Limb and cardiovascular event risk in type 1 and 2 diabetic patients with peripheral artery disease.

Background: Peripheral artery disease (PAD) is a risk factor for adverse limb events (LE) and cardiovascular events (CVE) that coexists with type 1 (T1) and 2 (T2) diabetes mellitus (DM). Little is known about comparative risk of LE and CVE in T1/T2 DM patients with PAD. Patients and methods: We queried our database of 40,144 patients ≥18 years old who underwent ankle brachial index (ABI) measurement from 01/1996-02/2020. We isolated T1/T2 DM patients with PAD diagnosed by ankle brachial index (ABI; low [<1.0] or elevated [>1.4]) and retrieved demographics including glycated hemoglobin (HbA1c). Primary outcomes were LE (critical limb ischemia/vascular amputation) and CVE (myocardial infarction/ischemic stroke). All-cause mortality was a secondary outcome. Multivariable Cox proportional regression yielded hazard ratios (HR) with 95% confidence intervals (CI) after adjusting for pertinent risk factors including age, hypertension, hyperlipidemia, smoking, and HbA1c. Results: Our study found 10,156 patients with PAD and DM (34% T1DM, 66% T2DM) with median follow-up time 34 mo (IQR 85 mo). T1DM patients were younger than T2DM (mean age 67 vs. 70 years), with higher median HbA1c (7.7 [IQR 1.9] vs. 6.7% [IQR 1.6]), and more prevalent hypertension, hyperlipidemia, CAD, and CKD. Antiplatelet and statin use was equivocal. Elevated ABI was more common in T1DM (47 vs. 28%). LE occurred in 23% and CVE in 12% patients. LE risk was higher in T1 than T2 DM patients (HR 1.58 [95% CI 1.44, 1.73], p<0.0001), but CVE and all-cause mortality were equivocal. These observations were preserved across ABI and HbA1c subgroup analyses. Conclusions: PAD patients with T1DM had a higher LE risk than those with T2DM, even after adjustment for glycemic control and pertinent risk factors, but CVE risk and all-cause mortality were equivocal. These data suggest a potential role for more intensive LE risk modification in PAD patients with T1DM, but further investigation is needed.

Antithrombotic Therapy After Venous Interventions: AJR Expert Panel Narrative Review.

Interventions for thrombotic and nonthrombotic venous disorders have increased with technical advances and more trained venous specialists. Antithrombotic therapy is essential to clinical and procedural success; however, postprocedural therapeutic regimens exhibit significant heterogeneity due to limited prospective randomized data and incomplete mechanistic understanding of the critical factors driving long-term patency. Postinterventional antithrombotic therapy for thrombotic venous disorders should adhere to existing venous thromboembolism management guidelines, which include 3-6 months of therapeutic anticoagulation at minimum and consideration of extended therapy in patients with higher risk of thrombosis because of procedural or patient factors. The added benefit of antiplatelet agents in the acute and intermediate period is unknown, having shown improved long-term stent patency in some retrospective studies. Dual- and/or triple-agent therapy should be limited based on individual risks of thrombosis and bleeding. The treatment of nonthrombotic disorders is more heterogeneous, though patients with limited flow, extensive stent material, or underlying prothrombotic states such as malignancy or chronic inflammation may benefit from single-agent or multiagent antithrombotic therapy. However, the agent, dose, and duration of therapy remain indeterminate. Future prospective studies are warranted to improve patient risk stratification and standardize postprocedural anti-thrombotic therapy in patients receiving venous interventions.

Peripheral artery disease and the risk of venous thromboembolism.

