Asymptomatic Females Are at Higher Risk for Perioperative TIA/Stroke and Males Are at Higher Risk for Long-Term Mortality after Carotid Artery Stenting: A Vascular Quality Initiative Analysis.

The study aims to review the sex differences with respect to transient ischemic attack (TIA)/stroke and death in the perioperative period and on long-term follow-up among asymptomatic patients treated with carotid stenting (CAS) in the vascular quality initiative (VQI). All cases reported to VQI of asymptomatic CAS (ACAS) patients were reviewed. The primary end point was risk of TIA/stroke and death in the in-hospital perioperative period and in the long-term follow-up. The secondary end point was to evaluate predictors of in-hospital perioperative TIA/stroke and mortality on long-term follow-up after CAS. There were 22,079 CAS procedures captured from January 2005 to April 2019. There were 5,785 (62.7%) patients in the ACAS group. The rate of in-hospital TIA/stroke was higher in female patients (2.7 vs. 1.87%, p = 0.005) and the rate of death was not significant (0.03 vs. 0.07%, p = 0.66). On multivariable logistic regression analysis, prior/current smoking history (odds ratio = 0.58 [95% confidence interval or CI = 0.39-0.87]; p = 0.008) is a predictor of in-hospital TIA/stroke in females. The long-term all-cause mortality is significantly higher in male patients (26.9 vs. 15.7%, p < 0.001). On multivariable Cox-regression analysis, prior/current smoking history (hazard ratio or HR = 1.17 [95% CI = 1.01-1.34]; p = 0.03), coronary artery disease or CAD (HR = 1.15 [95% CI = 1.03-1.28]; p = 0.009), chronic obstructive pulmonary disease or COPD (HR = 1.73 [95% CI = 1.55-1.93]; p < 0.001), threat to life American Society of Anesthesiologists (ASA) class (HR = 2.3 [95% CI = 1.43-3.70]; p = 0.0006), moribund ASA class (HR = 5.66 [95% CI = 2.24-14.29]; p = 0.0003), and low hemoglobin levels (HR = 0.84 [95% CI = 0.82-0.86]; p < 0.001) are the predictors of long-term mortality. In asymptomatic carotid disease patients, women had higher rates of in-hospital perioperative TIA/stroke and a predictor of TIA/stroke is a prior/current history of smoking. Meanwhile, long-term all-cause mortality is higher for male patients compared with their female counterparts. Predictors of long-term mortality are prior/current smoking history, CAD, COPD, higher ASA classification of physical status, and low hemoglobin level. These data should be considered prior to offering CAS to asymptomatic female and male patients and careful risks versus benefits discussion should be offered to each individual patient.

Proximal fixation of endovascular aortic device may not be associated with renal function decline after abdominal aortic aneurysm repair.

OBJECTIVE: Significant debate exists among providers who perform endovascular abdominal aortic aneurysm repair (EVAR) regarding the renal function change between suprarenal (SuF) and infrarenal (InF) fixation devices. The purpose of this study is to review our institution's experience using these devices in terms of renal function. METHODS: This is a retrospective review of all elective EVARs performed within a three-site health system (Florida, Minnesota, and Arizona) during the period of 2000 to 2018. The primary outcome was renal function decline on long-term follow-up depending on the anatomical fixation of the device (SuF vs InF). Secondary outcomes were length of hospitalization (LOH) and progression to hemodialysis. Multivariable regression analysis was performed to test for associations affecting LOH. RESULTS: There were 1130 elective EVARs included in our review. Of those, 670 (59.3%) had SuF and 460 (40.7%) InF. Long-term follow-up was 4.8 ± 3.7 years, and the rate of change in creatinine and estimated glomerular filtration rate (eGFR) were not statistically significant among groups (SuF vs InF). LOH was higher in those individuals with a SuF device (3.4 ± 2.2 vs 2.3 ± 1.0 days; P < .001). Ten patients with chronic kidney disease progressed to hemodialysis at 6.7 ± 3.8 years from EVAR. On Kaplan-Meier analysis, patients with chronic kidney disease with SuF were more likely to progress to hemodialysis (P = .039). On multivariable regression, female sex (Coef, 2.4; 95% confidence interval [CI], 0.17-0.41; P = .02), SuF (Coef, 9.5; 95% CI, 0.11-1.11; P < .0001), and intraoperative blood loss of greater than 150 mL (Coef, 15.4; 95% CI, 0.11-1.76; P < .0001) were predictors of prolonged LOH. CONCLUSIONS: Our three-site, single-institution data indicate that, although the starting eGFR was statistically lower in those individuals undergoing elective EVAR with InF, device fixation type did not affect the creatinine and eGFR on long-term follow-up. However, caution should be exercised at the time of abdominal aortic aneurysm repair in those individuals who already presented with renal dysfunction.

