Assessment and Management of NonQWave Myocardial Infarctions

1
Assessment and Management ofNon-Q-Wave
Myocardial Infarctions

• by
• Michael R. Tamberella, MD
• Resident Grand Grounds
• November 17, 1998

2
Case Presentation

• Ms. A.L. is an 84 y/o WF with CHF who presented
  to the OPD clinic with cough productive of yellow
  sputum and fever.
• She denied any CP, SOB, N/V, diaphoresis or
  abdominal pain

3
Case Presentation

• PMHx hyperlipidemia, remote pneumonia
• PSHx hysterectomy 1975, bladder tack
  1997
• Medications Zocor 40mg/day
• Allergies NKDA
• Social Hx lives with daughter, works in the
  catering business, Øtobacco, ØEtOH
• FmHx Father died of CVA, Mother died of MI

4
Case Presentation

• Physical Exam
• VS BP-110/70, P-105, R-24, T-101.0
• Gen Thin WF AOx4 in moderate respiratory
  distress
• HEENT WNL
• CV RRR with 2/6 holosystolic murmur at LLSB
• Lungs Bilateral coarse crackles, rhonchii but no
  wheezes
• Abd WNL
• Ext No C/C/E. 2 peripheral pulses
• Skin W/D/I

5
Case Presentation

• Labs 12.5
• 19.8 185 135 101 30
• 39.5 3.9 24 1.0
• CXR RML infiltrate

6
Case Presentation

• Discussion Patient was admitted and treated for
  community acquired pneumonia however, she
  deteriorated rapidly with acute respiratory
  distress was intubated and found to have EKG
  changes consistent with lateral ischemia. She
  was transferred to the CCU and ruled in for acute
  NQWMI with peak CK of 647 and MB of 22. She was
  treated with heparin, IV NTG, and ECASA. An echo
  revealed no resting segmental wall motion
  abnormalities and an ejection fraction of 20.
  Over 48 hours her condition improved, she was
  extubated and transferred back to the floor where
  she continued to do well and completed a 14 day
  course of antibiotics in the TCU then discharged
  to home and returned to her baseline level of
  activity.

7
Introduction

• Differences between Q and NQWMI
• Incidence
• Pathogenesis
• Clinical Presentation
• ECG
• Prognosis
• Evidence behind post MI testing

8
Introduction

• Distinction between QWMI and NQWMI was first
  proposed in the early 1980s based on evidence
  that the terms transmural and non-transmural did
  not correlate with anatomic findings at autopsy.
• NQWMIs represent less extensive area of
  infarction with lower peak CKs but with larger
  degree of jeopardized myocardium.

9
Incidence

• Up to 71 of all MIs
• Increasing over the last 10 years
• newer treatments
• increased public awareness of warning signs
• increased public awareness of risk factors
• HTN, Hyperlipidemia, tobacco

10
Pathogenesis

• Unstable eccentrically located plaques rupture
  causing lipid extravasation and a local
  pro-thrombotic state which leads to clot
  formation and obstruction of the lumen of an
  epicardial artery.

11
Pathogenesis

• QWMIs are characterized by occlusion of a
  proximal section of a coronary artery with an
  extensive area of cardiac necrosis
• NQWMIs are associated with transient reductions
  in blood flow without complete occlusion

12
Pathogenesis

• NQWMIs vs QWMIs
• smaller infarcted areas
• lower peak CKs
• higher percentage of patent infarct related
  arteries
• larger area of viable but jeopardized
  myocardium in the infarct zone

13
Pathogenesis

• NQWMI vs Unstable Angina
• greater degree of incomplete occlusion
• lower flow rate through the culprit artery
• myocardial necrosis

14
Pathogenesis

• Reflow in NQWMI occurs rapidly due to
• early thrombolysis
• decreased vasospasm
• rapid healing of underlying plaque rupture
• collateral blood flow
• anterograde flow through a subtotal thrombotic
  burden

15
Pathogenesis

• Patients with collaterals have
• better cardiac function
• more effective remodeling
• and are more likely to have NQWMI

16
Pathogenesis

• Keen et al
• Coronary angiography within 6 hours of AMI
• 58 Q and 28 NQWMI
• 91 of QWMIs had total occlusion of IRA vs
  39 of NQWMIs (p0.0001)
• 84 of QWMIs had thrombus vs 43 in NQWMI
  (p0.0002)
• 19 QWMIs had collaterals vs 45 in
  NQWMI (p0.06)

