Current Strategies to Guide the Antiplatelet Therapy in Acute Coronary Syndromes.

The role of antiplatelet therapy in patients with acute coronary syndromes is a moving target with considerable novelty in the last few years. The pathophysiological basis of the treatment depends on platelet biology and physiology, and the interplay between these aspects and clinical practice must guide the physician in determining the best therapeutic options for patients with acute coronary syndromes. In the present narrative review, we discuss the latest novelties in the antiplatelet therapy of patients with acute coronary syndromes. We start with a description of platelet biology and the role of the main platelet signal pathways involved in platelet aggregation during an acute coronary syndrome. Then, we present the latest evidence on the evaluation of platelet function, focusing on the strengths and weaknesses of each platelet's function test. We continue our review by describing the role of aspirin and P2Y12 inhibitors in the treatment of acute coronary syndromes, critically appraising the available evidence from clinical trials, and providing current international guidelines and recommendations. Finally, we describe alternative therapeutic regimens to standard dual antiplatelet therapy, in particular for patients at high bleeding risk. The aim of our review is to give a comprehensive representation of current data on antiplatelet therapy in patients with acute coronary syndromes that could be useful both for clinicians and basic science researchers to be up-to-date on this complex topic.

Clinical Outcomes of Percutaneous Left-Atrial Appendage Occlusion with Conscious Sedation without an Anesthesiologist on Site: Results from a Multicenter Study.

Background and Objectives: Percutaneous left-atrial appendage (LAA) occlusion is an important therapeutic option for preventing cardioembolic stroke in patients with non-valvular atrial fibrillation (AF) at high risk of thromboembolic events and with contraindications for oral anticoagulation (OAC). It is usually performed with transesophageal echocardiography (TOE) guidance under general anesthesia (GA). In this retrospective study, we present a multicenter experience of LAA occlusion performed with conscious sedation (CS) without an anesthesiologist on site. Materials and Methods: All the patients on the waiting list for LAA occlusion procedure at Infermi Hospital, Rivoli, and San Luigi Gonzaga University Hospital, Orbassano, from October 2018 to October 2022 were analyzed. All the procedures were performed with a Watchman/FLX LAA closure device under TOE and fluoroscopic guidance without an anesthesiologist on site. CS was performed with a combination of midazolam and fentanyl as needed. Results: One-hundred fifteen patients were included (age 76.4 ± 7.6 years, median CHA2DS2Vasc 4.4 ± 1.4). CS was performed using midazolam (mean dose 5.9 ± 2.1 mg), adding fentanyl for thirty-nine (33.9%) patients in case of poor tolerance for the procedure despite midazolam. The acute procedural success rate was 99.1%. We observed seven acute severe complications. No patients needed anesthesiological assistance during the procedure, and no cases of respiratory failure necessitating ventilation were reported. In a follow-up after 10 ± 9 months, one case of stroke (0.9%) and one case (0.9%) of transient ischemic attack (TIA) occurred. Conclusions: LAA occlusion performed under CS and without the presence of an anesthesiologist on site appears to be safe and effective. It can be an attractive alternative to general anesthesia (GA), as fewer resources are required.

Interventional Versus Conservative Strategy in Patients With Spontaneous Coronary Artery Dissections: Insights From DISCO Registry.

