Faculty Bibliography

OBJECTIVE: To evaluate the efficacy of endovascular therapy for maintaining patency and preserving limbs among patients with failing infrapopliteal bypass grafts. METHODS: We gathered data from a registry of catheter-based procedures for peripheral artery disease. Of 1554 arteriograms performed from 2006 to 2012, 30 patients had interventions for failing bypass vein grafts to infrapopliteal target vessels. The first intervention for each patient was used in this analysis. Duplex ultrasonography was used within 30 days after intervention and subsequently at 3-6 month intervals for graft surveillance. RESULTS: Interventions were performed for duplex ultrasonography surveillance findings in 21 patients and for symptoms of persistent or recurrent critical limb ischemia in 9 patients. Procedural techniques included cutting balloon angioplasty (83%), conventional balloon angioplasty (7%), and stent placement (10%). Procedural success was achieved in all cases. There were no procedure-related complications, amputations, or deaths within 30 days. By Kaplan-Meier analysis, 37% were free from graft restenosis at 12 months and 31% were at 24 months. Receiver operating characteristic analysis indicated that a lesion length of 1.75 cm best predicted freedom from restenosis (C statistic: 0.74). Residual stenosis (P=0.03), patency without reintervention (P=0.01), and assisted patency with secondary intervention (P=0.02) rates were superior for short lesions compared to long lesions. The cohort had acceptable rates of adverse clinical outcomes, with 96% of patients free from amputation at both 12 and 24 months; clinical outcomes were also better in patients with short lesions. CONCLUSIONS: In this single-center experience with endovascular therapies to treat failing infrapopliteal bypass grafts, rates of limb preservation were high, but the majority of patients developed graft restenosis within 12 months. Grafts with longer stenoses fared poorly by comparison. These data suggest that endovascular interventions to restore or prolong graft patency may be associated with maintained graft patency and that close follow up with vascular laboratory surveillance is essential.

Diabetes mellitus (DM) is a significant risk factor for loss of patency after endovascular intervention, but the contribution of glycemic control to infrapopliteal artery patency among patients with DM is unknown. All percutaneous infrapopliteal interventions among patients with DM from 2006 to 2013 were reviewed and pre-procedure fasting blood glucose (FBG) was recorded. The primary endpoint was primary patency at 1 year as determined by duplex ultrasound. A total of 309 infrapopliteal lesions in 149 patients with DM were treated with balloon angioplasty during the study period. The median FBG was 144 mg/dL. At 1 year, the rate of primary patency was 16% for patients with FBG above the median, compared to 46% for patients with FBG below the median (hazard ratio (HR) 1.82 for FBG >/=144, p=0.005). Amputation rates at 1 year trended higher among patients with high versus low FBG (24% vs 15%, p=0.1). One year major adverse limb event rates were also higher for patients with high versus low FBG (35% vs 23%, p=0.05). Although patients with high FBG were more likely to have insulin-requiring DM (73% vs 50%, p=0.003) the association of high FBG with loss of primary patency remained significant even after adjusting for insulin use as well as other lesion-specific characteristics (adjusted HR 1.8, 95% CI 1.2-2.8). In conclusion, high fasting blood glucose at the time of infrapopliteal balloon angioplasty is associated with significantly decreased primary patency and may also be a risk factor for major adverse limb events among patients with a threatened limb.