Endarterectomy for Iliac Occlusive Disease during Kidney Transplantation: A Multicenter Experience.

Little is known about the surgical challenges and outcomes of kidney transplantation (KT) in the face of severe iliac occlusive disease (IOD). We aim to examine our institution's experience and outcomes compared with all KT patients. Retrospective review of our multi-institutional transplant database identified patients with IOD requiring vascular surgery involvement for iliac artery endarterectomy at time of KT from 2000 to 2018. Clinical data, imaging studies, and surgical outcomes of 22 consecutive patients were reviewed. Our primary end-point was allograft survival. Secondary end-points included mortality and perioperative complications. A total of 6,757 KT were performed at our three sites (Florida, Arizona, and Minnesota); there were 22 (0.32%) patients receiving a KT with concomitant IOD requiring iliac artery endarterectomy. Mean patient age was 61.45 ± 7 years. There were 13 (59.1%) male patients. The most common etiology of renal failure was diabetic nephropathy in 10 patients (45.5%) followed by a combination of hypertensive/diabetic nephropathy in five patients (22.7%), and hypertensive nephrosclerosis in three patients (13.6%). The majority ( n = 16, 72.7%) of patients received renal allografts from deceased donors and six (27.3%) were recipients from living donors. Mean time from dialysis to transplantation was 2.9 ± 2.9 years. Mean follow-up was 3.5 ± 2.5 years. Mean length of hospital stay was 6.3 ± 4.3 days (range: 3-18 days). Graft loss within 90 days occurred in two (9.1%) patients, one due to renal vein thrombosis and another due to acute tubular necrosis. Overall allograft survival was 90.1% at 1-year and 86.4% at 3-year follow-up. Overall mortality occurred in 6 (27.3%) patients. Perioperative complications (Clavien-Dindo Grade 2-4) occurred in 13 (59.1%) patients, including 10 (45.5%) with acute blood loss anemia requiring transfusion, 2 (9.1%) reoperations for hematoma evacuation, 1 (4.5%) ischemic colitis requiring total abdominal colectomy, and 1 (4.5%) renal vein thrombosis requiring nephrectomy. IOD patients selected for KT are not common and although challenging, they have similar outcomes to our standard KT patients. The 1- and 3-year allograft survivals were 90.1 and 86.4% versus 96.0 and 90.3% in the general KT patient population. With these excellent outcomes, we recommend expanding the criteria for KT to include patients with IOD with prior vascular surgery consultation to prevent progression of IOD or prevention of wait list removal in select patients who are otherwise good candidates for KT.

Women have similar mortality but higher morbidity than men after elective endovascular abdominal aortic aneurysm repair.

