Percutaneous Intra-arterial Hyaluronidase Injection for Hyaluronic Acid Filler Embolism Threatening Skin Barrier Integrity: Implementation of a Stepwise Treatment Protocol.

BACKGROUND: Hyaluronic acid (HA) filler-induced vascular embolism that threatens skin integrity is an urgent situation. There is increasing evidence that percutaneous intra-arterial hyaluronidase injection is an effective therapeutic technique for it. However, until now, there is a lack of a unifying protocol about the technique. OBJECTIVES: This study aims to provide a conclusion of percutaneous intra-arterial hyaluronidase injection along with adjunctive measures on the treatment of occlusions precipitated by HA-based filler and develop a stepwise treatment protocol. METHODS: We searched PubMed for peer-reviewed studies, consensus statements, case series, and case reports using a variety of keywords. RESULTS: High-dose, pulsed hyaluronidase is the mainstay for the treatment of HA filler-induced embolism, but percutaneous intra-arterial hyaluronidase injection is a more effective technique. Until now, hyaluronidase is injected into three arteries percutaneously, including facial artery, supratrochlear artery, and superficial temporal artery. Furthermore, the adjunctive measures that may optimize clearance of an occlusion and/or skin barrier repair such as the use of image guidance and CGF should be considered. CONCLUSION: Vascular occlusions that threaten skin integrity are an urgent matter which requires accurate diagnosis and effective intervention. Percutaneous intra-arterial hyaluronidase injection along with adjunctive measures performed in a stepwise manner is key to an optimal outcome. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Geographic variation in clinical outcomes and anticoagulation among medicare beneficiaries with non-valvular atrial fibrillation.

Oral anticoagulants (OACs) have been used to prevent stroke/systemic embolism (SE) among patients with non-valvular atrial fibrillation (NVAF). To evaluate baseline clinical characteristics, incidence rates of stroke/SE and hospitalization for bleeding, and OAC use among elderly patients with NVAF in the US by geographic region. Patients with NVAF were selected from the US Centers for Medicare & Medicaid Services claims database (01JAN2013-31DEC2016). Twelve months of health plan enrollment was required before and after the NVAF diagnosis to evaluate baseline characteristics and outcomes, respectively. Each patient was assigned to a 3-digit zip code based on their primary residence, and geographic variation was visualized using ArcGIS Pro software. Over 2.8 million patients with NVAF were identified. Large geographic variation was observed in clinical characteristics, stroke/SE, hospitalization for bleeding, and OAC use among patients across the US. The zip codes with the highest mean CHA2DS2-VASc scores and frequency of prior bleeding also had the highest incidence of stroke/SE and hospitalization for bleeding. Across 3-digit zip codes, 35-63% of patients were untreated. Overall, the incidence of stroke/SE and hospitalization for bleeding were higher and OAC treatment was less frequent in zip codes located in the Southern US. Baseline clinical characteristics, incidence rates of stroke/SE and hospitalization for bleeding, and OAC usage vary considerably by 3-digit zip code in the US. The additional granularity provided in this study may help clinicians to identify small regions with high-risk of stroke/SE and hospitalization for bleeding and low use of OAC that may benefit from targeted care strategies.

Relationship Between Direct Oral Anticoagulant Doses and Clinical Outcomes in Elderly Patients With Non-Valvular Atrial Fibrillation　- ANAFIE Registry Sub-Analysis.

BACKGROUND: This sub-analysis of the ANAFIE Registry, a prospective, observational study of >30,000 Japanese non-valvular atrial fibrillation (NVAF) patients aged ≥75 years, assessed the prevalence of direct oral anticoagulant (DOAC) under-dose prevalence, identified the factors of under-dose prescriptions, and examined the relationship between DOAC dose and clinical outcomes.Methods and Results: Patients, divided into 5 groups by DOAC dose (standard, over-, reduced, under-, and off-label), were analyzed for background factors, cumulative incidences, and clinical outcome risk. Endpoints were stroke/systemic embolic events (SEE), major bleeding, and all-cause death during the 2-year follow-up. Of 18,497 patients taking DOACs, 20.7%, 3.8%, 51.6%, 19.6%, and 4.3%, were prescribed standard, over-, reduced, under-, and off-label doses. Factors associated with under-dose use were female sex, age ≥85 years, reduced creatinine clearance, history of major bleeding, polypharmacy, antiplatelet agents, heart failure, dementia, and no history of catheter ablation or cerebrovascular disease. After confounder adjustment, under-dose vs. standard dose was not associated with the incidence of stroke/SEE or major bleeding but was associated with a higher mortality rate. Patients receiving an off-label dose showed similar tendencies to those receiving an under-dose; that is, they showed the highest mortality rates for stroke/SEE, major bleeding, and all-cause death. CONCLUSIONS: Inappropriate low DOAC doses (under- or off-label dose) were not associated with stroke/SEE or major bleeding but were associated with all-cause death.

