Current status and needs for changes in critical care training: the voice of the young cardiologists.

AIMS: The implementation of the 2013 European Society of Cardiology (ESC) Core Curriculum guidelines for acute cardiovascular care (acc) training among European countries is unknown. We aimed to evaluate the current status of acc training among cardiology trainees and young cardiologists (<40 years) from ESC countries. METHODS AND RESULTS: The survey (March-July 2019) asked about details of cardiology training, self-confidence in acc technical and non-technical skills, access to training opportunities, and needs for further training in the field. Overall 614 young doctors, 31 (26-43) years old, 55% males were surveyed. Place and duration of acc training differed between countries and between centres in the same country. Although the majority of the respondents (91%) had completed their acc training, the average self-confidence to perform invasive procedures and to manage acc clinical scenarios was low-44% (27.3-70.4). The opportunities for simulation-based learning were scarce-18% (5.8-51.3), as it was previous leadership training (32%) and knowledge about key teamwork principles was poor (48%). The need for further acc training was high-81% (61.9-94.3). Male gender, higher level of training centres, professional qualifications of respondents, longer duration of acc/intensive care training, debriefings, and previous leadership training as well as knowledge about teamwork were related to higher self-confidence in all investigated aspects. CONCLUSIONS: The current cardiology training program is burdened by deficits in acc technical/non-technical skills, substantial variability in programs across ESC countries, and a clear gender-related disparity in outcomes. The forthcoming ESC Core Curriculum for General Cardiology is expected to address these deficiencies.

Organization of intensive cardiac care units in Europe: Results of a multinational survey.

BACKGROUND: The present survey aims to describe the intensive cardiac care unit organization and admission policies in Europe. METHODS: A total of 228 hospitals (61% academic) from 27 countries participated in this survey. In addition to the organizational aspects of the intensive cardiac care units, including classification of the intensive cardiac care unit levels, data on the admission diagnoses were gathered from consecutive patients who were admitted during a two-day period. Admission policies were evaluated by comparing illness severity with the intensive cardiac care unit level. Gross national income was used to differentiate high-income countries (n=13) from middle-income countries (n=14). RESULTS: A total of 98% of the hospitals had an intensive cardiac care unit: 70% had a level 1 intensive cardiac care unit, 76% had a level 2 intensive cardiac care unit, 51% had a level 3 intensive cardiac care unit, and 60% of the hospitals had more than one intensive cardiac care unit level. High-income countries tended to have more level 3 intensive cardiac care units than middle-income countries (55% versus 41%, p=0.07). A total of 5159 admissions were scored on illness severity: 63% were low severity, 24% were intermediate severity, and 12% were high severity. Patients with low illness severity were predominantly admitted to level 1 intensive cardiac care units, whereas patients with high illness severity were predominantly admitted to level 2 and 3 intensive cardiac care units. A policy mismatch was observed in 12% of the patients; some patients with high illness severity were admitted to level 1 intensive cardiac care units, which occurred more often in middle-income countries, whereas some patients with low illness severity were admitted to level 3 intensive cardiac care units, which occurred more frequently in high-income countries. CONCLUSION: More than one-third of the admitted patients were considered intermediate or high risk. Although patients with higher illness severity were mostly admitted to high-level intensive cardiac care units, an admission policy mismatch was observed in 12% of the patients; this mismatch was partly related to insufficient logistic intensive cardiac care unit capacity.

Fondaparinux: pharmacology and clinical experience in cardiovascular medicine.

Fondaparinux is a synthetic, five-saccharide chain, AT-dependent, anti-FXa agent. Studies showed that fondaparinux acts in prevention and treatment of venous thromboembolism and in ischemic heart disease, without significant bleeding risk. The drug inhibits thrombin generation, has long half-life and can be administered once-daily without laboratory monitoring. It may be used in HIT treatment.

Local inhibition of tissue factor reduces the thrombogenicity of disrupted human atherosclerotic plaques: effects of tissue factor pathway inhibitor on plaque thrombogenicity under flow conditions.

