Yonathan Hasin

ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM).

Authors/Task Force Members: Kenneth Dickstein (Chairperson) (Norway)*, Alain Cohen-Solal (France), Gerasimos Filippatos (Greece), John J.V. McMurray (UK), Piotr Ponikowski (Poland), Philip Alexander Poole-Wilson (UK), Anna Strömberg (Sweden), Dirk J. van Veldhuisen (The Netherlands), Dan Atar (Norway), Arno W. Hoes (The Netherlands), Andre Keren (Israel), Alexandre Mebazaa (France), Markku Nieminen (Finland), Silvia Giuliana Priori (Italy), Karl Swedberg (Sweden)

Recommendations for the use of cardiac troponin measurement in acute cardiac care

The release of cardiomyocyte components, i.e. biomarkers, into the bloodstream in higher than usual quantities indicates an ongoing pathological process. Thus, detection of elevated concentrations of cardiac biomarkers in blood is a sign of cardiac injury which could be due to supply-demand imbalance, toxic effects, or haemodynamic stress. It is up to the clinician to determine the most probable aetiology, the proper therapeutic measures, and the subsequent risk implied by the process. For this reason, the measurement of biomarkers always must be applied in relation to the clinical context and never in isolation. There are a large number of cardiac biomarkers, but they can be subdivided into four broad categories, those related to necrosis, inflammation, haemodynamic stress, and/or thrombosis. Their usefulness is dependent on the accuracy and reproducibility of the measurements, the discriminatory limits separating pathology from physiology, and their sensitivity and specificity for specific organ damage and/or disease processes. In recent years, cardiac biomarkers have become important adjuncts to the delivery of acute cardiac care. Therefore, the Working Group on Acute Cardiac Care of the European Society of Cardiology established a committee to deal with ongoing and newly developing issues related to cardiac biomarkers. The intention of the group is to outline the principles for the application of various biomarkers by clinicians in the setting of acute cardiac care in a series of expert consensus documents. The first of these will focus on cardiac troponin, a pivotal marker of cardiac injury/necrosis.

Early and late benefits of prasugrel in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis.

OBJECTIVESnWe evaluated the relative contributions of the loading and maintenance doses of prasugrel on events in a TRITON-TIMI 38 (TRial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet InhibitioN with Prasugrel-Thrombolysis In Myocardial Infarction) analysis.nnnBACKGROUNDnPrasugrel is superior to clopidogrel in preventing ischemic events in patients with an acute coronary syndrome who are undergoing percutaneous coronary intervention, but it is associated with an increased risk of major bleeding.nnnMETHODSnLandmark analyses for efficacy, safety, and net clinical benefit were performed from randomization to day 3 and from day 3 to the end of the trial.nnnRESULTSnSignificant reductions in ischemic events, including myocardial infarction, stent thrombosis, and urgent target vessel revascularization, were observed with the use of prasugrel both during the first 3 days and from 3 days to the end of the trial. Thrombolysis In Myocardial Infarction major non-coronary artery bypass graft bleeding was similar to clopidogrel during the first 3 days but was significantly greater with the use of prasugrel from 3 days to the end of the study. Net clinical benefit significantly favored prasugrel both early and late in the trial.nnnCONCLUSIONSnBoth the loading dose and maintenance dose of prasugrel were superior to clopidogrel for the reduction of ischemic events. This result emphasizes the importance of maintaining high levels of inhibition of platelet aggregation via P2Y(12) receptor inhibition, not only for the prevention of periprocedural ischemic events but also during long-term follow-up. The excess major bleeding observed with the use of prasugrel occurred predominantly during the maintenance phase. Approaches to reduce the relative excess of bleeding with prasugrel should focus on the maintenance dose (e.g., reduction in maintenance dose in previously reported high-risk subgroups, such as the elderly and those patients with low body weight). (A Comparison of CS-747 and Clopidogrel in Acute Coronary Syndrome Subjects Who Are to Undergo Percutaneous Coronary Intervention; NCT00097591).

