Antithrombotic Therapy Research Articles

Early Structural Valve Deterioration of Balloon Expandable Transcatheter Aortic Valve Leaflets Due to Intrinsic and Extrinsic Nodular Calcification in a Hemodialysis Patient: A Case Report

Abstract Background Several reports have shown that transcatheter aortic valves are comparable in durability to surgical aortic valves. However, early structural valve deterioration (SVD) is rarely reported to occur, especially in hemodialysis patients. Case Summary We present a case of rapidly progressive bioprosthetic aortic valve stenosis in a patient with end-stage renal disease (ESRD) secondary to diabetic nephropathy in an 83-year-old female admitted due to progressive dyspnea and orthopnea. A 23-mm sized SAPIEN3 bioprosthetic aortic valve showed normal function for the first year after transcatheter aortic valve implantation (TAVI), but then rapidly developed stenosis and required acute hospitalization for heart failure a year and a half after surgery. Emergent surgical aortic valve replacement (SAVR) with a 19-mm On-X valve (CryoLife, Kennesaw, GA, USA) was performed. Pathological examination of the explanted SAPIEN 3 valve demonstrated severely degenerated bioprosthetic pericardial leaflets with severe intrinsic and extrinsic nodular calcification, which could limit the leaflet motion. Discussion There is a lack of reports on the long-term procedural outcomes of TAVI in hemodialysis patients. The development of SVD in patients undergoing dialysis is multifactorial and has yet to be fully elucidated. In the presented case, the removed TAVI valve had severe extrinsic calcified nodules alongside a fibrin thrombus. Considering these pathological findings, antithrombotic therapy to prevent fibrin thrombus from adhering to the TAVI valve may be important to avoid early SVD.

Aspirin versus clopidogrel as a combination therapy with direct oral anticoagulant after coronary stent implantation in patients with atrial fibrillation

Abstract Background Patients with atrial fibrillation (AF) who undergo percutaneous coronary intervention (PCI) are recommended to receive dual antithrombotic therapy including an antiplatelet agent and direct anticoagulants (DOAC). We compared the effectiveness between aspirin and clopidodgrel for a combination therapy with DOAC in this population. Methods We analyzed patient data from the Korea National Health Insurance Service. A total of 9,157 patients with AF who received dual antithrombotic therapy after PCI were included. Patients were classified into the aspirin group and clopidogrel group, and 1:1 propensity score matching (PSM) was performed. The primary ischemic endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or systemic thromboembolism. A major bleeding event was defined as a bleeding event requiring hospitalization. Results After PSM, there were each 2,882 patients each in the aspirin and clopidogrel group. The incidence of the primary ischemic endpoint was similar in the two groups (22.8% vs. 21.8%, in the aspirin and clopidogrel group, hazard ratio [HR] for clopidogrel group: 0.909, 95% confidence interval [CI] 0.815 – 1.014). The incidence of each component of ischemic endpoint did not differ significantly between the two groups. All-cause mortality was increased in the clopidogrel group (HR 1.301, 95% CI 1.000 – 1.692). There was no significant difference in major bleeding events (HR 0.942, 95% CI 0.789 – 1.126). Conclusions For a dual antithrombotic therapy in patients with AF who had undergone PCI, aspirin and clopidogrel did not differ in terms of ischemic outcomes, but the use of aspirin was associated with slightly lower all-cause mortality.

#280 Effectiveness and safety of direct oral anticoagulants vs VKA in patients on chronic dialysis: a target trial emulation using nationwide registry data

Abstract Background and Aims The mortality and morbidity rates among patients on dialysis remain high and cardiovascular disease is the leading cause of death in this population. In chronic kidney disease (CKD), a major thromboembolic risk is paradoxically associated with a major haemorrhagic risk. Hence, the prescription of oral anticoagulants in CKD patients is challenging. Clinical trials of direct oral anticoagulants (DOAC) are scarce and inconclusive in patients who are receiving dialysis, for whom DOAC are not labelled in Europe. In an exhaustive French nationwide registry of patients undergoing chronic dialysis, we compared the effectiveness and safety of off-label DOAC use versus approved vitamin K antagonist (VKA). Method Data on patients on dialysis were extracted from the French Renal Epidemiology and Information Network (REIN) registry and merged with data from the French national healthcare system database (Système National des Données de Santé, SNDS). Patients on dialysis who had initiated treatment with an oral anticoagulant between January 1st, 2012, and December 31st, 2020, were eligible for inclusion. The primary safety outcome was the occurrence of major bleeding events and the primary effectiveness outcome was the occurrence of thrombotic events. Using target trial emulation design, we compared the safety and effectiveness outcomes for DOAC and VKA using propensity-score-weighted cause-specific Cox regression. Results 8 954 patients received an oral anticoagulant (483 DOAC and 8 471 VKA) for the first time after the initiation of dialysis. Over a median [interquartile range] follow-up period of 1.7 [0.8-3.2] years, 2 567 patients presented a first thromboembolic event and 1 254 patients had a bleeding event. After propensity score adjustment, the risk of a thromboembolic event was significantly lower in patients treated with a DOAC than in patients treated with a VKA (weighted hazard ratio (HR) [95% confidence interval (CI)]: 0.66 [0.46; 0.94] (Figure). A non-significant trend toward lower risk of major bleeding events was found in patients treated with a DOAC compared to patients treated with a VKA (weighted HR [95% CI]: 0.68 [0.41; 1.12]) (Figure). Sensitivity analyses showed the same trends. Conclusion The fact that patients on dialysis are excluded from large, cardiovascular-disease-focused randomized controlled trials (such as those with DOACs) significantly limits the evidence needed to make clinical decisions. Most of the retrospective cohort studies comparing these two drug classes were performed in the USA, where, in contrast to Europe, apixaban has been approved for the treatment of non-valvular fibrillation in patients on haemodialysis. Our real-world study of patients on dialysis is one of the first of its type to have assessed the effectiveness and safety of off-label DOAC prescription (relative to VKA prescription) in Europe. In a large group of dialysis patients initiating oral anticoagulation, the off-label use of DOACs was associated with a statistically significant lower risk of thromboembolic events, and a non-significant trend toward lower risk of bleeding relative to VKA use. These results are reassuring with regard to the off-label use of DOACs and might facilitate the establishment of an expert consensus and guidelines on antithrombotic therapy in patients with ESKD.

