Artificial intelligence of arterial Doppler waveforms to predict major adverse outcomes among patients with diabetes mellitus.

OBJECTIVE: Patients with diabetes mellitus (DM) are at increased risk for peripheral artery disease (PAD) and its complications. Arterial calcification and non-compressibility may limit test interpretation in this population. Developing tools capable of identifying PAD and predicting major adverse cardiac event (MACE) and limb event (MALE) outcomes among patients with DM would be clinically useful. Deep neural network analysis of resting Doppler arterial waveforms was used to detect PAD among patients with DM and to identify those at greatest risk for major adverse outcome events. METHODS: Consecutive patients with DM undergoing lower limb arterial testing (April 1, 2015-December 30, 2020) were randomly allocated to training, validation, and testing subsets (60%, 20%, and 20%). Deep neural networks were trained on resting posterior tibial arterial Doppler waveforms to predict all-cause mortality, MACE, and MALE at 5 years using quartiles based on the distribution of the prediction score. RESULTS: Among 11,384 total patients, 4211 patients with DM met study criteria (mean age, 68.6 ± 11.9 years; 32.0% female). After allocating the training and validation subsets, the final test subset included 856 patients. During follow-up, there were 262 deaths, 319 MACE, and 99 MALE. Patients in the upper quartile of prediction based on deep neural network analysis of the posterior tibial artery waveform provided independent prediction of death (hazard ratio [HR], 3.58; 95% confidence interval [CI], 2.31-5.56), MACE (HR, 2.06; 95% CI, 1.49-2.91), and MALE (HR, 13.50; 95% CI, 5.83-31.27). CONCLUSIONS: An artificial intelligence enabled analysis of a resting Doppler arterial waveform permits identification of major adverse outcomes including all-cause mortality, MACE, and MALE among patients with DM.

Reduced calf muscle pump function is a risk factor for venous thromboembolism: a population-based cohort study.

The calf muscle pump is a major determinate of venous return in the legs but has not been studied as a risk factor for venous thromboembolism (VTE). A population-based cohort study of Olmsted County, Minnesota residents was performed using calf pump function (CPF) measurements from venous plethysmography studies from 1998 to 2015. Patients with a history of VTE were excluded. Nursing validated VTE outcomes from the Rochester Epidemiology Project were identified after the index study date, and patients with reduced CPF (rCPF) were compared with patients with normal CPF. A total of 1532 patients with recorded CPF (28% air and 72% strain gauge plethysmography) were included; 591 (38.5%) had normal CPF, 353 (23.0%) had unilateral rCPF, and 588 (38.3%) had bilateral rCPF. Any VTE occurred in 87 patients (5.7%) after a median follow-up of 11.7 years (range, 0-22.0 years). Comparing patients with bilateral reduced to bilateral normal CPF, the unadjusted hazard ratio (HR) for incident VTE was 2.0 (95% confidence interval [CI], 1.2-3.4) and after adjusting for age, BMI, and Charlson Comorbidity Index, the HR was 1.68 (95% CI, 0.98-2.89). The adjusted HR for ipsilateral deep vein thrombosis was evaluated in 3064 legs comparing legs with reduced to normal CPF and was 1.71 (95% CI, 1.03-2.84). Mortality was significantly higher in both the bilateral (P < .001) and unilateral (P < .001) rCPF groups compared with normal CPF. Our results demonstrate that CPF is a risk factor for VTE in an otherwise low-risk ambulatory population and might be a useful component in risk stratification models.

Incidence of venous thromboembolism in patients with advanced stage ovarian cancer undergoing neoadjuvant chemotherapy: Is it time for thromboprophylaxis?

