1. Heart Attacks: Killers in Disguise!
[Title slide]
W. Frank Peacock, MD, FACEP Vice Chief, Emergency Department The Cleveland Clinic

2. Agenda What is an Acute Coronary Syndrome? (a heart attack)
Why do you care?
CAD is the number one killer in Scotland
Who gets ACS?
What are the symptoms?

3. Agenda When should you go to the hospital?
why you should go to the hospital?
How do we diagnosis it?
What happens if your diagnosed with it?
What can be done to prevent getting this?

4. How does the heart work?
Its just a pump, right?

5. Its also a gland Myocardial injury Fall in LV performance
Activation of RAAS, SNS, ET,
and others
ANP
BNP
Peripheral vasoconstriction
Hemodynamic alterations
Myocardial toxicity
Slide 10
Left ventricular dysfunction results from myocardial injury. Changes occur in the peripheral circulation that also affect cardiac function and contribute to the symptoms of HF.
Vasoconstrictors – those in the sympathetic nervous system and the Renin Angiotensin Aldostrerone (RAA) System, as well as arginine vasopressin and endothelin – become activated to increase afterload and preload by conserving Na+ ions and water. Vasodilators – hormones in the natriuretic peptide system, as well as endothelin – derived relaxing factor and prostaglandins – help to unload the left ventricle and promote natriuretic action. In other words the actions of ANP and BNP counteract the activation of the RAAS and sympathetic nervous system.
Remodeling and
progressive
worsening of
LV function
Morbidity and mortality
Heart failure symptoms

6. Epidemiology of CHD in the US
Single most frequent cause of death
656,000 deaths in 2002
1 of every 5 deaths
Incidence
Each year, 1.2 million Americans will have a new or recurrent coronary event, and >40% will die as a result
700,000 events will be first attacks; 500,000 will be recurrences
Prevalence
13 million Americans have a history of CHD (acute MI, other acute ischemic (coronary) heart disease, angina pectoris, atherosclerotic cardiovascular disease, and all other forms of heart disease)
CHD = coronary heart disease; MI = myocardial infarction. American Heart Association. Heart Disease and Stroke Statistics—2005 Update; 2005.

7. Epidemiology of CHD Scotland
Single most frequent cause of death
Incidence
Prevalence
CHD = coronary heart disease; MI = myocardial infarction. American Heart Association. Heart Disease and Stroke Statistics—2005 Update; 2005.

8. Risk for CHD Increases With Additional Risk Factors: INTERHEART Study
512
256
128 64 32 16 8 4 2 1
Odds ratio (99% Cl)
Smk
(1) DM
(2)
HTN
(3)
ApoB/A1
(4)
1+2+3
All 4
+Obes
+PS
All RFs
PS = psychosocial
Yusuf S, et al. Lancet. 2004;364:

9. Odds Ratio for 1st MI (99% CI)
INTERHEART: Impact on CV Risk of Multiple Risk Factors (Smoking, Lipids, Hypertension, Diabetes, Abdominal Obesity, Diet, ↓Physical Activity, Alcohol, Psychosocial*)
512
– Large int’l case-control study – 15,152 cases – 14,820 controls – 52 countries – Follow-up: 4 years
256
128 64 32
Odds Ratio for 1st MI (99% CI) 16
Smk = smoking
DM = diabetes
HTN = hypertension
Obes = abdominal obesity
Ps = psychosocial factors 8 4
Design Large international case-control study
Participants 15,152 cases; 14,820 controls; 52 countries
Objective To determine association of first MI with: Smoking Lipids Hypertension Diabetes Abdom.Obes. Diet Physical Alcohol Psychosocial activity consumption factors (eg, stress, depression)
Follow-up 4 years, February 1999–March 2003
Clinical Implications
9 simple and modifiable risk factors are strongly associated with acute MI worldwide
• These 9 risk factors account for >90% of the population attributable risk globally and in most regions
• Implementing preventive strategies based on our current knowledge would prevent the majority of premature CHD worldwide 2 1
Smk (1)
DM (2)
HTN (3)
ApoB- ApoA1 (4)
1+2+3
All 4
All 4 + Obes
All 4 + Ps
All risk factors
*eg, stress, depression
Note: odds ratio plotted on a doubling scale. .
Yusuf S, et al. Lancet. 2004;364:
Yusuf S, Hawken S, Ounpuu S, et al. Obesity and the risk of myocardial infarction in 27,000 participants from 52 countries: a case-control study. Lancet. 2005;366:

