Treatment Of Peripheral Arterial Disease Research Articles

Longitudinal outcomes following peripheral vascular intervention among older persons living with HIV.

Persons living with human immunodeficiency virus (HIV, PLWH) have an increased risk of peripheral artery disease (PAD) in comparison to the general population. However, a gap remains in understanding optimal management for this condition. This study assesses longitudinal outcomes associated with peripheral endovascular intervention (PVI) for PAD among PLWH. All Medicare fee-for-service patients undergoing femoropopliteal artery PVI between April 1, 2015 and December 31, 2018 were identified and stratified by HIV serostatus. The primary outcome was major adverse limb events (MALE), defined as major amputation or arterial embolism/thrombosis following an index procedure. The subdistribution hazard was used to evaluate the association between HIV serostatus and MALE, accounting for the competing risk of death. Results were adjusted for sociodemographics and major comorbidities. Of 168,553 patients who underwent PVI, 357 (0.21%) were PLWH. The average age was 77.0 ± 7.6 years; 80.3% had hypertension, 70.3% had hyperlipidemia, and 24.6% had tobacco use disorder. Compared to those without HIV, PLWH were younger and had a higher burden of cardiovascular risk factors. MALE were substantially more frequent among PLWH, with a cumulative incidence of 24.6%, compared to 14.5% among those without HIV. The adjusted subdistribution hazard ratio was 1.26 (95% CI 1.00-1.58, p = 0.05). The use of guideline-directed statin therapy was low in both groups in the 90 days following revascularization (57.9% in PLWH vs 58.1% in those without HIV, p = 0.95). Among US Medicare beneficiaries, PLWH had poorer long-term outcomes following PVI. Greater attention to the management of symptomatic PAD is warranted for the HIV population, particularly following revascularization.

The Association Between Ankle-Brachial Index and Daily Patterns of Physical Activity: Results From the Hispanic Community Health Study/Study of Latinos.

Peripheral artery disease (PAD) is associated with lower physical activity but less is known about its association with daily patterns of activity. We examined the cross-sectional association between ankle-brachial index (ABI) and objectively measured patterns of physical activity among Hispanic/Latino adults. We analyzed data from 7 688 participants (aged 45-74 years) in the Hispanic Community Health Study/Study of Latinos. ABI was categorized as low (≤0.90, indicating PAD), borderline low (0.91-0.99), normal (1.00-1.40), and high (>1.40, indicating incompressible ankle arteries). Daily physical activity metrics derived from accelerometer data included: log of total activity counts (LTAC), total log-transformed activity counts (TLAC), and active-to-sedentary transition probability (ASTP). Average differences between ABI categories in physical activity, overall and by 4-hour time-of-day intervals, were assessed using linear regression and mixed-effects models, respectively. In Hispanic/Latino adults, 5.3% and 2.6% had low and high ABIs, respectively. After adjustment, having a low compared to a normal ABI was associated with lower volume (LTAC = -0.13, p < .01; TLAC = -74.4, p = .04) and more fragmented physical activity (ASTP = 1.22%, p < .01). Having a low ABI was linked with more fragmented physical activity after 12 pm (p < .01). Having a high ABI was associated with lower volumes of activity (TLAC = -132.0, p = .03). Having a low or high ABI is associated with lower and more fragmented physical activity in Hispanic/Latino adults. In adults with low ABI, physical activity is more fragmented in the afternoon to evening. Longitudinal research is warranted to expand these findings to guide targeted interventions for PAD or incompressible ankle arteries.

A Framework for Characterizing Delays in Urgent Peripheral Arterial Disease Interventions

A Framework for Characterizing Delays in Urgent Peripheral Arterial Disease Interventions

Evaluation of the treatment volume and removal rate of Rheocarna: A novel adsorption-type blood purification device for patients with chronic limb-threatening ischemia.

