Geometrical Factors Affect Wall Shear Stress in Saccular Aneurysms of the Infrarenal Abdominal Aorta.

BACKGROUND: Low wall shear stress (WSS) is predictive of aortic aneurysm growth and rupture. Yet, estimating WSS in a clinical setting is impractical, whereas measuring aneurysm geometry is feasible. This study investigates the association between saccular aneurysm geometry of the infrarenal aorta and WSS. METHODS: Starting with a nonaneurysmal, patient-specific, computational fluid dynamics model of the aorta, saccular aneurysms of varying geometry were created by incrementally increasing the neck width and sac depth from 1 cm to 4 cm. The aspect ratio (the ratio between sac depth and neck width) varied between 0.25 and 4. The peak WSS, time-averaged WSS (TAWSS), and oscillatory shear index (OSI) were measured within the aneurysm sac. RESULTS: Decreasing the neck width from 4 cm to 1 cm decreased the peak WSS by 69% and the TAWSS by 83%. Increasing the sac depth from 1 cm to 4 cm decreased the peak WSS by 55% and the OSI by 37%. The aspect ratio was negatively correlated to peak WSS (Rs -0.85; P < 0.001). CONCLUSIONS: In saccular aneurysms of the infrarenal aorta, a smaller neck width, deeper aneurysm sac, and larger aspect ratio are associated with lower peak WSS.

Artificial intelligence for the vascular surgeon.

In recent years, artificial intelligence (AI) has permeated different aspects of vascular surgery to solve challenges in clinical practice. Although AI in vascular surgery is still in its early stages, there have been promising developments in its applications to vascular diagnosis, risk stratification, and outcome prediction. By establishing a baseline knowledge of AI, vascular surgeons are better equipped to use and interpret the data from these types of projects. This review aims to provide an overview of the fundamentals of AI and highlight its role in helping vascular surgeons overcome the challenges of clinical practice. In addition, we discuss the limitations of AI and how they affect AI applications.

Arterial spin labeling magnetic resonance imaging quantifies tissue perfusion around foot ulcers.

Objective: Tools that quantify tissue perfusion of the foot are deficient, contributing to the uncertainty in predicting ulcer healing potential. This pilot study aims to quantify peri-wound foot perfusion at various tissue depths using a novel application of pseudo-continuous arterial spin labeling magnetic resonance imaging. Methods: Ten diabetic patients with neuropathic wounds and 20 healthy volunteers without wounds were recruited. Wounds were graded according to the Wound, Ischemia, Foot Infection (WIfI) system. All subjects underwent a noncontrasted ASL MRI of the foot for perfusion measurements. For healthy volunteers, perfusion was compared at rest and during sustained toe flexion between four regions: lateral plantar, medial plantar, lateral calcaneal, and medial calcaneal. Evaluations of diabetic volunteers compared perfusion between four zones: wound, near border, far border, and remote. Remote zone perfusion in diabetics was compared with perfusion in the plantar foot of healthy volunteers. Results: There were 11 wounds, which were located over the metatarsal heads in five, the stump of a transmetatarsal amputation in three, the heel in two, and the mid foot in one. The median WIfI stage was 2. One patient had a WIfI ischemia grade of 1; the remaining patients' grades were 0. The mean ankle-brachial index was 1.0 ± 0.3. There were two patients with a WIfI foot infection grade of 1; the remaining patients' grades were 0. In healthy volunteers, plantar foot perfusion with sustained toe flexion was 43.9 ± 1.7 mL/100g/min and significantly higher than perfusion at rest (27.3 ± 2.7 mL/100g/min; P < .001). In diabetic patients, perfusion at the wound, near border, far border, and remote regions was 96.1 ± 10.7, 92.7 ± 9.4, 73.4 ± 8.2, and 62.8 ± 2.7 mL/100g/min. Although this perfusion pattern persisted throughout the depth of the wound, perfusion decreased with tissue depth. In the near border, perfusion at 20% of the wound depth was 124.0 ± 35.6 mL/100g/min and 69.9 ± 10.1 mL/100g/min at 100% (P = .006). Lastly, remote perfusion in diabetics was 2.3 times the plantar perfusion in healthy volunteers (27.3 ± 2.7 mL/100g/min; P < .001). Conclusions: The pattern of resting tissue perfusion around nonischemic diabetic foot ulcers was successfully quantified with arterial spin labeling magnetic resonance imaging. Diabetic patients with wounds were hyperemic compared with healthy volunteers. There was a 1.5-fold increase in peri-wound tissue perfusion relative to the rest of the foot. This study is the first step in developing a tool to assess the perfusion deficit in ischemic wounds.

