.9%) at initial subacute phase was a significant prognostic factor for late aorta-related complications (P<0.001). The Cox regression analysis indicated that low TLAR [hazard ratio (HR), 6.32; 95% confidence interval (CI): 2.72-14.69] and an enlargement of the false lumen area (HR, 6.09: 95% CI: 2.22-16.7) were independent predictors of aorta-related complications. Subanalysis revealed a TLAR of 52.9% or less increased the risk of future aorta-related complications, even when the aortic diameter was smaller than 40 mm (P<0.001). Conclusions:A narrow true lumen area at early subacute phase and an enlargement of the false lumen area are potentially good predictors to help us to identify a high-risk subgroup of patients who may benefit from earlier and more aggressive therapy. In particular, a narrow true lumen area is an independent risk factor for the future aorta-related complications, even when the aortic diameter is small.

ObjectivePreemptive thoracic endovascular aortic repair (TEVAR) has the potential to improve the prognosis of Stanford type B aortic dissection (TBAD), however it is important to determine whether it could be safely performed as a prophylactic treatment. This study aimed to determine the short- and long-term outcomes of preemptive TEVAR for uncomplicated TBAD with a small aortic aneurysm.DesignRetrospective multicenter analysis.MethodsWe analyzed 212 patients with medically treated uncomplicated subacute TBAD between July 2004 and October 2019 in two Japanese academic centers. The short- and long-term prognosis of patients who underwent preemptive TEVAR and the changes in aortic diameter over time after TEVAR were analyzed. Aorta-related complications, aortic-related death and postoperative complications were recorded and analyzed. Analysis was performed on an intension-to-treat basis.ResultsDuring follow-up, patients were divided into two groups: optimal medical treatment [OMT; n = 185 (87%)] and preemptive TEVAR [n = 27 (13%)]. In all cases, aortic enlargement was the reason for therapeutic intervention in the preemptive TEVAR group. Propensity score matching yielded a cohort of 27 control patients with OMT (group A) and 27 patients who underwent preemptive TEVAR (group B). Preoperative characteristics were similar between groups. In group B, only one patient developed type A dissection at a late stage and died from aortic rupture. Freedom from aortic-related death at 1/5/10 years was 100%/92%/92% in group B. Overall growth (mm/year) of max aorta was significantly smaller in the TEVAR group than in the control group (−3.7 ± 2.9 vs. 0.4 ± 5.6, p < 0.01), and the diameter of the false lumen was reduced (−8 ± 4.8 vs. −1.3 ± 8.0, p < 0.001).ConclusionsShort- and long-term outcomes of TEVAR for uncomplicated TBAD with a small aortic aneurysm were excellent, with few postoperative complications. After TEVAR, aortic remodeling was observed in the short term, suggesting that it may contribute to the prevention of aortic-related death due to rupture.

Limited aortic root repair for acute type A dissection is associated with greater risk of proximal reoperations compared to full aortic root replacement. Surgical outcomes for patients undergoing reoperative root replacement after previous dissection repair are unknown. This study seeks to determine outcomes for these patients to further inform the debate surrounding optimal upfront management of the aortic root in acute dissection. Retrospective record review of all patients who underwent full aortic root replacement after a previous type A dissection repair operation at a tertiary academic referral center from 2004-2020 was performed. Among 57 cases of reoperative root replacement after type A repair, 35 cases included concomitant aortic arch replacements, and 21 cases involved coronary reconstruction (unilateral or bilateral modified Cabrol grafts). There were 3 acute postoperative strokes and 4 operative mortalities (composite 30-day and in-hospital deaths, 7.0%). Mid-term outcomes were equivalent for patients who required arch replacement compared to isolated proximal repairs (81.8% vs 80.6% estimated 5-year survival, median follow-up 5.53 years. Reoperative root replacement after index type A dissection repairs, including those with concomitant aortic arch replacement and/or coronary reconstruction is achievable with acceptable outcomes at an experienced aortic center.

Objective In patients with stable hemodynamic status after an acute coronary syndrome (ACS), coronary artery bypass grafting (CABG) after preoperative investigations can provide outcomes comparable to those of emergency surgery. However, no established guidelines exist regarding the preparation period before surgery. We report the results of the use of an inpatient cardiac rehabilitation program followed by CABG after an ACS to improve post-operative outcomes and prognosis after discharge. Methods From 2005 to 2017, 471 patients underwent either isolated or combined CABG at our institution, and of those, the 393 who received isolated CABG were included in the analysis. Twenty-seven patients (6.9%) were admitted with ACS and underwent preoperative rehabilitation before undergoing CABG, with a subsequent review of surgical morbidity and mortality rates. Propensity score matching yielded a cohort of 26 patients who underwent preoperative rehabilitation (group A) and 26 controls (group B). Preoperative characteristics were similar between groups. Results The completion rate of the rehabilitation program was 96.3%. All programs were conducted with inpatients, with an average length of stay of 23 ± 12 days. All patients completed in-bed exercises, and 85% completed out-of-bed exercises. The 30-day postoperative mortality was 0% in both groups A and B, and the rate of postoperative major adverse cardiac or cerebrovascular events at 12 months did not differ significantly between groups (7.7% vs 3.9%, respectively; p = 1.0). The duration of mechanical ventilation (1.3 ± 0.3 vs 1.5 ± 0.3 days, respectively; p = 0.633), length of intensive care unit stay (4.4 ± 2.1 vs 4.8 ± 2.3 days, respectively; p = 0.584) and length of hospital stay (25 ± 13 vs 22 ± 9 days, respectively; p = 0.378) did not differ significantly between groups. Conclusions No complications of preoperative rehabilitation were observed, suggesting that it is an acceptable option for patients who experience ACS and undergo CABG. These results are promising in offering more robust designs of future trials.

