Identifying Sex Dimorphism in Peripheral Artery Disease with Platelet Mapping.

BACKGROUND: Clinical outcomes in women with peripheral artery disease (PAD) after revascularization procedures are worse compared to men, yet there is little in the existing literature as why this may be the case. Platelet Mapping is an emerging point-of-care viscoelastic technology that measures the comprehensive properties of a blood clot, including fibrin-platelet interactions. This prospective observational study aimed to characterize the clinical and Platelet Mapping profiles of female and male patients undergoing lower extremity revascularization, and to correlate Platelet Mapping distribution to thrombotic potential. METHODS: All patients with a diagnosis of PAD undergoing named vessel open or endovascular revascularization to re-establish inflow, outflow, or both, during December 2020 and January 2022 were prospectively included. Patients were followed clinically for thrombosis for up to 1 year. Platelet Mapping assays were performed in 3 clinical phases: preoperative, postoperative inpatient, and postoperative outpatient. Inferential analysis between female and male patient was performed. The quartile distribution of Platelet Mapping metrics associated with thrombosis was used to infer to thrombotic potential. RESULTS: One hundred seven patients were enrolled, of which 37 (34.6%) were female. Female patients had significantly lower rates of uncontrolled diabetes (2.7% vs. 18.6%), hypertension requiring combination therapy (37.8% vs. 58.6%), chronic kidney disease (27.0% vs. 51.4%), coronary artery disease (29.7% vs. 57.1%), and myocardial infarction (16.2% vs. 35.7%) (all P < 0.05). Platelet reactivity was significantly higher in female patients with greater platelet aggregation (75.9 ± 23.3 vs. 63.5 ± 28.8) and lower platelet inhibition (23.8 ± 23.4 vs. 36.8 ± 28.9) (all P < 0.01). This trend was consistent over time when stratified by the postoperative inpatient and postoperative outpatient clinical phases. There was no statistically discernible difference in the use of antiplatelet therapy between groups, yet female patients continued to exhibit greater platelet reactivity when analyzed by the type of pharmacologic regimen (platelet aggregation on mono-antiplatelet therapy: 80.6 ± 21.0 in women versus 69.4 ± 25.0 in men; platelet aggregation on dual antiplatelet therapy: 67.9 ± 23.8 in women versus 44.8 ± 31.8 in men) (all P < 0.01). Twenty-one patients experienced postoperative graft/stent thrombosis within the study period. In relation to the overall study population, patients with thrombosis had Platelet Mapping metrics above the 50th percentile of overall platelet aggregation distribution. CONCLUSIONS: There is a growing appreciation for the differences in etiology, disease progression, and outcomes of cardiovascular conditions as they relate to sex. In this cohort, traditional cardiovascular risk factors were in lower prevalence in female patients. Platelet reactivity was found to be higher across clinical phases and antiplatelet regimens. High platelet reactivity was also associated with an increased incidence of thrombosis after lower extremity revascularization. These hypothesis-generating findings provide the basis for further exploration of sex-specific coagulation profiling in PAD patients.

Clinical characteristics, treatment and outcomes of patients with spontaneous renal artery dissections.

OBJECTIVES: The natural history and optimal management of spontaneous renal artery dissections (SRADs) are poorly understood. We compared baseline characteristics, presentation, management, and outcomes between patients with symptomatic versus asymptomatic SRADs. METHODS: We performed a retrospective review of medical charts for patients diagnosed with SRAD at a single, tertiary care center. Patients were identified using billing codes. Patient demographics, medical history, clinical presentation, treatment, and follow up were recorded. We compared patients based on presence or absence of symptoms at the time of SRAD diagnosis. RESULTS: A total of 125 patients were included; 73 (58.4%) patients had symptoms at the time of SRAD diagnosis. Symptomatic patients were younger at the time of diagnosis (47.4 vs. 54.3 years, p = 0.008) and more likely male (74.0% vs. 44.2%, p = 0.005). Most patients received medical therapy (93.2% vs. 82.6%, p = 0.32). Endovascular therapy utilization was low in both groups (8.2% vs. 7.7%, p = 0.9). Outcomes between the two groups were comparable; renal function remained stable, and mortality was rare. CONCLUSION: Most patients who presented with SRAD were treated with medical therapy alone and usually experienced a benign course. Further studies are needed to understand the pathophysiology and natural history of renal artery dissections.

Utilization of Thromboelastography with Platelet Mapping to Predict Infection and Poor Wound Healing in Postoperative Vascular Patients.

