Midterm follow-up of composite graft replacement of the aortic root (30-year experience)-remarkably safe, effective, and durable.

Objectives: Contemporary operative choices for aortic root disease include aortic root replacement (ARR) and a variety of valve-sparing and aortic root-repair procedures. We evaluate ultra-long-term outcomes of ARR, focusing on survival, freedom from late reoperation, and adverse events. Methods: Prospectively kept records were used to accomplish long-term follow-up of patients who underwent ARR (4-pronged Yale survival assessment paradigm). Results: Between 1990 and 2020, 564 patients underwent ARR (mean 56 years, 84% male). A modified Cabrol procedure (Dacron coronary graft) was employed in 9.0% (51/564) and concomitant coronary artery bypass grafting in 9.4% (53/564). There were 12.8% (72/564) urgent/emergent and 7.4% (42/564) redo procedures. Operative mortality occurred in 12 patients (2.1%) overall, or 1.4% (8/554) of nondissection and 1.3% (6/468) of elective first-time operations. Six of the 12 deaths presented with acute type A dissection, urgent operation, or reoperative states. Operative mortality dropped to 0.6% during the past 10 years. In total, 11 patients developed endocarditis. Stroke occurred in 11 of 564 patients (2.0%), 4 of whom had presented with type A dissection. Late events included bleeding in 2.8% (16/564), thromboembolism in 1.4% (8/564), and reoperation of the root in 5 of 564 (0.9%) at 15 years and more distal aortic segments in 16/564 (2.8%). Survival was no different from age/sex-matched controls. Conclusions: This ultra-long-term experience finds ARR to be extraordinarily safe, effective, and durable, with minimal long-term bleeding, thromboembolism, or graft failure. This experience provides a standard of durability for ARR against which ultra-long-term outcomes with alternate procedures (valve-sparing, Ross, other) may be compared.

The role of anatomic shape features in the prognosis of uncomplicated type B aortic dissection initially treated with optimal medical therapy.

OBJECTIVE: Currently, the long-term outcomes of uncomplicated type B aortic dissection (TBAD) patients managed with optimal medical therapy (OMT) remain poor. Aortic expansion is a major factor that determines patient long-term survival. The objective of this study was to investigate the association between anatomic shape features and (i) OMT outcome; (ii) aortic growth rate for TBAD patients initially treated with OMT. METHODS: 108 CT images of TBAD in the acute and chronic phases were collected from 46 patients who were initially treated with OMT. Statistical shape models (SSM) of TBAD were constructed to extract shape features from the earliest initial CT scans of each patient by using principal component analysis (PCA) and partial least square (PLS) regression. Additionally, conventional shape features (e.g., aortic diameter) were quantified from the earliest CT scans as a baseline for comparison. We identified conventional and SSM features that were significant in separating OMT "success" and failure patients. Moreover, the aortic growth rate was predicted by SSM and conventional features using linear and nonlinear regression with cross-validations. RESULTS: Size-related SSM and conventional features (mean aortic diameter: p=0.0484, centerline length: p=0.0112, PCA score c1: p=0.0192, and PLS scores t1: p=0.0004, t2: p=0.0274) were significantly different between OMT success and failure groups, but these features were incapable of predicting the aortic growth rate. SSM shape features showed superior results in growth rate prediction compared to conventional features. Using multiple linear regression, the conventional, PCA, and PLS shape features resulted in root mean square errors (RMSE) of 1.23, 0.85, and 0.84 mm/year, respectively, in leave-one-out cross-validations. Nonlinear support vector regression (SVR) led to improved RMSE of 0.99, 0.54, and 0.43 mm/year, for the conventional, PCA, and PLS features, respectively. CONCLUSION: Size-related shape features of the earliest scan were correlated with OMT failure but led to large errors in the prediction of the aortic growth rate. SSM features in combination with nonlinear regression could be a promising avenue to predict the aortic growth rate.

Long-term follow-up of Cabrol fistula for uncontrollable bleeding: A life-saving procedure.

