Wennberg, Paul W.

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.

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.

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.

Background Patients with peripheral artery disease are at increased risk for major adverse cardiac events, major adverse limb events, and all‐cause death. Developing tools capable of identifying those patients with peripheral artery disease at greatest risk for major adverse events is the first step for outcome prevention. This study aimed to determine whether computer‐assisted analysis of a resting Doppler waveform using deep neural networks can accurately identify patients with peripheral artery disease at greatest risk for adverse outcome events. Methods and Results Consecutive patients (April 1, 2015, to December 31, 2020) undergoing ankle–brachial index testing were included. Patients were randomly allocated to training, validation, and testing subsets (60%/20%/20%). Deep neural networks were trained on resting posterior tibial arterial Doppler waveforms to predict major adverse cardiac events, major adverse limb events, and all‐cause death at 5 years. Patients were then analyzed in groups based on the quartiles of each prediction score in the training set. Among 11 384 total patients, 10 437 patients met study inclusion criteria (mean age, 65.8±14.8 years; 40.6% women). The test subset included 2084 patients. During 5 years of follow‐up, there were 447 deaths, 585 major adverse cardiac events, and 161 MALE events. After adjusting for age, sex, and Charlson comorbidity index, deep neural network analysis of the posterior tibial artery waveform provided independent prediction of death (hazard ratio [HR], 2.44 [95% CI, 1.78–3.34]), major adverse cardiac events (HR, 1.97 [95% CI, 1.49–2.61]), and major adverse limb events (HR, 11.03 [95% CI, 5.43–22.39]) at 5 years. Conclusions An artificial intelligence–enabled analysis of Doppler arterial waveforms enables identification of major adverse outcomes among patients with peripheral artery disease, which may promote early adoption and adherence of risk factor modification.

Introduction: Predictive algorithms using multiple clinical variables can identify patients at higher risk for abdominal aortic aneurysms (AAA), however they are cumbersome and cannot used directly by patients. A simple, cheap, noninvasive, and readily available (virtual) screening tool for identification of AAA could aid in screening algorithms. Aims: We sought to determine if a machine learning algorithm could predict the presence of an AAA by using a image of the face Methods: Diagnostic imaging studies were extracted from the electronic health record (EHR) from 5/7/2018 through 1/1/2023 and analyzed by a natural language processing algorithm previously validated to identify abdominal aortic aneurysms. Patient EHR profile pictures were extracted and matched to imaging studies. Various deep neural network (DNN) architectures were explored, all trained as classifiers on the face images along with clinical variables to predict clinical outcomes. All models used were CNNs with an EfficientNet architecture. Model performance was evaluated by standard metrics such as the area under the curve (AUC), specificities (Sp), and sensitivities (Sn). All performance metrics reported results from the test subset of the primary dataset and did not contain any observations considered during training. Results: A total of 5522 patients with facial images and AAA diagnostic studies were analyzed, among whom 1314 (23.8%) had a AAA. The optimal model had an AUC of 0.72 (Sn 0.44, Sp 0.83) for predicting AAA and remained similar in women (AUC 0.7), men (AUC 0.65), age >65 (AUC 0.63), and age <=65 (AUC 0.72) (Table). Conclusions: Using only an image of a patients face, the presence of an AAA could be identified with moderate performance in men, women, and in those less than 65. The model’s performance in demographics not typically screened for AAA may allow for targeted screening programs in these groups.

The anatomy of the human shoulder predisposes the neurovascular bundle to compression at different levels of the thoracic outlet during abduction of the arm. There are four possible levels of compression at the thoracic outlet pathway: at the costo-clavicular angle, the inter-scalenic angle, under the pectoralis minor muscle or at the level of the humeral head. The positional thoracic outlet compression (TOC) often remains completely asymptomatic. When symptomatic, compressions are collectively referred to as thoracic outlet syndrome (TOS) and may require surgery if physical therapy fails to improve symptoms. The “thoracic outlet compression with complications or sequelae” (the acronym of which is “TOC-CS”, which can be simplified as “TOX”) will almost invariably lead to surgery to release the compression, and other possible treatment targeting the complications as required. There is a continuum between TOC, TOS and TOX, which are simply different clinical stages of the same mechanical issue, just like the Rutherford grades represent different stages of lower extremity arterial disease. We believe that discriminating between TOC, TOS and TOX clarifies clinical definitions and their respective treatment options. TOC is to be considered as a physiological positional phenomenon, TOS requires medical or surgical treatment and surgery should be considered as a primary option in TOX.