Background: Peripheral artery disease (PAD) impacts 3-12% of patients worldwide and is characterized by endothelial dysfunction and inflammatory pathways which are also common to venous thromboembolism (VTE), but there is a paucity of evidence regarding VTE risk in PAD patients. We investigated whether PAD is an independent risk factor for VTE. Patients and methods: We reviewed medical records of patients undergoing ABI studies at Mayo Clinic from 01/1996-02/2020. We classified patients by ABI (low [<1.0], normal [1.0-1.4], or elevated [>1.4]), as well as by specific low ABI subgroup: severely reduced (ABI: 0.00-0.39), moderately reduced (0.40-0.69), mildly reduced (0.70-0.90), and borderline reduced (0.91-0.99). The primary outcome was incident VTE event (acute lower extremity deep vein thrombosis or pulmonary embolism) after ABI measurement. Multivariable Cox proportional regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) after adjusting for age, sex, active smoking, cancer, previous VTE, thrombophilia, anticoagulation, and revascularization. Results: 39,834 unique patients (mean age 66.3±14.3 years, median follow-up 34 months) were identified. 2,305 VTE events occurred in patients without PAD (13.0%), 2,218 in low ABI patients (13.0%), and 751 in elevated ABI patients (14.8%). After risk factor adjustment, VTE risk was modestly increased for PAD overall (HR: 1.12, 95% CI [1.06, 1.18]), including low ABI (HR: 1.11, 95% CI [1.04, 1.18]) and elevated ABI groups (HR: 1.15, 95% CI [1.04, 1.26]), compared to patients without PAD. The greatest VTE risk was in severely low ABI patients (HR: 1.46, 95% CI [1.31, 1.64]). Conclusions: In a large longitudinal cohort, we present strong clinical evidence of PAD, with low and elevated ABI, as an independent VTE risk factor, with the highest risk seen in patients with severely low ABI. Continued research is required to further investigate this relationship and its intersection with functional performance status to optimize VTE risk reduction or anticoagulation strategies in the PAD population.

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.

Outcomes with catheter-directed thrombolysis compared with anticoagulation alone in patients with acute deep venous thrombosis.

OBJECTIVE: The authors aimed to investigate the benefits and risks of catheter-directed thrombolysis (CDT) in acute deep venous thrombosis (DVT). BACKGROUND: The role of CDT in the management of DVT is evolving. Data on CDT versus anticoagulation alone in acute DVT is sparse. METHODS: We performed a systematic review and meta-analysis of published studies that compared CDT to anticoagulation alone in patients with acute DVT. RESULTS: We included 11 studies (four randomized control trials [RCTs] and seven observational studies) with a total of 8,737 patients. During hospital stay, patients who received CDT had higher odds of major bleeding (2.5% vs. 1.6%; OR 1.46, 95% CI [1.07, 1.98], p = .02), blood transfusion (10.8% vs. 6.2%; OR 1.8, 95% CI [1.52, 2.13], p < .001), and thromboembolism (15.5% vs. 10%; OR 1.67, 95% CI [1.47, 1.91], p < .001) compared with anticoagulation alone. At 6-month follow-up, patients who received CDT had higher venous patency (71.1% vs. 37.7%; OR 5.49, 95% CI [2.63, 11.5], p < .001) and lower postthrombotic syndrome (PTS; 27% vs. 40.7%; OR 0.44, 95% CI [0.22, 0.86], p = .02). During a mean follow-up duration of 30.5 ± 28 months, CDT group continued to have higher venous patency (79.6% vs. 71.8%; OR 3.79, 95% CI [1.54, 9.32], p = .004) and lower PTS (44.7% vs. 50.5%; OR 0.43, 95% CI [0.23, 0.78], p = .006), but no difference in thromboembolism. CONCLUSION: Compared with anticoagulation alone, CDT for patients with acute DVT was associated with a higher risk of complications, but a higher rate of venous patency and lower risk of postthrombotic syndrome at 2.5 years follow-up.

Natural history and management outcomes of segmental arterial mediolysis.