Impact of a DSS-supported medication review on the safety of drug therapy and quality of life in patients with antithrombotic therapy

Polypharmacy is common among patients with antithrombotic medication, giving rise to concerns about Drug-Related Problems (DRPs). Therefore, these patients would benefit from a Medication Review (MR) along with pharmacist counselling to reduce the risks accompanying polymedication. This prospective study presents a concept for MRs that are applicable in German community pharmacies and can efficiently support pharmacist counselling and improve the safety of drug therapy. As this is a major challenge in everyday pharmacy practice, we used a Decision Support System (DSS) to evaluate its ability to support the process of pharmacist-led MRs. The primary endpoint was the impact of a community pharmacist on the reduction of DRPs. We investigated the impact of the interventions resulting from MRs on patients taking at least one antithrombotic drug as part of their polymedication regimen. Secondary endpoints were the reduction in the number of patients with bleeding risks and the improvement of patients’ Quality of Life (QoL) and therapy adherence. Furthermore, the DSS used in the study was controlled for correct data assessment and plausibility of data. We selected adult patients who were taking no less than three different medications for long-term treatment, at least one of which had to be an antithrombotic drug, and who were customers in one of eight selected pharmacies over a period of 6 months. Data from 87 patients were analyzed with DSS-support. A total of 234 DRPs were identified by the pharmacist (2.7 DRPs per patient). MR reduced DRPs by 43.2% which, resulting to a reduction of 1.2 DRPs per patient. The intervention also led to a significant improvement in the patients’ QoL (assessed via EQ-5D-5L questionnaire; p < 0.001) and enhanced therapy adherence (assessed via A14 questionnaire; p < 0.001). The control of correct data assessment (with 93.8% concordance) and plausibility of data (with 91.7% concordance) of the DSS software were conducted by an external auditor. No significant effect was found for overall bleeding risk. The results of this study indicate that DSS-supported and structured MR conducted by pharmacists can contribute to a reduction in DRPs and significantly improve patient’s QoL and adherence to treatment.

Residual risk of thromboembolic events despite anticoagulation in Middle Eastern patients with atrial fibrillation. The JoFib study

ObjectivesTo investigate residual risk of thromboembolic events despite anticoagulation in patients with atrial fibrillation form the Middle East. Materials and methodsUsing data from the JoFib registry, we described the characteristics of patients treated with anticoagulants (n = 1654) and calculated the incidence rate for thromboembolic events. We constructed multivariable Cox proportional hazard models and calculated the population-attributable fraction to determine clinical factors predictive of residual thromboembolic events. ResultsDuring the one-year follow-up, 57 thromboembolic events occurred (incidence rate 4.1 per 100 person-years). In multivariable time-to-event analysis, prior thromboembolic events (aHR 3.8, 95 %CI 2.2–6.4, p < 0.001) and diabetes (aHR 2.3, 95 %CI 1.3–4.1, p = 0.004) were independently predictive of residual thromboembolism. Percentage of thromboembolic risk attributable to prior thromboembolic events was 30.9 % (95 %CI 13.9–44.6, p = 0.001) and was 37.1 % (95 %CI 8.8–56.6, p = 0.015) for diabetes. Furthermore, the effect of diabetes on thromboembolic events depends on the type of anticoagulant, with diabetes being significantly predictive of thromboembolic events in patients anticoagulated with warfarin (aHR 4.11, 95 %CI 1.81–9.37, p = 0.001), but not non-vitamin K antagonist oral anticoagulants (aHR 1.23, 95 %CI 0.51–2.97, p = 0.643) with a p = 0.045 for interaction. Prior thromboembolism was independently predictive of thromboembolic events in both anticoagulants (aHR 2.67, 95 %CI 1.28–5.58, p = 0.009; aHR 7.33, 95 %CI 3.05–17.65, p < 0.001; respectively; p = 0.084 for interaction). ConclusionsMiddle Eastern patients with atrial fibrillation remain at significant risk of thromboembolism and its recurrence despite anticoagulation, and especially in diabetic patients. Therefore, management should focus on controlling diabetes as well as other modifiable risk factors in addition to antithrombotic therapy.

