Left atrial appendage occlusion in patients with atrial fibrillation and large prevalence of prior intracranial bleeding.

BACKGROUND: Left atrial appendage occlusion (LAAO) represents an alternative approach for the prevention of cardioembolic stroke in patients with nonvalvular atrial fibrillation (NVAF) and contraindication for oral anticoagulation (OAC). The aim of our study was to analyse the outcomes in patients treated with LAAO, with a focus on cases with previous intracranial bleeding. METHODS: Sixty patients with NVAF underwent LAAO (75.4 ±â€Š9 years); mean CHA2DS2-VASc was 4.4 ±â€Š1.7, mean HAS-BLED 3.2 ±â€Š0.9. Thirty-two patients (53.3%) reported previous intracranial bleeding. Ischaemic and bleeding events recorded during follow-up were compared with expected event rates according to CHA2DS2-VASc and HAS-BLED scores. RESULTS: Device implantation was successful in 58 patients (96.7%). The antiplatelet therapy was tailored according to patients' bleeding risk. During follow-up (2.32 ±â€Š1.5 years) 3 ischaemic strokes and 1 transient ischaemic attack occurred, versus 13 total expected thromboembolic events (P = 0.033); 5 major bleedings were observed, versus 7 expected ones, if the patients were under OAC. Considering the combined endpoint (thromboembolic and major bleeding events) 9 events were observed versus 20 expected major events (P = 0.031). In the prespecified subgroup of patients with previous intracranial bleeding, two ischaemic strokes and one transient ischaemic attack were observed during follow-up versus six total expected thromboembolic events; no intracranial bleeding recurrence was recorded. Regarding the combined endpoint four major events were recorded versus nine expected ones. CONCLUSION: LAAO is an efficient and safe option for the prevention of cardioembolic stroke in patients with NVAF, high thromboembolic risk and contraindication to OAC, particularly in patients with previous intracranial bleeding.

[Percutaneous left atrial appendage closure in a patient with atrial fibrillation and Rendu-Osler-Weber disease]. / Chiusura percutanea dell'auricola sinistra in paziente con fibrillazione atriale e malattia di Rendu-Osler-Weber.

Atrial fibrillation is the most common cardiac arrhythmia worldwide and represents a major risk factor for cerebral embolic stroke. The standard therapy in the prevention of stroke is oral anticoagulation therapy (OAT). However, a considerable number of patients are unable to tolerate chronic OAT. Among these are patients with hereditary hemorrhagic telangiectasia. We present the case of a female patient affected by Rendu-Osler-Weber disease and atrial fibrillation with indication to OAT. Because of worsening bleeding episodes, this therapy was discontinued and we decided to perform percutaneous left atrial appendage occlusion (LAAO) with implantation of the WATCHMAN device (Boston Scientific). Post-procedural antithrombotic therapy with clopidogrel 75 mg/day was prematurely interrupted after 3 weeks because of significant bleeding recurrences. After 12 months, the patient is in good health, with rare episodes of minor bleeding. Echocardiography showed a well-positioned LAAO device, without thrombotic apposition. In conclusion, this case confirms that percutaneous LAAO is a valid therapeutic alternative to OAT and represents a successful strategy in high bleeding risk patients with a contraindication to OAT. By thorough assessment, a single antiplatelet therapy after device implantation and for a time-limited period might be considered, according to the latest recent evidence.

Pharmacogenomic Approach to Selecting Antiplatelet Therapy in Patients With Acute Coronary Syndromes: The PHARMCLO Trial.