OBJECTIVES: Our objectives were to determine the incidence, timing, and risk factors for venous thromboembolisms (VTEs) in patients with advanced stage epithelial ovarian cancer (EOC) who received neoadjuvant chemotherapy (NACT). We explored the utilization of direct-acting oral anticoagulants (DOACs) for VTE treatment. METHODS: This retrospective cohort study included patients with advanced stage EOC receiving NACT followed by interval cytoreductive surgery (ICS) at a single institution. Risk factors were compared between patients with versus without VTE between EOC diagnosis and 180 days after ICS. Bleeding complications were compared between patient who received a DOAC versus non-DOAC. RESULTS: VTE cases occurred amongst 33 of the 154 (21.4%) patients with 4 (2.6%) concurrent with EOC diagnosis, 9 (5.8%) between EOC diagnosis and NACT start, 13 (8.4%) between NACT start and ICS, and 7 (4.5%) within 180 days after ICS. There were no statistically significant differences in risk factors assessed (age, body mass index, functional status, histology, Khorana score, and smoking history) between patients with versus without VTE. Eleven patients (33.3%) received a DOAC for VTE treatment. There were no significant differences in number of intraoperative blood transfusions (p = 0.38), blood loss (p = 0.95), or bleeding complications (p = 0.53) between patients treated with a DOAC versus a non-DOAC. CONCLUSION: There is a high incidence of VTE events (21.4%) in patients with advanced stage EOC undergoing NACT. Two-thirds of the VTEs may have been prevented with thromboprophylaxis as they occurred between EOC diagnosis and ICS. These data support consideration of thromboprophylaxis in all patients with advanced stage EOC undergoing NACT.

Incidental pulmonary embolism in cancer and noncancer patients: Prospective cohort study.

BACKGROUND: Clinical picture and outcome of incidental pulmonary embolism (iPE) compared to symptomatic pulmonary embolism (sPE) remain unclear. METHODS: Demographics, recurrent venous thromboembolism (VTE), mortality, major bleeding, and clinically relevant nonmajor bleeding (CRNMB) were compared between iPE and sPE patients who were followed prospectively at Mayo Thrombophilia Clinic (March 1, 2013 to August 1, 2020). RESULTS: Out of 3576 VTE patients, 1417 (39.6%) had PE: 562 (39.7%) iPE and 855 sPE. Patients with cancer were more likely to have iPE (400 iPE vs. 314 sPE) compared to those without cancer (162 iPE vs. 541 sPE). VTE recurrence rate (all per 100 person-years) was similar in all iPE and sPE patients (3.34 vs. 3.68, p = .50), with cancer (4.16 vs. 4.89, p = .370), and without cancer patients (0.89 vs. 2.80, p = .25). Higher mortality observed in all patients with iPE compared to sPE (46.45 vs. 23.47, p < .001) and with cancer (56.41 vs. 45.77, p = .03) became not significant after adjustment for age, antiplatelet therapy, metastases, and cancer location. Noncancer iPE patients had higher mortality (15.95 vs. 7.18, p = .006) even after adjustment (p = .05). The major bleeding rate was also higher in all patients iPE compared to sPE (7.10 vs. 3.68, p = .03), but not after adjustment (p = .974); higher major bleeding rate in noncancer patients (6.49 vs. 1.25, p = .007) remained significant after adjustment (.02). CRNMB rate was similar to iPE and sPE patients. CONCLUSION: iPE represents a more serious clinical condition compared to sPE as indicated by the higher mortality and major bleeding but these differences reflect underlying comorbidities rather than the seriousness of the embolic event.

Venous thromboembolism after COVID-19 vaccination in patients with thrombophilia.

Patients with thrombophilia remain concerned about venous thromboembolism (VTE) risk with COVID-19 vaccinations. The aim of this study was to examine VTE outcomes in patients with inherited or acquired thrombophilia who were vaccinated for COVID-19. Vaccinated patients ≥18 years between November 1, 2020 and November 1, 2021 were analyzed using electronic medical records across the Mayo Clinic enterprise. The primary outcome was imaging confirmed acute VTE occurring 90 days before and after the date of the first vaccine dose. Thrombophilia patients were identified through laboratory testing results and ICD-10 codes. A total of 792 010 patients with at least one COVID-19 vaccination were identified. Six thousand sixty-seven of these patients were found to have a thrombophilia, among whom there was a total of 39 VTE events after compared to 51 VTE events before vaccination (0.64% vs. 0.84%, p = .20). In patients with Factor V Leiden or prothrombin gene mutation, VTE occurred in 27 patients before and in 29 patients after vaccination (0.61 vs. 0.65%, p = .79). In patients with antiphospholipid syndrome, VTE occurred in six patients before and four patients after vaccination (0.59% vs. 0.39%, p = .40). No difference was observed in the overall VTE rate when comparing the postvaccination 90 days to the prevaccination 90 days, adjusted hazard ratio 0.81 (95% confidence interval: 0.53-1.23). In this subgroup of COVID-19 vaccinated patients with thrombophilia, there was no increased risk for acute VTE postvaccination compared to the prevaccination timeframe. These results are consistent with prior studies and should offer additional reassurance to patients with inherited or acquired thrombophilia.

