Liedl, David

Background: Chronic venous insufficiency (CVI) can be evaluated using Duplex ultrasonography (US) and air plethysmography (PG), yet comparative performance remains unclear. Methods: We retrospectively identified patients who underwent venous insufficiency US and PG within a 90-day interval from March 1, 2015 through July 31, 2024. CVI severity was classified by the clinical (C) component of the Clinical, Etiologic, Anatomic, and Pathophysiologic (CEAP) classification system and categorized as mild (C0–2), moderate (C3), or severe (C4–6). PG and insufficiency US findings were compared across categories and machine learning models were trained to predict severe CVI. Results: We analyzed 1478 limbs from 839 patients who were predominantly women (62%) with a mean age of 61 years (± 14 years). Severe CVI was present in 32.3% of limbs. US detected venous incompetence in 67.4% of limbs overall and in 75.3% of severe CVI limbs. Abnormal PG findings occurred in 72.9% of limbs overall and in 88.5% of severe CVI limbs. PG parameters in machine learning models outperformed US parameters in predicting severe CVI (area under the receiver operating characteristic curve [AUROC] 0.82 vs 0.65). The top PG model (multilayer perceptron [MLP]) achieved an AUROC of 0.82, versus the best US model (gradient boosting) with an AUROC of 0.65. Limiting PG data to incompetence and obstruction parameters modestly reduced performance but remained higher than US (logistic regression AUROC 0.72). Conclusion: Our findings indicate that PG assessment in CVI offers superior performance compared to US. Overall, these results validate the quantitative whole-limb hemodynamic approach using PG, which provides a more complete understanding of the pathology behind CVI.

BACKGROUND: Lipodermatosclerosis (LDS) is a type of sclerosing panniculitis that predominantly involves the lower extremities and is characterized by erythema, hemosiderin pigmentation, and sclerotic skin lesions. LDS is a common reason for specialty consultations across clinical settings, including dermatology, vascular medicine, and occasionally the emergency department or internal medicine services. METHODS: To further evaluate the prevalence of venous hypertension in patients with LDS at the authors’ institution, they retrospectively reviewed the findings of lower extremity Doppler ultrasonography with or without segmental pressure (ie, venous ultrasonography) performed for adult patients with biopsy-confirmed LDS who were treated at the Clinic from January 1, 2000, through September 30, 2022. RESULTS: A total of 430 patients were included in the study. Venous ultrasonography findings were abnormal for 327 (76.0%) patients, whereas the other 103 (23.9%) patients had normal findings. Venous hemodynamics studies, including air plethysmography and continuous-wave Doppler ultrasonography, were performed for 33 patients with normal venous ultrasonography findings. Of these patients, 7 had mild valvular incompetence, 12 had abnormal calf muscle pump function, and 2 had pulsatility (backflow in the peripheral vein with elevated right atrial pressure) evident on continuous-wave Doppler ultrasonography. CONCLUSIONS: Overall, the findings extend previous observations that venous abnormalities are commonly present in patients with LDS and may contribute to its pathogenesis. However, a few patients with LDS have normal venous hemodynamics, which suggests that other factors also contribute to LDS pathogenesis.

Abstract Background Ankle-brachial indices (ABI) predict mortality and major cardiovascular events (MACE); however, they are unable to assess the severity of peripheral artery disease in patients with non-compressible vessels. Toe brachial indices (TBI) are less affected by non-compressibility and could be good predictors of cardiovascular morbidity and mortality. Purpose To evaluate the predictive value of TBI for MACE and all-cause mortality in a large population. Methods The initial ABIs and TBIs of all patients referred to a noninvasive vascular laboratory were obtained. We categorized patients based on the worse TBI from either leg, and each patient was classified as normal (>0.8), borderline (0.8-0.61), mild-moderate PAD (0.6 - 0.21) and severe PAD (≤0.2). MACE occurring after the study were identified using ICD9/10 and procedural CPT codes and included myocardial infarction, coronary revascularization, or stroke. Survival analysis was performed using the Kaplan-Meier method with log-rank test to compare survival curves between groups. Results Of 13551 patients, we excluded 643 (5%) in whom TBI could not be obtained. Patient characteristics can be found in Table 1. There were 4,924 MACE and 3,125 deaths during the median follow up time of 8.39 years (Table1). There was a significant difference of MACE incidence (p <0.001) and mortality (p<0.001) by TBI categories, and the curves separate before the 1-year mark (Figure 1A and B). Conclusion TBI is a good predictor of MACE and all-cause mortality in the short and long term and can be obtained in 95% of patients.

