STelevation myocardial infarction STEMI The basics Content Epidemiology

ST-elevation myocardial infarction (STEMI) The basics

Content Epidemiology Pathophysiology Symptoms & diagnosis

Epidemiology Pathophysiology Symptoms & diagnosis

ST-elevation myocardial infarction (STEMI) – Epidemiology 4 CVD is a major cause of death worldwide Cardiovascular disease 36% Other non-communicable diseases 23% 31% 9% Infectious diseases, maternal and perinatal conditions, and nutritional deficiencies Injuries CVD, cardiovascular disease World Health Organization 2014. Global health estimates 2014 summary tables: deaths by cause, age and sex, by WHO region, 2000 -2012.

ST-elevation myocardial infarction (STEMI) – Epidemiology 5 Global gender differences in deaths from cardiovascular disease Males Females 8% 3% 2% 10% 6% 2% 2% 7% 39% 45% Othercirculatory diseases Other diseases Cardiomyopathy, myocarditis, endocarditis Rheumaticheart diseases Hypertensiveheart diseases 36% Stroke 40% Ischaemic heart diseases World Health Organization 2013. Global Health Estimates Summary Tables: Deaths by Cause, Age and Sex by various regional grouping. http: //www. who. int/healthinfo/global_burden_disease/projections/en/

ST-elevation myocardial infarction (STEMI) – Epidemiology 6 Geographical differences in mortality from ischaemic heart disease (IHD), estimates 2012 Deaths (x 1000) from IHD in WHO regions 4% 12% 25% 7% Western Pacific South-East Asia Europe Eastern Mediterranean 31% 22% World Health Organization 2014. Global health estimates 2014 summary tables: deaths by cause, age and sex, by WHO region, 2000 -2012. The Americas Africa

ST-elevation myocardial infarction (STEMI) – Epidemiology Acute myocardial infarction (AMI): facts • AMI is a leading cause of death worldwide 1 • Approximately 42% of all deaths from cardiovascular disease are due to AMI 2 • Men have a higher risk than women for AMI 3 • Risk of AMI increases with advancing age for both genders 3 • Black men & women are more at risk than white men & women 3 • Incidence is increasing in developing and transitional countries, partly due to increasing longevity, urbanisation and lifestyle changes 3 1. Thygesen et al. J Am Coll Cardiol 2012; 60: 1581 -1598. 2. WHO Global Atlas on CV Disease, 2011. 3. Roger et al. Circulation 2012; 125: e 2 -e 220. 7

ST-elevation myocardial infarction (STEMI) – Epidemiology Mortality due to ACS around the world High-income countries Low- and middleincome countries • UK In-hospital mortality has fallen from ∼ 20% to ∼ 5% in the last 30 years 1 • USA In-hospital mortality 2: 5 -6%; 1 -year mortality 2: 7 -18% • India @ 30 days: 2. 1 – 6. 7% (DEMAT & CREATE registries)3 • China In-hospital: 4% (CRACE registry)3 • Eastern Europe In-hospital: 9% (Euro Heart Survey 2009 AMI Snapshot)3 • Middle East @ 12 months: 12% (Gulf RACE-2 registry)3 ACS, acute coronary syndrome 1. NICE Guidelines CG 16, 2013. 2. O’Gara et al. J Am Coll Cardiol 2013; 61(4): e 78 -e 140. 3. Vedanthan et al. Circ Res 2014; 114: 1959 -1975. 8

ST-elevation myocardial infarction (STEMI) – Epidemiology Declining incidence of STEMI: USA & AUSTRALIA Over the past couple decades, the incidence of STEMI has been declining in high-income countries: USA 1 Australia 2 • STEMI rates steadily fell between 1999 and 2008, while the incidence rate of non-STEMI slightly increased from 2002 to 2004 before slowly decreasing • Overall MI incidence rates steadily decreased over the 10 -year study period • STEMI rates have steadily fallen since 1993, while non-STEMI rates rose from 1997 to 2007 before starting to slowly decrease, affecting Australia’s overall incidence rate of MI 1. O’Gara et al. J Am Coll Cardiol. 2013; 61(4): e 78 -e 140. 2. Wong et al. Am J Cardiol. 2013; 112(2): 169 -73. 9

