In patients undergoing aortic-valve or mitral-valve replacement, either a mechanical or biologic prosthesis is used. Biologic prostheses have been increasingly favored despite limited evidence ...supporting this practice.
We compared long-term mortality and rates of reoperation, stroke, and bleeding between inverse-probability-weighted cohorts of patients who underwent primary aortic-valve replacement or mitral-valve replacement with a mechanical or biologic prosthesis in California in the period from 1996 through 2013. Patients were stratified into different age groups on the basis of valve position (aortic vs. mitral valve).
From 1996 through 2013, the use of biologic prostheses increased substantially for aortic-valve and mitral-valve replacement, from 11.5% to 51.6% for aortic-valve replacement and from 16.8% to 53.7% for mitral-valve replacement. Among patients who underwent aortic-valve replacement, receipt of a biologic prosthesis was associated with significantly higher 15-year mortality than receipt of a mechanical prosthesis among patients 45 to 54 years of age (30.6% vs. 26.4% at 15 years; hazard ratio, 1.23; 95% confidence interval CI, 1.02 to 1.48; P=0.03) but not among patients 55 to 64 years of age. Among patients who underwent mitral-valve replacement, receipt of a biologic prosthesis was associated with significantly higher mortality than receipt of a mechanical prosthesis among patients 40 to 49 years of age (44.1% vs. 27.1%; hazard ratio, 1.88; 95% CI, 1.35 to 2.63; P<0.001) and among those 50 to 69 years of age (50.0% vs. 45.3%; hazard ratio, 1.16; 95% CI, 1.04 to 1.30; P=0.01). The incidence of reoperation was significantly higher among recipients of a biologic prosthesis than among recipients of a mechanical prosthesis. Patients who received mechanical valves had a higher cumulative incidence of bleeding and, in some age groups, stroke than did recipients of a biologic prosthesis.
The long-term mortality benefit that was associated with a mechanical prosthesis, as compared with a biologic prosthesis, persisted until 70 years of age among patients undergoing mitral-valve replacement and until 55 years of age among those undergoing aortic-valve replacement. (Funded by the National Institutes of Health and the Agency for Healthcare Research and Quality.).
Endovascular treatment for aortic arch aneurysms often requires adjunctive use of hybrid debranching procedures to maintain branch vessel perfusion. This study describes early results with a novel ...branched arch endograft for total endovascular repair of distal arch aneurysms.
This US feasibility multicenter clinical trial evaluated 22 patients (mean age, 74.1 ± 10.5 years; 54.5% male) undergoing branched thoracic endovascular aortic repair in Ishimaru zone 2. This endograft was designed with a single side branch designed to facilitate aortic coverage proximal to the left subclavian artery while maintaining branch vessel patency. The pathologic features treated included fusiform (n = 10) and saccular (n = 12) aneurysms, with a mean aortic diameter of 5.7 ± 1.1 cm. The mean preoperative left-to-right brachial index was 1.0 ± 0.1.
The mean total treatment length was 17.6 ± 8.9 cm; 8 patients were treated with a single 10-cm graft for isolated arch disease. The primary endpoint of device delivery and branch vessel patency was achieved in 100% of patients, without 30-day death, stroke, or permanent paraplegia. The median duration of hospitalization was 4.0 days. Type I endoleaks at completion angiography were observed in 4 patients, and all resolved by 1 month without reintervention. All side branches were patent at 1 month. The Kaplan-Meier survival rate at 6 months was 94.7%.
Total endovascular repair of distal zone 2 arch aortic aneurysms can be achieved with a novel branched arch endograft. Future studies will evaluate the feasibility of this approach for aneurysms encompassing the brachiocephalic trunk and left carotid artery.