BACKGROUND: Plaque disruption and subsequent thrombus formation lead to acute coronary syndromes and progression of atherosclerotic disease. Tissue factor (TF) appears to mediate plaque thrombogenicity. Tissue factor pathway inhibitor (TFPI) is the major physiological inhibitor of TF. This study analyzes the role of TF on thrombogenicity of disrupted human atherosclerotic plaques and the therapeutic possibilities of its specific inhibition. METHODS AND RESULTS: Human atherosclerotic and normal arterial segments were exposed to heparinized blood at flow conditions modeling medium-grade coronary stenosis in the Badimon perfusion chamber. The antithrombotic effects of the specific inhibition of plaque TF was assessed by reduction in the deposition of radiolabeled platelets and fibrin(ogen) and immunohistochemical analysis of perfused arteries. TF activity was inhibited by both recombinant TFPI and a polyclonal antibody against human TF. Human lipid-rich plaques were more thrombogenic than less advanced atherosclerotic plaques. Specific inhibition of TF activity reduced plaque thrombogenicity, inhibiting both platelet and fibrin(ogen) deposition (580 versus 194 plateletsx10(6)/cm2; P<0.01, and 652 versus 172x10(12) molecules of Fg/cm2; P<0.05, respectively) and thrombosis (immunohistochemistry). CONCLUSIONS: This study documents the key role of TF activity in acute arterial thrombosis after atherosclerotic plaque disruption and provides evidence of the benefit of blocking plaque TF activity. Therefore the inhibition of the TF pathway opens a new therapeutic strategy in the prevention of acute coronary thrombosis after plaque disruption.

Direct antithrombins: new perspectives in cardiovascular medicine.

Thrombin converts fibrinogen to fibrin and is the most powerful activator of platelets thus playing a crucial role in arterial and venous thrombosis. The limitations of heparin, largely used in the therapy of arterial and venous thromboembolism, has prompted the development of new antithrombotic drugs, able to directly inhibit thrombin. They comprise hirudin, bivalirudin and argatroban, which are antithrombins for parenteral use, and the orally active ximelagatran which, once absorbed, is converted to the active compound melagatran. Hirudin is a polypeptide able to irreversibly block both the active site and the fibrin(ogen) binding site of thrombin; bivalirudin, a synthetic hirudin derivative, has the same binding sites of hirudin to thrombin but has a shorter pharmacological action and is safer for clinical use. Several clinical trials which tested these drugs in acute coronary syndromes, coronary angioplasty and venous thromboembolism. demonstrate that hirudin and bivalirudin are superior to heparin in significantly reducing cardiac major events. The advantage of hirudin and bivalirudin over heparin was also confirmed in adjuncts to thrombolytic therapy as well as in percutaneous angioplasty relating to thrombotic events but not to restenosis. Hirudin was also significantly better than both unfractionated heparin and low molecular weight heparin (LMWH) in the prophylaxis of venous thromboembolism in patients undergoing elective arthroplasty. Major bleeding associated to hirudin was not different from that observed with heparin. Preliminary data also indicate that melagatran/ximelagatran may be used in the prophylaxis of venous thromboembolism and in the prevention of arterial embolism in patients with non-valvular atrial fibrillation.

Cyclo-oxygenase-1 and cyclo-oxygenase-2 and cardiovascular system.

Prostaglandins play important roles in the pathophysiological mechanism of action of platelets and endothelial cells in the cardiovascular system. The two isoforms of cyclo-oxygenase, respectively cyclo-oxygenase-1 and cyclo-oxygenase-2, are differently expressed in these cells. Activated platelets show a relatively large amount of cyclo-oxygenase-1, whereas endothelial cells have the gene for cyclo-oxygenase-2, the expression of which follows cell activation. In the atherosclerosis lesion, prostaglandin synthesis is mainly mediated by the inducible cyclo-oxygenase-2 expressed in macrophages/foam cells, smooth muscle cells and endothelial cells. Aspirin, a selective platelet cyclo-oxygenase-1 inhibitor still remains the most extensively studied antiplatelet agent, even though there is growing evidence that many other compounds could be valuable either in association, or alternatives in antithrombotic therapy.

Pre-hospital treatment of STEMI patients. A scientific statement of the Working Group Acute Cardiac Care of the European Society of Cardiology.

In ST-elevation myocardial infarction (STEMI) the pre-hospital phase is the most critical, as the administration of the most appropriate treatment in a timely manner is instrumental for mortality reduction. STEMI systems of care based on networks of medical institutions connected by an efficient emergency medical service are pivotal. The first steps are devoted to minimize the patient's delay in seeking care, rapidly dispatch a properly staffed and equipped ambulance to make the diagnosis on scene, deliver initial drug therapy and transport the patient to the most appropriate (not necessarily the closest) cardiac facility. Primary PCI is the treatment of choice, but thrombolysis followed by coronary angiography and possibly PCI is a valid alternative, according to patient's baseline risk, time from symptoms onset and primary PCI-related delay. Paramedics and nurses have an important role in pre-hospital STEMI care and their empowerment is essential to increase the effectiveness of the system. Strong cooperation between cardiologists and emergency medicine doctors is mandatory for optimal pre-hospital STEMI care. Scientific societies have an important role in guideline implementation as well as in developing quality indicators and performance measures; health care professionals must overcome existing barriers to optimal care together with political and administrative decision makers.

