Outcomes of transcatheter aortic valve replacement in patients with cardiogenic shock.

AIMS: The safety and efficacy of transcatheter aortic valve replacement (TAVR) with contemporary balloon expandable transcatheter valves in patients with cardiogenic shock (CS) remain largely unknown. In this study, the TAVRs performed for CS between June 2015 and September 2022 using SAPIEN 3 and SAPIEN 3 Ultra bioprosthesis from the Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry were analysed. METHODS AND RESULTS: CS was defined as: (i) coding of CS within 24 h on Transcatheter Valve Therapy Registry form; and/or (ii) pre-procedural use of inotropes or mechanical circulatory support devices and/or (iii) cardiac arrest within 24 h prior to TAVR. The control group was comprised of all the other patients undergoing TAVR. Baseline characteristics, all-cause mortality, and major complications at 30-day and 1-year outcomes were reported. Landmark analysis was performed at 30 days post-TAVR. Cox-proportional multivariable analysis was performed to determine the predictors of all-cause mortality at 1 year. A total of 309 505 patients underwent TAVR with balloon-expandable valves during the study period. Of these, 5006 patients presented with CS prior to TAVR (1.6%). The mean Society of Thoracic Surgeons score was 10.76 ± 10.4. The valve was successfully implanted in 97.9% of patients. Technical success according to Valve Academic Research Consortium-3 criteria was 94.5%. In a propensity-matched analysis, CS was associated with higher in-hospital (9.9% vs. 2.7%), 30-day (12.9% vs. 4.9%), and 1-year (29.7% vs. 22.6%) mortality compared to the patients undergoing TAVR without CS. In the landmark analysis after 30 days, the risk of 1-year mortality was similar between the two groups [hazard ratio (HR) 1.07, 95% confidence interval (CI) 0.95-1.21]. Patients who were alive at 1 year noted significant improvements in functional class (Class I/II 89%) and quality of life (ΔKCCQ score +50). In the multivariable analysis, older age (HR 1.02, 95% CI 1.02-1.03), peripheral artery disease (HR 1.25, 95% CI 1.06-1.47), prior implantation of an implantable cardioverter-defibrillator (HR 1.37, 95% CI 1.07-1.77), patients on dialysis (HR 2.07, 95% CI 1.69-2.53), immunocompromised status (HR 1.33, 95% CI 1.05-1.69), New York Heart Association class III/IV symptoms (HR 1.50, 95% CI 1.06-2.12), lower aortic valve mean gradient, lower albumin levels, lower haemoglobin levels, and lower Kansas City Cardiomyopathy Questionnaire scores were independently associated with 1-year mortality. CONCLUSION: This large observational real-world study demonstrates that the TAVR is a safe and effective treatment for aortic stenosis patients presenting with CS. Patients who survived the first 30 days after TAVR had similar mortality rates to those who were not in CS.

The Single-access for Hi-risk PCI (SHiP) technique.

Currently, the Impella CP (Abiomed, Danvers, Massachusetts) percutaneous ventricular assist catheter requires implantation through a 14 French sheath. Additional arterial access is commonly obtained to perform therapeutic or diagnostic procedures. Multiple arterial access requires time and results in increased risk for vascular complications. Some patients may have limited arterial access. We describe the Single-access for Hi-risk PCI (SHiP) technique to allow for rapid and safer single access utilizing only the Impella access site. After the Impella catheter is placed in the standard fashion, a micropuncture needle is used to pierce the hemostasis valve of the Impella insertion sheath. After dilating the hemostasis valve and exchanging for a 0.035″ wire, up to a 7 French sheath can be inserted for PCI within the 14 French access sheath and alongside the 9 French portion of the Impella catheter. After PCI, the sheath is removed. We report on a case series of 17 patients using this technique. There were no instances of bleeding during the procedure or after removal of the PCI sheath, and no evidence of disruption of the Impella sheath.

Transcatheter Aortic Valve Replacement Outcomes in End-Stage Renal Disease Patients on Hemodialysis Requiring Midodrine.