Real world utilization of Andexanet alfa in the management of oral factor Xa inhibitor-associated gastrointestinal bleeding.

BACKGROUND: Andexanet alfa (AA) is approved for reversal of factor Xa inhibitor (FXaI) bleeds; however, there are limited reports of its use for gastrointestinal bleeding (GIB) in real-world populations. The objective of this study was to report real-world utilization and evaluation of the effectiveness of AA for FXaI-associated GIB. METHODS: This retrospective cohort study including consecutive patients receiving AA for FXaI-associated GIB (7/2018-2/2021). Demographics, blood product administration, hemostatic efficacy, rebleeding, thrombosis, and mortality rates were collected. Hemostatic efficacy (HE), based on corrected hemoglobin at 12 h compared to baseline, was categorized as excellent (<10% decrease), good (≤ 20% decrease), or poor (>20% decrease, > 2 units of additional coagulation intervention or death prior to repeat hemoglobin). Comparative transfusion requirements between efficacy groups was assessed by Wilcoxon-Rank test. RESULTS: Twenty-two patients were included (64% male, median (IQR) age 76 years (67, 80). Most patients (59%, n = 13) were on apixaban, and the primary anticoagulation indication was atrial fibrillation (64%, n = 14). Median initial hemoglobin was 7.5 g/dL (IQR 6.4, 8.8) and 50% (n = 11) were upper GIB. Hemostatic efficacy was excellent in 46% (n = 10), good in 23% (n = 5), and poor in 32% (n = 7). There was no statistically significant difference in red blood cells (RBCs) received between those with excellent/good hemostasis (median 2, IQR 1 to 2) and those with poor hemostasis (median 4, IQR 1.5 to 4.5). Two patients (9%) had arterial thrombotic events within 30 days of reversal. CONCLUSION: In this multicenter, single arm, real-world observational analysis of patients with factor Xa inhibitor associated GIB most patients achieved good hemostasis following administration of AA. There was a 9% 30-day thrombotic event rate. The lack of a control group limits the strength of the conclusions that can be drawn from this study.

Rivaroxaban for Thromboprophylaxis in High-Risk Ambulatory Patients with Cancer.

BACKGROUND: Ambulatory patients receiving systemic cancer therapy are at varying risk for venous thromboembolism. However, the benefit of thromboprophylaxis in these patients is uncertain. METHODS: In this double-blind, randomized trial involving high-risk ambulatory patients with cancer (Khorana score of ≥2, on a scale from 0 to 6, with higher scores indicating a higher risk of venous thromboembolism), we randomly assigned patients without deep-vein thrombosis at screening to receive rivaroxaban (at a dose of 10 mg) or placebo daily for up to 180 days, with screening every 8 weeks. The primary efficacy end point was a composite of objectively confirmed proximal deep-vein thrombosis in a lower limb, pulmonary embolism, symptomatic deep-vein thrombosis in an upper limb or distal deep-vein thrombosis in a lower limb, and death from venous thromboembolism and was assessed up to day 180. In a prespecified supportive analysis involving the same population, the same end point was assessed during the intervention period (first receipt of trial agent to last dose plus 2 days). The primary safety end point was major bleeding. RESULTS: Of 1080 enrolled patients, 49 (4.5%) had thrombosis at screening and did not undergo randomization. Of the 841 patients who underwent randomization, the primary end point occurred in 25 of 420 patients (6.0%) in the rivaroxaban group and in 37 of 421 (8.8%) in the placebo group (hazard ratio, 0.66; 95% confidence interval [CI], 0.40 to 1.09; P = 0.10) in the period up to day 180. In the prespecified intervention-period analysis, the primary end point occurred in 11 patients (2.6%) in the rivaroxaban group and in 27 (6.4%) in the placebo group (hazard ratio, 0.40; 95% CI, 0.20 to 0.80). Major bleeding occurred in 8 of 405 patients (2.0%) in the rivaroxaban group and in 4 of 404 (1.0%) in the placebo group (hazard ratio, 1.96; 95% CI, 0.59 to 6.49). CONCLUSIONS: In high-risk ambulatory patients with cancer, treatment with rivaroxaban did not result in a significantly lower incidence of venous thromboembolism or death due to venous thromboembolism in the 180-day trial period. During the intervention period, rivaroxaban led to a substantially lower incidence of such events, with a low incidence of major bleeding. (Funded by Janssen and others; CASSINI ClinicalTrials.gov number, NCT02555878.).

