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.

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.

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.

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.

Midterm Durability and Structural Valve Degeneration of Transcatheter Aortic Valve Replacement in a Federal Facility.

OBJECTIVE: Transcatheter aortic valve replacement (TAVR), previously reserved for patients of intermediate to prohibitive surgical risk, has now been expanded to patients of any surgical risk with severe aortic stenosis. Bioprostheses are prone to structural valve degeneration (SVD), a progressive and multifactorial process that limits valve durability. As the population undergoing TAVR shifts toward a lower-risk and younger profile, long-term durability is a crucial determinant for patient outcomes. Our objective was to determine the incidence and risk factors of SVD at midterm follow-up in a veteran TAVR population. METHODS: Patients undergoing TAVR at our federal facility were retrospectively evaluated for SVD and other endpoints with standardized consensus criteria. Multivariable Cox proportional hazards analysis was performed to evaluate risk factors for mortality and SVD. RESULTS: From 2013 to 2020, 344 patients (median age, 78 years) underwent TAVR. Survival from all-cause mortality was 91.3% at 1 year, 75.1% at 3 years, and 61.7% at 5 years. Cumulative freedom from SVD was 98.2% at 1 year, 96.5% at 3 years, and 93.7% at 5 years. All 13 patients with SVD met hemodynamic criteria, and 1 required intervention. Median time to hemodynamic SVD was 1.04 years. Independent risk factors for SVD included age (hazard ratio [HR] = 0.92, 95% confidence interval [CI]: 0.86 to 0.99) and valve size (HR = 0.19, 95% CI: 0.04 to 0.89). CONCLUSIONS: SVD was evident at a low but detectable rate at 5-year follow-up. Further understanding of TAVR biomechanics as well as continued longer-term follow-up will be essential for informing patient-specific risk of SVD.

Ascending thoracic aortic aneurysm growth is minimal at sizes that do not meet criteria for surgical repair.

BACKGROUND: Historic studies of nonsyndromic ascending thoracic aortic aneurysms (aTAAs) reported that the typical aTAA growth rate was approximately 0.6 mm/year, but data were limited due to relatively few studies using computed tomography (CT) imaging. Our purpose was to reevaluate the annual growth rate of nonsyndromic aTAAs that do not meet criteria for surgical repair in veterans in the contemporary era, using modern CT imaging suitable for highly accurate and reproducible aneurysm measurement. METHODS: Nonsurgical patients (diameter <5.5 cm) undergoing aneurysm surveillance at a Veterans Affairs Medical Center with repeat CT imaging performed 3 to 5 years apart were identified. Maximum diameter was determined by a single radiologist using multiplanar reformat-based measurements. Average rate of aneurysm growth was evaluated based on longest available follow-up. RESULTS: Sixty-seven patients were included. Average follow-up time was 4.06±0.83 years. Patients were exclusively male, with average age of 68.1±6.0 years, and the majority had a history of smoking (n=52, 78%), hypertension (n=52, 78%), and dyslipidemia (n=48, 72%). Average baseline aneurysm diameter was 44.0±3.2 mm and average growth rate was 0.11±0.31 mm/year, with no difference in growth rate between patients with initial diameter ≤45 vs. >45 mm. Only 3 patients experienced clinically significant changes in diameter with magnitude greater than 5% of baseline. CONCLUSIONS: In this veteran population, most patients did not experience significant annual aneurysm growth over up to 5 years of follow-up, regardless of initial diameter. Thus, in the modern era, aTAAs may not grow as quickly as previously described, which will be important in determining appropriate intervals for aneurysm surveillance based upon risk-benefit ratio.

Patient-Specific Biomechanics in Marfan Ascending Thoracic Aortic Aneurysms.