Chronic limb-threatening ischemia (CLTI) is a clinical syndrome defined by peripheral arterial disease (PAD) combined with rest pain, gangrene, or leg ulceration for longer than two weeks resulting in lower extremity amputation. In recent years, low-density lipoprotein apheresis (LDL-A) has been implemented for PAD treatment. However, it has not been possible to ensure insurance coverage for patients with lower LDL levels than 140 mg/dL under cholesterol-lowering drugs. Rheocarna is a novel adsorption-type blood purification device for the treatment of CLTI by adsorbing LDL and fibrinogen (Fib) that is not constrained by hypercholesterolemia and is not amenable to or nonresponsive to revascularization surgery. The only requirements for use are that the blood flow rate increases up to 200 mL/min gradually. To evaluate the applicability of this treatment procedure, we compared the removal rates of Fib and LDL following Rheocarna therapy using various blood treatment volumes (6, 10.5, and 19.5 L). Fib and LDL removal rates were about 20% and 15%-25% per treatment, with no significant differences between treatment volumes. Following treatment with Rheocarna, blood pressure tends to decrease at first, which later increases, and the higher the treatment volume, the longer the time of low blood pressure tended to be. Although no significant difference was found in the removal rate of Fib and LDL in response to increase volume to 6 L or beyond in this study, the 6 L volume is considered effective enough for the removal of Fib and LDL.

Five Year Survival in Medicare Patients Undergoing Interventions for Peripheral Arterial Disease: a Retrospective Cohort Analysis of Linked Registry Claims Data

To justify upfront risks of offering elective interventions for intermittent claudication (IC), patients should have reasonable life expectancy to derive durable clinical benefits. Open surgery for chronic limb threatening ischaemia (CLTI) is maximally beneficial in patients surviving ≥ 2 years. Our goal was to assess long term survival after IC and CLTI interventions. In a retrospective cohort analysis, the Vascular Quality Initiative (VQI) registry from 1 January 2010 to 31 May 2021 was queried for peripheral vascular intervention (PVI), infra-inguinal bypasses (IIB), and supra-inguinal bypasses (SIB) for IC and CLTI across 286 US centres. VQI linkage to Medicare insurance claims provided 5 year survival data. Multivariable analysis identified factors associated with 5 year mortality. There were 31 457 PVIs (44.7% IC, 55.3% CLTI), 7 978 IIBs (26.9% IC, 73.1% CLTI), and 2 149 SIBs (50.1% IC, 49.9% CLTI) recorded in the VQI. Among PVI, IIB, and SIB cohorts, average ages were 75, 73, and 72 years, respectively. Respective 5 year mortality after PVI for IC and CLTI was 37.2% and 71.1%; after IIB for IC and CLTI it was 37.8% and 60%; and after SIB for IC and CLTI it was 33.8% and 53.8%. On multivariable analysis, across all procedures, end-stage renal disease, CLTI, congestive heart failure, anaemia, chronic obstructive pulmonary disease, and prior amputation were independently associated with increased mortality. Pre-admission home living and pre-operative aspirin use were independently associated with decreased mortality. Long term survival in Medicare patients undergoing interventions in VQI centres for peripheral arterial disease is poor. Two thirds of CLTI patients and over one third of IC patients were not alive at 5 years. Intervening for IC in patients with high mortality risk should be avoided. For CLTI patients identified with decreased survival likelihood, intervention durability may be less important than invasiveness. Pre-operative medical optimisation should always be undertaken.

Abstract P3015: Mechanosensitive, Piezo2 Channels Mediate The Exaggerated Exercise Pressor Reflex In A Mouse Model Of Hind Limb Ischemia.

