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.

Cancer-associated non-bacterial thrombotic endocarditis-Clinical series from a single institution.

Premortem clinical presentation of cancer-associated non-bacterial thrombotic endocarditis (Ca-NBTE), therapy, and the clinal course is limited to case reports and small clinical series. An electronic search of Mayo Clinic records (03/31/2002-06/30/2022) with a subsequent manual review was performed to identify adult patients with echocardiographically detected NBTE and active malignancy, excluding those with infectious endocarditis or lupus anticoagulant/antiphospholipid antibodies. In this retrospective cohort study, we analyzed 115 Ca-NBTE patients (mean age 63.2 ± 9.7 years, 66.1% female) involving 71 (61.7%) mitral, 58 (50.4%) aortic, 8 (6.9%) tricuspid, and 1 (0.9%) pulmonary valve. The most common cancer was lung (n = 45 cases (39.1%), followed by pancreatic (n = 19, 16.5%), gynecological (17, 14.8%), gastrointestinal (n = 10, 8.7%), and 10 (8.7%) with hematologic malignancy; 6 patients had two active cancers. Embolic complications at presentation were frequent: 94 (81.7%) brain, 11 splenic, 10 renal, 6 coronary, and 4 to the extremities. Of 104 anticoagulated patients, 60 received low molecular weight heparin, 17 unfractionated heparin, 16 apixaban, 8 warfarin, and 3 rivaroxaban. There were 18 arterial thromboembolisms; the Kaplan-Meier estimates of the incidence at 2 years were consistent with a rate of 15.9% [95% Confidence Interval (CI) 9.9-23.3], including 14 strokes (12.4%, 95%CI, 7.1-19.2), and 8 other arterial emboli (10.5%, 95%CI, 4.7-18.9); there were 10 venous thromboembolisms (8.9%, 95%CI, 4.5-15.0). Fourteen major bleedings occurred (12.8%, 95%CI, 7.3-19.9) and 94 patients died during follow-up (77.9%, 95%CI, 71.1-85.8). Ca-NBTE predominantly affected women with lung adenocarcinoma or digestive tract cancers and manifested by stroke with high mortality and frequent embolic and bleeding complications during anticoagulation therapy.

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.

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.

Popliteal cysts are not a risk factor for lower extremity deep vein thrombosis.

BACKGROUND: Popliteal cysts (PC) result from distension of the gastrocnemio-semimembranosous bursa. Published reports indicate coincident PC and deep vein thrombosis (DVT). Whether the presence of PC increase the risk of deep vein thrombosis (DVT) remains unclear. METHODS: Lower extremity venous Duplex ultrasound (DUS) reports were evaluated across the Mayo Clinic Enterprise (Rochester, Minnesota, Jacksonville, Florida, Scottsdale, Arizona, and the Mayo Clinic Health System) in patients ≥ 18 years of age. Natural language processing (NLP) algorithms were created and validated to identify acute lower extremity DVT and PC from these reports. To determine whether there is a link between PC and lower extremity DVT, the frequency of PC among cases (ultrasounds with acute DVT) were compared to controls (ultrasounds without acute DVT). RESULTS: A total of 357,703 lower extremities venous DUS were performed in 237,052 patients (mean age 63.3 ± 16.6, 54.4% were female) between 1992 and 2021. Acute DVT was identified in 32,572 (9.1%) DUS, and PC in 32,448 (9.1%). PC were seen in a lower frequency (8.0%) of ultrasounds with acute DVT than those without (9.2%) acute DVT (OR: 0.85, 95% CI: 0.82 to 0.89, p < 0.001). In a multivariate logistic regression model after adjusting for age, sex, and race, PCs were not positively associated with acute DVT (adjusted OR: 0.84, 95% CI: 0.81 to 0.88). CONCLUSIONS: PC are an incidental finding or an alternative diagnosis on lower extremity venous DUS, a finding that increases significantly with age. PC were not a risk factor in the development of lower extremity DVT.

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.

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.

Calf vein thrombosis outcomes comparing patients with and without cancer.

Distal or calf deep vein thrombosis (DVT) are said to have low rates of propagation, embolization, and recurrence. The objective of this study was to determine outcomes among cancer patients with calf DVT compared to those without cancer. Consecutive patients with ultrasound confirmed acute calf DVT (3/1/2013-8/10/2019) were assessed for venous thromboembolism (VTE) recurrence and bleeding outcomes compared by cancer status. There were 830 patients with isolated calf DVT; 243 with cancer and 587 without cancer. Cancer patients were older (65.9 ± 11.4 vs. 62.0 ± 15.9 years; p = 0.006), with less frequent recent hospitalization (31.7% vs. 48.0%; p < 0.001), surgery (30.0% vs. 38.0%; p = 0.03), or trauma (3.7% vs. 19.9%; p < 0.001). The four most common cancers included hematologic malignancies (20.6%), lung (11.5%), gastrointestinal (10.3%), and ovarian/GYN (9.1%). Nearly half of patients had metastatic disease (43.8%) and 57% were receiving chemotherapy. VTE recurrence rates were similar for patients with (7.1%) and without cancer (4.0%; p = 0.105). Major bleeding (6.3% vs. 2.3%; p = 0.007) were greater for cancer patients while clinical relevant non major bleeding rates did not differ (7.1% vs. 4.6%; p = 0.159). In this retrospective analysis, cancer patients with calf DVT have similar rates of VTE recurrence but higher major bleeding outcomes compared to patients without cancer.