Classification and management strategy of spontaneous carotid artery dissection

ObjectiveSpontaneous carotid artery dissections (sCADs) are the common cause of stroke in middle-aged and young people. There is still a lack of clinical classification to guide the management of sCAD. We reviewed our experience with 179 patients with sCAD and proposed a new classification for sCAD with prognostic and therapeutic significance. MethodsThis is a retrospective review of prospectively collected data from June 2018 to June 2023 of patients with sCAD treated at a large tertiary academic institution in an urban city in China. Based on imaging results, we categorize sCAD into four types: type Ⅰ, intramural hematoma or dissection with <70% luminal narrowing; type Ⅱ, intramural hematoma or dissection with ≥70% luminal narrowing; type Ⅲ, dissecting aneurysm; type ⅣA, extracranial carotid artery occlusion; and type ⅣB, tandem occlusion. We compared the clinical data and prognostic outcomes among various types of sCADs. ResultsA total of 179 patients and 197 dissected arteries met the inclusion criteria. The mean age of the 179 patients with sCAD was 49.5 years, 78% were male, and 18 patients (10%) had bilateral sCAD. According to our classification, there were 56 type Ⅰ (28.4%), 50 type Ⅱ (25.4%), 60 type Ⅲ (30.5%), and 31 type Ⅳ (15.7%) dissections. During a mean hospitalization length of 11.4 ± 47.0 days, there were nine recurrent strokes (4.6%) after medical treatment, two type Ⅲ dissections (1.0%), seven type Ⅳ dissections (3.6%), all ipsilateral, and one death. Overall, there were seven (3.6%, 1 type Ⅰ dissection, 3 type Ⅱ dissections, 2 type Ⅲ dissections, and 1 type Ⅳ dissection) recurrent strokes and three (1.5%, all type Ⅲ dissections) recurrent transient ischemic attacks in patients treated with just medical therapy during the follow-up period, all ipsilateral, with a mean follow-up of 26 months (range, 3-59 months). These patients did not undergo further intervention due to the high difficulty associated with endovascular treatment (EVT) or the mild nature of recurrent cerebral ischemic symptoms. Twenty-nine type I dissections (51.8%) were completely recanalized after antithrombotic therapy. A total of 19 type II dissections (38%) and 44 type III dissections (73%) received EVT for persistent flow-limited dissections, enlargement of dissecting aneurysms, or aggravation of neurological symptoms despite antithrombotic therapy. Type Ⅳ dissections are more likely to lead to the occurrence of ischemic stroke and presented with more severe symptoms. Eight type IVB dissections (33%) received acute phase intervention due to distal thromboembolism or aggravation of neurological symptoms after medical treatment. In terms of cerebral ischemic events and mortality, there were no statistically significant differences among the four types of sCAD (all P > .05). Favorable outcome was achieved in 168 patients (93.9%). ConclusionsThis study proposed a novel and more comprehensive classification method and the modern management strategy for sCAD. Antithrombotic therapy is beneficial to reduce the risk of recurrent stroke for stable sCAD. Non-emergent EVT can be an alternative therapeutic approach for patients who meet indications as in type II to IVA dissections. Urgent procedure with neurovascular intervention is necessary for some type IVB dissections. The short-term results of EVT for sCAD are encouraging, and long-term device-related and functional outcomes should undergo further research.

New insights and novel perspectives in bileaflet mechanical heart valve prostheses thromboresistance

BackgroundAlthough well-known for their thromboresistance, bileaflet mechanical heart valves (BMHV) require lifelong anti-thrombotic therapy. This must be associated with a certain level of thrombogenicity. Since both thromboresistance and thrombogenicity are explained by the blood-artificial surface or liquid-solid interactions, the aim of the present study was to explore BMHV thromboresistance from new perspectives. The wettability of BMHV pyrolytic carbon (PyC) occluders was investigated in under-liquid conditions. The submerged BMHV wettability clarifies the mechanisms involved in the thromboresistance.MethodsThe PyC occluders of a SJM Regent™ BMHV were previously laser irradiated, to create a surface hierarchical nano-texture, featuring three nano-configurations. Additionally, four PyC occluders of standard BMHV (Carbomedics, SJM Regent™, Bicarbon™, On-X®), were investigated. All occluders were evaluated in under-liquid configuration, with silicon oil used as the working droplet, while water, simulating blood, was used as the surrounding liquid. The under-liquid droplet-substrate wetting interactions were analyzed using contact angle goniometry.ResultsAll the standard occluders showed very low contact angle, reflecting a pronounced affinity for non-polar molecules. No receding of the contact line could be observed for the untreated occluders. The smallest static contact angle of around 61° could be observed for On-X® valve (the only valve made of full PyC). The laser-treated occluders strongly repelled oil in underwater conditions. A drastic change in their wetting behaviour was observed depending on the surrounding fluid, displaying a hydrophobic behaviour in the presence of air (as the surrounding medium), and showing instead a hydrophilic nature, when surrounded by water.ConclusionsBMHV “fear” water and blood. The intrinsic affinity of BMHV for nonpolar fluids can be translated into a tendency to repel polar fluids, such as water and blood. The blood-artificial surface interaction in BMHV is minimized. The contact between blood and BMHV surface is drastically reduced by polar-nonpolar Van der Waals forces. The “hydro/bloodphobia” of BMHV is intrinsically related to their chemical composition and their surface energy, thus their material: PyC indeed. Pertaining to thromboresistance, the surface roughness does not play a significant role. Instead, the thromboresistance of BMHV lies in molecular interactions. BMHV wettability can be tuned by altering the surface interface, by means of nanotechnology.