The exercise pressor reflex (EPR) is a reflexive mechanism in which blood pressure and heart rate increase in response to afferent neuron activation by skeletal muscle contraction. Patients with peripheral artery disease (PAD) have an exaggerated EPR, contributing to exercise intolerance, morbidity and mortality. Recently, we developed a mouse model which we used to determine the effect of femoral artery ligation (FAL) on the EPR. We observed that the EPR is exaggerated 72 hrs following FAL in mice. Stimulation of metabolically active afferent neurons was not different between FAL and control. In contrast, the responses induced by static contraction (stimulation of both mechanically and metabolically sensitive afferent fibers) and passive stretch (preferential stimulation of mechanically sensitive afferent neurons) were exaggerated in FAL mice when compared to control. These exaggerated responses were not affected by SB-705498 (a TRPv1 receptor inhibitor) but were nearly abolished by Gadolinium (a mechanical sensitive group III afferent neuron inhibitor) and significantly reduced by GsMTx-4 (a selective inhibitor of the PIEZO2 receptor).. Furthermore, we observed that PIEZO2 expression was upregulated in the dorsal root ganglia (DRG) from FAL mice compared to controls. Importantly, FAL mice displayed a decreased exercise capacity when compared to control mice, verifying that this mouse model mimics human PAD and supporting the notion that an exaggerated EPR contributes to exercise intolerance. These results further indicate that the exaggerated EPR in FAL is mediated, in part, by the PIEZO2 receptor. To explore this, we generated mice with a conditional, DRG targeted, deletion of Piezo2 . In these mice, we observed that the responses to static contraction and passive stretch were significantly reduced compared to control. Moreover, we performed whole-cell voltage-clamp on dissociated DRG observing increased negative pressure induced inward currents in the setting of FAL while these currents were decreased in the Piezo2 -/- DRG. These data indicate that PIEZO2 expression may serve as a therapeutic target in the treatment of PAD.

Longitudinal Pathways Between Physical Activity, Depression, and Perceived Stress in Peripheral Artery Disease.

One-fifth of the patients with peripheral artery disease (PAD) experience depression and stress. Depression and stress may impact patients' abilities to be physically active, a key recommendation for supporting overall PAD management to improve symptoms and reduce the risk of cardiovascular events. We aimed to study interrelationships between 1-year longitudinal trajectories of depression, stress, and physical activity following a PAD diagnosis. Patients with new or worsening PAD symptoms enrolled at 10 US PORTRAIT study (Patient-Centered Outcomes Related to Treatment Practices in Peripheral Arterial Disease: Investigating Trajectories) vascular specialty clinics (CT, LA, MI, MO, NC, OH, and RI) were assessed at baseline, 3, 6, and 12 months between June 2, 2011 and December 3, 2015. Depressive symptoms were measured with the 8-item Patient Health Questionnaire, perceived stress with the 4-item Perceived Stress Scale and physical activity with items from the INTERHEART study. Path analysis was used to examine the longitudinal relationship between depression and physical activity and perceived stress and physical activity. A total of 766 patients were included (mean age of 68.2 [±9.4] years; 57.7% male). Overall, 17.8% reported significant depressive symptoms, 36.0% experienced increased perceived stress, and 44.1% were sedentary upon PAD diagnosis. A decrease in physical activity preceded a rise in subsequent depressive symptoms (β ranges -0.45 [95% CI, -0.80 to -0.09]; -0.81 [95% CI, -1.19 to 0.42]) over the course of 1 year. Low physical activity scores at the initial presentation were followed by high perceived stress at 3 months (β=-0.44 [95% CI, -0.80 to -0.07]). In symptomatic PAD, a decrease in physical activity was followed by an increased risk of depressive symptoms and perceived stress at subsequent intervals over the course of 1 year following PAD diagnosis and treatment. Integrated behavioral health approaches for PAD, addressing physical activity and managing depression or distress, are indicated as collective PAD treatment goals.

Consensus minimum core data elements adapted to peripheral vascular intervention in the drug-eluting era: Consensus report from the Registry Assessment of Peripheral Interventional Devices (RAPID) Pathways “LEAN” working group

Registry Assessment of Peripheral Interventional Devices (RAPID) initiated the Pathways Program to provide a transparent, collaborative forum in which to pursue insights into multiple unresolved questions on benefit-risk of paclitaxel-coated devices, including understanding the basis of the mortality signal, without a demonstrable potential biological mechanism, and whether the late mortality signal could be artifact intrinsic to multiple independent prospective randomized data sources that did not prespecify death as a long-term end point. In response to the directive, the LEAN-Case Report Form working group focused on enhancements to the RAPID Phase I Minimum Core Data set through the addition of key clinical modifiers that would be more strongly linked to longer-term mortality outcomes after peripheral arterial disease intervention in the drug-eluting device era, with the goal to have future mortality signals more accurately examined.

A Novel Endovascular Robotic System for Treatment of Lower Extremity Peripheral Arterial Disease: First-in-Human Experience.