Direct oral anticoagulants for cancer-associated venous thromboembolism: a systematic review and meta-analysis.

Direct oral anticoagulants (DOACs) are an emerging treatment option for patients with cancer and acute venous thromboembolism (VTE), but studies have reported inconsistent results. This systematic review and meta-analysis compared the efficacy and safety of DOACs and low-molecular-weight heparins (LMWHs) in these patients. MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, and conference proceedings were searched to identify relevant randomized controlled trials. Additional data were obtained from the original authors to homogenize definitions for all study outcomes. The primary efficacy and safety outcomes were recurrent VTE and major bleeding, respectively. Other outcomes included the composite of recurrent VTE and major bleeding, clinically relevant nonmajor bleeding (CRNMB), and all-cause mortality. Summary relative risks (RRs) were calculated in a random effects meta-analysis. In the primary analysis comprising 2607 patients, the risk of recurrent VTE was nonsignificantly lower with DOACs than with LMWHs (RR, 0.68; 95% CI, 0.39-1.17). Conversely, the risks of major bleeding (RR, 1.36; 95% CI, 0.55-3.35) and CRNMB (RR, 1.63; 95% CI, 0.73-3.64) were nonsignificantly higher. The risk of the composite of recurrent VTE or major bleeding was nonsignificantly lower with DOACs than with LMWHs (RR, 0.86; 95% CI, 0.60-1.23). Mortality was comparable in both groups (RR, 0.96; 95% CI, 0.68-1.36). Findings were consistent during the on-treatment period and in those with incidental VTE. In conclusion, DOACs are an effective treatment option for patients with cancer and acute VTE, although caution is needed in patients at high risk of bleeding.

Artificial intelligence for the evaluation of peripheral artery disease using arterial Doppler waveforms to predict abnormal ankle-brachial index.

BACKGROUND: Patients with peripheral artery disease (PAD) are at increased risk for major adverse limb and cardiac events including mortality. Developing screening tools capable of accurate PAD identification is a necessary first step for strategies of adverse outcome prevention. This study aimed to determine whether machine analysis of a resting Doppler waveform using deep neural networks can accurately identify patients with PAD. METHODS: Consecutive patients (4/8/2015 - 12/31/2020) undergoing rest and postexercise ankle-brachial index (ABI) testing were included. Patients were randomly allocated to training, validation, and testing subsets (70%/15%/15%). Deep neural networks were trained on resting posterior tibial arterial Doppler waveforms to predict normal (> 0.9) or PAD (⩽ 0.9) using rest and postexercise ABI. A separate dataset of 151 patients who underwent testing during a period after the model had been created and validated (1/1/2021 - 3/31/2021) was used for secondary validation. Area under the receiver operating characteristic curves (AUC) were constructed to evaluate test performance. RESULTS: Among 11,748 total patients, 3432 patients met study criteria: 1941 with PAD (mean age 69 ± 12 years) and 1491 without PAD (64 ± 14 years). The predictive model with highest performance identified PAD with an AUC 0.94 (CI = 0.92-0.96), sensitivity 0.83, specificity 0.88, accuracy 0.85, and positive predictive value (PPV) 0.90. Results were similar for the validation dataset: AUC 0.94 (CI = 0.91-0.98), sensitivity 0.91, specificity 0.85, accuracy 0.89, and PPV 0.89 (postexercise ABI comparison). CONCLUSION: An artificial intelligence-enabled analysis of a resting Doppler arterial waveform permits identification of PAD at a clinically relevant performance level.

Single versus multiple and incidental versus symptomatic subsegmental pulmonary embolism: clinical characteristics and outcome.