A Single Institution 30-Year Review of Abnormal First Rib Resection for Thoracic Outlet Syndrome.

OBJECTIVES: Congenital abnormalities of the first rib (ABNFR) are a rare cause of thoracic outlet syndrome (TOS). The range of abnormalities have not been clearly documented in the literature. Surgical decompression in these patients presents with increased complexity secondary to anomalous anatomy. Our goal is to review an institutional experience of first rib resection (FRR) performed for ABNFRs, to present a novel classification system, and to analyze outcomes according to clinical presentation. METHODS: A prospectively collected database was used to identify individuals with ABNFRs who underwent FRR for TOS between 1990-2021. These individuals were identified both by preoperative imaging and intraoperative descriptions of the first rib after resection. Demographic, clinical, perioperative and pathological data were reviewed. ABNFRs were classified into 3 categories according to anatomical criteria: (I) Hypoplastic, (II) Fused, and (III) Hyperplastic. Outcomes were rated using the standardized Quick Disability of Arm Shoulder and Hand Scores (QDS), Somatic Pain Scores (SPS) and Derkash Scores (DkS). RESULTS: Among the 2200 cases of TOS, there were 19 patients (0.8%) with ABNFR who underwent FRR. Average age at surgery was 30.5 (range 11-74), including 13 men and 6 women. Presentations included 9 arterial (ATOS), 6 neurogenic (NTOS), and 4 venous (VTOS) cases. There were 6 class I, 6 class II, and 7 class III ABNFRs. Among 6 NTOS patients there were 4 abnormal nerve conduction tests and 5 positive anterior scalene muscle blocks. Among the 9 patients with ATOS, thrombolysis was attempted in 5 patients, and of these, 3 ultimately required surgical thrombectomy. Of 4 VTOS cases, 2 were managed with thrombolysis, and 2 with anticoagulation alone. The approach for FRR was transaxillary in all patients. Secondary procedures included 1 pectoralis minor tenotomy, 1 scalenectomy, and 1 contralateral rib resection. No major neurological or vascular complications occurred. There was 1 patient who required surgical evacuation of a hematoma. Intraoperative chest tube placement was required in 5 patients secondary to pleural entry during dissection. There was an overall improvement in symptoms over an average follow-up of 7.4 months. QDS reduced from 49.7 pre-op to 22.1 (P < 0.05). SPS improved from 3.4 pre-op to 1.8. DkS scores were good to excellent in 79% of patients. Residual symptoms were noted in 7, and ATOS accounted for 5 (70%) of these. All patients were able to return to work. CONCLUSIONS: Despite increased complexity, ABNFRs may be safely resected via transaxillary approach with low incidence of complications, very good symptom relief, and excellent outcomes. Congenital ABNFRs may by classified into 3 categories (hypoplastic, fused, and hyperplastic) with a variety of presentations, including ATOS, NTOS, and VTOS. Classification of ABNFRs allows concise description of abnormal anatomy which facilitates comparison between series and provides direction for surgical management to ultimately optimize patient outcomes.

Deep Venous Stenting Improves Healing of Lower Extremity Venous Ulcers.