Efficacy and safety of non-vitamin K antagonist oral anticoagulants in patients (≥80 years of age) with atrial fibrillation: systematic review and meta-analysis.

Findings of prior studies about the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) in patients (≥80 years of age) with atrial fibrillation (AF) are controversial. So we performed a meta-analysis to evaluate the efficacy and safety of NOACs versus vitamin K antagonists (VKAs) in patients (≥80 years of age) with AF. A systematic review of PubMed, Cochrane, Embase, Web of Science and Chinese BioMedical databases was conducted until 1 October 2022. Studies reporting the effects and safety of NOACs versus warfarin in patients (≥80 years of age) with AF were included. Two authors independently performed study selection and data extraction. Discrepancies were resolved by consensus or through an independent third reviewer. Data were synthesised according to the Preferred Reporting Items for Systematic Reviews guidelines. We identified 15 studies providing data of 70 446 participants (≥80 years of age) suffering from AF. According to the meta-analysis (odds ratio (OR) (95% confidence interval, CI)), NOACs conferred better efficacy profile than VKAs in stroke and systemic embolism (0.8 (0.73-0.88)) and all-cause mortality (0.61 (0.57-0.65)). Otherwise, NOACs conferred a better safety profile than VKAs in major bleeding (0.76 (0.70-0.83)) and intracranial haemorrhage (ICH; 0.57 (0.47-0.68)). In conclusion, for patients (≥80 years of age) with AF, the risks of stroke and systemic embolism, all-cause mortality, were lower in NOACs compared to warfarin. The risks of major bleeding and ICH were also lower in NOACs compared to warfarin. NOACs showed better efficacy and safety than warfarin.

Neutrophil-lymphocyte ratio and clinical outcomes in 19,697 patients with atrial fibrillation: Analyses from ENGAGE AF- TIMI 48 trial.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is the ratio between neutrophil and lymphocyte counts measured in peripheral blood. NLR is easily calculable based on a routine blood test available worldwide and may reflect systemic inflammation. However, the relationship between NLR and clinical outcomes in atrial fibrillation (AF) patients is not well-described. METHODS: We calculated NLR at baseline in ENGAGE AF-TIMI 48, a randomized trial comparing edoxaban versus warfarin in patients with AF followed for 2.8 years (median). The association of baseline NLR with major bleeding events, major adverse cardiac events (MACE), cardiovascular death, stroke/systemic embolism, and all-cause mortality were calculated. RESULTS: The median baseline NLR in 19,697 patients was 2.53 (interquartile range 1.89-3.41). NLR was associated with major bleeding events (HR 1.60; 95% CI 1.41-1.80), stroke/systemic embolism (HR 1.25; 95% CI, 1.09-1.44), MI (HR 1.73; 95% CI 1.41-2.12), MACE (HR 1.70; 95% CI 1.56-1.84), CV (HR 1.93; 95% CI 1.74-2.13) and all-cause mortality (HR 2.00; 95% CI 1.83-2.18). The relationships between NLR and outcomes remained significant after adjustment for risk factors. Edoxaban consistently reduced major bleeding. MACE, and CV death across NLR groups vs. warfarin. CONCLUSIONS: NLR represents a widely available, simple, arithmetic calculation that could be immediately and automatically reported during a white blood cell differential measurement to identify patients with AF at increased risk of bleeding, CV events, and mortality.

Evaluation of the Time to Onset and Outcome of Lenalidomide-induced Thrombosis and Embolism Using Spontaneous Reporting Database.

