Objective To define the timing and intensity of cardiovascular risk after severe acute respiratory syndrome coronavirus 2 infection across the pre-Delta, Delta, and Omicron eras. Patients and Methods We conducted a population-based retrospective cohort study of 162,471 adults with severe acute respiratory syndrome coronavirus 2 infection from March 1, 2020 to December 31, 2023 using the Rochester Epidemiology Project, a medical records-linkage system covering a 27-county region in Minnesota and Wisconsin. Outcomes included major adverse cardiovascular events, thrombotic events, and dysrhythmias, identified using validated International Classification of Diseases, 10th Revision codes. Cumulative incidence accounted for the competing risk of death, and multivariable Cox regression assessed age- and variant-specific risk. Results Over a median follow-up of 1.9 years (interquartile range, 1.2-2.4 years), 4922 individuals experienced major adverse cardiovascular events. Risk was highest within 30 days after infection and declined thereafter (P<.0001). During this early hazard window, adults aged ≥80 years had substantially higher adjusted risk in the pre-Delta and Delta eras compared with Omicron (pre-Delta hazard ratio, 3.89 [95% CI, 3.17-4.77]; Delta hazard ratio, 2.91 [95% CI, 2.28-3.71]). Thrombotic events showed a similar early, age-dependent pattern, peaking during the pre-Delta and Delta eras. Early dysrhythmia rates rose steeply with age and peaked during the Delta era, exceeding 60 events per 1000 person-months among adults aged ≥80 years. Late dysrhythmia incidence was stable across eras, reflecting persistent age-related risk. Conclusion Cardiovascular events after corona virus disease 2019 infection clustered within the first 30 days, with variation by age and variant era. This early concentration, most pronounced among older adults during the pre-Delta and Delta eras, is supportive of a clinically relevant hazard window while distinguishing observed patterns from causal inference. These findings support targeted, time-sensitive cardiovascular monitoring in higher-risk populations.

OBJECTIVE:To assess the clinical characteristics of small abdominal aortic aneurysms (AAAs) for growth patterns, growth rates, time to repair, and adverse outcomes relative to surveillance imaging intervals. PATIENTS AND METHODS:Patients with small AAAs (30-45 mm in diameter) and at least 1 follow-up imaging study were eligible for inclusion (January 1, 2014, through December 31, 2019). Variables impacting time to repair, rupture, or death were assessed. RESULTS:Of 2044 unique patients with AAAs, a random sample of 299 patients (mean ± SD age, 70.5 ± 9.0 years; 18.7% female) were divided into slow-/no- (≤2 mm per year; n=116), intermediate- (>2 to <5 mm per year; n=150), and rapid- (≥5 mm per year; n=33) growth categories. During 10.0-year median follow-up, 61.2% of the patients (n=183) underwent repair. Rapid-growth AAAs were more likely to undergo repair (88% vs intermediate 81.7% or slow/no growth 26.5%; P<.001), required earlier repair (P<.001), and were more likely to die during follow-up (79% vs 41% or 56%; P=.045). Predictors of time to repair included index AAA size, diabetes mellitus, and β-blocker or diuretic therapy. Ruptures (n=1) or impending ruptures (n=4) during follow-up were greatest in the rapid- (n=2, 6.1%; P<.001) compared with the intermediate- (n=3, 2.0%) or slow-/no- (0%) growth groups. CONCLUSION:Growth rate characteristics of AAAs influence repair-free survival, time to repair, overall survival, and rupture-free survival.

Thrombophilic states in the setting of living donor liver transplantation raises concerns regarding perioperative thromboembolism in the donor, as well as the potential transfer of inherited prothrombotic tendencies through mutated, hepatically synthesised coagulation factors. Screening practices for thrombophilia remain heterogeneous across centers and may result in donor exclusion based on local policies. However, accumulating evidence over the past decade suggests that most prospective donors are asymptomatic, and those with heterozygous inherited thrombophilias-such as Factor V Leiden or Prothrombin G20210A mutation-can safely undergo donation with standard perioperative thromboprophylaxis for recipient and donors. These states are unlikely to be transmitted to the recipient, as extrahepatic synthesis of coagulation proteins contributes to maintaining hemostatic balance. In contrast, donors with a prior history of thromboembolism, high-risk genotypes (e.g., homozygous or compound heterozygous states), or high-risk acquired thrombophilias should generally be excluded owing to an increased risk of thrombotic complications.

