Increased ischemic complications in fenestrated and branched endovascular abdominal aortic repair compared with standard endovascular aortic repair.

OBJECTIVE: Ischemic complications (including in the lower extremity, visceral, spinal, and pelvic territories) following standard endovascular aortic repair (EVAR) are well recognized but fortunately uncommon. The incidence of such complications following fenestrated and branched aortic repair (F/BEVAR) has not been well defined in the literature. The objective of this study was to compare the incidence of ischemic complications between EVAR and F/BEVAR and to elucidate potential risk factors for these complications. METHODS: We identified all patients who underwent EVAR from 2003 to 2017 or F/BEVAR from 2012 to 2017 in the national Vascular Quality Initiative database. We assessed differences in perioperative ischemic outcomes with methods including logistic regression and inverse probability of treatment propensity score weighting, using a composite end point of lower extremity ischemia, intestinal ischemia, stroke, or new dialysis as the primary end point. RESULTS: The data comprised 35,379 EVAR patients and 3374 F/BEVAR patients. F/BEVAR patients were more likely to be female, have had previous aneurysm repairs, and be deemed unfit for open aneurysm repair; they were less likely to have ruptured aneurysms; and they had higher estimated blood losses, contrast volumes, and fluoroscopy and procedure times. The incidence of any ischemic event (7.7% vs 2.2%) as well as the incidences of the component end points of lower extremity ischemia (2.3% vs 1.0%), intestinal ischemia (2.7% vs 0.7%), stroke (1.5% vs 0.3%), and new hemodialysis (3.1% vs 0.4%) were all significantly increased (all P < .001) in F/BEVAR compared with standard EVAR. After propensity adjustment, F/BEVAR conferred increased odds of any ischemic complication (1.8), intestinal ischemia (2.0), lower extremity ischemia (1.3), new hemodialysis (10.2), and stroke (2.3). CONCLUSIONS: Rates of lower extremity ischemia, intestinal ischemia, new dialysis, and stroke each range from 0% to 1% for standard EVAR and 1% to 3% for F/BEVAR. The incidence of perioperative ischemic complications following F/BEVAR is significantly increased compared to EVAR. The real-world data in this study should help guide decision-making for surgeons and patients as well as serve as one metric for progress in device and technique development. Improvements in ischemic complications may come from continued technology development such as smaller sheaths, improved imaging to decrease procedure time and contrast volume, embolic protection, and increased operator skill with wire and catheter manipulation.

Endovascular Creation of Arteriovenous Fistulae for Hemodialysis Access with a 4 Fr Device: Clinical Experience from the EASE Study.

BACKGROUND: The use of arteriovenous fistula (AVF) is hampered by long surgical wait times, slow maturation, and upwards of 60% that do not mature. We describe our clinical experience in using a system with a 4F catheter profile for endovascular AVF creation in patients on hemodialysis. METHODS: This was a multioperator, single-center, single-arm, prospective study intended to evaluate safety and efficacy of a 4 Fr endovascular AVF (endoAVF) system for the creation of vascular access in hemodialysis patients. The study was performed after institutional review board approval at Italian Hospital (Asuncion, Paraguay). Patients were followed up at regular intervals through 6 months to determine procedural, maturation, and cannulation success as well as intervention rate and patency. RESULTS: From May to November 2016, 32 patients underwent the endoAVF procedure with no device-related adverse events. An endoAVF was successfully created in the proximal forearm for all 32 patients (20 between the radial artery and radial vein; 12 between the ulnar artery and ulnar vein). Wrist access was used for 72% (23/32) of the procedures for the arterial catheter and 59% (19/32) of the procedures for the venous catheter. The device successfully created an endoAVF in every patient for a technical success rate of 100% (32/32). The device- or procedure-related serious adverse event rate was 3% (1/32); one patient experienced a venous guidewire perforation successfully managed with a stent graft. Primary and cumulative patency rates through 6 months were 83% and 87%, respectively, with an intervention rate of 0.21 per patient-year. Physiological suitability, as defined by target flow rates ≥500 ml/min and cannulation vessel diameters ≥4 mm, was achieved in 91% (29/32) of patients by 90 days. Successful 2-needle cannulation was achieved in 78% (21/27) by 90 days, with mean time to cannulation of 43 ± 14 days. Functional cannulation, as defined by successful 2-needle cannulation for two-thirds of the dialysis sessions within 1 month, was achieved in 95% (20/21) of the patients who were successfully cannulated for an overall rate of 74% (20/27). All patients who achieved functional cannulation had their central venous catheters (CVCs) removed before the 90-day follow-up for a CVC removal rate of 74% (20/27). CONCLUSIONS: The 4 Fr endoAVF system allowed for multiple access and fistula creation site options to tailor the procedure to individual patient anatomy. Furthermore, the outcomes are comparable to previous generation endoAVF technology, with a potentially improved safety profile because of the use of arteries at the wrist for access.