BACKGROUND: The optimal management of patients with spontaneous coronary artery dissection remains debated. METHODS: Patients enrolled in the DISCO (Dissezioni Spontanee Coronariche) Registry up to December 2020 were included. The primary end point was major adverse cardiovascular events, a composite of all-cause death, nonfatal myocardial infarction, and repeat percutaneous coronary intervention (PCI). Independent predictors of PCI and medical management were investigated. RESULTS: Among 369 patients, 129 (35%) underwent PCI, whereas 240 (65%) were medically managed. ST-segment-elevation myocardial infarction (68% versus 35%, P<0.001), resuscitated cardiac arrest (9% versus 3%, P<0.001), proximal coronary segment involvement (32% versus 7%, P<0.001), and Thrombolysis in Myocardial Infarction flow 0 to 1 (54% versus 20%, P<0.001) were more frequent in the PCI arm. In-hospital event rates were similar. Between patients treated with PCI and medical therapy, there were no differences in terms of major adverse cardiovascular events at 2 years (13.9% versus 11.7%, P=0.467), all-cause death (0.7% versus 0.4%, P=0.652), myocardial infarction (9.3% versus 8.3%, P=0.921) and repeat PCI (12.4% versus 8.7%, P=0.229). ST-segment-elevation myocardial infarction at presentation (odds ratio [OR], 3.30 [95% CI, 1.56-7.12]; P=0.002), proximal coronary segment involvement (OR, 5.43 [95% CI, 1.98-16.45]; P=0.002), Thrombolysis in Myocardial Infarction flow grade 0 to 1 and 2 (respectively, OR, 3.22 [95% CI, 1.08-9.96]; P=0.038; and OR, 3.98 [95% CI, 1.38-11.80]; P=0.009) and luminal narrowing (OR per 5% increase, 1.13 [95% CI, 1.01-1.28]; P=0.037) were predictors of PCI, whereas the 2B-angiographic subtype predicted medical management (OR, 0.25 [95% CI, 0.07-0.83]; P=0.026). CONCLUSIONS: Clinical presentation and procedural variables drive the choice of the initial therapeutic approach in spontaneous coronary artery dissection. If PCI is needed, it seems to be associated with a similar risk of short-to-mid-term adverse events compared to medical treatment. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04415762.

[Spontaneous coronary artery dissection: update on treatment and strategies to improve the diagnostic and therapeutic pathway]. / La dissezione coronarica spontanea: update sul trattamento e sulle strategie per migliorare il percorso diagnostico-terapeutico.

Spontaneous coronary dissection is an infrequent cause of acute coronary syndrome, which has been understood only recently in terms of pathophysiology, presentation, diagnosis and treatment. In particular, new evidence has emerged on its treatment in the interventional and medical fields, especially on the management of antiplatelet therapy, which is presented in this review; moreover, the local experience of the registry of spontaneous coronary dissections DISCO and its role in improving the management of these patients are reported.

Epilepsy and syncope - A case report and narrative review of arrhythmias connected to temporal lobe epilepsy.

We present the case of a 28-years-old male presenting to the Emergency Department for relapsing episodes of "déjà vu" and syncope. After a diagnostic workup by a multidisciplinary team, the simultaneous EEG and ECG monitoring showed an asystole associated with EEG anomalies in right fronto-temporal region of the brain. The brain MRI revealed an ischemic lesion concordant with EEG anomalies. In the suspicion of an ictal asystole, we decided not to implant a permanent pacemaker as the first line therapy but started a targeted anti-epileptic therapy. No more syncopal episodes nor dysrhythmias occurred during recovery and almost two years follow-up.

[Management of ST-elevation myocardial infarction in a patient with aspirin hypersensitivity without oral P2Y12 inhibitors]. / Gestione dell'infarto miocardico con sopraslivellamento del tratto ST in un paziente con ipersensibilità all'aspirina senza l'uso di inibitori orali del recettore P2Y12.

Aspirin hypersensitivity is a neglected issue, especially in the setting of ST-elevation myocardial infarction (STEMI). Nevertheless, in such context a prompt platelet inhibition remains crucial. We report the case of a patient presenting with STEMI, aspirin hypersensitivity and emesis causing inadequate intake of P2Y12 inhibitors managed with intravenous cangrelor therapy and aspirin desensitization. Possible options in the management of aspirin hypersensitivity in the acute phase are discussed. In selected patients with STEMI and aspirin hypersensitivity, particularly in the suspect of suboptimal enteric absorption of P2Y12 inhibitors, the use of cangrelor until aspirin desensitization is completed can be considered; bridge therapy to desensitization with glycoprotein IIb/IIIa inhibitors can be considered on a case by case basis, despite the scarce supporting evidence - bridge therapy with indobufen is not recommended due to the limited literature data.

Gender Differences in the Presentation and Outcomes of Hospitalized Patients With COVID-19.

Gender-related differences in COVID-19 clinical presentation, disease progression, and mortality have not been adequately explored. We analyzed the clinical profile, presentation, treatments, and outcomes of patients according to gender in the HOPE-COVID-19 International Registry. Among 2,798 enrolled patients, 1,111 were women (39.7%). Male patients had a higher prevalence of cardiovascular risk factors and more comorbidities at baseline. After propensity score matching, 876 men and 876 women were selected. Male patients more often reported fever, whereas female patients more often reported vomiting, diarrhea, and hyposmia/anosmia. Laboratory tests in men presented alterations consistent with a more severe COVID-19 infection (eg, significantly higher C-reactive protein, troponin, transaminases, lymphocytopenia, thrombocytopenia, and ferritin). Systemic inflammatory response syndrome, bilateral pneumonia, respiratory insufficiency, and renal failure were significantly more frequent in men. Men more often required pronation, corticosteroids, and tocilizumab administration. A significantly higher 30-day mortality was observed in men vs women (23.4% vs 19.2%; P = .039). Trial Numbers: NCT04334291/EUPAS34399.