BACKGROUND: Segmental arterial mediolysis (SAM) is a poorly understood, nonatherosclerotic, noninflammatory disease resulting from arterial medial degeneration. Patients may present with aneurysm, dissection, stenosis, or bleeding from visceral or renal arteries. Treatment algorithms are poorly characterized. METHODS: A retrospective review of all patients diagnosed with SAM was performed at our institution. Patients were identified by established criteria that include clinical presentation in combination with radiographic and serologic findings. Demographics, presenting symptoms, diagnostic evaluation, management, and outcomes were reviewed. RESULTS: There were 117 patients diagnosed with SAM between 2000 and 2016; 67.5% (n = 79) were male. Mean age was 52.7 years (range, 23.4-90 years); 69.2% (n = 81) presented with acute abdominal pain, 22.2% (n = 26) with flank pain, and 19.7% (n = 23) with back pain; 15.4% (n = 18) had abdominal pain longer than 30 days; 13.7% (n = 16) had acute hypertension, and 5.1% (n = 6) were hypotensive; 10.3% (n = 12) were asymptomatic. There were 93 (79.5%) dissections and 61 (52.1%) aneurysms. Hemorrhage was seen in 10 (8.5%). The celiac axis was affected in 54.7% (n = 64), renal arteries in 49.6% (n = 5 8), superior mesenteric artery in 43.6% (n = 51), and inferior mesenteric artery in 2.6% (n = 3). After diagnosis of SAM, aspirin was prescribed in 60.7% (n = 71). Statins were prescribed in 29.9% (n = 35). Antihypertensive medications were prescribed in 65% (n = 76), including beta blockers in 42.7% (n = 50); 40.2% (n = 47) of patients were prescribed anticoagulation. Interventions were performed in 26 (22%) patients; 13 had endovascular intervention only, 9 open surgery only, and 4 open and endovascular interventions. Of the 17 patients undergoing endovascular intervention, 19 procedures were performed, most commonly embolization (78.9% [n = 15]), followed by stenting (10.5% [n = 2]). Of the 13 patients undergoing open surgery, 14 procedures were performed, including arterial bypass (50% [n = 7]) and splenectomy with aneurysm ligation (15.4% [n = 2]). Other surgery involved thrombectomy (21.4% [n = 3]) and angioplasty (14.3% [n = 2]). Only 11.5% (n = 3) experienced a perioperative complication, including one hematoma, one abscess, and one death secondary to ongoing hemorrhage. Follow-up imaging was performed in 96.6% (n = 112). Mean follow-up was 1258 days (range, 2-5017 days). Of these, 27.7% (n = 31) had regression, 43.8% (n = 49) stability, and 28.6% (n = 32) progression. Average time between initial diagnosis and progression was 666 days. CONCLUSIONS: SAM is an uncommon disease that may require intervention; it is therefore important that the vascular surgery community be aware of this disease. Follow-up imaging is required to monitor for disease progression.

Cardiac Troponin T and Right Ventricular Systolic Pressure Predict Cardiovascular and Mortality Risk in Kidney Transplant Candidates.

BACKGROUND: Patients presenting for kidney transplant (KTx) evaluation are subject to high rates of mortality and cardiovascular (CV) events pre- and post-KTx. CV and mortality risk assessment is needed. METHODS: We evaluated cardiac troponin T (cTnT) as a predictor of CV events and mortality in a racially diverse cohort with significant CV disease burden presenting for KTx evaluation. Right ventricular systolic pressure (RVSP) was also assessed in predicting these outcomes. The population consisted of 561 patients presenting for KTx evaluation from 2011 to 2013 at Mayo Clinic, Arizona. A cutoff value for cTnT and RVSP that was most associated with CV events or mortality was derived. Multivariate Cox regression analysis was used to assess cTnT, RVSP, traditional, and other risk factors for the outcomes of interest. RESULTS: Mean age was 53.5 ± 13.7 years and the median follow-up after KTx evaluation was 48.0 months. The cohort was 70.6% (n = 392) White, 11.4% (n = 63) Black, 8.5% (n = 47) Native American, and 3.1% (n = 17) Asian. Preexisting CV disease at the time of evaluation was prevalent in 24.4% (n = 137) of patients. During follow-up, 66.3% (n = 372) received a KTx and 21.9% (n = 123) had a composite event (16.8% death, 6.6 % CV events). It was found that 70.7% (n = 87) of events occurred in patients who were not transplanted; 53.5% (n = 300) had an elevated cTnT (≥0.01 ng/mL, median 0.02 ng/mL) and 84.1% (n = 344) of patients with RVSP data had an elevated RVSP (>25 mm Hg). Time to event analysis identified a cTnT ≥0.036 ng/mL and RVSP ≥31 mm Hg to be best predictive of CV events and mortality. Smoking, CV disease, hypoalbuminemia, RVSP, and cTnT independently predicted CV events and mortality. CONCLUSION: Elevated cTnT and RVSP were independently predictive of CV events and mortality in the cohort. Clinicians should consider the value of RVSP and cTnT as markers of CV risk in KTx evaluation.