BACKGROUND: Long standing, recalcitrant venous ulcers fail to heal despite standard compression therapy and wound care. Stenting of central veins has been reported to assist in venous ulcer healing. This study reports outcomes of deep venous stenting for central venous obstruction in patients with recalcitrant venous ulcers at a single comprehensive wound care center. METHODS: A single center retrospective analysis was conducted of patients with CEAP (Clinical, Etiology, Anatomy, and Pathophysiology) 6 disease that had undergone deep venous stenting in addition to wound care and compression therapy. Intra-operative details, wound healing, and stent patency rates were recorded. Stent patency and intra-operative details were compared between the healed and unhealed groups. RESULTS: Between 2010 and 2019, 15 patients met inclusion criteria (mean age: 63 years old, 12 males). Pre-operative mean wound area was 14.1 cm2 with mean wound duration of 30 months. 93% of patients healed the ulcers at mean healing time of 10.6 months. Wound recurrence rate was 57% with mean recurrence time of 14.8 months. Ten patients presented with an inferior vena cava (IVC) filter, 4 in the healed group and 6 in the unhealed group. The common iliac vein was stented in all patients. Extension into the IVC was required in 4, the common femoral vein in 11, and femoral vein in 2 patients. The average stent length was 190cm. During the follow-up period, primary patency rates in healed patients (mean follow-up time: 19.2 months) was 83% and 59% in the unhealed group (mean follow-up time: 36.6 months); secondary patency rates were 83% and 89%, respectively. CONCLUSIONS: In patients with recalcitrant venous ulcers with central venous obstruction, deep venous stenting resulted in a high rate of healing. However, a prolonged 10 month healing time was observed and despite high stent patency, wound recurrence rate was high.

The evolving role of endovascular therapy in the management of arterial thoracic outlet syndrome.

OBJECTIVE: Over the past two decades, vascular surgeons have successfully incorporated endovascular techniques to the routine care of patients with arterial thoracic outlet syndrome (ATOS). However, no reports have documented the impact of endovascular therapy. This study describes the trends in management of ATOS by vascular surgeons and outcomes after both endovascular and open repair of the subclavian artery. METHODS: We queried a single-institution, prospectively maintained thoracic outlet syndrome database for ATOS cases managed by vascular surgeons. For comparison, cases were divided into two equal time periods, January 1986 to August 2003 (P-1) vs September 2003 to March 2021 (P-2), and by treatment modality, open vs endovascular. Clinical presentation, outcomes, and the involvement of vascular surgeons in endovascular therapy were compared between groups. RESULTS: Of 2200 thoracic outlet syndrome cases, 51 were ATOS (27 P-1, 24 P-2) and underwent 50 transaxillary decompressive operations. Forty-eight cases (92%) presented with ischemic symptoms. Thrombolysis was done in 15 (29%). During P-1, vascular surgeons performed none of the catheter-based interventions. During P-2, vascular surgeons performed 60% of the angiograms, 50% of thrombolysis, and 100% of stent grafting. Subclavian artery pathology included 16 aneurysms (31%), 15 stenoses (29%), and 19 occlusions (37%). Compared with open aneurysmal repair, endovascular stent graft repairs took less time (241 vs 330 minutes; P = .09), incurred lower estimated blood loss (103 vs 150 mL; P = .36), and had a shorter length of stay (2.4 vs 5.0 days; P = .10). Yet the endovascular group had decreased primary (63% vs 77%; P = .481), primary assisted (75% vs 85%; P = .590), and secondary patency rates (88% vs 92%; P = .719), at a mean follow-up time of 3.0 years for the endovascular group and 6.9 years for the open group (P = .324). These differences did not achieve statistical significance. Functionally, 84% of patients were able to resume work or school. A majority of patients (88%) had a good to excellent functional outcome based on their Derkash score. Somatic pain scores and QuickDASH (disabilities of the arm, shoulder, and hand) scores decreased postoperatively, 2.9 vs 0.8 (P = .015) and 42.6 vs 12.6 (P = .004), respectively. CONCLUSIONS: This study describes the evolving role of endovascular management of ATOS over the past two decades and documents the expanded role of vascular surgeons in the endovascular management of ATOS at a single institution. Compared with open repair, stent graft repair of the subclavian artery may be associated with shorter operative times, less blood loss, but decreased patency, without changes in long-term functional outcomes.

Surgical resection and graft replacement for primary inferior vena cava leiomyosarcoma: A multicenter experience.