Does there exist an obesity paradox in COVID-19? Insights of the international HOPE-COVID-19-registry.

BACKGROUND: Obesity has been described as a protective factor in cardiovascular and other diseases being expressed as 'obesity paradox'. However, the impact of obesity on clinical outcomes including mortality in COVID-19 has been poorly systematically investigated until now. We aimed to compare clinical outcomes among COVID-19 patients divided into three groups according to the body mass index (BMI). METHODS: We retrospectively collected data up to May 31st, 2020. 3635 patients were divided into three groups of BMI (<25 kg/m2; n = 1110, 25-30 kg/m2; n = 1464, and >30 kg/m2; n = 1061). Demographic, in-hospital complications, and predictors for mortality, respiratory insufficiency, and sepsis were analyzed. RESULTS: The rate of respiratory insufficiency was more recorded in BMI 25-30 kg/m2 as compared to BMI < 25 kg/m2 (22.8% vs. 41.8%; p < 0.001), and in BMI > 30 kg/m2 than BMI < 25 kg/m2, respectively (22.8% vs. 35.4%; p < 0.001). Sepsis was more observed in BMI 25-30 kg/m2 and BMI > 30 kg/m2 as compared to BMI < 25 kg/m2, respectively (25.1% vs. 42.5%; p = 0.02) and (25.1% vs. 32.5%; p = 0.006). The mortality rate was higher in BMI 25-30 kg/m2 and BMI > 30 kg/m2 as compared to BMI < 25 kg/m2, respectively (27.2% vs. 39.2%; p = 0.31) (27.2% vs. 33.5%; p = 0.004). In the Cox multivariate analysis for mortality, BMI < 25 kg/m2 and BMI > 30 kg/m2 did not impact the mortality rate (HR 1.15, 95% CI: 0.889-1.508; p = 0.27) (HR 1.15, 95% CI: 0.893-1.479; p = 0.27). In multivariate logistic regression analyses for respiratory insufficiency and sepsis, BMI < 25 kg/m2 is determined as an independent predictor for reduction of respiratory insufficiency (OR 0.73, 95% CI: 0.538-1.004; p = 0.05). CONCLUSIONS: HOPE COVID-19-Registry revealed no evidence of obesity paradox in patients with COVID-19. However, Obesity was associated with a higher rate of respiratory insufficiency and sepsis but was not determined as an independent predictor for a high mortality.

Strange case of biventricular heart failure.

Acute heart failure (HF) is commonly caused by a cardiomyopathy with one or more precipitating factor. Here, a case in which a cardiomyopathy is precipitated by pulmonary embolism (PE). A 77-year-old man is admitted for breathlessness and leg swelling. A mild reduction of left ventricular (LV) ejection fraction is found, with moderately increased LV wall thickness and pulmonary hypertension; clinical examination revealed signs of congestion with bilateral leg swelling, and mild signs of left HF with the absence of pulmonary congestion on chest X-ray. The ECG showed Mobitz I second-degree atrioventricular block. The clinical scenario led us to the diagnosis of infiltrative cardiomyopathy due to cardiac amyloidosis (CA) precipitated by PE. Pulmonary embolism is an overlooked precipitant of HF and can be the first manifestation of an underlying misdiagnosed cardiomyopathy, especially CA. 3,3-Diphosphono-1,2-propanodicarboxylic acid scan is a cornerstone in the diagnosis of Transthyretin amyloidosis (ATTR) cardiac amyloidosis.

Efficacy and Safety of Clopidogrel, Prasugrel and Ticagrelor in ACS Patients Treated with PCI: A Propensity Score Analysis of the RENAMI and BleeMACS Registries.

