Asprosin, a Fasting-Induced Glucogenic Protein Hormone.

Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin. Asprosin is secreted by white adipose, circulates at nanomolar levels, and is recruited to the liver, where it activates the G protein-cAMP-PKA pathway, resulting in rapid glucose release into the circulation. Humans and mice with insulin resistance show pathologically elevated plasma asprosin, and its loss of function via immunologic or genetic means has a profound glucose- and insulin-lowering effect secondary to reduced hepatic glucose release. Asprosin represents a glucogenic protein hormone, and therapeutically targeting it may be beneficial in type II diabetes and metabolic syndrome.

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.

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.

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.

Correction: Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease.

[This corrects the article DOI: 10.1371/journal.pgen.1009679.].

Integrative analysis of genomic variants reveals new associations of candidate haploinsufficient genes with congenital heart disease.

Numerous genetic studies have established a role for rare genomic variants in Congenital Heart Disease (CHD) at the copy number variation (CNV) and de novo variant (DNV) level. To identify novel haploinsufficient CHD disease genes, we performed an integrative analysis of CNVs and DNVs identified in probands with CHD including cases with sporadic thoracic aortic aneurysm. We assembled CNV data from 7,958 cases and 14,082 controls and performed a gene-wise analysis of the burden of rare genomic deletions in cases versus controls. In addition, we performed variation rate testing for DNVs identified in 2,489 parent-offspring trios. Our analysis revealed 21 genes which were significantly affected by rare CNVs and/or DNVs in probands. Fourteen of these genes have previously been associated with CHD while the remaining genes (FEZ1, MYO16, ARID1B, NALCN, WAC, KDM5B and WHSC1) have only been associated in small cases series or show new associations with CHD. In addition, a systems level analysis revealed affected protein-protein interaction networks involved in Notch signaling pathway, heart morphogenesis, DNA repair and cilia/centrosome function. Taken together, this approach highlights the importance of re-analyzing existing datasets to strengthen disease association and identify novel disease genes and pathways.

Myths and methodologies: Cardiopulmonary exercise testing for surgical risk stratification in patients with an abdominal aortic aneurysm; balancing risk over benefit.

The extent to which patients with an abdominal aortic aneurysm (AAA) should exercise remains unclear, given theoretical concerns over the perceived risk of blood pressure-induced rupture, which is often catastrophic. This is especially pertinent during cardiopulmonary exercise testing, when patients are required to perform incremental exercise to symptom-limited exhaustion for the determination of cardiorespiratory fitness. This multimodal metric is being used increasingly as a complementary diagnostic tool to inform risk stratification and subsequent management of patients undergoing AAA surgery. In this review, we bring together a multidisciplinary group of physiologists, exercise scientists, anaesthetists, radiologists and surgeons to challenge the enduring 'myth' that AAA patients should be fearful of and avoid rigorous exercise. On the contrary, by appraising fundamental vascular mechanobiological forces associated with exercise, in conjunction with 'methodological' recommendations for risk mitigation specific to this patient population, we highlight that the benefits conferred by cardiopulmonary exercise testing and exercise training across the continuum of intensity far outweigh the short-term risks posed by potential AAA rupture.

Readmissions After Surgical Aortic Valve Replacement: Influence of Prosthesis Type.