Objective: Surgeons shy away from using the Cabrol fistula (perigraft space to right atrium [RA] shunt) due to unfamiliarity, concern for persistent left-to-right shunting, and fear of "painting-over" anastomotic defects that will result in later problems. We review nearly 2 decades of experience with application of the Cabrol fistula in a large thoracic aortic practice, with emphasis on precise surgical techniques, early and late outcomes, and detailed radiographic analysis. Methods: Operative records of all procedures in which the Cabrol fistula was used were retrieved and analyzed, with precise review of the details of construction of each Cabrol fistula and clinical and radiologic (echocardiographic and computed tomographic) patient follow-up. Results: The Cabrol fistula successfully controlled the bleeding in all cases. There were no late false aneurysms at any anastomotic sites. There was no continued flow through any fistula. Good perioperative and long-term survival was achieved in these complex cases that found themselves at a very dangerous crux before application of the Cabrol fistula. Conclusions: The Cabrol fistula is an important tool for the thoracic aortic surgeon to have in the toolbox. We found the Cabrol fistula to be extremely effective at controlling bleeding, with no late persistent fistula flow and no late false aneurysm formation. Without the fistula, outcome in these patients would likely have been lethal. We recommend the Cabrol fistula technique strongly for life-saving application in rare cases of bleeding uncontrollable by conventional methods.

Genetic Overlap of Spontaneous Dissection of Either the Thoracic Aorta or the Coronary Arteries.

Ascending thoracic aortic dissection (ATAD) is a well-known vascular cause of sudden death. Spontaneous coronary artery dissections (SCAD) are emerging as an important cause of early-onset myocardial infarction and sudden death. Genetic variants in multiple connective tissue genes have been recognized to underlie ATAD; other genetic variants have similarly been recognized to underlie SCAD. Little data are available regarding any genetic commonality between ATAD and SCAD. Our objective is to determine and characterize any genetic overlap between genes coding for ATAD and SCAD. We identified and reviewed 17 retrospective and prospective genetic studies of thoracic aortic dissection and SCAD published between 2016 and 2022 identified through PubMed and Orbis. Articles highlighting the significant plausible triggers for ATAD or SCAD individually were analyzed. No previous study reviewed both ATAD and SCAD genetics together. Separate lists of causative genes were constructed for ATAD and SCAD-and then commonalities were sought. A Venn diagram was constructed to display the genetic overlap and common physiologic pathways involved. We identified a definite, meaningful overlap of 15 independent genes based on a genome-wide association study or other genetic methods. The associated genetic pathways involved various biologic processes including elastin degradation, smooth muscle cell function, and the TGFß-pathway. The overlapping genes included the following: COL3A1, TGFB2, SMAD3, MYLK, TGFBR2, TGFBR1, LOX, FBN1, NOTCH1, ELN, COL5A1, COL5A2, COL1A2, MYH11, and TLN1. The corresponding molecular pathways were investigated and correlated for both diseases. We are not aware of other studies searching for genetic commonalities between ATAD and SCAD. We have successfully identified overlapping genes-and their corresponding molecular pathways-for ATAD and SCAD. We hope that these insights will lead to further clinical and scientific understanding of each disease through study of their fundamental commonalities.

Bicuspid aortopathy does not require earlier surgical intervention.

OBJECTIVES: Guidelines for surgical correction of patients with ascending thoracic aortic aneurysm (ATAA) with a bicuspid aortic valve (BAV) have oscillated over the years. In this study, we outline the natural history of the ascending aorta in patients with BAV and trileaflet aortic valve (TAV) ATAA followed over time, to ascertain if their behavior differs and to determine if a different threshold for intervention is required. METHODS: Aortic diameters and long-term complications (ie, adverse aortic events) of 2428 patients (554 BAV and 1874 TAV) with ATAA before operative repair were reviewed. Growth rates, yearly complication rates, event-free survival, and risk of complications as a function of aortic size were calculated. Long-term follow-up and precise cause of death granularity was achieved via a comprehensive 6-pronged approach. RESULTS: Aortic growth rate in patients with BAV vs TAV ATAA was 0.20 and 0.17 cm/year, respectively (P = .009), with the rate increasing with increasing aortic size. Yearly adverse aortic events rates increased with ATAA size and were lower for patients with BAV. The relative risk of adverse aortic events exhibited an exponential increase with aortic diameter. Patients with BAV had a lower all-cause and ascending aorta-specific adverse aortic events hazard. Age-adjusted 10-year event-free survival was significantly better for patients with BAV, and BAV emerged as a protective factor against type A dissection, rupture, and ascending aortic death. CONCLUSIONS: The threshold for surgical repair of ascending aneurysm with BAV should not differ from that of TAV. Prophylactic surgery should be considered at 5.0 cm for patients with TAV (and BAV) at expert centers.

Aortic Size at the Time of Type A and Type B Dissections.