17
Pathogenesis

• Keen et al
• Findings suggest that the key angiographic
  difference between QWMI and NQWMI is the presence
  of some form of residual perfusion through the
  infarct related artery
• This perfusion pattern contributes to the high
  incidence of post-MI angina, infarct extension
  and recurrent MI

18
Clinical Presentation

• Diagnosis made by combination of history, ECG
  findings and laboratory evaluation

19
Clinical Presentation

• Symptoms range from no pain to mild epigastric
  discomfort to severe crushing substernal chest
  pain.
• i.e. similar to any acute chest pain syndrome

20
Clinical Presentation

• Typical picture is that of substernal chest pain
  with autonomic symptoms, and ST segment
  depression which persists following the
  resolution of the pain

21
Clinical Presentation

• Unstable presentations such as hypotension, CHF,
  and cardiogenic shock are rare with NQWMI since
  there tends to be a smaller area of damaged
  myocardium

22
ECG Findings

• Unlike QWMI which often present with ST segment
  elevation, NQWMIs often present with a variety
  of ECG changes including ST segment depression,
  ST segment elevation, T wave inversion and no ST
  segment changes at all.

23
ECG Findings

• Kleiger et al
• Found that up to 14 of patients with suspected
  NQWMI developed late Q-waves (after 3 days) with
  no evidence of infarct extension.
• Thus ECGs should be repeated for up to 3 days
  following enzyme peak before categorizing
  patients as having a Q or Non-Q MI

24
Prognosis

• Depends on
• Size of myocardial infarction
• left ventricular function
• presence of arrhythmias

25
Prognosis

• Nicod et al
• 1869 patients with acute MI, 1425 Q and 444 NQ
• One year follow-up
• Primary end point - in-hospital and one year
  mortality

26
Prognosis
In hospital mortality
1-year mortality
Q-wave
11.5
9.2
Non-Q-wave
8.1
13.7
p-value
Plt0.06
Plt0.05
27
Prognosis

• Zareba et al
• 549 patients with acute MI, 363 Q and 186 NQ
• Primary end point - any subsequent cardiac event
• Follow-up 40 months

28
Prognosis - Zareba et al
0.30 0.20 0.10 0
Cardiac Event Rate
0
200
400
600
800
1000
Days
29
Prognosis
Zareba et al
Cardiac event
Q-wave
15.7
Non-Q-wave
16.7
p value
NS
30
Prognosis - Zareba et alPost infarct angina
0.40 0.30 0.20 0.10 0.0
Q-wave p0.0452
Non-Q p0.0002
Chest pain
Chest pain
Cardiac Event Rate
No chest pain
No chest pain
0 400 600 1000 0
400 600 1000
Days
31
Prognosis - TIMI II

• Secondary analysis of 2634 patients
• All patients received thrombolytics
• Primary end point - Death or MI
• 1867 Q-wave and 767 Non-Q-wave MIs

32
Prognosis - TIMI II

• Analysis of differences between Q and NQWMI
• At baseline
• ECG
• Angiography
• Discharge testing
• Follow-up period

33
Prognosis - TIMI II

• Findings at Baseline
• Patients with Q-wave MIs were more likely to be
  male, have anterior MIs and were less likely to
  have used nitrates in the week prior to their MI
  compared to the NQWMI counterparts.

34
Prognosis - TIMI II

• ECG Findings
• QWMIs - More leads with ST segment elevation
• Greater deflection of the ST segments
• Higher percentage of patients with more than
  0.3mV ST segment deflection.

35
Prognosis - TIMI II

• ECG Findings
• Patients with NQWMI were more likely to have
  normalization of ST segments following
  thrombolytics than their counterparts with QWMI.

