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.

Noninvasive Peripheral Artery Disease Screening Tools: A Deficient Knowledge among French Vascular Residents from 4 Medical Schools.

BACKGROUND: Ankle-brachial index (ABI) at rest, postexercise ABI, and toe-brachial index (TBI) are essential diagnostic tools recommended for peripheral artery disease (PAD) diagnosis. Our study investigates the level of knowledge on these 3 tests among vascular medicine residents from 4 French medical schools in France. METHODS: We included 19 vascular medicine residents in a cross-sectional study. During an annual obligatory seminar, all residents accepted to fill 3 questionnaires concerning knowledge about these 3 tests. RESULTS: All residents accepted to fill 3 questionnaires. None of the residents correctly knows how to perform all pressure measurements (ABI, postexercise ABI, and TBI). Two residents had the knowledge to perform the whole ABI at rest procedure, whereas no resident had the knowledge to perform neither the postexercise ABI (P = 0.48) nor the TBI (P = 0.48). Twelve residents correctly completed the question regarding the interpretation of ABI at rest, whereas 2 correctly completed the postexercise ABI question (P = 0.001) and 4 the TBI question (P = 0.02). The number of residents who have performed more than 20 measurements is higher regarding ABI at rest than postexercise ABI and TBI (84%, 5%, and 37% respectively; P < 0.001 and P = 0.006 respectively) and significantly less often in postexercise ABI than TBI (5% vs. 37%; P = 0.04). CONCLUSIONS: This study shows for the first time that residents' knowledge of pressure measurements (resting-ABI, postexercise ABI, and TBI) of 4 French medical school are insufficient although the importance of pressure measurement has been strongly highlighted by the newly released PAD guidelines (2016) for PAD diagnosis.

Effect of atrial fibrillation duration on plasma von Willebrand factor level.

AIMS: von Willebrand factor (VWF) is an independent risk factor for adverse events in patients with non-valvular atrial fibrillation (NVAF). However, it is unclear if VWF level remains elevated and predictive of stroke during entire course of NVAF. METHODS AND RESULTS: In order to determine if VWF is a time-dependent blood variable, VWF antigen measured by latex immunoassay in 425 NVAF patients and 100 controls with normal sinus rhythm (NSR) was analyzed according to NVAF duration (<1 month: n = 76, 1-12 months: n = 98, and >12 months: n = 251). The mean VWF antigen level in NVAF patients with <1-month duration (167 ± 59%) was not different compared to those with 1-12 months (157 ± 50%, P = .24) and >12 months duration (156 ± 54%, P = .11) but higher compared to NSR controls (143 ± 48%, P = .003). Higher VWF level correlated with higher CHADS2 scores and with progressing intensity of blood stasis in the left atrium and thrombus formation in all three time periods of atrial fibrillation duration. Patients not treated with warfarin had VWF 30% higher in the first month compared to following months. CONCLUSIONS: von Willebrand Factor is steadily elevated throughout the course of dysrhythmia in NVAF patients treated with warfarin and in those with higher intensity of left atrium blood stasis.

Relationship between body mass index and left atrial appendage thrombus in nonvalvular atrial fibrillation.

Atrial fibrillation and obesity are two major growing epidemics in the United States and globally. Obese people are at the increased risk of developing atrial fibrillation. The contribution of obesity as an independent risk factor for stroke in the setting of atrial fibrillation remains unclear. We tested the hypothesis that non-valvular atrial fibrillation (NVAF) patients with increased body mass index (BMI) would be at increased risk for the development of left atrial appendage thrombus (LAAT). Consecutive, anticoagulation naïve patients with NVAF referred for a transesophageal echocardiogram (TEE) between January 1, 2007 and October 21, 2009 were approached for study participation. All clinical, laboratory, and TEE measurement data were collected prospectively. Within a group of 400 anticoagulation naïve NVAF patients (mean age 63 ± 15 years, 28 % women; 17 % with LAAT) the prevalence of LAAT was similar across all BMI categories (normal 13 %, overweight 19 %, obese 16 %, morbidly obese 16 %; p = 0.71). Despite a higher CHADS2 score and a higher prevalence of both hypertension and diabetes mellitus, elevated BMI was not an independent predictor of LAAT when analyzed as either a continuous variable, across BMI WHO categories, a dichotomous variable stratified at values above versus below 27 kg/m(2), or BMI stratified on atrial fibrillation duration. Despite a higher prevalence of major risk factors for thromboembolism, the prevalence of LAAT was not increased in overweight, obese, and morbidly obese patients.

