Temporal evolution of ascending aortic aneurysm wall stress predicts all-cause mortality.

OBJECTIVES: Diameter-based risk stratification for elective repair of ascending aortic aneurysm fails to prevent type A dissection in many patients. Aneurysm wall stresses may contribute to risk prediction; however, rates of wall stress change over time are poorly understood. Our objective was to examine aneurysm wall stress changes over 3-5 years and subsequent all-cause mortality. METHODS: Male veterans with <5.5 cm ascending aortic aneurysms and computed tomography at baseline and 3- to 5-year follow-up underwent three-dimensional aneurysm model construction. Peak circumferential and longitudinal wall stresses at systole were calculated using finite element analysis. Temporal trends were assessed by mixed-effects modelling. Changes in aortic wall stresses, diameter and length over time were evaluated as predictors of subsequent 3-year all-cause mortality by Cox proportional hazards modelling. RESULTS: Sixty-two male veterans were included in the study. Yearly changes in geometric and biomechanical measures were 0.12 mm/year (95% confidence interval, 0.04-0.20) for aortic diameter, 0.41 mm/year (0.12-0.71) for aortic length, 1.19 kPa/year -5.94 to 8.33) for peak circumferential stress, and 0.48 kPa/year (-3.89 to 4.84) for peak longitudinal stress. Yearly change in peak circumferential stress was significantly associated with hazard of death-hazard ratio for peak circumferential stress growth per 10 kPa/year, 1.27 (95% CI, 1.02-1.60; P = 0.037); hazard ratio for peak circumferential stress growth ≥ 32 kPa/year, 8.47 (95% CI, 2.42-30; P < 0.001). CONCLUSIONS: In this population of nonsurgical aneurysm patients, large temporal changes in peak circumferential stress, but not aortic diameter or length, was associated with all-cause mortality. Biomechanical stress and stress changes over time may be beneficial as additional risk factors for elective surgery in small aneurysms.

Evaluating the safety and efficacy of a novel polysaccharide hemostatic system during surgery: A multicenter multispecialty prospective randomized controlled trial.

Background: Operative blood loss is associated with postoperative morbidity and mortality in surgery. Hemostatic agents are used as adjuncts for hemostasis during surgery and help to prevent postoperative bleeding. We evaluated the safety and efficacy of an investigational polysaccharide hemostatic (PH) topical product compared to a U.S. Food and Drug Administration (FDA)-approved control in clinical use comprising microporous polysaccharide hemospheres (MPH) to achieve hemostasis of bleeding surfaces during surgery. Study design: This prospective multicenter trial enrolled patients undergoing open elective cardiac, general, or urologic surgery. Patients were stratified by bleeding severity and therapeutic area, then randomized 1:1 to receive PH or MPH. Bleeding assessments occurred intraoperatively using a novel bleeding assessment methodology. Primary endpoint was noninferiority as compared with control via effective hemostasis at 7 min. Patients were monitored and followed daily in the postoperative period until time of discharge and again at 6 weeks. Overall survival was assessed in oncology patients at 24 months. Safety of PH vs. MPH was determined by comparing relative incidence of adverse events. Results: Across 19 centers, 324 (161 PH, 163 MPH) patients were randomized (48 % general surgery, 27 % cardiac surgery, and 25 % urologic surgery). PH was noninferior to MPH and met the primary endpoint of hemostatic success at 7 min at a non-inferiority margin of 10 %. No significant differences were found in adverse event rates. Six deaths were reported within the 6-week follow-up period. No difference in overall survival was observed at 2 years (76 % PH vs. 74 % MPH, P = .66) for patients undergoing cancer operations. Conclusion: Across three therapeutic areas, PH was noninferior to MPH at all hemostasis assessment time points with no safety concerns. PH is an effective alternative to MPH for hemostasis during surgery.ClinicalTrials.gov Identifier: NCT02359994.

Impact of nondiameter aortic indices on surgical eligibility: Results from the Treatment in Thoracic Aortic Aneurysm: Surgery Versus Surveillance (TITAN: SvS) randomized controlled trial.

