Atrial Fibrillation and Stroke Symptoms in the REGARDS Study

Background It is unknown if stroke symptoms in the absence of a stroke diagnosis are a sign of subtle cardioembolic phenomena. The objective of this study was to examine associations between atrial fibrillation (AF) and stroke symptoms among adults with no clinical history of stroke or transient ischemic attack (TIA). Methods and Results We evaluated associations between AF and self‐reported stroke symptoms in the national, prospective REGARDS (Reasons for Geographic and Racial Differences in Stroke) cohort. We conducted cross‐sectional (n=27 135) and longitudinal (n=21 932) analyses over 8 years of follow‐up of REGARDS participants without stroke/transient ischemic attack and stratified by anticoagulant or antiplatelet agent use. The mean age was 64.4 (SD±9.4) years, 55.3% were women, and 40.8% were Black participants; 28.6% of participants with AF reported stroke symptoms. In the cross‐sectional analysis, comparing participants with and without AF, the risk of stroke symptoms was elevated for adults with AF taking neither anticoagulants nor antiplatelet agents (odds ratio [OR], 2.22; 95% CI, 1.89–2.59) or antiplatelet agents only (OR, 1.92; 95% CI, 1.61–2.29) but not for adults with AF taking anticoagulants (OR, 1.08; 95% CI, 0.71–1.65). In the longitudinal analysis, the risk of stroke symptoms was also elevated for adults with AF taking neither anticoagulants nor antiplatelet agents (hazard ratio [HR], 1.41; 95% CI, 1.21–1.66) or antiplatelet agents only (HR, 1.23; 95% CI, 1.04–1.46) but not for adults with AF taking anticoagulants (HR, 0.86; 95% CI, 0.62–1.18). Conclusions Stroke symptoms in the absence of a stroke diagnosis may represent subclinical cardioembolic phenomena or “whispering strokes.” Future studies examining the benefit of stroke symptom screening may be warranted.

CVIT expert consensus document on primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) update 2022

Primary Percutaneous Coronary Intervention (PCI) has significantly contributed to reducing the mortality of patients with ST-segment elevation myocardial infarction (STEMI) even in cardiogenic shock and is now the standard of care in most of Japanese institutions. The Task Force on Primary PCI of the Japanese Association of Cardiovascular Interventional and Therapeutics (CVIT) society proposed an expert consensus document for the management of acute myocardial infarction (AMI) focusing on procedural aspects of primary PCI in 2018. Updated guidelines for the management of AMI were published by the European Society of Cardiology (ESC) in 2017 and 2020. Major changes in the guidelines for STEMI patients included: (1) radial access and drug-eluting stents (DES) over bare-metal stents (BMS) were recommended as a Class I indication, (2) complete revascularization before hospital discharge (either immediate or staged) is now considered as Class IIa recommendation. In 2020, updated guidelines for Non-ST-Elevation Myocardial Infarction (NSTEMI) patients, the followings were changed: (1) an early invasive strategy within 24 h is recommended in patients with NSTEMI as a Class I indication, (2) complete revascularization in NSTEMI patients without cardiogenic shock is considered as Class IIa recommendation, and (3) in patients with atrial fibrillation following a short period of triple antithrombotic therapy, dual antithrombotic therapy (e.g., DOAC and single oral antiplatelet agent preferably clopidogrel) is recommended, with discontinuation of the antiplatelet agent after 6 to 12 months. Furthermore, an aspirin-free strategy after PCI has been investigated in several trials those have started to show the safety and efficacy. The Task Force on Primary PCI of the CVIT group has now proposed the updated expert consensus document for the management of AMI focusing on procedural aspects of primary PCI in 2022 version.

Ranger™ paclitaxel-coated balloon versus conventional balloon angioplasty for treatment of failing arteriovenous fistulas and grafts in haemodialysis patients: A retrospective cohort study