BACKGROUND/AIM: Lenalidomide (LND) is an oral antineoplastic agent used in the treatment of various malignant hematologic diseases, including multiple myeloma. Major adverse events of LND include myelosuppression, pneumonia, and thromboembolism. Thromboembolism is an adverse drug reaction (ADR) associated with poor outcomes, therefore anticoagulants are administered prophylactically. However, LND-induced thromboembolism has not been clearly characterized from clinical trials. The purpose of this study was to evaluate the incidence, timing, and outcome details of thromboembolism caused by LND using the JADER (Japanese Adverse Drug Event Report) database. PATIENTS AND METHODS: ADRs due to LND reported from April 2004 to March 2021 were selected. Data on thromboembolic adverse events were analyzed and relative risks were estimated using reported odds ratios (RORs) and 95% confidence intervals (CIs). In addition, the time of onset and outcome of thromboembolism were analyzed. RESULTS: There were 11,681 adverse events attributed to LND. Of these, 306 were thromboembolisms. The most frequently reported thrombosis with the highest ROR was deep vein thrombosis (DVT) (165 cases, ROR=7.12, 95%CI=6.09-8.33). The median onset of DVT (quartiles, 25-75%) was 80 (28-155) days. The parameter value (ß) was 0.87 (0.76-0.99), suggesting the onset of DVT early in treatment. The prognosis of DVT due to LND was recovery and remission in 34% and 43% of patients, respectively, but 7.9% did not recover. CONCLUSION: DVT is the most frequent thromboembolism in LND, and early treatment is important.

Safety and efficacy of direct oral anticoagulants versus vitamin K antagonists in atrial fibrillation electrical cardioversion: An update systematic review and meta-analysis.

BACKGROUND: A systematic evaluation focused on efficacy and safety for electrical cardioversion of atrial fibrillation (AF) among different Direct Oral Anticoagulants (DOACs) has not been previously performed. In this setting, we conducted a meta-analysis of studies evaluating DOACs vs vitamin K antagonists (VKA) as common comparator. METHODS: We searched Cochrane Library, Pubmed, Web Of Science and Scopus databases for all English-only articles concerning studies that have estimated the effect of DOACs and VKA on stroke, transient ischemic attack or systemic embolism (SSE) and major bleeding (MB) events in AF patients undergoing electrical cardioversion. We selected 22 articles comprising 66 cohorts and 24,322 procedures (12,612 with VKA). RESULTS: During follow-up (studies' median 42 days), 135 SSE (52 DOACs and 83 VKA) and 165 MB (60 DOACs and 105 VKA) were recorded. The overall pooled effects, DOACs vs VKA, was estimated by an univariate Odds Ratio of 0.92 (0.63-1.33; p = 0.645) for SSE and 0.58 (0.41-0.82; p = 0.002) for MB; at bivariate evaluation, adjusting for study type, were respectively 0.94 (0.55-1.63; p = 0.834) and 0.63 (0.43-0.92, p = 0.016). Each single DOAC showed similar and non statistically different results in outcome occurrence compared to VKA as well as when Apixaban, Dabigatran, Edoxaban and Rivaroxaban were indirectly compared to each other. CONCLUSIONS: In patients undergoing electrical cardioversion, compared to VKA, DOACs have similar thromboembolic protection with lower major bleeding incidence. Single molecule does not show difference in event rate compared to each other. Our findings, provide useful information about safety and efficacy profile of DOACs and VKA.

A Rare Case of Hydrophilic Polymer Embolization After Transcatheter Aortic Valve Replacement.

ABSTRACT: Endovascular procedures that use a hydrophilic polymer-coated device carry a risk of embolization and ischemic complications when used intravascularly. Because these coatings are increasingly used worldwide, it is important to identify potential adverse effects early. Cutaneous complications of hydrophilic polymer emboli are rare and not commonly described in the literature. Therefore, we report a case of hydrophilic polymer embolization with cutaneous findings in a patient who underwent a recent transcatheter aortic valve replacement.

Prognostic impact of heart rate during atrial fibrillation on clinical outcomes in elderly non-valvular atrial fibrillation patients: ANAFIE Registry sub-cohort study.