SAFETY AND EFFICACY OF A LIGHT ANTITHROMBOTIC REGIMEN AFTER LEFT ATRIAL APPENDAGE OCCLUSION: INSIGHTS FROM THE LOGIC (LEFT ATRIAL APPENDAGE OCCLUSION IN PATIENTS WITH GASTROINTESTINAL OR INTRACRANIAL BLEEDING) INTERNATIONAL MULTICENTER REGISTRY

Abstract Background Antithrombotic therapy (AT) after left atrial appendage occlusion (LAAO) in patients with non–valvular atrial fibrillation (NVAF) has the purpose of preventing device related thrombosis (DRT), avoiding embolic events; nevertheless, the correct antithrombotic regimen after LAAO is still under debate. Aims Aim of this substudy of the observational LOGIC registry was to describe the efficacy and safety of a light antithrombotic regimen, comprising single antiplatelet therapy or none, compared to a standard antithrombotic regimen, after a successful LAAO. Methods Patients with NVAF that underwent LAAO were previously included in the LOGIC registry. Patients receiving single or no AT were considered as light therapy group, while other regimen were considered as standard regimen group. Outcomes of interest were: death from any causes and cardiovascular death, ischemic stroke, transient ischemic attack and systemic embolization, any bleeding and major bleeding at 12 months. Results. Six hundred and twenty–eight patients were considered in the analysis, 31.4% received a light antithrombotic regimen. There were no differences in overall and cardiovascular mortality (5.1% Vs 6.7%, p=0.426 and 2.0% Vs 1.4%, p=0.553 respectively). Cerebrovascular stroke and transient ischemic attack were similar between the two groups (1.5% Vs 1.4%, p=0.898 and 1.5% Vs 1.3%, p=0.847). Light regimen was not associated with an increased rate of systemic embolism (1.0% Vs 0.7%, p=0.447 and HR 0.88 [95% CI: 0.34 – 2.27; p=0.79]). Conclusions An AT regimen based on single or no antithrombotic therapy after LAAO seems to be safe in patients with high–bleeding risk, without increasing cerebrovascular or peripheral ischemic events.

PERCUTANEOUS CORONARY INTERVENTIONS IN PATIENTS TREATED WITH ORAL ANTICOAGULANT THERAPY: BASELINE CLINICAL CHARACTERISTICS OF THE PERSEO REGISTRY

Abstract Background International guidelines recommend a dual antithrombotic therapy (DAT) with direct oral anticoagulant (DOAC) for patients on chronic oral anticoagulant therapy (OAT) undergoing percutaneous coronary intervention with stent implantation (PCI–S). However, the implementation of practice Guidelines in the “real world” is often a complex exercise. Aim of the multicenter prospective observational PERSEO (PERcutaneouS coronary intErventions in patients treated with Oral anticoagulant therapy) registry was to evaluate the management of the different antithrombotic regimens strategies in patients with an indication for OAT undergoing PCI–S in a “real world” setting and its association with clinical outcomes. Methods The PERSEO registry has been designed to enrol patients requiring OAT and treated by PCI–S in 25 Italian Cardiology Centres. No exclusion criteria have been defined. The primary end–point was a combined measure of efficacy and safety outcome (NACE), including major bleeding events + major adverse cardiac and cerebral events at one year follow up in patients treated with DOAC compared to vitamin K antagonists. Results From February 2018 to February 2022, a total of 1233 patients were enrolled: mean age 74±9 years, 900 males and 333 females. The primary indication for OAT was atrial fibrillation (1066 patients, 87%) while an acute coronary syndrome was the leading reason for PCI–S (789 patients, 64%). Of those, 271 patients had an ST elevation myocardial infarction at admission. Mean CHA2DVAS2C score and HASBLED score were respectively 4±2 and 4±1. Six patients died during hospitalization and 1227 were discharged alive: 1027 on triple antithrombotic therapy (oral anticoagulant and dual antiplatelet therapy), 196 patients on DAT (oral anticoagulant and single antiplatelet therapy) and 4 patients on oral anticoagulant alone. The majority of patients enrolled were discharged on DOAC (1006 patients, 82%), whereas only a minority received vitamin K antagonists (221 patients, 18%). Conclusions The Italian PERSEO Registry is the largest prospective observational study comparing different antithrombotic strategies in patients with an indication for OAT undergoing PCI–S in a “real world” setting. Baseline characteristics, depicted a population at high thrombotic and haemorrhagic risk. In agreement with current guidelines the majority of patients were discharged on DOAC, yet the use of a DAT was still limited to a minority of the patients included.