BACKGROUND:Left ventricular (LV) thrombus (LVT) recurrence risk influences decision-making regarding oral anticoagulation (OAC) duration. OBJECTIVES:The aim of the study was to evaluate risk of LVT recurrence and factors associated with recurrence. METHODS:This was a multicenter, retrospective cohort of patients with resolved LVT, diagnosed by echocardiography. Clinical and echocardiographic characteristics at LVT diagnosis and resolution were evaluated for association with recurrence. Multivariable Cox proportional hazards regression was used to identify determinants of LVT recurrence. RESULTS:Among 252 patients (mean age 64.5 years, 78.6% male), LVT recurred in 36 (14.3%). Although LV systolic function at the time of presentation was similar between those with and without recurrence, patients who developed recurrent LVT had lower LV ejection fraction (LVEF) (34.0% vs 40.0%; P = 0.04) and more frequently had LV apical aneurysm (25.0% vs 6.5%; P = 0.001) at LVT resolution. Continuing OAC after LVT resolution was associated with less recurrence (54.7% vs 25.0%; P = 0.005). In multivariable analysis, LV apical aneurysm (HR: 3.12; 95% CI: 1.43 to 6.84) and previous ischemic stroke (HR: 2.75; 95% CI: 1.22-6.17) were associated with higher rates of recurrence, whereas higher LVEF (HR: 0.96 per 1% increase; 95% CI: 0.95-0.99) and OAC continuation (HR: 0.27; 95% CI: 0.13-0.58) were associated with decreased recurrence. CONCLUSIONS:In this population, LVT recurred in 14% of patients and was associated with LV apical aneurysm and prior stroke, whereas lower rates of recurrence were associated with higher LVEF and continuation of OAC. Echocardiographic characteristics at the time of LVT resolution were associated with LVT recurrence.

Background:Venous thromboembolism (VTE) recurrence on anticoagulation (ROA) and anticoagulant failure (ACF) are frequently described but poorly defined. Objectives:To determine the incidence and causes of ROA and ACF in patients with VTE. The secondary aim was to describe the management of these cases, including anticoagulation selection and dosing strategies. Methods:Patients with acute VTE enrolled in the Mayo Clinic VTE Registry from 2013 to 2022 were included. Charts of patients with VTE recurrence despite anticoagulation were reviewed. ROA was defined as any new thrombotic event in patients prescribed and recently taking anticoagulants. ACF was defined as ROA in the absence of modifiable risk factors. Results:Of the 4980 patients included, 150 (3.0%) ROA events occurred in 130 patients. Altered absorption (n = 40, 26.7%), medication dosing (n = 35, 23.3%), and recent interruption of therapy (n = 37, 24.7%) were frequently documented reasons for ROA events. Malignancy was present in 107 (71.3%) patients, with 47 (43.9%) having metastatic malignancy. ROA was attributed to a modifiable cause in 75 (50.0%) patients. In 26 (17.3%) patients, there were no identifiable reasons for failure, and these were labeled as ACF. After a recurrent VTE event, 92 (61.3%) patients were transitioned to an alternative anticoagulant, with the most frequent being enoxaparin. However, 27 (18.0%) patients remained on the same medication at an increased dose, and 27 (18.0%) did not have any change in therapy. There were 4 (2.7%) patients with unclear management strategies. Conclusion:ROA can affect 3% of patients with VTE. Nearly half of ROA events are preventable with careful review of medications and patient characteristics. When not modifiable, the most used strategy for managing patients with ACF is to transition to another anticoagulant, usually enoxaparin. Our practice strategy for evaluating and managing ROA is outlined.

Background: Left ventricular thrombus (LVT) is a serious thromboembolic complication in patients with cardiomyopathies. Evidence supporting direct oral anticoagulant (DOAC) therapy in LVT is limited. Objectives: We evaluated the effectiveness and safety of DOACs compared with vitamin K antagonists (VKAs) in patients with LVT. Methods: A multisite retrospective cohort study was performed, including patients with LVT diagnosed by echocardiography from 2018-2023 who were treated with either DOACs or VKAs. Primary outcome was the incidence of stroke and systemic embolism (SSE). Secondary outcomes included LVT resolution, major bleeding, and all-cause mortality. Results: A total of 182 patients with LVT met inclusion criteria, of which 70 (38.5%) were treated with only DOACs and 112 (61.5%) with only VKAs. The mean age was 66 years, and 74% of the patients were male. The median follow-up duration was 363.5 days (IQR, 139-950). No significant difference between the groups was observed in the incidence of SSE (DOAC, 5.7% vs VKA, 5.4%; P = 1.0), the incidence of LVT resolution (DOAC: 81.4% vs VKA: 87%; P = .35), the median time to LVT resolution (DOAC, 96 days vs VKA, 102 days; P = .22), or mortality (DOAC, 14.3% vs VKA, 11.6%; P = .6). However, VKAs were associated with a significantly higher incidence of major bleeding compared with DOACs (9% vs 1.4%; P = .02). Conclusion: LVT treated solely with either DOACs or VKAs had similar incidences of SSE, LVT resolution, time to LVT resolution, and mortality. VKA therapy, however, was associated with a higher incidence of major bleeding events.

