ACS

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ACS a simplified approach

• Shawn Dowling

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Case 1

• 68F. Known CAD (CABG 10 yrs ago). L RSCP over
  past few weeks. States RSCP same as prior but
  brought on by walking one to two blocks
  relieved with rest.
• What are the 3 features of typical CP?
• What kind of angina is this (stable or unstable)?
• What Class of Angina?
• You get ready to tell Bryan about the cardiac RF
  and he tunes out and ignores you..why?

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• Typical CP
• RSCP
• Brought on by exertion/stress
• Relieved with rest/NTG

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• Stable angina
• Angina brought on by exertion and relieved with
  predictable measures (rest, NTG)
• Unstable angina/ACS
• New onset angina w/i past 2/12 and at least CCS
  III
• Rest angina lasting gt20 min presenting w/i one
  week of angina
• Change from baseline

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Pathophysiology of Stable and Unstable Plaques
Thin fibrous cap Thrombus Thick fibrous
cap Smooth muscle cells Lipid rich coreof
McDonalds Media
Unstable plaque
Stable plaque
What is an ACS? How does it relate to this?
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Why distinguish between stable angina and UA/ACS?

• Stable Angina
• Typically represents a stable, fixed lesion that
  has had time to develop collaterals, Sx reflect
  inadequate myocardial O2 supply
• Unstable angina/ACS
• Represents an acute plaque rupture and
  thrombosis

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Terminology

• Acute Coronary Syndromes is the preferred
  terminology to refer a spectrum of disease
  related to myocardial ischemia
• (stable angina)
• Unstable Angina
• NSTEMI
• STEMI

/- abN ECG, -ve markers
/- abN ECG, ve markers
STE on ECG, ve markers
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CCS Classification CCS Classification
Class 0 Asymptomatic
Class I on strenuous activity
Class II on moderate activity  ? 2 blocks or 2 flights of stairs
Class III on mild activity  ? 2 blocks or 2 flights of stairs
Class IV rest or minimal activity
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• What are some secondary causes of MI? (I.e.
  myocardial ischemia not secondary to coronary
  artery plaque rupture)

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Secondary Causes of MI

• Exclude secondary causes (10-15 )
• Coronary vasospasm
• Anemia
• Hypoxemia
• Uncontrolled HTN
• Arrhythmias
• Heart Failure
• Infection
• Drugs i.e. cocaine
• Thyrotoxicosis

? Supply of Myo02
? Demand of Myo02
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• What are some features of the character of Chest
  Pain that make you worry?
• What about reproducible chest wall pain?
• What about response to NTG?

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Goodacre et al. How Useful are Clinical Features
in the Diagnosis of Acute, Undifferentiated Chest
Pain? Academic Emergency Medicine, vol. 9, no. 3,
2002.
Features Predictive of AMI
Thanks Adam
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Goodacre et al. How Useful are Clinical Features
in the Diagnosis of Acute, Undifferentiated Chest
Pain? Academic Emergency Medicine, vol. 9, no. 3,
2002.
Features Predictive of ACS
Thanks Adam
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Case 1s ECG
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• What percentage of people will have a normal ECG
  and have an ACS?
• How about non-specific ST-T changes?
• What carries a higher mortality past 60 days
• STE or STD?

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ECG changes
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GUSTO 2B ST DepressionA High Risk Finding
ST ?
P ? 0.001
ST ?
T-wave inversion
CM Gibson 2002
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Case 2

• 71M. L precordial CP, radiating to L arm/jaw, x
  25 minutes (about 1H ago). Onset with exertion,
  relieved with rest and taking his wifes NTG.
• Cardiac RF smoker, DM, HTN
• ECG NSST changes
• Trop was already sent off b4 you saw the pt.
• Who is going to wait for the 6, 8 or 10H trop?

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Case 3

• 75M. Known CAD, MI last year. EMS bringing pt in
  for abdo pain (sharp, RUQ). They patch in and
  fax ECG- ? STEMI.

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Do you call the cath lab?
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• You get his most recent ECG from 6 months ago and
  it is completely unchanged
• Prior ECHO reports shows LV aneurysm secondary to
  prior MI.