OBJECTIVES: Traditional criterion for intervention on an asymptomatic ascending aortic aneurysm has been a maximal aortic diameter of 5.5 cm or more. The 2022 American College of Cardiology/American Heart Association aortic guidelines adopted cross-sectional aortic area/height ratio, aortic size index, and aortic height index as alternate parameters for surgical intervention. The objective of this study was to evaluate the impact of using these newer indices on patient eligibility for surgical intervention in a prospective, multicenter cohort with moderate-sized ascending aortic aneurysms between 5.0 and 5.4 cm. METHODS: Patients enrolled from 2018 to 2023 in the randomization or registry arms of the multicenter trial, Treatment In Thoracic Aortic aNeurysm: Surgery versus Surveillance, were included in the study. Clinical data were captured prospectively in an online database. Imaging data were derived from a core computed laboratory. RESULTS: Among the 329 included patients, 20% were female. Mean age was 65.0 ± 11.6 years, and mean maximal aortic diameter was 50.8 ± 3.9 mm. In the one-third of all patients (n = 109) who met any 1 of the 3 criteria (ie, aortic size index ≥3.08 cm/m2, aortic height index ≥3.21 cm/m, or cross-sectional aortic area/height ≥ 10 cm2/m), their mean maximal aortic diameter was 52.5 ± 0.52 mm. Alternate criteria were most commonly met in women compared with men: 20% versus 2% for aortic size index (P < .001), 39% versus 5% for aortic height index (P < .001), and 39% versus 21% for cross-sectional aortic area/height (P = .002), respectively. CONCLUSIONS: One-third of patients in Treatment In Thoracic Aortic aNeurysm: Surgery versus Surveillance would meet criteria for surgical intervention based on novel parameters versus the classic definition of diameter 5.5 cm or more. Surgical thresholds for aortic size index, aortic height index, or cross-sectional aortic area/height ratio are more likely to be met in female patients compared with male patients.

Height and body surface area versus wall stress for stratification of mid-term outcomes in ascending aortic aneurysm.

Objectives: Current diameter-based guidelines for ascending thoracic aortic aneurysms (aTAA) do not consistently predict risk of dissection/rupture. ATAA wall stresses may enhance risk stratification independent of diameter. The relation of wall stresses and diameter indexed to height and body surface area (BSA) is unknown. Our objective was to compare aTAA wall stresses with indexed diameters in relation to all-cause mortality at 3.75 years follow-up. Methods: Finite element analyses were performed in a veteran population with aortas ≥ 4.0 cm. Three-dimensional geometries were reconstructed from computed tomography with models accounting for pre-stress geometries. A fiber-embedded hyperelastic material model was applied to obtain wall stress distributions under systolic pressure. Peak wall stresses were compared across guideline thresholds for diameter/BSA and diameter/height. Hazard ratios for all-cause mortality and surgical aneurysm repair were estimated using cause-specific Cox proportional hazards models. Results: Of 253 veterans, 54 (21 %) had aneurysm repair at 3.75 years. Indexed diameter alone would have prompted repair at baseline in 17/253 (6.7 %) patients, including only 4/230 (1.7 %) with diameter < 5.5 cm. Peak wall stresses did not significantly differ across guideline thresholds for diameter/BSA (circumferential: p = 0.15; longitudinal: p = 0.18), but did differ for diameter/height (circumferential: p = 0.003; longitudinal: p = 0.048). All-cause mortality was independently associated with peak longitudinal stresses (p = 0.04). Peak longitudinal stresses were best predicted by diameter (c-statistic = 0.66), followed by diameter/height (c-statistic = 0.59), and diameter/BSA (c-statistic = 0.55). Conclusions: Diameter/height improved stratification of peak wall stresses compared to diameter/BSA. Peak longitudinal stresses predicted all-cause mortality independent of age and indexed diameter and may aid risk stratification for aTAA adverse events.

