Citations

Background: Ca-NBTE primarily affects the mitral valve (MV) and aortic valve (AV), with rare involvement of the right heart valves. Premortem descriptions of this condition are limited to a few case reports. This study presents an initial clinical series focusing on patients with Ca-NBTE specifically affecting their right heart valves. We describe the underlying cancers, types of valve lesions, and associated embolic complications. Patients and Methods: A electronic search of medical records (March 31, 2002, to June 30, 2022) was followed by a manual review to identify adult patients with echocardiographically detected NBTE, active cancer, and no infectious endocarditis or lupus anticoagulant/antiphospholipid antibodies. Results: Out of 115 identified patients with Ca-NBTE (mean age 63.2±9.7 years, 66.1% female), there were 8 cases (7.0%) affecting right heart valves (mean age 64.5±12.1 years, 3 females) with underlying cancer: pancreatic (n=3), lung (n= 2), genitourinary (n=1), gastric (n=1) and neck sarcomatoid carcinoma (n=1). TV was affected in 8 patients and PV in one case; 4 patients had Ca-NBTE limited only to PV, 2 patients had MV and TV, 1 patient had mitral, aortic and TV, and 1 patient with pancreatic cancer had all four valves affected by NBTE. 5 patients had embolic complications to the brain with one patient in that group also experiencing emboli to the kidney and spleen. Out of 4 patients with NBTE limited to TV, two still had brain emboli, one had only pulmonary embolism, and one patient had no embolic complications. Conclusion: Around 7% of Ca-NBTE cases involve the right heart valves, with half of these cases limited to the TV. The cancer profile in these cases resembles that seen in left heart valve involvement.

Introduction: Warfarin is a commonly prescribed anticoagulant for treating atrial fibrillation, mechanical valves, and venous thromboembolism. Warfarin dose management remains challenging due to dosing variability between patients and warfarin’s narrow therapeutic window. Time in therapeutic range (TTR) is critical to warfarin’s safety and efficacy, but TTR typically remains low (40-50%) in community practices. Specialized anticoagulation clinics and protocolized approaches can increase TTR but have great administrative burdens and health care costs. Aim: To develop standardized optimal warfarin dose decision support using a machine learning model based on time series anticoagulation data and patient demographic characteristics Methods: The dataset included 12,497 warfarin patients monitored in the anticoagulation tracker of electronic medical records across the Mayo Clinic Enterprise. The dataset contained time series anticoagulation data (warfarin dose, INR, INR target range) and patient demographic characteristics. We implemented an offline deep reinforcement learning model (DRL) to predict the cumulative warfarin dose for the days until the next INR test based on a patient’s historical anticoagulation data. Prior approaches utilized traditional supervised learning methods such as regression or Long Short Term Memory (LSTM) neural networks to approximate a function mimicking the behavior of the training data. On the other hand, DRL learned an optimal dosing policy through continuous interaction and feedback from the training data. The key advantage of DRL is the model can learn to behave differently (and potentially better) for suboptimal clinical states in the data such as overdosing or underdosing. To evaluate the DRL model we compared the predicted warfarin doses with the physician-prescribed doses Results: DRL model’s prediction accuracy was 96.96%, outperforming our implementation of a baseline LSTM model with a prediction accuracy of 70.58%. Further evaluation of the DRL model indicated that the model correctly adjusted the warfarin dose at time steps when patients had out-of-range INRs. Conclusions: Offline deep reinforcement learning demonstrates potential in supporting warfarin dose management to maximize TTR.

Introduction: Pulmonary vein thrombosis (PVT) is often diagnosed incidentally but data on its management and outcomes are sparse. Methods: We queried our institutional health record to identify patients ≥18 years of age diagnosed with PVT. Demographics, medications, risk factors, diagnostics, treatment, and sequelae were collected by manual chart review. Suspected tumor thrombus cases were excluded. Results: Seventy-two patients with PVT were identified (median age 62 years, 50% male). The cohort was mostly white (85%), overweight (BMI 26 kg/m), with frequent comorbidities including hypertension (44%), hyperlipidemia (38%), atrial fibrillation/flutter (29%), and history of venous thromboembolism (21%). The most common PVT risk factors were active malignancy (54%), lobectomy (21%), surgery within 30 days (19%), and extrinsic vein compression (15%). Most PVT were diagnosed by CT (86%) and affected a single vein (86%), mostly commonly the left upper PV (32%). Laboratory studies revealed median platelet count 243 х 10 9 cells/L (n=58) and D-dimer elevated in 6 patients when measured (67%, n=9). About one-third of patients were on therapeutic anticoagulation (37%) at PVT diagnosis. Most patients were started on new anticoagulation (78%, n=56), with unfractionated heparin as the most common initial therapy (68%). Of those anticoagulated, few were treated with a limited duration (20%, n=11, median 54 d, IQR 95) while most received indefinite anticoagulation (80%, n=45), primarily warfarin (45%), apixaban (24%), or enoxaparin (21%). Serial imaging was obtained in 69% (n=50, median 65 d, IQR 116) and demonstrated resolution of PVT in 32 (64%) patients. Common PVT complications noted were as follows: 4 year risk of LA thrombus (26%, 12/16 anticoagulated), mechanical ventilation (13%), pneumonia (9%), and ischemic stroke (9%, 5/6 anticoagulated). Conclusions: PVT is often associated with active malignancy, lobectomy, recent surgery, and extrinsic vein compression. Most PVT resolve on serial imaging. Clinicians should be aware of potential high-risk sequelae including LA thrombus and stroke as well as high anticoagulation failure rates when managing PVT.

