Outcomes of Peripheral Vascular Interventions via Retrograde Pedal Access for Chronic Limb-Threatening Ischemia in a Multicenter Registry.

Purpose: To describe the use and 1-year outcomes of retrograde pedal access during peripheral vascular interventions (PVI) for chronic limb-threatening ischemia (CLTI). Materials and Methods: From October 2016 to September 2017, 159 patients (mean age 71±10 years; 112 men) undergoing PVI via retrograde pedal access were enrolled in the multicenter Vascular Quality Initiative (VQI) registry. The pedal access approach included retrograde femoral (40%), antegrade femoral (26%), retrograde to antegrade femoral (22%), and pedal only (11%). A comparator group of 1972 patients (mean age 69±12 years; 1129 men) having a contralateral retrograde femoral access was established for propensity matching, which resulted in 156 patients per group. Procedure characteristics, technical success, and access site complications were compared. Major adverse limb events (MALE) and amputation-free survival (AFS) at 1 year were analyzed using the Kaplan-Meier method and Cox proportional hazard models to calculate hazard ratios (HR) and 95% confidence intervals (CI). Results: Technical failure was similar for retrograde femoral and pedal access (7% vs 13%, p=0.07). Complications were rare and included access site hematoma (2 vs 5, p=0.32) and target artery thrombosis (0 vs 2) for the femoral vs pedal access groups, respectively. The rates of MALE at 1 year were significantly lower after retrograde femoral access (24%) compared with pedal access (38%; log-rank p=0.01; HR 1.95, 95% CI 1.15 to 3.30). AFS estimates at 1 year were similar: 86% for retrograde femoral and 83% for pedal access (log-rank p=0.37; HR 1.32, 95% CI 0.73 to 2.39), as were major amputation estimates: 10% for retrograde femoral access and 13% for pedal access group (log-rank p=0.21; HR 1.58, 95% CI 0.77 to 3.26). Conclusion: In this analysis of multicenter registry data, retrograde pedal access in patients with CLTI had similar technical success and early complications in comparison with traditional contralateral retrograde femoral access. The rates of MALE were higher after pedal access but AFS was similar, indicating a tradeoff between limb salvage and repeat interventions.

Surveillance and Management of Troponin Elevation after Vascular Surgery.

BACKGROUND: Postopertive troponin elevation may occur without typical or atypical cardiac symptoms and is associated with an increased 30-day morbidity and mortality. The objective of the study was to implement a quality improvement initiative of postoperative troponin surveillance algorithm aimed at intensifying medical management after vascular surgery. METHODS: We conducted a single-center study of postoperative troponin surveillance after vascular surgery (n = 201) at a tertiary care, academic medical center from January to December 2016. Troponin surveillance was performed on postoperative days 1-3 after carotid endarterectomy, endovascular aortic repair, infrainguinal bypass, open abdominal aortic aneurysm repair, peripheral vascular intervention, and suprainguinal bypass, regardless of cardiac symptoms. Patients with troponin I elevation (>0.034 ng/mL) were managed with a treatment algorithm which included single or dual antiplatelet (AP) agent, high-intensity statin therapy, smoking cessation consultation, and outpatient cardiology consultation and stress testing. Patients with troponin elevation ≥1.0 ng/mL received inpatient cardiology consultation. We assessed adherence to the protocol for intensification of best medical therapy defined as high-dose statin therapy, increase in AP therapy, and smoking cessation consultation according to the established algorithm. RESULTS: Troponin elevation was recorded in 17% (34/201) of patients and was associated with cardiac symptoms in 8 patients (24%), while 26 (76%) patients had an asymptomatic abnormal troponin on postoperative surveillance. One patient was excluded due to death immediately after SUPRA, resulting in 200 patients. Troponin elevation ≥1.0 ng/mL occurred in 11 asymptomatic patients (5.5%). Any intensification of medical therapy was instituted in 76% of patients with elevated troponin and included high-intensity statin therapy (58%), increase in AP therapy (18%), and smoking cessation consultation (66%). Once an elevated troponin level was recognized, 52% of our patients received cardiology consultation with an increased likelihood (100%) in patients with troponin ≥1 ng/mL (P < 0.001). Adherence to outpatient stress testing was 66%. Intensification of medical therapy was not significantly different between patients with abnormal troponin values, >0.034-1.0 (n = 23) versus ≥1.0 ng/mL (n = 10); statin therapy (P = 1.0), AP (P = 0.34), and smoking cessation (P = 1.0). One-year mortality was higher in patients with postoperative troponin elevation than those with normal postoperative troponin levels (12% vs. 2.4%; P = 0.03). CONCLUSIONS: Routine postoperative troponin surveillance results in intensification of statin therapy in patients with asymptomatic troponin elevation. Further study is needed to determine if this approach reduces long-term cardiovascular morbidity and mortality.