To assess the feasibility and first-in-human experience of a novel endovascular robotic system for treatment of lower extremity peripheral arterial disease (PAD). Between November 2021 and January 2022, consecutive patients with obstructive lower extremity PAD and claudication (Rutherford 2-5) with >50% stenosis demonstrated on angiography were enrolled in this study. Lower extremity peripheral arterial intervention was performed using the endovascular robotic system, which consisted of a bedside unit and an interventional console. The primary endpoints were technical success, defined as the successful manipulation of the lower extremity peripheral arterial devices using the robotic system, and safety. The secondary endpoints were clinical success, defined as 50% residual stenosis at the completion of the robot-assisted procedure without major adverse cardiac events and radiation exposure. In total, 5 patients with PAD were enrolled in this study (69.2±6.0 years; 80% men). The novel endovascular robotic system successfully completed the entire procedure of endovascular treatment of lower extremity PAD. Conversion to manual operation, including advancement, retracement, rotation of the guidewires, catheters, sheaths, deployment, and release of the balloons and stent grafts, was not necessary. We achieved the criteria for clinical procedural and technical success in all patients. No deaths, myocardial infarctions, or ruptures occurred in the period up to 30 days after the procedure, and no device-related complications were observed. The robotic system operator had 97.6% less radiation exposure than that at the procedure table, with a mean of 1.40±0.49 μGy. This study demonstrated the safety and feasibility of the robotic system. The procedure reached technical and clinical performance metrics and resulted in significantly lower radiation exposure to the operators at the console compared with that at the procedure table. There were some reports about several robotic systems used in the peripheral arterial disease, but no robotic system was able to perform entire procedure of endovascular treatment of lower extremity peripheral arterial disease (PAD).To solve this problem, we designed a remote-control novel endovascular robotic system. It was the first robotic system that can perform entire procedure of endovascular treatment of PAD worldwide. A novelty retrieval report about this is provided in the supplementary materials.The robotic system is compatible with all commercial endovascular surgical devices currently available in the market, including guidewires, catheters and stent delivery systems. It can perform all types of motion, such as forward, backward, and rotation to meet the requirements of all types of endovascular procedures. During the operation, the robotic system can perform these operations in a fine-tuned manner, so it is easy to cross the lesions, which is the key factor influencing the success rate of the operation. In addition, the robotic system can effectively reduce the exposure time to radiation, thereby reducing the risk of occupational injury.

Intravascular Ultrasound in Endovascular Interventions for Peripheral Artery Disease

Intravascular Ultrasound in Endovascular Interventions for Peripheral Artery Disease

Treatment of Peripheral Artery Disease Using Injectable Biomaterials and Drug-Coated Balloons: Safety and Efficacy Perspective.

The possibility of injectable biomaterials being used in the therapy of peripheral artery disease (PAD) is investigated in this article. We conducted a thorough review of the literature on the use and efficacy of biomaterials (BMs) and drug-coated balloons (DCBs). These BMs included hydrogels, collagen scaffolds, and nanoparticles. These BMs could be used alone or in combination with growth factors, stem cells, or gene therapy. The treatment of peripheral artery disease with DCBs is increasingly common in the field of interventional angiology. Studies have been carried out to examine the effectiveness of paclitaxel-coated balloons such as PaccocathTM in lowering the frequency with which further revascularization operations are required. PCB angioplasty and angioplasty without paclitaxel did not significantly vary in terms of mortality, according to the findings of a recent meta-analysis that included the results of four randomized controlled studies. On the other hand, age was found to be a factor that predicted mortality. There was a correlation between the routine utilization of scoring balloon angioplasty along with DCBs and improved clinical outcomes in de novo lesions. In both preclinical and clinical testing, the SelutionTM DCB has demonstrated efficacy and safety, but further research is required to determine whether or not it is effective and safe over the long term. In addition, we reviewed the difficulties involved in bringing injectable BMs-based medicines to clinical trials, including the approval processes required by regulatory bodies. Injectable BMs have a significant amount of therapeutic promise for PAD, which highlights the need for more research and clinical studies to be conducted in this field. In conclusion, this research focuses on the potential of injectable BMs and DCBs in the treatment of PAD as well as the hurdles that must be overcome in order to translate these treatments into clinical trials. In this particular field, there is a demand for further research as well as clinical trials.