Mapping the global geographic potential of Zika virus spread.

The Americas are presently experiencing the most serious known outbreak of Zika virus (ZIKV). Here, we present a novel set of analyses using environmental characteristics, vector mosquito distributions, and socioeconomic risk factors to develop the first map to detail global ZIKV transmission risk in multiple dimensions based on ecological niche models. Our model predictions were tested against independent evaluation data sets, and all models had predictive ability significantly better than random expectations. The study addresses urgent knowledge gaps regarding (1) the potential geographic scope of the current ZIKV epidemic, (2) the global potential for spread of ZIKV, and (3) drivers of ZIKV transmission. Our analysis of potential drivers of ZIKV distributions globally identified areas vulnerable in terms of some drivers, but not for others. The results of these analyses can guide regional education and preparedness efforts, such that medical personnel will be better prepared for diagnosis of potential ZIKV cases as they appear.

Retrievable inferior vena cava filters can be placed and removed with a high degree of success: Initial experience.

OBJECTIVES: Evaluate the success rate of retrievable inferior vena cava filter (IVC) removal in a tertiary care practice. BACKGROUND: Retrievable IVC filters became readily available in the United States following Food and Drug Administration approval in 2003, and their use has increased dramatically. They represent an attractive option for patients with contraindications to anticoagulation who may only need short-term protection against pulmonary embolism. METHODS: All patients who had undergone placement of a retrievable IVC filter at Mayo Clinic between 2003 and 2005 were retrospectively reviewed to evaluate our initial experience with retrievable inferior vena cava filters at a large tertiary care center. RESULTS: During a three-year-period of time, Mayo Clinic, Rochester, MN placed 892 IVC filters of which 460 were retrievable. Of the 460 retrievable filters placed (249 Günther Tulip®, 207 Recovery®, and 4 OptEase®), retrieval was attempted in 223 (48.5%). Of 223 initial attempts, 196 (87.9%) were initially successful and 27 (12.1%) were unsuccessful. Of the 27 unsuccessful initial retrieval attempts, 23 (85.2%) were because of the presence of significant thrombus within the filter and 4 (14.8%) were because of tilting and strut perforation. Of the 23 filters containing significant thrombus, 9 (39.1%) were later retrieved after a period of anticoagulation and resolution of the thrombus. CONCLUSIONS: Retrievable IVC filters can be removed with a high degree of success. Approximately one in ten retrievable IVC filter removal attempts may fail initially, usually because of significant thrombus within the filter. This does not preclude possible removal at a later date.

Abdominal aortic calcium, coronary artery calcium, and cardiovascular morbidity and mortality in the Multi-Ethnic Study of Atherosclerosis.