Recommendations for the use of natriuretic peptides in acute cardiac care : A position statement from the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care

Recommendations for the use of natriuretic peptides in acute cardiac care : A position statement from the Study Group on Biomarkers in Cardiology of the ESC Working Group on Acute Cardiac Care

Comparison of Treatment and Outcome of Acute Coronary Syndrome in Patients With Versus Patients Without Diabetes Mellitus

The aim was to evaluate management and outcomes in patients with diabetes mellitus (DM) with acute coronary syndrome (ACS). The EHS-ACS-II was a multinational survey conducted in 2004 that included 6,385 consecutive patients with ACS. The management and outcomes of patients with and without DM were compared. DM was recognized in 1,587 patients (25%) with ACS. Patients with DM had a less favorable risk-factor profile, less typical presentation, and longer delay in seeking medical attention; presented more frequently with arrhythmias, heart failure, renal failure, and major bleeding; and had higher in-hospital and 1-year mortality. They were treated more often with diuretics and inotropic agents and less often with antiaggregants (glycoprotein IIb/IIIa and clopidogrel). Insulin was administered to 53% of patients with DM during hospitalization and 31% at discharge. Patients with DM with ST-elevation (STE) myocardial infarction underwent similar primary percutaneous and coronary interventions (but received less thrombolytic therapy). Patients with DM with non-STE ACS underwent less in-hospital revascularization and had significantly higher 1-year mortality. Multivariable analyses showed DM as a predictor of 1-year mortality (odds ratio 1.37, 95% confidence interval 1.09 to 1.71), but not in-hospital mortality. In conclusion, given the current treatment, patients with and without DM with ACS had similar in-hospital adjusted mortality, but patients with DM had increased 1-year mortality. Patients with DM with non-STE ACS posed a higher risk group.

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 patients 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 patients 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.

Acute myocardial uptake of digoxin in humans: Correlation with hemodynamic and electrocardiographic effects

Acute myocardial uptake of digoxin was measured at a constant paced heart rate (75 beats/min) for 30 min after an intravenous bolus injection of 500 micrograms of digoxin in 14 patients with ischemic heart disease. Myocardial digoxin content, determined by serial measurement of aortocoronary sinus digoxin concentration gradients and coronary sinus blood flow, was expressed relative to coronary sinus blood flow at rest and correlated with simultaneous hemodynamic and electrocardiographic changes. Myocardial digoxin uptake was extensive (4.1 +/- 0.7% of total injected dose at 30 min) and prolonged, with rapid initial uptake (75.3 +/- 6.6% of maximum at 3 min), followed by a variable phase of slower accumulation. Peak left ventricular positive first derivative of left ventricular pressure (dP/dt) increased progressively (p less than 0.01), with a similar time course to that of myocardial digoxin accumulation; maximal change was 18.5 +/- 4.7% at 27 min. The ratio of inotropic effect to myocardial digoxin content did not vary significantly over the period of the experiment. However, peak inotropic effects in individual patients were not significantly related to peak myocardial digoxin content. The spontaneous PR interval increased transiently, with a peak increase of 5.9 +/- 1.8% (p less than 0.05) 12 min after digoxin administration. It is concluded that after intravenous bolus administration, 1) peak effects of digoxin on atrioventricular (AV) conduction occur early, whereas positive inotropic effects increase progressively for greater than or equal to 27 min; and 2) digoxin accumulation in the human myocardium is prolonged and is a determinant of inotropic effects, but not of prolongation of AV node conduction.

Determinants of acute hemodynamic and electrophysiologic effects of verapamil in humans: role of myocardial drug uptake.

Summary To examine the relationship between myocardial verapamil content (MVC) and acute effects in humans, coronary sinus catheterization was used in 22 patients to determine myocardial uptake of verapamil after bolus intravenous (i.v.) verapamil (4 mg) injection. Verapamil-induced effects on hemodynamic and electrophysiologic parameters were measured simultaneously and correlated with MVC per unit baseline coronary sinus blood flow (MVC:F). Myocardial uptake of verapamil was rapid: peak MVC (1.2 ± 0.2% of injected dose) occurred at 5.4 ± 0.4 min; at 30 min, residual MVC was 71.1 ± 3.4% of maximum. Peak MVC:F in individual patients was inversely related to the extent of coronary artery disease (p < 0.005) but not to left ventricular (LV) systolic function. Verapamil produced significant (p < 0.001) early reductions in arterial pressure and systemic vascular resistance (SVR); cardiac index (CI) increased, left ventricular (LV) positive dP/dt was unchanged. Verapamil prolonged (p < 0.01) PR and AH intervals (maximum at 12–18 min) and atrioventricular (AV) nodal effective and functional refractory periods (ERP, FRP) (maximum at 30 min). In individual patients, the extent of changes in AH intervals (r = 0.69; p < 0.05) and LV dP/dt(r = 0.62; p < 0.05) correlated with peak MVC:F. We conclude that after i.v. injection, verapamil uptake by the human myocardium is rapid and more extensive in patients with minor coronary artery disease. Despite the hysteresis between MVC and drug effects, MVC is a determinant of inotropic and electrophysiologic effects of verapamil.

