Nasim Hedayati

Implementation of an aortic screening program in clinical practice: Implications for the Screen for Abdominal Aortic Aneurysms Very Efficiently (SAAAVE) Act

OBJECTIVE Screening for abdominal aortic aneurysms (AAA) significantly reduces aneurysm-related death. In January 2007, the Federal government enacted Medicare coverage guideline to screen persons at risk for the presence of an AAA, the Screen for Abdominal Aortic Aneurysms Very Efficiently (SAAAVE) Act. The purpose of this study is to evaluate the efficacy and costs of a large scale screening effort for identifying AAAs in patients in clinical practice. METHODS A regional veterans affairs mandate for screening for AAA was implemented in February 2007. Data were extracted through the Northern California Veterans Affairs (VA) Service Network to identify veteran males 65-75 years of age who ever smoked at least 100 cigarettes during their lifetime. An AAA was defined as an aortic diameter 3.0 cm or greater. A Decision Support Systems software (LumiData, Minneapolis, Minn) package tracked true costs of conducting a large AAA screening protocol in the Northern California VA Health Care System. RESULTS A total of 2918 patients (average age, 71 +/- 6 years) were screened for AAA over a 1-year period from February 2007 to February 2008. An AAA was diagnosed in 5.1% (148/2918) of patients. Two hundred ninety patients out of the 2918 (9.9%) were inappropriately screened. The aneurysm distribution was as follows: 83% (123/148) of the aneurysms were 3.0-4.4 cm, 13% (19/148) were 4.5-5.5 cm, and 4.1% (6/148) were greater than 5.5 cm. Incidental findings of isolated iliac artery aneurysms were found in 0.1% (3/2918) of patients. The cost of AAA screening per patient is

Treatment and outcomes of aortic endograft infection

53. CONCLUSION The results of a large AAA screening effort in clinical practice reflect the results reported in the major clinical trials at a reasonable cost. The identification of large iliac artery aneurysms in the screening has not been previously reported.

Effects of Gender on Gene Expression in the Blood of Ischemic Stroke Patients

OBJECTIVE This study examined the medical and surgical management and outcomes of patients with aortic endograft infection after abdominal endovascular aortic repair (EVAR) or thoracic endovascular aortic repair (TEVAR). METHODS Patients diagnosed with infected aortic endografts after EVAR/TEVAR between January 1, 2004, and January 1, 2014, were reviewed using a standardized, multi-institutional database. Demographic, comorbidity, medical management, surgical, and outcomes data were included. RESULTS An aortic endograft infection was diagnosed in 206 patients (EVAR, n = 180; TEVAR, n = 26) at a mean 22 months after implant. Clinical findings at presentation included pain (66%), fever/chills (66%), and aortic fistula (27%). Ultimately, 197 patients underwent surgical management after a mean of 153 days. In situ aortic replacement was performed in 186 patients (90%) using cryopreserved allograft in 54, neoaortoiliac system in 21, prosthetic in 111 (83% soaked in antibiotic), and 11 patients underwent axillary-(bi)femoral bypass. Graft cultures were primarily polymicrobial (35%) and gram-positive (22%). Mean hospital length of stay was 23 days, with perioperative 30-day morbidity of 35% and mortality of 11%. Of the nine patients managed only medically, four of five TEVAR patients died after mean of 56 days and two of four EVAR patients died; both deaths were graft-related (mean follow-up, 4 months). Nineteen replacement grafts were explanted after a mean of 540 days and were most commonly associated with prosthetic graft material not soaked in antibiotic and extra-anatomic bypass. Mean follow-up was 21 months, with life-table survival of 70%, 65%, 61%, 56%, and 51% at 1, 2, 3, 4, and 5 years, respectively. CONCLUSIONS Aortic endograft infection can be eradicated by excision and in situ or extra-anatomic replacement but is often associated with early postoperative morbidity and mortality and occasionally with a need for late removal for reinfection. Prosthetic graft replacement after explanation is associated with higher reinfection and graft-related complications and decreased survival compared with autogenous reconstruction.

Gender-related variation in the clinical presentation and outcomes of critical limb ischemia.