Postoperative opioid prescribing patterns and use after vascular surgery.

The aim of this study was to assess postoperative opioid prescribing patterns, usage, and pain control after common vascular surgery procedures in order to develop patient centered best-practice guidelines. We performed a prospective review of opioid prescribing after seven common vascular surgeries at a rural, academic medical center from December 2016 to July 2017. A standardized telephone questionnaire was prospectively administered to patients ( n = 110) about opioid use and pain management perceptions. For comparison we retrospectively assessed opioid prescribing patterns ( n = 939) from July 2014 to June 2016 normalized into morphine milligram equivalents (MME). Prescribers were surveyed regarding opioid prescription attitudes, perceptions, and practices. Opioids were prescribed for 78% of procedures, and 70% of patients reported using opioid analgesia. In the prospective group, the median MMEs prescribed were: VEIN (31, n = 16), CEA (40, n = 14), DIAL (60, n = 17), EVAR (108, n = 8), INFRA (160, n = 16), FEM TEA (200, n = 11), and OA (273, n = 4). The median proportion of opioids used by patients across all procedures was only 30% of the amount prescribed across all procedures (range 14-64%). Patients rated the opioid prescribed as appropriate (59%), insufficient (16%), and overprescribed (25%), and pain as very well controlled (47%), well controlled (47%), poorly controlled (4%), and very poorly controlled (2%). In conclusion, we observed significant variability in opioid prescribing after vascular procedures. The overall opioid use was substantially lower than the amount prescribed. These data enabled us to develop guidelines for opioid prescribing practice for our patients.

Image Fusion and 3-Dimensional Roadmapping in Endovascular Surgery.

Practitioners of endovascular surgery have historically used 2-dimensional (2D) intraoperative fluoroscopic imaging, with intravascular contrast opacification, to treat complex 3-dimensional (3D) pathology. Recently, major technical developments in intraoperative imaging have made image fusion techniques possible, the creation of a 3D patient-specific vascular roadmap based on preoperative imaging which aligns with intraoperative fluoroscopy, with many potential benefits. First, a 3D model is segmented from preoperative imaging, typically a computed tomography scan. The model is then used to plan for the procedure, with placement of specific markers and storing of C-arm angles that will be used for intraoperative guidance. At the time of the procedure, an intraoperative cone beam computed tomography is performed, and the 3D model is registered to the patient's on-table anatomy. Finally, the system is used for live guidance in which the 3D model is codisplayed with overlying fluoroscopic images. There are many applications for image fusion in endovascular surgery. We have found it to be particularly useful for endovascular aneurysm repair (EVAR), complex EVAR, thoracic EVAR, carotid stenting, and for type 2 endoleaks. Image fusion has been shown in various settings to lead to decreased radiation dose, less iodinated contrast use, and shorter procedure times. In the future, fusion models may be able to account for vessel deformation caused by the introduction of stiff wires and devices, and the user-dependent steps may become more automated. In its current form, image fusion has already proven itself to be an essential component in the planning and success of complex endovascular procedures.

Early extubation reduces respiratory complications and hospital length of stay following repair of abdominal aortic aneurysms.