Background: Patients with dialysis-dependent end-stage renal disease (ESRD) taking midodrine may be at high risk for poor outcomes following transcatheter aortic valve replacement (TAVR). We evaluated dialysis-dependent ESRD patients taking midodrine. Methods: We conducted a retrospective analysis of non-clinical trial TAVR patients from February 2012 to December 2020 from 11 facilities in a Western US health system. Patient groups included ESRD patients on midodrine before TAVR (ESRD [+M]), ESRD patients without midodrine (ESRD [-M]), and non-ESRD patients. The endpoints of 30-day and 1-year mortality were represented by Kaplan-Meier survival estimator and compared by log-rank test. Results: Forty-five ESRD (+M), 216 ESRD (-M), and 6898 non-ESRD patients were included. ESRD patients had more comorbid conditions, despite no significant difference in predicted Society of Thoracic Surgeons mortality risk between ESRD (+M) and ESRD (-M) (8.7% vs. 9.2%, p = 0.491). Thirty-day mortality was significantly higher for ESRD (+M) patients vs. ESRD (-M) patients (20.1% vs. 5.6%, p = 0.001) and for ESRD (+M) vs. non-ESRD patients (2.5%, p < 0.001). One-year mortality trended higher for ESRD (+M) vs. ESRD (-M) patients (41.9% vs. 29.8%, p = 0.07), and was significantly higher for ESRD (+M) vs. non-ESRD patients (10.7%, p < 0.001). Compared to ESRD (-M), ESRD (+M) patients had a higher incidence of 30-day stroke (6.7% vs. 1.4%, p = 0.033), 30-day vascular complications (6.7% vs. 0.9%, p = 0.011), and a lower rate of discharge to home (62.2% vs. 84.7%, p < 0.001). In contrast, ESRD (-M) patients had no significant differences from non-ESRD patients for these outcomes. Conclusions: Our experience suggests ESRD patients on midodrine are a higher acuity population with worse survival after TAVR, compared to ESRD patients not on midodrine. These findings may help with risk stratification for ESRD patients undergoing TAVR.

Safety and efficiency of percutaneous coronary intervention using a standardised optical coherence tomography workflow.

BACKGROUND: While intravascular imaging guidance during percutaneous coronary intervention (PCI) improves outcomes, routine intravascular imaging usage remains low, in part due to perceived inefficiency and safety concerns.  Aims: The LightLab (LL) Initiative was designed to evaluate whether implementing a standardised optical coherence tomography (OCT) workflow impacts PCI safety metrics and procedural efficiency. METHODS: In this multicentre, prospective, observational study, PCI procedural data were collected over 2 years from 45 physicians at 17 US centres. OCT-guided PCI incorporating the LL workflow (N=264), a structured algorithm using routine pre- and post-PCI OCT imaging, was compared with baseline angiography-only PCI (angio) (N=428). Propensity score analysis identified 207 matched procedures. Outcomes included procedure time, radiation exposure, contrast volume, device utilisation, and treatment strategy. RESULTS: Compared with angiography alone, LL workflow OCT-guided PCI increased the median procedural time by 9 minutes but reduced vessel preparation time (2 min LL workflow vs 3 min angio; p<0.001) and resulted in less unplanned additional treatment (4% LL workflow vs 10% angio; p=0.01). With LL workflow OCT guidance, fewer cineangiography views were needed compared to angiography guidance, leading to decreased radiation exposure (1,133 mGy LL workflow vs 1,269 mGy angio; p=0.02), with no difference in contrast utilisation between groups (p=0.28). Furthermore, LL workflow OCT guidance resulted in fewer predilatation balloons and stents being used, more direct stent placement, and greater stent post-dilatation than angiography-guided PCI. CONCLUSIONS: The incorporation of a standardised pre- and post-PCI OCT imaging workflow improves procedural efficiency and safety metrics, at a cost of a modestly longer procedure time.

Use of Mechanical Circulatory Support in Chronic Total Occlusion Percutaneous Coronary Intervention.

