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Platelets play crucial roles in the pathophysiology of thrombosis and myocardial infarction. Protein kinase C ε (PKCε) is virtually absent in human platelets and its expression is precisely regulated during human megakaryocytic differentiation. On the basis of what is known on the role of platelet PKCε in other species, we hypothesized that platelets from myocardial infarction patients might ectopically express PKCε with a pathophysiological role in the disease. We therefore studied platelet PKCε expression from 24 patients with myocardial infarction, 24 patients with stable coronary artery disease and 24 healthy subjects. Indeed, platelets from myocardial infarction patients expressed PKCε with a significant frequency as compared to both stable coronary artery disease and healthy subjects. PKCε returned negative during patient follow-up. The forced expression of PKCε in normal donor platelets significantly increased their response to adenosine diphosphate-induced activation and adhesion to subendothelial collagen. Our data suggest that platelet generations produced before the acute event retain PKCε-mRNA that is not down-regulated during terminal megakaryocyte differentiation. Results are discussed in the perspective of peri-infarctual megakaryocytopoiesis as a critical component of myocardial infarction pathophysiology.

We report the case of a 65­-year-old woman admitted for inferior ST-segment elevation myocardial infarction complicated by complete atrioventricular block. The patient was under treatment with a novel oral anticoagulant (NOAC, rivaroxaban) because of a history of recurrent idiopathic pulmonary embolism. Emergency angiography showed complete acute thrombotic occlusion of the right coronary artery. After manual thrombectomy, there was no angiographic evidence of underlying atherosclerosis, therefore no further percutaneous coronary intervention was performed. Subsequent clinical course was uneventful. Laboratory tests demonstrated the presence of a heterozygous mutation of the factor II gene (G20210A), confirming the clinical evidence of a thrombophilic state. As rivaroxaban seemed to be ineffective in preventing spontaneous coronary thrombosis in this patient, antithrombotic therapy was shifted to warfarin plus low-dose aspirin. No further ischemic events occurred during the 1-year follow-up. It can be hypothesized that factor Xa inhibition by NOACs, such as rivaroxaban, could be insufficient in case of a thrombophilic state due to thrombin mutation. A brief review of the current literature on use of NOACs in acute coronary syndromes is also reported.

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.

We report the case of a 34-year-old female treated with radiotherapy and chemotherapy for non-Hodgkin lymphoma at the age of 16. The patient came to our attention because of progressive dyspnea on effort and a positive result on a pharmacologic stress echo test. Coronary angiography revealed focal critical ostial stenosis of the left main coronary artery. Considering the high surgical risk due to possible post-radiation thoracic adherence and the young patient age, she underwent successful stenting of the left main stenosis with drug-eluting stent, followed by an intravascular ultrasound-guided post-dilation and final kissing balloon inflation. The procedure was uncomplicated.Heart diseases are among the frequently seen long-term effects of chemo/radiotherapy used for lymphoma treatment. The pathogenesis of radiation-induced coronary artery disease is complex and not yet fully understood, the mechanism is multifactorial and likely involves direct damage from radiation exposure or mediated by inflammatory cytokine secretion. Surgery management is often challenging due to radiation sequences, and a percutaneous approach is therefore used. The risk of long-term radiotherapy damage depends on radiation dose and the field of exposure. Modern techniques with lower radiation exposure and smaller treatment volumes may reduce these risks in future.

Platelets play crucial roles in the pathophysiology of thrombosis and myocardial infarction. Protein kinase C [epsilon] (PKC[epsilon]) is virtually absent in human platelets and its expression is precisely regulated during human megakaryocytic differentiation. On the basis of what is known on the role of platelet PKC[epsilon] in other species, we hypothesized that platelets from myocardial infarction patients might ectopically express PKC[epsilon] with a pathophysiological role in the disease. We therefore studied platelet PKC[epsilon] expression from 24 patients with myocardial infarction, 24 patients with stable coronary artery disease and 24 healthy subjects. Indeed, platelets from myocardial infarction patients expressed PKC[epsilon] with a significant frequency as compared to both stable coronary artery disease and healthy subjects. PKC[epsilon] returned negative during patient follow-up. The forced expression of PKC[epsilon] in normal donor platelets significantly increased their response to adenosine diphosphate-induced activation and adhesion to subendothelial collagen. Our data suggest that platelet generations produced before the acute event retain PKC[epsilon]-mRNA that is not down-regulated during terminal megakaryocyte differentiation. Results are discussed in the perspective of peri-infarctual megakaryocytopoiesis as a critical component of myocardial infarction pathophysiology.