Aspirin and clopidogrel high on-treatment platelet reactivity and genetic predictors in peripheral arterial disease.

OBJECTIVES: Our aims were to examine the prevalence and genetic predictors of aspirin and clopidogrel high on-treatment platelet reactivity (HoTPR), and associated adverse cardiovascular outcomes in patients with peripheral arterial disease (PAD). BACKGROUND: The association of aspirin and clopidogrel HoTPR with outcomes in PAD remains unclear. METHODS: This is a prospective cohort study of patients with angiographically documented PAD involving carotid and lower extremity arteries. Aspirin and clopidogrel HoTPR (using the VerifyNow Assay) and associated genetic predictors were compared to clinical outcomes. The primary end-point was a composite of major adverse cardiovascular events: all-cause mortality, myocardial infarction, stroke, target vessel revascularization (TVR) and limb-loss in patients who underwent extremity intervention. RESULTS: The study was stopped prematurely due to slow patient enrolment. Of 195 patients enrolled, the primary analysis was performed in 154 patients taking both drugs. Aspirin HoTPR was present in 31 (20%) and clopidogrel HoTPR in 76 (49%) patients. There was a trend toward more primary composite outcome events with PRU ≥ 235 (52% freedom-from-event rate vs. 70% for PRU < 235; P = 0.09). TVR was higher in those with PRU ≥ 235 (20 vs. 6%, unadjusted P = 0.02). There was no association between aspirin HoTPR and combined outcomes. Single nucleotide polymorphisms in serum paraoxonase/arylesterase 1 (PON1) gene was associated with aspirin HoTPR (P = 0.005) while SNP in phospholipase A2, group III (PLA2G3) gene was associated with clopidogrel HoTPR (P = 0.002). CONCLUSION: Clopidogrel HoTPR was significantly associated with TVR, while aspirin HoTPR was not associated with adverse clinical outcomes in patients with PAD.

Endovascular recanalization of infrapopliteal occlusions in patients with critical limb ischemia.

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.

Nitinol self-expanding stents vs. balloon angioplasty for very long femoropopliteal lesions.

PURPOSE: To compare the patency rates and clinical outcomes of balloon angioplasty vs. nitinol stent placement for patients with short (≤150 mm) as compared to long (>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, while 115 patients had long 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.

Association of elevated fasting glucose with lower patency and increased major adverse limb events among patients with diabetes undergoing infrapopliteal balloon angioplasty.

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.

Endovascular therapy is effective treatment for focal stenoses in failing infrapopliteal vein grafts.

BACKGROUND: 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- to 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% of the patients 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 with 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.

Mid-term outcomes following endovascular re-intervention for iliac artery in-stent restenosis.

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.

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

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

Radiofrequency and laser vein ablation for patients receiving warfarin anticoagulation is safe, effective, and durable.