It remains unexplored if the clinical picture and outcome of subsegmental pulmonary embolism (SSPE) differ between single versus multiple, and incidental versus symptomatic embolism. Consecutive patients anticoagulated for SSPE at the Mayo Thrombophilia Clinic (03/01/2013-12/31/2020) were followed forward to assess venous thromboembolism (VTE) recurrence, mortality, major bleeding, and clinically relevant non-major bleeding (CRNMB); expressed as a rate per 100 person-years. Among 3878 VTE patients, 1541 had pulmonary embolism including 224 (14.6%) with SSPE either single (n = 139) or multiple (n = 85; 46 bilateral and 39 unilateral emboli); 134 had incidental and 90 symptomatic SSPE. Patients with single were less often symptomatic and less often had coexisting DVT than multiple SSPE. Patients with incidental had a two-fold higher frequency of cancer compared to symptomatic SSPE. During the study period, 1 patient with single and 2 with multiple SSPE had VTE recurrence (rate of 1.14 vs 3.63, p = 0.280). Single SSPE patients experienced 2 episodes of major bleeding (rate of 2.36) while the multiple SSPE group had no major bleeding. Seven patients in each group had CRNMB events (rate of 8.20 vs 13.58 for single and multiple SSPE, respectively, p = 0.282). Patients with single SSPE had a higher death rate compared to multiple SSPE (43.07 vs 22.22, p = 0.031) but no difference was noted after adjusting for cancer (p = 0.388). Also, incidental had similar clinical outcomes to symptomatic SSPE.Interpretation Anticoagulated SSPE patients with single and multiple as well as incidental and symptomatic have a different clinical profile but similar clinical outcomes.

Catheter directed compared to systemically delivered thrombolysis for pulmonary embolism: a systematic review and meta-analysis.

To compare the efficacy and safety of systemic and catheter directed thrombolysis for patients with pulmonary embolism. Pubmed and Cochrane Central Register of Controlled Trials were systematically searched from inception to May 31st 2020 to identify relevant studies. Outcomes of interest were in-hospital mortality and major bleeding including intracranial hemorrhage. We included 8 observational studies comprising 11,932 patients with PE. Catheter directed thrombolysis was associated with lower in-hospital mortality [RR 0.52; 95% confidence interval (CI) 0.40-0.68]. Although there was no difference in major bleeding by treatment strategy (RR 0.80; 95% CI 0.37-1.76), intracranial hemorrhage was lower in patients receiving catheter directed therapy (RR 0.66; 95% CI, 0.47-0.94).The certainty in these estimates was low. Non-randomized studies suggest that catheter directed delivery of thrombolytic therapy may be associated with lower in-hospital mortality and intracranial hemorrhage rates. These results may help inform management strategies for health care and pulmonary embolism response teams (PERT) involved in the management of high risk patients with massive or submassive pulmonary emboli.

Treatment of Cancer-Associated Venous Thromboembolism with Low-Molecular-Weight Heparin or Direct Oral Anticoagulants: Patient Selection, Controversies, and Caveats.

The treatment of venous thromboembolism (VTE) in patients with cancer is challenging because these patients have increased risks of both recurrent VTE and major bleeding, along with patient-specific and cancer-related factors that influence the approach to treatment. Historically, anticoagulant therapy with low-molecular-weight heparin (LMWH), given for both initial and long-term treatment, has been the preferred approach recommended by practice guidelines. Most recently, the National Comprehensive Cancer Network (NCCN) guidelines indicate that the direct oral anticoagulants (DOACs) apixaban, edoxaban, or rivaroxaban are preferred for patients without gastric or gastroesophageal lesions. DOACs have been associated with an increased risk of major bleeding in patients with gastrointestinal and possibly genitourinary cancers, and DOACs should either not be used (especially in those with intact intraluminal tumors) or be used with caution in patients with these cancers. Fatal or life-threatening bleeding occurs with similar frequency with DOACs or LMWH, and most major bleeding with DOACs can be managed with transfusion and standard measures. The patient's willingness and ability to comply with LMWH injections, and their treatment preference, should also be considered. Patients with cancer who have VTE should be treated with anticoagulation for a minimum of 6 months. Anticoagulation should be continued indefinitely while cancer is active or under treatment or if there are persistent risk factors for recurrent VTE. This article summarizes the evidence from clinical trials of LMWH and DOACs that underpins the NCCN guideline recommendations, addresses several controversies and caveats regarding anticoagulant treatment, and offers evidence-based, practical suggestions on patient selection for treatment with DOACs. IMPLICATIONS FOR PRACTICE: Several randomized trials support the addition of direct oral anticoagulants (DOACs) to the therapeutic armamentarium for cancer-associated venous thromboembolism (VTE). These agents come with unique risks and patient- and cancer-specific variables that must be evaluated during the course of a patient's cancer care. This narrative review discusses findings from clinical trials of low-molecular-weight heparin and DOACs for the treatment of cancer-associated VTE, evidence that supports the recent National Comprehensive Cancer Network guideline recommendations. A personalized approach to treatment is proposed that addresses patient selection for treatment with DOACs, factors that influence efficacy and safety, controversies and caveats, and suggestions for their resolution in clinical practice.