The use of mechanical circulatory support (MCS) in chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has received limited study. We analyzed the clinical and angiographic characteristics, and procedural outcomes of 7,171 CTO PCIs performed between 2012 and 2021 at 35 international centers. Mean age was 64.5 ± 10 years, mean left ventricular ejection fraction was 50 ± 13%. MCS was used in 4.5%, prophylactically in 78.7%, and urgently in 21.3%. The most common type of MCS overall was Impella CP (Abiomed) (55.5%), followed by intra-aortic balloon pump (14.8%) and TandemHeart (LivaNova Inc.) (10.0%). Prophylactic MCS patients were more likely to have diabetes mellitus (55% vs 42%, p <0.001) and had more complex lesions compared with cases without prophylactic MCS (Japan-CTO score: 2.80 ± 1.22 vs 2.39 ± 1.27, p <0.001). Cases with prophylactic MCS had similar technical (86% vs 87%, p = 0.643) but lower procedural (80% vs 86%, p = 0.028) success rates and higher rates of periprocedural major cardiac adverse events compared with no prophylactic MCS use (6.55% vs 1.68%, p <0.001). Urgent MCS use was associated with lower technical (68% vs 87%, p <0.001) and procedural (39% vs 86%, p <0.001) success rates and higher major cardiac adverse events compared with no-MCS use (32.26% vs 1.68%, p <0.001). The differences persisted in multivariable analyses. In summary, in this contemporary multicenter registry, MCS was used in 4.5% of CTO PCIs, mostly prophylactically (78.7%). Elective MCS cases had similar technical success but a higher risk of complications. Urgent MCS cases had lower technical and procedural success and higher periprocedural major complication rates.

Transcatheter Aortic Valve Replacement for Severe Aortic Regurgitation in Patients With a Left Ventricular Assist Device.

BACKGROUND: There are limited invasive treatment options for patients with end-stage heart failure and left ventricular assist device (LVAD) who develop severe aortic valve regurgitation (AR). One option for such patients is transcatheter aortic valve replacement (TAVR). There are limited data on outcomes of patients with LVAD who receive TAVR for severe AR. We present a series of 4 consecutive patients with LVAD who underwent TAVR for severe AR. METHODS AND RESULTS: This is a retrospective chart review of 4 consecutive patients with LVAD who underwent TAVR for severe AR. All 4 patients underwent TAVR with a 34-mm self-expanding valve (Medtronic). One patient received a 29-mm balloon-expandable valve (Edwards Lifesciences) within the self-expanding valve (SEV) to postdilate the SEV and minimize paravalvular leak (PVL). All 4 procedures were technically successful. The patient who received rescue valve-in-valve TAVR continued to have persistent mild to moderate PVL. CONCLUSION: Although technically challenging, TAVR is a feasible option for carefully selected LVAD patients with severe AR. Procedural issues to consider include oversizing the transcatheter heart valve (THV) while being cognizant of the risks of annular rupture and valve dislocation, anticipating and avoiding ventricular migration of the THV and being ready to postdilate the THV if necessary, to limit hemodynamically significant PVL.

Comparable Outcomes for Transcarotid and Transfemoral Transcatheter Aortic Valve Replacement at a High Volume US Center.

With continued growth of transcatheter aortic valve replacement (TAVR), safe alternative access remains important for patients without adequate transfemoral (TF) access. Registry-based outcomes with transcarotid (TC) TAVR are favorable compared to transapical or transaxillary/subclavian, but TC vs TF comparisons have not been made. Our objective was to compare outcomes between TF and TC access routes for TAVR at a high-volume United States center. Methods: We retrospectively evaluated all TF and TC TAVR procedures from June 11, 2014 (first TC case) through December 31, 2019. The primary outcomes were 30-day stroke and 30-day mortality. Secondary outcomes were 1-year stroke, 1-year survival, and 30-day and 1-year life-threatening/major bleeding, vascular complications, and myocardial infarction. Propensity score weighted (PSW) models were used to compare risk-adjusted TF and TC outcomes. Of 1,465 TAVR procedures, 1319 (90%) were TF and 146 (10%) were TC. Procedure time and length of stay did not differ between groups. Unadjusted 30-day stroke (TF = 2.0%, TC = 2.7%, P = 0.536) and mortality (TF = 2.1%, TC = 2.7%, P = 0.629) were similar between groups. PSW 30-day stroke (odds ratio (OR) (95% confidence interval (CI)) = 0.8 (0.2-2.8)) and mortality (OR (95% CI) = 0.8 (0.2-3.0)) were similar between groups. Unadjusted and PSW 30-day major/life threatening bleeding, major vascular complications, and myocardial infarction did not differ between groups. Survival at one year was 90% (88%-92%) for TF patients and 87% (81%-93%) for TC patients (unadjusted P = 0.28, PSW hazard ratio = 1.0 (0.6-1.7)). Transcarotid TAVR is associated with similar outcomes compared to transfemoral TAVR at an experienced, high-volume center.