OBJECTIVE: To evaluate the predictive value of abdominal aortic calcium (AAC) for incident cardiovascular disease (CVD) independent of coronary artery calcium (CAC). APPROACH AND RESULTS: We evaluated the association of AAC with CVD in 1974 men and women aged 45 to 84 years randomly selected from the Multi-Ethnic Study of Atherosclerosis participants who had complete AAC and CAC data from computed tomographic scans. AAC and CAC were each divided into following 3 percentile categories: 0 to 50th, 51st to 75th, and 76th to 100th. During a mean of 5.5 years of follow-up, there were 50 hard coronary heart disease events, 83 hard CVD events, 30 fatal CVD events, and 105 total deaths. In multivariable-adjusted Cox models including both AAC and CAC, comparing the fourth quartile with the ≤ 50th percentile, AAC and CAC were each significantly and independently predictive of hard coronary heart disease and hard CVD, with hazard ratios ranging from 2.4 to 4.4. For CVD mortality, the hazard ratio was highly significant for the fourth quartile of AAC, 5.9 (P=0.01), whereas the association for the fourth quartile of CAC (hazard ratio, 2.1) was not significant. For total mortality, the fourth quartile hazard ratio for AAC was 2.7 (P=0.001), and for CAC, it was 1.9, P=0.04. Area under the receiver operating characteristic curve analyses showed improvement for both AAC and CAC separately, although improvement was greater with CAC for hard coronary heart disease and hard CVD, and greater with AAC for CVD mortality and total mortality. Sensitivity analyses defining AAC and CAC as continuous variables mirrored these results. CONCLUSIONS: AAC and CAC predicted hard coronary heart disease and hard CVD events independent of one another. Only AAC was independently related to CVD mortality, and AAC showed a stronger association than CAC with total mortality.

Efficacy and Safety of Therapeutic-Dose Heparin vs Standard Prophylactic or Intermediate-Dose Heparins for Thromboprophylaxis in High-risk Hospitalized Patients With COVID-19: The HEP-COVID Randomized Clinical Trial.

Importance: Hospitalized patients with COVID-19 are at risk for venous and arterial thromboembolism and death. Optimal thromboprophylaxis dosing in high-risk patients is unknown. Objective: To evaluate the effects of therapeutic-dose low-molecular-weight heparin (LMWH) vs institutional standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19. Design, Setting, and Participants: The HEP-COVID multicenter randomized clinical trial recruited hospitalized adult patients with COVID-19 with D-dimer levels more than 4 times the upper limit of normal or sepsis-induced coagulopathy score of 4 or greater from May 8, 2020, through May 14, 2021, at 12 academic centers in the US. Interventions: Patients were randomized to institutional standard prophylactic or intermediate-dose LMWH or unfractionated heparin vs therapeutic-dose enoxaparin, 1 mg/kg subcutaneous, twice daily if creatinine clearance was 30 mL/min/1.73 m2 or greater (0.5 mg/kg twice daily if creatinine clearance was 15-29 mL/min/1.73 m2) throughout hospitalization. Patients were stratified at the time of randomization based on intensive care unit (ICU) or non-ICU status. Main Outcomes and Measures: The primary efficacy outcome was venous thromboembolism (VTE), arterial thromboembolism (ATE), or death from any cause, and the principal safety outcome was major bleeding at 30 ± 2 days. Data were collected and adjudicated locally by blinded investigators via imaging, laboratory, and health record data. Results: Of 257 patients randomized, 253 were included in the analysis (mean [SD] age, 66.7 [14.0] years; men, 136 [53.8%]; women, 117 [46.2%]); 249 patients (98.4%) met inclusion criteria based on D-dimer elevation and 83 patients (32.8%) were stratified as ICU-level care. There were 124 patients (49%) in the standard-dose vs 129 patients (51%) in the therapeutic-dose group. The primary efficacy outcome was met in 52 of 124 patients (41.9%) (28.2% VTE, 3.2% ATE, 25.0% death) with standard-dose heparins vs 37 of 129 patients (28.7%) (11.7% VTE, 3.2% ATE, 19.4% death) with therapeutic-dose LMWH (relative risk [RR], 0.68; 95% CI, 0.49-0.96; P = .03), including a reduction in thromboembolism (29.0% vs 10.9%; RR, 0.37; 95% CI, 0.21-0.66; P < .001). The incidence of major bleeding was 1.6% with standard-dose vs 4.7% with therapeutic-dose heparins (RR, 2.88; 95% CI, 0.59-14.02; P = .17). The primary efficacy outcome was reduced in non-ICU patients (36.1% vs 16.7%; RR, 0.46; 95% CI, 0.27-0.81; P = .004) but not ICU patients (55.3% vs 51.1%; RR, 0.92; 95% CI, 0.62-1.39; P = .71). Conclusions and Relevance: In this randomized clinical trial, therapeutic-dose LMWH reduced major thromboembolism and death compared with institutional standard heparin thromboprophylaxis among inpatients with COVID-19 with very elevated D-dimer levels. The treatment effect was not seen in ICU patients. Trial Registration: ClinicalTrials.gov Identifier: NCT04401293.