QT prolongation and sudden cardiac death risk in hypertrophic cardiomyopathy.

INTRODUCTION: Risk assessment for sudden cardiac death (SCD) in hypertrophic cardiomyopathy (HCM) remains complex. The goal of this study was to assess electrocardiogram (ECG)-derived risk factors on SCD in a large HCM population Methods: Retrospective review of adults with HCM evaluated at Mayo Clinic, Rochester, MN from 1 December 2002 to 31 December 2012 was performed. Data inclusive of ECG and 24-hour ambulatory Holter monitor were assessed. SCD events were documented by ventricular fibrillation (VF) noted on implantable cardioverter defibrillator (ICD), or appropriate VT or VF-terminating ICD shock. RESULTS: Overall, 1615 patients (mean age 53.7 ± 15.2 years; 943 males, 58.4%) were assessed, with mean follow-up 2.46 years and 110 SCD events. Via logistic regression (n = 820), the odds of SCD increased with increasing number of conventional risk factors. With one risk factor the OR was 4.88 (p < .0001; CI 2.22-10.74), two risk factors the OR was 6.922 (p < .0001; CI 2.94-16.28) and three or more risk factors, the OR was 13.997 (p < .0001; CI 5.649-34.68). Adding QTc > 450 to this logistic regression model had OR 1.722 (p = .04, CI 1.01-2.937) to predict SCD. QTc ≥ 450 was a significant predictor for death (HR 1.88, p = .021, CI 1.10-3.20). There was no correlation between sinus bradycardia, sinus tachycardia, first degree AV block, atrial fibrillation, left bundle branch block, right bundle branch block, premature atrial complexes, premature ventricular complexes, supraventricular tachycardia, PR interval, QRS interval and SCD. CONCLUSIONS: Prolonged QTc was a risk factor for SCD and death even when controlling for typical risk factors.

Cardiac Troponin T Risk Stratification Model Predicts All-Cause Mortality Following Kidney Transplant.

BACKGROUND: We evaluated the role of increased cardiac troponin T (cTnT), vascular, and cardiac diseases in predicting 5 and 10-year all-cause mortality after kidney transplantation. METHODS: We reviewed a cohort of 764 kidney transplant recipients and analyzed pertinent cardiovascular risk factors at the time of transplant evaluation. Proportional hazards regression analysis with bootstrapping method was utilized to provide a risk stratification score for mortality. RESULTS: Mean age was 58.8 years (SD 12.1) and median follow-up was 7.0 years (range 1 day to 18.0 years). Fifty-four percent of patients (n = 415) had cTnT measured (median 0.02 ng/mL, range 0.01-4.91). Fifty-three percent (n = 407) had vascular disease, 59% (n = 448) had diabetes, and 44% (n = 336) had cardiac disease pre-transplant. Sixty percent (n = 460) required dialysis. Older age, increased cTnT, pre-transplant vascular and cardiac diseases predicted mortality in multivariate analysis. We derived 2 scoring systems with and without cTnT - the ACV and ACTV scores (age, cardiac disease, elevated cTnT, and vascular disease) - as predictors of mortality after kidney transplant. Point assignments were: age 60-69 years (1), age ≥70 years (2), cardiac disease (1), cTnT ≥0.04 ng/mL (1), and vascular disease (1). Both scoring systems significantly predicted mortality. The ACTV score better delineated risk stratification across score levels (0-2, 3-4, and 5 points). CONCLUSIONS: We developed a risk schema predictive of all-cause mortality after kidney transplant in a derivation cohort. The ACTV score, including an elevated cTnT, provided superior prediction compared to a scoring system without cTnT. Further studies to validate these findings are needed.