BACKGROUND: Guidelines for sinus of Valsalva (SOV)-thoracic aortic aneurysms in Marfan syndrome recommend size-based criteria for elective surgical repair. Biomechanics may provide a better prediction of dissection risk than diameter. Our aim was to determine magnitudes of wall stress in the aortic root of Marfan patients using finite element analyses. METHODS: Forty-six Marfan patients underwent patient-specific 3-dimensional SOV-thoracic aortic aneurysm geometry reconstruction using imaging data. Finite element analyses were performed to determine wall stress distributions at SOV, sinotubular junction (STJ), and ascending aorta (AscAo) at systole. RESULTS: Peak circumferential stresses were 432.8 ± 111 kPa, 408.1 ± 88.3 kPa, and 321.9 ± 83.8 kPa at the SOV, STJ, and AscAo, respectively, with significant differences between SOV and AscAo (P < 3.08E-07), and STJ and AscAo (P < 2.26E-06). Peak longitudinal wall stresses were 352 ± 73.9 kPa, 277.5 ± 89.5 kPa, and 200.6 ± 81 kPa at SOV, STJ, and AscAo, respectively, with significant differences between SOV and STJ (P < 6.01E-06), SOV and AscAo (P < 9.79E-13), and STJ and AscAo (P < 3.34E-07). Diameter was not correlated to wall stresses. Comparison of wall stresses in aneurysm <5 cm vs ≥5 cm and <4.5 cm vs ≥4.5 cm showed no significant differences in wall stresses in the circumferential or longitudinal direction. CONCLUSIONS: Peak wall stresses in Marfan SOV- thoracic aortic aneurysm were greatest in SOV than STJ than AscAo. Diameter was poorly correlated to peak stresses such that current guidelines with 5 cm cutoff had significant overlap in peak stresses in patients with <5 cm vs ≥5 cm. Use of patient-specific Marfan aneurysm models may identify patients with high wall stresses and small aneurysms who could benefit from earlier surgical repair to prevent aortic dissection.

Wall stresses of early remodeled pulmonary autografts.

OBJECTIVE: The Ross procedure is an excellent option for children or young adults who need aortic valve replacement because it can restore survival to that of the normal aged-matched population. However, autograft remodeling can lead to aneurysmal formation and reoperation, and the biomechanics of this process is unknown. This study investigated postoperative autograft remodeling after the Ross procedure by examining patient-specific autograft wall stresses. METHODS: Patients who have undergone the Ross procedure who had intraoperative pulmonary root and aortic specimens collected were recruited. Patient-specific models (n = 16) were developed using patient-specific material property and their corresponding geometry from cine magnetic resonance imaging at 1-year follow-up. Autograft ± Dacron for aneurysm repair and ascending aortic geometries were reconstructed to develop patient-specific finite element models, which incorporated material properties and wall thickness experimentally measured from biaxial stretching. A multiplicative approach was used to account for prestress geometry from in vivo magnetic resonance imaging. Pressure loading to systemic pressure (120/80) was performed using LS-DYNA software (LSTC Inc, Livermore, Calif). RESULTS: At systole, first principal stresses were 809 kPa (25%-75% interquartile range, 691-1219 kPa), 567 kPa (485-675 kPa), 637 kPa (555-755 kPa), and 382 kPa (334-413 kPa) at the autograft sinotubular junction, sinuses, annulus, and ascending aorta, respectively. Second principal stresses were 360 kPa (310-426 kPa), 355 kPa (320-394 kPa), 272 kPa (252-319 kPa), and 184 kPa (147-222 kPa) at the autograft sinotubular junction, sinuses, annulus, and ascending aorta, respectively. Mean autograft diameters were 29.9 ± 2.7 mm, 38.3 ± 5.3 mm, and 26.6 ± 4.0 mm at the sinotubular junction, sinuses, and annulus, respectively. CONCLUSIONS: Peak first principal stresses were mainly located at the sinotubular junction, particularly when Dacron reinforcement was used. Patient-specific simulations lay the foundation for predicting autograft dilatation in the future after understanding biomechanical behavior during long-term follow-up.