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Showing papers in "Vascular Medicine in 2022"


Journal ArticleDOI
TL;DR: In this article , the authors conducted a subanalysis of the Registry of AngioVac Procedures in Detail (RAPID) multicenter registry representing 47 (20.1%) of 234 participants in the registry.
Abstract: Background: Right heart thrombi can be a source of considerable morbidity and mortality, especially when associated with pulmonary embolism. Methods: To understand the safety and procedural efficacy associated with vacuum-assisted thrombectomy using the AngioVac System (AngioDynamics, Latham, NY, USA) to remove right heart thrombi, we conducted a subanalysis of the Registry of AngioVac Procedures in Detail (RAPID) multicenter registry representing 47 (20.1%) of 234 participants in the registry. Forty-two (89.4%) patients had thrombi located in the right atrium alone, three (6.4%) in the right ventricle alone, and two (4.3%) in both the right atrium and ventricle. Four (8.5%) patients had concomitant caval thrombi, three (6.4%) also had catheter-related thrombi, and one (2.1%) patient had both caval and catheter-related thrombi with their right heart thrombi. Results: Extracorporeal bypass time was less than 1 hour for 39 (83.0%) procedures. Seventy to 100% removal of thrombus was achieved in 59.6% of patients. Estimated blood loss was less than 250 cc for 43 procedures (91.6%). Mean hemoglobin decreased from 10.7 ± 2.2 g/dL preoperatively to 9.6 ± 1.6 g/dL postoperatively. Transfusions were administered for eight procedures (17.0%), with only one (2.1%) patient receiving more than 2 units of blood. Six patients (12.8%) experienced procedure-related adverse events, including three (6.4%) patients who experienced distal emboli and three (6.4%) patients who developed bleeding-related complications. All adverse events resolved prior to discharge. There was one death (2.1%) reported that was not procedure related. Conclusion: Vacuum-assisted thrombectomy can be performed safely in patients with right heart thrombi. ClinicalTrials.gov Identifier: NCT04414332.

7 citations


Journal ArticleDOI
TL;DR: In this article , a systematic review aimed to examine the association between frailty assessments and postoperative outcomes in patients with vascular disease and found significant associations (p < 0.05) were established between mortality, 30-day morbidity, non-home discharge, adverse events, failure to rescue, patient requiring care after discharge, and amputation following critical limb ischaemia.
Abstract: One in 10 independently living adults aged 65 years old and older is considered frail, and frailty is associated with poor postoperative outcomes. This systematic review aimed to examine the association between frailty assessments and postoperative outcomes in patients with vascular disease. Electronic databases - MEDLINE, Embase, and the Cochrane Library - were searched from inception until January 2022, resulting in 648 articles reviewed for potential inclusion and 16 studies selected. Demographic data, surgery type, frailty measure, and postoperative outcomes predicted by frailty were extracted from the selected studies. The risk of bias was assessed using the Newcastle-Ottawa Scale. The selected studies (mean age: 56.1-76.3 years) had low-to-moderate risk of bias and included 16 vascular (elective and nonelective) surgeries and eight frailty measures. Significant associations (p < 0.05) were established between mortality (30-day, 90-day, 1-year, 5-year), 30-day morbidity, nonhome discharge, adverse events, failure to rescue, patient requiring care after discharge, and amputation following critical limb ischaemia. The strongest evidence was found between 30-day mortality and frailty. Composite 30-day morbidity and mortality, functional status at discharge, length of stay, spinal cord deficit, and access site complications were found to be nonsignificantly associated with frailty. With frailty being significantly associated with several adverse postoperative outcomes, preoperative frailty assessments can potentially be clinically useful in helping practitioners predict and guide the pre-, peri-, and postoperative management of frail with vascular disease.

5 citations


Journal ArticleDOI
TL;DR: With frailty being significantly associated with several adverse postoperative outcomes, preoperative frailty assessments can potentially be clinically useful in helping practitioners predict and guide the pre-, peri-, and postoperative management of frail with vascular disease.
Abstract: One in 10 independently living adults aged 65 years old and older is considered frail, and frailty is associated with poor postoperative outcomes. This systematic review aimed to examine the association between frailty assessments and postoperative outcomes in patients with vascular disease. Electronic databases – MEDLINE, Embase, and the Cochrane Library – were searched from inception until January 2022, resulting in 648 articles reviewed for potential inclusion and 16 studies selected. Demographic data, surgery type, frailty measure, and postoperative outcomes predicted by frailty were extracted from the selected studies. The risk of bias was assessed using the Newcastle–Ottawa Scale. The selected studies (mean age: 56.1–76.3 years) had low-to-moderate risk of bias and included 16 vascular (elective and nonelective) surgeries and eight frailty measures. Significant associations (p < 0.05) were established between mortality (30-day, 90-day, 1-year, 5-year), 30-day morbidity, nonhome discharge, adverse events, failure to rescue, patient requiring care after discharge, and amputation following critical limb ischaemia. The strongest evidence was found between 30-day mortality and frailty. Composite 30-day morbidity and mortality, functional status at discharge, length of stay, spinal cord deficit, and access site complications were found to be nonsignificantly associated with frailty. With frailty being significantly associated with several adverse postoperative outcomes, preoperative frailty assessments can potentially be clinically useful in helping practitioners predict and guide the pre-, peri-, and postoperative management of frail with vascular disease.