Background: Aim was to compare the safety and patency efficacy outcomes between Ranger™ paclitaxel-coated balloon (PCB)- versus conventional balloon angioplasty (POBA) in the treatment of haemodialysis access-related conduit stenosis. Methods: Retrospective single-centre, multi-investigator, consecutive, double-arm comparative cohort study. About 130 end-stage renal failure Asian patients with dysfunctional arteriovenous fistula (AVF) or arteriovenous graft underwent PCB or POBA fistuloplasty between November 2018 and June 2020. All stenotic lesions were prepared with high pressure non-compliant balloon angioplasty prior to PCB angioplasty. All patients received at least one antiplatelet agent for 3 months duration post procedure. Results: Mean age was 66.0 ± 10 years and 79/130 (61%) were males. PCB arm ( n = 65) versus POBA arm ( n = 65). Majority were AVFs circuits (122/130, 94%). Main indication for intervention was dropping access flow (98/130, 76%). About 172 lesions were treated (56% POBA, 44% PCB), and the juxta-anastomosis (JAS) was the main target lesion (87/172, 51%). There were no significant differences in safety outcomes (30-day adverse events, access thrombosis, abandoned AVF and death) between treatment groups. Mean time to target lesion reintervention (TLR) was longer in PCB-treated lesions (7.1 ± 2.7 vs 5.8 ± 3.2 months, p = 0.03), especially amongst recurrent lesions (7.3 ± 2.4 vs 5.7 ± 3.2, p = 0.02). Mean time to circuit reintervention was also longer in PCB-treated circuits (6.9 ± 2.8 vs 5.8 ± 3.7months, p = 0.04). There were 16 deaths (12%), all attributed to patient’s underlying comorbidities. Conclusions: Fistuloplasty with Ranger™ PCB for failing arteriovenous circuits in end-stage renal failure patients, is a safe and efficacious modality compared to POBA in terms of longer freedom from TLR.

Effects of Clopidogrel, Prasugrel and Ticagrelor on Microvascular Function and Platelet Reactivity in Patients With Acute Coronary Syndrome Undergoing Coronary Artery Stenting. A Randomized, Blinded, Parallel Group Trial

Aims: In this pre-specified analysis of the “endothelium, stent and antiplatelet therapy” study, we investigate the impact of antiplatelet therapies on microvascular function in patients undergoing stenting for an acute coronary syndrome.Methods and Results: Fifty-six patients [age: 63(55–67) years, males, 10 diabetics, 27 non-ST-elevation myocardial infarction] were randomized to receive clopidogrel, ticagrelor or prasugrel in form of oral loading 2 h before stenting followed by oral therapy. Investigators were blinded to the allocation. Laser-Doppler microvascular function and ADP-induced platelet aggregation capacity were measured at baseline, 2 h after oral antiplatelet loading, and 1 day, 1 week and 1 month after stenting during chronic therapy with the same antiplatelet agent. Platelet aggregation decreased in all groups 2 h after oral loading, with a significantly larger effect in the prasugrel group (P = 0.009). Similarly, prasugrel and ticagrelor loading was followed by an increase in microvascular reactive hyperemia (P = 0.007 and P = 0.042 compared to clopidogrel). This effect disappeared one day after coronary intervention, with a significant decrease in the prasugrel group (P = 0.026). Similarly, analysis of microvascular conductance showed a larger increase in the prasugrel group 2 h after loading (P = 0.022 among groups), and a decrease in all groups after stenting.Conclusions: Oral loading with prasugrel (and less consistently ticagrelor) is associated with improved microvascular function and stronger platelet inhibition in acute coronary syndrome patients. The microvascular effect was however lost 1 day after stenting and during subsequent follow-up. Further studies are necessary to clarify the the long-term effects and potential benefits of P2Y12 inhibitors on microvascular damage.ClINICALTRIALS.gov N°: NCT01700322EUDRACT-N°: 2011-005305-73.

Heparin-induced thrombocytopenia and cardiovascular surgery

Clinicians generally counsel patients with a history of heparin-induced thrombocytopenia (HIT) to avoid heparin products lifelong. Although there are now many alternative (nonheparin) anticoagulants available, heparin avoidance remains challenging for cardiac surgery. Heparin is often preferred in the cardiac surgery setting based on the vast experience with the agent, ease of monitoring, and reversibility. To “clear” a patient with a history of HIT for cardiac surgery, hematologists must first confirm the diagnosis of HIT, which can be challenging due to the ubiquity of heparin exposure and frequency of thrombocytopenia in patients in the cardiac intensive care unit. Next, the “phase of HIT” (acute HIT, subacute HIT A/B, or remote HIT) should be established based on platelet count, immunoassay for antibodies to platelet factor 4/heparin complexes, and a functional assay (eg, serotonin release assay). As long as the HIT functional assay remains positive (acute HIT or subacute HIT A), cardiac surgery should be delayed if possible. If surgery cannot be delayed, an alternative anticoagulant (preferably bivalirudin) may be used. Alternatively, heparin may be used with either preoperative/intraoperative plasma exchange or together with a potent antiplatelet agent. The optimal strategy among these options is not known, and the choice depends on institutional experience and availability of alternative anticoagulants. In the later phases of HIT (subacute HIT B or remote HIT), brief intraoperative exposure to heparin followed by an alternative anticoagulant as needed in the postoperative setting is recommended.