Segmental Arterial Mediolysis: Abdominal Imaging of and Disease Course in 111 Patients.

OBJECTIVE: The purpose of this study is to identify the imaging characteristics of segmental arterial mediolysis (SAM) at presentation and establish the longitudinal course of disease. MATERIALS AND METHODS: We retrospectively identified patients with SAM at a single institution from 2000 through 2015. Diagnosis was based on published guidelines with multidisciplinary consensus. Imaging studies obtained at initial evaluation were reviewed to evaluate imaging findings and vascular territory distribution. All subsequent follow-up imaging studies were reviewed to assess for progression, stability, or regression. RESULTS: We identified 111 patients (79 men and 32 women; median age, 51 years) who met the diagnostic criteria for SAM. Abdominal pain was the most common presentation (74%), followed by flank pain (21%). SAM most commonly affected the renal arteries (47%), superior mesenteric artery (46%), celiac trunk (46%), hepatic artery (23%), iliac arteries (18%), and splenic artery (14%). The most common imaging findings were dissection (86%), aneurysm (57%), beading or webs (28%), occlusion (19%), and a rind or wall thickening (15%). The 247 available follow-up imaging studies for 97 patients (median follow-up, 12 months) showed progression in 19 patients (20%), with either stability or regression observed in the remaining patients. CONCLUSION: SAM most commonly affects the renal arteries, superior mesenteric artery, and celiac artery. Dissections and aneurysms are the most common imaging findings. Follow-up imaging studies show stability or regression in most patients.

Clinical Review of the Pharmacogenomics of Direct Oral Anticoagulants.

PURPOSE: There is growing interest in the use of pharmacogenomics to optimize the safety and efficacy of anticoagulation therapy. While the pharmacogenomics of warfarin have been well-studied, the pharmacogenomics of direct oral anticoagulants (DOACs) continue to be a fledgling, but growing, field of interest. We present a pertinent clinical review of the present state of research on the pharmacogenomics of DOACs. METHODS AND RESULTS: The present article is a review of pertinent clinical and scientific research on the pharmacogenomics of DOACs between January 2008 and December 2017 using MEDLINE and the United States National Institutes of Health Clinical Trials Registry. Many studies have identified single-nucleotide polymorphisms (SNPs) in genes responsible for DOAC metabolism that impacted serum DOAC concentration but had uncertain clinical significance. CONCLUSIONS: As such, there is currently no strong evidence for the use of pharmacogenomic testing in optimizing the safety and efficacy of DOAC therapy. Nonetheless, genes of interest have been identified for each DOAC that may be of potential clinical utility. Further research is currently underway to elucidate the value of pharmacogenomics in this increasingly prescribed therapy.

Peripheral arterial disease preoperatively may predict graft failure and mortality in kidney transplant recipients.

Patients with end-stage renal disease undergoing kidney transplant often have diffuse atherosclerosis and high cardiovascular morbidity and mortality rates. We analyzed the correlation of peripheral arterial disease (PAD), here quantified by an abnormal ankle-brachial index (ABI) measured within the 5 years prior to kidney transplant, with graft failure and mortality rates (primary end points) after adjusting for known cardiovascular risk factors (age, sex, smoking history, hypertension, diabetes, stroke, known coronary artery disease or heart failure, years of dialysis). Of 1055 patients in our transplant population, 819 had arterial studies within the 5 years prior to transplant. Secondary end points included myocardial infarction; cerebrovascular accident; and limb ischemia, gangrene, or amputation. Low ABI was an independent and significant predictor of organ failure (OR, 2.77 (95% CI, 1.68-4.58), p<0.001), secondary end points (HR, 1.39 (95% CI, 0.97-1.99), p<0.076), and death (HR, 1.84 (95% CI, 1.26-2.68), p=0.002). PAD was common in this population: of 819 kidney transplant recipients, 46% had PAD. Low ABI was associated with a threefold greater risk of graft failure, a twofold greater risk of death after transplant, and a threefold greater risk of secondary end points. Screening for PAD is important in this patient population because of the potential impact on long-term outcomes.