BACKGROUND: Endovascular therapies are increasingly used for treatment of critical limb ischemia (CLI). Infrapopliteal (IP) occlusions are common in CLI, and successful limb salvage may require restoration of arterial flow in the distribution of a chronically occluded vessel. We sought to describe the procedural characteristics and outcomes of patients with IP occlusions who underwent endovascular intervention for treatment of CLI. METHODS: All patients with IP interventions for treatment of CLI from 2006 to 2012 were included. Angiographic and procedural data were compared between patients who underwent intervention for IP occlusions vs IP stenosis. Restenosis was determined by Doppler ultrasound imaging. Limb salvage was the primary end point of the study. Additional end points included primary patency, primary assisted patency, secondary patency, occlusion crossing success, procedural success, and amputation-free survival. RESULTS: A total of 187 patients with CLI underwent interventions for 356 IP lesions, and 77 patients (41%) had interventions for an IP occlusion. Patients with an intervention for IP occlusion were more likely to have zero to one vessel runoff (83% vs 56%; P < .001) compared with interventions for stenosis. Compared with IP stenoses, IP occlusions were longer (118 +/- 86 vs 73 +/- 67 mm; P < .001) and had a smaller vessel diameter (2.5 +/- 0.8 vs 2.7 +/- 0.5 mm; P = .02). Wire crossing was achieved in 83% of IP occlusions, and the overall procedural success for IP occlusions was 79%. The overall 1-year limb salvage rate was 84%. Limb salvage was highest in the stenosis group, slightly lower in the successful occlusion group, and lowest in the failed occlusion group (92% vs 75% vs 58%, respectively; P = .02). Unsuccessfully treated IP occlusions were associated with a significantly higher likelihood of major amputation (hazard ratio, 5.79; 95% confidence interval, 1.89-17.7) and major amputation or death (hazard ratio, 2.69; 95% confidence interval, 1.09-6.63). CONCLUSIONS: Successful endovascular recanalization of IP occlusions can be achieved with guidewire and support catheter techniques in most patients. In patients selected for an endovascular-first approach for IP occlusions in CLI, this strategy can be successfully implemented with favorable rates of limb salvage.

BACKGROUND: Current guidelines recommend that patients with peripheral arterial disease (PAD) cease smoking and be treated with aspirin, statin medications, and angiotensin-converting enzyme (ACE) inhibitors. The combined effects of multiple guideline-recommended therapies in patients with symptomatic PAD have not been well characterized. METHODS AND RESULTS: We analyzed a comprehensive database of all patients with claudication or critical limb ischemia (CLI) who underwent diagnostic or interventional lower-extremity angiography between June 1, 2006 and May 1, 2013 at a multidisciplinary vascular center. Baseline demographics, clinical data, and long-term outcomes were obtained. Inverse probability of treatment propensity weighting was used to determine the 3-year risk of major adverse cardiovascular or cerebrovascular events (MACE; myocardial infarction, stroke, or death) and major adverse limb events (MALE; major amputation, thrombolysis, or surgical bypass). Among 739 patients with PAD, 325 (44%) had claudication and 414 (56%) had CLI. Guideline-recommended therapies at baseline included use of aspirin in 651 (88%), statin medications in 496 (67%), ACE inhibitors in 445 (60%), and smoking abstention in 528 (71%) patients. A total of 237 (32%) patients met all four guideline-recommended therapies. After adjustment for baseline covariates, patients adhering to all four guideline-recommended therapies had decreased MACE (hazard ratio [HR], 0.64; 95% CI, 0.45 to 0.89; P=0.009), MALE (HR, 0.55; 95% CI, 0.37 to 0.83; P=0.005), and mortality (HR, 0.56; 95% CI, 0.38 to 0.82; P=0.003), compared to patients receiving less than four of the recommended therapies. CONCLUSIONS: In patients with claudication or CLI, combination treatment with four guideline-recommended therapies is associated with significant reductions in MACE, MALE, and mortality.

OBJECTIVES: The aim of this study was to determine the associations between statin use and major adverse cardiovascular and cerebrovascular events (MACCE) and amputation-free survival in critical limb ischemia (CLI) patients. BACKGROUND: CLI is an advanced form of peripheral arterial disease associated with nonhealing arterial ulcers and high rates of MACCE and major amputation. Although statin medications are recommended for secondary prevention in peripheral arterial disease, their effectiveness in CLI is uncertain. METHODS: We reviewed 380 CLI patients who underwent diagnostic angiography or therapeutic endovascular intervention from 2006 through 2012. Propensity scores and inverse probability of treatment weighting were used to adjust for baseline differences between patients taking and not taking statins. RESULTS: Statins were prescribed for 246 (65%) patients. The mean serum low-density lipoprotein (LDL) level was lower in patients prescribed statins (75 +/- 28 mg/dl vs. 96 +/- 40 mg/dl, p < 0.001). Patients prescribed statins had more baseline comorbidities including diabetes, coronary artery disease, and hypertension, as well as more extensive lower extremity disease (all p values <0.05). After propensity weighting, statin therapy was associated with lower 1-year rates of MACCE (stroke, myocardial infarction, or death; hazard ratio [HR]: 0.53; 95% confidence interval [CI]: 0.28 to 0.99), mortality (HR: 0.49, 95% CI: 0.24 to 0.97), and major amputation or death (HR: 0.53, 95% CI: 0.35 to 0.98). Statin use was also associated with improved lesion patency among patients undergoing infrapopliteal angioplasty. Patients with LDL levels >130 mg/dl had increased HRs of MACCE and mortality compared with patients with lower levels of LDL. CONCLUSIONS: Statins are associated with lower rates of mortality and MACCE and increased amputation-free survival in CLI patients.