Comparison of apixaban versus aspirin for the prevention of latent bioprosthetic aortic valve thrombosis: study protocol for a prospective randomized trial.

The optimal antithrombotic strategy early after aortic valve replacement surgery with a biological valve remains controversial due to lack of high-quality evidence. Either oral anticoagulants or acetylsalicylic acid should be considered for the first 3 months. Hypo-attenuated leaflet thickening on cardiac computed tomography has been associated with latent bioprosthetic valve thrombosis and may be prevented with anticoagulation. We hypothesize that anticoagulation with apixaban is superior to single antiplatelet therapy with acetylsalicylic acid in reducing hypo-attenuated leaflet thickening of bioprosthetic aortic valve prostheses. In this prospective, open-label, randomized trial, patients undergoing isolated aortic valve replacement surgery with rapid deployment bioprosthetic valves will be randomized. The treatment group will receive 5 mg of apixaban twice a day for the first 3 months and 100 mg of acetylsalicylic acid thereafter. The control group will be administered 100 mg of acetylsalicylic acid once a day, indefinitely. After the 3-month treatment period, a contrast-enhanced electrocardiogram-gated cardiac computed tomography will be performed to identify hypo-attenuated leaflet thickening of the bioprosthetic valve. The primary objective of the study is to assess the impact of apixaban on the prevention of hypo-attenuated leaflet thickening at 3 months. The secondary and exploratory endpoints will be clinical outcomes and safety profiles of the two strategies. Antithrombotic therapy after aortic valve replacement is used to prevent valve thrombosis and systemic thromboembolism. Latent bioprosthetic valve thrombosis is a precursor of clinically significant prosthetic valve dysfunction or thromboembolic events. The hallmark feature of latent bioprosthetic valve thrombosis is hypo-attenuated leaflet thickening on cardiac computed tomography. Subclinical leaflet thrombosis occurs frequently in bioprosthetic aortic valves, more commonly in transcatheter than in surgical valves. There is no evidence on the effect of direct oral anticoagulants on the incidence of hypo-attenuated leaflet thickening after surgical aortic valve replacement with rapid deployment bioprostheses. ClinicalTrials.gov NCT06184113. Registered on December 28, 2023.

PAPILLARY FIBROELASTOMA: AN UNUSUAL CAUSE OF TRANSIENT ISCHEMIC ATTACK

Abstract Papillary fibroelastomas (PFEs) are small, avascular benign tumors. Despite that, PFEs could lead to important clinical consequences such as transient ischemic attack and myocardial infarction. A 65–year–old female patient was admitted to our ER presenting a transient ischemic attack characterized by retrograde amnesia lasting about an hour. She had a history of systemic scleroderma and left breast cancer treated with local radiotherapy. In our hospital she underwent a neurological examination and a head CT which were negative for ongoing acute pathologies. An electrocardiogram was performed which showed sinus rhythm at 65 bpm. A transthoracic echocardiogram was also performed revealing a floating mass arising from left ventricular outflow tract between aortic and mitral valves. The transesophageal echocardiogram confirmed a solitary lesion approximately 2 centimeters long localized between A2 and A3 mitral valve scallops. The patient was therefore referred for surgery. During surgery the mass was found to arise from anterior mitral annulus and was resected. The histopathological examination of the mass confirmed the morphologic diagnosis of papillary fibroelastoma. Histologically PFEs are made up of a single layer of endocardial cells covering a matrix of collagen. The main risk factors for the development of PFEs are iatrogenic causes, such as radiotherapy, and autoimmune diseases such as systemic scleroderma. In 54% of cases PFEs are asymptomatic at the time of diagnosis. Since over 95% of PFEs present on the left side of the heart, systemic embolism is the most frequent presentation typically as transient ischemic attacks. Initial evaluation is accomplished with echocardiography. PFEs appear as echo–dense and pedunculated masses. Cardiac computed tomography and magnetic resonance imaging are second line modalities in PFEs evaluation. Definitive diagnosis of PFE requires pathological confirmation. Surgical resection remains the treatment of choice for all symptomatic patients. For symptomatic patients who are not surgical candidate, long term antiplatelets or anticoagulation therapy should be initiated. Asymptomatic patients should have surgical resection if the size of the tumor is &amp;gt; 1 cm. PFEs are associated with significant morbidity and mortality. Echocardiography remains the most utilized diagnostic modality. Surgical treatment should always be considered. Antithrombotic therapy should be considered in non–surgical candidates.