Transcarotid versus transthoracic access for transcatheter aortic valve replacement: A propensity-matched analysis.

OBJECTIVE: Transcarotid access for transcatheter aortic valve replacement is emerging as an alternative to more traditional nonfemoral access options such as transapical or transaortic; however, comparative data are limited. The purpose of the study was to analyze outcomes after transcatheter aortic valve replacement using transcatheter compared with transthoracic (transapical/transaortic) access. METHODS: The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy Registry was queried for patients who underwent transcarotid, transapical, or transaortic transcatheter aortic valve replacement with the SAPIEN 3 (Edwards Lifesciences, Irvine, Calif) transcatheter heart valve between June 2015 and July 2019. Thirty-day unadjusted outcomes were evaluated, and propensity score matching and logistic regression were used to compare transcatheter access with transthoracic access. RESULTS: In the propensity-matched analysis, 667 transcarotid transcatheter aortic valve replacement procedures were compared with 1334 transthoracic procedures. Transcarotid transcatheter aortic valve replacement was associated with lower mortality (4.2% vs 7.7%, P = .004), less new-onset atrial fibrillation (2.2% vs 12.1%, P < .0001), fewer readmissions at 30 days (9.8% vs 16.1%, P = .0006), shorter median length of stay (3.0 vs 6.0 days, P < .0001), shorter median intensive care unit stay (25 vs 47.2 hours, P < .0001), and greater 30-day Kansas City Cardiomyopathy Questionnaire score improvement from baseline (25.1 vs 20.8, P = .007). Stroke (4.3% vs 3.7%, P = .44) and major vascular complications (1.4% vs 1.9%, P = .40) were similar. CONCLUSIONS: Transcatheter aortic valve replacement using transcarotid access is associated with lower 30-day mortality, less atrial fibrillation, shorter intensive care unit and overall length of stay, fewer readmissions, greater improvement in Kansas City Cardiomyopathy Questionnaire scores, and no significant difference in stroke or major vascular complications compared with transthoracic access.

Amino-terminal pro-B-type natriuretic peptide and high-sensitivity C-reactive protein as predictors of sudden cardiac death among women.

BACKGROUND: Plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) have been found to predict risk of sudden cardiac death (SCD) in patients with known cardiac disease, and C-reactive protein levels have been found to predict risk among apparently healthy men. However, there are no data on SCD risk prediction for either of these markers in a population of women unselected on the basis of cardiovascular disease. METHODS AND RESULTS: In a prospective, nested, case-control analysis within the 121,700-participant Nurses' Health Study, 99 cases of definite or probable SCD were identified and matched to 294 controls. In multivariable models that adjusted for coronary heart disease risk factors, glomerular filtration rate, and other biomarkers, the trend across quartiles approached significance for NT-proBNP (rate ratio=2.37 for comparison of the highest and lowest quartile; P for trend=0.05) but not for high-sensitivity C-reactive protein (P for trend=0.60). When examined continuously, both NT-proBNP and high-sensitivity C-reactive protein were significantly associated with SCD risk in age- and fasting-adjusted models (P for linear trend=0.04 and 0.03). Adjustment for coronary heart disease risk factors and other biomarkers strengthened the relationship with NT-proBNP and SCD (relative risk for 1-SD increment=1.49; 95% confidence interval, 1.09 to 2.05; P=0.01) but eliminated the relationship with high-sensitivity C-reactive protein (P=0.34). Women with NT-proBNP levels above the prespecified cut point of 389 pg/mL were at a markedly increased risk of SCD in both models (rate ratio=5.68; 95% confidence interval, 1.78 to 18.2; P=0.003). CONCLUSIONS: In this population of women, baseline levels of NT-proBNP were associated with subsequent risk of SCD. If this association is confirmed in larger prospectively studied populations, these findings might provide another useful marker contributing to efforts to screen and prevent SCD among women.

A light-activated theranostic nanoagent for targeted macrophage ablation in inflammatory atherosclerosis.