We report the case of a 65--year-old woman admitted for inferior ST-segment elevation myocardial infarction complicated by complete atrioventricular block. The patient was under treatment with a novel oral anticoagulant (NOAC, rivaroxaban) because of a history of recurrent idiopathic pulmonary embolism. Emergency angiography showed complete acute thrombotic occlusion of the right coronary artery. After manual thrombectomy, there was no angiographic evidence of underlying atherosclerosis, therefore no further percutaneous coronary intervention was performed. Subsequent clinical course was uneventful. Laboratory tests demonstrated the presence of a heterozygous mutation of the factor II gene (G20210A), confirming the clinical evidence of a thrombophilic state. As rivaroxaban seemed to be ineffective in preventing spontaneous coronary thrombosis in this patient, antithrombotic therapy was shifted to warfarin plus low-dose aspirin. No further ischemic events occurred during the 1-year follow-up. It can be hypothesized that factor Xa inhibition by NOACs, such as rivaroxaban, could be insufficient in case of a thrombophilic state due to thrombin mutation. A brief review of the current literature on use of NOACs in acute coronary syndromes is also reported.

Non-ST-elevation acute coronary syndromes (NSTE-ACS) represent one of the most common clinical presentations of ischemic heart disease. Patients with NSTE-ACS are a heterogeneous population, with different clinical features and prognosis. A significant proportion of this population is medically managed, without any revascularization. In the Italian EYESHOT and French FAST-MI registries, patients managed with a conservative strategy were 40% and 35%, respectively. NSTE-ACS patients not undergoing coronary revascularization are at higher risk of adverse cardiovascular events and have a worse prognosis, including short- and long-term mortality, compared with those receiving revascularization. Patients with NSTE-ACS medically managed consist of three different subgroups: those not undergoing coronary angiography, those receiving coronary angiography and without significant coronary artery disease, and those with significant coronary artery disease at angiography but not receiving revascularization. Patients presenting with NSTE-ACS for whom a conservative strategy without coronary angiography is planned should be selected very carefully and coronary angiography should not be denied because of the lack of on-site cath-lab facilities. In addition, advanced age alone, in the absence of severe comorbidities or frailty, should not be considered as a reason for denying coronary angiography and, in general, optimal treatment. Given that evidence-based data are lacking, a careful balance between benefits and risks is needed in the decision to perform or not coronary angiography and/or revascularization in patients with important comorbidities, or frailty, or advanced age. In this decisional process, it should be also taken into consideration the role of coronary anatomy in risk stratification and treatment guidance.NSTE-ACS patients managed without revascularization less frequently receive guideline-recommended pharmacological treatment. Dual antiplatelet therapy is recommended for 12 months also in medically managed patients, after careful balance of ischemic and bleeding risk. Indeed, in this group of patients it is mandatory to optimize pharmacological treatment, including antiplatelet therapy, in order to improve clinical outcome. In NSTE-ACS not undergoing revascularization, the proportion of patients discharged with dual antiplatelet therapy should be increased in comparison to current clinical practice, and the use of ticagrelor instead of clopidogrel should be considered in selected patients.

La fibrillazione atriale è l’aritmia sopraventricolare più frequente nella popolazione e rappresenta il principale fattore di rischio per ictus cardioembolico. Il trattamento standard nella prevenzione di tale complicanza è la terapia anticoagulante orale (TAO). Tuttavia, un numero considerevole di pazienti è caratterizzato da un elevato profilo di rischio emorragico, fra i quali quelli affetti da patologie emorragiche ereditarie come la malattia di Rendu-Osler-Weber.Presentiamo il caso di una paziente, affetta da teleangectasia emorragica ereditaria, con fibrillazione atriale ed indicazione, secondo il CHA2DS2-VASc risk score, alla TAO. La mancata tollerabilità alla terapia, dovuta ad un netto incremento degli episodi emorragici, portava alla sospensione della TAO e all’indicazione ad intervento percutaneo di chiusura dell’auricola sinistra con impianto di dispositivo (WATCHMAN, Boston Scientific). La terapia antitrombotica post-impianto (clopidogrel 75 mg/die) è stata precocemente sospesa dopo 3 settimane a causa della recidiva di sanguinamenti significativi. Dopo 12 mesi, la paziente è in buona salute con rari episodi di sanguinamenti minori ed evidenza ecocardiografica di corretto posizionamento del dispositivo intracardiaco in assenza di apposizioni trombotiche.In conclusione, l’intervento percutaneo di chiusura di auricola si conferma essere una valida e sicura alternativa nei pazienti con fibrillazione atriale ed elevato rischio emorragico controindicante la TAO. Previa approfondita valutazione del rischio/beneficio, riteniamo sia possibile anche considerare una singola terapia antiaggregante dopo impianto del dispositivo, in linea con le ultime recenti evidenze.

The increasing rate of cardiovascular diseases, the improved survival after the acute phase, the aging of the population and the implementation of primary prevention caused an exponential increase in outpatient cardiac performance, thereby making it difficult to maintain a balance between the citizen-patient request and the economic sustainability of the healthcare system. On the other side, the prescription of many diagnostic tests with a view to defensive medicine and the related growth of patients' expectations, has led several scientific societies to educational campaigns highlighting the concept that \"less is more\".The present document is aimed at providing the general practitioner with practical information about a prompt diagnosis of signs/symptoms (angina, dyspnea, palpitations, syncope) of the major cardiovascular diseases. It will also provide an overview about appropriate use of diagnostic exams (echocardiogram, stress test), about the appropriate timing of their execution, in order to ensure effectiveness, efficiency, and equity of the health system.