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.

Resolution of acute lower extremity deep vein thrombosis with rivaroxaban compared to warfarin.

Thrombosis resolution is an important component of treatment for deep vein thrombosis (DVT) and multiple anticoagulants are now available. It is unknown whether rivaroxaban contributes to a higher degree of thrombus resolution compared to conventional anticoagulation with warfarin. Our objective was to compare thrombus resolution for rivaroxaban versus warfarin treated patients with acute lower extremity DVT. Consecutive patients treated for proximal or distal lower extremity DVT with rivaroxaban were identified from the Mayo Thrombophilia Clinic Anticoagulants Registry (November 2015-June 2016) and compared to patients treated with warfarin. Ultrasonography/Doppler images were analyzed by two independent radiologists blinded to anticoagulant and using a standardized assessment algorithm. A total of 111 patients with DVT were studied. Sixty-three rivaroxaban treated patients were compared to 48 warfarin treated patients over a median follow up of 92 and 97 days, respectively. Percentage of patients with total or partial resolution of thrombosis was similar in rivaroxaban and warfarin treated groups (95.2% vs. 91.7%, p = 0.46, respectively); also the proportion of patients with total thrombus resolution was not significantly different (38.1% vs. 29.2%, p = 0.42, respectively). There was no significant difference in the proportion of patients with no thrombus resolution between rivaroxaban and warfarin treated groups either (4.8% vs. 2.1%, p = 0.63). Thrombus propagation with warfarin therapy was observed in 6.3% of patients treated with warfarin and in none of the patients from the rivaroxaban group (p = 0.08). Resolution of acute lower extremity DVT in patients treated with rivaroxaban is similar to those treated with warfarin.

Comparison of apixaban to rivaroxaban and enoxaparin in acute cancer-associated venous thromboembolism.

To provide direct comparison between apixaban and rivaroxaban in patients with acute cancer-associated venous thromboembolism (Ca-VTE), consecutive patients treated with apixaban, rivaroxaban, or enoxaparin at Mayo Thrombophilia Clinic (March 1, 2013 to January 31, 2018)) were followed prospectively. The primary effectiveness outcome was venous thromboembolism (VTE) recurrence, and the secondary was mortality. The primary safety outcome was major bleeding, the secondary clinically relevant safety outcome was non-major bleeding (CRNMB), and the third a composite of major and CRNMB. There were 750 patients treated for acute Ca-VTE with apixaban (n = 224), rivaroxaban (n = 163), and enoxaparin (n = 363) within 14 days of diagnosis and for at least 3 months, or until study event. Recurrent VTE was diagnosed in 11 receiving apixaban, 7 receiving rivaroxaban (apixaban vs rivaroxaban hazard ratio (HR) 1.31, 95% confidence interval (95% CI) 0.51-3.36) and 17 in the enoxaparin receiving group (apixaban vs enoxaparin HR 1.14, 95% CI: 0.54, 2.42 and rivaroxaban vs enoxaparin HR 0.85, 95% Cl: 0.36, 2.06). There were 82 deaths in apixaban, 74 rivaroxaban (apixaban vs rivaroxaban HR 1.67, 95% Cl: 1.20, 2.33) and 171 in enoxaparin group (rivaroxaban vs enoxaparin HR 0.73, 95% Cl: 0.56, 0.96). Major bleeding occurred in 11 apixaban, 12 rivaroxaban (apixaban vs rivaroxaban HR 0.73, 95% Cl: 0.32, 1.66) and 21 enoxaparin group (apixaban vs enoxaparin HR 0.89, 95% Cl: 0.43, 1.84 and rivaroxaban vs enoxaparin HR 1.23, 95% Cl: 0.61, 2.50). The CRNMB rate was higher in rivaroxaban compared to apixaban (P = .03) and LMWH (P = .01) groups. Recurrence of VTE and major bleeding were similar in apixaban, rivaroxaban, and enoxaparin groups. Rivaroxaban was associated with higher CRNMB but lower mortality compared to apixaban and enoxaparin.