4 citations


Journal ArticleDOI
TL;DR: In this paper , two cohorts were established based on the revascularization type (percutaneous vascular interventions (PVI) or lower-extremity bypass). Frailty was assessed by the 5-item modified frailty index (mFI-5) and the VQI-derived risk analysis index (RAI).
Abstract: Multiple frailty screening tools are implemented; however, it is unclear whether they perform in a comparable way for both frailty detection and prediction of perioperative outcomes in patients undergoing lower-extremity revascularization.Patients undergoing lower-extremity revascularization were identified from the Vascular Quality Initiative (VQI) national database. Two cohorts were established based on the revascularization type (percutaneous vascular interventions (PVI) or lower-extremity bypass). Frailty was assessed by the 5-item modified frailty index (mFI-5) and the VQI-derived risk analysis index (RAI).Out of 134,081 patients undergoing PVI, frailty was identified in 67% by mFI-5 and 28% by RAI. Similarly, out of 41,316 patients in the bypass cohort, frailty was identified in 69% by mFI-5 and 16% by RAI. There was little agreement between the two frailty tools for both vascular cohorts (PVI: kappa: 0.17; bypass: kappa: 0.13). In an adjusted analysis, frailty as assessed by mFI-5 and RAI was associated with higher odds of mortality in both cohorts (p < 0.001). A significant association between frailty and unplanned amputations was only noted in the bypass cohort when RAI was applied (OR: 1.50, p < 0.01). The addition of frailty to traditional PAD risk factors marginally improved model performance to predict mortality and unplanned major amputations.There was significant variation in frailty detection by mFI-5 and RAI. Although frailty was associated with mortality, the predictive value of these tools in predicting outcomes in PAD was limited. Future research should focus on designing new frailty screening tools specific to the PAD population.

4 citations


Journal ArticleDOI
TL;DR: In this article , the effect of SGLT-2 inhibitors on pulse wave velocity (PWV) was investigated in six randomized controlled trials (RCTs) for adults with or without type 2 diabetes mellitus (T2DM).
Abstract: Background: Arterial stiffness represents an established cardiovascular risk marker. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have significant cardio-protective effects. Herein we sought to determine the effect of SGLT-2 inhibitors on pulse wave velocity (PWV). Methods: We searched PubMed, Cochrane Library, and grey literature from inception to 7 th February 2022 for randomized controlled trials (RCTs) enrolling adult subjects with or without type 2 diabetes mellitus (T2DM), assigned to a SGLT-2 inhibitor versus control and addressing their effect on PWV. We set as primary efficacy outcome the change in PWV with SGLT-2 inhibitors versus placebo or control. Results: We pooled data from six trials in a total of 452 enrolled participants assigned either to SGLT-2 inhibitor or control. Overall, SGLT-2 inhibitor treatment compared to control resulted in a nonsignificant decrease in PWV. Exclusion of a trial utilizing cardiac magnetic resonance imaging for the assessment of PWV demonstrated that SGLT-2 inhibitors induce a significant reduction in PWV by 0.21 m/s. When we restricted our analysis to RCTs enrolling subjects with T2DM, we observed that SGLT-2 inhibitor compared to control resulted in a significant decrease in PWV by 0.17 m/s. Conclusion: SGLT-2 inhibitors do not decrease PWV in patients with established cardiovascular disease or cardiovascular risk factors. However, we have shown that SGLT-2 inhibitors lead to a slight, but significant decrease in PWV in patients with T2DM. The latter finding is of great value, based on the significant correlation between PWV and micro- and macro-vascular complications of T2DM.

4 citations


Journal ArticleDOI
TL;DR: In this paper , a cross-sectional study used 98 healthy participants (19-77 years, 53 females) that wore an activPAL monitor on the thigh for 6.4 ± 0.8 days to objectively measure sedentary activity and completed a popliteal ultrasound assessment to determine FMD.
Abstract: Acute, laboratory-based bouts of prolonged sitting attenuate lower-limb arterial endothelial-dependent vasodilation. However, the impact of habitual sedentary patterns on popliteal artery endothelial health is unclear. We tested the hypothesis that greater habitual total sedentary time, more time spent in prolonged sedentary bouts, and fewer sedentary breaks would be associated with worse popliteal flow-mediated dilation (FMD) responses.This cross-sectional study used 98 healthy participants (19-77 years, 53 females) that wore an activPAL monitor on the thigh for 6.4 ± 0.8 days to objectively measure sedentary activity and completed a popliteal ultrasound assessment to determine FMD. Both relative (%baseline diameter) and absolute (mm) FMD were calculated. Using bivariate correlation and multiple regression analyses, we examined if there were relationships between sedentary outcomes and FMD while statistically controlling for any potential confounders.In the multiple regression model, age (p = 0.006, β = -0.030, 95% CI = -0.051, -0.009) and total time in sedentary bouts > 1 hour (p = 0.031, β = -0.005, 95% CI = -0.009, -0.001) were independent predictors of relative FMD. Age (β = -0.002, 95% CI = -0.003, -0.001), mean blood flow (β = 0.013, 95% CI = 0.002, 0.024), moderate-intensity physical activity (β = 155.9E-5, 95% CI = 22.4E-5, 289.4E-5), sedentary breaks (β = 0.036, 95% CI = 0.007, 0.066), and total time spent in sedentary bouts > 1 hour (β = -25.02E-5, 95% CI = -47.67E-5, -2.378E-5) were predictors of absolute FMD (all, p < 0.047). All independent outcomes remained significant after partially controlling for all other predictor variables (all, p < 0.031).Habitual prolonged sedentary bouts and sedentary breaks, but not total sedentary time, were predictors of popliteal endothelial-dependent vasodilatory function. The patterns by which sedentary time is accumulated may be more important than the total sedentary time on lower-limb arterial health.

4 citations


Journal ArticleDOI
TL;DR: Although frailty was associated with mortality, the predictive value of these tools in predicting outcomes in PAD was limited and future research should focus on designing new frailty screening tools specific to the PAD population.
Abstract: Background: Multiple frailty screening tools are implemented; however, it is unclear whether they perform in a comparable way for both frailty detection and prediction of perioperative outcomes in patients undergoing lower-extremity revascularization. Methods: Patients undergoing lower-extremity revascularization were identified from the Vascular Quality Initiative (VQI) national database. Two cohorts were established based on the revascularization type (percutaneous vascular interventions (PVI) or lower-extremity bypass). Frailty was assessed by the 5-item modified frailty index (mFI-5) and the VQI-derived risk analysis index (RAI). Results: Out of 134,081 patients undergoing PVI, frailty was identified in 67% by mFI-5 and 28% by RAI. Similarly, out of 41,316 patients in the bypass cohort, frailty was identified in 69% by mFI-5 and 16% by RAI. There was little agreement between the two frailty tools for both vascular cohorts (PVI: kappa: 0.17; bypass: kappa: 0.13). In an adjusted analysis, frailty as assessed by mFI-5 and RAI was associated with higher odds of mortality in both cohorts (p < 0.001). A significant association between frailty and unplanned amputations was only noted in the bypass cohort when RAI was applied (OR: 1.50, p < 0.01). The addition of frailty to traditional PAD risk factors marginally improved model performance to predict mortality and unplanned major amputations. Conclusion: There was significant variation in frailty detection by mFI-5 and RAI. Although frailty was associated with mortality, the predictive value of these tools in predicting outcomes in PAD was limited. Future research should focus on designing new frailty screening tools specific to the PAD population.

