Gregory G. Westin

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.

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.

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.

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.

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.

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.

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

We sought to evaluate the procedural characteristics and clinical outcomes of endovascular repair for iliac artery (IA) in‐stent restenosis (ISR).

PTMS37 Corticospinal response characterization with controllable pulse parameter transcranial magnetic stimulation (cTMS)

Cathodal tDCS was performed over the unaffected hemisphere with the hypothesis to reduce the inhibitory effects of the unaffected hemisphere over the affected hemisphere. Methods: We studied ten patients affected by stroke associated severe spasticity in upper limb. Cathodal TDCS stimulation was performed over the unaffected motor cortex and the reference overt the frontal region. A placebo stimulation was performed four weeks before the active stimulation in each patient. Active stimulation was set at 1 mA for 20 minutes/day for 5 days. NIH scale and Ashworth scales and a video were performed before and immediately after the placebo and active stimulation. Motor nerve conduction velocity and F wave and H reflex were recorded from abductor digiti minimi. The patients were monitored after one, two, four and eight weeks from the active treatment. Results: Active tDCS the patients produced greater improvement in flexor tone of wrist and hand fingers than placebo stimulation. At follow up visits at one, two, four and eight weeks a significant decrease of passive muscle tone was noted on the treated muscles in all patients. After 8 weeks from the therapy all patients showed persistent reduction in muscle tone. There were no adverse events associated with tDCS. H reflex is reduced in amplitude in most of patients after cathodal tDCS. Conclusions: TDCS reduce hypertonia of the wrist and finger muscles for at least 4 weeks and in some cases for 8 weeks from the treatment. TDCS represents an additional instrument in the treatment of spasticity which should be considered. Cortical inhibitory effects of the cathodal stimulation over the unaffected hemisphere is sueggested.

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.