INTRODUCTION: Prosthesis choice during aortic valve replacement (AVR) weighs lifelong anticoagulation with mechanical valves (M-AVR) against structural valve degeneration in bioprosthetic valves (B-AVR). METHODS: The Nationwide Readmissions Database was queried to identify patients who underwent isolated surgical AVR between January 1, 2016 and December 31, 2018, stratifying by prothesis type. Propensity score matching was used to compare risk-adjusted outcomes. Readmission at 1 y was estimated with Kaplan-Meier (KM) analysis. RESULTS: Patients (n = 109,744) who underwent AVR (90,574 B-AVR and 19,170 M-AVR) were included. B-AVR patients were older (median 68 versus 57 y; P < 0.001) and had more comorbidities (mean Elixhauser score: 11.8 versus 10.7; P < 0.001) compared to M-AVR patients. After matching (n = 36,951), there was no difference in age (58 versus 57 y; P = 0.6) and Elixhauser score (11.0 versus 10.8; P = 0.3). B-AVR patients had similar in-hospital mortality (2.3% versus 2.3%; P = 0.9) and cost (mean: $50,958 versus $51,200; P = 0.4) compared with M-AVR patients. However, B-AVR patients had shorter length of stay (8.3 versus 8.7 d; P < 0.001) and fewer readmissions at 30 d (10.3% versus 12.6%; P < 0.001) and 90 d (14.8% versus 17.8%; P < 0.001), and 1 y (P < 0.001, KM analysis). Patients undergoing B-AVR were less likely to be readmitted for bleeding or coagulopathy (5.7% versus 9.9%; P < 0.001) and effusions (9.1% versus 11.9%; P < 0.001). CONCLUSIONS: B-AVR patients had similar early outcomes compared to M-AVR patients, but lower rates of readmission. Bleeding, coagulopathy, and effusions are drivers of excess readmissions in M-AVR patients. Readmission reduction strategies targeting bleeding and improved anticoagulation management are warranted in the first year following AVR.

Editor's Choice - Trends in Management and Outcomes of Type B Aortic Dissection: A Report From the International Registry of Aortic Dissection.

OBJECTIVE: To describe the trends in management and outcomes of patients with acute type B aortic dissection in the International Registry of Acute Aortic Dissection. METHODS: From 1996 - 2022, 3 908 patients were divided into similar sized quartiles (T1, T2, T3, and T4). In hospital outcomes were analysed for each quartile. Survival rates following admission were compared using Kaplan-Meier analyses with Mantel-Cox Log rank tests. RESULTS: Endovascular treatment increased from 19.1% in T1 to 37.2% in T4 (ptrend < .001). Correspondingly, medical therapy decreased from 65.7% in T1 to 54.0% in T4 (ptrend < .001), and open surgery from 14.8% in T1 to 7.0% in T4 (ptrend < .001). In hospital mortality decreased in the overall cohort from 10.7% in T1 to 6.1% in T4 (ptrend < .001), as well as in medically, endovascularly and surgically treated patients (ptrend = .017, .033, and .011, respectively). Overall post-admission survival at three years increased (T1: 74.8% vs. T4: 77.3%; p = .006). CONCLUSION: Considerable changes in the management of acute type B aortic dissection were observed over time, with a significant increase in the use of endovascular treatment and a corresponding reduction in open surgery and medical management. These changes were associated with a decreased overall in hospital and three year post-admission mortality rate among quartiles.

Endovascular Repair in Patients with Marfan Syndrome: Concerns Amid Controversy.

Endovascular aortic repair is widely used to treat patients with degenerative aneurysms or aortic dissection within the distal aorta. Thoracic endovascular aortic repair (TEVAR) is generally associated with fewer short-term complications than open surgical repair, which is particularly important for older patients with significant comorbid conditions. However, for patients with Marfan syndrome, a heritable thoracic aortic disease associated with aortic dilatation, dissection, and rupture, the utility of endovascular aortic repair remains questionable. Marfan patients have friable aortic tissue and are typically treated at a relatively young age with few comorbidities; they therefore have less operative risk and need a durable solution. Furthermore, those who need distal aortic repair tend to have chronic aortic dissection. Although TEVAR is generally superior to open surgery with regard to short-term complications, it is less durable, and TEVAR reintervention rates are highest in patients with chronic aortic dissection. Thus, Marfan patients seeking definitive aortic repair are often better served by open repair. Nonetheless, TEVAR may be useful in patients with Marfan syndrome as a bridge to open repair or as treatment for late complications of previous open repair.

AIM2 Inflammasome Activation Contributes to Aortic Dissection in a Sporadic Aortic Disease Mouse Model.