Background: Smooth muscle cell (SMC) phenotypic reprogramming toward a mixed synthetic-proteolytic state is a central feature of aortic root aneurysm in Marfan syndrome (MFS). Previous work identified Klf4 as a potential mediator of SMC plasticity in MFS. Methods: MFS ( Fbn1 C1041G/+ ) mouse strains with an inducible vascular SMC fluorescent reporter ( MFS SMC ) with or without SMC-specific deletion of Klf4 exons 2 to 3 ( MFS SMC-Klf4Δ ) were generated. Simultaneous SMC tracing and Klf4 loss-of-function ( Klf4Δ mice) was induced at 6 weeks of age. Aneurysm growth was assessed via serial echocardiography (4–24 weeks). Twenty-four-week-old mice were assessed via histology, RNA in situ hybridization, and aortic single-cell RNA sequencing. Results: MFS mice demonstrated progressive aortic root dilatation compared with control (WT SMC ) mice regardless of Klf4 genotype ( P <0.001), but there was no difference in aneurysm growth in MFS SMC-Klf4Δ versus MFS SMC ( P =0.884). Efficient SMC Klf4 deletion was confirmed via lineage-stratified genotyping, RNA in situ hybridization, and immunohistochemistry. Single-cell RNA sequencing of traced SMCs revealed a highly similar pattern of phenotype modulation marked by loss of contractile markers (eg, Myh11, Cnn1 ) and heightened expression of matrix genes (eg, Col1a1, Fn1 ) between Klf4 genotypes. Pseudotemporal quantitation of SMC dedifferentiation confirmed that Klf4 deletion did not alter the global extent of phenotype modulation, but reduced expression of 23 genes during this phenotype transition in MFS SMC-Klf4Δ mice, including multiple chondrogenic genes expressed by only the most severely dedifferentiated SMCs (eg, Cytl1, Tnfrsf11b ). Conclusions: Klf4 is not required to initiate SMC phenotype modulation in MFS aneurysm but may exert regulatory control over chondrogenic genes expressed in highly dedifferentiated SMCs.

Background: The role of increased smooth muscle cell (SMC) integrin αv signaling in Marfan syndrome (MFS) aortic aneurysm remains unclear. Herein, we examine the mechanism and potential efficacy of integrin αv blockade as a therapeutic strategy to reduce aneurysm progression in MFS. Methods: Induced pluripotent stem cells (iPSCs) were differentiated into aortic SMCs of the second heart field (SHF) and neural crest (NC) lineages, enabling in vitro modeling of MFS thoracic aortic aneurysms. The pathological role of integrin αv during aneurysm formation was confirmed by blockade of integrin αv with GLPG0187 in Fbn1 C1039G/+ MFS mice. Results: iPSC–derived MFS SHF SMCs overexpress integrin αv relative to MFS NC and healthy control SHF cells. Furthermore, integrin αv downstream targets (FAK [focal adhesion kinase]/Akt Thr308 /mTORC1 [mechanistic target of rapamycin complex 1]) were activated, especially in MFS SHF. Treatment of MFS SHF SMCs with GLPG0187 reduced p-FAK/p-Akt Thr308 /mTORC1 activity back to control SHF levels. Functionally, MFS SHF SMCs had increased proliferation and migration compared to MFS NC SMCs and control SMCs, which normalized with GLPG0187 treatment. In the Fbn1 C1039G/+ MFS mouse model, integrin αv, p-Akt Thr308 , and downstream targets of mTORC1 proteins were elevated in the aortic root/ascending segment compared to littermate wild-type control. Mice treated with GLPG0187 (age 6–14 weeks) had reduced aneurysm growth, elastin fragmentation, and reduction of the FAK/Akt Thr308 /mTORC1 pathway. GLPG0187 treatment reduced the amount and severity of SMC modulation assessed by single-cell RNA sequencing. Conclusions: The integrin αv-FAK-Akt Thr308 signaling pathway is activated in iPSC SMCs from MFS patients, specifically from the SHF lineage. Mechanistically, this signaling pathway promotes SMC proliferation and migration in vitro. As biological proof of concept, GLPG0187 treatment slowed aneurysm growth and p-Akt Thr308 signaling in Fbn1 C1039G/+ mice. Integrin αv blockade via GLPG0187 may be a promising therapeutic approach to inhibit MFS aneurysmal growth.