BACKGROUND: Early extubation after cardiac surgery is associated with decreased hospital stay and resource savings with similar mortality and has led to the widespread use of early extubation protocols. In the Vascular Quality Initiative, there is significant regional variation in the frequency of extubation in the operating room (endovascular aneurysm repair [EVAR], 77%-97%; open repair, 30%-70%) after repair of intact abdominal aortic aneurysms (AAAs). However, the effects of extubation practices on patient outcomes after repair of AAAs are unclear. METHODS: All patients undergoing repair of an intact AAA in the Vascular Study Group of New England from 2003 to 2015 were evaluated. Patients undergoing concomitant procedures or conversions were excluded. Timing of extubation was stratified for EVAR (operating room, <12 hours, >12 hours) and open repair (operating room, <12 hours, 12-24 hours, >24 hours). Prolonged hospital stay was defined as >2 days after EVAR and >7 days after open repair. Univariate and multivariable analyses were completed, and independent predictors of extubation outside of the operating room were identified. RESULTS: There were 5774 patients evaluated (EVAR, 4453; open repair, 1321). After both EVAR and open repair, respiratory complications, prolonged hospital stay, and discharge to a skilled nursing facility (SNF) increased with intubation time. After adjustment, the odds of complications increased with each 12-hour delay in extubation: respiratory (EVAR: odds ratio [OR], 4.3 [95% confidence interval (CI), 3.0-6.1]; open repair: OR, 1.8 [95% CI, 1.5-2.2]), prolonged hospital stay (EVAR: OR, 2.7 [95% CI, 2.0-3.8]; open repair: OR, 1.3 [95% CI, 1.1-1.4]), and discharge to SNF (EVAR: OR, 2.0 [95% CI, 1.5-2.8]; open repair: OR, 1.4 [95% CI, 1.1-1.6]). Predictors of extubation outside of the operating room after EVAR included increasing age (OR, 1.5; 95% CI, 1.2-1.8), congestive heart failure (OR, 1.9; 95% CI, 1.2-3.0), chronic obstructive pulmonary disease (OR, 2.0; 95% CI, 1.4-2.9), symptomatic aneurysm (OR, 3.8; 95% CI, 2.3-5.7), and increasing diameter (OR, 1.01; 95% CI, 1.01-1.01). After open repair, increasing age (OR, 1.4; 95% CI, 1.1-1.6), congestive heart failure (OR, 1.8; 95% CI, 1.01-3.3), dialysis (OR, 2.8; 95% CI, 1.7-70), symptomatic aneurysm (OR, 2.8; 95% CI, 1.9-4.3), and hospital practice patterns (OR, 1.01; 95% CI, 1.01-1.01) were predictive of extubation outside of the operating room. CONCLUSIONS: The benefits of early extubation in cardiac patients are also seen after AAA repair. Suitable patients should be extubated in the operating room to decrease respiratory complications, length of stay, and discharge to an SNF. Early extubation protocols should be considered to reduce regional variation in extubation practices and to improve patient outcomes.

The perioperative effect of concomitant procedures during open infrarenal abdominal aortic aneurysm repair.

BACKGROUND: Open repair of abdominal aortic aneurysms (AAAs) is occasionally performed in conjunction with additional procedures; however, how these concomitant procedures affect outcome is unclear. This study determined the frequency of additional procedures during elective open AAA repair and the effect on perioperative outcomes. METHODS: All elective infrarenal open AAA repairs between January 2003 and November 2014 in the Vascular Study Group of New England (VSGNE) were identified. Patients were grouped by concomitant procedures, which included no concomitant procedure, renal artery bypass, lower extremity bypass, other abdominal procedure, or thromboembolectomy. Analyses were performed using multivariable logistic regression. RESULTS: Of 1314 patients who underwent elective AAA repair, 153 (11.6%) had a concomitant procedure, including renal bypass in 27 (2.1%), lower extremity bypass in 28 (2.1%), other abdominal procedures in 64 (4.9%), and thromboembolectomy in 48 (3.7%). Independent risk factors for 30-day mortality were renal bypass (odds ratio [OR], 7.2; 95% confidence interval [CI], 1.9-27.7), other abdominal procedures (OR, 4.8; 95% CI, 1.6-14.1), and thromboembolectomy (OR, 8.8; 95% CI, 3.1-24.9). Deterioration of renal function was predicted by renal bypass (OR, 5.1; 95% CI, 2.1-12.4) and thromboembolectomy (OR, 3.7; 95% CI, 1.8-7.6). Lower extremity bypass and thromboembolectomy were predictive of postoperative leg ischemia (OR, 8.9; 95% CI, 2.7-29.0; OR, 11.2; 95% CI, 4.4-28.8, respectively), and thromboembolectomy was also predictive of postoperative bowel ischemia (OR, 4.4; 95% CI, 1.6-12.0). CONCLUSIONS: Performing additional procedures during infrarenal open AAA repair is associated with increased morbidity and mortality in the postoperative period. Careful deliberation of the operative risks and the necessity of the additional interventions are therefore advised during operative planning. This study also highlights the importance of avoiding perioperative thromboembolic events.