Major adverse events associated with inducible cardiac ischemia during treadmill exercise testing for peripheral artery disease.

BACKGROUND: The coexistence of coronary artery disease and peripheral artery disease (PAD) is well-established. Whether myocardial ischemia by electrocardiography during treadmill testing to evaluate PAD severity is associated with adverse cardiac and limb events has not been established. The aim of the current study is to assess the risk of major adverse cardiac events (MACE), major adverse limb events (MALE), and all-cause mortality in patients with evidence of myocardial ischemia on ECG compared with those without ischemia in patients undergoing treadmill testing for PAD evaluation. METHODS: Patients undergoing treadmill exercise ankle-brachial index (ABI) evaluation (January 1, 2003, to December 31, 2006) were identified using the Mayo Clinic Gonda Vascular Laboratory database. Patients with ischemia by electrocardiogram (ECG) were age and sex matched to patients without ischemia. Outcomes were compared by ECG category. RESULTS: Of 4128 patients who underwent treadmill exercise, 170 (4.1%) had inducible myocardial ischemia by ECG. These were matched with 340 patients without ischemia. The positive ECG group had a higher percentage of diabetes mellitus (31.2% vs 21.8%; P = .02), carotid artery disease (22.4% vs 13.2%; P = .009), exercise-induced angina (14.1% vs 2.9%; P < .0001), and dyspnea (60.6% vs 35.6%; P < .0001). While the resting ABI was similar, the postexercise ABI was lower in the positive ECG group (0.5 vs 0.7; P = .04). After a median follow-up of 8 years, MACE were significantly greater in the positive ECG group (62.4% vs 46.5%; P < .001). MALE were significantly less frequent (17.1% vs 23.2%; P = .02), without an increased risk of amputation. In multivariable analysis, inducible ischemia was associated with higher incidence of MACE (hazard ratio, 1.65; 95% confidence interval, 1.25-2.16; P < .001) and lower incidence of MALE (hazard ratio, 0.51; 95% confidence interval, 0.31-0.84; P < .05). CONCLUSIONS: ECG monitoring during vascular treadmill testing identified a subset of patients with more frequent MACE but less MALE.

Spontaneous visceral artery dissections in otherwise normal arteries: Clinical features, management, and outcomes compared with fibromuscular dysplasia.

OBJECTIVE: Visceral artery dissection with otherwise normal-appearing arteries (VADNA), diagnosed on imaging and suggestive of segmental arterial mediolysis, is a poorly understood disease entity. Study objectives were to define the clinical features, management, and outcomes of patients with VADNA compared with patients with fibromuscular dysplasia (FMD). METHODS: In this single-center retrospective cohort study, consecutive patients with a diagnosis of VADNA or FMD evaluated in the Mayo Clinic Gonda Vascular Center (January 1, 2000-April 1, 2017) were identified. Patient demographics, symptom presentation, management, composite adverse arterial events (recurrent arterial dissection, stroke or transient ischemic attack, myocardial infarction, mesenteric or renal infarction, or need for revascularization), and overall survival were compared between VADNA and FMD patients. RESULTS: There were 103 VADNA patients (age [mean ± standard deviation], 51.7 ± 11.0 years; 27.9% female) and 248 FMD controls (49.8 ± 8.9 years; 81.8% female) identified. The most common symptom for VADNA patients was abdominal or flank pain (80.6%). For FMD, chest pain, headache, and dizziness were more frequent presenting complaints. The median follow-up was longer for VADNA patients (42 months; interquartile range, 9-76 months) compared with FMD patients (19 months; interquartile range, 0.6-52 months; P < .001). During this time interval, there were twofold more composite arterial events in the VADNA group compared with the FMD group (17% vs 8.1%; P = .01). This difference was primarily driven by recurrent dissections. All-cause mortality was low and similar for both groups (3.8% vs 0.4%; P = .10). CONCLUSIONS: VADNA patients carry a higher risk of recurrent arterial events compared with those with FMD. This difference was primarily driven by recurrent dissections.