4 citations


Journal ArticleDOI
TL;DR: In this paper , an anchor-based method was used to determine minimal clinically important differences for small, moderate, and large changes in daily step counts and time spent in moderate-to-vigorous physical activity (MVPA) following both supervised and home-based exercise programs in symptomatic patients with peripheral artery disease (PAD).
Abstract: Introduction: We estimated minimal clinically important differences (MCID) for small, moderate, and large changes in daily step counts and time spent in moderate-to-vigorous physical activity (MVPA) following both supervised and home-based exercise programs in symptomatic patients with peripheral artery disease (PAD). Methods: Patients were randomized to either 12 weeks of a supervised exercise program (n = 60), a home-based exercise program (n = 60), or an attention-control group (n = 60). Results: Using the anchor-based method to determine MCID, the MCID value for a large change in health-related quality of life (HRQoL) was an increase of 1211 total daily steps and an increase in 11 minutes in the time spent in MVPA following 12 weeks of exercise intervention. Using the distribution-based method, the MCID values for small, moderate, and large changes in total daily steps in the home-based exercise group were 558, 1396, and 2233 steps/d, respectively, and the corresponding changes in the time spent in MVPA were 6, 15, and 23 minutes. Similar distribution-based MCID scores were noted for the supervised exercise group. Conclusion: Following 3 months of home-based and supervised exercise programs for patients with PAD and claudication, increases of 11 minutes in time spent in MVPA and 1211 total daily steps were associated with large anchor-based MCID increases in HRQoL. The clinical implication is that patients with PAD and claudication should be encouraged to increase daily steps, particularly by walking an additional 11 minutes each day in MVPA, which is associated with a large meaningful increase in HRQoL.

4 citations


Journal ArticleDOI
TL;DR: Vacuum-assisted thrombectomy can be performed safely in patients with right heart thrombi, and one death was reported that was not procedure related.
Abstract: Background: Right heart thrombi can be a source of considerable morbidity and mortality, especially when associated with pulmonary embolism. Methods: To understand the safety and procedural efficacy associated with vacuum-assisted thrombectomy using the AngioVac System (AngioDynamics, Latham, NY, USA) to remove right heart thrombi, we conducted a subanalysis of the Registry of AngioVac Procedures in Detail (RAPID) multicenter registry representing 47 (20.1%) of 234 participants in the registry. Forty-two (89.4%) patients had thrombi located in the right atrium alone, three (6.4%) in the right ventricle alone, and two (4.3%) in both the right atrium and ventricle. Four (8.5%) patients had concomitant caval thrombi, three (6.4%) also had catheter-related thrombi, and one (2.1%) patient had both caval and catheter-related thrombi with their right heart thrombi. Results: Extracorporeal bypass time was less than 1 hour for 39 (83.0%) procedures. Seventy to 100% removal of thrombus was achieved in 59.6% of patients. Estimated blood loss was less than 250 cc for 43 procedures (91.6%). Mean hemoglobin decreased from 10.7 ± 2.2 g/dL preoperatively to 9.6 ± 1.6 g/dL postoperatively. Transfusions were administered for eight procedures (17.0%), with only one (2.1%) patient receiving more than 2 units of blood. Six patients (12.8%) experienced procedure-related adverse events, including three (6.4%) patients who experienced distal emboli and three (6.4%) patients who developed bleeding-related complications. All adverse events resolved prior to discharge. There was one death (2.1%) reported that was not procedure related. Conclusion: Vacuum-assisted thrombectomy can be performed safely in patients with right heart thrombi. ClinicalTrials.gov Identifier: NCT04414332.

4 citations


Journal ArticleDOI
TL;DR: Cardiovascular manifestations in adults with hEDS/HSD, especially females, are typically mild and readily assessed by echocardiography, and should be considered on the differential for patients with CeAD or SCAD who also have joint hypermobility.
Abstract: Introduction: Mitral valve prolapse and aortic root dilatation are reported in association with hypermobile Ehlers–Danlos syndrome (hEDS), but the full phenotypic spectrum of cardiovascular complications in this condition has not been studied in the aftermath of updated nosology and diagnostic criteria. Methods: We performed a retrospective review of 258 patients (> 94% adults) referred to a multidisciplinary clinic for evaluation of joint hypermobility between January 2017 and December 2020 and diagnosed with hEDS or a hypermobility spectrum disorder (HSD) to determine the incidence and spectrum of cardiovascular involvement. Results: Mitral valve prolapse was present in 7.5% and thoracic aortic dilatation in 15.2%. Aortic dilatation was more frequent in individuals with hEDS (20.7%) than with HSD (7.7%) and similarly prevalent between males and females, although was mild in > 90% of females and moderate-to-severe in 50% of males. Five individuals (1.9%) with hEDS/HSD had extra-aortic arterial involvement, including cervical artery dissection (CeAD, n = 2), spontaneous coronary artery dissection (SCAD, n = 2), and SCAD plus celiac artery pseudoaneurysm (n = 1). This is the first series to report the prevalence of CeAD and SCAD in hEDS/HSD. Conclusions: Cardiovascular manifestations in adults with hEDS/HSD, especially females, are typically mild and readily assessed by echocardiography. Since the risk of progression has not yet been defined, adults with hEDS/HSD who are found to have aortic dilatation at baseline should continue ongoing surveillance to monitor for progressive dilatation. Cardiovascular medicine specialists, neurologists, and neurosurgeons should consider hEDS/HSD on the differential for patients with CeAD or SCAD who also have joint hypermobility.

