Search

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.

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. However, a considerable number of patients are unable to support chronic OAC. Among these are patients with hereditary hemorrhagic telangiectasia. We present a case of a female patient affected by Rendu-Osler- Weber disease who developed permanent atrial fibrillation with a CHA2DS2-VASc risk score of three. OAC was indicated despite her high bleeding risk. Therefore, an increase of muco-cutaneous and nose bleedings (BARC 2) with several admissions to the Emergency Department and multiple cauterizations influenced a worsening of her quality of life. On that basis OAC was discontinued. After a multidisciplinary evaluation, we decided to perform percutaneous intervention of left atrial appendage closure with implantation of Watchman device. As anti-platelet post procedural therapy, considering her high bleeding risk, we adopted single anti-thrombotic strategy with clopidogrel 75 mg/die, discontinued after three weeks due to increasing in recurrent nosebleeds, needed another cauterization. After 12 month follow up, the patient is in good health, with rare episodes of minor bleedings and a successful and well positioning of the intra-cardiac device, without thrombotic apposition, was evidenced at following echocardiographic examinations. In conclusion percutaneous intervention of LAA closure is confirmed to be an alternative and successful strategy in high bleeding risk patient with a contraindication to OAC. By thorough assessment, a single anti-thrombotic therapy with clopidogrel 75 mg/die, after device implantation and for a time-limited

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.

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.

NSTE-ACS patients are a heterogeneous population, with different clinical features and prognosis. A large proportion of them is medically managed, without any revascularization. In the EYSHOT and FAST-MI registries such patients were 40% and 35%, respectively. These patients are at higher risk of adverse cardiovascular events and have a worse prognosis compared with those receiving revascularization. Medically managed NSTE-ACS patients consist of different subgroups: those not undergoing coronary angiography, those without significant coronary artery disease, and those with coronary stenoses not referred to revascularization. Patients with NSTE-ACS for whom a conservative strategy without coronary angiogram is planned must be very carefully selected. In patients with comorbidities, frailty, or advanced age, a careful balance between benefits and risks is needed to choice the management strategy (perform or not coronary angiography and/or revascularization), as evidence-based medicine data are lacking in the setting of frailty and comorbidities. 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 (DAPT) is recommended for 12months also in medically managed patients, after careful balancing of ischemic and bleeding risk. In these patients it is mandatory to optimize pharmacological treatment, including antiplatelet therapy, to improve outcome. In NSTE-ACS medically managed, the proportion of patients discharged with DAPT should be increased in comparison with current practice, and the use of ticagrelor in place of clopidogrel should be considered in selected patients.

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.

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.

Background— It is known that a significant number of patients experiencing an acute myocardial infarction have normal coronary arteries or nonsignificant coronary disease at coronary angiography (CA). Computed tomography coronary angiography (CTCA) can identify the presence of plaques, even in the absence of significant coronary stenosis. This study evaluated the role of 64-slice CTCA in detecting and characterizing coronary atherosclerosis in these patients. Methods and Results— Consecutive patients with documented acute myocardial infarction but without significant coronary stenosis at CA underwent late gadolinium-enhanced magnetic resonance and CTCA. Only the 50 patients with an area of myocardial infarction identified by late gadolinium-enhanced magnetic resonance were included in the study. All of the coronary segments were assessed for the presence of plaques. CTCA identified 101 plaques against the 41 identified by CA: 61 (60.4%) located in infarct-related arteries (IRAs) and 40 (39.6%) in non-IRAs. In the IRAs, 22 plaques were noncalcified, 17 mixed, and 22 calcified; in the non-IRAs, 5 plaques were noncalcified, 8 mixed, and 27 calcified ( P =0.005). Mean plaque area was greater in the IRAs than in the non-IRAs (6.1±5.4 mm 2 versus 4.2±2.1 mm 2 ; P =0.03); there was no significant difference in mean percentage stenosis (33.5%±14.6 versus 31.7%±12.2; P =0.59), but the mean remodeling index was significantly different (1.25±0.41 versus 1.08±0.21; P =0.01). Conclusions— CTCA detects coronary plaques in nonstenotic coronary arteries that are underestimated by CA, and identifies a different distribution of plaque types in IRAs and non-IRAs. It may therefore be valuable for diagnosing coronary atherosclerosis in acute myocardial infarction patients without significant coronary stenosis.