PURPOSE: To compare the patency rates and clinical outcomes of balloon angioplasty vs. nitinol stent placement for patients with short (150 mm) femoropopliteal (FP) occlusive lesions. METHODS: Between 2006 and 2011, 254 patients (134 men; mean age 68 years) underwent FP angioplasty. The majority of patients (64%) were treated for critical limb ischemia. One hundred thirty-nine (55%) patients had short FP lesions 150 mm. The mean lesion length was 78+/-43 mm in the short FP lesion group and 254+/-58 mm in the long FP lesion group. Duplex ultrasound follow-up with a peak systolic velocity ratio >/=2.0 was used to define restenosis. RESULTS: The overall procedure success rate was 98%. One hundred forty-eight (58%) patients underwent stent placement. The mean number of stents deployed for treatment of short FP lesions was 1.0+/-0.4 vs. 2.0+/-0.7 for long FP lesions (p<0.001). The primary patency rate of short FP lesions treated with balloon angioplasty vs. stenting was 66% vs. 63% at 1 year (p=0.7). For long FP lesions, the 1-year primary patency rates of balloon angioplasty vs. stenting were 34% vs. 49% (p=0.006). Balloon angioplasty of long FP lesions was also associated with significantly lower assisted primary and secondary patency compared to stenting (p<0.05 for all comparisons). Sustained clinical improvement was >90% at 30 days but declined to 62% to 75% at 1 year. CONCLUSION: Balloon angioplasty and stent placement result in similar patency rates and clinical outcomes for shorter to medium-length FP lesions. In comparison, stent placement in long FP lesions is associated with superior outcomes to balloon angioplasty, even when multiple stents are required. Procedure success and clinical improvement can be achieved in the majority of patients, but rates of restenosis remain high.

OBJECTIVE: While the standard has been to define motor threshold (MT) using EMG to measure motor cortex response to transcranial magnetic stimulation (TMS), another method of determining MT using visual observation of muscle twitch (OM-MT) has emerged in clinical and research use. We compared these two methods for determining MT. METHODS: Left motor cortex MTs were found in 20 healthy subjects. Employing the commonly-used relative frequency procedure and beginning from a clearly suprathreshold intensity, two raters used motor evoked potentials and finger movements respectively to determine EMG-MT and OM-MT. RESULTS: OM-MT was 11.3% higher than EMG-MT (p<0.001), ranging from 0% to 27.8%. In eight subjects, OM-MT was more than 10% higher than EMG-MT, with two greater than 25%. CONCLUSIONS: These findings suggest using OM yields significantly higher MTs than EMG, and may lead to unsafe TMS in some individuals. In more than half of the subjects in the present study, use of their OM-MT for typical rTMS treatment of depression would have resulted in stimulation beyond safety limits. SIGNIFICANCE: For applications that involve stimulation near established safety limits and in the presence of factors that could elevate risk such as concomitant medications, EMG-MT is advisable, given that safety guidelines for TMS parameters were based on EMG-MT.