4 citations


Journal ArticleDOI
TL;DR: In this article , the authors performed a retrospective review of 258 patients referred to a multidisciplinary clinic for evaluation of joint hypermobility between January 2017 and December 2020 and diagnosed with hypermobile Ehlers-Danlos syndrome (hEDS) or a hypermobile spectrum disorder (HSD) to determine the incidence and spectrum of cardiovascular involvement.
Abstract: Introduction: Mitral valve prolapse and aortic root dilatation are reported in association with hypermobile Ehlers-Danlos syndrome (hEDS), but the full phenotypic spectrum of cardiovascular complications in this condition has not been studied in the aftermath of updated nosology and diagnostic criteria. Methods: We performed a retrospective review of 258 patients (> 94% adults) referred to a multidisciplinary clinic for evaluation of joint hypermobility between January 2017 and December 2020 and diagnosed with hEDS or a hypermobility spectrum disorder (HSD) to determine the incidence and spectrum of cardiovascular involvement. Results: Mitral valve prolapse was present in 7.5% and thoracic aortic dilatation in 15.2%. Aortic dilatation was more frequent in individuals with hEDS (20.7%) than with HSD (7.7%) and similarly prevalent between males and females, although was mild in > 90% of females and moderate-to-severe in 50% of males. Five individuals (1.9%) with hEDS/HSD had extra-aortic arterial involvement, including cervical artery dissection (CeAD, n = 2), spontaneous coronary artery dissection (SCAD, n = 2), and SCAD plus celiac artery pseudoaneurysm (n = 1). This is the first series to report the prevalence of CeAD and SCAD in hEDS/HSD. Conclusions: Cardiovascular manifestations in adults with hEDS/HSD, especially females, are typically mild and readily assessed by echocardiography. Since the risk of progression has not yet been defined, adults with hEDS/HSD who are found to have aortic dilatation at baseline should continue ongoing surveillance to monitor for progressive dilatation. Cardiovascular medicine specialists, neurologists, and neurosurgeons should consider hEDS/HSD on the differential for patients with CeAD or SCAD who also have joint hypermobility.

Journal ArticleDOI
TL;DR: Although many participants reported improved walking ability after LER, a substantial proportion remained severely disabled, and these observations may help motivate providers, patients, and medical systems to improve awareness and engagement in SET referral after Ler.
Abstract: Background: Peripheral artery disease (PAD) affects 200 million people worldwide and is associated with impaired quality of life, increased morbidity, and mortality. Supervised exercise therapy (SET) and lower-extremity revascularization (LER) are both proven strategies to improve patient symptoms. Short and long-term functional outcomes after LER for symptomatic PAD in a large, international cohort have not previously been described. Methods: The VOYAGER PAD trial (ClinicalTrials.gov identifier: NCT02504216) enrolled subjects after LER for symptomatic PAD (Rutherford category 2–6). Participants completed the Walking Impairment Questionnaire (WIQ) at baseline, 1, 3 and 6 months, and every 6 months thereafter. The primary outcome analysis was degree of difficulty walking two blocks at each of the aforementioned time points. Difficulty walking three blocks and climbing one flight of stairs at these time points was also analyzed. Data about supervised and home exercise therapy before or after revascularization were not collected in the VOYAGER PAD trial. Results: Of the 5614 VOYAGER PAD participants completing the WIQ at baseline, three-quarters presented with claudication and one-quarter with critical limb ischemia. Of these, the majority (62% with claudication and 74% with CLI) reported inability or much difficulty walking two blocks prior to LER. Walking improved after LER regardless of revascularization strategy, but one-fifth with claudication and one-third with CLI reported continued inability or much difficulty walking two blocks 1 month after LER. Participants who reported improved walking ability 1 month after LER experienced a durable functional result out to 3 years. Although the proportion of participants reporting significant baseline difficulty climbing one flight of stairs or walking three blocks differed, the trend in immediate and sustained improvement after LER was similar to that observed for walking two blocks. Conclusion: In this large, international cohort undergoing LER for symptomatic PAD, nearly two-thirds reported inability or much difficulty walking two blocks at baseline. Although many participants reported improved walking ability after LER, a substantial proportion remained severely disabled. These observations may help motivate providers, patients, and medical systems to improve awareness and engagement in SET referral after LER.

Journal ArticleDOI
TL;DR: It is shown that SGLT-2 inhibitors lead to a slight, but significant decrease in PWV in patients with type 2 diabetes mellitus, based on the significant correlation between PWV and micro- and macro-vascular complications of T2DM.
Abstract: Background: Arterial stiffness represents an established cardiovascular risk marker. Sodium-glucose co-transporter-2 (SGLT-2) inhibitors have significant cardio-protective effects. Herein we sought to determine the effect of SGLT-2 inhibitors on pulse wave velocity (PWV). Methods: We searched PubMed, Cochrane Library, and grey literature from inception to 7th February 2022 for randomized controlled trials (RCTs) enrolling adult subjects with or without type 2 diabetes mellitus (T2DM), assigned to a SGLT-2 inhibitor versus control and addressing their effect on PWV. We set as primary efficacy outcome the change in PWV with SGLT-2 inhibitors versus placebo or control. Results: We pooled data from six trials in a total of 452 enrolled participants assigned either to SGLT-2 inhibitor or control. Overall, SGLT-2 inhibitor treatment compared to control resulted in a nonsignificant decrease in PWV. Exclusion of a trial utilizing cardiac magnetic resonance imaging for the assessment of PWV demonstrated that SGLT-2 inhibitors induce a significant reduction in PWV by 0.21 m/s. When we restricted our analysis to RCTs enrolling subjects with T2DM, we observed that SGLT-2 inhibitor compared to control resulted in a significant decrease in PWV by 0.17 m/s. Conclusion: SGLT-2 inhibitors do not decrease PWV in patients with established cardiovascular disease or cardiovascular risk factors. However, we have shown that SGLT-2 inhibitors lead to a slight, but significant decrease in PWV in patients with T2DM. The latter finding is of great value, based on the significant correlation between PWV and micro- and macro-vascular complications of T2DM.