10. What does an ACS feel like?

11. Symptoms of CAD NONE…….. Sudden Cardiac Death Chest Pain
Usually a pressure
Not seconds
Anginal equivalents
Jaw or shoulder pain
Nausea & vomiting
Shortness of breath
Weak & dizzy
Diaphoresis

12. Symptoms of Heart Attack
Anginal equivalents
Jaw/shoulder pain
Nausea & vomiting
Shortness of breath
Weak & dizzy
Diaphoresis
Classic presentation
Chest pressure
Elephant
Sweating
Nausea/vomiting
Radiation of pain
Shortness of breath

13. Who gets “Equivalents”?
Women
Diabetics
Elderly
Heart Transplant patients
Patients who can’t perceive/communicate well?
Drunk
Mentally ill

14. Options for Transport of Patients With STEMI and Initial Reperfusion Treatment
Hospital fibrinolysis:
door-to-needle
within 30 min
Not PCI
capable
Call 9-1-1
Call fast
EMS on-scene
Encourage 12-lead ECGs
Consider prehospital fibrinolytic if capable and EMS-to-needle within 30 min
Onset of symptoms of STEMI
9-1-1
EMS
dispatch
EMS triage plan
Inter-hospital
transfer
PCI
capable
GOALS 5
min 8
min
EMS Transport
Patient
EMS
Prehospital fibrinolysis
EMS-to-needle
within 30 min
EMS transport
EMS-to-balloon within 90 min
Patient self-transport
Hospital door-to-balloon
within 90 min
This slide summarizes the essential concept of a triage plan for patients with chest pain and underscores the importance of time-to-treatment. Effective treatment delivered within the “Golden Hour” following symptom onset and reducing the total ischemic time to less than 2 hours preserves myocardium and is associated with reduced mortality.
For patients with STEMI, reperfusion may be accomplished by fibrinolysis or primary angioplasty. The choice of specific strategy depends on how the patient is being transported and the capabilities of the receiving hospital. The objective is to keep the total ischemic time to 120 minutes or less:
Prehospital fibrinolysis should be started within 30 minutes of the arrival of EMS if EMS has fibrinolytic capability and the patient meets the criteria for fibrinolysis;
Door-to-needle time should be 30 minutes or less for patients who are fibrinolysis candidates when EMS does not have fibrinolytic capability;
Door-to-balloon time should be 90 minutes or less when fibrinolysis is not an option and transport to a PCI-capable hospital is an option. .
Dispatch
1 min
Golden hr = 1st 60 min
Total ischemic time: within 120 min
Adapted with permission from Antman EM, et al. Available at:
Accessed November 1, 2005.
Antman EM, Anbe DT, Armstrong PW, et al, American College of Cardiology, American Heart Association, Canadian Cardiovascular Society. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction—executive summary. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to revise the 1999 guidelines for the management of patients with acute myocardial infarction). J Am Coll Cardiol. 2004;44:

15. What happens in the Ambulance?
Paramedics take your history and perform a brief exam IV
Oxygen
Put on the monitor
May receive nitroglycerin under the tongue. (tingle, get a H/A)
Maybe: ECG, thrombolytic (clot dissolver)

16. What happens when you get to the hospital?

17. ED Visits - US 130,000,000 annually 10.4 M chest pain (8.0%) 6.24 M
suspected or actual
cardiac
4.1 M
sent home non-cardiac
50,000 MIs
3.1 M
non-cardiac
(50%)
1.2 M
AMI
(20%)
1.5 M UA
(24%)
374,400
sudden death
(6%)

18. Spectrum of Acute Coronary Syndromes
Presentation
Ischemic Discomfort at Rest
No ST-segment
Elevation
ST-segment
Elevation
Emergency
Department
Cardiac
Markers – + + +
In-hospital
6-24 hours
Unstable Angina (UA)
Non-Q-wave MI
(NSTEMI)
Q-wave MI
(STEMI)
Adapted from Braunwald E, et al. Available at:

19. STEMI: Brief Physical Exam in the Emergency Department
Airway, Breathing, Circulation (ABC)
Vital signs, general observation
Presence or absence of jugular venous distension
Pulmonary auscultation for rales
Cardiac auscultation for murmurs or gallops
Presence or absence of stroke
Presence or absence of pulses
Presence or absence of systemic hypoperfusion (cool, clammy, pale/ashen)
Antman EM, et al. Available at: Accessed November 1, 2005.