An interpretable machine learning model for the prevention of contrast-induced nephropathy in patients undergoing lower extremity endovascular interventions for peripheral arterial disease

BackgroundContrast-induced nephropathy (CIN) is a postprocedural complication associated with increased morbidity and mortality. An important risk factor for development of CIN is renal impairment. Identification of patients at risk for acute renal failure will allow physicians to make appropriate decisions to minimize the incidence of CIN. We developed a machine learning model to stratify risk of acute renal failure that may assist in mitigating risk for CIN in patients with peripheral artery disease (PAD) undergoing endovascular interventions. MethodsWe utilized the American College of Surgeons National Surgical Quality Improvement Program database to extract clinical and laboratory information associated with 14,444 patients who underwent lower extremity endovascular procedures between 2011 and 2018. Using 11,604 cases from 2011 to 2017 for training and 2840 cases from 2018 for testing, we developed a random forest model to predict risk of 30-day acute renal failure following infra-inguinal endovascular procedures. ResultsEight variables were identified as contributing optimally to model predictions, the most important being diabetes, preoperative BUN, and claudication. Using these variables, the model achieved an area under the receiver-operating characteristic (AU-ROC) curve of 0.81, accuracy of 0.83, sensitivity of 0.67, and specificity of 0.74. The model performed equally well on white and nonwhite patients (Delong p-value = 0.955) and patients age < 65 and patients age ≥ 65 (Delong p-value = 0.659). ConclusionsWe develop a model that fairly and accurately stratifies 30-day acute renal failure risk in patients undergoing lower extremity endovascular procedures for PAD. This model may assist in identifying patients who may benefit from strategies to prevent CIN.

Doctors, not facilities, perform procedures

Chow et al 1 Chow C.Y. Mathlouthi A. Zarrintan S. Swafford E. Siracuse J.J. Malas M.B. Outcomes of elective peripheral endovascular interventions for peripheral arterial disease performed in hospital outpatient departments versus ambulatory surgical centers versus office-based labs. J Vasc Surg. 2023; 77: 1732-1740 Google Scholar have provided us with an interesting paper that details differences in equipment utilization, risk factors, complications, and technical outcomes in outpatient facilities where patients with peripheral arterial disease are treated. Typical of a paper from a Vascular Quality Initiative data review, we are overwhelmed with facts and figures. However, in this forest of data, there is one tree that stands out. Patients’ demographics, comorbidities, indications, and treatment will differ depending on whether they are treated in a hospital outpatient department (HOPD), ambulatory surgical center (ASC), or outpatient-based lab (OBL). Outcomes of elective peripheral endovascular interventions for peripheral arterial disease performed in hospital outpatient departments, ambulatory surgical centers and office-based labsJournal of Vascular SurgeryVol. 77Issue 6PreviewA recent shift in the location where peripheral endovascular interventions (PVI) are performed has occurred, from traditional settings such as hospital outpatient departments (HOPD), to ambulatory surgical centers (ASC) and outpatient-based laboratories (OBL). Different settings may influence the safety and efficacy of the PVI, as well as how it is done. This study aims to compare the postprocedural outcomes and intraprocedural details between the three settings. Full-Text PDF

Impact of Dual Eligibility on Surgical Outcomes After Lower Extremity Bypass or Peripheral Vascular Intervention