Journal ArticleDOI
TL;DR: The VOYAGER PAD trial (ClinicalTrials.gov identifier: NCT02504216) enrolled subjects after LER for symptomatic PAD (Rutherford category 2-6). Participants completed the Walking Impairment Questionnaire (WIQ) at baseline, 1, 3 and 6 months, and every 6 months thereafter as discussed by the authors .
Abstract: Background: Peripheral artery disease (PAD) affects 200 million people worldwide and is associated with impaired quality of life, increased morbidity, and mortality. Supervised exercise therapy (SET) and lower-extremity revascularization (LER) are both proven strategies to improve patient symptoms. Short and long-term functional outcomes after LER for symptomatic PAD in a large, international cohort have not previously been described. Methods: The VOYAGER PAD trial (ClinicalTrials.gov identifier: NCT02504216) enrolled subjects after LER for symptomatic PAD (Rutherford category 2–6). Participants completed the Walking Impairment Questionnaire (WIQ) at baseline, 1, 3 and 6 months, and every 6 months thereafter. The primary outcome analysis was degree of difficulty walking two blocks at each of the aforementioned time points. Difficulty walking three blocks and climbing one flight of stairs at these time points was also analyzed. Data about supervised and home exercise therapy before or after revascularization were not collected in the VOYAGER PAD trial. Results: Of the 5614 VOYAGER PAD participants completing the WIQ at baseline, three-quarters presented with claudication and one-quarter with critical limb ischemia. Of these, the majority (62% with claudication and 74% with CLI) reported inability or much difficulty walking two blocks prior to LER. Walking improved after LER regardless of revascularization strategy, but one-fifth with claudication and one-third with CLI reported continued inability or much difficulty walking two blocks 1 month after LER. Participants who reported improved walking ability 1 month after LER experienced a durable functional result out to 3 years. Although the proportion of participants reporting significant baseline difficulty climbing one flight of stairs or walking three blocks differed, the trend in immediate and sustained improvement after LER was similar to that observed for walking two blocks. Conclusion: In this large, international cohort undergoing LER for symptomatic PAD, nearly two-thirds reported inability or much difficulty walking two blocks at baseline. Although many participants reported improved walking ability after LER, a substantial proportion remained severely disabled. These observations may help motivate providers, patients, and medical systems to improve awareness and engagement in SET referral after LER.

Journal ArticleDOI
TL;DR: Habitual prolonged sedentary bouts and sedentary breaks, but not total sedentary time, were predictors of popliteal endothelial-dependent vasodilatory function, suggesting that the patterns by which sedentaryTime is accumulated may be more important than the total Sedentary time on lower-limb arterial health.
Abstract: Introduction: Acute, laboratory-based bouts of prolonged sitting attenuate lower-limb arterial endothelial-dependent vasodilation. However, the impact of habitual sedentary patterns on popliteal artery endothelial health is unclear. We tested the hypothesis that greater habitual total sedentary time, more time spent in prolonged sedentary bouts, and fewer sedentary breaks would be associated with worse popliteal flow-mediated dilation (FMD) responses. Methods: This cross-sectional study used 98 healthy participants (19–77 years, 53 females) that wore an activPAL monitor on the thigh for 6.4 ± 0.8 days to objectively measure sedentary activity and completed a popliteal ultrasound assessment to determine FMD. Both relative (%baseline diameter) and absolute (mm) FMD were calculated. Using bivariate correlation and multiple regression analyses, we examined if there were relationships between sedentary outcomes and FMD while statistically controlling for any potential confounders. Results: In the multiple regression model, age (p = 0.006, β = −0.030, 95% CI = −0.051, −0.009) and total time in sedentary bouts > 1 hour (p = 0.031, β = −0.005, 95% CI = −0.009, −0.001) were independent predictors of relative FMD. Age (β = −0.002, 95% CI = −0.003, −0.001), mean blood flow (β = 0.013, 95% CI = 0.002, 0.024), moderate-intensity physical activity (β = 155.9E−5, 95% CI = 22.4E−5, 289.4E−5), sedentary breaks (β = 0.036, 95% CI = 0.007, 0.066), and total time spent in sedentary bouts > 1 hour (β = −25.02E−5, 95% CI = −47.67E−5, −2.378E−5) were predictors of absolute FMD (all, p < 0.047). All independent outcomes remained significant after partially controlling for all other predictor variables (all, p < 0.031). Conclusions: Habitual prolonged sedentary bouts and sedentary breaks, but not total sedentary time, were predictors of popliteal endothelial-dependent vasodilatory function. The patterns by which sedentary time is accumulated may be more important than the total sedentary time on lower-limb arterial health.

Journal ArticleDOI
TL;DR: In this paper , a systematic review assesses the appropriateness of IVUS as an imaging modality for guiding peripheral intervention through evidence collection and clinical appraisal of studies and concludes that IVUS-guided peripheral intervention in arterial and venous diagnosis and treatment was superior to other imaging techniques alone.
Abstract: Although angiography has been the primary imaging modality used in peripheral vascular intervention, this technique has major limitations due to the evaluation of three-dimensional vessels in two dimensions. Intravascular ultrasound (IVUS) is an important adjunctive tool that can address some of these limitations. This systematic review assesses the appropriateness of IVUS as an imaging modality for guiding peripheral intervention through evidence collection and clinical appraisal of studies. Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a cohort of 48 studies (29 arterial; 19 venous) detailing IVUS use in peripheral vascular intervention were extracted. Qualitative assessment of the studies evaluated pre- and postprocedure efficacy of IVUS and revealed that IVUS-guided peripheral intervention in arterial and venous diagnosis and treatment was superior to other imaging techniques alone. Each study in the cohort was further assessed for reliability and validity using the Oxford Centre for Evidence Based Medicine (CEBM) level of evidence scale. The majority of both arterial (79.3%) and venous (73.7%) studies received a 2b rating, the second highest level of evidence rating. The evidence to date indicates that IVUS results in better clinical outcomes overall and should be more widely adopted as an adjunctive imaging modality during peripheral intervention. (PROSPERO Registration No.: CRD42021232353)