How to use C-reactive protein in acute coronary care

C-reactive protein is an acute phase protein and an established marker for detection, risk stratification, and monitoring of infections and inflammatory and necrotic processes. Because C-reactive protein is sensitive but not specific, its values must be interpreted in the clinical context. In patients with acute myocardial infarction (AMI), C-reactive protein increases within 4–6 h of symptoms, peaks 2–4 days later, and returns to baseline after 7–10 days.1nnC-reactive protein has gained interest recently as a marker for risk stratification in acute coronary syndrome (ACS) when measured by high-sensitivity C-reactive protein assays. These assays have greater analytical sensitivity and reliably measure C-reactive protein concentrations within the reference range with low imprecision (5–10%).2 Because of evidence that atherosclerosis is an inflammatory disease, high-sensitivity C-reactive protein can be used as a biomarker of risk in primary prevention and in patients with known cardiovascular disease.3 The aim of this review is to evaluate the use of C-reactive protein in patients with acute coronary disease.nnC-reactive protein is a non-specific first-line host defence mechanism.4 With stimulation by cytokines (e.g. interleukins and tumour necrosis factor-alpha), C-reactive protein synthesis in hepatocytes occurs within 4–6 h. Concentrations can rise 1000-fold or more over 24–48 h. C-reactive protein has been detected in atherosclerotic plaques; its possible role in atherosclerogenesis is summarized in Figurexa01 , but is still a matter of debate.5 Genetic variants account for 35–40% of the variability in high-sensitivity C-reactive protein.6 nnnnFigurexa01 nPossible pathophysiological effects of C-reactive protein in atherosclerosis. Aggregated C-reactive protein selectively binds LDL and VLDL in serum, thereby potentially participating in the mechanisms involved in plaque formation and destabilization, and shows some of the key properties of antibodies and may contribute to immune responses by activation of antigen presenting cells. Procoagulant effects have been reported in vitro as …

Hypothyroid dependent myocardial angiotensin receptor trafficking is involved in improved cardiac performance after heat acclimation

AIMSnThe renin-angiotensin system (RAS) plays a key role in heat acclimation, a process which induces adaptive changes in cardiac function. These changes are mediated in part by reduced thyroid hormone activity and improve myocardial function during and following exposure to various (non-heat) stresses such as ischemia. The aim of this study was to examine the role of RAS in the development of the heat acclimated protected heart.nnnMAIN METHODSnThree treatment groups were used: (1) C, controls; (2) AC, heat acclimated rats (1mo 34 degrees C,); and (3) HAEL, heat acclimated euthyroid rats treated with 3ng/ml of eltroxine. A Langendorff perfusion apparatus was used to measure hemodynamic parameters at baseline and following administration of angiotensin-II, losartan and PD123319 in isolated hearts. Protein and mRNA levels of angiotensin receptors were measured.nnnKEY FINDINGSnBoth C and HAEL animals showed increased contractility and a drop in coronary flow during angiotensin II exposure whereas AC animals did not have an inotropic response or vasoconstriction. Significantly different patterns of AT1 and AT2 receptor densities (a 50% reduction and a 30% increase in outer cell membrane AT1 and AT2 receptors respectively) were observed in AC animals compared to the other two groups. AT receptor mRNA levels were similar in all treatment groups.nnnSIGNIFICANCEnThe attenuated response of heat acclimated hearts to angiotensin is mediated by reduced thyroxine levels and is associated with a shift in AT1 receptors from the outer to the inner membrane. This shift appears to be caused by modified posttranslational trafficking of AT receptors.