Pulmonary venous thrombosis in a patient with COVID-19 infection.

OBJECTIVES: Infection with the SARS-COV2 virus (COVID-19) may be complicated by thrombotic diathesis. This complication often involves the pulmonary microcirculation. While macrovascular thrombotic complications of the lung may include pulmonary artery embolism, pulmonary artery thrombus in situ has also been hypothesized. Pulmonary vein thrombosis has not been described in this context. METHODS/RESULTS: Herein, we provide a case of an otherwise healthy male who developed an ischemic stroke with left internal carotid thrombus. Further imaging revealed pulmonary emboli with propagation through the pulmonary veins into the left atrium. This left atrial thrombus provides a source of atypical "paradoxic arterial embolism". CONCLUSIONS: Thrombotic outcomes in the setting of severe COVID 19 pneumonia may include macrovascular venous thromboembolism, microvascular pulmonary vascular thrombosis and arterial thromboembolism. Pulmonary vein, herein described, provides further mechanistic pathway for potential arterial embolic phenomenon.

Primary pulmonary artery sarcoma versus pulmonary thromboembolism: a multimodal imaging comparison.

Primary pulmonary artery sarcoma (PPAS) is a rare malignancy that is commonly mistaken for pulmonary embolism due to similarities in clinical presentation and radiographic findings. Distinct radiographic findings to help differentiate between the two diseases are highlighted in the case presented. (1) Several nuances in various imaging modalities have been identified to help distinguish pulmonary artery sarcoma from pulmonary thromboembolic disease. (2) The wall eclipsing sign is considered pathognomonic for pulmonary artery sarcoma. (3) Positron emission tomography/computed tomography may help reduce time between diagnosis and treatment, which may ultimately prolong survival. (4) Providers should be well versed on the subtle differences on imaging to prevent future delays in diagnosis and treatment.

Extending venous thromboembolism secondary prevention with apixaban in cancer patients: The EVE trial.

BACKGROUND: Cancer-associated venous thromboembolism (VTE) carries a high rate of recurrence and death. Guidelines recommend continued anticoagulation therapy as long as active cancer persists. Apixaban 2.5 mg twice daily is the FDA-approved dose for secondary prevention regardless of VTE causation. Whether this apixaban dose is appropriate for secondary VTE prevention in cancer patients is not clear. The rationale and design of this investigator initiated phase III, multicenter, randomized, double-blind, trial assessing apixaban 2.5 mg vs 5 mg twice daily for 12 months for the secondary VTE prevention in cancer patients (n = 370) who have completed 6 months (but no more than 12 months) of anticoagulation is provided (NCT03080883). METHODS/DESIGN: The primary study objective is to estimate differences in the combined rate of major plus clinically relevant non-major bleeding for apixaban 2.5 mg vs 5 mg twice daily. Secondary efficacy outcome is to assess rates of venous or arterial thromboembolism. Participating centers are chosen from the Academic and Community Cancer Research United (ACCRU) consortium. CONCLUSION: We anticipate these trial results to provide evidence supporting low-dose apixaban as a safe agent for secondary prevention of cancer-associated VTE for patients who have already completed 6-12 months of anticoagulation.

Effectiveness and safety of apixaban and rivaroxaban for acute venous thromboembolism therapy in patients with extremes in bodyweight.