Projections of Drug-Drug Interactions Caused by Time-Dependent Inhibitors of Cytochrome P450 1A2, 2B6, 2C8, 2C9, 2C19, and 2D6 Using In Vitro Data in Static and Dynamic Models.

In vitro time-dependent inhibition (TDI) kinetic parameters for cytochrome P450 (CYP) 1A2, 2B6, 2C8, 2C9, 2C19, and 2D6, were determined in pooled human liver microsomes for 19 drugs (and 2 metabolites) for which clinical drug-drug interactions (DDI) are known. In vitro TDI data were incorporated into the projection of the magnitude of DDIs using mechanistic static models and Simcyp®. Results suggest that for the mechanistic static model, use of estimated average unbound exit concentration of the inhibitor from the liver resulted in a successful prediction of observed magnitude of clinical DDIs and was similar to Simcyp®. Overall, predictions of DDI magnitude (i.e., fold increase in AUC of a CYP-specific marker substrate) were within 2-fold of actual values. Geometric mean-fold errors were 1.7 and 1.6 for static and dynamic models, respectively. Projections of DDI from both models were also highly correlated to each other (r2 = 0.92). This investigation demonstrates that DDI can be reliably predicted from in vitro TDI data generated in HLM for several CYP enzymes. Simple mechanistic static model equations as well as more complex dynamic PBPK models can be employed in this process. Significance Statement Cytochrome P450 time-dependent inhibitors (TDI) can cause drug-drug interactions (DDI). An ability to reliably assess the potential for a new drug candidate to cause DDI is essential during drug development. In this report, TDI data for 19 drugs (and 2 metabolites) were measured and used in static and dynamic models to reliably project the magnitude of DDI resulting from inhibition of CYP1A2, 2B6, 2C8, 2C9, 2C19, and 2D6.

Impact of Oral Anticoagulation on Clinical Outcomes in Postoperative Atrial Fibrillation.

INTRODUCTION: The impact of postoperative oral anticoagulation (OAC) with warfarin on postoperative atrial fibrillation (POAF) after coronary artery bypass grafting (CABG) was the focus of this examination of patients from the randomized endo-vein graft prospective (REGROUP) Trial. MATERIAL AND METHODS: REGROUP was a prospective randomized Veterans Affairs cooperative study comparing endoscopic versus open vein harvest in elective CABG patients (March 2014-April 2017) at 16 Veterans Affairs facilities. This study compared new-onset POAF patients who were treated with warfarin versus no-warfarin. Outcomes included stroke during active follow-up and a major adverse cardiac event composite of mortality, acute myocardial infarction, and repeat revascularization during active and passive follow-up. RESULTS: Of the 316/1103 (28.6%) of REGROUP patients who developed new-onset POAF, 45 patients were excluded - mainly for preoperative warfarin use. Of the remaining 269 patients, 85 received OAC with warfarin (OAC group); 184 did not (no-OAC group). Stroke rates during active follow-up (32 [IQR 24-38] mo) were 3.5% OAC group versus 5.4% no-OAC group (P = 0.76); major adverse cardiac eventrates were 20% OAC versus 11.4% no-OAC (P = 0.06). On longer follow-up of (median 4.61 [IQR 3.9-5.1] y), discharge OAC use was associated with all-cause mortality after adjusting for Society of Thoracic Surgeons mortality risk (20.0% versus 11.4% no-OAC use; HR = 2.00, 95% CI: 1.05-3.81, P = 0.035). CONCLUSIONS: REGROUP patients with POAF treated with OAC had similar stroke and higher mortality rates versus no-OAC patients. Further investigation of the risk-benefit ratio of OAC in post-CABG patients and which POAF patient subgroups might derive the most benefit with anticoagulation appears warranted.

Sex differences in ascending aortic size reporting and growth on chest computed tomography and magnetic resonance imaging.