Background An inherited predisposition is an important factor in the etiology of myocardial infarction (MI) at a young age. However, the extent of the risk for early-onset MI in relatives of young patients is still unclear, due to the paucity of family history data. Hence familial aggregation of early-onset MI was investigated in a cohort of relatives of Italian patients who had survived MI who occurred at the age of 45 or earlier. Methods In the framework of a case–control study, lifetime data and early-onset MI status for 11,696 relatives of cases and 8897 relatives of controls were collected using a standardized questionnaire. Results Occurrence of early-onset MI in females was very uncommon (Kaplan–Meier risk = 0.6%, 95% confidence interval (CI): 0.38–0.82%, for female case relatives), and significantly lower than that for male case relatives (5.0%, 95% CI: 4.41–5.56%). The hazard ratio (HR) for case relatives was approximately 3-fold greater than that for control aunts (taken as reference category). Risk for early-onset MI to siblings (HR = 1.7, 95% CI: 1.33–2.18) was significantly different from that to parents (HR = 0.9, 95% CI: 0.71–1.16). The familial risk ratio λ R was 2.6 (95% CI: 2.30–2.89) for case relatives, using control parents as reference population for early-onset MI risk estimates (i.e. 37 per 100,000 in fathers and 7 per 100,000 in mothers). Conclusion We evaluated the risk of early-onset MI by category of relatives, obtaining evidence for familial aggregation of the disease in this Italian sample and providing figures for genetic counselling and planning genetic epidemiological studies.

Background— It is known that 9% to 31% of women and 4% to 14% of men with acute myocardial infarction have normal coronary arteries or nonsignificant coronary disease at angiography. These patients represent a diagnostic and therapeutic challenge. Multislice computed tomography (CT) can noninvasively identify the presence of coronary plaques even in the absence of significant coronary artery stenosis. This study evaluated the role of 64-slice CT, in comparison with coronary angiography, in detecting and characterizing coronary atherosclerosis in patients with acute myocardial infarction without significant coronary artery stenosis. Methods and Results— Thirty consecutive patients with acute myocardial infarction but without significant coronary stenosis at coronary angiography underwent 64-slice CT. All coronary segments were quantitatively analyzed by means of coronary angiography (CA-QCA) and 64-slice CT (CT-QCA). Forty-seven (10.4%) of the 450 coronary segments were not evaluable by CT. The mean proximal reference diameters at CT-QCA and CA-QCA were, respectively, 2.88�0.75 mm and 2.65�0.9 mm; the overall correlation between CT-QCA and CA-QCA for quantification of reference diameter was r s =0.77; P s =0.11; P =0.03. Overall CT-QCA showed the presence of 50 plaques, of which only 11 were detected by CA-QCA. CT-QCA identified 25 plaques in infarct-related coronary arteries. Positive remodeling was present in 38 of the 50 plaques (76%), with a higher prevalence in the coronary plaques not visualized by CA-QCA (82.1% versus 54.5%). Conclusions— CT-QCA correlates well with CA-QCA in terms of coronary reference diameter analysis, but not stenosis quantification. Multislice CT can detect coronary atherosclerotic plaques in segments of nonstenotic coronary arteries that are underestimated by CA and may have an incremental diagnostic value for the diagnosis of acute myocardial infarction in patients without significant coronary stenosis at CA.