OBJECTIVE: Primary leiomyosarcoma of the inferior vena cava (IVC) is best managed with surgical resection when technically feasible. However, consensus is lacking regarding the best choice of conduit and reconstruction technique. The aim of the present multicenter study was to perform a comprehensive assessment through the VLFDC (Vascular Low Frequency Disease Consortium) to determine the most effective method for caval reconstruction after resection of primary leiomyosarcoma of the IVC. METHODS: A multicenter, standardized database review of patients who had undergone surgical resection and reconstruction of the IVC for primary leiomyosarcoma from 2007 to 2017 was performed. The demographics, periprocedural details, and postoperative outcomes were analyzed. RESULTS: A total of 92 patients (60 women and 32 men), with a mean age of 60.1 years (range, 30-88 years) were treated. Metastatic disease was present in 22%. The tumor location was below the renal veins in 49 (53%), between the renal and hepatic veins in 52 (57%), and above the hepatic veins in 13 patients (14%). The conduits used for reconstruction included ringed polytetrafluoroethylene (PTFE; n = 80), nonringed PTFE (n = 1), Dacron (n = 1), autogenous vein (n = 1), bovine pericardium (n = 4), and cryopreserved tissue (n = 5). Complete R0 resection was accomplished in 73 patients (79%). In-hospital mortality was 2%, with a median length of stay of 8 days. The primary patency of PTFE reconstructed IVCs was 97% and 92% at 1 and 5 years, respectively, compared with 73% at 1 and 5 years for the non-PTFE reconstructed IVCs. The overall 1-, 3-, and 5-year survival for the entire cohort were 94%, 86%, and 65%, respectively CONCLUSIONS: The findings from our multi-institutional study have demonstrated that complete en bloc resection of IVC leiomyosarcoma with vascular surgical reconstruction in selected patients results in low perioperative mortality and is associated with excellent long-term patency. A ringed PTFE graft was the most commonly used conduit for caval reconstruction, yielding excellent long-term primary patency.

Elective Resection of Symptomatic Arteriovenous Fistulae and Grafts in Patients with Functioning Renal Allografts at A High Volume Transplant Hospital.

OBJECTIVE: Patients with functioning renal allografts may need ligation of pre-existing hemodialysis conduits. Chronic immunosuppression for renal allografts may adversely affect wound healing and perioperative complications following these procedures. We sought to analyze outcomes following elective ligation and resection of symptomatic arteriovenous (AV) access in immunosuppressed patients with renal allografts no longer requiring dialysis at a high-volume renal transplant hospital. METHODS: We retrospectively reviewed procedure codes for hemodialysis access resection and revision from 2014-2020 at a single academic tertiary care hospital. Patients who underwent complete or subtotal dialysis access resection with a functioning renal allograft were included for analysis of preoperative, operative, and postoperative outcomes. We performed descriptive statistics, and student's t-test using Microsoft Excel. RESULTS: Thirty-four patients met inclusion criteria. The majority were male, 56%, and the most common causes of renal failure were hypertension and diabetes, respectively. Ligation and resection of proximal upper extremity access was performed in 68%. The mean operative time was 126 minutes with pain being the most common indication for intervention. Four patients required arterial reconstruction. Mean postoperative follow-up was 13 months. Arm pain and swelling resolved in 100% and 88% of patients following AV access resection, respectively. No impairment in mean postoperative glomerular filtration rates were noted. One patient required hemodialysis and died three months after fistula resection following complications from treatment of a newly diagnosed neuroendocrine tumor and subsequent fungemia, CONCLUSION: Elective operative resection of symptomatic AV access may be performed safely in immunosuppressed patients with functioning renal transplants. The risk of allograft impairment and/or failure as a result of AV access resection in our series was low. Elective ligation and resection can be achieved with low mortality, excellent symptomatic relief, and few wound complications despite chronic immunosuppression.

Trainee Experience in Simulation-Based Education of Open Vascular Surgery.