Journal ArticleDOI
TL;DR: It is demonstrated that a genome-wide PRS can discriminate risk of PAD and other cardiovascular diseases and add a PAD PRS to clinical risk models may help improve detection of prevalent, but undiagnosed disease.
Abstract: Introduction: Peripheral artery disease (PAD) is a major cause of cardiovascular morbidity and mortality, yet timely diagnosis is elusive. Larger genome-wide association studies (GWAS) have now provided the ability to evaluate whether genetic data, in the form of genome-wide polygenic risk scores (PRS), can help improve our ability to identify patients at high risk of having PAD. Methods: Using summary statistic data from the largest PAD GWAS from the Million Veteran Program, we developed PRSs with genome data from UK Biobank. We then evaluated the clinical utility of adding the best-performing PRS to a PAD clinical risk score. Results: A total of 487,320 participants (5759 PAD cases) were included in our final genetic analysis. Compared to participants in the lowest 10% of PRS, those in the highest decile had 3.1 higher odds of having PAD (95% CI, 3.06–3.21). Additionally, a PAD PRS was associated with increased risk of having coronary artery disease, congestive heart failure, and cerebrovascular disease. The PRS significantly improved a clinical risk model (Net Reclassification Index = 0.07, p < 0.001), with most of the performance seen in downgrading risk of controls. Combining clinical and genetic data to detect risk of PAD resulted in a model with an area under the curve of 0.76 (95% CI, 0.75–0.77). Conclusion: We demonstrate that a genome-wide PRS can discriminate risk of PAD and other cardiovascular diseases. Adding a PAD PRS to clinical risk models may help improve detection of prevalent, but undiagnosed disease.

Journal ArticleDOI
TL;DR: In this article , the authors used summary statistic data from the largest PAD GWAS from the Million Veteran Program (MVP) to develop genome-wide polygenic risk scores (PRSs) with genome data from UK Biobank and evaluated the clinical utility of adding the best-performing PRS to a PAD clinical risk score.
Abstract: Introduction: Peripheral artery disease (PAD) is a major cause of cardiovascular morbidity and mortality, yet timely diagnosis is elusive. Larger genome-wide association studies (GWAS) have now provided the ability to evaluate whether genetic data, in the form of genome-wide polygenic risk scores (PRS), can help improve our ability to identify patients at high risk of having PAD. Methods: Using summary statistic data from the largest PAD GWAS from the Million Veteran Program, we developed PRSs with genome data from UK Biobank. We then evaluated the clinical utility of adding the best-performing PRS to a PAD clinical risk score. Results: A total of 487,320 participants (5759 PAD cases) were included in our final genetic analysis. Compared to participants in the lowest 10% of PRS, those in the highest decile had 3.1 higher odds of having PAD (95% CI, 3.06–3.21). Additionally, a PAD PRS was associated with increased risk of having coronary artery disease, congestive heart failure, and cerebrovascular disease. The PRS significantly improved a clinical risk model (Net Reclassification Index = 0.07, p < 0.001), with most of the performance seen in downgrading risk of controls. Combining clinical and genetic data to detect risk of PAD resulted in a model with an area under the curve of 0.76 (95% CI, 0.75–0.77). Conclusion: We demonstrate that a genome-wide PRS can discriminate risk of PAD and other cardiovascular diseases. Adding a PAD PRS to clinical risk models may help improve detection of prevalent, but undiagnosed disease.

Journal ArticleDOI
TL;DR: In this paper , a systematic review of studies examining the impact of physical behaviours on low-flow-mediated constriction (L-FMC) in adults is presented. But, it is unclear whether aerobic fitness and movement (or lack thereof) influences the effect of vascular vasoconstrictor function.
Abstract: The cardiovascular benefits of physical exercise are well established. The vasoreactivity that occurs during reductions in local arterial blood flow, termed low-flow-mediated constriction (L-FMC), is a measure of endothelial-dependent vasoconstrictor function. It is unclear whether aerobic fitness and movement (or lack thereof) influences L-FMC. We systematically reviewed studies examining the impact of physical behaviours on L-FMC. To be included, cross-sectional and interventional studies had to examine the impact of a physical behaviour on L-FMC in adults. There were no language or date of publication restrictions. Sources were searched in May, 2021 and included Scopus, Embase, MEDLINE, CINAHL, and Academic Search Premier. National Institutes of Health quality assessment tools were used. Fourteen studies (15 arms; 313 participants; 398 total observations from four arteries) met the inclusion criteria. The study quality varied from four out of 14 (controlled intervention scoring) to nine out of 12 (longitudinal intervention with no control group scoring) with the total points dependent upon the study design. Conflicting results were reported for acute prolonged sitting studies (attenuated L-FMC: n = 1; no change: n = 1) and resistance exercise (increased L-FMC: n = 2; no change: n = 2). Most observational studies examining aerobic fitness (3/4 studies) and aerobic exercise interventions (4/5 studies) observed a favourable effect on L-FMC. Overall, the included studies support that higher aerobic fitness and engaging in aerobic exercise training may augment L-FMC responses. Our systematic review highlights the heterogeneity between studies and identifies current gaps and future directions to better our understanding of (in)activity, exercise, and posture on endothelial vasoconstrictor function. PROSPERO Registration No.: CRD42021248241.

Journal ArticleDOI
TL;DR: In this article , the authors present a historical review of research on exercise training for peripheral artery disease (PAD), which is associated with increased cardiovascular morbidity and mortality as well as decreased functional ability.
Abstract: Peripheral artery disease (PAD), a prevalent manifestation of atherosclerosis, is associated with increased cardiovascular morbidity and mortality as well as decreased functional ability. Exercise training for PAD is acknowledged to be a highly effective treatment, which improves walking ability and cardiovascular risk. The historical development of this treatment has not been the focus of a report. Therefore, we present a historical review of research on exercise training for PAD. Overall, this body of knowledge has provided strong evidence of the efficacy of supervised exercise training (SET) to improve walking ability for patients with claudication due to PAD. SET, using intermittent bouts of walking exercise to moderate claudication pain on a treadmill, is considered the most efficacious mode of exercise to improve walking ability in patients with claudication. This compelling evidence published over the past 60 years was evaluated by the Centers for Medicare & Medicaid Services in 2017, which culminated in a national coverage determination for SET to improve symptomatic PAD. Future directions include determining optimal delivery strategies for SET and further elucidation of the mechanisms of improvement in walking ability resulting from SET. In addition, alternative forms of exercise should be evaluated and effective home- and community-based exercise interventions should be assessed. There is an enormous need to increase the inclusion of women and racial and ethnic minority groups in studies. It is to be hoped that researchers will continue with new innovative research and persistence in the treatment of claudication due to PAD.