Dissertação de Mestrado Integrado em Medicina Veterinária Perante a suspeita de intoxicação aguda, a abordagem célere e sistemática ao doente, permite uma rápida prestação de cuidados específicos. A triagem, recolha da história clínica, avaliação e intervenção médica de urgência, o diagnóstico e a terapêutica são processos chave nessa abordagem. O diagnóstico, por norma, é suportado por um painel analítico inicial. O recurso a testes imediatos (“point of care”), permite avaliar não só a condição geral dos doentes em tempo real, mas também os efeitos que os xenobióticos possam ter a nível orgânico e que se traduzam, nomeadamente, em alterações do equilíbrio hidroeletrólitico e estado ácido base. O presente estudo pretendeu avaliar as alterações analíticas, detetadas através da ferramenta ePOC (“Enterprise Point of Care”), em animais suspeitos de intoxicação por inseticidas anticolinesterásicos e a sua eventual influência no diagnóstico e implementação da terapêutica. A amostra estudada consistiu em 14 canídeos, que na triagem médica apresentavam sintomas inespecíficos e outros compatíveis com intoxicação aguda por insecticidas anticolinesterásicos: tremores musculares (93%), hipersiália (64%), hipertermia (57%), cianose (50%), diarreia (57%) e vómito (36%). Foram colhidas amostras de sangue para a realização do teste ePOC e para ulterior análise toxicológica.Os resultados obtidos através do ePOC mostraram diminuição da pressão parcial de dióxido de carbono (pCO2) (64%), aumento da concentração de lactato (36%), aumento dos valores de hemoglobina e hematócrito (50%), hiperglicémia (36%) e aumento dos valores de creatinina (50%), não havendo, contudo, relação estatisticamente significativa entre as variáveis testadas e o diagnóstico toxicológico (p>0.05). Porém, em todos os animais considerados acidémicos houve detecção de compostos do grupo dos inseticidas anticolinesterásicos na análise toxicológica. O estudo clínico individualizado de cada caso permitiu verificar que, apesar da sintomatologia similar, os animais apresentavam distúrbios ácido-base diferentes, sendo por isso também necessária uma abordagem terapêutica diferenciada, fulcral especialmente em condições críticas. Estudos futuros, com uma amostra de maior dimensão e preferencialmente com exposição a diferentes xenobióticos, poderão permitir uma avaliação mais exata e abrangente da relação entre a etiologia das intoxicações e as alterações hidroeletrolíticas e de gases sanguíneas verificadas. ABSTRACT - Clinical Approach to Poisoning in Canidae by Anticholinesterase Insecticides and use of immediate tests (Point of Care) - Faced with a suspected acute intoxication, a prompt and systematic approach to the patient, allows a fast provision of specific care. The triage, history taking, assessment and emergency medical intervention, diagnosis and treatment are key processes in this approach. The diagnosis is usually supported by an initial analytic panel. The use of immediate testing ("point of care"), allows the evaluation, not only of the patient’s general condition in real time, but also the effects that xenobiotics may have at an organic level, which may result in electrolyte and acid base disorders. The presente study intended to evaluate the analytical changes detected by ePOC ("Enterprise Point of Care") in animals suspected of poisoning by anticholinesterase insecticides and their possible influence on the diagnostic and therapeutic implementation. The sample consisted of 14 canines, which had nonspecific symptoms and other compatible with acute poisoning by anticholinesterase insecticides: muscle tremors (93%), hypersialia (64%), fever (57%), cyanosis (50%), diarrhea (57%) and vomiting (36%). Blood samples were collect to perform ePOC testing and for further toxicological analysis. Analytical changes (ePOC) showed a decreased partial pressure of carbon dioxide (pCO2) (64%), an increased lactate concentration (36%), na increase in hemoglobin and hematocrit levels (50%), hyperglycemia (36%) and an increased serum creatinine values (50%), without, however, statistically significant relationship between the variables tested and toxicological diagnosis (p> 0.05). Nevertheless, in all animals considered acidemic, toxicological analysis showed the detection of anticholinesterase insecticides. The individualized clinical study of each case has shown, that despite the similar symptoms, the animals had different acid-base disorders and is, therefore, also required a different therapeutic approach, especially in critical conditions. Further studies with a larger sample and preferably with exposure to different xenobiotics may allow a more accurate and comprehensive evaluation of the relationship between the etiology of poisoning and blood gas and electrolyte changes observed.

We thank Opolski et al for their comments and appreciate their interest in our study.1 They raise several points, which we address below. As the authors note, coronary atherosclerosis is a common finding also in asymptomatic patients; indeed, we think that, in the special setting of patients with acute myocardial infarction proven by cardiac magnetic resonance imaging and without significant coronary stenosis, coronary atherosclerosis is often underestimated because of an apparently normal coronary angiogram. As a consequence, the diagnosis may be challenged, and patients may not receive an adequate secondary prevention therapy. The mechanisms of myocardial infarction in this setting are certainly multiple and are not related exclusively to atherosclerosis, but we think that the different distributions of …