BACKGROUND: Elderly patients with atrial fibrillation (AF) are at a higher risk for all-cause mortality and heart failure. Rate control is an essential component in AF management. This exploratory study assessed the relationship between resting heart rate during AF at baseline and clinical outcomes in Japanese elderly non-valvular AF (NVAF) patients, using the All Nippon AF In the Elderly Registry (ANAFIE) dataset. METHODS: This sub-cohort included patients who agreed to participate and presented with AF at enrollment in the ANAFIE study. They were categorized into six groups according to the resting heart rate during AF. Outcomes included 2-year cumulative incidences of stroke/systemic embolic events (SEE), ischemic stroke, major bleeding, cardiovascular (CV) events, CV death, all-cause death, and net clinical outcome, a composite of stroke/SEE, major bleeding, and all-cause death. RESULTS: Of the 8292 patients included in this sub-cohort (paroxysmal, 1496; non-paroxysmal, 6796), 90 % of patients were using anticoagulants. Higher heart rate was more frequently reported in women and in patients with paroxysmal AF and was associated with increased use of direct oral anticoagulants (DOACs) and antiarrhythmic drugs. Heart rate ≥110 beats per minute (bpm) was associated with a significantly higher incidence of cardiac events and numerically higher incidences of CV death and all-cause death compared with a heart rate of 60 to <80 bpm, all of which were driven by an increased risk in patients with non-paroxysmal AF. Hazard ratios by the type of anticoagulant for each clinical outcome were comparable across all heart rate categories, indicating no significant interactions. CONCLUSIONS: Elderly Japanese patients with non-paroxysmal NVAF and a heart rate ≥110 bpm have an increased risk of cardiac events. There was no interaction between heart rate category and the relative risk of adverse clinical events in patients taking DOACs compared with those taking warfarin.

Acute Myocardial Infarction Due to Coronary Artery Embolism during Chemotherapy with mFOLFOX-6 Plus Bevacizumab for Metastatic Colon Cancer.

Bevacizumab, a monoclonal antibody against vascular endothelial growth factor, may be associated with arterial embolisms. We herein report a case of acute myocardial infarction caused by coronary embolism during combination chemotherapy with mFOLFOX-6 and bevacizumab in a patient with metastatic colon cancer. Thromboembolism occurred only in the distal right posterolateral branch without stenotic lesions or plaque rupture in the proximal branch of the right coronary artery. Sole thromboaspiration was successfully performed; the final angiogram demonstrated no stenosis in the right coronary artery. Bevacizumab may be associated with acute coronary syndrome in patients with coronary risk factors, despite no significant coronary narrowing.

Use of liquid concentrated growth factor in the management of necrotic tissue after facial vascular complications induced by hyaluronic acid injection.

INTRODUCTION: HA fillers may induce facial vascular embolism. The resulting tissue ischemia and necrosis are severe iatrogenic complications for which no effective treatments are available. OBJECTIVE: This single-center case series studied the use of liquid CGF in the management of facial tissue necrosis due to HA injection. METHODS: All 12 patients with facial tissue necrosis (2 mild, 3 moderate, 7 severe) were previously treated with hyaluronidase injection in outside hospitals. They received a routine injection of hyaluronidase (dose of 400-1500 U) at the site of ischemia immediately after admission to the authors' hospital, but CGF was also injected. CGF injection was repeated once weekly until wound healing. Efficacy was assessed at 4 weeks (mean, 24.08 days). RESULTS: No patient experienced wound expansion or aggravation or infection at the sites of necrosis. A complete healing rate of 91.67% was noted at the 4-week follow-up. No scarring was evident in patients with mild to moderate necrosis. Those with moderate necrosis exhibited varied degrees of scarring after recovery, and scarring was evident in those with severe necrosis. No severe adverse effects occurred. CONCLUSION: CGF promoted the healing of ischemic and necrotic tissue wounds induced by facial vascular embolism following injection of HA fillers. CGF should be considered as a nonsurgical treatment method for vascular embolism following HA filler injection.

A RIVA-DM Subanalysis Investigating Patients With Nonvalvular Atrial Fibrillation and Type 2 Diabetes Aged Under Versus Over 80 Years.

