1. Coronary Artery Disease
UHCW Cardiology Teaching
Dr Chris McAloon

2. Case One 65 year old man Playing golf Sudden onset chest pain
Crushing, central, severe
Vomiting
No previous chest pain
HTN, Ex-Smoker
Otherwise well
GTN helped – not resolved

3. History – what information do you need to elicit?
Pain
Character / Radiation / GTN spray effect
Was this pain like your previous Angina/ MI pain?
Autonomic features
Risk factors
Smoker / Hypertension / Diabetes Hyperlipidaemia / Family history
Previous MI / CABG / PCI / CVA
Differentials
What makes cardiac chest pain?
What does PCI and CANG stand for?
What differentials do you have for chest pain?
What differentials do they get?

4. Cardiac Sounding Chest Pain
Central Crushing Chest Pain
Exertional chest pain
Occurs at rest
Radiation
Neck, arms (classically left)
Levine’s Sign
Clenched fist over chest
Breathless
Autonomic features

5. Isn’t Chest Pain always ACS?
ECS ACS NTE Guidelines 2011

6. Examination Nicotine Stains GTN spray Xanthelasma Scar’s Evidence DM
Chest
Legs
Evidence DM
BP/ Pulse/ Failure

7. Examination 65 year old 35 year old Valve/ Congenital surgery CABG
Ankles/shins for SVG scar
Radial for graft scar
CABG
35 year old
Metallic Click
Look left lateral
Cyanosis etc
Valve/ Congenital surgery

8. Acute Coronary Syndrome
ECS ACS Guidelines 2011

9. ESC Definition ACS Pain
ECS ACS Guidelines 2011

10. Pathophysiology ACS
Spectrum of acute coronary syndromes according to electrocardiographic and biochemical markers of myocardial necrosis (troponin T, troponin I, and creatine kinase MB), in patients presenting with acute cardiac chest pain
Grech E D , Ramsdale D R BMJ 2003;326:
©2003 by British Medical Journal Publishing Group

11. Plaque and Thrombin Formation
Ischaemic Heart Disease
Diagram of an unstable plaque with superimposed luminal thrombus
Unstable angina and non-ST segment elevation myocardial infarction are generally associated with white, platelet-rich, and only partially occlusive thrombus. Microthrombi can detach and embolise downstream, causing myocardial ischaemia and infarction. In contrast, ST segment elevation (or Q wave) myocardial infarction has red, fibrin-rich, and more stable occlusive thrombus.
Grech E D , Ramsdale D R BMJ 2003;326:
©2003 by British Medical Journal Publishing Group

12. Ruptured Atheromatous Plaque and Occlusive Thrombus
STEMI
Histological appearance of a ruptured atheromatous plaque (bottom arrow) and occlusive thrombus (top arrow) resulting in acute myocardial infarction
Occlusion epicardial artery
Grech E D , Ramsdale D R BMJ 2003;326:
©2003 by British Medical Journal Publishing Group

13. ECG: ST elevation ECG Changes Site of Infarction Vessel Occluded V1-V3
Anteroseptal
LAD
V4, V5, AVL, I
Anterior Lateral
LAD, diagonal
Widespread
1, AVL, V1-V6
Large Anterior
Prox LAD (could be LMS
- Pump probs
II, III, AVF
Inferior
RCA (or Cx)
- Bradyarrhythmia
↓ ST V1-V2
↑ ST in post leads
Posterior
NB remember Cx occlusion can be silent on the ECG

14. ANTERIOR STEMI ST elevation V1-V6, reciprocal changes in II, III, AVF

15. Infero-posterior STEMI ST elevation in II, III and AF, R wave and ST depression in V1-2

16. Size of the Problem: England and Wales 2009-10
STEMI
31,412 in
Frequency falling
NSTEMI
Estimated 100, 000 in
Recorded frequency rising
50% not managed on ACU/ CCU
BCS Recommendations Acute Coronary Care Oct 2011

17. 30 Day Mortality Mortality rate of STEMI and NSTEMI simliar at 30 days
BCS Recommendations Acute Coronary Care Oct 2011

18. STEMI Initial Diagnosis
Regional wall abnormalities occur within seconds coronary arter occlusion
ECS ACS STE Guidelines 2011

19. 300mg Aspirin/ 600mg Clopidogrel Reperfusion: PCI / Fibrinolysis
Management of STEMI
THINK REPERFUSION STRATEGY:
■ Primary PCI if available (CALL THE CATH LAB) ■ Thrombolysis if not, then refer to PCI centre
(GTN) ↓
High Flow Oxygen (15L)
300mg Aspirin/ 600mg Clopidogrel
Analgesia: Morphine + Metoclopramide
Reperfusion: PCI / Fibrinolysis