This study examined the effects of gender on RNA expression after ischemic stroke (IS). RNA obtained from blood of IS patients (n = 51; 153 samples at ≤ 3, 5, and 24 hours) and from matched controls (n = 52) were processed on Affymetrix microarrays. Analyses of covariance for stroke versus control samples were performed separately for both genders and the regulated genes for females compared with males. In all, 242, 227, and 338 male-specific genes were regulated at ≤ 3, 5, and 24 hours after IS, respectively, of which 59 were regulated at all time points. Overall, 774, 3,437, and 571 female-specific stroke genes were regulated at ≤ 3, 5, and 24 hours, respectively, of which 152 were regulated at all time points. Male-specific stroke genes were associated with integrin, integrin-liked kinase, actin, tight junction, Wnt/β-catenin, RhoA, fibroblast growth factors (FGF), granzyme, and tumor necrosis factor receptor (TNFR)2 signaling. Female-specific stroke genes were associated with p53, high-mobility group box-1, hypoxia inducible factor (HIF)1α, interleukin (IL)1, IL6, IL12, IL18, acute-phase response, T-helper, macrophage, and estrogen signaling. Cell death signaling was overrepresented in both genders, although the molecules and pathways differed. Gender affects gene expression in the blood of IS patients, which likely implies gender differences in immune, inflammatory, and cell death responses to stroke.

The X-Chromosome Has a Different Pattern of Gene Expression in Women Compared With Men With Ischemic Stroke

Critical limb ischemia (CLI) is a major cause of limb loss and mortality among patients with advanced peripheral artery disease. Our objective was to evaluate the gender-specific differences in patient characteristics and clinical outcomes among patients with CLI. We performed a retrospective analysis of 97 women and 122 men presenting with CLI who underwent angiography from 2006 to 2010. Baseline demographics, procedural details, and lesion characteristics were assessed for each patient. Kaplan–Meier analysis was used to assess long-term patient and lesion-level outcomes. Cox proportional hazard modeling was used to evaluate the relationship between gender and major adverse cardiovascular events (MACE). Compared to men, women were less likely to have a history of coronary artery disease (39% vs 54%, p = 0.02) or diabetes (57% vs 70%, p = 0.05) but had similar baseline medical therapy. At angiography, women were more likely to have significant femoropopliteal (77% vs 67%, p = 0.02) and multi-level infrainguinal disease (63% vs 51%, p = 0.02). Women were also more likely to undergo multi-vessel percutaneous intervention (69% vs 55%, p = 0.05), but had similar rates of limb salvage after percutaneous intervention or surgical bypass (HR 0.94 [95% CI 0.45–1.94], p = 0.9). During follow-up, women had higher rates of subsequent major adverse cardiovascular events (HR 1.63 [95% CI 1.01–2.63], p = 0.04). In conclusion, women with CLI are more likely to present with femoropopliteal and multi-level infrainguinal disease. Despite similar rates of limb salvage, women with CLI have an increased rate of subsequent major adverse cardiovascular events.

Early duplex scanning after infrainguinal endovascular therapy

Background and Purpose— Differences in ischemic stroke between men and women have been mainly attributed to hormonal effects. However, sex differences in immune response to ischemia may exist. We hypothesized that differential expression of X-chromosome genes in blood immune cells contribute to differences between men and women with ischemic stroke. Methods— RNA levels of 683 X-chromosome genes were measured on Affymetrix U133 Plus2.0 microarrays. Blood samples from patients with ischemic stroke were obtained at ⩽3 hours, 5 hours, and 24 hours (n=61; 183 samples) after onset and compared with control subjects without symptomatic vascular diseases (n=109). Sex difference in X-chromosome gene expression was determined using analysis of covariance (false discovery rate ⩽0.05, fold change ≥1.2). Results— At ⩽3, 5, and 24 hours after stroke, there were 37, 140, and 61 X-chromosome genes, respectively, that changed in women; and 23, 18, and 31 X-chromosome genes that changed in men. Female-specific genes were associated with post-translational modification, small-molecule biochemistry, and cell–cell signaling. Male-specific genes were associated with cellular movement, development, cell-trafficking, and cell death. Altered sex specific X-chromosome gene expression occurred in 2 genes known to be associated with human stroke, including galactosidase A and IDS, mutations of which result in Fabry disease and Hunter syndrome, respectively. Conclusions— There are differences in X-chromosome gene expression between men and women with ischemic stroke. Future studies are needed to decipher whether these differences are associated with sexually dimorphic immune response, repair or other mechanisms after stroke, or whether some of them represent risk determinants.