Intro: Venous thromboembolism (VTE) is a common cause of death among cancer patients, second only to cancer progression. Identifying factors predicting worse outcomes among cancer patients with VTE would be useful clinically. For cancer patients with pulmonary emboli (PE), it remains unclear whether concomitant leg deep vein thrombosis (DVT) as a source for further embolization adversely impacts this risk. The aim of this project was to determine the impact of residual DVT on adverse outcomes among cancer patients suffering acute PE. Methods: Consecutive patients with confirmed acute PE (March 1, 2013 - June 30, 2021) underwent ultrasound (US) imaging and were divided into two groups depending on the presence or absence of leg DVT. PE severity was classified based on AHA criteria. Patients were followed prospectively for VTE recurrence, major and clinically relevant non-major bleeding (CRNMB) and all-cause mortality. Results: Over the study interval, 1,035 cancer patients with PE were enrolled (Table 1). Of these, 375 (36.2%) had leg DVT confirmed by US. Patients with leg DVT were older (64.2 vs 61.4 years, p = 0.01), heavier (90.2 vs 85.1 kg, p <0.001), with lower metastatic disease prevalence (49.1% vs 57.1%, p = 0.01) compared to those without leg DVT. Cancer type distribution also differed between groups. PE patients with DVT more often had prostate, genitourinary, and hematologic cancers while those without DVT more often had pancreatic and breast cancers. Patients with DVT more often had symptomatic PE (48.2% vs. 35.9%, p < 0.001), massive (2.9% vs 0.5%, p < 0.001), and submassive (22.0% vs 7.6%, p < 0.001). Patients with DVT more often received unfractionated heparin (39.5% vs 18.7%, p < 0.001) whereas those without DVT were more frequently treated with low molecular weight heparin (57.5% vs. 44.3%, p <0.001), and apixaban (16.4% vs. 11.7%, p < 0.05). Anticoagulant duration, VTE recurrence, major bleeding and CRNMB were similar between groups (Table 2). Conclusion: Among a large cohort of cancer patients with pulmonary emboli, significant clinical and cancer specific differences exist comparing those with and without leg DVT.While theoretically increasing the risk of recurrent embolization, the presence of residual DVT does not appear to adversely impact important outcomes among cancer patients adequately treated with anticoagulation.

Purpose/Introduction: Patients with cancer and venous thromboembolism (VTE) have higher complication rates including thrombosis recurrence and bleeding. Real world prospective clinical outcome estimates of VTE management comparing cancer and non-cancer patients are limited. To assess VTE recurrence, major bleeding, and clinically relevant non-major bleeding (CRNMB) in patients with cancer and without cancer, the prospective Mayo Clinic Thrombophilia Clinic Registry was analyzed. Methods: Upon recruitment, consecutive patients with confirmed acute VTE (03/01/2013 - 04/30/2023) were treated in a standardized, guideline-sanctioned, protocol driven strategy incorporating shared patient-decision making. Patients were divided into groups based on cancer status. After enrollment, patients were actively followed at 3 month intervals, in person whenever feasible, by mailed questionnaire or scripted phone interview to assess vital status, medication compliance, VTE recurrence, major bleeding and CRNMB. Results: Over the study time-frame, 2,064 patients (53.8% male, 46.2% female) with a cancer and 2,647 patients (54.9% male, 45.1% female) without cancer were enrolled. The most common cancers were gastrointestinal (n=423, 20.5%), pancreatic (n=287, 13.9%), genitourinary (n=198, 9.6%), hematologic (n=171, 8.3%), and lung cancer (n=170, 8.2%). Patients with cancer were older, had lower weight and lower platelet counts compared to non-cancer patients (Table1). Pulmonary embolism (PE, 52.6% vs 43.7%, p<0.001), upper extremity DVT (9.1% vs 6.0%, p<0.001), and splanchnic DVT (11.1% vs 6.9%, p<0.001) were more frequent among cancer patients. In contrast, leg DVT was more frequent among non-cancer patients (65.4% vs.47.2%, p<0.001). While mean duration of anticoagulation was similar between groups, notable differences in 3 month and > 9 month durations were evident as were initial anticoagulant choices (Table 1). Despite a well-organized protocol driven and guideline sanctioned management strategy, patients with active cancer experienced a 2.2-fold higher rate of VTE recurrence (p<0.001) and a 1.8 fold higher rate of major bleeding (p<001) compared to non-cancer patients (Table 2). CRNMB rates did not differ by cancer status. Conclusions: In this large prospective, guideline-driven and patient-centric registry of VTE management, patients with cancer had significantly higher rate of VTE recurrence and major bleeding, compared to non-cancer patients. These data provide important estimates for power calculations for future randomized trials of VTE treatment.