PURPOSE: Diameter-based guidelines for prophylactic repair of ascending aortic aneurysms have led to routine aortic evaluation in chest imaging. Despite sex differences in aneurysm outcomes, there is little understanding of sex-specific aortic growth rates. Our objective was to evaluate sex-specific temporal changes in radiologist-reported aortic size as well as sex differences in aortic reporting. METHOD: In this cohort study, we queried radiology reports of chest computed tomography or magnetic resonance imaging at an academic medical center from 1994 to 2022, excluding type A dissection. Aortic diameter was extracted using a custom text-processing algorithm. Growth rates were estimated using mixed-effects modeling with fixed terms for sex, age, and imaging modality, and patient-level random intercepts. Sex, age, and modality were evaluated as predictors of aortic reporting by logistic regression. RESULTS: This study included 89,863 scans among 46,622 patients (median [interquartile range] age, 64 [52-73]; 22,437 women [48%]). Aortic diameter was recorded in 14% (12,722/89,863 reports). Temporal trends were analyzed in 7194 scans among 1998 patients (age, 68 [60-75]; 677 women [34%]) with ≥2 scans. Aortic growth rate was significantly higher in women (0.22 mm/year [95% confidence interval 0.17-0.28] vs. 0.09 mm/year [0.06-0.13], respectively). Aortic reporting was significantly less common in women (odds ratio, 0.54; 95% CI, 0.52-0.56; p < 0.001). CONCLUSIONS: While aortic growth rates were small overall, women had over twice the growth rate of men. Aortic dimensions were much less frequently reported in women than men. Sex-specific standardized assessment of aortic measurements may be needed to address sex differences in aneurysm outcomes.

2022 ACC/AHA guideline for the diagnosis and management of aortic disease: A report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes). METHODS: A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate. STRUCTURE: Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease.

Aortic area/height ratio, peak wall stresses, and outcomes in veterans with tricuspid versus bicuspid aortic valve-associated ascending thoracic aortic aneurysms.

BACKGROUND: In ascending thoracic aortic aneurysm risk stratification, aortic area/height ratio is a reasonable alternative to maximum diameter. Biomechanically, aortic dissection may be initiated by wall stress exceeding wall strength. Our objective was to evaluate the association between aortic area/height and peak aneurysm wall stresses in relation to valve morphology and 3-year all-cause mortality. METHODS: Finite element analysis was performed on 270 ascending thoracic aortic aneurysms (46 associated with bicuspid and 224 with tricuspid aortic valves) in veterans. Three-dimensional aneurysm geometries were reconstructed from computed tomography and models developed accounting for prestress geometries. Fiber-embedded hyperelastic material model was applied to obtain aneurysm wall stresses during systole. Correlations of aortic area/height ratio and peak wall stresses were compared across valve types. Area/height ratio was evaluated across peak wall stress thresholds obtained from proportional hazards models of 3-year all-cause mortality, with aortic repair treated as a competing risk. RESULTS: Aortic area/height 10 cm2/m or greater coincided with 23/34 (68%) 5.0 to 5.4 cm and 20/24 (83%) 5.5 cm or greater aneurysms. Area/height correlated weakly with peak aneurysm stresses: for tricuspid valves, r = 0.22 circumferentially and r = 0.24 longitudinally; and for bicuspid valves, r = 0.42 circumferentially and r = 0.14 longitudinally. Age and peak longitudinal stress, but not area/height, were independent predictors of all-cause mortality (age: hazard ratio, 2.20 per 9-year increase, P = .013; peak longitudinal stress: hazard ratio, 1.78 per 73-kPa increase, P = .035). CONCLUSIONS: Area/height was more predictive of high circumferential stresses in bicuspid than tricuspid valve aneurysms, but similarly less predictive of high longitudinal stresses in both valve types. Peak longitudinal stress, not area/height, independently predicted all-cause mortality. VIDEO ABSTRACT.

Ascending thoracic aortic aneurysm elongation occurs in parallel with dilatation in a nonsurgical population.