ANMCO/SIMEU consensus document on the use of reversal agents for antithrombotic therapies in patients with ongoing bleeding or at high risk of haemorrhagic events.

In recent decades, an incredible evolution in antithrombotic therapies used for treating patients with atherosclerosis, atrial fibrillation, and venous thromboembolism has been observed, leading to the availability of increasingly safe drugs. Nonetheless, bleeding complications remain a significant concern, with considerable health, social, and economic implications. To improve the acute management of patients experiencing or at risk for major bleeding events, specific reversal agents for antithrombotic drugs have been recently developed. While these agents demonstrate effectiveness in small-scale pharmacodynamic studies and clinical trials, it is imperative to balance the benefits of reversing antiplatelet or anticoagulant therapy against the risk of prothrombotic effects. These risks include the potential loss of antithrombotic protection and the prothrombotic tendencies associated with bleeding, major surgery, or trauma. This joint document of the Italian Association of Hospital Cardiologists (Associazione Nazionale Medici Cardiologi Ospedalieri) and the Italian Society of Emergency Medicine (Società Italiana di Medicina d'Emergenza-Urgenza) delineates the key features and efficacy of available reversal agents. It also provides practical flowcharts to guide their use in patients with active bleeding or those at elevated risk of major bleeding events.

The Safety and Efficacy of Epicardial Carbon Dioxide Insufflation Compared With Conventional Epicardial Access

BackgroundEpicardial (Epi) access is commonly required during ventricular tachycardia ablation. Conventional Epi (ConvEpi) access targets a “dry” pericardial space presenting technical challenges and risk of complications. Recently, intentional puncture of coronary venous branches with Epi carbon dioxide insufflation (EpiCO2) has been described as a technique to improve Epi access. The safety of this technique relative to conventional methods remains unproven. ObjectivesThe authors sought to compare the feasibility and safety of EpiCO2 to ConvEpi access. MethodsAll patients at a high-volume center undergoing Epi access between January 2021 and December 2023 were included and grouped according to ConvEpi or EpiCO2 approach. Access technique was according to the discretion of the operator. ResultsEpi access was attempted in 153 cases by 17 different operators (80 ConvEpi vs 73 EpiCO2). There was no difference in success rate whether the ConvEpi or EpiCO2 approach was used (76 [95%] cases vs 67 [91.8%] cases; P = 0.4). Total Epi access time was shorter in the ConvEpi group compared with the EpiCO2 group (16.3 ± 11.6 minutes vs 26.9 ± 12.7 minutes; P < 0.001), though the total procedure duration was similar. Major Epi access–related complications occurred in only the ConvEpi group (6 [7.5%] ConvEpi vs 0 [0%] EpiCo2; P = 0.02). Bleeding ≥80 mL was more frequently observed following ConvEpi access (14 [17.5%] cases vs 4 [5.5%] cases; P = 0.02). After adjusting for age, repeat Epi access, and antithrombotic therapy, EpiCO2 was associated with a reduction in bleeding ≥80 mL (OR: 0.27; 95% CI: 0.08-0.89; P = 0.03). ConclusionsEpiCO2 access is associated with lower rates of major complication and bleeding when compared with ConvEpi access.

BETWEEN SCYLLA AND CHARYBDIS: MULTIPLE LEFT ATRIAL THROMBI DESPITE ORAL ANTICOAGULATION AND ANTIPLATELET THERAPY IN A PATIENT CANDIDATE FOR LEFT ATRIAL APPENDAGE OCCLUSION

Abstract Introduction Left atrial (LA) thrombosis usually occurs in patients affected by atrial fibrillation (AF), generally involving the left atrial appendage (LAA). We present the unexpected echocardiographic finding of multiple LA thrombi despite an adequate antithrombotic strategy. Case Presentation A 76–year–old lady underwent transesophageal echocardiographic examination (TOE) to assess eligibility for percutaneous LAA occlusion (LAAO) procedure due to high bleeding risk. Her medical history included AF and a recent percutaneous coronary revascularization; therefore, her antithrombotic therapy included apixaban 2.5 mg bid and clopidogrel 75 mg od. The TOE showed LA structural and functional remodeling with spontaneous echo contrast and multiple thrombi involving the LAA (one [12 x 9 mm] overflowing the orifice and attached to the Coumadin Ridge and the second [12 x 7 mm] attached and arising from the tunnel of patent foramen ovale). Mitral valve stenosis was excluded (Fig.1). Due to TOE findings, the patient was not considered eligible for percutaneous LAAO. Due to the concomitant very high thromboembolic risk, despite the previous intracranial bleeding, we decided to stop apixaban and to start parenteral anticoagulation for 3 weeks with low–molecular weight heparin (100 UI/kg bid) followed by the switch to a vitamin k antagonist (VKA). We also prescribed a hematological evaluation to exclude a hypercoagulability disorder. Our patient’s daughter was a carrier of a mutation in both the methylenetetrahydrofolatereductase and Thrombin genes. A TOE after 30 days showed the persistence of LA thrombi, although with significantly reduced size and mobility (Fig.2). The follow–up was clinically uneventful. We suggested to continue anticoagulation therapy with VKA, and we planned a new TOE after 4 weeks. Discussion Although proper anticoagulation decreases cardioembolic risk in patients with AF, atrial thrombosis may occur due to LA remodeling, high CHA2DS2–VASc score and other factors, including hypercoagulability disorders. The presence of multiple LA thrombi represents a challenge for clinicians, especially in case of concomitant high thromboembolic and bleeding risk. However, the best treatment strategies for these extreme conditions are not defined, so far. Therefore, the therapeutic choice is often tailored to the single patient and based on the clinical judgment, bearing in mind that avoiding Charybdis means passing to close to Scylla and vice versa.