BACKGROUND: Simulation continues to be an important adjunct to vascular surgery training, yet the optimal implementation of simulation to complement conventional surgical training continues to evolve. This study aims to find areas for improvement in current simulation-based training of open vascular skills by characterizing the experience of vascular trainees attending a national simulation-based course. METHOD: This was a survey study conducted at the simulation course of the Annual UCLA/SVS Symposium: A Comprehensive Review and Update of What's New in Vascular and Endovascular Surgery, a national vascular surgery meeting. The survey consisted of 17 questions and was administered on paper or electronically via the Audience Response System, before the start of the course. The survey assessed the participants' experience in formal training, simulation training, and comfort with open surgical procedures. RESULTS: Between 2013 and 2018, the survey was completed by 150 participants of which 65% were vascular fellows. Only 48% of the participants had formal training in suturing and surgical instruments. Most participants had formal training in basic vascular techniques and advanced vascular operations. In 71%, simulation was incorporated into basic technique training and 60% in open surgical training. Simulation training was most commonly utilized in learning anastomotic techniques and open abdominal aortic aneurysm repair. Simulation skills were deemed translatable to the operating room by 59% of participants. Most participants were comfortable performing open vascular procedures. However, 68% of participants were uncomfortable performing an abdominal aortic aneurysm repair. CONCLUSIONS: There continues to be a significant portion of trainees who do not undergo a simulation-based education. Current simulation training is being targeted to meet trainee needs in open vascular surgery, specifically open aneurysm repair. Nonetheless, trainees continue to have doubts regarding applicability of simulation-based skills to the operating theater. Further studies investigating access to simulation education as well as its translatability are needed.

Phlegmasia cerulea dolens associated with acute coronavirus disease 2019 pneumonia despite supratherapeutic warfarin anticoagulation.

Patients with acute coronavirus disease 2019 (COVID-19) respiratory infection are associated with concomitant thromboembolic complications and a hypercoagulable state. Although these mechanisms are not completely understood, unique alterations in the serum markers for hemostasis and thrombosis have been detected. A high index of suspicion is required by vascular surgeons for patients presenting with this novel virus. We present the case of a 51-year-old man with acute COVID-19 pneumonia who developed phlegmasia cerulea dolens despite chronic warfarin therapy and a supratherapeutic international normalized ratio.

Caval Reconstruction with Undersized Ringed Graft after Resection of Inferior Vena Cava Leiomyosarcoma.

BACKGROUND: The en bloc resection of inferior vena cava (IVC) leiomyosarcoma often necessitates IVC reconstruction. The objective of this study is to examine outcomes after IVC reconstruction and determine optimal graft sizing. METHODS: A retrospective review was conducted of all IVC reconstructions after IVC leiomyosarcoma resection at a single institution. Cross-sectional dimensions at the IVC resection margins were measured on preoperative imaging. The tumor location was based on the most superiorly involved region of the IVC and was classified as infrarenal, between hepatic and renal veins, or superior to the hepatic veins. Perioperative details and long-term outcomes including graft sizing, graft patency, morbidity, and mortality were recorded. RESULTS: Between 2007 and 2017, 12 patients (6 females, mean age: 64.5 years, age range: 46-80 years) underwent IVC leiomyosarcoma resection and reconstruction. All reconstructions were performed with ringed polytetrafluoroethylene (PTFE); graft sizes ranged from 12 mm to 16 mm. The tumor location was exclusively infrarenal in seven patients, between the renal and hepatic veins in two patients, and involved multiple segments in three patients. Larger graft sizes were utilized in reconstructing more superior segments of the IVC. Grafts were typically undersized and based on the diameter of the superior resection margin with 12 mm grafts approximately correlating to a 20 mm diameter, 14 mm to 25 mm, and 16 mm to 30 mm. The average undersizing ratio was 0.6. At a mean follow-up time of 43 ± 27 months, radiographic graft patency was 92%, overall survival was 83%, and disease-free survival was 25%. CONCLUSIONS: After en bloc resection of IVC leiomyosarcoma, caval reconstruction with an undersized ringed PTFE has acceptable patency. Grafts sizes should be based on the IVC diameter superior to the tumor and undersizing by approximately 40% appears to be associated with acceptable patency rates. Further multiinstitutional studies should be performed to best determine the optimal treatment of this rarely encountered tumor.

Paneled Saphenous Vein Grafts Compared to Internal Jugular Vein Grafts in Venous Reconstruction after Pancreaticoduodenectomy.