BACKGROUND: Postoperative infection and wound dehiscence rates are higher than expected in peripheral artery disease and contribute significantly to limb loss and mortality. Microvascular pathology characterized by microthrombi and increased platelet aggregation have been cited as contributing factors to poor wound healing and infection. The emergence of viscoelastic assays, such as thromboelastography with platelet mapping (TEG-PM), have been utilized to identify prothrombotic states and may provide insight into a patient's microvascular coagulation profile. This prospective, observational study aimed to determine if TEG-PM could predict poor wound healing or infection following lower extremity revascularization. METHODS: All patients undergoing revascularization between December 2020 and January 2022 were prospectively included and followed for wound complications or non-surgical site infections of the index limb. TEG-PM metrics at the first postoperative follow-up in the nonevent group was compared to the TEG-PM sample preceding the diagnosis of infection/dehiscence in the event group. Cox proportional hazards (PH) regression was used to model the predictive value of viscoelastic parameters. Cut-point analysis to determine high-risk groups was determined by performing receiver operating characteristic curve analysis. RESULTS: Of the 102 patients, 18.6% experienced infection/dehiscence. The TEG-PM sample analyzed in the event group was, on average, 19.5 days prior to the diagnosis of an event. The event group had significantly higher maximum clot amplitude (MA) (47.3 mm ± 16.0 vs. 30.6 mm ± 15.3, P < 0.01), higher platelet aggregation (71.3% ± 27.7 vs. 31.2% ± 24.0, P < 0.01), and lower platelet inhibition (28.7% ± 27.7 vs. 68.7% ± 24.1, P < 0.01). Cox PH analysis identified platelet aggregation as an independent and consistent predictor of infection (hazard ratio = 1.04, 95% confidence interval 1.03-1.06, P < 0.01). An optimal cut-point of > 33.2 mm MA, > 46.6% platelet aggregation, or < 55.8% platelet inhibition identifies those with infection/dehiscence with 79.0-89.5% sensitivity. CONCLUSIONS: These are the first data to provide a quantitative link between prothrombotic viscoelastic coagulation profiles with the development of infection/dehiscence. Based on the cut-points of > 33.2 mm MA, > 46.6% platelet aggregation, or < 55.8% platelet inhibition, we recommend consideration of an enhanced antimicrobial or antithrombotic approach for these high risk groups.

Pregnancy conditions and complications associated with the development of varicose veins.

BACKGROUND: Pregnancy is a known risk factor for developing varicose veins (VV). However, pregnancy is often considered a homogeneous entity and few studies have examined if specific characteristics and complications of pregnancy may influence VV formation. This study sought to identify which pregnancy-specific factors are associated with the development of VV. METHODS: All women who gave birth (live or still) between 1998 and 2020 within a multicenter health care system were identified retrospectively and followed through all hospital encounters (inpatient and outpatient). The primary outcome was VV, defined as any encounter with a primary diagnosis code for VV or a procedure for VV. The study period for each woman was the time from the first to last encounter. Extended Cox regression modeling evaluated the association between VV and pregnancy-related factors as a time-varying covariates while controlling for patient comorbidities. RESULTS: There were 156,622 women with a median follow-up of 8.3 years (interquartile range, 2.7-16.6 years) included. During this time, 225,758 deliveries occurred. The 10- and 20-year freedom from VV was 97.0% (95% CI, 96.8%-97.1%) and 92.7% (95% CI, 92.4%-93.0%), respectively, from the estimated start of first pregnancy. Overall, 4028 patients (2.57%) developed VV during the follow-up period and 1594 (1.02%) underwent a procedure for VV. After risk adjustment, increasing parity was significantly associated with VV, with each subsequent pregnancy increasing hazard of developing VV (parity = 1: hazard ratio [HR], 1.78; 95% CI, 1.55-1.99; P < .001; parity ≥6: HR, 4.83; 95% CI, 2.15-1.99-10.9; P < .001), Other significant pregnancy factors included excessive weight gain in pregnancy (HR, 1.44; 95% CI, 1.09-1.91; P = .011), post-term pregnancy (HR, 1.12; 95% CI, 1.02-1.21; P = .021), pre-eclampsia (HR, 0.79; 95% CI, 0.70-0.90; P < .001), and postpartum transfusion of platelets, plasma, or cryoprecipitate (HR, 2.05; 95% CI, 1.19-3.53; P = .001). CONCLUSIONS: Increasing parity, excessive weight gain in pregnancy, post-term pregnancy, and pre-eclampsia affect the development of VV after pregnancy. Although VV after pregnancy are likely underreported and true incidence is unknown, women should be counseled about the impact of these factors on VV development after pregnancy.

Rates of Conversion from Dry to Wet Gangrene Following Lower Extremity Revascularization.

