Hakaim, Albert G.

Purpose: Supervised walking exercise is a critical component of rehabilitation for patients with peripheral artery disease (PAD); however, various barriers could limit participation in such programs, highlighting the need for accessible exercise strategies that may facilitate a gradual transition to more intensive physical activity while improving vascular function and walking performance in this population. We examined the hypothesis that static muscular stretching would improve microvascular function and walking ability in patients with PAD. Methods: Thirty-six PAD patients, classified as Fontaine Stage II or III, were randomized into stretching or non-stretching groups. The stretching group performed daily calf stretching using an ankle dorsiflexion splint for 30 minutes, 5 days a week, for 4 weeks. The six-minute walk test (6MWT) and a vascular occlusion test were used to assess changes in walking ability and calf microvascular function before and after the intervention. Results: Microvascular hyperemic reperfusion significantly increased in the treatment group (4958±1111 to 5749±1459 %*s, p=0.034), with no change observed in the control group (5502±1231 to 5022±1160 %*s, p=0.155). 6MWT total walking distance increased in all participants (260±88 to 285±85 m, p=0.004). A moderate but non-significant correlation was observed between the changes in 6MWT and total walking distance and reperfusion index in the treatment group (r=0.45, p=0.26). Conclusions: Static muscular stretching improves microvascular perfusion in the calf muscles, which may contribute to improvement in walking ability in patients with PAD. This low-cost and time-saving intervention may serve as a gradual transition to traditional supervised walking exercise rehabilitation, especially in patients with severely impaired walking ability.

Introduction: Peripheral artery disease (PAD), an atherosclerotic disease of the peripheral arteries, also results in microvascular dysfunction. PAD patients are recommended to undergo supervised walking and medical management; however, compliance with supervised walking programs is limited due to inconvenience and pain, necessitating alternative non-pharmacological interventions. We have shown that daily muscle stretching improved microvascular function in aged rats. This prompted us to study the effect of daily muscle stretching on microvascular function of the calf muscles in PAD patients. Methods: A randomized, single-blinded study was conducted on 24 PAD patients. Patients were assigned to either stretching or placebo stretching using a dorsiflexion splint (Image 1) for 30 min/day, 5 days/wk for 4 wks. Calf muscle oxygen saturation (smO 2 ) was recorded using near-infrared spectroscopy during the six-minute walking test (6MWT) before (Visit 1) and after (Visit 2) stretching or placebo stretching. The percentage decrease in smO 2 (from baseline) at minute 1 (Δ1) and minute 2 (Δ2) of the 6MWT was determined. Two-way ANOVA was used to compare Δ1 and Δ2 between the stretching and placebo stretching groups. Results: The mean age of the patients was 74.1±11.4 yrs with 52% (13/23) males. There was no significant difference in the changes in smO 2 during the 6MWT at either minute 1 (Δ1: 44.1±7.3% vs 27.1±7.0%, p=0.12) or minute 2 (Δ2: 78.7±8.2% vs 58.1±7.9%, p=0.08) between the stretching group and placebo stretching group at Visit 1. In contrast, at Visit 2, there was a significantly greater change in smO 2 at minute 2 (D2: 83.1±8.2% vs 51.3±7.9%, p=0.008) in the stretching group compared to the placebo stretching group with a trend towards a statistically greater change in smO 2 at minute 1 (Δ1: 39.0±7.3% vs 20.4±7.0%, p=0.06) (Image 2). Conclusion: Daily stretching of the calf muscles for 4 weeks is associated with increased oxygen extraction by the calf muscles during walking.