20. STEMI: Acute Medical Therapy
General treatment
measures
Analgesics
Nitrates
Oxygen
β-blockers (decrease heart rate)
Primary PCI or coronary thrombolysis (primary PCI preferred after 3 hours)
Aspirin ( mg, acute dose)
Heparin
If PCI:
– Clopidogrel
– GP IIb/IIIa inhibitors
Infarct size
limitation
Reperfusion
Antithrombotic and antiplatelet therapy
Antman EM, et al. Available at: Accessed November 1, 2005.

21. Chest Pain on a Saturday morning
While the physician was examining the ECG, the patient became unconscious and the rhythm on the monitor changed…

22. Chest Pain on a Saturday morning
12:01 100J DC cardioversion, patient immediately in NSR
12:03 Clot box brought to room and catheterization lab team notified
12:04 IV line started, 325 mg aspirin chewed and metoprolol given
12:10 Open cath table and staff available, heparin iv and clopidogrel po given
12:19 Patient’s stretcher rolls

23. Goals of Reperfusion Therapy
Patient
Transport
In-hospital
Reperfusion
D-N ≤ 30 min
5 min
< 30 min
D-B ≤ 90 min
Methods of Speeding Time to Reperfusion
Media campaign
Patient education
Greater use of 9-1-1
MI protocol
Critical pathway
Quality improvement program
Bolus lytics
Dedicated PCI team
Prehospital ECG and Prehospital Rx, if possible
Adapted with permission from: Antman EM, et al. Available at: Accessed November 1, 2005.

24. Time from Symptom Onset to Treatment Predicts 1 Year Mortality—Primary PCI
The relative risk of 1 year mortality increases by 7.5% for each 30 minute delay.
Roughly 1% every 3 minutes
Y=2.86 (± 1.45) X X2 P<.001
De Luca G, et al. Circulation. 2004;109:

25. Meta-analysis of 50,246 Patients in Lytic Trials (Juice to squeeze)
per 1000 treated patients
Absolute benefit 20 40 60 80 3 6 9 12 15 18 21 24
Time to Treatment
Boersma E, et al. Lancet.1996;348:771

26. Primary PCI vs Thrombolysis in STEMI: Meta-analysis (23 RCTs, N=7739)25
Short-term Outcomes
(4-6 weeks)
P<.0001
Bonferroni correction
6 variables: p <0.0083 20
P<.0001 15
P=.0002
P<.0001
Frequency (%)
PCI
P=.032 10
Thrombolytic therapy 5
P<.0001
This meta-analysis encompassed 23 trials in which 3872 patients with STEMI were randomized to primary percutaneous transluminal coronary angioplasty (PTCA) and 3867 patients were randomized to thrombolytic therapy. Stents were used in 12 of the 23 trials and in 8 trials GP IIb/IIIa inhibitors were used.
Results indicated that the incidence of every short-term clinical outcome of interest was significantly higher in patients receiving thrombolytic agents than it was in those who underwent primary PTCA.
Results with PTCA continued to be superior to those with thrombolysis during long-term follow-up and were independent of the type of thrombolytic agent used (76% received a fibrin-specific agent rather than streptokinase) and whether or not the patient was transferred to primary PTCA.
Death
Nonfatal MI
Recurrent
Ischemia
Hemor-
rhagic
Stroke
Major
Bleed
Death, Nonfatal
Reinfarction,
or Stroke
Adapted with permission from Keeley EC, et al. Lancet. 2003;361:13-20.
Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003;361:13-20.