BACKGROUND: Venous resection during pancreaticoduodenectomy for the excision of pancreatic cancer allows for a more complete resection with negative margins, which increases survival. When the resected vein is greater than 3 cm, reconstruction with an interposition graft is recommended. However, consensus regarding the optimal venous conduit has not been reached. The objective of this study is to compare outcomes between the paneled saphenous vein graft (SVG) and internal jugular vein graft (IJVG) in portomesenteric venous reconstructions after pancreaticoduodenectomy. METHOD: A retrospective review was performed of patients undergoing pancreaticoduodenectomy requiring an interposition graft for venous reconstruction between 2011 and 2019. Patients were stratified based on the type of conduit used (paneled SVG or IJVG). Preoperative patient characteristics, reconstruction details, and postoperative outcomes including graft patency were recorded. RESULTS: During the study period, 18 patients met inclusion criteria (10 female, mean age: 63 years, age range: 41-82 years). Thirteen patients underwent reconstruction with paneled SVG and five with IJVG. Comparing SVG and IJVG groups, there were no significant differences in venous resection length, venous diameters at the resection margins, or splenic vein ligation rate. For the paneled SVG, the average length of harvested vein was 168 mm which rendered 3-paneled grafts with an average diameter of 12 mm. The time to complete the venous reconstructions did not differ between the two groups (SVG: 263+/-204 min, IJVG: 216+/-77 min, P = 0.63). There were five graft thrombosis, three in the SVG group (mean follow-up time of 17 months) and two in the IJVG group (mean follow-up time of 8 months). All but one of the graft thromboses occurred during the index hospitalization. There was one donor site seroma and wound dehiscence in the SVG group and none in the IJVG group. Hospital length of stay was longer for the IJVG group (IJVG: 15.2 days, SVG: 10.2 days, P = 0.03). However, in-hospital and late mortality did not differ between the groups. CONCLUSIONS: Paneled SVG and IJVG are both versatile and durable conduits for venous reconstruction after pancreaticoduodenectomy, able to accommodate a wide range of venous defects. In this small series, SVG has comparable outcomes to IJVG. Paneled SVG is a suitable alternative to IJVG for portomesenteric reconstruction.

Undersized Mitral Annuloplasty Increases Strain in the Proximal Lateral Left Ventricular Wall.

BACKGROUND: Recurrence of mitral regurgitation (MR) after undersized mitral annuloplasty (MA) for ischemic MR is as high as 60%, with the recurrence rate likely due to continued dilation of the left ventricle (LV). To better understand the causes of recurrent MR, we studied the effect of undersized MA on strain in the LV wall. We hypothesize that the acute change in ventricular shape induced by MA will cause increased strain in regions nearest the mitral valve. METHODS: Finite element models were previously reported, based on cardiac magnetic resonance images of 5 sheep with mild to moderate ischemic MR. A 24-mm saddle-shaped rigid annuloplasty ring was modeled and used to simulate virtual MA. Longitudinal and myofiber strains were calculated at end-diastole and end-systole, with preoperative early diastolic geometry as the reference state. RESULTS: The undersized MA significantly increased longitudinal strain at end-diastole in the lateral LV wall. The effect was greatest in the proximal-lateral endocardial surface, where longitudinal strain after MA was approximately triple the preoperative strain (11.17% ± 2.15% vs 3.45% ± 0.92%, p = 0.0057). In contrast, postoperative end-diastolic fiber strain decreased in this same region (2.53% ± 2.14% vs 7.72% ± 1.79%, p = 0.0060). There were no significant changes in either strain type at end-systole. CONCLUSIONS: Undersized MA increased longitudinal strain in the proximal lateral LV wall at end-diastole. This procedure-related strain at the proximal-lateral LV wall may foster continued LV enlargement and subsequent recurrence of mitral regurgitation.

Neochord placement versus triangular resection in mitral valve repair: A finite element model.

