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Abstract

The efficacy of cardioprotective strategies can be quantified by myocardial salvage as an indicator of therapeutic benefit. Salvage is calculated as the difference between the area at risk (AAR) and the final infarct size (FIS). AAR has been quantified by angiographic assessment followed by quantification of FIS by biochemical ischaemic markers or imaging modalities such as cardiovascular magnetic resonance (CMR). Angiographical methods may overestimate AAR and since methodological differences may exist between different modalities, the use of different modalities for estimating AAR and FIS may not be recommended. 99m Technetium (Tc)-Sestamibi single-photon emission tomography (SPECT) allows quantification of AAR and FIS by tracer injection prior to revascularization and after 1 month, respectively. SPECT provides the most validated measure of myocardial salvage and has been utilized in multiple randomized clinical trials. However, SPECT is logistically challenging, expensive, and includes radiation exposure. More recently, a large number of studies have suggested that CMR can determine salvage in a single examination by combining measures of myocardial oedema in the AAR exposed to ischaemia reperfusion with FIS quantification by late gadolinium enhancement. The T1- and T2-weighted CMR approaches for quantification of AAR utilize non-contrast, early and late gadolinium enhancement techniques. The technical progress, high spatial resolution and the potential for retrospective quantification of the AAR makes CMR the most appropriate technique for assessment of myocardial salvage. However, the optimum CMR technique for assessment of myocardial AAR remains to be defined. Consequently, we recommend a comprehensive CMR protocol to ensure reliable assessment of myocardial salvage.

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Salvage of threatened myocardium is the principal mechanism by which patients with acute myocardial infarction (AMI) benefit from reperfusion. The combination of interventional and medical treatment has reduced mortality and morbidity significantly. Consequently, large patient numbers are required in clinical trials that aim at demonstrating improved survival of a new treatment. To diminish the need for large population sizes, numerous trials have used surrogate endpoints, including imaging measures of infarct size after coronary revascularization and indirect estimates of tissue damage by release of biomarkers, resolution of ST-segment elevation and myocardial blush grade. 1 , 2 Although these endpoints have predictive power in large cohorts, the usefulness in the individual patient and in small-sized study populations is moderate. 3 More recent clinical studies have used FIS and myocardial salvage as the primary endpoint ( Table 1 ). 4–7 Techniques that allow quantification of myocardial salvage provide advantages compared with those measuring only FIS: (i) quantification of salvage rather than FIS eliminates inter-individual variability and reduces requirement to the study population size, (ii) they permit proof-of-concept studies to test the potential efficacy of new therapeutic approaches in smaller study groups, and importantly (iii) they may provide further insight into the pathophysiology of ischaemia-reperfusion injury. The electrocardiogram may be used to estimate area at risk (AAR), but not FIS. 8 Indirect measures of salvage can be calculated from angiographic estimates of AAR combined with estimates of FIS by imaging techniques or biochemical markers. Echocardiography is the preferred clinical method for evaluation of left ventricular (LV) function in patients with AMI. However, there are currently no specific echocardiographic measures of myocardial salvage. 99m Technetium (Tc)-Sestamibi single-photon emission tomography (SPECT) and cardiovascular magnetic resonance (CMR) provide the assessment of myocardial salvage, using paired quantification of AAR and FIS either from two separate studies before and after revascularization, or retrospectively in one step when the patient has been treated and stabilized. The aim of the present review is to provide an overview of the current methods used for quantification of myocardial salvage in preclinical studies and clinical trials assessing the efficacy of reperfusion therapy and cardioprotection in AMI.

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The Task Force for the diagnosis and management of syncope of the European Society of Cardiology (ESC)

Developed with the special contribution of the European Heart Rhythm Association (EHRA)

Endorsed by: European Academy of Neurology (EAN), European Federation of Autonomic Societies (EFAS), European Federation of Internal Medicine (EFIM), European Union Geriatric Medicine Society (EUGMS), European Society of Emergency Medicine (EuSEM)

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Table of Contents

1. Preamble    1886

2. Introduction    1887

 2.1 What is new in the 2018 version?    1889

3. Definitions, classification, and pathophysiology    1889

 3.1 Definitions    1889

 3.2 Classification and pathophysiology of syncope and transient loss of consciousness    1890

   3.2.1 Syncope    1890

   3.2.2 Non-syncopal forms of (real or apparent) transient loss of consciousness    1890

4. Diagnostic evaluation and management according to risk stratification    1892

 4.1 Initial evaluation    1892

   4.1.1 Diagnosis of syncope    1893

   4.1.2 Management of syncope in the emergency department based on risk stratification    1895

 4.2 Diagnostic tests    1900

   4.2.1 Carotid sinus massage    1900

   4.2.2 Orthostatic challenge    1901

      4.2.2.1 Active standing    1901

      4.2.2.2 Tilt testing    1903

   4.2.3 Basic autonomic function tests    1904

      4.2.3.1 Valsalva manoeuvre    1904

      4.2.3.2 Deep breathing    1904

      4.2.3.3 Other autonomic function tests    1904

      4.2.3.4 Twenty-four-hour ambulatory and home blood pressure monitoring    1904

   4.2.4 Electrocardiographic monitoring (non-invasive and invasive)    1905

      4.2.4.1 In-hospital monitoring    1905

      4.2.4.2 Holter monitoring    1905

      4.2.4.3 Prospective external event recorders    1905

      4.2.4.4 Smartphone applications    1906

      4.2.4.5 External loop recorders    1906

      4.2.4.6 Remote (at home) telemetry    1906

      4.2.4.7 Implantable loop recorders    1906

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