OBJECTIVE: Sex disparities regarding outcomes for women after open and endovascular abdominal aortic aneurysm repair have been well-documented. The purpose of this study was to review whether these disparities were also present at our institution for elective endovascular aneurysm repair (EVAR) and whether specific factors predispose female patients to negative outcomes. METHODS: All elective EVARs were identified from our three sites (Florida, Minnesota, and Arizona) from 2000 to 2018. The primary outcome was in-hospital mortality and three-year mortality. Secondary outcomes included complications requiring return to the operating room, length of hospitalization (LOH), intensive care unit (ICU) days, and location of discharge after hospitalization. Multivariable logistic regression models were used to assess for the risk of complications. RESULTS: There were 1986 EVARs; 1754 (88.3%) were performed in male and 232 (11.7%) in female patients. Female patients were older (79 years [interquartile range (IQR), 72-83 years] vs 76 years [IQR, 70-81 years]; P < .001), had a lower body mass index (median, 26.1 kg/m2 [IQR, 22.1-31.0 kg/m2] vs 28.3 kg/m2 [IQR, 25.3-31.6 kg/m2]; P < .001 and hematocrit (median, 37.6% [IQR, 33.4%-40.6%] vs 39.4% [IQR, 35.6%-42.6%]; P < .001) and had higher glomerular filtration rate (median, 84.4 mL/min per 1.73m2 [IQR, 62.3-103 mL/min/1.73 m2] vs 51.1 mL/min/1.73 m2 [IQR, 41.8-60.8 mL/min/1.73 m2]; P < .001. Female patients were also more likely to be active smokers (15.3% vs 13.1%; P < .001) and have chronic obstructive pulmonary disease (24.7% vs 15.3%; P = .001). They were less likely to have coronary artery disease (31.6% vs 45.6%; P < .001). Aneurysms in women were slightly smaller in size (median, 54 mm [IQR, 50.0-58.0 mm] vs 55 mm [IQR, 51.0-60.0 mm]; P = .004). In-hospital mortality and mortality at the 3-year follow-up was not significant between female and male patients (0.86% vs 0.17%; P = .11 and 38.4% vs 36.2%; P = .57). However, female patients returned to the operating room with a greater frequency than male patients (3.9% vs 1.4%; P = .011). LOH (mean, 3.4 ± 3.8 days vs 2.5 ± 2.4 days; P < .001) and ICU days (mean, 0.3 ± 2.0 days vs 0.1 ± 0.5 days; P < .001) were longer for female patients. After hospitalization, female patients were discharged to rehabilitation facilities in greater proportion (12.7% vs 3.1%; P < .001) than their male counterparts. On multivariable analysis, female sex was associated with a return to the operating room (odds ratio, 6.4; 95% confidence interval [CI], 1.4-3.5; P = .02), longer LOH (Coef 4.0; 95% CI, 1.0-2.5; P = .00007), more ICU days (Coef 2.8; 95% CI, 1.1-3.0; P = .005), and a greater likelihood of posthospitalization rehabilitation facility placement (odds ratio, 5.8; 95% CI, 1.5-2.4; P = .0001). CONCLUSIONS: Our three-site, single-institution data support sex disparities to the detriment of female patients regarding return to the operating room after EVAR, LOH, ICU days, and discharge to rehabilitation facility. However, we found no differences for in-hospital or 3-year mortality.

A multi-institutional review of endovenous thermal ablation of the saphenous vein finds male sex and use of anticoagulation are predictors of long-term failure.

BACKGROUND: To review long-term outcomes and saphenous vein (SV) occlusion rate after endovenous ablation (EVA) for symptomatic varicose veins. METHODS: A review of our EVA database (1998-2018) with at least 3-years of clinical and sonographic follow-up. The primary end point was SV closure rate. RESULTS: 542 limbs were evaluated. 358 limbs had radiofrequency and 323 limbs had laser ablations; 542 great saphenous veins (GSV), 106 small saphenous veins (SSV) and 33 anterior accessory saphenous veins (AASV) were treated. Follow-up was 5.6 ± 2.3 years; 508 (74.6%) veins were occluded, 53 (7.8%) partially occluded and 120 (17.6%) were patent. On multivariable Cox regression analysis, male sex (HR 1.6, 95% CI [0.46-018], p = 0.012) and use anticoagulation (HR 2.0, 95% CI [0.69-0.34], p = 0.044) were predictors of long-term failure. On Kaplan-Meier curve, we had an 86.3% occlusion rate. CONCLUSION: Our experience revealed a 5-year closure rate of 86.3%. Ablations have satisfactory occlusion rate.

Prevalence of Intracranial Aneurysms in Patients with Infrarenal Abdominal Aortic Aneurysms: A Multicenter Experience.