BACKGROUND: The absent in melanoma 2 (AIM2) inflammasome induces pyroptosis, tissue inflammation, and extracellular matrix destruction. We tested the hypothesis that the AIM2 inflammasome contributes to aortic aneurysm and dissection (AAD) development by promoting pyroptosis in smooth muscle cells (SMCs). METHODS: We examined AIM2 expression in aortic tissues from patients with ascending thoracic aortic aneurysm (ATAA) and aortic dissection (ATAD) and from organ donor controls. AIM2's role in AAD development was evaluated in AIM2-deficient mice in a sporadic AAD model induced by challenging mice with a high-fat diet and angiotensin II infusion. The direct effects of dsDNA on SMC death in vitro were studied. RESULTS: Western blot analyses showed that AIM2 was increased in ATAD compared to ATAA and control tissue. Immunofluorescence demonstrated increased AIM2 in SMCs and macrophages in the aortic media and adventitia of dissected tissue. Increased AIM2 abundance was associated with increased cleavage of caspase-1 and cleavage of gasdermin-D, indicating activation of pyroptosis. In a mouse model of sporadic AAD induced by high-fat diet and angiotensin II infusion, AIM2-deficient mice showed significant reduction in aortic dissection, but not aneurysm formation in all aortic segments, versus wild-type mice. Finally, treating cultured human aortic SMCs with double-stranded DNA induced AIM2 expression, caspase-1 cleavage, and gasdermin-D cleavage; these effects were reduced by silencing AIM2 and caspase-1 genes, suggesting involvement of the AIM2 inflammasome in cytosolic DNA-induced activation of SMC pyroptosis. CONCLUSIONS: Activation of the AIM2 inflammasome cascade contributes to aortic degeneration and dissection, in part, by activating pyroptosis.

Nothing like a good feud to spark competition: First use of the total artificial heart.

As a native Houstonian, the notoriety surrounding Dr. Denton A Cooley's implantation of the total artificial heart on Good Friday, April 4, 1969, was inescapable. At the time, Drs. Cooley and Michael E. DeBakey were the two most famous surgeons in Houston and much of the world. They had worked together professionally for 18 years, revolutionizing cardiothoracic surgery and mastering aortic surgery from beginning to end. However, this working relationship ended abruptly, and one of the most famous feuds in medicine began. Little did I know at the time that I would train with both men, work in both their respective institutions (which are located on the most competitive block of the Texas Medical Center), and play a role four decades later as their relationship rekindled. Here, I recount what I have come to learn about these events.

Use of a self-expanding transcatheter valve for a degenerated INTUITY valve.

Valve-in-valve transcatheter aortic valve replacement for degenerated surgical bioprosthesis is becoming a more common therapeutic option. Rapid-deployment valves are novel, have distinct structural differences from standard surgical valves, and are increasingly used in minimal-access surgery. We report the case of a 61-year-old man who developed severe stenosis of an Edwards INTUITY Elite rapid-deployment valve and who subsequently underwent successful valve-in-valve placement of a self-expanding transcatheter valve. To our knowledge, this is the first description of the technical aspects of and considerations for using the self-expanding transcatheter platform in the Edwards INTUITY Elite valve.

What is the optimal timing for thoracic endovascular aortic repair in uncomplicated Type B aortic dissection?