Journal ArticleDOI
TL;DR: In this paper , the feasibility, safety, and preliminary efficacy of a treadmill walking (TM) versus a total body recumbent stepping (TBRS) exercise program for treatment of peripheral artery disease (PAD) were compared.
Abstract: Background: Treadmill walking is the most commonly recommended exercise modality in supervised exercise therapy (SET) for peripheral artery disease (PAD); however, other modalities may be equally effective and more tolerable for patients. The primary aim of this single-blind, randomized pilot study was to compare the feasibility, safety, and preliminary efficacy of a treadmill walking (TM) versus a total body recumbent stepping (TBRS) exercise program for treatment of PAD (i.e., "Stepper Study").. Methods: Participants (n = 19) enrolled in a 12-week SET program and were randomized to either a TM (n = 9) or TBRS (n = 10) exercise group that followed current SET exercise guidelines. Feasibility, safety, and efficacy outcomes were assessed. Results: SET attendance was 86% and 71%, respectively, for TBRS and TM groups (p = 0.07). Session exercise dose (metabolic equivalents of task [MET] minutes) (mean [SD]) for TM was 117.6 [27.4] compared to 144.7 [28.7] in the TBRS group (p = 0.08). Study-related adverse events were nine in 236 training hours and three in 180 training hours for the TBRS and TM groups, respectively. There were no significant differences between groups for improvement in 6-minute walk distance (mean [SD]) (TM: 133.2 ft [53.5] vs TBRS: 154.8 ft [49.8]; p = 0.77) after adjusting for baseline 6-minute walk distance. Conclusion: This is the first randomized study comparing TBRS to TM exercise in SET using current SET guidelines. This pilot study showed that TBRS is a feasible and safe exercise modality in SET. This study provides preliminary efficacy of the use of TBRS exercise in SET programs following current guidelines. Larger studies should be conducted to confirm these findings.

letters-and-commentsDOI
TL;DR: This study retrospectively analyzed adult patients in the Blue Cross Blue Shield-sponsored Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry who were newly initiated on warfarin therapy for VTE and entered in the registry between April 1, 2010 and October 31, 2020.
Abstract: Clinical evidence regarding combination anticoagulant– antiplatelet therapy has largely focused on atrial fibrillation (AF) as the primary indication for anticoagulation. Expert recommendations from the American College of Cardiology (ACC) discourage the use of so-called ‘triple therapy’, that is, anticoagulation and dual antiplatelet therapy (aspirin and a P2Y12 inhibitor), in patients on preexisting antiplatelet therapy who develop a new venous thromboembolism (VTE).1 However, this guidance is extrapolated from evidence in AF without robust data in the VTE population, which has distinct demographics, comorbidities, and timevarying risk of recurrent thrombosis.2 To address this gap, we explored a multicenter cohort of patients initiated on warfarin therapy for management of VTE. Our study aimed to evaluate the frequency and outcomes of antiplatelet therapy in addition to warfarin for patients with VTE. We retrospectively analyzed adult patients in the Blue Cross Blue Shield-sponsored Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry who were newly initiated on warfarin therapy for VTE and entered in the registry between April 1, 2010 and October 31, 2020.3,4 The University of Michigan institutional review board approved the study. Patients with a history of atrial fibrillation/flutter, heart valve replacement, and/or antiphospholipid antibody syndrome were excluded. Patient data were abstracted from the time of enrollment through the earliest of either the first adverse event, discontinuation of warfarin, or last follow-up before October 31, 2020. Patient characteristics were assessed at enrollment, while adverse events were assessed at each follow-up visit. Adjusted associations between number of antiplatelets and event outcomes were examined using Cox proportional hazards. Of the 2918 patients initiating warfarin for treatment of VTE, 1333 (45.7%) were men with a mean (SD) age of 61.0 (16.4) years. During the study period, 820 patients (28.1%) received warfarin plus one or more antiplatelet medications, compared to 2098 (71.9%) who received warfarin monotherapy (online Supplementary Table 1). Patients on combination warfarin and antiplatelet therapy had a higher incidence of documented coronary artery disease, prior myocardial infarction, and coronary revascularization. Compared to the warfarin monotherapy group, the combination warfarin–antiplatelet group had a higher average RIETE bleed score (2.5 vs 2.0, p < 0.001).5,6 Aspirin monotherapy was the most common antiplatelet regimen (83.4%), followed by dual antiplatelet therapy (11.0%) and P2Y12 inhibitor monotherapy (5.1%). The warfarin monotherapy reference group experienced 3.3 thrombotic events per 100-patient-years, compared to warfarin plus single antiplatelet (2.7 per 100-patient-years, p = 0.190) or warfarin plus dual antiplatelet (2.2 per 100-patient-years, p = 0.773; Figure 1). The warfarin monotherapy reference group experienced 20.0 overall bleeding events per 100-patient-years, compared to warfarin plus single antiplatelet (24.7 per 100-patient-years, p = 0.013) or warfarin plus dual antiplatelet (58.9 per 100-patientyears, p < 0.001; Figure 1). Association of adding antiplatelet therapy to warfarin for management of venous thromboembolism with bleeding and other adverse events


Journal ArticleDOI
Abstract: Background: Treadmill walking is the most commonly recommended exercise modality in supervised exercise therapy (SET) for peripheral artery disease (PAD); however, other modalities may be equally effective and more tolerable for patients. The primary aim of this single-blind, randomized pilot study was to compare the feasibility, safety, and preliminary efficacy of a treadmill walking (TM) versus a total body recumbent stepping (TBRS) exercise program for treatment of PAD (i.e., "Stepper Study").. Methods: Participants (n = 19) enrolled in a 12-week SET program and were randomized to either a TM (n = 9) or TBRS (n = 10) exercise group that followed current SET exercise guidelines. Feasibility, safety, and efficacy outcomes were assessed. Results: SET attendance was 86% and 71%, respectively, for TBRS and TM groups (p = 0.07). Session exercise dose (metabolic equivalents of task [MET] minutes) (mean [SD]) for TM was 117.6 [27.4] compared to 144.7 [28.7] in the TBRS group (p = 0.08). Study-related adverse events were nine in 236 training hours and three in 180 training hours for the TBRS and TM groups, respectively. There were no significant differences between groups for improvement in 6-minute walk distance (mean [SD]) (TM: 133.2 ft [53.5] vs TBRS: 154.8 ft [49.8]; p = 0.77) after adjusting for baseline 6-minute walk distance. Conclusion: This is the first randomized study comparing TBRS to TM exercise in SET using current SET guidelines. This pilot study showed that TBRS is a feasible and safe exercise modality in SET. This study provides preliminary efficacy of the use of TBRS exercise in SET programs following current guidelines. Larger studies should be conducted to confirm these findings.