BACKGROUND: Advanced age and type 2 diabetes (T2D) are common in patients with nonvalvular atrial fibrillation (NVAF). We evaluated the impact of age on the effectiveness and safety of rivaroxaban versus warfarin in this population. METHODS: We analyzed electronic health record data from November 2010, to December 2019 including adults with NVAF and T2D, newly started on rivaroxaban or warfarin. Propensity score-overlap weighted hazard ratios (HRs) for stroke/systemic embolism (SSE), hospitalization for major or clinically relevant nonmajor bleeding (CRNMB), vascular death, major adverse limb events (MALE), major bleeding, and intracranial hemorrhage (ICH) were calculated for older (≥80 years) and younger (<80 years) cohorts. RESULTS: We included 32 078 rivaroxaban and 83 971 warfarin users (6606 rivaroxaban and 25,335 warfarin patients were aged ≥80 years). No significant interaction for rivaroxaban versus warfarin by age was observed for any outcome, including SSE (HR = 1.05 vs 0.95), hospitalization for major or CRNMB (HR = 1.06 vs 0.90), vascular death (HR = 0.92 vs 0.90), MALE (HR = 0.80 vs 0.76), major bleeding or ICH. CONCLUSIONS: The effectiveness and safety of rivaroxaban versus warfarin remained consistent across patient age subgroups.

Trends in reporting embolic and thrombotic events after COVID-19 vaccination: A retrospective, pharmacovigilance study.

With the progression of global vaccination against coronavirus disease 2019 (COVID-19), embolic and thrombotic events (ETEs) following COVID-19 vaccination continue to be reported. To date, most reports on the type of COVID-19 vaccine and ETEs have been based on clinical trials, and other reports include a small number of cases. Further, the relationship between the type of COVID-19 vaccine and ETEs has not been clarified. It is important to elucidate trends in the development of ETEs after vaccination, which is a crucial concern for both prospective patients and healthcare providers. In this retrospective, pharmacovigilance study, we analyzed the Vaccine Adverse Event Reporting System (VAERS) reports from January 1, 2020 to June 18, 2021, and performed signal detection and time-to-onset analysis of adverse events by calculating the reported odds ratio (ROR) to understand ETE trends after COVID-19 vaccination based on the vaccine type. Using VAERS, we could collect data about several ETEs associated with COVID-19 vaccination. Nine adverse events associated with ETEs were reported following the administration of viral vector vaccines. The median time to ETE onset was 6 (interquartile range: 2-17) days for mRNA vaccines and 11 (interquartile range: 4-21) days for viral vector vaccines. This study suggests that VAERS aids in disequilibrium analysis to examine the association between vaccine type and ETEs after COVID-19 vaccination. Additionally, the tendency to develop ETEs and the number of days taken to develop ETEs varied depending on the type of the COVID-19 vaccine. Thus, vaccinators and healthcare providers should consider the primary diseases associated with ETEs while selecting vaccines for administration and carefully monitor patients following vaccination for potential ETEs based on the characteristics of vaccine type-specific onset period.

Effect of Polypharmacy on Clinical Outcomes in Elderly Patients With Non-Valvular Atrial Fibrillation　- A Sub-Analysis of the ANAFIE Registry.

BACKGROUND: This All Nippon AF in the Elderly (ANAFIE) Registry sub-analysis evaluated the impact of polypharmacy on 2-year outcomes in a large, elderly (aged ≥75 years) Japanese population with non-valvular atrial fibrillation (NVAF).Methods and Results: The ANAFIE Registry was a multicenter, prospective, observational study with a 24-month follow-up period. Of 32,275 enrolled NVAF patients, 31,419 were grouped by the number of prescribed concomitant medications (other than oral anticoagulants [OACs]): 0-4 [38.8%], 5-8 [43.3%], and ≥9 [17.9%]). Patients receiving more concomitant medications were older, had poor renal function, and suffered more comorbidities than those receiving fewer concomitant medications. Several patient background factors, including diabetes mellitus, myocardial infarction, and chronic kidney disease, were significantly correlated with an increased number of concomitant medications. With increasing medications, OAC prescription rates decreased, but the warfarin prescription rate increased, and the cumulative incidence rates of stroke/systemic embolic events (SEE), major bleeding, gastrointestinal bleeding, fracture/falls, cardiovascular events, cardiovascular death, and all-cause death significantly increased (each, P<0.05). In multivariate analysis, increasing medications was independently associated with increases in these events, except for stroke/SEE. There were no significant interactions between the number of medications and anticoagulant treatment with direct OAC or warfarin concerning the incidence of these events. CONCLUSIONS: Polypharmacy was frequent among elderly patients with NVAF who were older with more comorbidities, and was independently associated with a higher incidence of extracranial events.