Application of duplex ultrasound imaging in determining in-stent stenosis during surveillance after mesenteric artery revascularization

OBJECTIVES Duplex ultrasound scanning (DUS) has benefit for intraoperative and subsequent evaluation of surgical bypasses in the lower extremities. The utility of DUS after endovascular revascularizations is not established. This study was performed to evaluate whether DUS findings after infrainguinal endovascular interventions for critical limb ischemia (CLI) were predictive of need for reintervention or amputation. METHODS To identify the study cohort, peripheral interventions for CLI (Rutherford grades 4, 5, 6) over a 24-month period (2006-2007) were reviewed. DUS findings were considered indicative of hemodynamic stenosis if the peak systolic velocity (PSV) was ≥ 180 cm/s or the PSV velocity ratio was ≥ 2.0. Demographic, clinical, procedural, and outcomes were examined. SVS and TASC II classifications and reporting standards were used. Arteriograms were reviewed and treated segments were categorized as patent (<30% residual stenosis) or abnormal (≥ 30% residual stenosis). RESULTS There were 122 infrainguinal interventions for CLI in 113 patients (53% male; mean age 71 years). Risk factors included diabetes: 61%; renal failure: 20%; and smoking (within 1 year): 40%. DUS was performed within 30 days of the index procedure in 90 cases. Fifty patients had an abnormal early duplex and 40 patients had a normal duplex. In patients with a normal duplex ultrasound the amputation rate was 5% vs 20% in the group with an abnormal duplex (P = .04). Primary patency was 56% in the normal duplex group and 46% in the abnormal duplex group (P = .18). Early duplex ultrasound was able to identify a residual stenosis not seen on completion angiography in 56% of cases. CONCLUSIONS Duplex scanning detects residual stenosis missed with conventional angiography after infrainguinal interventions. An abnormal DUS in the first 30 days after an intervention is associated with an increased risk of amputation. This suggests a possible role for intraprocedural DUS, as well as routine postprocedure DUS, close clinical follow-up, and consideration of reintervention for residual abnormalities in patients treated for CLI.

The Contemporary Safety and Effectiveness of Lower Extremity Bypass Surgery and Peripheral Endovascular Interventions in the Treatment of Symptomatic Peripheral Arterial Disease

OBJECTIVE Currently, there are no well-established duplex ultrasound (DUS) criteria for the evaluation of the mesenteric arteries after stenting for occlusive disease. Previous studies suggested DUS velocity criteria in the native superior mesenteric artery (SMA) overestimate stenosis in stented arteries, but most studies have not evaluated DUS imaging after SMA stenting longitudinally. This study was undertaken to determine the accuracy of DUS after mesenteric artery revascularization and, in particular, to evaluate the utility of DUS imaging for the detection of in-stent stenosis (ISS) of the SMA. METHODS A retrospective record review was performed for all patients who underwent SMA stenting for chronic mesenteric ischemia at a single institution from January 2004 to May 2011. RESULTS Mesenteric artery occlusive disease resulted in 24 patients undergoing mesenteric stenting of the SMA alone (n = 20) or the SMA and celiac artery simultaneously (n = 3). The mean ± standard deviation peak systolic velocity (PSV) in 13 prestent DUS images of the SMA was 464 ± 130 cm/s. Prestenting angiography revealed an average SMA stenosis of 79% ± 14%. After stenting, completion angiography in each case revealed <20% residual stenosis. No significant correlation was identified between SMA PSV and angiographic stenosis before and after stenting (P > .05). Follow-up SMA DUS imaging showed an average PSV of 335 ± 138 cm/s at 0.9 ± 1.5 months, 360 ± 143 cm/s at 4.8 ±2.6 months, and 389 ± 95 cm/s at 14.4 ± 5.1 months. A significant difference existed between the prestent and the first poststent mean SMA PSV (P < .05), but no significant difference existed between each poststenting interval. Eight reinterventions for SMA ISS were performed, with a mean elevated in-stent SMA PSV of 505 ± 74 vs 341 ± 145 cm/s in patients who did not undergo reintervention. Angiography before the eight reinterventions demonstrated an average SMA ISS of 53% ± 25%. In-stent SMA PSV decreased from 505 ± 74 to 398 ± 108 cm/s after the reintervention (P < .05). CONCLUSIONS Consistent with other reports, our data demonstrate the PSV in successfully stented SMAs remains higher than the PSV threshold of 275 cm/s used for the diagnosis of high-grade native SMA stenosis. In addition, in-stent SMA PSVs did not significantly change over DUS surveillance for patients who did not undergo reintervention. Thus, obtaining a baseline DUS early after mesenteric stenting should be considered to compare future surveillance DUS. An increase above this baseline or an in-stent SMA PSV approaching 500 cm/s should be considered suspicious for ISS, but larger prospective studies will be required to validate these preliminary findings.