OBJECTIVES: Rapid diameter growth is a criterion for ascending thoracic aortic aneurysm repair; however, there are sparse data on aneurysm elongation rate. The purpose of this study was to assess aortic elongation rates in nonsyndromic, nonsurgical aneurysms to understand length dynamics and correlate with aortic diameter over time. METHODS: Patients with <5.5-cm aneurysms and computed tomography angiography imaging at baseline and 3-5 years follow-up underwent patient-specific three-dimensional aneurysm reconstruction using MeVisLab. Aortic length was measured along the vessel centreline between the annulus and aortic arch. Maximum aneurysm diameter was determined from imaging in a plane normal to the vessel centreline. Average rates of aneurysm growth were evaluated using the longest available follow-up. RESULTS: Over the follow-up period, the mean aortic length for 67 identified patients increased from 118.2 (95% confidence interval: 115.4-121.1) mm to 120.2 (117.3-123.0) mm (P = 0.02) and 15 patients (22%) experienced a change in length of ≥5% from baseline. The mean annual growth rate for length [0.38 (95% confidence interval: 0.11-0.65) mm/year] was correlated with annual growth rate for diameter [0.1 (0.03-0.2) mm/year] (rho = 0.30, P = 0.01). Additionally, annual percentage change in length [0.3 (0.1-0.5)%/year] was similar to percentage change in diameter [0.2 (0.007-0.4)%/year, P = 0.95]. CONCLUSIONS: Aortic length increases in parallel with aortic diameter at a similar percentage rate. Further work is needed to identify whether elongation rate is associated with dissection risk. Such studies may provide insight into why patients with aortic diameters smaller than surgical guidelines continue to experience dissection events.

Formal consensus study on surgery to replace the aortic valve in adults aged 18-60 years.

OBJECTIVE: There is uncertainty about surgical procedures for adult patients aged 18-60 years undergoing aortic valve replacement (AVR). Options include conventional AVR (mechanical, mAVR; tissue, tAVR), the pulmonary autograft (Ross) and aortic valve neocuspidisation (Ozaki). Transcatheter treatment may be an option for selected patients. We used formal consensus methodology to make recommendations about the suitability of each procedure. METHODS: A working group, supported by a patient advisory group, developed a list of clinical scenarios across seven domains (anatomy, presentation, cardiac/non-cardiac comorbidities, concurrent treatments, lifestyle, preferences). A consensus group of 12 clinicians rated the appropriateness of each surgical procedure for each scenario on a 9-point Likert scale on two separate occasions (before and after a 1-day meeting). RESULTS: There was a consensus that each procedure was appropriate (A) or inappropriate (I) for all clinical scenarios as follows: mAVR: total 76% (57% A, 19% I); tAVR: total 68% (68% A, 0% I); Ross: total 66% (39% A, 27% I); Ozaki: total 31% (3% A, 28% I). The remainder of percentages to 100% reflects the degree of uncertainty. There was a consensus that transcatheter aortic valve implantation is appropriate for 5 of 68 (7%) of all clinical scenarios (including frailty, prohibitive surgical risk and very limited life span). CONCLUSIONS: Evidence-based expert opinion emerging from a formal consensus process indicates that besides conventional AVR options, there is a high degree of certainty about the suitability of the Ross procedure in patients aged 18-60 years. Future clinical guidelines should include the option of the Ross procedure in aortic prosthetic valve selection.

Association of 3-Year All-Cause Mortality and Peak Wall Stresses of Ascending Thoracic Aortic Aneurysms in Veterans.