Heparin and secondary prevention of acute myocardial infarction.

Patients surviving acute myocardial infarction (AMI) may experience several clinical events (reinfarction, congestive heart failure, sudden death) still responsible for high mortality rates. AMI early complicated by residual angina, left ventricular dysfunction, or malignant arrhythmias has a worse prognosis. Secondary prevention of myocardial infarction and death has been the end point of many clinical trials in the past two decades. It is well known that beta blockers prevent sudden death if administered chronically after AMI. Meta-analysis of controlled randomized trials demonstrated a significant reduction in reinfarction and vascular death with long-term antiplatelet treatment. Oral anticoagulants prevent fatal and non-fatal reinfarction and show a trend towards lower mortality rates, though treated patients have a higher incidence of haemorrhagic events, particularly stroke. Early administration of heparin gave contradictory results on short-term prevention of myocardial infarction and death after AMI. Data on long-term heparin therapy point out a significant reduction in recurrent AMI and a trend towards a decrease in general mortality.

Wall passivation for unstable angina.

The disruption of an atherosclerotic plaque in a coronary artery, appears to be fundamental for the development of arterial thrombosis and resultant ischaemia. Platelets play a central role in the pathogenesis of unstable angina; they can aggregate and cause mechanical obstruction if large enough. In addition, they can lead to fibrin deposition and extension of the thrombus. The fundamental goal in the treatment of unstable angina is to control the acute disease process that leads to vascular occlusion. In addition to the currently available pharmacological agents used to treat unstable angina, newer agents such as the direct thrombin inhibitors and the glycoprotein IIb/IIIa receptor antagonists may be more effective in achieving 'passivation'. This article summarizes the role of the vessel wall and its interaction with platelets in arterial thrombosis. The different pharmacological approaches used in achieving passivation of platelets in unstable angina are described.

Endogenous cytokine antagonists during myocardial ischemia and thrombolytic therapy.

We tested the idea that cytokine antagonists are released during acute myocardial ischemia to counteract proinflammatory effects of cytokines. We investigated changes in plasma concentrations of the anticytokine molecules alpha-melanocyte-stimulating hormone (alpha-MSH), interleukin-1 receptor antagonist (IL-1ra), and soluble tumor necrosis factor receptor (sTNFr) in patients with acute myocardial infarction (AMI) or unstable angina (UA). Blood samples were collected at presentation in the coronary care unit, at 3-hour intervals for 24 hours, and daily for 4 days thereafter. There were no significant differences in the concentrations of cytokine antagonists in patients with AMI or UA. However, whereas concentrations of alpha-MSH were increased in early samples of patients with AMI or UA who were treated with a thrombolytic agent, they were consistently low in untreated patients. IL-1ra concentrations likewise were greater 3 and 6 hours after treatment in patients who underwent thrombolysis, whereas there was no significant difference in plasma sTNFr between the two groups. We suggest that during myocardial ischemia and thrombolysis anticytokine molecules released from the injured myocardium become available to reduce inflammation caused by cytokines and other mediators of inflammation.

[Immunological parameters in subjects with essential arterial hypertension. I. Lymphocyte subpopulations]. / Osservazioni su alcuni parametri immunologici in soggetti con ipertensione arteriosa essenziale. I. Sottopopolazioni linfocitarie.

Peripheral venous blood lymphocytes were defined, in 21 subjects with essential hypertension and 20 controls, on the basis of reactivity with monoclonal antibodies OKT3, OKT4, OKT8, OK1Ia. Total lymphocyte count, OKT3+ and OKT4+ cells percentage were similar in normal and hypertensive. OKT8+ cells percentage was significantly lower only in hypertensive stage II and III patients (WHO classification).

[Immunological parameters in subjects with essential arterial hypertension. II. Serological observations]. / Osservazioni su alcuni parametri immunologici in soggetti con ipertensione arteriosa essenziale. II. Rilievi sierologici.

M, G, and A immunoglobulins as well as C3 and C4 complement fractions were determined in 20 patients with essential hypertension: all the values were in the normal range. Nearly half of the patients had an abnormally high value of circulating immune complexes as determined with Clq binding assay and/or with CIC test. The rise of circulating immune complexes is not related to the stage of arterial hypertension.