Peripheral Artery Disease (PAD) is a vascular disease that affects over 8 million Americans. PAD patients commonly have difficulty walking due to pain in the legs during physical exertion. Supervised walking therapy has been recommended to improve walking performance and attenuate disease progression; however, this therapy remains underutilized in PAD patients. Recently, there has been evidence to suggest that stretching accomplished via an ankle dorsiflexion splint may improve vascular health and walking performance in PAD; however, it is currently unknown how this protocol affects tissue oxygenation (StO 2 ). The purpose of this study was to determine the impact of 4 wks of ankle dorsiflexion stretching on measures of tissue oxygenation in patients with PAD. Thirteen PAD patients (67.7 ± 7.9 years) were randomized to a stretch (n = 9) or a non-stretch control (n = 4) group. Patients in the stretch were instructed to wear the splint for 30 min/day, 5 days/wk for 4 wks. A 5-min vascular occlusion test was administered before and after the intervention. Measures of StO 2 recovery were calculated following the vascular occlusion test and while completing a 6-minute walk test (6MWT). All measures of StO 2 were derived via Near-Infrared Spectroscopy. Repeated measures ANOVA was used to analyze data. There was a significant improvement in StO 2 recovery in the stretch group compared to the control (Stretch: 0.35 ± 0.25 %/sec vs 0.53 ± 0.29 %/sec; Control: 0.57 ± 0.43 %/sec vs 0.32 ± 0.19 %/sec; p = 0.002). During the 6MWT, patients completing the stretching protocol significantly improved oxygen extraction in the first minute of the test (-0.63 ± 0.05 StO 2 vs -0.73 ± 0.09 StO 2 ); however, this improvement was not significantly different compared to changes in the control group. These results indicate an improvement in microvascular reactivity and oxygen extraction following 4 wks of splint-based stretching. This stretching intervention holds potential therapeutic value for PAD patients and warrants further investigation.

Chronic mesenteric ischemia (CMI) can be treated with surgical revascularization or with angioplasty and stenting. As experience has been gained, endovascular treatment appears safe and effective in selected patients. Currently, surgical revascularization has better success and patency rates but also a higher short- and midterm mortality and morbidity, especially in patients at high surgical risk. A 72-year-old female with severe respiratory dysfunction presented with CMI resulting in profound malnutrition. Serial percutaneous interventions averted urgent surgery and reversed the mesenteric ischemia. Nine months later, after repeated angioplasty and stenting had failed, elective uncomplicated iliomesenteric bypass, in a medically optimized patient, resolved the ischemia. At an 18-month follow-up, the graft remained widely patent and the patient asymptomatic with a body weight corresponding to her ideal body weight. Compared to surgical revascularization, reocclusion or restenosis occurs more frequently after endovascular treatment of CMI, and reintervention may be necessary. Nevertheless, percutaneous intervention effectively provides relief from mesenteric ischemia and has lower perioperative complication rates compared to surgery in patients at high surgical risk. After initial relief of the CMI, the patient's condition may improve, allowing for more definitive secondary surgical revascularization, if needed.

The aim of this study was to determine the maximal aneurysm diameter (MAD), the total aneurysm volume (TAV), the intra-aneurysm vascular channel (IAVC), and total thrombus volume (TTV) and compare changes in those parameters during a 12-month time period. In addition, these parameters for three different endovascular grafts were compared. A retrospective review of 42 patients who had undergone endovascular aneurysm repair (EVAR) between July 1999 and March 2001, and without evidence of an endoleak or migration, was performed. The minimum follow-up in this group was 12 months. The three grafts deployed were Dacron-stainless steel bifurcated grafts with suprarenal fixation [Zenith; Cook, Inc. ( n = 14)], Dacron stainless steel aorto uni-iliac grafts with suprarenal fixation [custom-made ( n = 10)], and externally supported Dacron nitinol bifurcated grafts [AneuRx; Medtronic, Inc. ( n = 18)]. Volumetric measurements were obtained from CT images performed preoperatively, at 1 month and 12 months thereafter, using a 3-D Magicview 1000 workstation (Siemens, Inc.). Regardless of the type of endograft, a significant Change in MAD and TAV ( P = 0.008), IAVC ( P = 0.031), and TTV ( P = 0.001) was observed over the 12-month postoperative period. Both maximum diameter and total aneurysm volume appear to reflect accurately successful aneurysm exclusion. We conclude that both two-dimensional, maximal aneurysm diameter and three-dimensional, total aneurysm volume accurately reflect changes in morphology after endovascular aneurysm repair.