Cholesterol crystal induced arterial inflammation and destabilization of atherosclerotic plaque.

Evolution of plaque that is prone to rupture is characterized by inflammation and physical changes. Accumulation of low-density lipoprotein in the sub-intima provides esterified cholesterol (ESC) to macrophages and smooth muscle cells that convert it into free cholesterol (FRC) by cholesteryl ester hydrolases (CEHs). Membrane-bound cholesterol carriers transport FRC to high-density lipoprotein (HDL). Impaired HDL transport function and altered composition can lead to extracellular accumulation of FRC, whereas impaired membrane carrier activity can lead to intracellular FRC accumulation. Saturation of FRC can result in cholesterol crystallization with cell death and intimal injury. Disequilibrium between ESC and FRC can impact foam cell and cholesterol crystal (CC) formation. Cholesterol crystals initiate inflammation via NLRP3 inflammasome leading to interleukin-1ß (IL-1ß) production inducing C-reactive protein. Eventually, crystals growing from within the plaque and associated inflammation destabilize the plaque. Thus, inhibition of inflammation by antagonists to IL-1ß or agents that dissolve or prevent CC formation may stabilize vulnerable plaques.

Safety and mortality outcomes for direct oral anticoagulants in renal transplant recipients.

PURPOSE: Direct oral anticoagulants (DOACs) are increasingly used in renal transplant recipients (RTR), but relatively understudied in this population. We assess the safety of post-transplant anticoagulation with DOACs compared to warfarin. METHODS: We conducted a retrospective study of RTRs at the Mayo Clinic sites (2011-present) that were anticoagulated for greater than 3 months excluding the 1st month post-transplant. The main safety outcomes were bleeding and all-cause mortality. Concomitant antiplatelet and interacting drugs were noted. DOAC dose adjustment was assessed according to common US prescribing practices, guidelines, and/or FDA labeling. RESULTS: The median follow-up was longer for RTRs on warfarin (1098 days [IQR 521, 1517]) than DOACs (449 days [IQR 338, 942]). Largely, there were no differences in baseline characteristics and comorbidities between RTRs on DOACs (n = 208; apixaban 91.3%, rivaroxaban 8.7%) versus warfarin (n = 320). There was no difference in post-transplant use of antiplatelets, immunosuppressants, most antifungals assessed, or amiodarone. There was no significant difference in incident major bleeding (8.4 vs. 5.3%, p = 0.89), GI bleeding (4.4% vs. 1.9%, p = 0.98), or intra-cranial hemorrhage (1.9% vs. 1.4%, p = 0.85) between warfarin and DOAC. There was no significant difference in mortality in the warfarin group compared to DOACs when adjusted for follow-up time (22.2% vs. 10.1%, p = 0.21). Rates of post-transplant venous thromboembolism, atrial fibrillation or stroke were similar between the two groups. 32% (n = 67) of patients on DOACs were dose reduced, where 51% of those reductions were warranted. 7% of patients that were not dose reduced should have been. CONCLUSIONS: DOACs did not have inferior bleeding or mortality outcomes compared to warfarin in RTRs. There was greater use of warfarin compared to DOACs and a high rate of improper DOAC dose reduction.

Comparative Effectiveness of Anticoagulants in Patients With Cancer-Associated Thrombosis.

