McBane, Robert D.

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.

Post-pulmonary embolism syndrome (PPES) encompasses a diverse spectrum of long-term complications that are associated with persistent dyspnea, exercise intolerance, and a decrease in quality of life. The PPES constellation ranges from life-threatening conditions such as chronic thromboembolic pulmonary hypertension (CTEPH) to nonlife-threatening but still debilitating conditions such as chronic thromboembolic pulmonary disease (CTED) or post-PE deconditioning. The safety and efficacy of exercise and cardiopulmonary rehabilitation programs to prevent and manage these symptoms in PPES has not been well established. Herein, we review contributors to PPES and synthesize the evidence for exercise training after PE to treat and prevent PPES.

Objective Diffuse alveolar hemorrhage (DAH) is a life‐threatening presentation of antineutrophil cytoplasmic antibody–associated vasculitis (AAV). Patients with AAV are at an increased risk of venous thromboembolic events (VTEs). These manifestations can co‐occur; however, the prognosis and management of these patients are poorly understood. Methods In this retrospective observational study, we included patients diagnosed with AAV who presented with both DAH and VTE during the same outpatient visit or in the same inpatient treatment episode. Results Among 121 patients with proven DAH secondary to AAV managed at our institution, 14 (11.6%) were also diagnosed with VTE. Patients were predominantly men (71%) with median age at diagnosis of 67 (interquartile range 56–72) years. Five patients were diagnosed with DAH followed by VTE, four patients were diagnosed with VTE before developing DAH (T‐AAV), and five patients were diagnosed with VTE and DAH simultaneously (HT‐AAV). Inferior vena cava filters were placed in 13 patients (93%). Although most patients received systemic anticoagulation within 30 days of DAH diagnosis, anticoagulation management was individualized based on clinical presentation. One patient with preexisting interstitial lung disease died of respiratory failure after initially presenting with pulmonary embolism and later developing DAH during hospitalization. Bleeding complications, including recurrent DAH or retroperitoneal hematoma, were observed in six patients (43%). Three patients (21%) experienced progression or recurrence of VTE within 90 days. Conclusion Management of patients with DAH and VTE is challenging and should be guided by the severity of DAH, additional organ manifestations of AAV, and risk stratification of the presenting VTE.

Abstract Use of Direct oral anticoagulants (DOAC) has increased exponentially since their introduction in 2010. Over the years they have been used without any systematic oversight, there have been ongoing concerns related to inappropriate or incorrect dosing, incorrect duration, and non-adherence to the drugs leading to adverse patient outcomes. Several factors have been attributed to DOAC non-adherence such as presence or fear of adverse effects, affordability, lack of perceived benefit, or concerns for reversibility. These barriers impact both primary (first time prescription) and secondary adherence (longer term prescription). Poor adherence can lead to adverse outcomes such as stroke, death, and higher medical resource utilization hence increased cost to the patient and payors. This study was conducted as a quality improvement (QI) initiative to improve the adherence to the prescription DOACS. We included patients 18 years old, a diagnosis of Atrial fibrillation and flutter who had a primary care provider writing the prescription for chronic DOAC therapy. Patients with venous thrombosis, pregnancy or who were institutionalized were excluded. The charts were reviewed for primary and secondary adherence using Surescripts functionality which can provide baseline information about prescription fills from the participating pharmacies. In the preimplementation phase we identified 1030 patients meeting inclusion criteria associated with the pilot sites within Mayo Clinic practice in preceding 6 months. For this population, Surescripts data found that the rates of primary and secondary adherence to be 84% and 86% respectively. We then implemented a 6-month pilot where we created workflow for a pharmacy led DOAC management unit. Herein, once a DOAC prescription was made for patients meeting inclusion criteria, they would enter a registry where the pharmacy team would review the charts for primary adherence by utilizing Surescripts data. If adherent these patients would be marked for follow up in the secondary adherence phase. However, if non adherent, the team would initiate intervention including engagement with patient online services which was further escalated to phone calls by the pharmacy team. Once the barriers were identified several remediation approaches were incorporated in the process, these included education about DOACS, medicare education, social work assistance to even switching to warfarin if necessary. The same process was followed for secondary adherence management. In the intervention cohort, we had 411 patients during the pilot, for primary adherence 87.1% of patients were adherent at baseline and an additional 3.4% became adherent with interventions, while 9.5% remain nonadherent. The primary causes of nonadherence, amongst 9.5%, were cost (86%) while 1% were concerned about side effects and 3% were concerned about lack of perceived benefit. The inverntions lead to impoved adherence in most patients and very few patients were transitioned to warfarin. For secondary adherence 92% of the patients were adherent without any intervention, an additional 4% of patients benefited with the interventions of the DOAC management unit with approaches to address cost considerations, while another 4% remained nonadherent where cost remained the primary reason for nonadherence, other reasons being lack of perceived benefit and side effect concerns. In summary, with active intervention, in our patient population we were able to improve the primary adherence from 84% to 91% and secondary adherence from 86% to 96% . Cost remained the biggest barrier for adherence followed by concern for side effects and lack of perceived benefit. Our engaged team of pharmacy staff was able to manage those concerns with the education and cost mitigation strategies leading to improved adherence. Based on previously published literature even a 5% difference in adherence to DOACS can make a huge difference in population-based outcomes. Our work was able to demonstrate a positive impact of the intervention, highlighting the need for a well-managed DOAC unit especially for complex care populations.