27. What if the ECG is not diagnostic?
(As it is in >95%)

28. Blood Markers Necrosis Something has to die Strain
Natriuretic peptides
Other
Inflammation
Plaque rupture
Ischemia changes the blood

29. ACS Sequence and Timing
All Ischemia
Some Ischemia, Some Necrosis
All Necrosis
Plaque Rupture
Onset of Pain
ED Presentation
Discharge
-12 to 0 hrs
12 to 24 hrs
Amount of Tissue
Time
IMA
cTn
Ischemia
Muscle death
Ventricular Overload
BNP
<> means click the mouse to advance to next in animation
We start with a time line of events in an ACS presentation <>
A plaque ruptures, which leads to chest pain, which provokes a patient to present to the hospital emergency room, and we label presentation as time zero <>
Looking at the amount of tissue involved <>, we can see that the tissue starts ischemic, and prolonged ischemia leads to necrosis, or infarct. <>
IMA rises rapidly with the onset of ischemia, and we believe starts to fall as more of the muscle converts from ischemic to necrotic <>
Troponin, on the other hand, starts to rise slowly with the onset of necrosis, peaks at about 24 hours after presentation (6 hours or so after all the tissue is necrotic and no more is ischemia), and falls slowly over several days. <>
BNP rises once the remaining healthy muscle is required to compensate for the lost pump function of the heart, and therefore may be elevated at the time of discharge. <>
Therefore, there is a progression from ischemia (IMA), to necrosis (troponin) to muscle overload (BNP). These three markers together reveal what is happening during the ACS event.
BNP

30. Appearance of necrosis markers10 20 30 40 50 60 70 80 2 4 6 8 12 18 24 32 48 72
Hours After Onset of MI
CKMB
Myoglobin
TnI
Hospital arrival
Established release kinetics of necrosis markers have consistently demonstrated the sequential release of myoglobin, CKMB and Troponin, respectively. The early rise of myoglobin is also met with an early decline (within 12 hours), making this an important, dynamic surveillance marker in the initial hours post event. It’s dynamic nature also documents the potential value of rapid sequential testing of myoglobin as a way of confirming an acute event vs a pre-existing non cardiac necrotic source. CKMB has greater specificity, is a standardized and trusted immunoassay, and is released within a few hours post AMI. Finally, cardiac Troponin is a highly specific marker but lacks good sensitivity in the first few hours post event.
It is clear that these markers complement each other in providing early sensitivity Myoglobin/CKMB with better specificity Troponin I & T. Studies have examined the potential role of using these markers in a panel approach vs any single marker in isolation.

31. Disease vs Events? Oxygen supply diminishes with disease progression
Time
Oxygen
Oxygen supply diminishes with disease progression
Oxygen demand changes daily and during life
Ischemia occurs when O2 demand exceeds supply

32. What is in the future?
New better markers

33. What is IMA?
Human Serum Albumin (HSA) is a circulating protein in blood with a metal binding site at the N-terminus.
The N-terminus is altered during an ischemic event, resulting in Ischemia Modified Albumin (IMA™). IMA is unable to bind metals at the N-terminus.
Ischemia Modified Albumin = IMA
HSA is the most common protein in blood.
There is a metal binding site at the N-terminus of IMA – for transition metals copper, cobalt and nickel.
It was discovered that exposure to ischemic tissue alters the end terminus of HSA in such a way that it can no longer bind metals.
The conversion of HSA to IMA is mediated by free radical production (see later slides). The organ specificity (ie: to myocardial ischemia) is not well understood.
Bar Or et al, European Journal of Biochemistry, 2001

34. Chest Pain at Presentation
12% ACS
13% Rule Out
75% Grey Zone
Current EP Protocol
EP Protocol with good NPV ischemia marker
25% ACS
35% Rule Out
40% Grey Zone
Without IMA, the chest pain challenge is what to do with 75% of chest pain patients for whom a diagnosis can not be made at presentation, and therefore are subjected to serial blood draws, and other time consuming and expensive procedures such as provocative testing, myocardial perfusion imaging, echocardiography, angiography, and so on.
With IMA, the number of patients who can be discharged early is almost three times as many (the test presently only has indications for use as a rule out).
The potential value of a positive IMA test is to expedite diagnostic evaluation or suggesting more rapid or intensive therapy in higher risk patients.
Therefore number of patients in the “Grey Zone” is considerably reduced.
Excellent clinical data exists to show the value of IMA as a rule out, and additional clinical studies are under way to investigate the value of IMA as a rule in.