BACKGROUND: Although clopidogrel is still frequently used in patients with acute coronary syndromes (ACS), its efficacy is hampered by interpatient response variability caused by genetic polymorphisms associated with clopidogrel's metabolism. OBJECTIVES: The goal of this study was to evaluate whether selecting antiplatelet therapy (clopidogrel, prasugrel, or ticagrelor) on the basis of a patient's genetic and clinical characteristics leads to better clinical outcomes compared with the standard of care, which bases the selection on clinical characteristics alone. METHODS: Patients hospitalized for ACS were randomly assigned to standard of care or the pharmacogenomic arm, which included the genotyping of ABCB1, CYP2C19*2, and CYP2C19*17 using an ST Q3 system that provides data within 70 min at each patient's bedside. The patients were followed up for 12 ± 1 month for the primary composite endpoint of cardiovascular death and the first occurrence of nonfatal myocardial infarction, nonfatal stroke, and major bleeding defined according to Bleeding Academic Research Consortium type 3 to 5 criteria. RESULTS: After enrolling 888 patients, the study was prematurely stopped. Clopidogrel was used more frequently in the standard-of-care arm (50.7% vs. 43.3%), ticagrelor in the pharmacogenomic arm (42.6% vs. 32.7%; p = 0.02), and prasugrel was equally used in both arms. The primary endpoint occurred in 71 patients (15.9%) in the pharmacogenomic arm and in 114 (25.9%) in the standard-of-care arm (hazard ratio: 0.58; 95% confidence interval: 0.43 to 0.78; p < 0.001). CONCLUSIONS: A personalized approach to selecting antiplatelet therapy for patients with ACS may reduce ischemic and bleeding events. (Pharmacogenetics of Clopidogrel in Patients With Acute Coronary Syndromes [PHARMCLO]; NCT03347435).

Rapid and portable, lab-on-chip, point-of-care genotyping for evaluating clopidogrel metabolism.

BACKGROUND: Dual antiplatelet therapy with aspirin and a platelet P2Y12 receptor inhibitors (clopidogrel, prasugrel, ticagrelor) is a cornerstone of antithrombotic treatment in patients with acute coronary syndromes (ACS). Clopidogrel has been the standard of care for nearly a decade; however, its clinical efficacy is influenced by a considerable inter-patient variability in response, clearly associated to cytochrome P (CYP) enzyme genetic variations. We used a novel point-of-care lab-on-chip instrument to genotype ACS patients in order to identify carriers of the ATB-binding cassette ABCB1 3435, CYP2C19*2 and CYPC2C19*17 alleles and adjust the pharmacological approach accordingly. METHODS AND RESULTS: Between October 2012 and January 2013, 160 ACS patients were enrolled at the Cardiology Unit of the Ospedale Niguarda Cà Granda and genotyped at the patients' point-of-care using the newly developed Q3 portable real-time PCR instrument, which remarkably scored the CYP2C19*2, CYP2C19*17, and ABCB1 3435 alleles in a time of 70 min from DNA extraction to final genotype calls; concordance with the other gold-standard genotyping techniques was 100%. CONCLUSIONS: The Q3 instrument proved to be as reliable as the current conventional techniques. As genotyping in the ACS setting cannot be delegated to centralised clinical laboratories for reasons of time, genotyping at the patients' bedside provides an opportunity to conduct large-scale randomised trials in order to assess whether adding genotype data to clinical variables improves clinical outcomes.

[Genetic basis of ischemic heart disease. Do women have distinctive characteristics?]. / Le basi genetiche della cardiopatia ischemica. C'è qualcosa di peculiare nelle donne?

More women die every year from cardiovascular disease than men from any other cause. Several fundamental variations have been reported in the mechanisms underlying coronary artery disease, which suggest that its genetic basis varies by gender. Such differences are not limited to gonadal hormones and can be seen in the physiology of atherosclerosis, including plaque components, endothelial function and hemostasis. It is possible to speculate that genetic factors are different in men and women and probably involve biological pathways that have not yet been identified. To date, studies performed by means of the candidate gene approach have identified several genetic variants associated with coronary artery disease in women. However, these scientific data have not been translated into clinical practice. It has recently become possible to search for common gene variants that affect the susceptibility to myocardial infarction on the basis of our knowledge of common single nucleotide polymorphisms and haplotypes across the human genome using genome-wide genotyping technologies. Currently more than 20 gene regions have been associated with ischemic heart disease using this approach. However, so far we do not know several genetic variants differently associated with risk of ischemic heart disease in men and women. A challenge for the near future will therefore be to identify genetic variants that maximally differentiate males from females, and also to identify possible relationships between genes and environment and genes and hormones in both sexes.