The impact of concomitant procedures during endovascular abdominal aortic aneurysm repair on perioperative outcomes.

BACKGROUND: Concomitant procedures during endovascular aneurysm repair (EVAR) of an abdominal aortic aneurysm are performed to facilitate endograft delivery, to simultaneously treat unrelated conditions, or to resolve intraoperative pitfalls. The frequency and perioperative impact of these procedures are not well described. This study aimed to assess the frequency and perioperative impact of various concomitant procedures performed at the time of EVAR. METHODS: We included all elective EVARs in the Vascular Study Group of New England between January 2003 and November 2014 and identified those with and those without concomitant procedures. Multivariable logistic regression analysis was used to establish the independent association between concomitant procedures and perioperative outcomes. RESULTS: The study included 4033 patients, with 1168 (29.0%) patients undergoing one or more additional procedures. Independent risk factors for 30-day mortality were concomitant femoral endarterectomy (odds ratio [OR], 4.8; 95% confidence interval [CI], 2.1-11.2) and renal angioplasty or stenting (OR, 3.1; 95% CI, 1.2-8.3). Postoperative bowel ischemia was associated with hypogastric embolization (OR, 3.8; 95% CI, 1.1-13.4) and iliac angioplasty or stenting (OR, 3.5; 95% CI, 1.3-9.6). Leg ischemia was associated with unplanned graft extension (OR, 2.3; 95% CI, 1.02-5.0), other artery reconstruction (OR, 5.2; 95% CI, 1.8-15.1), thromboembolectomy (OR, 5.2; 95% CI, 1.3-20.8), and repair of arterial injury (OR, 4.6; 95% CI, 1.2-18.3). Risk factors for deterioration of renal function were iliofemoral bypass (OR, 3.9; 95% CI, 1.3-12.2), other artery reconstruction (OR, 2.7; 95% CI, 1.3-5.8), renal angioplasty or stenting (OR, 2.5; 95% CI, 1.3-4.6), and repair of arterial injury (OR, 4.5; 95% CI, 1.6-12.2). Myocardial infarction was associated with femorofemoral bypass (OR, 3.9; 95% CI, 1.7-8.7), other artery reconstruction (OR, 3.9; 95% CI, 1.6-9.2), and repair of arterial injury (OR, 6.1; 95% CI, 1.8-21.0). Wound complications were predicted by femorofemoral bypass (OR, 13.4; 95% CI, 5.8-31.1). CONCLUSIONS: Concomitant procedures during EVAR are associated with increased postoperative morbidity and mortality. The need for performing concomitant procedures should be carefully considered. The morbidity associated with intraoperative complications highlights the importance of avoidance of arterial injury and thromboembolic events where possible.

Nitrite activates AMP kinase to stimulate mitochondrial biogenesis independent of soluble guanylate cyclase.

Nitrite, a dietary constituent and endogenous signaling molecule, mediates a number of physiological responses including modulation of ischemia/reperfusion injury, glucose tolerance, and vascular remodeling. Although the exact molecular mechanisms underlying nitrite's actions are unknown, the current paradigm suggests that these effects depend on the hypoxic reduction of nitrite to nitric oxide (NO). Mitochondrial biogenesis is a fundamental mechanism of cellular adaptation and repair. However, the effect of nitrite on mitochondrial number has not been explored. Herein, we report that nitrite stimulates mitochondrial biogenesis through a mechanism distinct from that of NO. We demonstrate that nitrite significantly increases cellular mitochondrial number by augmenting the activity of adenylate kinase, resulting in AMP kinase phosphorylation, downstream activation of sirtuin-1, and deacetylation of PGC1α, the master regulator of mitochondrial biogenesis. Unlike NO, nitrite-mediated biogenesis does not require the activation of soluble guanylate cyclase and results in the synthesis of more functionally efficient mitochondria. Further, we provide evidence that nitrite mediates biogenesis in vivo. In a rat model of carotid injury, 2 weeks of continuous oral nitrite treatment postinjury prevented the hyperproliferative response of smooth muscle cells. This protection was accompanied by a nitrite-dependent upregulation of PGC1α and increased mitochondrial number in the injured artery. These data are the first to demonstrate that nitrite mediates differential signaling compared to NO. They show that nitrite is a versatile regulator of mitochondrial function and number both in vivo and in vitro and suggest that nitrite-mediated biogenesis may play a protective role in the setting of vascular injury.