36
Prognosis - TIMI II

• Angiographic findings
• TIMI 3 flow more likely in NQWMI
• No difference in degree of stenosis
• Similar collateral flow

37
Prognosis - TIMI II

• Pre-discharge testing
• NQWMI patients had better ejection fractions
• QWMI patients were more likely to have CHF
• NQWMI patients had more reinfarction
• One year mortality rate was similar

38
Prognosis - TIMI II
NQ
p0.24
Cumulative Death rate
0 10 20
Q
0 13 26 39 52
Weeks
39
Prognosis - Chung et al

• Predictors of Mortality (age gt70)
• Advanced age
• Advanced NYHA classification
• Advanced Killip classification
• Higher peak CKs
• Depressed LVEF

40
Post MI Testing
Low Level Exercise Stress Symptom Limited
Exercise Stress Nuclear Imaging Dobutamine
Echocardiography Coronary Angiography
41
Post MI Testing

• Why test
• Who has inducible ischemia after MI?
• Evaluate the presence of viable myocardium behind
  stenotic lesions
• Who will benefit from early revascularization

42
Post MI Testing

• Issues to consider
• Hemodynamic Stability of Patient
• Cost
• Risk Stratification - who has jeopardized
  myocardium

43
Post MI Testing - Bissett et al
100
Jeopardized Myocardium
75
50
with jeopardized myocardium
25
Ant. NQ Inf NQ Ant Q Inf Q
44
Post-MI Testing

• Which testing modality best predicts recurrent
  cardiac event?

Rest ECG
Ambulatory ECG
Recurrent Event
Exercise ECG
Thallium Scintigraphy
?
45
Post-MI Testing - Moss et al

• 936 patients with MI within last 6 months
• All patients underwent rest ECG, ambulatory ECG,
  exercise ECG and stress thallium
• Primary end-point first recurrent cardiac event
  (death, MI or unstable angina)
• Follow-up every 4 months for an average of 23
  months

46
Post-MI Testing - Moss et al
Rest
Ambulatory
0.0 0.1 0.2 0.3 0.4
0.0 0.1 0.2 0.3 0.4
Cardiac Event Rate
Cardiac Event Rate
0 200 400 600 800 1000
0 200 400 600 800 1000
Days
Days
Exercise
Thallium
0.0 0.1 0.2 0.3 0.4
Cardiac Event Rate
0.0 0.1 0.2 0.3 0.4
Cardiac Event Rate
0 200 400 600 800 1000
0 200 400 600 800 1000
Days
Days
47
Post MI testing - Moss et al

• ST segment depression on exercise testing or
  ambulatory ECG did not predict subsequent cardiac
  events
• Reversible defects by thallium correlated with
  late cardiac events but results were not
  statistically significant

48
Post MI testing - Moss et al

• Only resting ECG ST segment depression accurately
  predicted risk of recurrent cardiac event
• Study included Q and Non-Q-wave MI but subgroup
  analysis did not differ

49
Low-level Exercise Stress

• Can patients with recent MI exercise?
• What is a low-level exercise test?
• What is the implication of a positive low-level
  exercise stress test

50
Low-level Exercise Stress

• Krone et al
• 141 patients with NQWMI within 2 months of MI
• Exercise Stress to 5 mets
• Follow-up q 3 months x4 then yearly up to 4
• Endpoint - cardiac death and non-fatal MI

51
Low-level Exercise Stress

• Krone et al
• Patients with ischemic changes had more events at
  1 year (plt0.05)
• Pulmonary congestion most important risk factor
  
• Positive stress test plus pulmonary congestion
  had an incidence of 71.4, negative test and
  pulmonary congestion - incidence 5.3. (p0.002,
  odds ratio 45)
• In patients without pulmonaray congestion, low
  level testing added no discriminatory value

52
Symptom Limited Stress Test

• Jain et al
• Low-level exercise stress vs symptom limited
• Internal Control
• 150 patients with acute MI (65 NQ, 85 Q)
• Exercise stress test approximately 1 week post MI
• Tests were evaluated at 70 max HR and at symptom
  limited end point
• Mean follow-up 15 months
• End point - recurrent cardiac event (MI,
  revascularization)

53
Symptom Limited Stress Test

• Jain et al
• 60 positive tests (34 at low level and 26 at
  symptom limited)
• No patient suffered any acute complications

54
Symptom Limited Stress Test

• Jain et al - Who had a positive test and when?