Dual eligibility for Medicare and Medicaid is more common among Black and lower socioeconomic status patients than traditional Medicare and has been associated with worse health outcomes. Given that peripheral artery disease (PAD) disproportionately affects this underserved population, we sought to assess the impact of dual eligibility on surgical outcomes after lower extremity bypass (LEB) or peripheral vascular intervention (PVI) for PAD. A retrospective analysis was conducted of all LEB and PVI procedures between 2010 and 2018 with Medicare-match data in the VQI-VISION (Vascular Quality Initiative Vascular Implant Surveillance and Interventional Outcomes Network) database. The sample was restricted to first-record LEB or PVI procedures in fee-for-service beneficiaries over the age of 65 who were either covered by traditional Medicare alone or were dually eligible for Medicare and Medicaid. The two groups were compared with identify baseline demographic differences. Inverse probability weighting with Cox regression was used to determine adjusted associations with death, major amputation, and amputation-free survival (AFS), for which, the time to major amputation was calculated with death as a competing risk. Of 46,032 patients in our sample, 12,872 (28.0%) were dually eligible for Medicare and Medicaid, whereas 33,160 (72.0%) had traditional Medicare only. Similar proportions of dually eligible and traditional Medicare patients underwent LEB (18.5%) and PVI (81.5%) for PAD. Before inverse probability weighting, dually eligible patients were more likely than traditional Medicare patients to be female (48.0% vs 37.9%, P < .00001), Black (25.1% vs 10.0%, P < .00001), and have lower median household income ($50,885 vs $60,306, P < .0001). On unadjusted analysis, rates of long-term mortality (42.3% vs 35.1%, P < .0001) and major amputation (19.4% vs 10.7%, P < .0001) were higher in the dually eligible cohort. After inverse probability weighting, dually eligible patients had a higher hazard of death relative to traditional Medicare patients after LEB or PVI for PAD (hazard ratio [HR]: 1.39 [95% confidence interval (CI): 1.34-1.45], P < .0001) as well as a higher hazard of major amputation (HR: 1.27 [95% CI: 1.19-1.36], P < .0001). On Fine-Gray analysis of AFS, dually eligible patients were found to have a 21% higher hazard of amputation or death (HR: 1.21 [95% CI: 1.14-1.27], P < .0001) (Fig). Findings were similar when LEB and PVI were analyzed separately. Compared with traditional Medicare, dual eligibility was associated with higher hazards of death and major amputation and lower AFS after LEB or PVI for PAD. This suggests possible deficiencies in insurance coverage or coordination for dually eligible patients with PAD, requiring further investigation.

E-Selectin/AAV Gene Therapy Promotes Myogenesis and Skeletal Muscle Recovery in a Mouse Hindlimb Ischemia Model.

The response to ischemia in peripheral artery disease (PAD) depends on compensatory neovascularization and coordination of tissue regeneration. Identifying novel mechanisms regulating these processes is critical to the development of nonsurgical treatments for PAD. E-selectin is an adhesion molecule that mediates cell recruitment during neovascularization. Therapeutic priming of ischemic limb tissues with intramuscular E-selectin gene therapy promotes angiogenesis and reduces tissue loss in a murine hindlimb gangrene model. In this study, we evaluated the effects of E-selectin gene therapy on skeletal muscle recovery, specifically focusing on exercise performance and myofiber regeneration. C57BL/6J mice were treated with intramuscular E-selectin/adeno-associated virus serotype 2/2 gene therapy (E-sel/AAV) or LacZ/AAV2/2 (LacZ/AAV) as control and then subjected to femoral artery coagulation. Recovery of hindlimb perfusion was assessed by laser Doppler perfusion imaging and muscle function by treadmill exhaustion and grip strength testing. After three postoperative weeks, hindlimb muscle was harvested for immunofluorescence analysis. At all postoperative time points, mice treated with E-sel/AAV had improved hindlimb perfusion and exercise capacity. E-sel/AAV gene therapy also increased the coexpression of MyoD and Ki-67 in skeletal muscle progenitors and the proportion of Myh7+ myofibers. Altogether, our findings demonstrate that in addition to improving reperfusion, intramuscular E-sel/AAV gene therapy enhances the regeneration of ischemic skeletal muscle with a corresponding benefit on exercise performance. These results suggest a potential role for E-sel/AAV gene therapy as a nonsurgical adjunct in patients with life-limiting PAD.

Association between corrected QT interval and long-term cardiovascular outcomes in elderly patients who had undergone endovascular therapy for lower extremity arterial disease.