Is Infection an Independent Risk Factor for Venous Thromboembolism? A Population-Based, Case-Control Study.

BACKGROUND: The independent association of recent infection with venous thromboembolism is uncertain. The study aims were to test both overall infection (site unspecified) and specific infection sites as potential risk factors for deep vein thrombosis and pulmonary embolism adjusting for other known venous thromboembolism factors. METHODS: By using Rochester Epidemiology Project resources, we identified all Olmsted County, Minnesota, residents with objectively diagnosed incident deep vein thrombosis or pulmonary embolism over the 13-year period 1988 to 2000 (cases; n = 1303) and 1 to 2 residents without venous thromboembolism matched to each case on age, sex, and incident venous thromboembolism date (controls; n = 1494). Using conditional logistic regression, we tested recent infection and infection site(s) for an association with venous thromboembolism, adjusting for body mass index, smoking, current/recent hospitalization with/without surgery, nursing home confinement, active cancer, trauma/fracture, leg paresis, prior superficial vein thrombosis, transvenous catheter/pacemaker, ischemic heart disease, congestive heart failure, chronic lung or renal disease, serious liver disease, asthma, diabetes mellitus, hormone therapy, and pregnancy/postpartum. RESULTS: A total of 513 cases (39.4%) and 189 controls (12.7%) had an infection in the previous 92 days (odds ratio, 4.5; 95% confidence interval, 3.6-5.5; P < .0001). In a multivariable analysis adjusting for common venous thromboembolism risk factors, pneumonia and symptomatic urinary tract, oral, intra-abdominal, and systemic bloodstream infections were associated with significantly increased odds of venous thromboembolism. CONCLUSIONS: Infection as a whole and specific infection sites in particular are independent risk factors for venous thromboembolism and should be considered as potential indications for venous thromboembolism prophylaxis.

Relationship of Aortic Wall Distensibility to Mitral and Aortic Valve Calcification: The Multi-Ethnic Study of Atherosclerosis.

Data are limited on whether valvular calcification is associated with aortic wall stiffness. We tested whether aortic valve calcification (AVC) and/or mitral valve calcification (MVC) is inversely associated with aortic distensibility (AD). Cross-sectional study conducted in a subset of the Multi-Ethnic Study of Atherosclerosis (MESA) included 3676 MESA participants aged 44 to 84 years with AD measured with magnetic resonance imaging and with AVC and MVC measured with noncontrast cardiac computed tomography scans. Both AVC and MVC were divided into 3 categories: zero, < median values (low), and ≥ median values (high) for patients with nonzero values. Overall, 88% (n = 3256) and 92% (n = 3365) of participants had zero AVC and MVC, while 6% (n = 211) and 4% (n = 156) had low, and 6% (n = 209) and 4% (n = 155) had high values of AVC and MVC, respectively. The AVC was independently associated with AD after adjusting for age, gender, and ethnicity ( P = .035). No association was noted between AVC groups and AD after adjustment for all covariates or MVC groups and AD in any model.

Hepatocyte growth factor is associated with progression of atherosclerosis: The Multi-Ethnic Study of Atherosclerosis (MESA).