OBJECTIVES: To investigate the association of extremes in bodyweight (EBW) and outcomes in patients with acute venous thromboembolism (VTE). Recurrent VTE, major bleeding, and clinically relevant non-major bleeding were compared between patients with bodyweight <60 kg, 60-120 kg, and >120 kg. METHODS: Consecutive patients enrolled in the Mayo Clinic VTE Registry (03/28/2013-8/31/2019) with acute VTE were followed prospectively. Patient status was assessed in person, by mailing a written questionnaire, or by a scripted phone interview. RESULTS: Among 2577 patients with weight ranging from 27.0 kg to 263.2 kg, 2123 (82%) had a bodyweight between 60 and 120 kg, 223 (8.7%) had bodyweight < 60 kg, and 230 (8.9%) had bodyweight >120 kg. Patients with bodyweight <60 kg treated with DOACs had higher 3- and 6-month incidence of major bleeding compared to the bodyweight 60-120kg group (4.4% vs 1.1%, P = .03, and 4.4% vs 1.4%, P = .05, respectively). Patients with bodyweight >120 kg and cancer on rivaroxaban had higher VTE recurrence compared to bodyweight 60-120kg group (P = .01). CONCLUSIONS: Treatment of acute VTE is associated with a higher incidence of bleeding in patients with bodyweight <60 kg. A higher VTE recurrence rate occurred only in cancer patients with bodyweight >120 kg on rivaroxaban.

Treatment of upper extremity deep vein thrombosis with apixaban and rivaroxaban.

Randomized controlled trials leading to the approval of apixaban and rivaroxaban for venous thromboembolism (VTE) did not include patients with upper extremity deep vein thrombosis (UE-DVT). We sought to evaluate the safety and effectiveness of rivaroxaban and apixaban for the treatment of acute UE-DVT. Consecutive patients with VTE enrolled into the Mayo Clinic VTE Registry, between March 1, 2013 and December 31, 2019, were followed prospectively. Clinical, demographic and imaging data were collected at the time of study recruitment. Patients with a diagnosis of acute UE-DVT who received rivaroxaban, apixaban, LMWH or warfarin were included. Recurrent VTE, major bleeding, clinical-relevant non-major bleeding (CRNMB), and death were assessed at 3-month intervals. During the study period, 210 patients with acute UE-DVT were included; 63 were treated with apixaban, 39 with rivaroxaban, and 108 with LWMH and/or warfarin. Overall 51% had catheter-associated UE-DVT, 60% had a diagnosis of malignancy, and 14% had concurrent pulmonary embolism. Malignancy was more common in patients treated with LMWH/warfarin (67% vs 52%, P = .03). At 3 months of follow up, one (0.9%) recurrent VTE occurred in a patient treated with LMWH/warfarin and one (1.0%) patient treated with apixaban or rivaroxaban (P = .97). Major bleeding occurred in three patients treated with LMWH/warfarin, and in none of those treated with apixaban or rivaroxaban (P = .09). Clinical-relevant non-major bleeding occurred in one patient (0.9%) treated with LWMH/warfarin and two patients (2.0%) treated with apixaban or rivaroxaban (P = .53). Treatment of UE-DVT with apixaban or rivaroxaban appears to be as safe and effective as LMWH/warfarin.

Calf muscle pump function as a predictor of all-cause mortality.

Calf muscle pump (CMP) promotes venous return from the lower extremity and contributes to preload and cardiac output. Impaired CMP function may reflect a measure of frailty or cumulative disease burden or may impede cardiac function. The study objective was to test the hypothesis that impaired CMP negatively impacts survival. Consecutive adult patients who underwent venous strain gauge plethysmography at the Mayo Clinic Gonda Vascular Laboratory (January 1, 1998 - December 31, 2011) were assessed for overall survival. Patients with venous incompetence, venous obstruction or unilateral calf pump dysfunction were excluded. Risk of mortality was assessed with Cox proportional hazard ratios and after adjusting for Charlson Comorbidity Index variables. Over the study period, 2728 patients were included in the analysis. Compared to patients with normal CMP, those with impaired CMP were older (p < 0.001), predominantly female (p = 0.01) and had higher mean Charlson scores (p < 0.001). Patients with impaired CMP had a higher mortality rate at 5 (8.9% vs 2.4%), 10 (17.5% vs 5.9%), and 15 years (22.8% vs 8.3%) compared to those with normal CMP (p < 0.001 for each comparison). Of patients with heart failure, those with impaired CMP had worse survival at each 5-year increment compared to those with normal CMP (p < 0.05 at each increment). In conclusion, impaired CMP appears to be an independent predictor of poor outcomes after adjusting for variables within the Charlson Comorbidity Index. The association between impaired CMP, heart failure, and mortality may represent a negative impact on circulatory function or a surrogate measure of frailty.