INTRODUCTION: Real-life data comparing clopidogrel, prasugrel, and ticagrelor for unselected patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) are lacking, as are data for the temporal distribution of ischemic and bleeding risks. METHODS: A total of 19,825 patients were enrolled from the RENAMI and BleeMACS registries. Both were multicenter, retrospective, observational registries including the data and outcomes of consecutive patients with ACS who underwent primary PCI and were discharged with dual antiplatelet therapy (DAPT). We evaluated the long-term outcome stratified by the different antiplatelet agents. RESULTS: A total of 14,105 patients (71.2%) were treated with clopidogrel, 2364 patients (11.9%) with prasugrel and 3356 patients (16.9%) with ticagrelor. After propensity score matching, at 1 year, prasugrel reduced the incidence of net adverse clinical events (NACE; a composite endpoint of all-cause death, myocardial infarction [MI] and Bleeding Academic Research Consortium [BARC] 3-5 bleeding) (4.2% vs.7.6%, p = 0.002) and of major adverse cardiovascular events (MACE; a composite endpoint of death and MI) compared with clopidogrel (2.6% vs. 5.2%, p = 0.007). Ticagrelor decreased rates of MACE compared with clopidogrel (2.7% vs. 6.2%, p < 0.001), but not of NACE (6.6% vs. 8.7%, p = 0.07). Ticagrelor presented similar performance in terms of MACE compared with prasugrel (2.8% vs. 2.4%, p = 0.56), with a trend towards a reduction in MI (0.2% vs. 0.4%, p = 0.56), but with higher risk of BARC 3-5 bleedings (3.8% vs. 1.7%, p = 0.04). In the daily risk analysis, clopidogrel presented a binomial distribution with a peak of ischemic risk at 3 months, which decreased towards bleedings; prasugrel had a constant equivalence between opposite risks; and ticagrelor constantly reduced recurrent MIs despite higher risk of BARC 3-5 events. CONCLUSION: In real life, ticagrelor is more effective in reducing ischemic events during the first year after ACS, despite an increased risk of major bleedings, while prasugrel assures a better balance between ischemic and bleeding recurrent events.

Average daily ischemic versus bleeding risk in patients with ACS undergoing PCI: Insights from the BleeMACS and RENAMI registries.

BACKGROUND: The risk of recurrent ischemia and bleeding after percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) may vary during the first year of follow-up according to clinical presentation, and medical and interventional strategies. METHODS: BleeMACS and RENAMI are 2 multicenter registries enrolling patients with ACS treated with PCI and clopidogrel, prasugrel, or ticagrelor. The average daily ischemic and bleeding risks (ADIR and ADBR) in the first year after PCI were the primary end points. The difference between ADBR and ADIR was calculated to estimate the potential excess of bleeding/ischemic events in a given period or specific subgroup. RESULTS: A total of 19,826 patients were included. Overall, in the first year after PCI, the ADBR was 0.008085%, whereas ADIR was 0.008017% (P = .886). In the first 2 weeks ADIR was higher than ADBR (P = .013), especially in patients with ST-segment elevation myocardial infarction or incomplete revascularization. ADIR continued to be, albeit non-significantly, greater than ADBR up to the third month, whereas ADBR became higher, although not significantly, afterward. Patients with incomplete revascularization had an excess in ischemic risk (P = .003), whereas non-ST-segment elevation ACS patients and those on ticagrelor had an excess of bleeding (P = .012 and P = .022, respectively). CONCLUSIONS: In unselected ACS patients, ADIR and ADBR occurred at similar rates within 1 year after PCI. ADIR was greater than ADBR in the first 2 weeks, especially in ST-segment elevation myocardial infarction patients and those with incomplete revascularization. In the first year, ADIR was higher than ADBR in patients with incomplete revascularization, whereas ADBR was higher in non-ST-segment elevation ACS patients and in those discharged on ticagrelor.

Daily risk of adverse outcomes in patients undergoing complex lesions revascularization: A subgroup analysis from the RAIN-CARDIOGROUP VII study (veRy thin stents for patients with left mAIn or bifurcatioN in real life).