20. STEMI Management Successful Thrombolysis
ST segment resolution 50% at 90 minutes
ECS Revasculration Guidelines 2011

21. Standards STEMI Management
Direct paramedic transfer to PPCI centre or timely inter-hospital transfer
PPCI with first medical contact-to-balloon time <120 minutes
Monitoring on CCU (including for repatriated patients)
Early initiation of secondary prevention and cardiac rehabilitation
ECS Revasculration Guidelines 2011

22. The Changing Face STEMI Mx
BCS Recommendations Acute Coronary Care Oct 2011

23. The Changing Face STEMI Mx
95% England covered by PPCI networks
Thrombolysis remains in place in remote centres
Geography impacts time to PPCI centre
30% Thrombolysis fail to reperfuse and need immediate rescue PCI

24. ECS ACS STE Guidelines 2011

25. What is Percutaneous Coronary Intervention (PCI)?
Disruption of occlusion using a balloon
Stent deployed to maintain anterograde blood flow
Types
Primary PCI – PCI within 2 hours
Rescue PCI – PCI after failed thrombolysis
Facilitated PCI – PCI bridged with lytic therapy
Time delayed PPCI

26. Distal Embolisation of a Platelet-Rich Thrombus causing Occlusion of Intramyocardial Arteriole
NSTEMI
Distal embolisation of a platelet-rich thrombus causing occlusion of intramyocardial arteriole (arrow). Such an event may result in micro-infarction and elevation of markers of myocardial necrosis
Grech E D , Ramsdale D R BMJ 2003;326:
©2003 by British Medical Journal Publishing Group

27. Case Two 48 year old lady Shopping Central dull Pain on walking
Not relieved GTN spray
Gets on exertion normally
Recently distant decreasing to onset pain
Pain last night in bed

28. Worrying ECG?
Electrocardiogram of a 48 year old woman with unstable angina (top). Note the acute ischaemic changes in leads V1 to V5 (arrows). Coronary angiography revealed a severe mid-left anterior descending coronary artery stenosis (arrow, bottom left), which was successfully stented (bottom right)‏
Grech E D , Ramsdale D R BMJ 2003;326:
©2003 by British Medical Journal Publishing Group

29. What do you do as the SHO clerking patient in A+E?

30. Defining Angina Pectoris
Stable Angina
pattern of frequency, intensity, ease of provocation, or duration does not change over several weeks
Accelerating Angina
 change in the pattern of stable angina
greater ease of provocation, more prolonged episodes, and episodes of greater severity or more frequent use of sublingual GTN
Unstable Angina
 pattern of chest pain changes abruptly

31. Three Presentations UA
Angina at rest—Also prolonged, usually > 20 minutes
Angina of new onset—At least CCS class III in severity
Angina increasing—Previously diagnosed angina that has become more frequent, longer in duration, or lower in threshold (change in severity by > 1 CCS class to at least CCS class III)

32. Angina Pectoris CCS Classification
Class I – Pain strenuous exertion
Class II – Slight limitation ordinary exertion
Class III – Marked limitation physical exertion
Class IV – Pain on any exertion
CCS = Canadian Cardiology Society
The anaerobic threshold is crossed and the patient develops symptomatic angina pectoris. 
Supply and demand

33. TIMI Risk Score ≥3 risk factors for coronary artery disease
≥50% coronary stenosis on angiography
ST segment change >0.5 mm
≥2 anginal episodes in 24 hours before presentation
Elevated serum concentration of cardiac markers
Use of aspirin in 7 days before presentation

34. High TIMI score and Mortality
Rates of death from all causes and non-fatal myocardial infarction at 14 days, by TIMI risk score. Note sharp rate increase when score ≥ 3
Grech E D , Ramsdale D R BMJ 2003;326:
©2003 by British Medical Journal Publishing Group

35. Bleeding Risk
Crusade bleeding score
ECS ACS Guidelines 2011

36. NSTEMI Outcome Based Location
BCS Recommendations Acute Coronary Care Oct 2011

37. Simplified management pathway for patients with unstable angina or non-ST segment elevation myocardial infarction.
Simplified management pathway for patients with unstable angina or non-ST segment elevation myocardial infarction
Grech E D , Ramsdale D R BMJ 2003;326:
©2003 by British Medical Journal Publishing Group

38. Acute Management of NSTEMI-ACS
Aspirin 300mg
Clopidogrel 300mg (600mg if going to the lab)
LMWH
Bisoprolol / Atorvastatin 80mg ON/ ACE/ARB (can be next day)
GTN Spray/ Infusion
HIGH RISK patients: GPIIbIIIa
Cath Lab within 48-96hrs