Credible computational fluid dynamic (CFD) simulations of aortic dissection are challenging, because the defining parallel flow channels—the true and the false lumen—are separated from each other by ...a more or less mobile dissection membrane, which is made up of a delaminated portion of the elastic aortic wall. We present a comprehensive numerical framework for CFD simulations of aortic dissection, which captures the complex interplay between physiologic deformation, flow, pressures, and time-averaged wall shear stress (TAWSS) in a patient-specific model. Our numerical model includes (1) two-way fluid–structure interaction (FSI) to describe the dynamic deformation of the vessel wall and dissection flap; (2) prestress and (3) external tissue support of the structural domain to avoid unphysiologic dilation of the aortic wall and stretching of the dissection flap; (4) tethering of the aorta by intercostal and lumbar arteries to restrict translatory motion of the aorta; and a (5) independently defined elastic modulus for the dissection flap and the outer vessel wall to account for their different material properties. The patient-specific aortic geometry is derived from computed tomography angiography (CTA). Three-dimensional phase contrast magnetic resonance imaging (4D flow MRI) and the patient’s blood pressure are used to inform physiologically realistic, patient-specific boundary conditions. Our simulations closely capture the cyclical deformation of the dissection membrane, with flow simulations in good agreement with 4D flow MRI. We demonstrate that decreasing flap stiffness from
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kPa (a) increases the displacement of the dissection flap from 1.4 to 13.4 mm, (b) decreases the surface area of TAWSS by a factor of 2.3, (c) decreases the mean pressure difference between true lumen and false lumen by a factor of 0.63, and (d) decreases the true lumen flow rate by up to 20% in the abdominal aorta. We conclude that the mobility of the dissection flap substantially influences local hemodynamics and therefore needs to be accounted for in patient-specific simulations of aortic dissection. Further research to accurately measure flap stiffness and its local variations could help advance future CFD applications.
The developmental origin of vascular smooth muscle cells (VSMCs) has been increasingly recognized as a major determinant for regional susceptibility or resistance to vascular diseases. As a human ...material-based complement to animal models and human primary cultures, patient induced pluripotent stem cell iPSC-derived VSMCs have been leveraged to conduct basic research and develop therapeutic applications in vascular diseases. However, iPSC-VSMCs (induced pluripotent stem cell VSMCs) derived by most existing induction protocols are heterogeneous in developmental origins. In this review, we summarize signaling networks that govern in vivo cell fate decisions and in vitro derivation of distinct VSMC progenitors, as well as key regulators that terminally specify lineage-specific VSMCs. We then highlight the significance of leveraging patient-derived iPSC-VSMCs for vascular disease modeling, drug discovery, and vascular tissue engineering and discuss several obstacles that need to be circumvented to fully unleash the potential of induced pluripotent stem cells for precision vascular medicine.
Thoracic endovascular aortic repair has radically transformed the treatment of descending thoracic aortic aneurysms. However, when aneurysms involve the aortic arch in the region of the left ...subclavian artery, branch vessel preservation must be considered. Branched aortic endografts have provided a new option to maintain branch patency.
Six investigative sites enrolled 31 patients in a nonrandomized, prospective investigational device exemption feasibility trial of a single branched aortic endograft for the management of aneurysms that include the distal aortic arch. The Gore TAG thoracic branch endoprosthesis (W. L. Gore & Associates, Inc, Flagstaff, Ariz), an investigational device, allows for graft placement proximal to the left subclavian artery and incorporates a single side branch for left subclavian perfusion.
All 31 patients (100%) had undergone successful implantation of the investigational device in landing zone 2. Men slightly outnumbered women (51.6%). Their average age was 74.1 ± 10.4 years. The aneurysm morphology was fusiform in 12 and saccular in 19 patients, with a mean maximum aortic diameter of 54.8 ± 10.9 mm. The mean follow-up period for the cohort was 25.2 ± 11.1 months. We have reported the patient outcomes at 1 month and 1 year. At 1 month, the side branch patency was 100% and the freedom from core laboratory-reported device-related endoleak (types I and III) was 96.7%, without 30-day death or permanent paraplegia. One patient experienced a procedure-related stroke. Through 1 year, five patients had died; none of the deaths were related to the device or procedure (clinical endpoint committee adjudicated). One thoracic reintervention was required. No conversions were required, and no aneurysm growth (core laboratory) was reported. One case of the loss of side branch patency was diagnosed in the left subclavian artery in an asymptomatic individual from computed tomography at 6 months, with no reported subsequent adverse events due to loss of patency. Endoleaks were reported by the core laboratory in five patients at 12 months (two, type II; and three, indeterminate).
The present investigational device exemption feasibility study has reported the preliminary results of the use of a single side branch endograft to treat patients with proximal descending thoracic aortic aneurysms.