Racial Disparities in Outcomes of Endovascular Procedures for Peripheral Arterial Disease: An Evaluation of California Hospitals, 2005–2009

Background— Treatment for symptomatic peripheral artery disease includes lower extremity bypass surgery (LEB) and peripheral endovascular interventions (PVIs); however, limited comparative effectiveness data exist between the 2 therapies. We assessed the safety and effectiveness of LEB and PVI in patients with symptomatic claudication and critical limb ischemia. Methods and Results— In a community-based clinical registry at 2 large integrated healthcare delivery systems, we compared 883 patients undergoing PVI and 975 patients undergoing LEB between January 1, 2005 and December 31, 2011. Rates of target lesion revascularization were greater for PVI than for LEB in patients presenting with claudication (12.3±2.7% and 19.0±3.5% at 1 and 3 years versus 5.2±2.4% and 8.3±3.1%, log-rank P<0.001) and critical limb ischemia (19.1±4.8% and 31.6±6.3% at 1 and 3 years versus 10.8±2.5% and 16.0±3.2%, log-rank P<0.001). However, in comparison with PVI, LEB was associated with increased rates of complications up to 30 days following the procedure (37.1% versus 11.9%, P<0.001). There were no differences in amputation rates between the 2 groups. Findings remained consistent in sensitivity analyses by using propensity methods to account for treatment selection. Conclusions— In patients with symptomatic peripheral artery disease, in comparison with LEB, PVI was associated with fewer 30-day procedural complications, higher revascularization rates at 1 and 3 years, and no difference in subsequent amputations.

Y chromosome gene expression in the blood of male patients with ischemic stroke compared with male controls.

BACKGROUND Racial/ethnic disparities in treatment outcomes of peripheral arterial disease (PAD) are well documented. Compared with non-Hispanic (NH) whites, blacks and Hispanics are more likely to undergo amputation and less likely to undergo bypass surgery for limb salvage. Endovascular procedures are being increasingly performed as first line of therapy for PAD. In this study, we examined the outcomes of endovascular PAD treatments based on race/ethnicity in a contemporary large population-based study. METHODS We used Patient Discharge Data from Californias Office of Statewide Health Planning and Development to identify all patients over the age of 35 who underwent a lower extremity arterial intervention from 2005 to 2009. A look-back period of 5 years was used to exclude all patients with prior lower extremity arterial revascularization procedures or major amputation. Cox proportional hazards regression was used to compare amputation-free survival and time to death within 365 days. Logistic regression was used for comparison of 1-month myocardial infarction, 1-month major amputation, 1-month all-cause mortality, 12-month major amputation, 12-month reintervention, and 12-month all-cause mortality rates among NH white, black, and Hispanic patients. These analyses were adjusted for age, gender, insurance status, severity of PAD, comorbidities, history of coronary artery angioplasty or bypass surgery, or history of carotid endarterectomy. RESULTS Between 2005 and 2009, a total of 41,507 individuals underwent PAD interventions, 25,635 (61.7%) of whom underwent endovascular procedures. There were 17,433 (68%) NH whites, 4,417 (17.2%) Hispanics, 1,979 (7.7%) blacks, 1,163 (4.5%) Asian/Native Hawaiians, and 643 (2.5%) others in this group. There was a statistically significant difference in the amputation-free survival within 365 days among the NH white, Hispanic, and black groups (P < 0.0001); the hazard ratio for amputation within 365 days was 1.69 in Hispanics (95% confidence interval [CI] 1.51-1.90, P < 0.0001) and 1.68 in blacks (95% CI 1.44-1.96, P < 0.001) compared with NH whites following endovascular procedures after adjusting for age, gender, insurance status, comorbidities, severity of PAD, history of coronary artery angioplasty or bypass surgery, or history of carotid endarterectomy. After adjusting for the aforementioned confounders, the first reintervention within 12 months was also significantly associated with race/ethnicity (P = 0.002). Odds ratio for reintervention was 1.17 in blacks (95% CI 1.06-1.30, P = 0.002) and 1.084 in Hispanics (95% CI 1.00-1.16, P = 0.04) compared with NH whites. CONCLUSIONS In this contemporary large population-based study, we demonstrated that even among matched cohorts Hispanics and blacks have worse amputation-free survival than NH whites following endovascular therapy. Our study also found that Hispanics and blacks are more likely to undergo lower extremity arterial reinterventions than NH whites. Further research is crucial in understanding if higher reintervention rates in Hispanics and blacks are because of more severe disease and/or poor access to proper follow-up care and optimal medical management.