39. Timing Early Invasive Strategy
High risk (GRACE >140) within 24 hours
At Stafford discuss with Stoke
Intermediate risk (GRACE < 140) and high risk criterion within 72 hours
Low risk with recurrent symptoms
Stress Test

40. Anti-thrombotic Therapy
ECS ACS Guidelines 2011

41. Prasugrel Thienopyridine related to Clopidogrel
Active metabolite irreversible inhibitor of ADP receptor
Effective when Clopidogrel Resistance
More rapid/ greater/ more consistent platelet inhibition
No drug interactions
Licensed used STEMI going PPCI

42. Prasugrel vs Clopidogrel
Figure 1. Cumulative Kaplan-Meier Estimates of the Rates of Key Study End Points during the Follow-up Period. Panel A shows data for the primary efficacy end point (death from cardiovascular causes, nonfatal myocardial infarction [MI], or nonfatal stroke) (top) and for the key safety end point (Thrombolysis in Myocardial Infarction [TIMI] major bleeding not related to coronary-artery bypass grafting) (bottom) during the full follow-up period. The hazard ratio for prasugrel, as compared with clopidogrel, for the primary efficacy end point at 30 days was 0.77 (95% confidence interval [CI], 0.67 to 0.88; P<0.001) and at 90 days was 0.80 (95% CI, 0.71 to 0.90; P<0.001). Data for the primary efficacy end point are also shown from the time of randomization to day 3 (Panel B) and from 3 days to 15 months, with all end points occurring before day 3 censored (Panel C). In Panel C, the number at risk includes all patients who were alive (regardless of whether a nonfatal event had occurred during the first 3 days after randomization) and had not withdrawn consent for follow-up. The P values in Panel A for the primary efficacy end point were calculated with the use of the Gehan-Wilcoxon test; all other P values were calculated with the use of the log-rank test.
Wiviott SD et al. N Engl J Med 2007;357:

43. Prasugrel vs Clopidogrel
Figure 2. Hazard Ratios and Rates of the Primary End Point, According to Selected Subgroups of Study Patients. The primary end point was defined as death from cardiovascular causes, nonfatal myocardial infarction (MI), or nonfatal stroke. The percentages are Kaplan-Meier estimates of the rate of the end point at 15 months. For each subgroup, the size of the square is proportional to the number of patients in the subgroups and represents the point estimate of the treatment effect. The overall treatment effect of prasugrel as compared with clopidogrel is represented by the diamond, and the dashed vertical line represents the corresponding overall point estimate. None of the P values for interactions were significant. Glycoprotein IIb/IIIa-receptor antagonist use was that during the index hospitalization.
Wiviott SD et al. N Engl J Med 2007;357:

44. Ticagrelor Cyclopentyl-triazolo-pyrimidine
Reversible inhibitor of ADP receptor
Rapid/ Predictable action
CYP450 interaction
NICE approval October 2011 ACS

45. Ticagrelor vs Clopidogrel
Figure 1. Cumulative Kaplan-Meier Estimates of the Time to the First Adjudicated Occurrence of the Primary Efficacy End Point. The primary end point - a composite of death from vascular causes, myocardial infarction, or stroke - occurred significantly less often in the ticagrelor group than in the clopidogrel group (9.8% vs. 11.7% at 12 months; hazard ratio, 0.84; 95% confidence interval, 0.77 to 0.92; P<0.001).
Wallentin L et al. N Engl J Med 2009;361:

46. Ticagrelor vs Clopidogrel
Figure 2. Cumulative Kaplan-Meier Estimates of the Time to the First Major Bleeding End Point, According to the Study Criteria. The time was estimated from the first dose of the study drug in the safety population. The hazard ratio for major bleeding, defined according to the study criteria, for the ticagrelor group as compared with the clopidogrel group was 1.04 (95% confidence interval, 0.95 to 1.13).
Wallentin L et al. N Engl J Med 2009;361:

47. Prescribing in CKD
ECS ACS Guidelines 2011

48. Secondary Prevention for IHD
Immediately
Aspirin ± PPI (Bleeding risk)
Clopidogrel (12 months)
B Blocker
ACEi- if intolerant give ARB
Atorvastatin 80mg
GTN Spray PRN
15 minute rule
Lifestyle
Diet
Physical Activity
Stop Smoking
Cardiac Rehab
Sex and stairs rule

49. Summary Definitions ACS Incidence and Prevalence Pathophysiology
Differential Diagnoses
STEMI Intervention – current evidence
NSTEMI intervention – current evidence
Antithrombotic therapy use
New anti-thrombotics