150 patients
NQ
Q
65
85
Low level positive
Low level positive
25
9
26
Sx limited positive
Sx limited positive
34
The incidence of a positive test was
significantly greater at the symptom limited end
point (plt0.0001)

55
Symptom Limited Stress Test
Jain et al.
Predictive Value
50 Cardiac Events
12 lost to F/U
150 patients
Test
- Test
19
31
P0.001
Low level
Sx limited
84 of patients with a negative test had no
subsequent cardiac event
16
31
P0.001
56
Symptom Limited Stress Test

• Jain et al - Conclusions
• Pre-discharge symptom limited exercise stress
  test is safe
• Symptom-limited testing more accurately reflects
  functional capacity
• Symptom-limited testing will identify more
  patients with inducible myocardial ischemia
• Symptom-limited testing may allow earlier
  identification of high risk patients and
  therefore early revascularization

57
Nuclear Imaging
Exercise
Dipyridamole
Thallium
Dobutamine
Tc 99
Adenosine
58
Nuclear ImagingAdenosine Thallium

• Adenosine is very short acting primary coronary
  artery vasodilator that when combined with
  nuclear imaging (i.e. thallium) displays
  heterogenity of coronary bed blood flow

59
Nuclear ImagingAdenosine Thallium

• Mahmarium et al
• Evaluate the role of Adenosine Thallium post MI
• 92 patients
• Adenosine thallium 5 days post MI and
• Coronary arteriography
• Follow-up average of 15 months
• Endpoint - Cardiac death, reinfarction, unstable
  angina or pulmonary edema

60
Nuclear ImagingAdenosine Thallium

• Mahmarium et al

PDS lt20 LV
Freedom from cardiac events
LVEF gt 40
0 20 40 60 80 100
PDS gt 20 LV
LVEF lt 40
0 6 12 18 24
plt0.001 plt0.001
Months
61
Nuclear ImagingAdenosine Thallium

• Mahmarian et al
• Thus small perfusion defects and greater ejection
  fractions correlated with improved event free
  survival

62
Nuclear ImagingDipyridamole Thallium

• Brown et al
• Predictive value of dipyridamole versus coronary
  angiography
• 50 patients
• Testing performed 3 days post MI
• Follow-up - one year
• End point - recurrent MI, or chest pain and ECG
  changes

63
Nuclear ImagingDipyridamole Thallium

• Brown et al

In hospital events
50
20 Tests 30 - Tests
9 events 0 events
64
Nuclear ImagingDipyridamole Thallium

• Brown et al
• In Hospital Follow-up
• The only predictor of in hospital event was
  infarct zone redistribution
• stenosis, multivessel disease, collateral flow,
  and infarct zone wall motion abnormality were not
  statistically significant predictors of cardiac
  events
• EF trended towards improved outcome but not
  statistically significant (p0.06)

65
Nuclear ImagingDipyridamole Thallium

• Brown et al
• Long term Follow-up
• 3 patients reached the endpoint during the long
  term follow-up period
• 2 NQWMI
• 1 Unstable angina

All had infarct zone thallium redistribution
66
Nuclear ImagingDipyridamole Thallium

• Brown et al
• Long term Follow-up
• 12 0f 20 positive tests developed either early or
  late cardiac events.
• 0 of 30 negative tests had events
• plt0.0001

67
Nuclear ImagingDipyridamole Thallium

• Brown et al
• Conclusions
• Dipyridamole Thallium is safe
• The presence of jeopardized myocardium regardless
  of coronary anatomy is the best predictor of
  subsequent events
• Early risk statification with Dipyridamole
  Thallium allows directed approach to
  revascularization after infarction
• Negative testing safely identifies low risk
  patients who can forego further invasive testing

68
Dobutamine Echocardiography

• Allows differentiation of fixed and reversible
  myocardial dysfunction
• Allows estimation of left ventricular function at
  rest and with stress

69
Dobutamine Echocardiography

• Smart et al
• 63 patients with acute MI
• Dobutamine Echo within 7 days of infarct
• All patients received thrombolytics
• Repeat echo 4 weeks later

70
Dobutamine Echocardiography

• Smart et al
• Results
• No arrhythmic complications
• 51 of 63 successfully followed-up

71
Dobutamine Echocardiography

• Smart et al

51 patients
4 week follow-up 22 reversible defects
29 fixed defects
19 reversible defects
3 reversible defects
dobutamine
low-dose dobutamine was a good predictor of
eventual reversible defects
72
Dobutamine Echocardiography

• Smart et al
• Patients with reversible defects had
  significantly lower peak CKs (plt0.001) and more
  NQWMI (plt0.01)
• Combination of peak CKlt 1000, NQWMI and
  reversible defects at low dose dobutamine echo
  identified all 22 of 22 patients with reversible
  defects at 4 weeks