Importance: Patterns of clinical utilization and comparative effectiveness of anticoagulants for cancer-associated thrombosis (CAT) remain largely unexplored. Objectives: To assess patterns of and factors associated with anticoagulant use and to evaluate the comparative effectiveness of contemporary anticoagulants in patients with active cancer in a clinical setting. Design, Setting, and Participants: This retrospective cohort study obtained deidentified OptumLabs electronic health record claims data from January 1, 2012, to September 30, 2019. Adult patients (≥18 years of age) with a primary cancer diagnosis (except skin cancer) during at least 1 inpatient or 2 outpatient visits within 6 months before the venous thromboembolism (VTE) date were included. Data were analyzed from April 2020 to September 2021. Exposures: The patients were grouped according to the anticoagulant prescribed: (1) direct oral anticoagulants (DOACs), (2) low-molecular-weight heparin (LMWH), and (3) warfarin. Main Outcomes and Measures: Odds ratios (ORs) were used to present the association between factors of interest and utilization of anticoagulants. Main efficacy outcomes included risk of VTE recurrence and all-cause mortality. Main safety outcomes included the risk of hospitalization due to major bleeding. Relative treatment effect estimates were expressed as hazard ratios (HRs) with 95% CIs. Results: This study included 5100 patients (mean [SD] age, 66.3 [12.3] years; 2670 [52.4%] women; 799 [15.7%] Black, 389 [7.6%] Hispanic, and 3559 [69.8%] White individuals). Overall, 2512 (49.3%), 1488 (29.2%), and 1460 (28.6%) filled prescriptions for DOACs, LMWH, and warfarin, respectively. The median (IQR) treatment duration was 3.2 (1.0-6.5) months for DOACs, 3.1 (1.0-6.8) months for warfarin, and 1.8 (0.9-3.8) months for LWMH. Patients with lung (OR, 2.07; 95% CI, 1.12-3.65), urological (OR, 1.94; 95% CI,1.08-3.49), gynecological (OR, 4.25; 95% CI, 2.31-7.82), and colorectal (OR, 2.26; 95% CI, 1.20-4.32) cancer were associated with increased prescriptions for LMWH compared with DOACs. LMWH (HR, 1.47; 95% CI, 1.14-1.90) and warfarin (HR, 1.46; 95% CI, 1.13-1.87) were associated with an increased risk of VTE recurrences compared with DOACs. LMWH was associated with an increased risk of major bleeding (HR, 2.27; 95% CI, 1.62-3.20) and higher all-cause mortality (HR, 1.61; 95% CI, 1.15-2.25) compared with DOACs. Conclusions and Relevance: In this comparative effectiveness study of claims-based data, patients with CAT received anticoagulation for a remarkably short duration in clinical settings. DOACs was associated with a lower risk of VTE recurrence, major bleeding, and mortality. Warfarin may still be considered for patients with contraindications to DOACs and those with poor persistence on LMWH.

Genetic QT Score and Sleep Apnea as Predictors of Sudden Cardiac Death in the UK Biobank.

Introduction: The goal of this study was to evaluate the association between a polygenic risk score (PRS) for QT prolongation (QTc-PRS), QTc intervals and mortality in patients enrolled in the UK Biobank with and without sleep apnea. Methods: The QTc-PRS was calculated using allele copy number and previously reported effect estimates for each single nuclear polymorphism SNP. Competing-risk regression models adjusting for age, sex, BMI, QT prolonging medication, race, and comorbid cardiovascular conditions were used for sudden cardiac death (SCD) analyses. Results: 500,584 participants were evaluated (56.5 ±8 years, 54% women, 1.4% diagnosed with sleep apnea). A higher QTc-PRS was independently associated with the increased QTc interval duration (p<0.0001). The mean QTc for the top QTc-PRS quintile was 15 msec longer than the bottom quintile (p<0.001). Sleep apnea was found to be an effect modifier in the relationship between QTc-PRS and SCD. The adjusted HR per 5-unit change in QTc-PRS for SCD was 1.64 (95% CI 1.16 - 2.31, p=0.005) among those with sleep apnea and 1.04 (95% CI 0.95 - 1.14, p=0.44) among those without sleep apnea (p for interaction =0.01). Black participants with sleep apnea had significantly elevated adjusted risk of SCD compared to White participants (HR=9.6, 95% CI 1.24 - 74, p=0.03). Conclusion: In the UK Biobank population, the QTc-PRS was associated with SCD among participants with sleep apnea but not among those without sleep apnea, indicating that sleep apnea is a significant modifier of the genetic risk. Black participants with sleep apnea had a particularly high risk of SCD.

ACR Appropriateness Criteria® Sudden Onset of Cold, Painful Leg: 2023 Update.