BACKGROUND: There is a paucity of data regarding the conversion rate from dry gangrene to wet gangrene after lower extremity revascularization. This study aimed to determine the rate of conversion from dry to wet gangrene within 30 days post-procedure in patients who underwent endovascular or open revascularization for critical limb ischemia. Secondary aims included determining the time to conversion and associated risk factors with conversion. METHODS: A multicenter, retrospective review was performed utilizing the MGH/Brigham Healthcare System's Research Patient Data Registry (RPDR). All adult patients who had lower extremity dry gangrene that underwent a revascularization procedure (endo, open, hybrid) from April 2002 to March 2020 were included. Patients who had no lower extremity gangrene, a concurrent amputation with the revascularization procedure, or wet gangrene on initial presentation were excluded. Univariate analysis was performed using the Fisher's exact test and Wilcoxon rank-sum test. RESULTS: There were 1,518 patients identified who underwent revascularization; 194 (12.8%) patients met inclusion criteria and served as our study cohort. There were 15 (7.7%) conversions from dry to wet gangrene within 30 days post-procedure. The mean time to conversion was 13.5 ± 8.6 days. Univariate analysis did not identify any associated risk factors for conversion. CONCLUSIONS: The rate of dry to wet gangrene conversion post revascularization is 7.7% within 30 days. The mean time of conversion is 13.5 ± 8.6 days.

A systematic review of spinal cord ischemia prevention and management after open and endovascular aortic repair.

OBJECTIVE: Spinal cord ischemia (SCI) is one of the most devastating complications after descending thoracic aortic (DTA) and thoracoabdominal aortic (TAA) repairs. Patients who develop SCI have a poor prognosis, with mortality rates reaching 75% within the first year after surgery. Many factors have been shown to increase the risk of this complication, including the extent of TAA repair, length of aortic and collateral network coverage, embolization, and reduced spinal cord perfusion pressure. As a result, a variety of treatment strategies have been developed. We aimed to provide an up-to-date review of SCI rates with associated treatment algorithms from open and endovascular DTA and TAA repair. METHODS: Using PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines, a literature review with the MeSH (medical subject headings) terms "spinal cord ischemia," "spinal cord ischemia prevention and mitigation strategies," "spinal cord ischemia rates," and "spinal cord infarction" was performed in the Cochrane and PubMed databases to find all peer-reviewed studies of DTA and TAA repair with SCI complications reported. The search was limited to 2012 to 2021 and English-language reports. MeSH subheadings, including diagnosis, complications, physiopathology, surgery, mortality, and therapy, were used to further restrict the included studies. Studies were excluded if they were not of humans, had not pertained to SCI after DTA or TAA operative repair, and if the study had primarily discussed neuromonitoring techniques. Additionally, studies with <40 patients or limited information regarding SCI protection strategies were excluded. Each study was individually reviewed by two of us (S.L. and A.D.) to assess the type and extent of aortic pathology, operative technique, SCI protection or mitigation strategies, rates of overall and permanent SCI symptoms, associations with SCI on multivariate analysis, and mortality. RESULTS: Of the 450 studies returned by the MeSH search strategy, 41 met the inclusion criteria and were included in the final analysis. For the endovascular DTA repair patients, the overall SCI rates ranged from 0% to 10.6%, with permanent SCI symptoms ranging from 0% to 5.1%. The rate of overall SCI after endovascular and open TAA repair was 0% to 35%. The permanent SCI symptom rate was reported by only one study of open repair at 1.1%. The permanent SCI symptom rate after endovascular TAA repair was 2% to 20.5%. CONCLUSIONS: The present review has provided an up-to-date review of the current rates of SCI and the prevention and mitigation strategies used during DTA and TAA repair. We found that a multimodal approach, including a bundled institutional protocol, staging of multiple repairs, preservation of the collateral blood flow network, augmented spinal cord perfusion, selective cerebrospinal fluid drainage, and distal aortic perfusion during open TAA repairs, appears to be important in reducing the risk of SCI.

Natural history of penetrating atherosclerotic ulcers in aortic branch vessels.