OBJECTIVE: The objective of this study was to evaluate the efficacy, durability, and safety of radiofrequency ablation (RFA) and endovenous laser ablation (EVLA) of the great saphenous vein (GSV) and small saphenous vein (SSV) to treat symptomatic venous reflux in patients receiving therapeutic anticoagulation. METHODS: Patients treated at a single institution with RFA or EVLA while receiving warfarin (Coumadin) anticoagulation were identified retrospectively along with a consecutive sample of patients not receiving anticoagulation who were similarly treated. Patients' demographics, comorbidities, procedural details, and follow-up data were obtained from electronic medical records. Outcomes of interest included the rates of persistent vein ablation, bleeding, deep venous thrombosis (DVT), and endothermal heat-induced thrombosis. Groups were compared using χ2 tests, Fisher exact test, Kaplan-Meier curves, and Cox proportional hazard modeling. RESULTS: There were 100 procedures performed in 65 patients receiving anticoagulation and 127 procedures in 89 control patients. Mean follow-up time was 467 days. The most common indications for anticoagulation were atrial fibrillation (52%), remote DVT (29%), and mechanical heart valves (8%). Patients receiving anticoagulation were on average older (67 years vs 52 years), were more likely to be male (51% vs 27%), and had higher rates of coronary disease (9% vs 0%) and hypertension (55% vs 20%), although they were more likely to have never smoked (86% vs 69%). There were 127 RFA procedures (56%) and 100 EVLA procedures (44%); 189 procedures treated the GSV or its tributaries (83%), and 38 treated the SSV (17%). At 1 year, the target vessel remained ablated after 96% of procedures performed with anticoagulation and in 99% of controls; at 18 months, rates were 92% vs 95% (P = .96). Rates of persistent ablation did not differ significantly by vessel treated (P = .28), EVLA vs RFA (P = .36), or use of antiplatelet therapy (P = .92). One patient had bleeding from a phlebectomy site 2 days postprocedurally when supratherapeutic on warfarin; this was controlled with pressure. DVT in the ipsilateral leg occurred within 90 days after 1 of 100 (1%) procedures in patients receiving anticoagulation and 2 of 127 (1.6%) procedures in control patients; endothermal heat-induced thrombosis rates were similarly 1 of 100 (1%) procedures in patients receiving anticoagulation and 1 of 127 (0.8%) in control patients. CONCLUSIONS: This is the largest series to date reporting >30-day follow-up for patients undergoing venous ablation procedures while receiving anticoagulation and the longest follow-up reported of any series. Durability, safety, and efficacy of vein ablation in patients receiving anticoagulation are comparable to those in control patients. Anticoagulation should not be considered a contraindication to endothermal ablation of the GSV or SSV for symptomatic venous reflux.

Pulse Width Affects Scalp Sensation of Transcranial Magnetic Stimulation.

BACKGROUND: Scalp sensation and pain comprise the most common side effect of transcranial magnetic stimulation (TMS), which can reduce tolerability and complicate experimental blinding. OBJECTIVE: We explored whether changing the width of single TMS pulses affects the quality and tolerability of the resultant somatic sensation. METHODS: Using a controllable pulse parameter TMS device with a figure-8 coil, single monophasic magnetic pulses inducing electric field with initial phase width of 30, 60, and 120 µs were delivered in 23 healthy volunteers. Resting motor threshold of the right first dorsal interosseus was determined for each pulse width, as reported previously. Subsequently, pulses were delivered over the left dorsolateral prefrontal cortex at each of the three pulse widths at two amplitudes (100% and 120% of the pulse-width-specific motor threshold), with 20 repetitions per condition delivered in random order. After each pulse, subjects rated 0-to-10 visual analog scales for Discomfort, Sharpness, and Strength of the sensation. RESULTS: Briefer TMS pulses with amplitude normalized to the motor threshold were perceived as slightly more uncomfortable than longer pulses (with an average 0.89 point increase on the Discomfort scale for pulse width of 30 µs compared to 120 µs). The sensation of the briefer pulses was felt to be substantially sharper (2.95 points increase for 30 µs compared to 120 µs pulse width), but not stronger than longer pulses. As expected, higher amplitude pulses increased the perceived discomfort and strength, and, to a lesser degree the perceived sharpness. CONCLUSIONS: Our findings contradict a previously published hypothesis that briefer TMS pulses are more tolerable. We discovered that the opposite is true, which merits further study as a means of enhancing tolerability in the context of repetitive TMS.

Determination of motor threshold using visual observation overestimates transcranial magnetic stimulation dosage: safety implications.

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.

Association between statin medications and mortality, major adverse cardiovascular event, and amputation-free survival in patients with critical limb ischemia.

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.

Adherence to guideline-recommended therapy is associated with decreased major adverse cardiovascular events and major adverse limb events among patients with peripheral arterial disease.

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.

Pulse width dependence of motor threshold and input-output curve characterized with controllable pulse parameter transcranial magnetic stimulation.

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 µs 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 µs, 95% CI [181 µs, 210 µs]. 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.