INTRODUCTION: Percutaneous coronary intervention (PCI) for complex lesions, including unprotected left main (ULM) and bifurcations, is gaining a relevant role in treating coronary artery disease with good outcomes, also thanks to new generation stents. The daily risk of adverse cardiovascular events and their temporal distribution after these procedures is not known. METHODS: All consecutive patients presenting with a critical lesion of ULM or bifurcation treated with very thin struts stents, enrolled in the RAIN-Cardiogroup VII study, were analyzed. The daily risk of major acute cardiovascular events (MACE), target lesion revascularization (TLR) and stent thrombosis (ST) and their temporal distribution in the first year of follow-up was the primary endpoint. Differences among subgroups (ULM, patient presentation, kind of stent polymer) were the secondary endpoint. RESULTS: 2745 patients were included, mean age 68 ±â€¯11 years, 33.3% diabetics, 54.5% had an acute coronary syndrome (ACS); 88.5% of treated lesions were bifurcations, 27.2% ULM. Average daily risk was 0.022% for MACE, 0.005% for TLR and 0.004% for ST, in the first year. Bimodal distribution of adverse events, especially TLR, with an early peak in the first 50 days and a late one after 150 days, was observed. Patients with ULM presented a significantly higher daily risk of events, and ACS patients presented higher MACE risk. No difference emerged according to the type of stent polymer. CONCLUSIONS: The daily risk of adverse events in the first year after complex PCI in our study is acceptably low. PCI on ULM carries a higher risk of complications.

Impact of Final Kissing Balloon and of Imaging on Patients Treated on Unprotected Left Main Coronary Artery With Thin-Strut Stents (From the RAIN-CARDIOGROUP VII Study).

Few data are available about the impact on outcomes of procedural strategies for percutaneous coronary intervention with thin-struts stents on unprotected left main (ULM): 792 patients with an ULM stenosis treated with percutaneous coronary intervention with thin-strut stents were enrolled in the present multicenter registry. Target lesion revascularization (TLR) was the primary end point. MACE (a composite of all-cause death, myocardial infarction, TLR, and stent thrombosis) and its single components, along with target vessel revascularization were the secondary end points. Subgroup analyses were performed according to complex versus noncomplex bifurcation lesions. After 16 months, 5.5% of patients experienced a TLR. At multivariate analysis, provisional stenting (odds ratio [OR] 0.46: 0.85 to 0.23, p = 0.006), use of imaging (OR 0.45: 0.23 to 0.98, p = 0.003) and final kissing balloon (FKB) (OR 0.41: 0.83 to 0.21, p = 0.001) reduced risk of TLR. FKB reduced risk of overall TLR only for 2 stents-strategy (6.2% vs 32.4%, p <0.05), but not for provisional strategy (3.8% vs 3.7%, p = 0.67). Intracoronary imaging reduced risk of overall TLR both for provisional (2.2% vs 5.4%) and for 2-stents strategy (7.3% vs 14.1% p <0.05 for both, all confidence interval 95%). In conclusion, TLR for ULM patients treated with thin-strut stents is infrequent. Provisional stenting was noninferior compared with 2-stents apart from complex lesions. Benefit from intracoronary imaging is consistent for different strategies, whereas that from FKB persists only for 2-stents.

Does asymptomatic recurrent diffuse capillary C4d complement deposition impair cardiac allograft function?

BACKGROUND: The aim of this study was to evaluate whether asymptomatic recurrent (≥2) antibody-mediated rejection (pAMR 1+), defined as diffuse capillary C4d immunostaining (rAMR) on endomyocardial biopsies (EMBs), during the first year after heart transplantation impairs left ventricular (LV) function. METHODS: Fifty-four consecutive heart transplant patients who survived well (New York Heart Association ≤2 and EF≥55%) the first month after transplantation were enrolled and prospectively underwent 490 echocardiographies and EMB. Asymptomatic rAMR without histopathologic findings was evaluated as a risk factor for deterioration of graft function. Primary endpoint, assessed 1 year after transplantation, was development of LV dysfunction and/or adverse remodeling according to pre-specified echo parameters. RESULTS: During the first year from transplantation, rAMR occurred in five patients. Recurrent AMR was associated with a significant higher risk to develop LV concentric hypertrophy (OR 3.6, 95% CI: 1.8-7.0, P=.02) or reduced lateral S' peak velocity (OR 2.3, 95% CI: 1.5-3.6, P=.03). Patients with rAMR showed significative adverse graft remodeling (ΔLV end-diastolic volume: +16±12.3 vs -0.2±14.4 mL; P=.02) and deterioration of graft function (Δlateral S' peak velocity: -3.3±3 vs -0.4±2.9 cm/s; P=.03). CONCLUSIONS: Recurrent asymptomatic diffuse capillary C4d immunostaining may play a role in the early development of cardiac allograft adverse remodeling and dysfunction.