Background In previous carotid revascularization trials, stroke as a qualifying symptom has had the greatest importance as a predictor of subsequent outcomes. However, the importance of stroke, TIA, amaurosis fugax, and asymptomatic status has not been analyzed together and comparatively as predictors of outcome for carotid stenosis in a randomized clinical trial (RCT). Methods Qualifying events were analyzed for the 1321 symptomatic patients in the Carotid Revascularization Endarterectomy versus Stenting Trial (CREST) and were modeled as predictors of the primary outcome (stroke, myocardial infarction, and death during a 30-day peri-procedural period, or ipsilateral stroke over the follow-up period out to 4 years); the potential predictive value was also tested for the outcome of stroke and death. The model included other potential predictors such as age, sex, and treatment. Results The distribution of pre-randomization qualifying events among symptomatic patients in CREST was 572 strokes, 550 TIA, and 199 amaurosis fugax. Relative to symptomatic patients qualifying for the study with stroke, the risk of subsequent primary endpoint was 15% lower for those qualifying with TIA (HR=0.85; 95% CI = 0.57 - 1.28), 36% lower for those qualifying with amaurosis fugax (HR=0.64; 95% CI = 0.3 - 1.23), and 48% lower for asymptomatic patients (HR=0.52; 95% CI = 0.35 - 0.76). The risk of stroke or death was 11% lower for TIA (HR=0.89; 95% CI = 0.57 - 1.40), 18% lower for amaurosis fugax (HR=0.82; 95% CI = 0.42 - 1.60), and 57% lower for asymptomatic patients (HR=0.43; 95% CI = 0.28 - 0.67) when compared to symptomatic patients qualifying with stroke. The risk for patients with stroke or TIA did not differ significantly, and the risk for asymptomatic patients and patients with amaurosis fugax did not differ significantly. Conclusion Outcomes in patients with carotid disease were predicted in descending order by stroke, TIA, amaurosis fugax, and asymptomatic status in a large RCT. Asymptomatic status and amaurosis fugax have a comparatively benign prognosis. Better understanding of these predictors may help in determining who will benefit from carotid revascularization and how quickly they may benefit given the perioperative risks.

Mesenchymal stem cells (MSCs) have been shown to improve regeneration of injured tissues in vivo. Several in vitro studies and animal models have demonstrated improvement in MSCs paracrine effects under hypoxic conditions. Moreover, several studies suggested that the pro B-type natriuretic peptide (pro-BNP) could be involved in the stimulation of postischemic vascular regeneration. The purpose of this study was to investigate the effect of critical limb ischemia, in a human model, on in-situ adipose derived mesenchymal stem cells (ADMSCs) and to determine whether serum levels of N-terminal pro-BNP correlate with ADMSCs counts and associated paracrine effects. Lipoaspirate samples of ≥ 10mL were collected from ischemic limbs (ischemic group) and compared to control (without ischemia). MSCs were characterized by frequency, viability, differentiation potential, cytokines expression, and cell surface markers. Serum NT pro-BNP was measured as well. MSCs counts were 9-to-10-fold higher in patients with ischemic limbs (mean 7952 MSC/mL ± 542) than controls (mean 790 MSC/mL ± 65). Pro-BNP levels (1878-4757 pg/mL) were approximately 8-to-26-fold higher than in age- and sex-matched controls. Furthermore, there were positive correlations between pro-BNP levels and MSCs counts in the ischemic group. In conclusion, patients with critical limb ischemia (CLI) have higher levels of pro-BNP and MSCs counts than controls. Increased levels of pro-BNP and MSCs counts can be considered humoral and cellular surrogates of ischemia and hypoxia in patients with CLI. This supports recent studies that suggest that the increase production of peripheral BNP may be a stem cells-mediated response to stimulate angiogenesis in the ischemic skeletal muscles.

This study examines whether surgical resection of carotid body tumors (CBTs) is acceptable in light of potential significant neurologic complications. This IRB-approved retrospective study analyzed data from 24 patients undergoing surgical treatment for CBTs between April 1998 and April 2017 at Mayo Clinic (Florida campus only). For patients who underwent multiple CBT resections, only data from the first surgery was used in this analysis. CBT resection occurred in 24 patients with the following demographics: fourteen patients (58.3%) were female, median age was 56.5 years, median BMI was 29. A prior history of neoplasm was found in ten patients (41.7%). A known family history of paraganglioma was present in five patients (20.8%). Two patients were positive for succinate dehydrogenase mutation (8.3%). Multiple paragangliomas were present in seven patients (29.2%). There was nerve sacrifice in three patients (12.5%) during resection. Carotid artery reconstruction and patch angioplasty occurred in one patient (4.2%). Complete resection occurred in 24 patients (100.0%). Postoperatively, one patient (4.2%) suffered stroke. No mortalities occurred within or beyond 30 days of surgery. Persistent cranial nerve injury occurred in two patients (8.3%) with vocal cord paralysis. There was no recurrence of CBT through last follow-up. Five patients (20.8%) were diagnosed with other neoplasms after resection, including basal cell carcinoma, contralateral carotid body tumor, glomus vagale, and glomus jugulare. There was 100% survival at 1 year in patients followed for that time ( n = 17). Surgical treatment remains the first-line curative treatment to relieve symptoms and ensure non-recurrence. While acceptable, neurologic complications are significant and therefore detailed preoperative informed consent is mandatory.