Abstract Background Antiphospholipid syndrome (APS) is diagnosed when vascular thrombosis or pregnancy morbidity occurs in the presence of persistent antiphospholipid antibodies (aPL). Although IgM-isotype antibodies are part of the laboratory criteria, their clinical value remains uncertain. We evaluated real-world aPL testing patterns to quantify the prevalence of isolated IgM positivity. Methods We analyzed aPL testing data across the Mayo Clinic sites between January 2006 and July 2025, lined up with the publication of the revised Sapporo (Sydney) classification criteria. For each patient, we identified the first time in which any aPL test was performed. We assessed available results for Lupus anticoagulant (LA), anticardiolipin (aCL) isotypes IgG and IgM, and anti–beta 2 glycoprotein (B2GP1) isotypes IgG and IgM. Positivity rates were calculated for each marker, and a subgroup of patients who had results for all three test categories at the initial workup was identified. In this cohort, we assessed the distribution of single, double, and triple positivity. We also quantified the number and percentage of patients who were positive only for IgM isotypes (aCL or B2GP1), with negative LA and IgG at initial testing. Antibodies were considered positive based on international criteria and internal standards. aCL and B2GP1 were positive if ≥40 units. LA positivity followed ISTH SSC guidelines, requiring demonstration of a phospholipid-dependent inhibitor in the following assays: screening, mixing, and confirmatory steps in DRVVT or aPTT-based platelet neutralization procedure (PNP), Staclot LA delta and HEX LA delta assays. Criteria for a positive result was as follows: DRVVT: prolonged screen and inhibited mix with screen/confirm ratio >1.2; Staclot LA delta: >7 seconds; PNP: shortening of the APTT clotting time with PNP by ≥5 seconds before 2023 and ≥2 seconds thereafter; HEX LA delta >13 seconds. Results A total of 99,814 unique patients underwent testing for at least one aPL marker. The most frequently tested was LA (n = 75,085), with a positivity rate of 10.29% (7,730/75,085). Among antibody isotypes, positivity rates were 1.2% (846/69,539) for aCL IgG, 1.7% (1,198/69,640) for aCL IgM, 1.9% (732/37,791) for B2GP1 IgG, and 2.0% (762/37,601) for B2GP1 IgM. Among the 30,274 patients who underwent simultaneous testing for LA, aCL IgG/IgM, and B2GP1 IgG/IgM, 1.3% (n = 407) were triple-positive, 1.4% (n = 427) were double-positive, and 9.9% (n = 3,009) had a single positive marker. The remaining 87.3% (n = 26,431) tested negative for all three. Of the 3,009 patients with only one positive marker, 9.8% (n = 296) were positive exclusively for aCL IgM, and 7.4% (n = 224) were positive exclusively for B2GP1 IgM. Among all fully tested patients, 2.2% (668/30,274) were positive for only IgM isotypes (either aCL or B2GP1) in the absence of IgG and LA positivity. Specifically, 0.9% (n = 296) were exclusively positive for aCL IgM and 0.7% (n = 224) for B2GP1 IgM. Additionally, 0.5% (n = 148) were simultaneously positive for both aCL IgM and B2GP1 IgM, without associated IgG or LA markers. Had only IgG and LA been assayed, 17.4 % (668/3843) of initially positive patients—and one-third of those classified as triple-positive—would have been missed. Conclusion Within this large-scale analysis of real-world APS test ordering practice, less than one-third of orders included a comprehensive characterization. Isolated IgM positivity, defined as aCL or B2GP1 IgM in the absence of IgG and LA, was infrequent yet represents a sizable proportion of initial positive aPL testing. How these results impact APS diagnosis and management of APS requires further study.