TAKOTSUBO SYNDROME PRECEDING THE INDEX EVENT: A DANGEROUS CLINICAL SETTING

Abstract We describe the case of a 68–year–old patient who presented to the Emergency Department following an unwitnessed syncopal episode with slow recovery of consciousness. On admission, the patient had dyspnoea together with physical signs of pulmonary congestion. Cardiac ultrasound showed severe left ventricular dysfunction with an ejection fraction of 30%, and apical and paraapical akinesis. The admission electrocardiogram showed sinus tachycardia and diffuse repolarization abnormalities, hs TnI was elevated and BNP vl blood gas analysis were unremarkable. During observation in the Emergency Department, the patient experienced epileptic seizure, promptly resolved by intravenous Midazolam. Contrast–enhanced chest CT ruled out aortic dissection disclosing a clinically irrelevant subsegmental pulmonary embolism. A non–contrast CT scan of the brain yielded negative results. In consideration of the atypical clinical presentation and scattered evidence of an acute coronary syndrome, the patient was admitted to our Cardiac Intensive Care Unit (CICU) for additional diagnostic workup delaying coronary angiography in the presence of stable TnI elevation. Three hours after admission the patient continued showing altered consciousness and a subsequent brain CT was performed, demonstrating an intraparenchymal hemorrhagic spreading. Repeat ECGs showed precordial T wave inversion and prolongation of the QT interval. These data, together with LV apical dysfunction, raised the suspicion of Takotsubo syndrome secondary to an acute cerebrovascular event. During the hospital stay, recovery of consciousness, spontaneous absorption of the cerebral hemorrhagic spread and complete recovery of left ventricular function at repeat cardiac ultrasound examinations were observed, confirming the almost unequivocal diagnosis of Takotsubo syndrome. The patient was discharged uneventfully and was scheduled for an outpatient coronary CT scan. This case underscores the crucial importance of a thorough clinical assessment in the management of complex patients in the presence of nonunivocal clinical signs and misleading blood test and imaging data. Moreover, Takotsubo syndrome is a protean clinical entity that can precede the index event as in our patient, i.e. cerebral hemorrhage. Misclassification of these patients as having an acute coronary syndrome could have led to the initiation of antithrombotic therapy, with potential fatal outcomes for the patient.

The Impact of Changing Antithrombotic Management in Patients With Atrial Fibrillation and Ischemic Cerebrovascular Events Despite Anticoagulation.

Patients with atrial fibrillation (AF) are at increased risk of ischemic cerebrovascular events despite anticoagulants (AC). We aim to evaluate whether changing AC or adding antiplatelet therapy to anticoagulants (AP + AC) in patients with AF presenting with acute ischemic stroke (AIS) or transient ischemic attack (TIA) despite AC, decreases the risk of recurrent AIS/TIA compared to patients continued on same AC regimen. Patients with AF on AC presenting with AIS or TIA at our center between 2011- 2021 were included. Data on Demographics, index event, antithrombotic therapy before and after index event, recurrent AIS/TIA, or major bleeding events (MBE) were extracted. Cox proportional hazards models were used to compare outcomes between AC unchange vs AC change, and AP + AC vs AC only groups. One hundred eighty-five patients were included (mean age 78.3years; 62% males, median follow-up 9months (IQR 1-34)). Seventeen patients (9%) had AC change, 100 (54%) received AP + AC, 39 (21%) had recurrent AIS/TIA, and 27 (15%) had MBE following index event. No difference was observed between AC unchange vs AC change and AP + AC vs AC only groups regarding recurrent AIS/TIA (HR 1.72 [.65-4.57], P = .27 and HR 1.02 [.53- 1.98], P = .95, respectively) or MBE (HR .85 [.19-3.67], P = .83 and HR 1.49 [.67-3.33)], P = .33, respectively). Fourteen vascular neurologists treated this cohort and 9(64%) implemented AC changes. In this single center retrospective study of 185 patients with AF and AIS/TIA despite AC, changing AC or adding AP agents did not decrease the risk of ischemic cerebrovascular events.

Severe Adverse Event Related to Holding Antithrombotic Therapy Before Breast Biopsy.

Severe Adverse Event Related to Holding Antithrombotic Therapy Before Breast Biopsy.