Prior studies suggest high prevalence of intracranial aneurysms (IA) in patients with infrarenal abdominal aortic aneurysms (AAA). We reviewed our multicenter experience in clinical detection/treatment of IAs in AAA patients and estimated the risk of IA in patients with AAA relative to patients without AAA. We reviewed cases of vascular surgery infrarenal AAA repairs at three Mayo Clinic sites from January 1998 to December 2018. Concurrent controls were randomly matched in a 1:1 ratio by age, sex, smoking history, and head imaging characteristics. Conditional logistic regression was used to calculate odds ratios. We reviewed 2,300 infrarenal AAA repairs. Mean size of AAA at repair was 56.9 ± 11.4 mm; mean age at repair, 75.8 ± 8.0 years. 87.5% of the cases ( n = 2014) were men. Head imaging was available in 421 patients. Thirty-seven patients were found to have 45 IAs for a prevalence of 8.8%. Mean size of IA was 4.6 ± 3.5 mm; mean age at IA detection, 72.0 ± 10.8 years. Thirty (81%) out of 37 patients were men. Six patients underwent treatment for IA: four for ruptured IAs and two for unruptured IAs. All were diagnosed before AAA repair. Treatment included five clippings and one coil-assisted stenting. Time from IA diagnosis to AAA repair was 16.4 ± 11.0 years. Two of these patients presented with ruptured AAA, one with successful repair and a second one that resulted in death. Odds of IA were higher for patients with AAA versus those without AAA (8.8% [37/421] vs. 3.1% [13/421]; OR 3.18; 95% confidence interval, 1.62-6.27, p < 0.001). Co-prevalence of IA among patients with AAA was 8.8% and is more than three times the rate seen in patients without AAA. All IAs were diagnosed prior to AAA repair. Surveillance for AAA after IA treatment could have prevented two AAA ruptures and one death.

Female Sex is a Marker for Higher Morbidity and Mortality after Elective Endovascular Aortic Aneurysm Repair: A National Surgical Quality Improvement Program Analysis.

BACKGROUND: The adverse gender disparities for women after open abdominal aortic aneurysm (AAA) repair have been well documented. The purpose of this study is to review whether these disparities extend to elective endovascular aneurysm repair (EVAR). METHODS: Nonruptured, elective AAA was identified from the American College of Surgeons' National Quality Improvement Program (NSQIP) Targeted Participant Use File for EVAR from 2012 to 2017. The primary outcome was mortality. Secondary outcomes included lower extremity ischemia requiring intervention (LEIRI) and prolonged operative time (>120 min). Multivariable logistic regression models were used to assess the risk of mortality, LEIRI, and prolonged operative time among women compared with men. RESULTS: There were 14,019 EVAR procedures captured. A total of 3,367 were included for analysis after limiting to nonruptured, elective cases for diagnosis of AAA with a Current Procedural Terminology procedure code for EVAR. Of those, 2,764 (82.1%) were performed in men and 603 (17.9%) in women. Female patients were older (median [interquartile range (IQR)] 77 years [70-82] versus 74 years [68-80], P < 0.001), more likely to smoke (35.5% versus 29.6%, P = 0.005), and less likely to have diabetes (12.4% versus 17.8%, P = 0.001). Women had slightly smaller AAA size (median [IQR] 5.4 cm [5.0-5.9] versus 5.5 cm [5.1-6.0], P < 0.001) and were more likely to have prior abdominal operations (35.3% versus 23.1%, P < 0.001). The operative time was longer among women (median 114 min. [85-150] versus 105 min. [82-140], P < 0.001). Postoperatively, mortality was higher in female patients (1.8% versus 0.9%, P = 0.036), LEIRI occurred in higher proportion among female patients (2.7% versus 1.2%, P = 0.009), and their hospital stay was also longer (median 2 days [1-3] versus 1 day [1-2] days, P < 0.001). On multivariable logistic regression analysis, hematocrit level <30 vol% versus ≥30 vol% (odds ratio (OR) 5.5, 95% confidence interval (CI) 2.1-14.5, P < 0.001) was associated with increased mortality. Although not statistically significant, there was also evidence that the odds of mortality were also greater among women (OR 2.0, 95% CI 0.98-4.2, P = 0.06). LEIRI was more likely among women (OR 2.1, 95% CI 1.2-3.9, P = 0.015) and patients with a smoking history (OR 1.8, 95% CI 1.0-3.2, P = 0.044). Finally, odds of prolonged operative time were higher among women (OR 1.4, 95% CI 1.2-1.7, P < 0.001) and patients with chronic obstructive pulmonary disease (OR 1.2, 95% CI 1.0-1.5, P = 0.033) or partial/total dependent functional status (OR 2.2, 95% CI 1.3-3.7, P = 0.003). CONCLUSIONS: Although EVAR has improved overall surgical AAA outcomes, the NSQIP data in elective EVAR demonstrate continued sex disparities in morbidity and mortality after AAA surgical repair to the detriment of female patients.