Journal ArticleDOI
TL;DR: The included studies support that higher aerobic fitness and engaging in aerobic exercise training may augment L-FMC responses and identify current gaps and future directions to better understanding of (in)activity, exercise, and posture on endothelial vasoconstrictor function.
Abstract: The cardiovascular benefits of physical exercise are well established. The vasoreactivity that occurs during reductions in local arterial blood flow, termed low-flow-mediated constriction (L-FMC), is a measure of endothelial-dependent vasoconstrictor function. It is unclear whether aerobic fitness and movement (or lack thereof) influences L-FMC. We systematically reviewed studies examining the impact of physical behaviours on L-FMC. To be included, cross-sectional and interventional studies had to examine the impact of a physical behaviour on L-FMC in adults. There were no language or date of publication restrictions. Sources were searched in May, 2021 and included Scopus, Embase, MEDLINE, CINAHL, and Academic Search Premier. National Institutes of Health quality assessment tools were used. Fourteen studies (15 arms; 313 participants; 398 total observations from four arteries) met the inclusion criteria. The study quality varied from four out of 14 (controlled intervention scoring) to nine out of 12 (longitudinal intervention with no control group scoring) with the total points dependent upon the study design. Conflicting results were reported for acute prolonged sitting studies (attenuated L-FMC: n = 1; no change: n = 1) and resistance exercise (increased L-FMC: n = 2; no change: n = 2). Most observational studies examining aerobic fitness (3/4 studies) and aerobic exercise interventions (4/5 studies) observed a favourable effect on L-FMC. Overall, the included studies support that higher aerobic fitness and engaging in aerobic exercise training may augment L-FMC responses. Our systematic review highlights the heterogeneity between studies and identifies current gaps and future directions to better our understanding of (in)activity, exercise, and posture on endothelial vasoconstrictor function. PROSPERO Registration No.: CRD42021248241

Journal ArticleDOI
Zhenyu Guo, Xu Li, Tao Wang, Xiaohu Yang, Longhua Fan 
TL;DR: Clinical and experimental findings implicated hyperhomocysteinemia as a key factor in the development of venous ulceration, and further research is needed to appraise the effectiveness of HHcy-lowering therapy in the prevention of venOUS ulcers in patients with varicose veins.
Abstract: Introduction: Venous ulceration is a multifactorial disease, and whether hyperhomocysteinemia (HHcy) promotes deterioration from primary varicose veins to venous ulcers remains unproven. Methods: This study retrospectively analyzed clinical data from 717 patients to investigate the potential correlation between HHcy and primary varicose veins ulcer formation, including 611 patients without ulcers (control group) and 106 with ulcers (case group). Results: In this study, 46.2% (49/106) of patients in the case group and 17.5% (107/611, p < 0.001) in the control group suffered from HHcy. Multivariate logistic analysis revealed that HHcy was closely associated with the incidence of venous ulceration in patients with primary varicose veins (p < 0.001). Propensity score matching created 101 matched pairs of patients with and without ulcers, and the analysis pointed to a potential link between HHcy and ulcer formation in the context of primary varicose veins (p < 0.001). Additional experiments showed that HHcy could induce endothelial dysfunction and phenotypic switching of vascular smooth muscle cells. Conclusion: Both clinical and experimental findings implicated HHcy as a key factor in the development of venous ulceration. Further research is needed to appraise the effectiveness of HHcy-lowering therapy in the prevention of venous ulcers in patients with varicose veins.

Journal ArticleDOI
TL;DR: Evidence is suggested that evidence is available to support an independent positive association between Lp(a) levels and the risk of future PAD outcomes.
Abstract: Background: Despite strong association of elevated lipoprotein (a) (Lp(a)) levels with incident coronary and cerebrovascular disease, data for incident peripheral artery disease (PAD) are less robust. The main objective of the present systematic review was to analyze the association between elevated Lp(a) levels and PAD outcomes. Methods: This systematic review was performed according to PRISMA guidelines. A literature search was performed to detect randomized clinical trials or observational studies with a cohort design that evaluated the association between Lp(a) levels and PAD outcomes. Results: Fifteen studies including 493,650 subjects were identified and considered eligible for this systematic review. This systematic review showed that the vast majority of the studies reported a significant association between elevated Lp(a) levels and the risk of PAD outcomes. The elevated Lp(a) levels were associated with a higher risk of incident claudication (RR: 1.20), PAD progression (HR: 1.41), restenosis (HR: 6.10), death and hospitalization related to PAD (HR: 1.37), limb amputation (HR: 22.75), and lower limb revascularization (HR: 1.29 and 2.90). In addition, the presence of elevated Lp(a) values were associated with a higher risk of combined PAD outcomes, with HRs in a range between 1.14 and 2.80, despite adjusting for traditional risk factors. Heterogeneity of results can be explained by different patient populations studied and varying Lp(a) cut-off points of Lp(a) analyzed. Conclusion: This systematic review suggests that evidence is available to support an independent positive association between Lp(a) levels and the risk of future PAD outcomes. PROSPERO Registration No.: 289253.



Journal ArticleDOI
TL;DR: In this article , anticoagulation, antiplatelet therapy, anti-thrombotic therapy, bleeding, thrombosis, venous thromboembolism (VTE) was discussed.
Abstract: Keywords anticoagulation, anti-platelet therapy, anti-thrombotic therapy, bleeding, thrombosis, venous thromboembolism (VTE)