ST-elevation myocardial infarction (STEMI) – Epidemiology 10 Populations based on data from the USA ~30% Proportion of STEMI patients who are women 13. 3% Proportion of STEMI patients who are non-white 23% O’Gara et al. J Am Coll Cardiol. 2013; 61(4): e 78 -e 140. Proportion of STEMI patients who are diabetic

ST-elevation myocardial infarction (STEMI) – Epidemiology 11 Direct and indirect costs of cardiovascular disease and stroke, USA 2011 Billions of dollars 24. 6 33. 6 Heart disease 46. 4 215. 6 Hypertension Stroke Other CVD Mozaffarian et al. Circulation 2015; 131: e 29 -e 322.

ST-elevation myocardial infarction (STEMI) – Epidemiology 12 Forecast EU 2020: Healthcare costs of CVD to rise to 98. 7 € billion 24. 6 17. 3 33. 6 16. 1 France Germany 4. 5 Italy 215. 6 46. 4 8. 8 Spain Sweden UK 18. 2 33. 8 18. 2 Modified from Figure 2 of the CEBR analysis on the economic cost of cardiovascular diseases from 2014 -2020 in six European economies CVD, cardiovascular diseases

ST-elevation myocardial infarction (STEMI) – Epidemiology 13 Costs associated with AMI • Mean (median) cost of AMI 1*: $11, 664 ($7, 342) 35000 • The average costs are higher for diabetics 1 30000 • Mean (median) cost for follow-up through 1 year 1**: $32, 279 ($27, 430) • The cost of AMI is on the rise in China 2 • Data from Beijing shows a 56. 8% increase from 2007 to 2012 (even after adjusting for inflation) Average cost (mean, range) of AMI in USD 25000 $24, 695 20000 15000 10000 $5, 966 5000 $7, 386 $6, 747 $5, 025 $[WERT] 0 US Only EU Only Western Northern Eastern Southern AMI, acute myocardial infarction; US, United States; EU, European Union; All monetary figures are shown in US Dollar *Based on 18 studies from the US, EU and Australasia **Based on 3 US studies and 1 Swiss registry 1. Nicholson et al. Clinico. Econom Outcomes Res 2016; 8: 495 -506. 2. Zhang et al. Medicine 95(5): e 2677.

ST-elevation myocardial infarction (STEMI) – Epidemiology 14 Changing global burden of disease (% total DALYS), in 2004 and predicted for 2030 7. 0 2004 % total DALYS 6. 0 2030 5. 0 4. 0 3. 0 2. 0 1. 0 0 Ischaemic heart disease DALYs, disability adjusted life years Adapted from WHO Global Atlas on CV Disease, 2011. Cerebrovascular disease Diabetes mellitus

15 Pathophysiology Epidemiology Pathophysiology Symptoms & diagnosis

ST-elevation myocardial infarction (STEMI) – Pathophysiology 16 Acute coronary syndrome (ACS) One disease process but different clinical manifestations and different management strategies First Medical Contact (FMC) Chest pain Working diagnosis Acute coronary syndrome ECG Persistent STelevation ST/T abnormalities Normal or undetermined ECG Troponin rise/fall Troponin normal Biochemistry Imaging Diagnosis STEMI, ST-elevation myocardial infarction NSTEMI, non ST-elevation myocardial infarction Hamm et al. Eur Heart J 2011; 32: 2999 -3054. STEMI NSTEMI Unstable angina

ST-elevation myocardial infarction (STEMI) – Pathophysiology 17 Thrombus formation in MI and other ACS Due to plaque rupture, subendothelial adhesion molecules are exposed to flowing blood Primary haemostasis Tissue factor (thromboplastin) released (most likely from macrophages) Platelet adhesion Platelet activation Secondary haemostasis Platelet aggregation Coagulation cascade Fibrin strands form a meshwork around activated platelets Thrombus forms Wennerblom and Holmberg. Eur Heart J 1984; 5(4): 266 -274. Viskin and Belhassen. Am Heart J 1990; 120(3): 661 -671.