Population-based studies have reported the association between prolonged corrected QT (QTc) intervals and an increased risk of adverse cardiovascular events. Data regarding the association between longer QTc intervals and incident cardiovascular outcomes in patients with lower extremity arterial disease (LEAD) are scarce. To examine the impact of QTc interval on long-term cardiovascular outcomes in elderly patients with symptomatic LEAD. This cohort study extracted data from the Tzu-chi Registry of ENDovascular Intervention for Peripheral Artery Disease (TRENDPAD) and enrolled 504 patients aged ≥ 70 treated with endovascular therapy for atherosclerotic LEAD from July 1, 2005, to December 31, 2019. The main outcomes of interest were all-cause mortality and major adverse cardiovascular events (MACE). Multivariate analysis was conducted using the Cox proportional hazard model to determine independent variables. We performed interaction analysis between corrected QT and other covariates and Kaplan-Meier analysis to compare the outcome of interest among the groups stratified by the tercile of QTc intervals. A total of 504 patients [235 men (46.6%); mean age, 79.9 ± 6.2 years; mean QTc interval, 459 ± 33 msec] entered the final data analysis. We categorized the baseline patient characteristics according to terciles of QTc intervals. During the median follow-up time of 3.15 (interquartile ranges, 1.65-5.42) years, we noted 264 deaths and 145 MACEs. The 5-year rates of freedom from all-cause mortality (71% vs. 57% vs. 31%, P < 0.001) and MACEs (83% vs. 67% vs. 46%, P < 0.001) were significantly different among the tercile groups. Multivariate analysis showed that a 1-SD increase in the QTc interval increased the risk of all-cause mortality [hazard ratio (HR) 1.49, P < 0.001] and MACEs (HR 1.59, P < 0.001) after adjusting for other covariates. The interaction analysis showed that QTc interval and C-reactive protein levels were most strongly associated with death (HR = 4.88, 95% CI 3.09-7.73, interaction P < 0.001) and MACEs (HR = 7.83, 95% CI 4.14-14.79, interaction P < 0.001). In elderly patients with symptomatic atherosclerotic LEAD, a prolonged QTc interval is associated with advanced limb ischemia, multiple medical comorbidities, increased risk of MACEs, and all-cause mortality.

Serum Levels of Matrix Metalloproteinases in Patients Undergoing Endovascular Intervention for Peripheral Arterial Disease

Matrix metalloproteinases (MMPs) play a significant role in the development and progression of atherosclerotic vascular disease. The purpose of this study was to measure and document the profile of plasma-circulating MMPs in patients with peripheral arterial disease (PAD) undergoing endovascular revascularization. This was a single-center prospective observational study with 80 patients with PAD enrolled. They underwent percutaneous balloon angioplasty and/or angioplasty with stent. Exclusion criteria were acute limb ischemia, active inflammation, wet gangrene, liver disease, end-stage renal failure, and cancer. Patients that underwent open or hybrid (open and endovascular) approach were also excluded from the study. Venous blood samples were taken preoperatively, 24hr, and 6months postoperatively. The values of MMP-2, MMP-3, MMP-7, MMP-9, and their inhibitors (tissue inhibitor of metalloproteinases [TIMP]), TIMP-1 and TIMP-2 were measured. The mean age was 67.1years, and 66 of them (82.5%) were male. During the clinical follow-up (mean 35.8% months), 12 patients died (16.4%), 15 (20.5%) of them had a major adverse limb event (MALE), and 14 (19.2%) of them had a major adverse cardiovascular event (MACE). There was a statistically significant rise in the values of MMP-2, MMP-3, and MMP-7 at 6months postoperatively, when compared to the preoperative and 24hr postoperative values. There was no correlation of MMP and TIMP values with mortality, MALE, and MACE events. The present single-center prospective study documented increased circulating levels of MMPs postoperatively in PAD patients undergoing endovascular treatment. Vascular trauma caused by angioplasty could trigger the expression of MMPs and TIMPs, but the absence of any association with clinical complications requires further investigation.

Abstract 298: Roles Of Tet2 In Vascular Regeneration For Peripheral Artery Disease