Background To review long-term outcomes and saphenous vein (SV) occlusion rate after endovenous ablation (EVA) for symptomatic varicose veins. Methods A review of our EVA database (1998–2018) with at least 3-years of clinical and sonographic follow-up. The primary end point was SV closure rate. Results 542 limbs were evaluated. 358 limbs had radiofrequency and 323 limbs had laser ablations; 542 great saphenous veins (GSV), 106 small saphenous veins (SSV) and 33 anterior accessory saphenous veins (AASV) were treated. Follow-up was 5.6 ± 2.3 years; 508 (74.6%) veins were occluded, 53 (7.8%) partially occluded and 120 (17.6%) were patent. On multivariable Cox regression analysis, male sex (HR 1.6, 95% CI [0.46–018], p = 0.012) and use anticoagulation (HR 2.0, 95% CI [0.69–0.34], p = 0.044) were predictors of long-term failure. On Kaplan-Meier curve, we had an 86.3% occlusion rate. Conclusion Our experience revealed a 5-year closure rate of 86.3%. Ablations have satisfactory occlusion rate.

AbstractThe study aims to review the sex differences with respect to transient ischemic attack (TIA)/stroke and death in the perioperative period and on long-term follow-up among asymptomatic patients treated with carotid stenting (CAS) in the vascular quality initiative (VQI). All cases reported to VQI of asymptomatic CAS (ACAS) patients were reviewed. The primary end point was risk of TIA/stroke and death in the in-hospital perioperative period and in the long-term follow-up. The secondary end point was to evaluate predictors of in-hospital perioperative TIA/stroke and mortality on long-term follow-up after CAS. There were 22,079 CAS procedures captured from January 2005 to April 2019. There were 5,785 (62.7%) patients in the ACAS group. The rate of in-hospital TIA/stroke was higher in female patients (2.7 vs. 1.87%, p = 0.005) and the rate of death was not significant (0.03 vs. 0.07%, p = 0.66). On multivariable logistic regression analysis, prior/current smoking history (odds ratio = 0.58 [95% confidence interval or CI = 0.39–0.87]; p = 0.008) is a predictor of in-hospital TIA/stroke in females. The long-term all-cause mortality is significantly higher in male patients (26.9 vs. 15.7%, p < 0.001). On multivariable Cox-regression analysis, prior/current smoking history (hazard ratio or HR = 1.17 [95% CI = 1.01–1.34]; p = 0.03), coronary artery disease or CAD (HR = 1.15 [95% CI = 1.03–1.28]; p = 0.009), chronic obstructive pulmonary disease or COPD (HR = 1.73 [95% CI = 1.55–1.93]; p < 0.001), threat to life American Society of Anesthesiologists (ASA) class (HR = 2.3 [95% CI = 1.43–3.70]; p = 0.0006), moribund ASA class (HR = 5.66 [95% CI = 2.24–14.29]; p = 0.0003), and low hemoglobin levels (HR = 0.84 [95% CI = 0.82–0.86]; p < 0.001) are the predictors of long-term mortality. In asymptomatic carotid disease patients, women had higher rates of in-hospital perioperative TIA/stroke and a predictor of TIA/stroke is a prior/current history of smoking. Meanwhile, long-term all-cause mortality is higher for male patients compared with their female counterparts. Predictors of long-term mortality are prior/current smoking history, CAD, COPD, higher ASA classification of physical status, and low hemoglobin level. These data should be considered prior to offering CAS to asymptomatic female and male patients and careful risks versus benefits discussion should be offered to each individual patient.