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To delineate temporal and spatial dynamics of vascular smooth muscle cell (SMC) transcriptomic changes during aortic aneurysm development in Marfan syndrome (MFS). Approach and Results: We performed ...single-cell RNA sequencing to study aortic root/ascending aneurysm tissue from
(MFS) mice and healthy controls, identifying all aortic cell types. A distinct cluster of transcriptomically modulated SMCs (modSMCs) was identified in adult
mouse aortic aneurysm tissue only. Comparison with atherosclerotic aortic data (ApoE
mice) revealed similar patterns of SMC modulation but identified an MFS-specific gene signature, including plasminogen activator inhibitor-1 (
) and Kruppel-like factor 4 (
). We identified 481 differentially expressed genes between modSMC and SMC subsets; functional annotation highlighted extracellular matrix modulation, collagen synthesis, adhesion, and proliferation. Pseudotime trajectory analysis of
SMC/modSMC transcriptomes identified genes activated differentially throughout the course of phenotype modulation. While modSMCs were not present in young
mouse aortas despite small aortic aneurysm, multiple early modSMCs marker genes were enriched, suggesting activation of phenotype modulation. modSMCs were not found in nondilated adult
descending thoracic aortas. Single-cell RNA sequencing from human MFS aortic root aneurysm tissue confirmed analogous SMC modulation in clinical disease. Enhanced expression of TGF-β (transforming growth factor beta)-responsive genes correlated with SMC modulation in mouse and human data sets.
Dynamic SMC phenotype modulation promotes extracellular matrix substrate modulation and aortic aneurysm progression in MFS. We characterize the disease-specific signature of modSMCs and provide temporal, transcriptomic context to the current understanding of the role TGF-β plays in MFS aortopathy. Collectively, single-cell RNA sequencing implicates TGF-β signaling and
overexpression as potential upstream drivers of SMC modulation.
The feasibility and effectiveness of delaying surgery to transfer patients with acute type A aortic dissection-a catastrophic disease that requires prompt intervention-to higher-volume aortic surgery ...hospitals is unknown. We investigated the hypothesis that regionalizing care at high-volume hospitals for acute type A aortic dissections will lower mortality. We further decomposed this hypothesis into subparts, investigating the isolated effect of transfer and the isolated effect of receiving care at a high-volume versus a low-volume facility.
We compared the operative mortality and long-term survival between 16 886 Medicare beneficiaries diagnosed with an acute type A aortic dissection between 1999 and 2014 who (1) were transferred versus not transferred, (2) underwent surgery at high-volume versus low-volume hospitals, and (3) were rerouted versus not rerouted to a high-volume hospital for treatment. We used a preference-based instrumental variable design to address unmeasured confounding and matching to separate the effect of transfer from volume.
Between 1999 and 2014, 40.5% of patients with an acute type A aortic dissection were transferred, and 51.9% received surgery at a high-volume hospital. Interfacility transfer was not associated with a change in operative mortality (risk difference, -0.69%; 95% CI, -2.7% to 1.35%) or long-term mortality. Despite delaying surgery, a regionalization policy that transfers patients to high-volume hospitals was associated with a 7.2% (95% CI, 4.1%-10.3%) absolute risk reduction in operative mortality; this association persisted in the long term (hazard ratio, 0.81; 95% CI, 0.75-0.87). The median distance needed to reroute each patient to a high-volume hospital was 50.1 miles (interquartile range, 12.4-105.4 miles).
Operative and long-term mortality were substantially reduced in patients with acute type A aortic dissection who were rerouted to high-volume hospitals. Policy makers should evaluate the feasibility and benefits of regionalizing the surgical treatment of acute type A aortic dissection in the United States.
Management of the aortic root is a challenge for surgeons treating acute type A aortic dissection.
We performed a retrospective review of the acute type A aortic dissection experience at Stanford ...Hospital between 2005 and 2015 and identified patients who underwent either limited root repair or aortic root replacement. Differences in baseline characteristics were balanced with inverse probability weighting to estimate the average treatment effect on the controls. Weighted logistic regression was used to evaluate in-hospital mortality. Weighted Cox proportional hazards regression was used to evaluate differences in the hazard for mid-term death. Reoperation was evaluated with death as a competing risk with the Fine-Gray subdistribution hazard.
After we excluded patients managed either nonoperatively or with definitive endovascular repair, there were 293 patients without connective tissue disease who underwent either limited root repair or aortic root replacement. There was no difference in weighted perioperative mortality, odds ratio 0.89 (95% confidence interval CI, 0.44-1.76, P = .7), and there was no difference in weighted survival, hazard ratio 1.12 (95% CI, 0.54-2.31, P = .8). Risk of reoperation was greater in limited root repair (11.8%, 95% CI, 0.0%-23.8%) than for root replacement (0%), P < .001.
Limited root repair was associated with increased risk of late reoperation after repair of acute type A aortic dissection. Surgeons with adequate experience may consider aortic root replacement in well-selected patients. However, given good outcomes after limited root repair, surgeons should not feel compelled to perform this more-complex operation.
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