Nitric oxide and nitrite-based therapeutic opportunities in intimal hyperplasia.

Vascular intimal hyperplasia (IH) limits the long term efficacy of current surgical and percutaneous therapies for atherosclerotic disease. There are extensive changes in gene expression and cell signaling in response to vascular therapies, including changes in nitric oxide (NO) signaling. NO is well recognized for its vasoregulatory properties and has been investigated as a therapeutic treatment for its vasoprotective abilities. The circulating molecules nitrite (NO(2)(-)) and nitrate (NO(3)(-)), once thought to be stable products of NO metabolism, are now recognized as important circulating reservoirs of NO and represent a complementary source of NO in contrast to the classic L-arginine-NO-synthase pathway. Here we review the background of IH, its relationship with the NO and nitrite/nitrate pathways, and current and future therapeutic opportunities for these molecules.

Nitrite-generated NO circumvents dysregulated arginine/NOS signaling to protect against intimal hyperplasia in Sprague-Dawley rats.

Vascular disease, a significant cause of morbidity and mortality in the developed world, results from vascular injury. Following vascular injury, damaged or dysfunctional endothelial cells and activated SMCs engage in vasoproliferative remodeling and the formation of flow-limiting intimal hyperplasia (IH). We hypothesized that vascular injury results in decreased bioavailability of NO secondary to dysregulated arginine-dependent NO generation. Furthermore, we postulated that nitrite-dependent NO generation is augmented as an adaptive response to limit vascular injury/proliferation and can be harnessed for its protective effects. Here we report that sodium nitrite (intraperitoneal, inhaled, or oral) limited the development of IH in a rat model of vascular injury. Additionally, nitrite led to the generation of NO in vessels and SMCs, as well as limited SMC proliferation via p21Waf1/Cip1 signaling. These data demonstrate that IH is associated with increased arginase-1 levels, which leads to decreased NO production and bioavailability. Vascular injury also was associated with increased levels of xanthine oxidoreductase (XOR), a known nitrite reductase. Chronic inhibition of XOR and a diet deficient in nitrate/nitrite each exacerbated vascular injury. Moreover, established IH was reversed by dietary supplementation of nitrite. The vasoprotective effects of nitrite were counteracted by inhibition of XOR. These data illustrate the importance of nitrite-generated NO as an endogenous adaptive response and as a pathway that can be harnessed for therapeutic benefit.

Nasal tip complications of primary cleft lip nasoplasty.

BACKGROUND AND PURPOSE: Complications of primary nasoplasty, at the time of definitive primary cheiloplasty, are underreported in the literature. This study endeavors to examine the occurrences of these complications at our cleft-craniofacial center, in an effort to identify causative factors and management strategies. A case series of patients with postoperative nasal complications after primary cleft lip nasal surgery is presented. METHODS: A retrospective chart review of primary cleft lip nasal repairs was conducted at our cleft-craniofacial center between January 2003 and December 2007. Consecutive cases of 3 staff surgeons were evaluated. Specific data points included number and type of complications, subsequent required interventions, and relevant history, with particular attention paid to the details of the primary nasoplasty. RESULTS: Eighty-six primary cleft lip nasoplasties were completed between the years 2003 and 2007. Six complications (6.9%) related to the primary cleft lip nasoplasty were identified. Four patients (4.6%) experienced nasal tip infections; all 4 required surgical drainage. Twenty-four patients (27.9%) undergoing primary cleft lip and nose repair had postoperative nostril conformers placed, and 2 (8.3%) of them experienced complications deemed conformer related. CONCLUSIONS: Postoperative nasal complications of primary cheiloplasty occur and are likely underreported. In this series, complications resulted from infection, often occurring late, and secondary to the use of nostril conformers. Surgeon awareness and caregiver education, to identify the early signs of postoperative nasal complications, are critical to the successful treatment of these occurrences. Although this study did not intend on examining antibiotic use, the significance of nasal tip infections might support the regular use of antibiotics in this population, and the use of postoperative nostril conformers must be followed closely.