Higher Long-Term Mortality with Carotid Artery Stenting in Asymptomatic Male Compared with Female Patients in the Southeastern Vascular Study Group.

BACKGROUND: To review the sex differences among symptomatic and asymptomatic patients treated with carotid endarterectomy (CEA) and carotid artery stenting (CAS) in the Southeastern Vascular Study Group (SEVSG), a regional quality group of the Vascular Quality Initiative (VQI). METHODS: All cases reported by the SEVSG members of symptomatic and asymptomatic patients were included in this retrospective review of CEA and CAS. Primary end point was 3-year survival difference between male and female patients. Secondary end points included in-hospital myocardial infarction (MI), transient ischemic attack (TIA)/stroke, and mortality differences between symptomatic and asymptomatic male and female patients. Cox proportional hazard regression was used to assess 3-year survival differences. RESULTS: There were 8,303 CEA and 1,876 CAS procedures performed in 29 centers from January 2011 to December 2018. From those, 4,650 (56.0%) and 938 (50.1%) were asymptomatic CEA and CAS, respectively. There were 2,760 (59.4%) male patients in the asymptomatic CEA and 597 (63.9%) in the asymptomatic CAS groups. After CEA, the rates of in-hospital MI (P = 0.034), TIA/stroke (P < 0.001), and death (P < 0.001) were significantly higher in symptomatic patients. MIs were more frequent in females with asymptomatic disease (P = 0.041). After CAS, the rate of TIA/stroke was higher in symptomatic patients (P = 0.030). There were no differences according to sex in the CAS group. On follow-up, asymptomatic male patients treated with CAS had a higher 3-year all-cause mortality compared with their female counterparts (7.0% vs. 1.8%; P = 0.015). On multivariable Cox regression analysis, male sex (HR = 2.63 [95% CI = 1.058-6.536]; P = 0.038) and lower hemoglobin levels (HR = 0.72 [95% CI = 0.597-0.857]; P < 0.001) were predictors of death in asymptomatic male patients treated with CAS. CONCLUSIONS: In our SEVSG region, postoperative MIs, TIA/stroke, and deaths were higher in symptomatic CEA patients. MIs were more frequent in asymptomatic CEA females. Postoperative TIA/stroke was more frequent in symptomatic CAS patients. After CAS, asymptomatic male patients had higher 3-year all-cause mortality than female patients. On multivariable Cox regression analysis, male sex and lower hemoglobin levels were predictors of death in these asymptomatic male patients treated with CAS. Long-term mortality risk in asymptomatic males should be considered before offering CAS. Further national VQI analysis of our asymptomatic and symptomatic male and female patients treated with CEA and CAS would be warranted.

Succinate causes pathological cardiomyocyte hypertrophy through GPR91 activation.

BACKGROUND: Succinate is an intermediate of the citric acid cycle as well as an extracellular circulating molecule, whose receptor, G protein-coupled receptor-91 (GPR91), was recently identified and characterized in several tissues, including heart. Because some pathological conditions such as ischemia increase succinate blood levels, we investigated the role of this metabolite during a heart ischemic event, using human and rodent models. RESULTS: We found that succinate causes cardiac hypertrophy in a GPR91 dependent manner. GPR91 activation triggers the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), the expression of calcium/calmodulin dependent protein kinase IIδ (CaMKIIδ) and the translocation of histone deacetylase 5 (HDAC5) into the cytoplasm, which are hypertrophic-signaling events. Furthermore, we found that serum levels of succinate are increased in patients with cardiac hypertrophy associated with acute and chronic ischemic diseases. CONCLUSIONS: These results show for the first time that succinate plays an important role in cardiomyocyte hypertrophy through GPR91 activation, and extend our understanding of how ischemia can induce hypertrophic cardiomyopathy.