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.

Introduction/Background: Peripheral arterial disease (PAD) exhibits reduced hyperemic response in the affected legs following stimuli such as pressure-cuff-induced occlusion or exercise. Therefore, an analysis of the perfusion changes in the calf muscle using a widely available imaging modality such as ultrasound could serve as a complementary tool to existing methods such as ankle-brachial index (ABI) for PAD detection. Research Questions/Hypothesis: This study evaluates the utility of ultrasound perfusion imaging and estimation technique in the calf muscle to differentiate PAD affected legs based on their flow response to external pressure and exercise. Methods/Approach: Data acquisition was performed using a research ultrasound system (Vantage NXT, Verasonics) with an ultrasound probe secured inside a probe fixation device and positioned to the calf muscle of the subject. Two separate studies were performed on each subject: 1) A flow variations response to external pressure study, 2) a flow variation response to exercise. For the pressure study, a pressure cuff was wrapped around the subject’s thigh and inflated during the study using an automatic rapid cuff inflation device. Data was continuously acquired for 6 minutes including 1 minute of baseline, 3 minutes of pressure cuff occlusion, 2 minutes of post-occlusion acquisition. The exercise study consisted of data acquisition in the seated position with 1 minute of baseline, 30 repetitions of plantar flexion using a calf training device, and 2 minutes of post-exercise acquisition. The acquired data were then clutter-filtered and denoised for perfusion visualization. Four metrics including post-occlusion/post-exercise to baseline flow intensity/density variation (POBFIV, PEBFIV, POBFDV, PEBFDV) were obtained for analysis. Results/Data: Figure 1 shows perfusion imaging results during the pressure and the exercise studies for two example legs, one healthy and one of a clinically diagnosed PAD patient (mild disease), respectively. Percentage-wise POBFIV, PEBFIV, POBFDV, and PEBFDV values were 44%, 57%, 197%, and 2231% for the healthy leg and 12%, 27%, 63%, and 181% for the PAD leg, respectively, shown in Table 1. Conclusion: The proposed method shows promise in differentiating PAD-affected legs from healthy individual’s through evaluating the hyperemic response to external pressure and exercise. Statistical analysis of the results for a cohort of healthy and PAD-affected legs will constitute future work.

Introduction: The ankle-brachial index (ABI) is the most common method for detecting peripheral arterial disease (PAD), but its sensitivity is limited, especially in patients with poorly compressible vessels. This study proposes a novel ultrasound-based approach for PAD diagnosis by analyzing calf muscle perfusion responses to pressure-cuff occlusion and exercise, interpreted using machine learning (ML) techniques. Methods: Under an IRB approved protocol and signed IRB-approved written consent, 48 participants, 43 symptomatic with abnormal ABI and 5 healthy volunteers were recruited for this study. High-frame-rate ultrasound B-mode image data (500 frames/s) were collected from 64 legs and categorized into two classes based on clinical diagnosis: Abnormal ABI (54 legs) and Healthy (10 legs). Legs with normal ABI from symptomatic patients were excluded to avoid diagnostic ambiguity, as these cases may lie within the diagnostic gray zone for PAD. Each leg underwent a 9-minute scanning protocol comprising 1 minute of baseline, 3 minutes of pressure cuff occlusion (using an automatic rapid inflation/deflation device), 2 minutes post-occlusion, 1 minute of plantar flexion exercise, and 2 minutes post-exercise. The ultrasound data were processed using singular-value decomposition (SVD) clutter filtering and noise equalization to generate Power-Doppler perfusion images at 2 frames per second. The PAD prediction pipeline involved data augmentation to address class imbalance and limited sample size, followed by histogram-based thresholding to extract blood pixels—intensity thresholding was avoided due to variability in pixel intensities. Blood pixel counts were calculated over time and used to train nine machine learning classification models (Figure 1). Results: The best-performing ML classification model achieved an accuracy of 77%, with the median accuracy across all models ranging between 70% and 72%. Notably, an ensemble model that combined Logistic Regression, Gradient Boosting, and Support Vector Machines using a majority voting strategy yielded the highest accuracy of 81% (Table 1). Conclusion: We proposed a novel ultrasound-based perfusion estimation method for diagnosing peripheral arterial disease (PAD), with data analyzed using ML approach. Although this is a feasibility study, the observed diagnostic accuracy exceeding 80% is promising. With further research and larger datasets, this approach has the potential to become a valuable tool for PAD.