Risk of aortic dissection in ascending thoracic aortic aneurysms is not sufficiently captured by size-based metrics. From a biomechanical perspective, dissection may be initiated when wall stress exceeds wall strength. Our objective was to assess the association between aneurysm peak wall stresses and 3-year all-cause mortality. Finite element analysis was performed in 273 veterans with chest computed tomography for surveillance of ascending thoracic aortic aneurysms. Three-dimensional geometries were reconstructed and models developed accounting for prestress geometries. A fiber-embedded hyperelastic material model was applied to obtain circumferential and longitudinal wall stresses under systolic pressure. Patients were followed up to 3 years following the scan to assess aneurysm repair and all-cause mortality. Fine-Gray subdistribution hazards were estimated for all-cause mortality based on age, aortic diameter, and peak wall stresses, treating aneurysm repair as a competing risk. When accounting for age, subdistribution hazard of mortality was not significantly increased by peak circumferential stresses (p = 0.30) but was significantly increased by peak longitudinal stresses (p = 0.008). Aortic diameter did not significantly increase subdistribution hazard of mortality in either model (circumferential model: p = 0.38; longitudinal model: p = 0.30). The effect of peak longitudinal stresses on subdistribution hazard of mortality was maximized at a binary threshold of 355kPa, which captured 34 of 212(16%) patients with diameter <5 cm, 11 of 36(31%) at 5.0-5.4 cm, and 11 of 25(44%) at ≥5.5 cm. Aneurysm peak longitudinal stresses stratified by age and diameter were associated with increased hazard of 3-year all-cause mortality in a veteran cohort. Risk prediction may be enhanced by considering peak longitudinal stresses.

Regional and directional delamination properties of healthy human ascending aorta and sinotubular junction.

PURPOSE: Acute type A aortic dissection (AD) is a catastrophic event associated with high mortality. Biomechanics can provide an understanding of the forces that lead the initial intimal tear to propagate, resulting in aortic dissection. We previously studied the material properties of normal human aortic roots. In this study, our objective was to determine the regional and directional delamination properties of healthy human ascending aorta (AscAo) and sinotubular junction (STJ). RESULTS: From 19 healthy donor hearts, total 107 samples from the AscAo and STJ were collected and tested along the circumferential and longitudinal directions. Specimens were subjected to uniaxial peeling testing with a manually created tear in the medial layer. The lateral AscAo subregion (greater curvature) had significantly lower delamination strength and dissection energy than anterior, medial, and posterior subregions in the longitudinal direction. Regionally, the delamination strength at AscAo was significantly lower than at STJ overall (p = 0.02) and in circumferential direction (p = 0.02) only. Directionally, the delamination strength at AscAo overall and in the anterior AscAo was significant lower in circumferential direction than longitudinal direction. Dissection energy demonstrated similar regional and directional trend as delamination strength. In addition, both dissection energy and delamination strength were correlated positively with thickness and negatively with age in the AscAo. In addition, the dissection energy was negatively related to stiffness at physiologic mean blood pressure. CONCLUSIONS: The greater curvature of the AscAo had the lowest delamination strength and dissection energy suggesting that region was most vulnerable to dissection propagation distally. Increased thickness of AscAo would be protective of dissection propagation while propagation would be more likely with increased AscAo stiffness.

2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes). METHODS: A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate. Structure: Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease.

2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines.

AIM: The "2022 ACC/AHA Guideline for the Diagnosis and Management of Aortic Disease" provides recommendations to guide clinicians in the diagnosis, genetic evaluation and family screening, medical therapy, endovascular and surgical treatment, and long-term surveillance of patients with aortic disease across its multiple clinical presentation subsets (ie, asymptomatic, stable symptomatic, and acute aortic syndromes). METHODS: A comprehensive literature search was conducted from January 2021 to April 2021, encompassing studies, reviews, and other evidence conducted on human subjects that were published in English from PubMed, EMBASE, the Cochrane Library, CINHL Complete, and other selected databases relevant to this guideline. Additional relevant studies, published through June 2022 during the guideline writing process, were also considered by the writing committee, where appropriate. STRUCTURE: Recommendations from previously published AHA/ACC guidelines on thoracic aortic disease, peripheral artery disease, and bicuspid aortic valve disease have been updated with new evidence to guide clinicians. In addition, new recommendations addressing comprehensive care for patients with aortic disease have been developed. There is added emphasis on the role of shared decision making, especially in the management of patients with aortic disease both before and during pregnancy. The is also an increased emphasis on the importance of institutional interventional volume and multidisciplinary aortic team expertise in the care of patients with aortic disease.