BACKGROUND AND AIMS: Hepatocyte growth factor (HGF) has previously been associated with risk of stroke, coronary heart disease, and atherosclerosis. We hypothesized that higher circulating HGF is associated with greater progression of measures of atherosclerosis: coronary artery calcium (CAC) and carotid plaque. METHODS: Participants aged 45-84 years from the prospective cohort study Multi-Ethnic Study of Atherosclerosis had HGF measured at baseline (between 2000 and 2002) and were followed for progression of atherosclerosis for up to 12 years. CAC was measured at all five exams using the Agatston method. Mixed-effects models were used to examine the association of HGF and CAC progression among 6695 participants with available data. Relative risk regression was used to assess the association between HGF and new or additional carotid plaque between exams 1 and 5 in 3400 participants with available data. All point estimates were adjusted for potential confounding variables. RESULTS: Each standard deviation higher HGF at baseline was associated with 2.9 Agatston units/year greater CAC progression (95% CI: 1.6-4.2, p < 0.0001), and the magnitude of this association differed by race/ethnicity (p value for interaction by race = 0.003). Each standard deviation higher HGF at baseline was associated with a 4% higher risk of new or additional carotid plaque (95% CI: 1.01-1.08, p = 0.005). CONCLUSIONS: Higher levels of HGF were significantly associated with greater progression of atherosclerosis in this large and diverse population. Circulating HGF continues to show promise as a potential clinical biomarker for cardiovascular disease.

Discrepancies in Prevalence of Peripheral Arterial Disease between Lower Extremities at Rest and Postexercise.

Background Lower extremity peripheral arterial disease (PAD) is a common medical condition causing substantial morbidity. Limited data exist on whether discrepancies in PAD prevalence exist between the lower extremities using resting ankle-brachial indices (ABIs) and postexercise pressures. Objective We predicted the prevalence of PAD between the lower extremities. Methods and Results Consecutive patients who had undergone a noninvasive arterial lower extremity study at Mayo Clinic, Rochester, MN, between January 1996 and December 2012 with suspected PAD were retrospectively reviewed. We identified 12,312 consecutive patients who underwent an arterial lower extremity and an exercise treadmill study. Prevalence of PAD was assessed at rest and after exercise using two criteria: a resting ABI ≤ 0.90 and a postexercise pressure decrease of > 30 mm Hg. Mean age was 67 ± 12 years and there were 4,780 (39%) women studied. At rest, we found a higher prevalence of PAD on the left extremity (27.4%) compared with the right (24.6%) ( p < 0.0001). After exercise, we found a higher prevalence of PAD on the right extremity (25.1%) compared with the left (19.0%) ( p < 0.0001). These discrepancies between the prevalence of PAD at rest and after exercise were present in women and men. Conclusion Using validated criteria of a resting ABI of ≤ 0.90 and postexercise ankle pressure decrease > 30 mm Hg, our results suggest that there is a significantly higher prevalence of PAD in the left lower extremity at rest, in contrast to a greater prevalence of abnormal postexercise testing in the right lower extremity. The reason(s) of these discrepancies remain to be studied.

ABO blood group is associated with peripheral arterial disease in African Americans: The Multi-Ethnic Study of Atherosclerosis (MESA).

INTRODUCTION: Peripheral artery disease (PAD) affects 8.5 million Americans and thus improving our understanding of PAD is critical to developing strategies to reduce disease burden. The objective of the study was to determine the association of ABO blood type with ankle brachial index (ABI) as well as prevalent and incident PAD in a multi-ethnic cohort. METHODS: The Multi-Ethnic Study of Atherosclerosis includes non-Hispanic White, African, Hispanic, and Chinese Americans aged 45-84. ABO blood type was estimated using ABO genotypes in 6027 participants who had ABI assessed at the baseline exam. Associations with ABO blood type were evaluated categorically and under an additive genetic model by number of major ABO alleles. After excluding those with ABI>1.4, prevalent PAD was defined as ABI≤0.9 at baseline and incident PAD as ABI≤0.9 for 5137 participants eligible for analysis. RESULTS: There were 222 prevalent cases and 239 incident cases of PAD. In African Americans, each additional copy of the A allele was associated with a 0.02 lower baseline ABI (p=0.006). Each copy of the A allele also corresponded to 1.57-fold greater odds of prevalent PAD (95% CI, 1.17-2.35; p=0.004), but was not associated with incident PAD. No associations were found in other racial/ethnic groups for ABI, prevalent PAD, or incident PAD across all races/ethnicities. CONCLUSIONS: Blood type A and the A allele count were significantly associated with baseline ABI and prevalent PAD in African Americans. Further research is needed to confirm and study the mechanisms of this association in African Americans.