Peripheral artery disease (PAD) is the manifestation of atherosclerosis in the extremity, causing blockage of blood vessels that reduces blood flow to the lower limb (ischemia). End-stage PAD patients require limb amputation, with increased risk of morbidity and mortality from heart attacks. Although PAD affects &gt;200 million individuals worldwide, surgery remains the only endpoint option that itself is associated with significant morbidity and mortality. Novel treatment for PAD is therefore urgently needed. Despite vascular smooth muscle cells (VSMC) being essential for normal vascular formation and repair, their role in PAD pathogenesis has been largely ignored. Our lab has long been specialised in studying VSMC biology, and was the first to identify a DNA demethylase, Tet2, as a master regulator of VSMC functions ( Liu et al, Circulation. 2013 ). We found without Tet2, VSMCs form pathological and weakened arteries that lead to restenosis, the precursor of atherosclerosis. Given the vital role VSMC in vessel formation, we hypothesise that restoring Tet2 expression to ischaemic tissues is critical for promoting angiogenesis, blood flow recovery and to prevent tissue caused by PAD. Using a VSMC-specific Tet2 knockout (VSM- Tet2 KO ) mouse line generated by the Liu lab at VCCRI, we studied the vasculo-protective role of TET2 in PAD by mimicking PAD through femoral artery ligation. Our preliminary data demonstrates: (1) severe tissue necrosis and amputation in the knockout mice following surgery that is not observed in controls (2) Loss of Tet2 reduces blood flow to the foot as suggested by laser doppler measurements. (3) Significantly retarded neovascularisation in ischemic muscle regions displayed by micro-computer tomography scans . These are the first data to demonstrate Tet2’s role in PAD.

C-31 | Impact of Marijuana Use on Prevalence and Interventions in Peripheral Artery Disease

The growing legalization of marijuana use warrants investigation of its various effects on the vasculature. We aim to determine whether marijuana users have an increased risk of peripheral artery disease (PAD) and subsequent surgical intervention. De-identified patient data from the National Inpatient Sample (NIS) from 2016-2019 were queried. Inclusion criteria included a diagnosis of marijuana use and peripheral artery disease. Patients were further stratified based on any percutaneous lower extremity vascular intervention. Data was analyzed using SPSS software in a binary logistic regression model, a p value <0.001 was considered statistically significant, and samples were standardized for comparison using predicted probabilities. Of the 30m+ patients in the NIS from 2016 to 2019, there were 623,768 patients diagnosed as marijuana users. These patients had an average age of 37.4 years, even distribution across genders, were more likely to be white and more likely to be elective admissions (p<0.001). Of these patients, 2,424 (0.38%) were concomitantly diagnosed with PAD. Marijuana users were at more than three times the risk of developing PAD (OR= 3.68, p<0.001) but had no statistically significant increased risk for mortality or requiring percutaneous intervention (p<0.001). Marijuana users are at a markedly increased risk of being diagnosed with PAD but are at no increased risk of requiring intervention nor mortality from their peripheral ischemia. Possible mechanisms for this increased risk may involve changes in coagulability and peripheral vascular tone from marijuana use. Vigilant monitoring for disease screening and progression should be initiated earlier in the outpatient setting in conjunction with cessation counseling.

C-58 | The In-Hospital Outcomes of Atherectomy for Peripheral Arterial Disease Among Obese and Non-Obese Patients: An Insight from the National Inpatient Sample Database

Atherectomy is one of the treatment options for symptomatic peripheral arterial disease (PAD). Previous studies have revealed an obesity paradox for PAD patients, with better outcomes in obese than non-obese patients. The purpose was to compare the in-hospital outcomes among obese and non-obese patients undergoing atherectomy. We performed a cross-sectional analysis on 105320 patients who underwent atherectomy for PAD based on ICD-10-PCS codes during hospitalization from January 2016 to December 2018 using the National Inpatient Sample database. They were stratified into obese (BMI ≥ 30) and non-obese groups (BMI <30). The primary outcome was in-hospital mortality. 105190 patients were included in the study (<18 years of age excluded), with 15170 obese and 90020 non-obese. The observed in-hospital mortality was 2.5% and 3.5 % in obese and non-obese groups, respectively, with a p-value of <0.001. There was a higher proportion of patients with smoking in non-obese vs. obese group (28.8% vs. 23.8%). The difference in mortality disappeared after adjusting for confounding factors (2.5% vs. 2.8% in obese vs. non-obese with p-value of 0.11). The obese group continued to have higher hospitalization costs, and more patients required discharge to skilled nursing facility even after adjusting for confounders (Table 1). Smoking was the major confounder while adjusting for other factors didn’t make any difference. Our analysis did not show any difference in in-hospital mortality among obese and non-obese patients undergoing atherectomy for PAD. The obesity paradox needs to be further studied in context of intervention for PAD.