Cilostazol Improves Hyperglycemia-Induced Impairment of Angiogenesis by Stimulating Adiponectin/Adiponectin Receptor1/Sirtuin1

Background: Cilostazol is an antiplatelet agent with vasodilating effects that functions by increasing the intracellular concentration of cyclic adenosine monophosphate. However, the effect of cilostazol on adiponectin is still unclear. Purpose: We investigated the effects of cilostazol on adiponectin/adiponectin receptors and the Sirtuin 1 (SIRT1)/AMP-activated protein kinase (AMPK) signaling pathway to prevent high glucose (HG)-induced impairment of angiogenesis in vitro and in vivo. Methods and Results: Human umbilical vein endothelial cells (HUVECs) and human aortic smooth muscle cells (HASMCs) were cocultured in HG conditions. Adiponectin concentrations in the supernatant were significantly increased when HASMCs were treated with cilostazol but not significantly changed when only HUVECs were treated with cilostazol. Cilostazol treatment restored the expression of the adipoR1 and SIRT1 proteins and upregulated the phosphorylation of AMPKa1 in the HUVECs treated with HG but not adipoR2. Cilostazol prevented apoptosis and stimulated proliferation, chemotactic motility and capillary-like tube formation in HG-treated HUVECs through the adipoR1/AMPK/SIRT1 signaling pathway. In cilostazol-treated mice, recovery of the blood flow ratio after hindlimb ischemia and circulating CD34+CD45dim cells were significantly attenuated by adipoR1 knockdown but not adipoR2 knockdown. The expression of SIRT1, phosphorylation of AMPKa1/acetyl-CoA carboxylase and Akt/endothelial nitric oxide synthase in ischemic muscles were significantly attenuated by gene knockdown of adipoR1. Conclusions: Cilostazol prevents HG-induced endothelial dysfunction in vascular endothelial cells and enhances angiogenesis in hyperglycemic mice by upregulating the expression of adiponectin/adipoR1 and its SIRT1/AMPK downstream signaling pathway.

Early argatroban and antiplatelet combination therapy in acute non-lacunar single subcortical infarct associated with mild intracranial atherosclerosis

Background Patients with acute non-lacunar single subcortical infarct (SSI) associated with mild intracranial atherosclerosis (ICAS) have a relatively high incidence of early neurological deterioration (END), resulting in unfavorable functional outcomes. Whether the early administration of argatroban and aspirin or clopidogrel within 6–12 h after symptom onset is effective and safe in these patients is unknown. Methods A review of the stroke database of Weihai Municipal Hospital, Cheeloo College of Medicine, Shandong University and Qingdao Center Hospital, Qingdao University Medical College in China was undertaken from May 2017 to January 2020 to identify all patients with non-lacunar SSI caused by ICAS within 6–12 h of symptom onset based on MRI screening. Patients were divided into two groups, one comprising those who received argatroban and mono antiplatelet therapy with aspirin or clopidogrel on admission (argatroban group), and the other those who received dual antiplatelet therapy (DAPT) with aspirin and clopidogrel during hospitalization (DAPT group). The primary outcome was recovery by 90 days after stroke based on a modified Rankin scale (mRS) score (0 to 1). The secondary outcome was END incidence within 120 h of admission. Safety outcomes were intracranial hemorrhage (ICH) and major extracranial bleeding. The probability of clinical benefit (mRS score 0–1 at 90 days) was estimated using multivariable logistic regression analysis. Results A total of 304 acute non-lacunar SSI associated with mild ICAS patients were analyzed. At 90 days, 101 (74.2%) patients in the argatroban group and 80 (47.6%) in the DAPT group had an mRS score that improved from 0 to 1 (P < 0.001). The relative risk (95% credible interval) for an mRS score improving from 0 to 1 in the argatroban group was 1.50 (1.05–2.70). END occurred in 10 (7.3%) patients in the argatroban group compared with 37 (22.0%) in the DAPT group (P < 0.001). No patients experienced symptomatic hemorrhagic transformation. Conclusions Early combined administration of argatroban and an antiplatelet agent (aspirin or clopidogrel) may be beneficial for patients with non-lacunar SSI associated with mild ICAS identified by MRI screening and may attenuate progressive neurological deficits. Trial registration Our study is a retrospectively registered trial.