Antibodies to cardiac Purkinje cells: further characterization in autoimmune diseases and atrioventricular heart block.

We confirmed the occurrence of IgG antibodies reacting with ox cardiac conducting tissue in the serum of some human subjects. These antibodies failed to react with all ox cardiac conducting tissue cells; they reacted only with the cells defined as Purkinje cells. Having checked 352 sera, we found that the prevalence of antibodies to Purkinje cells was 11% in normal subjects (no correlation with sex and age), 14% in systemic lupus erythematosus, 21% in rheumatoid arthritis, 18% in progressive systemic sclerosis, and 23% in Sjögren syndrome. In 50 patients with permanent pacemakers for chronic non-postinfarction atrioventricular (AV) block the prevalence was 30% (P = 0.008). In a selected set of 29 patients with clinically idiopathic AV block located at or below the level of the His bundle the prevalence was 34.5% (P = 0.006). The possible role of anti-Purkinje cell antibodies in autoimmune damage of cardiac conduction tissue is discussed.

[Early and late prognosis in acute myocardial infarct. A retrospective study in patients admitted to the coronary care unit in the past 10 years]. / La prognosi precoce e tardiva nell'infarto miocardico acuto. Studio retrospettivo in pazienti ricoverati in unità coronarica negli ultimi 10 anni.

The prognostic evaluation of the patient with an acute myocardial infarction is one of the most interesting unanswered problems. This is both because of its complexity and its implications in terms of secondary prevention. Several clinical studies have emphasized the reliability of the prognostic evaluation based on data collected during the first 24 hours. We therefore evaluated the prognostic relevance of 26 variables measured in the coronary care unit in 1914 patients admitted to our Unit as a result of acute myocardial infarction during the past 10 years. Twenty-four patients were lost to follow-up so that the evaluation refers to 1,890 patients, 1,506 of whom are males aged between 22 and 99 years (mean 58.1) and 384 are females aged between 29 and 88 years (mean 67.1); thus there is a greater prevalence of males. The sex-related difference in the age distribution is statistically significant. In-hospital mortality was analyzed using univariate and multivariate statistical methods (chi-squared test, multiple logistic regression analysis). The prognostic relevance of the considered variables in relation to the survival was analysed using the logrank test and using Cox's model. The variables associated with a greater risk of in-hospital death were found to be: age, presence of diabetes, anterior location of the infarct, arterial hypotension at admission, Killip class III and IV and the presence of ventricular tachyarrhithmias. In contrast, smokers had a lower in-hospital death risk. As to mortality during the follow-up, there was an association with age, female sex, pre-existent coronary disease, presence of high heart rate on admission, low peripheral tissue perfusion, x-ray documented pulmonary congestion, supraventricular tachiarrhythmias and intraventricular block. In contrast, the presence of obesity was associated with a reduced death risk during the follow-up. During the follow-up the most frequent cause of death was re-infarction, followed by sudden death, death from non-cardiac causes and heart failure.

Tissue factor modulates the thrombogenicity of human atherosclerotic plaques.

BACKGROUND: The thrombogenicity of a disrupted atherosclerotic lesion is dependent on the nature and extent of the plaque components exposed to flowing blood together with local rheology and a variety of systemic factors. We previously reported on the different thrombogenicity of the various types of human atherosclerotic lesions when exposed to flowing blood in a well-characterized perfusion system. This study examines the role of tissue factor in the thrombogenicity of different types of atherosclerotic plaques and their components. METHODS AND RESULTS: Fifty human arterial segments (5 foam cell-rich, 9 collagen-rich, and 10 lipid-rich atherosclerotic lesions and 26 normal, nonatherosclerotic segments) were exposed to heparinized blood at high shear rate conditions in the Badimon perfusion chamber. The thrombogenicity of the arterial specimens was assessed by 111In-labeled platelets. After perfusion, specimens were stained for tissue factor by use of an in situ binding assay for factor VIIa. Tissue factor in specimens was semiquantitatively assessed on a scale of 0 to 3. Platelet deposition on the lipid-rich atheromatous core was significantly higher than on all other substrates (P = .0002). The lipid-rich core also exhibited the most intense tissue factor staining (3 +/- 0.1 arbitrary units) compared with other arterial components. Comparison of all specimens showed a positive correlation between quantitative platelet deposition and tissue factor staining score (r = .35, P < .01). CONCLUSIONS: Our results show that tissue factor is present in lipid-rich human atherosclerotic plaques and suggest that it is an important determinant of the thrombogenicity of human atherosclerotic lesions after spontaneous or mechanical plaque disruption.