OBJECTIVE:Gastrointestinal bleeding (GIB) is a common complication associated with warfarin use. However, the optimal approach for anticoagulation reversal-whether with prothrombin complex concentrate (PCC), fresh frozen plasma (FFP), vitamin K (intravenous or oral), or no reversal-remains unclear as current literature and society guidelines do not provide definitive recommendations. METHODS:A retrospective analysis of emergency department patients with warfarin-associated GIB who presented to an academic health system was performed, comparing reversal with PCC, FFP, vitamin K only, or no reversal agent. The primary outcome was 30-day all-cause mortality. Secondary outcomes included rebleeding events and 30-day thrombotic events. Standardized guidelines for reporting were followed (STROBE). RESULTS:Of 815 patients, within 12 h of presentation, 10.7 % received reversal with PCC (with or without vitamin K), 12.9 % with FFP (with or without vitamin K), and 34.9 % with vitamin K alone; 41.5 % of patients received no reversal agent. Compared to all other groups, patients receiving PCC had significantly higher 30-day mortality (18.4 % [PCC] vs 5.7 % [FFP] vs 4.6 % [vitamin K] vs 5.6 % [no reversal], p < 0.001), which remained significant after adjusting for hemodynamic instability and ICU admission. There were no significant differences in rates of thrombotic event within 30 days (3.4 % vs 3.8 % vs 1.4 % vs 1.2 %, p = 0.20). CONCLUSIONS:Patients who received PCC had a threefold increase in mortality compared to FFP, vitamin K alone, or no reversal, even after adjusting for severity of the bleeding. Further research is necessary to understand factors leading to this observed mortality difference among patients with warfarin related GIB.

Hemorrhagic complications associated with regional anesthesia are extremely rare. The fifth edition of the American Society of Regional Anesthesia and Pain Medicine's Evidence-Based Guidelines on regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy reviews the published evidence since 2018 and provides guidance to help avoid this potentially catastrophic complication.The fifth edition of the American Society of Regional Anesthesia and Pain Medicine's Evidence-Based Guidelines on regional anesthesia in the patient receiving antithrombotic or thrombolytic therapy uses similar methodology as previous editions but is reorganized and significantly condensed. Therefore, the clinicians are encouraged to review the earlier texts for more detailed descriptions of methods, clinical trials, case series and pharmacology. It is impossible to perform large, randomized controlled trials evaluating a complication this rare; therefore, where the evidence is limited, the authors continue to maintain an 'antihemorrhagic' approach focused on patient safety and have proposed conservative times for the interruption of therapy prior to neural blockade. In previous versions, the anticoagulant doses were described as prophylactic and therapeutic. In this version, we will be using 'low dose' and 'high dose,' which will allow us to be consistent with other published guidelines and more accurately describe the dose in the setting of specific patient characteristics and indications. For example, the same 'high' dose may be used in one patient as a treatment for deep venous thrombosis (DVT) and in another patient as prophylaxis for recurrent DVT. Due to the increasing ability to obtain drug-specific assays, we have included suggestions for when ordering these tests may be helpful and guide practice. Like previous editions, at the end of each recommendation the authors have clearly noted how the recommendation has changed from previous editions.