To assess the predictive value of CT coronary angiography (CT-CA) in the stratification of patients with acute chest pain.We enrolled 48 patients (31 males and 17 females, mean age 61.0 +/- 14yrs) with acute chest pain of suspected coronary origin, without diagnostic alterations of the ECG and/or increase of the myocardial biomarkers. Sixty-four slice CT-CA was performed within 48-72 hours. Depending on the clinical judgment, the patients were dismissed or underwent conventional coronary angiography (CAG). Patients underwent clinical follow-up at 6 months, recording the prevalence of major cardiovascular events.One patient was excluded from the analysis because of poor image quality. CT-CA showed no coronary artery disease in 38.3% (18/47) of the patients, no significant coronary artery disease (50% lumen reduction) in 31.9% (15/47) of the patients, significant coronary artery disease (or = 50% lumen reduction) in 29.8% (14/47) of the patients. In 87.2% (41/47) of the patients no indication for CAG was present. In 6 (12,8%) patients with significant stenosis at CT-CA indication for CAG was present. In 50% (3/6) of these patients, CAG showed no significant coronary artery disease and in the remaining 50%(3/6) CAG was followed by percutaneous coronary angioplasty. At follow-up no major cardiovascular events were observed.CT-CA showed high sensitivity for the detection of significant coronary artery disease and a negative predictive value at 6-month follow-up.

Antiplatelet therapy is the cornerstone of treatment for patients with acute coronary syndromes in the acute phase and in long-term management. Over the last few years, new antiplatelet drugs have been developed and the therapeutic landscape has rapidly evolved.We review the available evidence and most recent data concerning all of the principal classes of antiplatelet agents, including aspirin, thienopyridines and glycoprotein IIb/IIIa inhibitors, as well the impact of the new drugs prasugrel and ticagrelor and the available data concerning cangrelor, elinogrel and PAR-1 inhibitors (still under development).This review considers the management of antiplatelet therapy in the light of recent advances, highlighting how to identify patients who will receive the greatest benefit from the older and newer agents, and underscoring the importance of carefully balancing the risks of ischaemia and bleeding in order to improve clinical outcomes. Finally, the paper discusses the potential role of functional and genetic tests in guiding the choice of antiplatelet therapy in a future perspective of 'personalised medicine'.

To evaluate the diagnostic accuracy of 64-slice computed tomography (CT) coronary angiography (CA) for the detection of significant coronary artery stenosis (or = 50% lumen reduction) as compared to invasive coronary angiography (ICA) in a population of patients with chest pain and high risk.44 patients (30 male; mean age 60.2+/- 12.1 yrs) with chest pain were prospectively enrolled. In patients with heart rateor = 70 bpm an oral dose of 100 mg of beta-blocker was administered. For CT-CA (Sensation 64, Siemens, Germany) an intravenous bolus of 100 ml of iodinated contrast material (Iomeron 400, Bracco, Italy) was injected. The average scan time was 13.3 +/- 0.9s. Two observers evaluated CT-CA vs. ICA as a reference standard for the detection of significant (or = 50% lumen reduction) coronary artery stenosis.ICA demonstrated the absence of coronary artery disease (CAD) in 13.6% of the patients (6/44), the presence of non significant CAD 4.6% (2/44), single vessel disease in 27.2% (12/44) and multi-vessel disease in 54.6% (24/44) of the patients. None of the patients was excluded from the study population. Ninety-three significant obstructive coronary lesions were observed. Sensitivity, specificity, positive and negative predictive value of CT-CA were 98.6% (70/71), 92.4% (97/105), 89.7% (70/78) and 99% (97/98), respectively. All patients with at least one significant coronary lesion were correctly identified by CT-CA.CT-CA is a reliable alternative to ICA in a selected population of patients with chest pain and high risk.

Background and objective Type 2 diabetes and increase in body mass index (BMI) are major risk factors for myocardial infarction. Recently the common variant rs9939609 in the fat mass and obesity-associated (FTO) gene was reported to associate with type 2 diabetes only through an effect on body mass index (BMI). In the present study we investigated whether rs9939609 variant in the FTO gene is directly associated with early-onset myocardial infarction. Method The Italian genetic study of early-onset myocardial infarction is a nationwide prospective case-control study involving 1842 patients hospitalised for a first myocardial infarction before the age of 45 years, and 1842 healthy subjects matched for age, gender and geographical origin. The following baseline data were collected for each case and control: age, gender, family history, body mass index, smoking habits, hypertension, hypercholesterolemia, diabetes, cocaine use, physical activity and alcohol consumption. Genotyping was performed using a Sequenome MassARRAY platform. Results The rs9939609 variant in FTO gene was significantly associated with early-onset myocardial infarction (odds ratio 1,25, 95% confidence interval 1.08 to 1.45; p=0.000015) with a multiplicative model of the effect. After adjusting for diabetes, BMI, hypercholesterolemia and smoking the rs9939609 risk allele was still significantly associated with early-onset myocardial infarction (odds ratio 1.20, 95% confidence interval 1.05–1.38; p=0.006), thus indicating that this variant has a direct effect on myocardial infarction, not mediated by BMI. As previously reported FTO genotype was also associated with an increase in BMI, more specifically the p-value of no association in the control group is equal to 0,01. Conclusions The rs9939609 variant in the FTO gene was significantly associated with the risk of early-onset myocardial infarction and with the increase in BMI. The rs9939609 variant in the FTO gene directly influences the risk of early-onset myocardial infarction.