Acute onset of a cold, painful leg, also known as acute limb ischemia, describes the sudden loss of perfusion to the lower extremity and carries significant risk of morbidity and mortality. Acute limb ischemia requires rapid identification and the management of suspected vascular compromise and is inherently driven by clinical considerations. The objectives of initial imaging include confirmation of diagnosis, identifying the location and extent of vascular occlusion, and preprocedural/presurgical planning. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision process support the systematic analysis of the medical literature from peer reviewed journals. Established methodology principles such as Grading of Recommendations Assessment, Development, and Evaluation or GRADE are adapted to evaluate the evidence. The RAND/UCLA Appropriateness Method User Manual provides the methodology to determine the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where peer reviewed literature is lacking or equivocal, experts may be the primary evidentiary source available to formulate a recommendation.

Patient Age at Diagnosis of Peripheral Artery Disease and Its Impact on Cardiovascular and Limb Outcomes.

Peripheral artery disease (PAD) prevalence increases with age, but the relation between age at PAD diagnosis and outcomes is unclear. We investigated the cardiovascular and limb outcomes of patients diagnosed with PAD at different ages. We studied patients with PAD aged ≥18 years who were diagnosed between 1996 and 2020 at Mayo Clinic. Patients were grouped by diagnosis age (<50, 50 to 59, 60 to 69, ≥70 years) and ankle brachial index (ABI): low ABI (<1.0) or elevated ABI (>1.4). Primary outcomes were cardiovascular events (CVEs; myocardial infarction or ischemic stroke) and limb events (LEs; critical limb ischemia or amputation). Competing risk analysis was performed to calculate adjusted hazard ratios. The cohort included 22,073 patients with PAD (low ABI: 77.1%; elevated ABI: 22.9%). CVEs were observed in 8.2% of patients and LEs in 15.6%. The highest CVE risk was observed in patients diagnosed with PAD before age 50 (compared with patients diagnosed after age 70; hazard ratio 2.33 [95% confidence interval 1.95 to 2.78]). CVE risk decreased with older age at diagnosis. Although younger groups demonstrated higher LE risk, there was no clear association with diagnosis age. These patterns of risk were seen both in low and elevated ABI subgroups but in greater magnitude with elevated ABI. Younger patients diagnosed with PAD face increased risk of myocardial infarction and ischemic stroke compared with patients diagnosed at an older age. CVE risk notably exceeds LE risk. In conclusion, younger age at PAD diagnosis may be an important risk factor, which warrants more aggressive interventions focused on CVE prevention.

Surgical Management of Aortic Regurgitation in Takayasu's Arteritis: A Systematic Review of Techniques and Outcomes.

IntroductionTakayasu's arteritis (TA) is an inflammatory condition that affects large vessels and frequently involves the aortic valve causing valve regurgitation. Surgical management is recommended for symptomatic severe aortic regurgitation (AR); however, the optimal surgical approach is yet unclear. This study aims to review surgical treatment options for AR in TA and determine which procedure has a lower chance of late postoperative events and/or mortality. MethodsAn electronic database search was performed within PubMed, EMBASE, Web of Science, and SCOPUS to identify articles from 1975 to 2016 focusing on surgical management of the AR in TA. ResultsTwenty seven studies encompassing a total of 194 cases (77% females) were included. Isolated aortic valve replacement (AVR) was performed in 105/194 cases (54%) (Group A), while combined aortic valve and root replacement (CAVRR) was performed in 87/194 (45%) (Group B). Prosthetic valve detachment was reported in 10/105 cases (9.5%) in group A and 1/87 cases (1.2%) in group B (p = 0.02). Dilation of the residual aorta was reported in 10/105 cases (9.5%) in group A and 1/87 cases (1.2%) in group B (p = 0.02). Any late (≥ 30 d) postoperative cardiac event was reported in 26/105 cases (24.8%) in group A, and in 7/87 cases (8.1%) in group B (p = 0.003). ConclusionsAlthough CAVRR is a more complex procedure, it might offer a better outcome in terms of late postoperative cardiac events compared to isolated AVR procedure. Future prospective studies are required to help determine the best surgical approach in such a population.