BACKGROUND: Aortic diameter at time of dissection remains an indispensable risk-determining characteristic for prophylactic repair of thoracic aortic aneurysms. Histograms of aortic size at the time of dissection have the potential to shed more light on this relationship. METHODS: Size of the thoracic aorta at the time of dissection was determined from imaging of 407 naturally occurring, acute, flap-type ascending or descending aortic dissections treated at 1 institution (1990-2022). Histograms were constructed to depict aortic size at the time of dissection. Data were analyzed by logistic regression. RESULTS: There were 170 (69.11%) of 246 type A dissections (median, 5.07 cm; interquartile range, 4.60-5.67 cm) and 130 (80.75%) of 161 type B dissections (median, 4.2 cm; interquartile range, 3.60-4.87 cm) that occurred at diameters <5.5 cm. By unadjusted regression, factors associated with significantly increased odds of type A dissection at diameters <5.5 cm were female sex (odds ratio [OR], 2.06; P = .023), hypertension (OR, 1.82; P = .036), and smoking (OR, 1.92; P = .029). Patients with bicuspid aortic valve had significantly decreased odds of type A dissection at diameters <5.5 cm (OR, 0.3; P = .047). The recent "left shift" to 5.0 cm in the criterion for ascending aortic intervention could prevent an additional 29.3% of type A dissections. CONCLUSIONS: Aortic diameter at the time of type A dissection is consistent with the new guidelines that recommend surgical intervention at 5.0 cm. Type B dissection occurs at small sizes and cannot be prevented with a size criterion.

KIF6 Trp719Arg Genetic Variant Increases Risk for Thoracic Aortic Dissection.

BACKGROUND: KIF6 (kinesin family member 6), a protein coded by the KIF6 gene, serves an important intracellular function to transport organelles along microtubules. In a pilot study, we found that a common KIF6 Trp719Arg variant increased the propensity of thoracic aortic aneurysms (TAA) to suffer dissection (AD). The present study aims for a definite investigation of the predictive ability of KIF6 719Arg vis à vis AD. Confirmatory findings would enhance natural history prediction in TAA. METHODS: 1108 subjects (899 aneurysm and 209 dissection patients) had KIF6 719Arg variant status determined. RESULTS: The 719Arg variant in the KIF6 gene correlated strongly with occurrence of AD. Specifically, KIF6 719Arg positivity (homozygous or heterozygous) was substantially more common in dissectors (69.8%) than non-dissectors (58.5%) (p = 0.003). Odds ratios (OR) for suffering aortic dissection ranged from 1.77 to 1.94 for Arg carriers in various dissection categories. These high OR associations were noted for both ascending and descending aneurysms and for homozygous and heterozygous Arg variant patients. The rate of aortic dissection over time was significantly higher for carriers of the Arg allele (p = 0.004). Additionally, Arg allele carriers were more likely to reach the combined endpoint of dissection or death (p = 0.03). CONCLUSIONS: We demonstrate the marked adverse impact of the 719Arg variant of the KIF6 gene on the likelihood that a TAA patient will suffer aortic dissection. Clinical assessment of the variant status of this molecularly important gene may provide a valuable "non-size" criterion to enhance surgical decision making above and beyond the currently used metric of aortic size (diameter).

Frailty predicts poor longer-term outcomes in patients following lower limb open surgical revascularization.

BACKGROUND: Frailty in vascular surgery patients is increasingly recognized as a marker of poor outcome. This provides particular challenges for patients with lower limb peripheral arterial disease who require surgical revascularization. This study aimed to assess the impact of frailty on short- and long-term outcome in this specific patient group using a specialty specific frailty score. METHODS: Patients undergoing open surgical revascularization for chronic limb ischemia (January 2015-December 2016) were assessed. Demographics, mode of admission, diagnosis, and site of surgery were recorded alongside a variety of frailty-specific characteristics. We calculated the previously validated Addenbrookes Vascular Frailty Score (AVFS) and Long AVFS (LAVFS). Primary outcome was 3-year mortality. RESULTS: Two hundred and sixty-one patients (75% men, median age 69 years) were studied. The median length of stay was 6 days with a 3-year mortality of 23%. The predictive power of vascular frailty scores showed that for 3-year mortality, area under the receiver operator curve values (AUROC) were specific for both the AVFS score (AUROC: 0.724, 95% CI: 0.654-0.794) and LAVFS Score (AUROC: 0.741, 95%CI: 0.670-0.813). Furthermore, the cumulative AVFS and LAVFS scores both predicted mortality over the follow-up period (P=0.0001) with increased mortality among patients with higher scores. CONCLUSIONS: Incremental worsening of frailty, determined using a specialty specific frailty score, predicts mortality risk in patients undergoing lower limb surgical revascularization.