73
Dobutamine Echocardiography

• Smart et al
• Conclusions
• Low dose dobutamine echo is safe
• Low dose dobutamine echo is useful for early
  detection of reversible dysfunction

74
Does early detection of reversible ischemia
leading to early revascularization matter?

• Barillia et al evaluated 21 patients with acute
  MI with low dose dobutamine echo
• 13 underwent revascularization
• Repeat echo performed at 40 days

75
Dobutamine Echocardiography

• Barillia et al
• Echocardiographic Score Index - calculated value
  based on degree of wall motion abnormality
• Higher scores represent more dyskinetic segments

76
Dobutamine Echocardiography

• Barillia et al

1.6
revascularized
medical treatment
1.4
Echo score index
1.2
1.0
Baseline Dobutamine Follow-up
P0.0002
77
Dobutamine Echocardiography

• Barillia et al
• Thus dobutamine echo predicts improvement in left
  ventricular function after revascularization
• Patients who have significant improvement in LV
  function with low dose dobutamine will likely
  benefit from revascularization

78
Coronary Angiography

• Rationale Patients with multivessel disease have
  much worse prognosis than single vessel disease
• However does patency of infarct related artery in
  patients with single vessel disease predict
  future cardiac events?

79
Cath vs Functional Study

• VANQWISH
• Conventional Wisdom More is better
• Multicenter Randomized Controlled Trial
• Conservative vs. Invasive post MI testing
• 920 patients (high risk patients excluded)
• 97 Men
• Follow-up minimum of one year (average 23 months)
• End point death or recurrent MI

80
Cath vs Functional Study

• VANQWISH
• All patients received ECASA, and Diltiazem
• Patients were also eligible to receive NTG,
  ACE-I, beta blockers, heparin or thrombolytics

81
Cath vs Functional Study

• VANQWISH
• Conservative Group
• Radionuclide ventriculography
• Pre-discharge symptom limited treadmill or
  dipyridamole thallium
• Cath if patient had chest pain with ECG changes,
  positive exercise stress test or reversible
  defect on thallium

82
Cath vs Functional Study

• VANQWISH
• Invasive Group
• Coronary angiography as initial post MI test
• Revascularization option left up to individual
  investigators

83
Cath vs Functional Study

• VANQWISH
• Results
• Overall number of events did not differ between
  the 2 groups (p0.35)
• BUT...

84
Cath vs Functional Study
conservative

• VANQWISH

invasive
1.0
1.0
0.9
0.9
0.8
survival
event free
0.8
0.7
0.6
0.7
250 500 750 1000
250 500 750 1000 days

days
85
Cath vs Functional Study

• VANQWISH
• Frequency of death or MI was significantly higher
  in the invasive group

Death
Death or MI
At discharge 1 month 1 year
p 0.007
p 0.004
p 0.021
p 0.012
p 0.025
p 0.05
86
Cath vs Functional Study

• VANQWISH
• Other conclusions
• duration of hospitalization was longer in the
  invasive group (p0.024)
• no subgroup fared better with invasive testing

87
Cath vs Functional Study

• VANQWISH - Hazard ratio

No thrombolysis Thrombolysis Non-anterior
MI Anterior MI No prior MI Prior MI No ST segment
depression ST segment depression Age lt 60 Age gt 60
1.0
0.5
1.5
Conservative better Invasive better
88
Cath vs Functional Study

• VANQWISH - Summary
• There is no evidence that patients who undergo
  early invasive testing fare better. In fact there
  is a substantial risk to this approach at one
  year.
• Patients whose course is uncomplicated should
  undergo non-invasive testing first

89
Cath vs Functional Study

• VANQWISH - Summary
• Who should undergo catheterization?
• Unstable patients
• Patients with recurrent symptoms despite medical
  management
• Patients with inducible ischemia by non-invasive
  testing

90
Conclusions

• NQWMIs are characterized by smaller infarct
  zones but higher post-MI incidence of recurrent
  coronary events
• Functional studies accurately risk stratify high
  risk patients
• Patients with negative functional studies can be
  safely discharged without further testing

91
Conclusions

• NQWMIs are not simply mini Q wave MIs, they are
  unique entities with distinct prognostic
  indicators and deserve individualized assessments
  and treatments

92
The End
Special Thanks to Dr. Jim Warner
93
Prognosis - TIMI II