35. What if the markers are all negative?
(And they are in >90%)

36. If It Moves, Even Below Your Hospital’s Cutpoint, It Is Bad
Marker
Comparator
OR for 30 day MACE
95% CI
ing Tn
vs. stable Troponin
2.25
ing Tn
3.04
ing CKMB
vs. stable CKMB
0.67
ing CKMB
0.96
Logistic regression models showing the odds ratios for predicting ACS
MACE: MI, revascularization (PCI or CABG), or positive testing (>70% stenosis at
catheterization, [+] MPI or non-invasive stress testing) within 30 days of index visit.

37. All this testing… What’s the end result?
Most (88%) of the time, its negative
You go home
18% of the time, something is positive
ECG  IMMEDIATE Cath lab
Marker  URGENT Cath lab
Stress test  Semi-elective Cath lab

38. What happens in the Cath Lab?
Define the anatomy
Acutely closed vessel  fix it
Chronically closed vessel  nothing
Stenotic vessel: have options
~50%; either medicine or angioplasty works
>70%; most get angioplasty

39. Scotland Epidemiology

40. Prevalence of coronary heart disease in Scotland: Scottish Heart Health Study.
10,359 men and women aged years from 22 districts in the Scottish Heart Health Study
Described the prevalence rates of coronary heart disease in Scotland in and their relation to the geographical variation in mortality in these districts.
Coronary heart disease in Scotland was the highest reported to the WHO from
Angina was more common in men (5.5%) than in women (3.9%)
A history of MI was 3 times more common in men than women
Angina correlated well with mortality from coronary heart disease
Br Heart J Nov;64(5):295-8

41. 2001: The good news
The Cardiovascular Epidemiology Unit at the University of Dundee celebrated its 20th anniversary with a 40 % decline in coronary mortality rate
The steep decline in coronary mortality in Scotland mirrors the pattern in the rest of Britain.
Improvement is a combination of:
Heightened awareness of health issues
Improved diet and more exercise
Improvement in treatments.
Scotland's record on heart disease is much improved
Russia now has the highest coronary mortality rate.

42. 2003 British Women's Heart and Health Study
20% MI, angina, HF, CVA, PVD.
50% HTN, 12% smoked, 25% obese
50% w/ total cholesterol > 6.5 mmol/l, only 3% had low HDL
Age adjusted CVD prevalence
highest in Scotland: 25.0% (21.5% to 28.8%)
lowest in S. England: 15.4% (13.5% to 17.6%).
Woman in Scotland are 1.53 times more likely to have CVD
Of women with CVD
12% are smokers, 1/3 had uncontrolled HTN, 1/3 were obese
90% had a cholesterol > 5 mmol/l.
Only 41% were taking antiplatelet drugs and 22% were taking a statin.
Journal of Epidemiology and Community Health 2003;57:

43. In Scotland Coronary Heart Disease one of the leading causes of death
10,331 deaths in 2005
Scotland has one of the highest death rates from CHD in the western world
Due to
high rates of smoking
poor diet
deprivation

44. In the year ending March 31 2006
Scottish hospitals
48,962 hospital discharges for CHD
16,320 were for AMI(heart attack)
CHD discharges represented around 4% of all acute hospital discharges.
NHSScotland carried out
2,319 Coronary Artery Bypass Grafts 5,803 angioplasties
17,065 angiographies

45. http://www.isdscotland CHD mortality is strongly related to age.
0-44 year olds is 4.1 per 100,000
75+, the rate is  per 100,000
The incidence of CHD is higher in men, elderly and deprived areas of Scotland
Smoking
being overweight
raised blood pressure
raised level of cholesterol

46. Cost of Cardiovascular Disease in the UK
CVD cost the UK £29.1 billion in 2004
(exceeds the GDP of Kuwait)
29% (£8.5 billion) was due to Coronary Heart Disease
27% (£8.0 billion) Cerebrovascular Disease
CVD Cost break down
60% health care
23% productivity losses
17% informal care-related costs
Conclusions:
CVD is a leading public health problem in the UK measured by the economic burden of disease.
Heart 2006;92:

47. Small changes in UK cardiovascular risk factors could halve CHD mortality
The UK called for a 40% reduction in CVD mortality by 2010.
Potential reductions from the year 2000, were calculated for:
Continuation of recent risk factor trends
~10,685 fewer CAD deaths in 2010 than in 2000
Modest additional reductions in cholesterol and smoking
~51,270 fewer deaths
Optimistic changes in obesity, DM, and physical activity, would have relatively small effects.
Journal of Clinical Epidemiology 58 (2005) 733–740