Impact of Left Atrial Appendage Closure During Cardiac Surgery on the Occurrence of Early Postoperative Atrial Fibrillation, Stroke, and Mortality: A Propensity Score-Matched Analysis of 10 633 Patients.

BACKGROUND: Prophylactic exclusion of the left atrial appendage (LAA) is often performed during cardiac surgery ostensibly to reduce the risk of stroke. However, the clinical impact of LAA closure in humans remains inconclusive. METHODS: Of 10 633 adults who underwent coronary artery bypass grafting and valve surgery between January 2000 and December 2005, 9792 patients with complete baseline characteristics, surgery procedure, and follow-up data were included in this analysis. A propensity score-matching analysis based on 28 pretreatment covariates was performed and 461 matching pairs were derived and analyzed to estimate the association of LAA closure with early postoperative atrial fibrillation (POAF) (atrial fibrillation ≤30 days of surgery), ischemic stroke, and mortality. RESULTS: In the propensity-matched cohort, the overall incidence of POAF was 53.9%. In this group, the rate of early POAF among the patients who underwent LAA closure was 68.6% versus 31.9% for those who did not undergo the procedure (P<0.001). LAA closure was independently associated with an increased risk of early POAF (adjusted odds ratio, 3.88; 95% confidence interval, 2.89-5.20), but did not significantly influence the risk of stroke (adjusted hazard ratio, 1.07; 95% confidence interval, 0.72-1.58) or mortality (adjusted hazard ratio, 0.92; 95% confidence interval, 0.75-1.13). CONCLUSIONS: After adjustment for treatment allocation bias, LAA closure during routine cardiac surgery was significantly associated with an increased risk of early POAF, but it did not influence the risk of stroke or mortality. It remains uncertain whether prophylactic exclusion of the LAA is warranted for stroke prevention during non-atrial fibrillation-related cardiac surgery.

Platelet-predominate gene expression and reticulated platelets in nonvalvular atrial fibrillation: Effect of pulmonary veins isolation.

INTRODUCTION: Reticulated platelet (RP) content is increased in nonvalvular atrial fibrillation (NVAF). The purpose of this study was to determine if platelet content, morphology, and RP proportion are modulated by platelet genes. METHODS AND RESULTS: Expression of six platelet-predominate genes impacting platelet formation and release, platelet count, and RP content was assessed in NVAF patients before and 3-4 months after pulmonary veins isolation (PVI) and compared to normal sinus rhythm (NSR) controls. RNA from isolated platelets was reverse-transcribed assayed against selected genes utilizing real-time qPCR, and expressed as mean cycle threshold (ΔCt) using beta-2-microglobulin as endogenous control. RP content was assessed by flow cytometry. A fourfold lower expression of CFL1 gene coding for nonmuscle cofilin (7.8 ± 0.9 vs. 5.7 ± 1.6, P < 0.001) and twofold lower expression of four other genes were associated with similar platelet counts but fourfold higher (28.7+7.0 vs. 6.7+5.4, P < 0.001) RP content (%) in 97 NVAF cases compared to 51 NSR controls. Three to 4 months after PVI, RP decreased by 28%, while CFL1 gene expression increased over twofold but TUBA4A gene expression decreased almost twofold; NFE2 and MYL6 gene expression remained unchanged. CONCLUSIONS: NVAF is associated with notable downregulation of genes directing platelet production and size but increased RP content. PVI impacts the expression of many of these genes, implying a direct relationship between atrial fibrillation and platelet biogenesis.

Testicular vein thrombosis: Incidence of recurrent venous thromboembolism and survival.

PURPOSE: Testicular vein thrombosis (TVT) etiology, recurrence, and survival were compared with lower extremity deep vein thrombosis (DVT) in order to determine whether treatment guidelines for DVT could be applied to TVT. PATIENTS AND METHODS: An inception cohort of patients with confirmed TVT (January 1995-October 2015) was compared to a control group of patients with lower extremity DVT matched by age, gender, and diagnosis date. RESULTS: Thirty-nine men with TVT were identified; 15 (38%) with isolated TVT. Left testicular vein was affected in 77% patients; there were no cases of bilateral TVT. Cancer was over twofold more common in TVT patients (59% vs 28%, P = .01). Most cancers (78%) involved organs in proximity to the testicular vein. Although TVT patients were less frequently treated with anticoagulants (49% vs 97%, P = .0001), recurrence rates were similar to DVT group (TVT 4.2 vs DVT 1.1 per 100 patient-years, P = .11). Despite higher cancer prevalence, survival rates were similar between groups (31% vs 28%; P = .34). Major bleeding events were rare (one patient per group). CONCLUSIONS: Identifying TVT should prompt a search for a regional malignancy. Despite the high cancer prevalence and low utilization of anticoagulants, recurrent venous thrombosis and mortality rates are similar to DVT patients.