P.195 Giant aneurysm, tiny patient: flow diversion stenting of a giant MCA aneurysm in a young child

Background: A 3-year-old girl presented with a 6-day history of severe headaches. On examination, upper motor neuron signs were noted in the left upper and lower extremities with increased tone, reflexes, and a positive Babinski sign. MRI of the brain revealed a giant right middle cerebral artery (MCA) aneurysm with significant mass effect, associated with cerebral edema and ventricular effacement. CT and CT angiogram showed evidence of aneurysmal wall calcification and lamellar thrombosis within the aneurysmal sac. In addition, there was a smaller right MCA aneurysm in close proximity to the giant aneurysm. Methods: After a balloon occlusion test to assess collateral blood flow to the MCA territory, it was decided to treat both aneurysms with a flow diverting stent. Dual antiplatelet loading was done with aspirin and clopidogrel. The smallest available diameter of Pipeline Shield stent was deployed. Results: The patient remained neurologically unchanged. Early follow-up imaging demonstrated stent patency, reduced size and mass effect of the large aneurysm, reduced cerebral edema, and no flow into the smaller aneurysm. Conclusions: Flow diversion stenting may be employed successfully in pediatric patients, though has unique technical considerations including small size vessels and limited evidence for antiplatelet agent choice and dosing.

Antithrombotic strategy in patients with atrial fibrillation and acute coronary syndrome

Background Atrial fibrillation (AF) is frequent in patients admitted with acute coronary syndromes (ACS). The development of this arrhythmia occurs in 2–21% of patients with non ST-elevation ACS and 21% of ST-elevation ACS. According with the most recent European guidelines, a short period up to 1 week of triple antithrombotic therapy (TAT) is recommended, followed by dual antithrombotic therapy (DAT) using a NOAC and a single antiplatelet agent, preferably clopidogrel. Objective To compare the antithrombotic strategy (DAT vs TAT) used and its prognostic value in patients with AF and ACS. Methods Retrospective analysis of patients' data admitted with ACS in a multicentric registry between 10/2010–09/2019. TAT was defined as the prescription of dual antiplatelet therapy and one anticoagulant and DAT as one antiplatelet and one anticoagulant. Survival and rehospitalization were evaluated through Kaplan-Meier curve. Results 1067 patients were included, mean age 67±14 years, 72.3% male. Patients who developed de novo AF during hospitalization due to ACS were older (75±12 vs 66±14 years, p&lt;0.001) and with higher prevalence of cardiovascular risk factors and cardiovascular disease. AF was more often in patients with ST elevation ACS (53.4%). During hospitalization, AF patients were more often medicated with aspirin, glycoprotein inhibitor, heparin, fondaparinux and vitamin K antagonists. No difference was found regarding P2Y12 inhibitors. AF patients presented more often obstructive coronary disease (normal coronaries 5.4 vs 8.5%, p&lt;0.001) so they were more often submitted to PCI (79.5 vs 70.9%, p&lt;0.001). AF patients presented with higher rates of adverse in-hospital events as re-infarction, heart failure, shock, ventricular arrhythmias, cardiac arrest, stroke, major bleeding and death (p&lt;0.001). At discharge, AF patients were less prescribed with aspirin or ticagrelor, but the rate of clopidogrel prescription was higher, such as vitamin K antagonists or any of the new anticoagulants. In the AF group, 21.5% patients were discharged with TAT and 30.3% with DAT. Concerning patients discharged with TAT, 1-year follow-up revealed no significant differences in mortality (p=0.578), re-admission for cardiovascular causes (p=0.301) and total re-admission rates (p=0.291). Patients discharged with DAT had similar mortality (p=0.623) and re-admission for cardiovascular causes rates (p=0.138), but significant differences were identified regarding total re-admissions (p=0.024). Conclusions In patients with ACS and de novo AF, a low percentage of patients was discharged with oral anticoagulation (51.8%). In those whose anticoagulation was initiated, DAT was the preferred strategy. 1-year outcomes were not different between the antithrombotic strategy, except for all cause re-admission. FUNDunding Acknowledgement Type of funding sources: None.