ST-elevation myocardial infarction (STEMI) – Pathophysiology 18 Definition of STEMI A clinical syndrome defined by characteristic symptoms of myocardial ischaemia in association with persistent ECG ST-elevation and subsequent release of biomarkers of myocardial necrosis 1 RCA LCA STEMI: full thickness damage (myocardial cell death) of cardiac muscle 1 NSTEMI: partial thickness damage of cardiac muscle 1 = obstructed artery 2 = infarcted area distal to the blocked artery 2 RCA, right coronary artery; LCA, left coronary artery; NSTEMI, non-ST-elevation myocardial infarction

ST-elevation myocardial infarction (STEMI) – Pathophysiology 19 Advancing necrosis in MI Cell death does not occur immediately, depending on the collateral circulation, extent of the arterial occlusion, and other factors 1 At 30 -40 min, irreversible cell death of the myocardium begins and function is disrupted 1, 2 After approximately 6 -8 min, necrosis of the ischaemic myocardium sets in 1, 2 Early reperfusion is essential to prevent loss of myocardial function 15 min 40 min Normal 3 h Ischaemia ≥ 6 h TIME SAVED = MUSCLE SAVED Necrosis 1. Thygesen et al. J am Coll Cardiol 2012; 60: 1581 -1598. 2. Boersma et al. Lancet 1996; 348: 771 -775. .

ST-elevation myocardial infarction (STEMI) – Pathophysiology Major modifiable and non-modifiable risk factors for cardiovascular disease 20

ST-elevation myocardial infarction (STEMI) – Pathophysiology 21 Risk factors for IHD rarely occur alone Non-modifiable risk factor Socioeconomic factors Education Ageing Low income Modifiable risk factors Physical inactivity High-fat diet Obesity Alcohol Hypercholesterolaemia Hypertension Co-morbidities Type 2 diabetes Adapted from Global Health Risks. WHO, 2009. Smoking

ST-elevation myocardial infarction (STEMI) – Pathophysiology Other risk factors Gender Heredity and family history • Higher rates of coronary heart disease among men compared with pre-menopausal women 1 • Risk for post-menopausal women is similar to men 1 • Increased risk if first-degree blood relative had coronary heart disease or stroke 1 • Having a sibling with a history of CVD is associated with a 45% increased risk of CVD 3 • In terms of attributable deaths, globally, CV risk factors are 2: Summary • • • Raised blood pressure (accounting for 13% of global deaths) Tobacco use (9%) Raised blood glucose (6%) Physical inactivity (6%) Overweight and obesity (5%) 1. Fact Sheet on Cardiovascular disease risk factors, WHF 2011. 2. The Global Atlas of CV Disease, WHO 2011. 3. Mozaffarian et al. Circulation 2015; 131: e 29 -e 322. 22

23 Symptoms & diagnosis Epidemiology Pathophysiology Symptoms & diagnosis

ST-elevation myocardial infarction (STEMI) – Symptoms & diagnosis 24 Typical symptoms of acute myocardial infarction (AMI) • Onset may be sudden or gradual • Symptoms vary depending on the location of the infarct Chest pain or discomfort Often described as a tightness, heaviness or constriction in the chest Usually in the centre of the chest, but radiate to neck, jaw, stomach, shoulder, back and arms (typically left arm) Breathing difficulty / shortness of breath Due to left ventricular dysfunction or dynamic mitral regurgitation Profuse sweating Nausea and/or vomiting Dizziness Syncope Usually due to an arrhythmia or severe hypotension Tachycardia Due to sympathetic nerve activation Bradycardia Patients with inferior STEMI may have bradycardia due to vagus nerve activation Cardiogenic shock Due to impaired myocardial function Dörr. Heart 2010; 96(18): 1434 -1435. .