BACKGROUND: Uncomplicated Stanford Type B aortic dissection (un-TBAD) is characterized by a tear in the aorta distal to the left subclavian artery without ascending aorta and arch involvement. Optimized cardiovascular control (blood pressure and heart rate) is the current gold standard treatment according to current international guidelines. However, emerging evidence indicates that thoracic endovascular aortic repair (TEVAR) is both safe and effective in the treatment of un-TBAD with improved long-term survival outcomes in combination with optimal medical therapy (OMT) relative to OMT alone. However, the optimal timeframe for intervention is not entirely clarified. AIMS: This review critically addresses current state-of-the-art comparing TEVAR with OMT and corresponding clinical outcomes for un-TBAD based on timing of intervention. METHODS: We carried out a comprehensive literature search on multiple electronic databases including PUBMED and Scopus to collate all research evidence on timing of TEVAR in uncomplicated Type B aortic dissection. RESULTS: TEVAR has proven to be a safe and effective treatment for un-TBAD in combination with OMT through comparable survival outcomes, improved aortic remodeling, and relatively low periprocedural added risks. Though the timing of intervention remains controversial, it is becoming clear that performing TEVAR during the subacute phase of un-TBAD yields better outcomes compared to earlier and delayed (>90 days) intervention. CONCLUSIONS: Further research is required into both short- and long-term outcomes of TEVAR in addition to its optimal therapeutic window for un-TBAD. With stronger evidence, TEVAR is likely to be adopted as the gold-standard intervention for un-TBAD with definitive timeframe guidelines.

Subjective assessment underestimates surgical risk: On the potential benefits of cardiopulmonary exercise testing for open thoracoabdominal repair.

BACKGROUND: Initial clinical evaluation (ICE) is traditionally considered a useful screening tool to identify frail patients during the preoperative assessment. However, emerging evidence supports the more objective assessment of cardiorespiratory fitness (CRF) via cardiopulmonary exercise testing (CPET) to improve surgical risk stratification. Herein, we compared both subjective and objective assessment approaches to highlight the interpretive idiosyncrasies. METHODS: As part of routine preoperative patient contact, patients scheduled for major surgery were prospectively "eyeballed" (ICE) by two experienced clinicians before more detailed history taking that also included the American Society of Anesthesiologists score classification. Each patient was subjectively judged to be either "frail" or "not frail" by ICE and "fit" or "unfit" from a thorough review of the medical notes. Subjective data were compared against the more objective validated assessment of postoperative outcomes using established CPET "cut-off" metrics incorporating peak pulmonary oxygen uptake, V̇O2PEAK at the anaerobic threshold (V̇O2 -AT), and ventilatory equivalent for carbon dioxide that collectively informed risk stratification. These data were retrospectively extracted from a single-center prospective National Health Service database. Data were analyzed using the Chi-square automatic interaction detection decision tree method. RESULTS: A total of 127 patients were examined that comprised 58% male and 42% female patients aged 69 ± 10 years with a body mass index of 29 ± 7 kg/m2 . Patients were poorly conditioned with a V̇O2PEAK almost 20% lower than predicted for age, sex-matched healthy controls with 35% exhibiting a V̇O2 -AT < 11 ml/kg/min. Disagreement existed between the subjective assessments of risk with ∼34% of patients classified as not frail on ICE were considered unfit by notes review (p < .0001). Furthermore, ∼35% of patients considered not frail on ICE and ∼31% of patients considered fit by notes review exhibited a V̇O2 -AT < 11 ml/kg/min, and of these, ∼28% and ∼19% were classified as intermediate to high risk. CONCLUSIONS: These findings highlight the interpretive limitations associated with the subjective assessment of patient frailty with surgical risk classification underestimated in up to a third of patients compared to the validated assessment of CRF. They reinforce the benefits of a more objective and integrated approach offered by CPET that may help us to improve perioperative risk assessment and better direct critical care provision in patients scheduled for "high-stakes" surgery including open thoracoabdominal aortic aneurysm repair.

The misnomer of uncomplicated type B aortic dissection.