BACKGROUND: Recurrent mitral regurgitation after mitral valve repair is common, occurring in nearly 50% of patients within 10 years of surgery. Durability of repair is partly related to stress distribution over the mitral leaflets. We hypothesized that repair with neochords (NCs) results in lower stress than leaflet resection (LR). MATERIALS AND METHODS: Magnetic resonance imaging and 3D echocardiography were performed before surgical repair of P2 prolapse in a single patient. A finite element model of the left ventricle and mitral valve was created previously, and the modeling program LS-DYNA was used to calculate leaflet stress for the following repairs: Triangular LR; LR with ring annuloplasty (LR + RA); One NC; Two NCs; and 2NC + RA. RESULTS: (1) NC placement resulted in stable posterior leaflet stress: Baseline versus 2 NC at end diastole (ED), 12.1 versus 12.0 kPa, at end systole (ES) 20.3 versus 21.7 kPa. (2) In contrast, LR increased posterior leaflet stress: Baseline versus LR at ED 12.1 versus 40.8 kPa, at ES 20.3 versus 46.1 kPa. (3) All repair types reduced anterior leaflet stress: Baseline versus 2 NC versus LR 34.2 versus 25.8 versus 20.6 kPa at ED and 80.8 versus 76.8 versus 67.8 kPa at ES. (4) The addition of RA reduced leaflet stress relative to repair without RA. CONCLUSIONS: Neochord repair restored normal leaflet coaptation without creating excessive leaflet stress, whereas leaflet resection more than doubled stress across the posterior leaflet. The excess stress created by leaflet resection was partially, but not completely, mitigated by ring annuloplasty.

Finite Element Modeling of Mitral Valve Repair.

The mitral valve is a complex structure regulating forward flow of blood between the left atrium and left ventricle (LV). Multiple disease processes can affect its proper function, and when these diseases cause severe mitral regurgitation (MR), optimal treatment is repair of the native valve. The mitral valve (MV) is a dynamic structure with multiple components that have complex interactions. Computational modeling through finite element (FE) analysis is a valuable tool to delineate the biomechanical properties of the mitral valve and understand its diseases and their repairs. In this review, we present an overview of relevant mitral valve diseases, and describe the evolution of FE models of surgical valve repair techniques.

Residual Stress Impairs Pump Function After Surgical Ventricular Remodeling: A Finite Element Analysis.

BACKGROUND: Surgical ventricular restoration (Dor procedure) is generally thought to reduce left ventricular (LV) myofiber stress (FS) but to adversely affect pump function. However, the underlying mechanism is unclear. The goal of this study was to determine the effect of residual stress (RS) on LV FS and pump function after the Dor procedure. METHODS: Previously described finite element models of the LV based on magnetic resonance imaging data obtained in 5 sheep 16 weeks after anteroapical myocardial infarction were used. Simulated polyethylene terephthalate fiber (Dacron) patches that were elliptical and 25% of the infarct opening area were implanted using a virtual suture technique (VIRTUAL-DOR). In each case, diastole and systole were simulated, and RS, FS, LV volumes, systolic and diastolic function, and pump (Starling) function were calculated. RESULTS: VIRTUAL-DOR was associated with significant RS that was tensile (2.89 ± 1.31 kPa) in the remote myocardium and compressive (234.15 ± 65.53 kPa) in the border zone. VIRTUAL-DOR+RS (compared with VIRTUAL-DOR-NO-RS) was associated with further reduction in regional diastolic and systolic FS, with the greatest change in the border zone (43.5-fold and 7.1-fold, respectively; p < 0.0001). VIRTUAL-DOR+RS was also associated with further reduction in systolic and diastolic volumes (7.9%; p = 0.0606, and 10.6%; p = 0.0630, respectively). The resultant effect was a further reduction in pump function after VIRTUAL-DOR+RS. CONCLUSIONS: Residual stress that occurs after the Dor procedure is positive (tensile) in the remote myocardium and negative (compressive) in the border zone and associated with reductions in FS and LV volumes. The resultant effect is a further reduction in LV pump (Starling) function.

Posterior papillary muscle anchoring affects remote myofiber stress and pump function: finite element analysis.