Hospice care access inequalities: a systematic review and narrative synthesis.

BACKGROUND: Inequalities in access to hospice care is a source of considerable concern; white, middle-class, middle-aged patients with cancer have traditionally been over-represented in hospice populations. OBJECTIVE: To identify from the literature the demographic characteristics of those who access hospice care more often, focusing on: diagnosis, age, gender, marital status, ethnicity, geography and socioeconomic status. DESIGN: Systematic literature review and narrative synthesis. METHOD: Searches of Medline, PsycINFO, CINAHL, Web of Science, Assia and Embase databases from January 1987 to end September 2019 were conducted. Inclusion criteria were peer-reviewed studies of adult patients in the UK, Australia, New Zealand and Canada, receiving inpatient, day, outpatient and community hospice care. Of the 45 937 titles retrieved, 130 met the inclusion criteria. Narrative synthesis of extracted data was conducted. RESULTS: An extensive literature search demonstrates persistent inequalities in hospice care provision: patients without cancer, the oldest old, ethnic minorities and those living in rural or deprived areas are under-represented in hospice populations. The effect of gender and marital status is inconsistent. There is a limited literature concerning hospice service access for the LGBTQ+ community, homeless people and those living with HIV/AIDS, diabetes and cystic fibrosis. CONCLUSION: Barriers of prognostic uncertainty, institutional cultures, particular needs of certain groups and lack of public awareness of hospice services remain substantial challenges to the hospice movement in ensuring equitable access for all.

Regulation of nerve growth and patterning by cell surface protein disulphide isomerase.

Contact repulsion of growing axons is an essential mechanism for spinal nerve patterning. In birds and mammals the embryonic somites generate a linear series of impenetrable barriers, forcing axon growth cones to traverse one half of each somite as they extend towards their body targets. This study shows that protein disulphide isomerase provides a key component of these barriers, mediating contact repulsion at the cell surface in chick half-somites. Repulsion is reduced both in vivo and in vitro by a range of methods that inhibit enzyme activity. The activity is critical in initiating a nitric oxide/S-nitrosylation-dependent signal transduction pathway that regulates the growth cone cytoskeleton. Rat forebrain grey matter extracts contain a similar activity, and the enzyme is expressed at the surface of cultured human astrocytic cells and rat cortical astrocytes. We suggest this system is co-opted in the brain to counteract and regulate aberrant nerve terminal growth.

The Effect of Frailty on Long Term Outcomes in Vascular Surgical Patients.

OBJECTIVE: Frailty is a multidimensional vulnerability due to age associated decline. The impact of frailty on long term outcomes was assessed in a cohort of vascular surgical patients. METHODS: Patients aged over 65 years with a length of stay greater than two days admitted to a tertiary vascular unit over a single calendar year were included. Demographics, mode of admission, and diagnosis were recorded alongside a variety of frailty specific characteristics. Using the previously developed Addenbrookes Vascular Frailty Score (AVFS - 6 point score: anaemia on admission, lack of independent mobility, polypharmacy, Waterlow score > 13, depression, and emergency admission) the effect of frailty on five year mortality and re-admission rates was assessed using multivariable regression techniques. The AVFS was further refined to assess longer term outcomes. RESULTS: In total, 410 patients (median age 77 years) were included and followed up until death or five years from the index admission. One hundred and thirty-four were treated for aortic aneurysm, 75 and 96 for acute and chronic limb ischaemia respectively, 52 for carotid disease, and 53 for other pathologies. The in hospital mortality rate was 3.6%. The one, three, and five year survival rates were 83%, 70% and 59%; and the one, three, and five year re-admission free survival rates were 47%, 29%, and 22% respectively. Independent predictors of five year mortality were age, lack of independent mobility, high Charlson score, polypharmacy, evidence of malnutrition, and emergency admission (p < .010 for all). Patients with AVFS 0 or 1 had restricted mean survival times which were one year longer than those with AVFS 2 or 3 (p < .001), who in turn had restricted mean survival times over one year longer than those with AVFS of 4 or more (p < .001). CONCLUSION: Frailty factors are strong predictors of long term outcomes in vascular surgery. Further prospective studies are warranted to investigate its utility in clinical decision making.