Purpose. This study was done to evaluate the diagnostic accuracy of 64-slice computed tomography coronary angiography (CTCA) for the detection of significant coronary artery stenosis in the real clinical world. Materials and methods. From the CTCA database of our institution, we enrolled 145 patients (92 men, 52 women, mean age 63.4 +/- 10.2 years) with suspected coronary artery disease. All patients presented with atypical or typical chest pain and underwent CTCA and conventional coronary angiography (CA). For the CTCA scan (Sensation 64, Siemens, Germany), we administered an IV bolus of 100 ml of iodinated contrast material (Iomeprol 400 mgI/ml, Bracco, Italy). The CTCA and CA reports used to evaluate diagnostic accuracy adopted >= 50% and >= 70%, respectively, as thresholds for significant stenosis. Results. Eleven patients were excluded from the analysis because of the nondiagnostic quality of CTCA. The prevalence of disease demonstrated at CA was 63% (84/134). Sensitivity, specificity and positive and negative predictive values for CTCA on a per-segment, per-vessel, and per-patient basis were 75.6%, 85.1%, 97.6%; 86.9%, 81.8%, 58.0%; 48.2%, 68.1%, 79.6%; and 95.7%, 92.3%, 93.5%, respectively. Only two out of 134 eligible patients were false negative. Heart rate did not significantly influence diagnostic accuracy, whereas the absence or 164 minimal presence of coronary calcification improved diagnostic accuracy. The positive and negative likelihood ratios at the per-patient level were 2.32 and 0.041, respectively. Conclusions. CTCA in the real clinical world shows a diagnostic performance lower than reported in previous validation studies. The excellent negative predictive value and negative likelihood ratio make CTCA a noninvasive gold standard for exclusion of significant coronary artery disease.

ObjectivePlatelets 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.Methods and resultsWe 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.ConclusionsOur 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.

"Objectives The purpose of this study was to test whether the 9p21.3 variant rs1333040 influences the occurrence of new cardiovascular events and coronary atherosclerosis progression after early-onset myocardial infarction. Background 9p21.3 genetic variants are associated with ischemic heart disease, but it is not known whether they influence prognosis after an acute coronary event. Methods Within the Italian Genetic Study of Early-onset Myocardial Infarction, we genotyped rs1333040 in 1,508 patients hospitalized for a first myocardial infarction before the age of 45 years who underwent coronary angiography without index event coronary revascularization. They were followed up for major cardiovascular events and angiographic coronary atherosclerosis progression. Results Over 16,599 person-years, there were 683 cardiovascular events and 492 primary endpoints: 77 cardiovascular deaths, 223 reoccurrences of myocardial infarction, and 383 coronary artery revascularizations. The rs1333040 genotype had a significant influence (p = 0.01) on the primary endpoint, with an adjusted hazard ratio of 1.19 (95% confidence interval [CI]: 1.08 to 1.37) for heterozygous carriers and 1.41 (95% CI: 1.06 to 1.87) for homozygous carriers. Analysis of the individual components of the primary endpoints provided no significant evidence that the rs1333040 genotype influenced the hazard of cardiovascular death (p = 0.24) or the reoccurrence of myocardial infarction (p = 0.57), but did provide significant evidence that it influenced on the hazard of coronary revascularization, with adjusted heterozygous and homozygous ratios of 1.38 (95% CI: 1.17 to 1.63) and 1.90 (95% CI: 1.36 to 2.65) (p = 0.00015), respectively. It also significantly influenced the angiographic endpoint of coronary atherosclerosis progression (p = 0.002). Conclusions In early-onset myocardial infarction, the 9p21.3 variant rs1333040 affects the progression of coronary atherosclerosis and the probability of coronary artery revascularization during long-term follow-up. (J Am Coll Cardiol 2011;58:426-34) (C) 2011 by the American College of Cardiology Foundation"