BACKGROUND: Acute type B aortic dissection (TBAD) is a rare condition that can be divided into complicated (CoTBAD) and uncomplicated (UnCoTBAD) based on certain presenting clinical and radiological features, with UnCoTBAD constituting the majority of TBAD cases. The classification of TBAD directly affects the treatment pathway taken, however, there remains confusion as to exactly what differentiates complicated from uncomplicated TBAD. AIMS: The scope of this review is to delineate the literature defining the intervention parameters for UnCoTBAD. METHODS: A comprehensive literature search was conducted using multiple electronic databases including PubMed, Scopus, and EMBASE to collate and summarize all research evidence on intervention parameters and protocols for UnCoTBAD. RESULTS: A TBAD without evidence of malperfusion or rupture might be classified as uncomplicated but there remains a subgroup who might exhibit high-risk features. Two clinical features representative of "high risk" are refractory pain and persistent hypertension. First-line treatment for CoTBAD is TEVAR, and whilst this has also proven its safety and effectiveness in UnCoTBAD, it is still being managed conservatively. However, TBAD is a dynamic pathology and a significant proportion of UnCoTBADs can progress to become complicated, thus necessitating more complex intervention. While the "high-risk" UnCoTBAD do benefit the most from TEVAR, yet, the defining parameters are still debatable as this benefit can be extended to a wider UnCoTBAD population. CONCLUSION: Uncomplicated TBAD remains a misnomer as it is frequently representative of a complex ongoing disease process requiring very close monitoring in a critical care setting. A clear diagnostic pathway may improve decision making following a diagnosis of UnCoTBAD. Choice of treatment still predominantly depends on when an equilibrium might be reached where the risks of TEVAR outweigh the natural history of the dissection in both the short- and long-term.

Mid- and long-term outcomes of thoracic endovascular aortic repair in acute and subacute uncomplicated type B aortic dissection.

BACKGROUND: Uncomplicated type B aortic dissection (un-TBAD) has been managed conservatively with medical therapy to control the heart rate and blood pressure to limit disease progression, in addition to radiological follow-up. However, several trials and observational studies have investigated the use of thoracic endovascular aortic repair (TEVAR) in un-TBAD and suggested that TEVAR provides a survival benefit over medical therapy. Outcomes of TEVAR have also been linked with the timing of intervention. AIMS: The scope of this review is to collate and summarize all the evidence in the literature on the mid- and long-term outcomes of TEVAR in un-TBAD, confirming its superiority. We also aimed to investigate the relationship between the timing of TEVAR intervention and results. METHODS: We carried out a comprehensive literature search on multiple electronic databases including PubMed, Scopus, and EMBASE to collate and summarize all research evidence on the mid- and long-term outcomes of TEVAR in un-TBAD, as well as its relationship with intervention timing. RESULTS: TEVAR has proven to be a safe and effective tool in un-TBAD, offering superior mid- and long-term outcomes including all-cause and aorta-related mortality, aortic-specific adverse events, aortic remodeling, and need for reintervention. Additionally, performing TEVAR during the subacute phase of dissection seems to yield optimal results. CONCLUSION: The evidence demonstrating a survival advantage in favor TEVAR over medical therapy in un-TBAD means that with further research, particular trials and observational studies, TEVAR could become the gold-standard treatment option for un-TBAD patients.

Criteria for endovascular intervention in type B aortic dissection.

BACKGROUND: The use of thoracic endovascular aortic repair (TEVAR) for the management of uncomplicated type B aortic dissection (un-TBAD) remains controversial. There is a lack of consensus over whether pre-emptive TEVAR should be carried out in patients with un-TBAD at risk of progression to complicated TBAD. We present a review of current evidence and seek to suggest criteria where endovascular intervention in un-TBAD may prove beneficial relative to pharmacotherapy alone. METHODS AND MATERIALS: PubMed and Cochrane databases were searched using terms including: type B aortic dissection, risk factors, medical therapy, TEVAR, false lumen (FL) expansion, and mortality. Papers were selected based on title and abstract. RESULTS: Optimal medical therapy remains the mainstay treatment for patients with un-TBAD, however, patients with un-TBAD present with varying degrees of disease progression risk. Factors such as age, aortic morphology, history of connective tissue disorders, FL thrombosis, and aortic branch involvement may potentiate progression from un-TBAD to complicated TBAD. Short- and long-term outcomes associated with TEVAR for TBAD remain promising. CONCLUSION: Pre-emptive TEVAR may be beneficial in patients with un-TBAD presenting with the above factors, however, further prospective research into the optimal timing for TEVAR in un-TBAD is required.