Systematic review of efficacy of direct oral anticoagulants and vitamin K antagonists in left ventricular thrombus.

AIMS: Left ventricular thrombus (LVT) increases the risk of thrombotic events and mortality. Vitamin K antagonists (VKAs) used to treat LVT have several known risks, as a result of which direct oral anticoagulant (DOAC) use has recently increased. We aimed to evaluate the safety and efficacy of DOACs and VKAs in treating LVT. METHODS AND RESULTS: We searched PubMed, Embase, Cochrane Library trials, and Web of Science databases for studies published before 19 April 2022, involving DOAC versus VKA treatment for patients with LVT. This meta-analysis comprised 21 studies (total patients, n = 3172; DOAC group, n = 888; VKA group, n = 2284). A statistically significant reduction in bleeding events was observed in patients on DOACs vs. those on VKAs (risk ratio (RR) = 0.73, P = 0.004). Patients on DOACs residing in North American and European regions and those with ischaemic heart disease (IHD) had a significantly lower risk of bleeding events than patients residing in other regions or those with a different LVT aetiology, respectively (RR = 0.78, P = 0.04; RR = 0.38, P = 0.02; and RR = 0.63, P = 0.009). A statistically significant reduction in stroke in patients on DOACs versus VKAs (RR = 0.72, P = 0.03) was observed, and patients on DOACs residing in North America and those with IHD had a significantly lower risk of stroke (RR = 0.73, P = 0.04, and RR = 0.61, P = 0.03, respectively). Compared with VKAs, DOACs are statistically associated with an increase in LVT resolution at 1 month (RR = 1.96, P = 0.008). No statistical between-group difference in all-cause mortality (RR = 0.72, P = 0.05), systemic embolism (RR = 0.87, P = 0.74), stroke or systemic embolism (RR = 0.90, P = 0.50), and LVT resolution at the end of follow-up (RR = 1.06, P = 0.13) was observed. CONCLUSIONS: Compared with VKAs, DOACs significantly reduce the risk of bleeding events and stroke in LVT patients, but mortality was similar in both groups. The advantages are apparent not only in patients belonging to the predominantly white residential areas such as North American and European regions but also in patients with LVT due to IHD. DOACs show promising effects in treating LVT compared with VKAs.

Systemic embolism in amyloid transthyretin cardiomyopathy.

AIMS: Although systemic embolism is a potential complication in transthyretin amyloid cardiomyopathy (ATTR-CM), data about its incidence and prevalence are scarce. We studied the incidence, prevalence and factors associated with embolic events in ATTR-CM. Additionally, we evaluated embolic events according to the type of oral anticoagulation (OAC) and the performance of the CHA2 DS2 -VASc score in this setting. METHODS AND RESULTS: Clinical characteristics, history of atrial fibrillation (AF) and embolic events were retrospectively collected from ATTR-CM patients evaluated at four international amyloid centres. Overall, 1191 ATTR-CM patients (87% men, median age 77.1 years [interquartile range-IQR 71.4-82], 83% ATTRwt) were studied. A total of 162 (13.6%) have had an embolic event before initial evaluation. Over a median follow-up of 19.9 months (IQR 9.9-35.5), 41 additional patients (3.44%) had an embolic event. Incidence rate (per 100 patient-years) was 0 among patients in sinus rhythm with OAC, 1.3 in sinus rhythm without OAC, 1.7 in AF with OAC, and 4.8 in AF without OAC. CHA2 DS2 -VASc did not predict embolic events in patients in sinus rhythm whereas in patients with AF without OAC, only those with a score ≥4 had embolic events. There was no difference in the incidence rate of embolism between patients with AF treated with vitamin K antagonists (VKAs) (n = 322) and those treated with direct oral anticoagulants (DOACs) (n = 239) (p = 0.66). CONCLUSIONS: Embolic events were a frequent complication in ATTR-CM. OAC reduced the risk of systemic embolism. Embolic rates did not differ with VKAs and DOACs. The CHA2 DS2 -VASc score did not correlate well with clinical outcome in ATTR-CM and should not be used to assess thromboembolic risk in this population.

Cardiac Perforation Caused by Cement Embolism after Percutaneous Vertebroplasty: A Report of Two Cases.