Background: Whether oral anticoagulation (OAC) can be discontinued after the resolution of left ventricular thrombus (LVT) remains controversial, particularly in patients without risk factors such as left ventricular aneurysms. This study aimed to identify patients who may safely discontinue OAC. Methods: We conducted a retrospective cohort study of patients with LVT resolution who completed their anticoagulation course and excluded patients with left ventricular (LV) aneurysm. Clinical and echocardiographic factors were compared between patients who experienced LVT recurrence (n = 22) and those without recurrence during follow-up (n = 94). Results: The cohort had a mean age of 64.5 ± 15.0 years, and half (50%) were male. Most had an ischemic cardiomyopathy (64.6%). LVT recurred in 19% (22/116) of patients following initial resolution. Patients with recurrence were older (mean age 71.3 ± 11.9 vs. 63.4 ± 15.7 years, p = 0.03) and were more likely to have prior ischemic stroke and arterial thromboembolism (18.2% vs. 4.3%, p = 0.02 for both). At the time of thrombus resolution, LVEF was significantly lower among patients who had recurrence (33.4 ± 13.6% vs. 42.5 ± 15.5%, p = 0.012). Stroke, systemic embolism, and mortality rates were similar regardless of recurrence status. Recurrence risk by presence or absence of stroke and LEVF >50% on the LVT resolution echocardiogram is shown in Figure 1. Notably, no recurrences were observed among patients with both LVEF > 50% and no history of stroke (0/32), which was statistically significant compared to each other category. Conclusion: Among patients without left ventricular aneurysm who discontinued oral anticoagulation after LVT resolution, those with preserved LVEF (>50%) and no prior history of stroke had a very low risk of recurrence, with no events observed in this subgroup. These findings suggest that some patients may safely discontinue anticoagulation after LVT resolution.

Summary: Background: Peripheral arterial disease (PAD) increases cardiovascular (CV) morbidity and mortality, but remains underdiagnosed and undertreated. Several trials support low-dose direct oral anticoagulant (DOAC) use in PAD treatment, although this has yet to be widely adopted in clinical practice. Patients and methods: We conducted a retrospective study of patients who underwent ankle-brachial index testing (ABI) from 1996 – 2020 at Mayo Clinic. We included patients with PAD defined by abnormal ABI (<1.0 or >/=1.4). Primary outcomes evaluated were myocardial infarcts (MI), ischemic strokes (IS), critical limb ischemia (CLI)/amputation, bleeding events and all-cause mortality. DOAC and warfarin use were each compared to no anticoagulant use for the outcomes using univariate analysis and multivariate analysis. Results: 22,162 patients had abnormal ABI readings; 1,266 were on warfarin and 269 were on DOAC for any indication. Both the DOAC and warfarin groups showed significant a decrease in all-cause mortality. The DOAC group showed superior mortality outcomes with HR 0.50 [95% CI 0.40–0.63], p-value <0.001 compared to warfarin with HR 0.88 [95% CI 0.81–0.96], p-value <0.004. There appeared to be a similar trend for MI and CLI/amputation however this was not statistically significant. IS was similar with only warfarin being statistically significant. The DOAC group had improved bleeding outcomes compared to the warfarin group, HR 0.53 (95% CI 0.24–0.85), p-value 0.007. Notably, the addition of ASA for both AC groups resulted in significant HR >1. Conclusions: Our study shows that anticoagulation use, particularly DOACs, is associated with decreased all-cause mortality in patients with PAD. There appears to be a favorable trend for DOACs in MI, IS and CLI/amputation. Lastly, DOACs were found to have superior outcomes with bleeding events.

Background: The calf muscle pump is an understudied contributor to venous return from the lower extremity. This study aimed to determine if calf pump function (CPF) is independently associated with the severity of chronic venous disease classified by CEAP (Clinical-Etiology-Anatomy-Pathophysiology). Methods: The Mayo Clinic Vascular Laboratory database was analyzed from January 2015 through September 2023. Ambulatory adults who underwent venous air plethysmography were included. Venous plethysmography assessed the severity of venous incompetence, and CPF was measured as ejection fraction (EF) per leg. The clinical component (C0 through C6) of the CEAP score was evaluated for each extremity at the time of the study. Results: A total of 7760 limbs from 3733 patients were analyzed. The mean age was 62 years, with 62% women. Venous obstruction was detected in 3.2% of limbs. Venous incompetence severity was categorized as normal (44%), mild (26%), moderate (19%), and severe (10%). A significant trend of reduced CPF was observed with higher CEAP scores ( p < 0.001). Multivariable logistic regression, adjusted for age, sex, degree of venous incompetence, and obstruction showed reduced CPF was a significant predictor (odds ratio 1.84, CI: 1.5–2.2) of active/prior ulcer (C5 or C6). In contrast to more severely reduced CPF, mildly reduced CPF (EF 40–49%) was not associated with active/prior ulcers. Conclusion: This large contemporary study demonstrates that decreased CPF is associated with worse chronic venous disease. Importantly, we demonstrate for the first time that CPF is independently associated with active/prior venous ulcers after accounting for other venous physiologic parameters and demographics.