Long-term outcomes of total arch replacement versus proximal aortic replacement in acute type A aortic dissection: Meta-analysis of Kaplan-Meier-derived individual patient data.

OBJECTIVES: To evaluate the long-term outcomes of a conservative approach (with proximal aortic replacement with or without hemiarch replacement) versus an aggressive approach (with total aortic arch replacement) in the treatment of acute type A aortic dissection (ATAAD). METHODS: We performed a pooled analysis of Kaplan-Meier-derived individual patient data from studies with follow-up comparing the aforementioned approaches to treat patients with ATAAD. RESULTS: Eighteen studies met our eligibility criteria, comprising 5243 patients with follow-up (Conservative: 3676 patients; Aggressive: 1567 patients). We observed a statistically significant difference in overall survival favoring the aggressive approach (hazard ratios [HR] 0.86, 95% confidence interval [CI] 0.76-0.98, p = .022), but no statistically significant difference in the risk of reoperation (HR 0.89, 95% CI 0.66-1.2, p = .439) in the overall follow-up. Landmark analyses revealed that, in the first 3 months after the procedure, mortality rates were comparable between conservative and aggressive approaches (HR 1.04, 95% CI 0.88-1.24, p = .627), but the results beyond 3 months showed improved survival in patients undergoing the aggressive surgical procedure (HR 0.71, 95% CI 0.59-0.85, p < .001). The landmark analyses also revealed that, in the first 7 years after the procedure, reoperation rates were comparable between the approaches (HR 1.03, 95% CI 0.76-1.40, p = .848), but the results beyond 7 years showed a lower risk of reoperation in patients undergoing the aggressive surgical procedure (HR 0.10, 95% CI 0.01-0.75, p = .025). CONCLUSION: The aggressive approach seems to confer better long-term survival and lower risk of the need for reoperation in the follow-up of patients treated for ATAAD.

Single-Cell Transcriptome Analysis Reveals Dynamic Cell Populations and Differential Gene Expression Patterns in Control and Aneurysmal Human Aortic Tissue.

BACKGROUND: Ascending thoracic aortic aneurysm (ATAA) is caused by the progressive weakening and dilatation of the aortic wall and can lead to aortic dissection, rupture, and other life-threatening complications. To improve our understanding of ATAA pathogenesis, we aimed to comprehensively characterize the cellular composition of the ascending aortic wall and to identify molecular alterations in each cell population of human ATAA tissues. METHODS: We performed single-cell RNA sequencing analysis of ascending aortic tissues from 11 study participants, including 8 patients with ATAA (4 women and 4 men) and 3 control subjects (2 women and 1 man). Cells extracted from aortic tissue were analyzed and categorized with single-cell RNA sequencing data to perform cluster identification. ATAA-related changes were then examined by comparing the proportions of each cell type and the gene expression profiles between ATAA and control tissues. We also examined which genes may be critical for ATAA by performing the integrative analysis of our single-cell RNA sequencing data with publicly available data from genome-wide association studies. RESULTS: We identified 11 major cell types in human ascending aortic tissue; the high-resolution reclustering of these cells further divided them into 40 subtypes. Multiple subtypes were observed for smooth muscle cells, macrophages, and T lymphocytes, suggesting that these cells have multiple functional populations in the aortic wall. In general, ATAA tissues had fewer nonimmune cells and more immune cells, especially T lymphocytes, than control tissues did. Differential gene expression data suggested the presence of extensive mitochondrial dysfunction in ATAA tissues. In addition, integrative analysis of our single-cell RNA sequencing data with public genome-wide association study data and promoter capture Hi-C data suggested that the erythroblast transformation-specific related gene(ERG) exerts an important role in maintaining normal aortic wall function. CONCLUSIONS: Our study provides a comprehensive evaluation of the cellular composition of the ascending aortic wall and reveals how the gene expression landscape is altered in human ATAA tissue. The information from this study makes important contributions to our understanding of ATAA formation and progression.