Patients with cancer and venous thromboembolism (VTE) have higher complication rates of anticoagulation. However, studies supporting this data are relatively old reflecting the era of vitamin K inhibitors. To assess VTE recurrence, major bleeding, and clinically relevant non-major bleeding (CRNMB) in patients (March 1, 2013 to April 30, 2023) with cancer-associated VTE and patients without cancer, the prospective Mayo Clinic Thrombophilia Clinic Registry was analyzed. Over the study period, 4,711 patients with acute VTE were enrolled including 2,064 patients with cancer (mean age 62.5 ± 12.4, 46% female) and 2,647 patients without cancer (mean age 59.4 ± 16.0, 45% female). The most common cancers were gastrointestinal (n = 423, 21%), pancreatic (n = 287, 14%), and genitourinary (n = 198, 10%). Direct oral anticoagulants were used in 1,339 (65%) cancer and in 1,952 (74%) non-cancer patients. Among cancer patients, 12-month Kaplan–Meier probability of VTE recurrence was 2.4-fold greater (7.1% vs. 2.9%, p < 0.001) compared with the non-cancer group, including higher recurrent leg deep vein thrombosis (3.0% vs. 1.4%; p = 0.002) and pulmonary embolism (3.5% vs. 1.0%, p < 0.001). Patients with cancer also had 2.1-fold greater risk of major bleeding (6.3% vs. 3.0%; p < 0.001) including bleeding from the gastrointestinal tract (3.0 vs. 1.4, p = 0.01) compared with patients without cancer. Clinically relevant non-major bleeding events were similar between the groups. In this large prospective registry of VTE management, patients with cancer had significantly higher rates of VTE recurrence and major bleeding compared with patients without cancer, yet the rate of complications are substantially smaller relative to historic values of a prior vitamin K antagonist era.

Background: Low-dose direct oral anticoagulants (DOACs) have been studied in randomized controlled trials for extended prevention of venous thromboembolism (VTE) after 6 months at therapeutic doses. Objectives: This study examined the effectiveness, safety, and utilization of low-dose DOACs in a real-world cohort with dedicated analysis of cancer patients. Methods: Consecutive patients enrolled in the Mayo Clinic VTE Registry from March 1, 2013, to December 31, 2022, were followed prospectively for VTE recurrence, major bleeding (MB), and clinically relevant non-MB (CRNMB). Patients with events during the first 3 months were excluded. After anticoagulation for 3 months with either rivaroxaban or apixaban, characteristics and outcomes of patients continuing anticoagulation were evaluated by Cox regression and a nested case-control study. Results: In total, 466 patients (71% apixaban and 29% rivaroxaban) were identified on low-dose DOACs and 2273 in the full-dose group. Demographics between groups were mostly similar. Patients with active cancer as a provoking factor were less common in the overall low-dose DOAC group. In Cox regression analysis, VTE recurrence was not different between any groups. In noncancer patients, CRNMB but not MB was decreased in the low-dose group (hazard ratio [HR], 4.97; P < .001). In patients with cancer, low-dose DOACs were protective for MB (HR, 4.48; P = .001) and CRNMB (HR, 6.81; P < .001). Bleeding outcomes were the same in nested case-control analysis as well. Conclusion: Dose reduction maintains low recurrence rates but also decreases bleeding, with the most pronounced effect in the cancer population.

OBJECTIVE:Systems employing point-of-care (POC) INR monitoring with patient self-testing require test accuracy, data integrity, patient compliance, and prompt two-way communication for high quality warfarin management. With a goal of validating a POC Bluetooth capable device for prompt INR transfer to electronic medical record, two POC INR devices were compared against an internal plasma INR reference. METHODS:A multicenter study (February 14, 2023 - August 29, 2023) comparing concordance of two commercially available POC devices, Vantus and CoaguChek XS (Pro and Plus), against a plasma INR reference, was pursued among warfarin treated patients. Appropriateness of dosing decisions were assessed for each device. RESULTS:Across three Mayo Clinic sites, 151 warfarin treated patients agreed to participate. Atrial fibrillation (41.7 %), venous thromboembolism (33.1 %) and heart valve prosthesis (19.9 %) were common indications with target INR range 2.0-3.0 in 89 %. For the CoaguChek devices, 86.1 % of values fell within 0.4 INR units compared with plasma INR referent (CoaguChek - plasma INR correlation R2 = 0.95). For the Vantus device, 88.7 % of values fell within 0.4 INR units of plasma INR values (Vantus - plasma INR correlation R2 = 0.96). Mean (± standard deviation) deviation from plasma INR was 0.2 ± 0.3 for CoaguChek compared to 0.1 ± 0.2 for Vantus (p < 0.001). Using the plasma INR as the gold standard for dosing recommendations, appropriate dosing recommendations were similar between devices: CoaguChek 83.4 % vs Vantus 82.7 %. CONCLUSIONS:Compared to a plasma referent, INR values obtained from the CoaguChek and Vantus devices exhibited strong correlation with plasma INR values without systemic bias.