Ovarian Vein Thrombosis: Incidence of Recurrent Venous Thromboembolism and Survival.

OBJECTIVE: To identify the risk of venous thromboembolism recurrence, major bleeding, and mortality in patients with ovarian vein thrombosis so as to better define optimal treatment strategies. METHODS: Patients with ovarian vein thrombosis (1990-2015) and age- and gender-matched patients with contemporary leg deep vein thrombosis (DVT) were assessed for differences in etiology, venous thromboembolism recurrence, and survival in a case-control study. RESULTS: Over the timeframe of this study, only 219 ovarian vein thrombosis cases were identified compared with 13,417 leg DVTs. Median duration of follow-up was 1.23 years (interquartile range 0.25-4.14). Pulmonary embolism was identified at presentation in 6% of patients with ovarian vein thrombosis and 16% of those with DVT (P=.001). Frequent causes of ovarian vein thrombosis included cancer, hormonal stimulation, surgery, and hospitalization. Cancer was twofold more frequent in patients with ovarian vein thrombosis (44% compared with 21%; P<.01). Despite being less frequently treated with anticoagulation (ovarian vein thrombosis 54% compared with DVT 98%, P<.001), venous thromboembolism recurrence rates were similar between groups (ovarian vein thrombosis 2.3 compared with DVT 1.8 per 100 patient-years, P=.49). A personal history of venous thromboembolism and preceding surgery was found to be an independent risk factor for venous thromboembolism recurrence among those treated with anticoagulation (hazard ratio 6.7, P=.04 and hazard ratio 13.6, P=.03, respectively). There was no significant difference in overall survival. CONCLUSION: Ovarian vein thrombosis is a rare thrombotic condition with an incidence 60-fold lower compared with leg DVT in our institution. The striking association with cancer adversely affects overall survival rates in patients with ovarian vein thrombosis. Venous thromboembolism recurrence rates argue for anticoagulation with a direct oral anticoagulant or vitamin K antagonist, particularly in those with a history of venous thromboembolism.

Association of Soluble CD40 Ligand With Duration of Atrial Fibrillation and With Intensity of Spontaneous Echocardiographic Contrast.

OBJECTIVES: The authors tested the hypothesis that the inflammatory response of nonvalvular atrial fibrillation (NVAF) is associated with elevated soluble CD40 ligand (sCD40L). BACKGROUND: NVAF is generally believed to be an inflammatory disease process. sCD40L represents a sensitive in vivo indicator of platelet activation and may serve as an "inflammatory and thrombotic thermometer." METHODS: Plasma sCD40L was measured using enzyme-linked immunoadsorbent assay in 109 NVAF cases (60.9 ± 15 years of age; 26% women) and 48 normal sinus rhythm (NSR) controls (62.3 ± 15 years of age; 44% women). Patients were separated by arrhythmia duration of <1 month (n = 21), 1 to 12 months (n = 18), and >12 months (n = 70). RESULTS: Median sCD40L level was significantly higher in NVAF cases than in NSR controls (321 pg/ml vs. 238 pg/ml, respectively; p = 0.029). This difference was driven by higher levels in patients with NVAF duration for <1 month (552 pg/ml) and 1 to 12 months (328 pg/ml). NVAF patients with arrhythmia duration for over 1 year had sCD40L levels not significantly different from those of NSR controls. An sCD40L concentration of 552 pg/ml distinguished NVAF patients with dysrhythmia duration of <1 month (area under the curve [AUC] of 0.72; p = 0.0010) or duration for ≤12 months (AUC: 0.69; p = 0.0003) from NSR controls. Circulating sCD40L levels were also significantly higher among patients with mild spontaneous echocardiogram contrast (SEC) (p = 0.0378) and those with moderate SEC (p = 0.007) compared with NSR controls. CONCLUSIONS: sCD40L levels are significantly higher in NVAF patients than in NSR controls but only for up to 1 year after development of dysrhythmia. An sCD40L concentration of 552 pg/ml can help to assess development or recurrence of asymptomatic NVAF.