OBJECTIVES: We sought to evaluate the procedural characteristics and clinical outcomes of endovascular repair for iliac artery (IA) in-stent restenosis (ISR). BACKGROUND: An increasing percentage of patients with complex IA occlusive disease are treated with an endovascular approach, but the outcomes of IA-ISR have not been well described. METHODS: We analyzed all endovascular procedures for treatment of IA-ISR performed at our institution between July 2006-December 2010. The primary outcome was primary patency, defined as <50% stenosis as assessed by clinical examination and duplex ultrasonography (DUS). RESULTS: Forty-one lesions in 24 patients who underwent repeated endovascular intervention for treatment of IA-ISR. Most lesions were unilateral and involved the common IA (66%). The mean length of ISR was 30.1 +/- 14.1 mm with type I (focal) and II (diffuse) ISR occurring with the greatest frequency (34% and 39%, respectively). All patients underwent balloon angioplasty; adjunctive stenting zwas performed in 27 (66%) of the lesions. Type II ISR lesions more frequently required stenting (13/16 lesions, P = 0.02 compared with other patterns of ISR). Procedural success was 100% with a mean gain of 0.13 in the ankle-brachial index (P = 0.001). The 6- and 12-month primary patency rates were 96% and 82%, respectively. The 12-month primary-assisted patency rate was 90% with clinically driven target lesion revascularization (TLR) in three patients. CONCLUSIONS: Endovascular treatment of IA-ISR using an approach of balloon angioplasty followed by selective stenting is associated with high-patency rates and low rates of TLR at 1 year.

OBJECTIVES: The purpose of this study was to identify the relationship between angiographic patterns of restenosis and outcomes after endovascular treatment of femoro-popliteal in-stent restenosis (FP-ISR). BACKGROUND: ISR is a frequent clinical problem after femoro-popliteal stenting. METHODS: This was a single center study of all endovascular interventions for FP-ISR from 2006 to 2012. Class I ISR was defined as focal lesions 50 mm; and Class III ISR as stent chronic total occlusion. Recurrent ISR was defined as peak systolic velocity ratio > 2.4 by duplex ultrasound. RESULTS: Among 75 cases of FP-ISR, 28 (37%) were Class I, 22 (29%) were Class II, and 25 (33%) were Class III. The mean lesion length was 26 mm for Class I, 135 mm for Class II, and 178 mm for Class III ISR. Patients with Class III ISR more frequently had ISR extending into both the superficial femoral and popliteal artery (48% vs. 18%, P = 0.005). Balloon angioplasty was used most frequently to treat Class I ISR, while adjunctive atherectomy and/or stenting was used for almost all cases of Class III ISR. During 2-year follow-up, rates of repeat restenosis were 39% for Class I, 67% for Class II, and 72% for Class III ISR (P = 0.04). Rates of stent occlusion were 8% for Class I, 11% for Class II, and 52% for Class III ISR (P = 0.009). Class III ISR was associated with significantly increased risk of recurrent ISR (HR 2.4, 95% CI 1.1-5.6) and recurrent occlusion (HR 5.8, 95% CI 1.8-19.0) compared to other types of ISR. CONCLUSION: Angiographic patterns of FP-ISR are important determinants of subsequent outcomes. Repeat restenosis and occlusion remain common despite currently available technologies.

OBJECTIVE: To demonstrate the use of a novel controllable pulse parameter TMS (cTMS) device to characterize human corticospinal tract physiology. METHODS: Motor threshold and input-output (IO) curve of right first dorsal interosseus were determined in 26 and 12 healthy volunteers, respectively, at pulse widths of 30, 60, and 120 mus using a custom-built cTMS device. Strength-duration curve rheobase and time constant were estimated from the motor thresholds. IO slope was estimated from sigmoid functions fitted to the IO data. RESULTS: All procedures were well tolerated with no seizures or other serious adverse events. Increasing pulse width decreased the motor threshold and increased the pulse energy and IO slope. The average strength-duration curve time constant is estimated to be 196 mus, 95% CI [181 mus, 210 mus]. IO slope is inversely correlated with motor threshold both across and within pulse width. A simple quantitative model explains these dependencies. CONCLUSIONS: Our strength-duration time constant estimate compares well to published values and may be more accurate given increased sample size and enhanced methodology. Multiplying the IO slope by the motor threshold may provide a sensitive measure of individual differences in corticospinal tract physiology. SIGNIFICANCE: Pulse parameter control offered by cTMS provides enhanced flexibility that can contribute novel insights in TMS studies.