Dual Antithrombotic Therapy versus Anticoagulant Monotherapy for Major Adverse Limb Events in Patients with Concomitant Lower Extremity Arterial Disease and Atrial Fibrillation: A Propensity Score Weighted Analysis

Patients with symptomatic lower extremity arterial disease (LEAD) are recommended to receive antiplatelet therapy, while direct oral anticoagulants (DOACs) are standard for stroke prevention in patients with atrial fibrillation (AF). For patients with concomitant LEAD and AF, data comparing dual antithrombotic therapy (an antiplatelet agent used in conjunction with a DOAC) vs. DOAC monotherapy are scarce. This retrospective cohort study, based on data from the Taiwan National Health Insurance Research Database, aimed to compare the efficacy and safety of these antithrombotic strategies. Patients with AF who underwent revascularisation for LEAD between 2012 - 2020 and received any DOAC within 30 days of discharge were included. Patients were grouped by antiplatelet agent exposure into the dual antithrombotic therapy and DOAC monotherapy groups. Inverse probability of treatment weighting was used to mitigate selection bias. Major adverse limb events (MALEs), ischaemic stroke or systemic embolism, and bleeding outcomes were compared. Patients were followed until the occurrence of any study outcome, death, or up to two years. A total of 1 470 patients were identified, with 736 in the dual antithrombotic therapy group and 734 in the DOAC monotherapy group. Among them, 1 346 patients received endovascular therapy as the index revascularisation procedure and 124 underwent bypass surgery. At two years, dual antithrombotic therapy was associated with a higher risk of MALEs than DOAC monotherapy (subdistribution hazard ratio [SHR] 1.34, 95% confidence interval [CI] 1.15 - 1.56), primarily driven by increased repeat revascularisation. Dual antithrombotic therapy was also associated with a higher risk of major bleeding (SHR 1.43, 95% CI 1.05 - 1.94) and gastrointestinal bleeding (SHR 2.17, 95% CI 1.42 - 3.33) than DOAC monotherapy. In patients with concomitant LEAD and AF who underwent peripheral revascularisation, DOAC monotherapy was associated with a lower risk of MALEs and bleeding events than dual antithrombotic therapy.

Individualising Antithrombotic Strategies for Acute and Chronic Coronary Syndromes.

For patients presenting with acute or chronic coronary syndromes, current guideline recommendations and expert consensus provide a range of options for antithrombotic treatment. The European Society of Cardiology 2023 guidelines on the management of acute coronary syndrome emphasise the need to assess the risk of both ischaemic events and bleeding. Those with high bleeding risk warrant particular consideration of the duration and intensity of antithrombotic therapy combinations. A joint consensus of experts takes a similar approach, informed by two network meta-analyses that appraised all available antithrombotic treatments within or after the 12 months following coronary revascularisation and/or acute coronary syndrome and individual participant data from six trials. In this article, four case studies are used to illustrate how these guidelines and expert consensus recommendations can be applied in clinical practice.

Antithrombotic Treatment for Cervical Artery Dissection

Cervical artery dissection is the most common cause of stroke in younger adults. To date, there is no conclusive evidence on which antithrombotic therapy should be used to treat patients. To perform an individual patient data meta-analysis of randomized clinical trials comparing anticoagulants and antiplatelets in prevention of stroke after cervical artery dissection. PubMed.gov, Cochrane database, Embase, and ClinicalTrials.gov were searched from inception to August 1, 2023. Randomized clinical trials that investigated the effectiveness and safety of antithrombotic treatment (antiplatelets vs anticoagulation) in patients with cervical artery dissection were included in the meta-analysis. The primary end point was required to include a composite of (1) any stroke, (2) death, or (3) major bleeding (extracranial or intracranial) at 90 days of follow-up. Two independent investigators performed a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, and inconsistencies were resolved by a principal investigator. The primary outcome was a composite of (1) ischemic stroke, (2) death, or (3) major bleeding (extracranial or intracranial) at 90 days of follow-up. The components of the composite outcome were also secondary outcomes. Subgroup analyses based on baseline characteristics with a putative association with the outcome were performed. Logistic regression was performed using the maximum penalized likelihood method including interaction in the subgroup analyses. Two randomized clinical trials, Cervical Artery Dissection in Stroke Study and Cervical Artery Dissection in Stroke Study and the Biomarkers and Antithrombotic Treatment in Cervical Artery Dissection, were identified, of which all participants were eligible. A total of 444 patients were included in the intention-to-treat population and 370 patients were included in the per-protocol population. Baseline characteristics were balanced. There were fewer primary end points in those randomized to anticoagulation vs antiplatelet therapy (3 of 218 [1.4%] vs 10 of 226 [4.4%]; odds ratio [OR], 0.33 [95% CI, 0.08-1.05]; P = .06), but the finding was not statistically significant. In comparison with aspirin, anticoagulation was associated with fewer strokes (1 of 218 [0.5%] vs 10 of 226 [4.0%]; OR, 0.14 [95% CI, 0.02-0.61]; P = .01) and more bleeding events (2 vs 0). This individual patient data meta-analysis of 2 currently available randomized clinical trial data found no significant difference between anticoagulants and antiplatelets in preventing early recurrent events.