OBJECTIVE: Penetrating atherosclerotic ulcers (PAUs) in aortic branch vessels are rare. There is a paucity of data regarding their long-term natural history and associated management. This study aimed to determine the prevalence and natural history of aortic branch PAUs. METHODS: Institutional data on all patients with an aortic branch PAU from 2005 to 2020 were retrospectively reviewed. Branch PAUs were defined as any PAU in the iliac, mesenteric, or arch vessels. End points included symptoms, end-organ events, and interventions. All computed tomography angiographies (CTAs) for each patient were reviewed, and total diameter, ulcer width, and ulcer depth were recorded on each computed tomography scan for the branch PAUs. Rate of change was compared between groups (iliac vs arch and visceral vessels) using a linear mixed-effects model. RESULTS: Among 58,800 patients who underwent a CTA, 367 patients had an aortic PAU (prevalence: 0.6%) and 58 patients had a branch PAU (prevalence: 0.1%). Among those 58 patients, there were 66 ulcerated branches. There were 50 iliac (42 common iliac, 7 internal, and 1 external), 11 arch (8 left subclavian, 3 innominate), and 5 visceral ulcers (3 superior mesenteric artery, 1 celiac, and 1 renal). Mean age was 74.0 ± 8.8 years, and 86% of patients were male; 74% had hypertension, 79% had hyperlipidemia, and 59% had a concomitant aortic aneurysm. There were 45 PAU vessels with >1 CTA (total of 167 CTAs) with a median follow-up of 4.0 years (interquartile range: 2.0-6.2 years). Total vessel diameter increased in size by 0.27 mm/y but did not differ between groups (iliac vs visceral/arch vessels). PAU width and depth also did not significantly change over time, nor did it differ between groups. No branch PAUs caused symptoms, end-organ events, or rupture, nor required intervention due to symptoms and/or progression. Four PAUs spontaneously resolved (2 iliac, 2 other), and 1 iliac PAU progressed to a saccular aneurysm. CONCLUSIONS: This is one of the largest studies evaluating the natural history of branched PAUs objectively via CTA. Branch PAUs are rare-the prevalence was one-sixth that of aortic PAUs. There was minimal growth noted in a median follow-up of 4 years, and no PAUs required intervention for symptoms or progression. Asymptomatic branch PAUs may be safely observed.

Perioperative outcomes for carotid revascularization on asymptomatic dialysis-dependent patients meet Society for Vascular Society guidelines.

OBJECTIVE: The current Society for Vascular Surgery practice guidelines recommend carotid revascularization for asymptomatic disease in patients with at least a 3-year life expectancy and stenosis >60% when the expected perioperative stroke and death rate is <3%. Based on this recommendation, it was previously determined that asymptomatic patients who require dialysis would not meet the perioperative stroke and death thresholds nor the long-term survival benchmarks to justify carotid surgery. To determine whether carotid surgery for patients requiring dialysis is appropriate, the present study compared the perioperative outcomes after carotid revascularization for dialysis-dependent patients relative to nondialysis patients in a contemporary, national cohort. METHODS: The targeted vascular module from the American College of Surgeons National Surgical Quality Improvement Program was queried to identify patients who undergone carotid endarterectomy or carotid artery stenting for asymptomatic carotid disease from 2011 to 2018. The cohort was categorized as requiring or not requiring dialysis. The primary 30-day outcomes included mortality and the composite of stroke/death and stroke/death/myocardial infarction (MI). Univariate analyses were performed using the Fisher exact test and Wilcoxon rank sum test. Multivariable analyses were used to assess the independent associations of the estimated glomerular filtration rate and dialysis dependence with the stroke/death rate. RESULTS: A total of 17,579 patients met the inclusion criteria. Of these patients, 226 (1.3%) required dialysis at revascularization. No difference was found in the degree of severe stenosis (80%-99%) demonstrated by 69% of the dialysis cohort and 72% of the nondialysis cohort (P = .9). Of the dialysis and nondialysis cohorts, 5% and 3.6% underwent carotid artery stenting (P = .3). The dialysis-dependent patients were younger (68 vs 71 years; P < .001) and were more likely to have insulin-dependent diabetes (47% vs 12%; P < .001), congestive heart failure (8.4% vs 1.4%; P < .001), and severe chronic obstructive pulmonary disease (15% vs 10%; P = .03). In the dialysis and nondialysis cohort, 2 (0.9%) and 88 (0.5%) patients died (P = .3); 4 (1.8%) and 247 (1.4%) experienced strokes (P = .6); and 3 (1.3%) and 185 (1.1%) patients experienced MI (P = .5), respectively. The composite outcomes of stroke/death and stroke/death/MI was 2.2% (n = 5) and 1.8% (n = 319; P = .6) and 3.5% (n = 8) and 2.8% (n = 479; P = .4) in the dialysis and nondialysis cohorts, respectively. After multivariable analysis, neither the estimated glomerular filtration rate (adjusted odds ratio, 1.0; 95% confidence interval, 1.00-1.01; P = .26) nor dialysis dependence (adjusted odds ratio, 0.21; 95% confidence interval, 0.03-1.57; P = .13) was independently associated with the composite outcome of stroke/death. CONCLUSIONS: The 30-day carotid revascularization outcomes for asymptomatic disease in dialysis-dependent patients met the Society for Vascular Surgery guidelines in this national cohort and might be better than previously surmised. Hence, vascular surgeons could consider carotid revascularization for select dialysis-dependent patients with the appropriate expected longevity and perioperative risk.