The synthesis and utility of a multimodal theranostic nanoagent based upon magnetofluorescent nanoparticles for the treatment of inflammatory atherosclerosis is described. These particles are modified with near-infrared fluorophores and light-activated therapeutic moieties, which allow for the optical determination of agent localization and phototoxic activation at spectrally distinct wavelengths. The resulting agent is readily taken up by murine macrophages in vitro and is highly phototoxic, with an LD(50) of 430 pM. Intravenous administration results in the localization of the nanoagent within macrophage-rich atherosclerotic lesions that can be imaged by intravital fluorescence microscopy. Irradiation of the atheroma with 650 nm light activates the therapeutic component and results in eradication of inflammatory macrophages, which may induce lesion stabilization. Importantly, these agents display limited skin photosensitivity, are highly efficacious, and provide an integrated imaging and therapeutic nanoplatform for atherosclerosis.

Transcarotid Versus Subclavian/Axillary Access for Transcatheter Aortic Valve Replacement With SAPIEN 3.

BACKGROUND: Subclavian/axillary (TAx) access has become the most frequently used alternative access route for transcatheter aortic valve replacement (TAVR). Transcarotid (TC) TAVR has grown in popularity recently. Comparative data between these 2 contemporary access methods is lacking. METHODS: Data were extracted from The Society of Thoracic Surgeons/American College of Cardiology Transcatheter Valve Therapy (TVT) Registry™ (June 2015 to October 2019) for patients undergoing TAVR by TC or TAx access with the SAPIEN 3 and SAPIEN 3 Ultra (Edwards Lifesciences, Irvine, CA) transcatheter heart valves. Procedural, index hospitalization, and 30-day outcomes were analyzed for TC vs TAx groups after 1:2 propensity matching of patient baseline characteristics. RESULTS: The study included 3903 cases, of which 801 TC and 3102 TAx procedures were compared. After 1:2 propensity matching, TC TAVR was associated with similar 30-day mortality (4.3% vs 5.2%, P = .34) but a significantly lower risk of stroke (4.2% vs 7.4%; hazard ratio, 0.56; 95% confidence interval, 0.38-0.83; P = .003) compared with TAx access. Other outcomes that favored TC over TAx included shorter procedure time (117.0 vs 132.4 minutes; P < .001) and fluoroscopy time (16.6 vs 21.6 min; P < .001), lower contrast volume (78.5 vs 96.7 mL; P < .001), shorter length of stay in the intensive care unit (24.3 vs 25.0 hours; P = .02) and hospital (2.0 vs 3.0 days; P = .002), and more patients discharged to home (82.9% vs 74.6%; P < .001). CONCLUSIONS: TC TAVR is associated with similar mortality and a significant reduction in stroke compared with the TAx approach. If femoral access is precluded, TC may be a safe, or at times, preferred avenue of transcatheter valve delivery.

A novel technique for 14 French arteriotomy closure after percutaneous aortic valvuloplasty using two Mynx closure devices.

Management of large bore arterial access sites often represents a challenge during interventional procedures, and usually requires prolonged manual compression, though suture-mediated closure techniques have been described. We report our experience in using the Mynx vascular closure device to close a 14 French femoral arteriotomy in two patients undergoing percutaneous balloon aortic valvuloplasty.

The Carotid Artery as a Preferred Alternative Access Route for Transcatheter Aortic Valve Replacement.

BACKGROUND: In high-risk patients with severe aortic stenosis, transfemoral (TF) access for transcatheter aortic valve replacement (TAVR) is the preferred access route but is not always feasible. Compared with other alternative access routes, transcarotid (TC) access is often overlooked by many valvular heart teams. METHODS: We report our single-center experience of all patients undergoing TC (n = 25), transapical (TA) (n = 12), or TF (n = 100; limited to most recent cases) TAVR over a 1.5 year period. In-hospital and 30-day outcomes were retrospectively compared between groups using the Kruskal-Wallis and Wilcoxon rank sum tests. RESULTS: TAVR was successfully performed through the left or right carotid artery in all 25 patients. Procedurally, TC and TF procedures were faster than TA procedures (p < 0.001), and patients who underwent TC and TF procedures had shorter intensive care unit (ICU) hours (p = 0.05), ventilator hours (p < 0.001), and length of stay (LOS) (p = 0.01) compared to patients who underwent a TA procedure. No patients who underwent a TC procedure had in-hospital stroke, transient ischemic attack (TIA), or myocardial infarction (MI). One patient who underwent a TC procedure had a TIA by 30-day follow-up, which was not significantly different from the TF (2 patients) or TA groups (0 patients; p = 0.75). In-hospital mortality rates were the same between TC (1 patient) and TF (1 patient) procedures but were significantly greater for TA procedures (2 patients; p = 0.009). Thirty-day mortality rates were low and did not differ between the groups. CONCLUSIONS: In our US community hospital setting, TC-TAVR is a safe alternative to TF-TAVR in appropriate patients and has evolved to be our alternative access route of choice if TF access is not feasible.