BACKGROUND: Percutaneous vertebroplasty (PVP) is a minimally invasive surgical technique in which polymethyl methacrylate (PMMA) is injected into the weakened vertebral body to strengthen it. However, this procedure is associated with various complications, the most common being cement leakage. Cardiac perforation caused by cement escape into the venous system is another complication, which is rare but potentially life-threatening even if not treated promptly. CASE PRESENTATION: Here, we report two elderly patients who developed cardiac perforation caused by cement escape into veins following PVP. Both patients had a history of severe osteoporosis. On admission, they presented with lower back pain and limited movement. MRI revealed vertebral bodies compression fracture in both patients. Considering the advanced age of the patients, PVP was performed to avoid the risk of potential complications associated with nonoperative therapy. Unfortunately, the rare and fatal postoperative complication, cardiac perforation caused by cement escape into veins, occurred in both patients. Emergency open-heart surgery was performed to remove cement material and repair the heart, both patients recovered well and were discharged. CONCLUSIONS: Although PVP is a safe and minimally invasive surgical technique, it is associated with various serious complications as seen in the present cases. We therefore recommend that surgeons should be aware of such complications. Appropriate timing of surgical operation, meticulous surgical procedures, early intraoperative and postoperative monitoring of cement leakage may improve outcomes of patients with such complications.

Antithrombotic Therapy for Patients With Atrial Fibrillation and Bioprosthetic Valves　- Real-World Data From the Multicenter, Prospective, Observational BPV-AF Registry.

BACKGROUND: Although bioprosthetic valve (BPV) replacements are becoming more common within our aging society, there are limited prospective data on the appropriate antithrombotic therapy for East Asian patients with atrial fibrillation (AF) and BPV replacement. Antithrombotic therapy and thrombotic and hemorrhagic event rates in Japanese patients with AF and BPV replacement are investigated.Methods and Results:This multicenter, prospective, observational study enrolled patients with BPV replacement and AF. The primary efficacy outcome was stroke or systemic embolism, and the primary safety outcome was major bleeding. Of the 894 patients analyzed, 54.7%, 29.4%, and 9.6%, were treated with warfarin-based therapy, direct oral anticoagulant (DOAC)-based therapy, or antiplatelet therapy without anticoagulants, respectively; 6.3% did not receive any antithrombotic drugs. The mean observation period was 15.3±4.0 months. The event rates for stroke or systemic embolism and major bleeding were 1.95%/year and 1.86%/year, respectively. The multivariate adjusted hazard ratios for DOAC vs. warfarin were 1.02 (95% confidence intervals [CI], 0.30-3.41 [P=0.979]) for systemic embolic events and 0.96 (95% CI, 0.29-3.16 [P=0.945]) for major bleeding. CONCLUSIONS: Approximately 30% of patients with AF and BPV replacement were treated with DOAC. The risks of major bleeding and stroke or systemic embolism were similar between warfarin- and DOAC-treated patients with AF who had BPV replacement. Treatment with DOACs could be an alternative to warfarin in this population.

Meta-analysis comparing inappropriately low dose versus standard dose of direct oral anticoagulants in patients with atrial fibrillation.

BACKGROUND: The appropriateness of direct oral anticoagulant (DOAC) dosing has been the issue in the real-world setting, and inappropriately lower DOAC dose may not be as effective or safe as the standard dose in patients with atrial fibrillation (AF). Multiple real-world studies compared the inappropriately lower DOAC dose versus the standard dose, but their main findings were contradictory. METHODS: A meta-analysis was performed to compare the efficacy and safety of the inappropriately lower DOAC dose with the standard DOAC dose in patients with AF. Database searches through May 30, 2021, were performed using Medline and Google Scholar. The primary efficacy outcome was stroke or systemic embolism, and the primary safety outcome was major bleeding. The secondary outcome was all-cause mortality. RESULTS: A total of 16 studies were included in this meta-analysis. It revealed that the inappropriately lower DOAC dose was significantly associated with a higher event rate of stroke or systemic embolism compared with the DOAC standard dose (odds ratio 1.21 [95% CI 1.02-1.43], P = 0.03, I2 = 66%). There was no significant difference in the major bleeding event rate between these groups (1.03, [0.92-1.15], P = 0.62; I2 = 27%). CONCLUSION: The inappropriately lower DOAC dose should be avoided to optimize DOAC effectiveness in patients with AF.