ST-elevation myocardial infarction (STEMI) – Symptoms & diagnosis Diagnostic criteria for AMI Any one of the following criteria meets the diagnosis for AMI according to the Joint ESC/ACCF/AHA/WHF Task Force: A rise and/or fall of cardiac biomarkers (preferably troponin (c. Tn)) with at least one value above the 99 th percentile upper reference limit (URL) together with at least one of the following: + • Symptoms of ischaemia • New or presumed-new significant ST-segment-T wave (ST-T) changes or new left bundle branch block (LBBB) • Development of pathological Q waves in the ECG • Imaging evidence of new loss of viable myocardium or new regional wall motion abnormality • Identification of an intracoronary thrombus by angiography or autopsy Cardiac death with prior new ischaemic ECG changes and symptoms suggestive of myocardial ischaemia, without definitive biomarker evidence PCI-related MI* Stent thrombosis associated with MI* Coronary artery bypass grafting (CABG)-related MI* *See notes Thygesen et al. J Am Coll Cardiol 2012; 60(16): 1581 -1598. 25

ST-elevation myocardial infarction (STEMI) – Symptoms & diagnosis 26 Diagnosis of STEMI: ECG changes • ST-segment elevation with pathological Q-wave formation • Sometimes T-wave inversion may be found but it is a non-specific feature • ST-segment elevation indicates full thickness cardiac muscle injury, pathological Q-wave indicates muscle necrosis and T-wave inversion indicates muscle ischaemia QRS Segment R R ST Elevation ST Segment PR Segment T P PR Interval Q PR Segment P P Q S T-wave inversion ST depression ST Segment PR Segment T Q P Q S S QT Interval Normal ECG STEMI NSTEMI

ST-elevation myocardial infarction (STEMI) – Symptoms & diagnosis 27 Diagnosis of STEMI Cardiac markers • Troponin is the preferred biomarker for diagnosis Full blood count • Elevation of white blood cell count is usual • Erythrocyte sedimentation rate (ESR) and Creactive protein (CRP) may be elevated Chest X-ray Echocardiography • For assessing pulmonary oedema • Not essential, but helpful if ECG is inconclusive O’Gara et al. J Am Coll Cardiol 2013; 61(4): e 78 -e 140. .

ST-elevation myocardial infarction (STEMI) – Symptoms & diagnosis 28 STEMI types defined by ECG changes STEMI type Area affected Occluded vessel ECG findings ST segment elevation Prognosis Reciprocal STsegment depression Anterior wall of LV LAD branch of LCA Leads V 1 – V 6 Inferior leads II, III and a. VF Poor Antero-septal Area between LV and RV LAD septal branches Leads V 1 – V 4 Inferior leads II, III and a. VF) -- Lateral wall of LV 1 st diagonal branch of LAD and obtuse marginal branch of LCX Leads I, a. VL, V 5 and V 6 Inferior leads II, III and a. VF -- High lateral Superior portion of the lateral wall of LV 1 st diagonal branch of LAD Leads I and a. VL Inferior leads II, III and a. VF -- Antero-lateral Anterior and lateral wall of LV Proximal LAD or LAD + LCX Leads I, a. VL, V 4 – V 6 Inferior leads II, III and a. VF -- Inferior wall of LV RCA Leads II, III and a. VF Leads I and a. VL Posterior part of LV Posterior descending artery Leads V 7 – V 9 (posterior leads)b -- Right sided chest leads (V 3 R– V 6 R). -- RV infarctionc Gooda LV, left ventricle; RV, right ventricle; LAD, left anterior descending artery; LCX, left circumflex artery; LCA, left coronary artery; RCA, right coronary artery. a ~40% of these patients have a concomitant RV infarction and a poor prognosis; b Not directly visualised by the standard 12 -lead ECG – must be confirmed by 15 -lead ECG; C RV infarction is uncommon.

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