Ankle brachial index (ABI) can be unreliable in patients with non-compressible vessels. Our aim is to determine the feasibility of toe brachial index (TBI) and reporting criteria in a large population. We evaluated Doppler waveforms and segmental pressures in 26,719 limbs. TBI was obtained in 92.7%, mean TBI = 0.61 ± 0.25. TBI was obtained in 82%of limbs with unobtainable ABI. In hemodynamically normal subgroup (defined as those with normal ankle-brachial indices at rest and after exercise) the mean TBI was 0.84 ± 0.14. In severe PAD subgroup (defined as ABI < 0.5 and monophasic waveforms) the mean TBI was 0.16 ± 0.12. Limbs with a diagnosis of a PAD (ABI ≤ 0.9) had a TBI <0.8 in 99.5% of the cases, and <0.6 in 90% of the cases. A TBI of 0.8 had a negative predictive value for PAD of 0.99. A TBI cutoff of 0.6 had a positive predictive value for PAD of 0.95. Based on these results we propose defining normal TBI above 0.8, borderline between 0.8 and 0.61, abnormal TBI ≤ 0.6 and severe PAD as TBI ≤ 0.2. In conclusion TBI can be reliably measured in patients with PAD and offer valuable information when diagnosing PAD. We present our diagnostic criteria based on clinical data.

Background: Exercise stress testing uses metabolic equivalents of tasks (METs) to measure the energy cost of activities, aiding in the assessment of exercise capacity and cardiovascular health. Despite its significance, the correlation between calf muscle pump function (CPF) and exercise stress testing remains unexplored. We aimed to evaluate the relationship between CPF and peak METs as determined by cardiopulmonary treadmill exercise stress testing. Methods: The study included adults who underwent exercise cardiopulmonary stress testing and venous plethysmography at Mayo Clinic between April 2017 and March 2020. The protocols other than Bruce, Mayo, Modified Naughton, and Naughton protocols were excluded. The CPF ejection fraction (EF) was calculated per leg based on refill volumes post-exercise as a percentage of passive drain refill. The classification of CEAP (Clinical-Etiology-Anatomy-Pathophysiology) was utilized to better understand chronic venous insufficiency (CVI). Results: A total of 155 patients who underwent both exercise stress testing and venous plethysmography were included, with a mean age of 61.31 ± 14.03 years, and 84 (54.2%) were male. The peak measured METs for normal, unilaterally reduced, and bilaterally reduced CPF were 8.5 (2.5), 7.3 (2.1), and 7.1 (2.4), respectively (p=0.004, Figure 1). Multiple linear regression models were developed with METs as the outcome to determine if CPF was an independent predictor of METs on cardiopulmonary exercise stress testing. IIn model 1, the following independent variables were included: resting heart rate, peak heart rate, peak systolic blood pressure, recovery heart rate at minute 1, and worst EF (Table 1). In model 1, with only exercise parameters, lower EF was associated with lower METs (p=0.03). In a second analysis, variables identified as statistically significant with METs in the initial model were included, along with CEAP class (model 2) and CCI (model 3) (Table 2). In model 2, CEAP class 3 or higher was associated with decreased METs on the exercise stress test. This correlation implies that individuals with moderate to severe CVI may influence exercise capacity, demonstrating the interconnectedness of the cardiovascular system. Moreover, in model 3, the CCI, a predictor for mortality, was not significantly associated with METs. Conclusion: Our findings revealed that more severe CVI (CEAP class and reduced CPF) was associated with reduced exercise capacity after accounting for other factors.

Introduction: Peripheral artery disease impacts 202 million patients worldwide and is commonly diagnosed via ankle-brachial index. PAD is associated with endothelial dysfunction, which is also common to venous thromboembolism formation. Despite the suspected overlap in pathogenesis, few studies exist investigating the association between these pathologies. We investigated whether PAD with low or elevated ABI is an independent risk factor for VTE. Methods: We reviewed medical records of patients ≥18 years old undergoing ABI measurement with or without PAD symptoms from 01/01/1996 to 08/31/2018 and classified patients by ABI: severely low (ABI 0.00-0.39), moderately low (0.40-0.69), mildly low (0.70-0.90), borderline (0.91-0.99), normal (1.00-1.40), and elevated (>1.40). The primary outcome was incident VTE event after ABI measurement, defined as deep vein thrombosis or pulmonary embolism. Multivariable Cox proportional regression was used to calculate hazard ratios (HR) with 95% confidence intervals after adjusting for age, sex, active smoking, cancer or VTE history, thrombophilia, anticoagulation, and revascularization within 14 days of VTE. Results: In 39,384 unique patients (mean age 66.3±14.2 years, median follow-up 34 months), 5,141 VTE events were observed. Increased VTE risk was observed in PAD patients with severely low ABI (HR 1.26, 95%CI [1.02, 1.29]) compared to patients with normal ABI after multivariable regression. Patients with elevated ABI did not demonstrate an increased risk of VTE. Conclusions: Patients with severe PAD are at higher risk for VTE than patients with normal ABI, which may be due to a multifactorial pathophysiology of profound endothelial injury as well as immobility due to claudication. Further exploration of VTE incidence in patients with severe PAD stratified by functional status is warranted to determine the optimal strategy to minimize thromboembolic morbidity and mortality in this population.