The State of the Absorb Bioresorbable Scaffold: Consensus From an Expert Panel.

Significant progress has been made in the percutaneous coronary intervention technique from the days of balloon angioplasty to modern-day metallic drug-eluting stents (DES). Although metallic stents solve a temporary problem of acute recoil following balloon angioplasty, they leave behind a permanent problem implicated in very late events (in addition to neoatherosclerosis). BRS were developed as a potential solution to this permanent problem, but the promise of these devices has been tempered by clinical trials showing increased risk of safety outcomes, both early and late. This is not too dissimilar to the challenges seen with first-generation DES in which refinement of deployment technique, prolongation of dual antiplatelet therapy, and technical iteration mitigated excess risk of very late stent thrombosis, making DES the treatment of choice for coronary artery disease. This white paper discusses the factors potentially implicated in the excess risks, including the scaffold consideration and deployment technique, and outlines patient and lesion selection, implantation technique, and dual antiplatelet therapy considerations to potentially mitigate this excess risk with the first-generation thick strut Absorb scaffold (Abbott Vascular, Abbott Park, Illinois). It remains to be seen whether these considerations together with technical iterations will ultimately close the gap between scaffolds and metal stents for short-term events while at the same time preserving options for future revascularization once the scaffold bioresorbs.

Plasma and dietary magnesium and risk of sudden cardiac death in women.

BACKGROUND: Magnesium has antiarrhythmic properties in cellular and experimental models; however, its relation to sudden cardiac death (SCD) risk is unclear. OBJECTIVE: We prospectively examined the association between magnesium, as measured in diet and plasma, and risk of SCD. DESIGN: The analysis was conducted within the Nurses' Health Study. The association for magnesium intake was examined prospectively in 88,375 women who were free of disease in 1980. Information on magnesium intake, other nutrients, and lifestyle factors was updated every 2-4 y through questionnaires, and 505 cases of sudden or arrhythmic death were documented over 26 y of follow-up. For plasma magnesium, a nested case-control analysis including 99 SCD cases and 291 controls matched for age, ethnicity, smoking, and presence of cardiovascular disease was performed. RESULTS: After multivariable adjustment for confounders and potential intermediaries, the relative risk of SCD was significantly lower in women in the highest quartile compared with those in the lowest quartile of dietary (relative risk: 0.63; 95% CI: 0.44, 0.91) and plasma (relative risk: 0.23; 95% CI: 0.09, 0.60) magnesium. The linear inverse relation with SCD was strongest for plasma magnesium (P for trend = 0.003), in which each 0.25-mg/dL (1 SD) increment in plasma magnesium was associated with a 41% (95% CI: 15%, 58%) lower risk of SCD. CONCLUSIONS: In this prospective cohort of women, higher plasma concentrations and dietary magnesium intakes were associated with lower risks of SCD. If the observed association is causal, interventions directed at increasing dietary or plasma magnesium might lower the risk of SCD.

Unusual causes of intermittent claudication: popliteal artery entrapment syndrome, cystic adventitial disease, fibromuscular dysplasia, and endofibrosis.

In the general population, vascular causes of exercise-induced limb discomfort are most often the result of peripheral artery disease (PAD) due to atherosclerosis. However, several other clinical entities can often mimic the symptoms of atherosclerotic PAD of the lower extremities, particularly among younger patients with fewer risk factors for atherosclerosis, who often are more athletically fit than patients with PAD. Treatment for these entities often requires percutaneous or surgical intervention. This article reviews four uncommon vascular causes of exercise-induced limb discomfort: popliteal artery entrapment syndrome, cystic adventitial disease of the popliteal artery, fibromuscular dysplasia of the lower-extremity arteries, and endofibrosis of the iliac artery.