BACKGROUND: The role of posterior papillary muscle anchoring (PPMA) in the management of chronic ischemic mitral regurgitation (CIMR) is controversial. We studied the effect of anchoring point direction and relocation displacement on left ventricular (LV) regional myofiber stress and pump function. METHODS: Previously described finite element models of sheep 16 weeks after posterolateral myocardial infarction (MI) were used. True-sized mitral annuloplasty (MA) ring insertion plus different PPM anchoring techniques were simulated. Anchoring points tested included both commissures and the central anterior mitral annulus; relocation displacement varied from 10% to 40% of baseline diastolic distance from the PPM to the anchor points on the annulus. For each reconstruction scenario, myofiber stress in the MI, border zone, and remote myocardium as well as pump function were calculated. RESULTS: PPMA caused reductions in myofiber stress at end-diastole and end-systole in all regions of the left ventricle that were proportional to the relocation displacement. Although stress reduction was greatest in the MI region, it also occurred in the remote region. The maximum 40% displacement caused a slight reduction in LV pump function. However, with the correction of regurgitation by MA plus PPMA, there was an overall increase in forward stroke volume. Finally, anchoring point direction had no effect on myofiber stress or pump function. CONCLUSIONS: PPMA reduces remote myofiber stress, which is proportional to the absolute distance of relocation and independent of anchoring point. Aggressive use of PPMA techniques to reduce remote myofiber stress may accelerate reverse LV remodeling without impairing LV function.

Reactive oxygen species responsive nanoprodrug to treat intracranial glioblastoma.

Chemotherapy for intracranial gliomas is hampered by limited delivery of therapeutic agents through the blood brain barrier (BBB). An optimal therapeutic agent for brain tumors would selectively cross the BBB, accumulates in the tumor tissue and be activated from an innocuous prodrug within the tumor. Here we show brain tumor-targeted delivery and therapeutic efficacy of a nanometer-sized prodrug (nanoprodrug) of camptothecin (CPT) to treat experimental glioblastoma multiforme (GBM). The CPT nanoprodrug was prepared using spontaneous nanoemulsification of a biodegradable, antioxidant CPT prodrug and α-tocopherol. The oxidized nanoprodrug was activated more efficiently than nonoxidized nanoprodrug, suggesting enhanced therapeutic efficacy in the oxidative tumor microenvironment. The in vitro imaging of U-87 MG glioma cells revealed an efficient intracellular uptake of the nanoprodrug via direct cell membrane penetration rather than via endocytosis. The in vivo study in mice demonstrated that the CPT nanoprodrug passed through the BBB and specifically accumulated in brain tumor tissue, but not in healthy brain tissue and other organs. The accumulation preferably occurred at the periphery of the tumor where cancer cells are most actively proliferating, suggesting optimal therapeutic efficacy of the nanoprodrug. The nanoprodrug was effective in treating subcutaneous and intracranial tumors. The nanoprodrug inhibited subcutaneous tumor growth more than 80% compared with control. The median survival time of mice implanted with an intracranial tumor increased from 40.5 days for control to 72.5 days for CPT nanoprodrug. This nanoprodrug approach is a versatile method for developing therapeutic nanoparticles enabling tumor-specific targeting and treatment. The nontoxic, tumor-specific targeting properties of the nanoprodrug system make it a safe, low cost, and versatile nanocarrier for pharmaceuticals, imaging agents, and diagnostic agents.

Nanoprodrugs of NSAIDs: Preparation and Characterization of Flufenamic Acid Nanoprodrugs.

We demonstrated that hydrophobic derivatives of the nonsteroidal anti-inflammatory drug (NSAID)flufenamic acid (FA), can be formed into stable nanometer-sized prodrugs (nanoprodrugs) that inhibit the growth of glioma cells, suggesting their potential application as anticancer agent. We synthesized highly hydrophobic monomeric and dimeric prodrugs of FA via esterification and prepared nanoprodrugs using spontaneous emulsification mechanism. The nanoprodrugs were in the size range of 120 to 140 nm and physicochemically stable upon long-term storage as aqueous suspension, which is attributed to the strong hydrophobic interaction between prodrug molecules. Importantly, despite the highly hydrophobic nature and water insolubility, nanoprodrugs could be readily activated into the parent drug by porcine liver esterase, presenting a potential new strategy for novel NSAID prodrug design. The nanoprodrug inhibited the growth of U87-MG glioma cells with IC(50) of 20 µM, whereas FA showed IC(50) of 100 µM, suggesting that more efficient drug delivery was achieved with nanoprodrugs.