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Not all STE is STEMI

• Retrospective EKG review of 902 adult pts in ED
  admitted to CP centre
• Acute MI cause of ST elevation in only 15 of all
  pts
• Other 85 had alternative diagnosis
• LVH (25)
• LBBB (15)
• BER (12)
• RBBB (5)
• Undefined BBB (5)
• LV aneurysm (3)
• Pericarditis (1)
• Ventricular paced Rhythm (1)
• Undefined ST elevation in 17

Brady WJ. AM J Emerg Med 2001 1925-28 Thank
Mark
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• What percentage of patients are d/cd home with
  MI or ACS?
• Do these patients have a worse outcome?

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• 10 689 patients
• Data collected for 30d (hospitalised patients) or
  at 24 to 72hrs for non-hospitalised patients
  (repeat assessment, ECG, CK-MBs)

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• Final Diagnosis
• 894 (8.5) AMI
• 972 (9) unstable angina
• 21 non-ischemic cardiac problem
• 55 non-cardiac

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• 22 missed unstable angina (2.26)
• MC diagnosis
• stable angina, atypical chest pain
• 19 missed AMIs (2.1 of 894)
• MC diagnosis
• non-cardiac chest pain, pulmonary conditions and
  stable angina

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• Factors associated with non-hospitalisation for
  patients with missed ACI
• female
• lt55 yoa
• non-white
• chief complaint of SOB
• normal ECG
• 30d adjusted risk of mortality 1.7 times higher
  if not hospitalised (95 CI 0.7 to 5.2- NS)

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• Conclusion
• Rate of missed MIs is low, but the patients that
  are missed ? higher MR

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Case 4

• 75M. Hx of CAD.
• Presents with rest angina x 30 minutes.
• Any reliable tool to risk stratify this patients
  likelihood of a poor outcome in 14 days?
• Which historical features and investigations do
  you need to know?

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His story

• Hx
• Age gt65
• Smoker, DM, HTN
• Known stenosis gt 50
• Uses ASA

• Presentation
• ECG no ST deviation
• Enzymes
• Only 1 episode of angina in 24H

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• Risk of all-cause mortality, MI or recurrent
  angina requiring re-vascularization
• TIMI score gt4 considered high risk ACS

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• Caveats and Critique
• tested on admitted patients with unstable
  angina/NSTEMI
• Validation Phase not prospective
• cohort who qualified for enrolment in a phase III
  study (?generalisabilty to all-comers with chest
  pain)
• CKMB was the marker in TIMI but now use Troponin
  without study to prove similarly predictive

Thanks Adam
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Case 5

• 57F. DM, high chol, smoker. L precordial CP,
  rads to shoulder. Lasting 35 minutes now and
  associated with nausea diaphoresis. VSS.
• What is the first thing you want to do (cannot
  answer ABCs)?

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• What percentage of patients with an AMI will have
  a clearly diagnostic ECG at presentation (STE or
  STD)
• 50

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TroponinT

• Highly cardiac specific
• Not found in serum of healthy volunteers (as
  opposed to CK, CK-MB)
• Following myocardial injury, troponin is leaked
  into serum

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Troponin Sensitivity
Time from onset of Sx Approximate Sensitivity
6 hrs 60
8 hrs 80
10 hrs 90
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• Onset of elevation
• 3-6H
• Peak
• 12-18H
• Remain elevated for
• 5-7 days

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Troponin T

• What causes an increased TnT?
• CARDIAC
• Ischemia/ infarction
• Cardiomyopathy
• Pericarditis/Myocarditis
• Cardiac contusion
• Hypertensive emergencies
• Pulmonary embolus
• Renal failure
• Electrical injury
• Sepsis

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TROPONINS T AND IAS PREDICTORS OF MORTALITY
Cardiac Mortality
Total Mortality
6.9
6.4
7
6
5.0
5
4
3.3
3
2.0
1.7
2
1
0
PTS
1993
1057
RR
1641
792
RR
Trop.
Neg Pos
Neg Pos
6
7
No. Trials
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Case 6

• 89M. Hx of ESRD (MWF dialysis). RSCP today x 30
  min. The usual trifecta DM, HTN, high chol.
• ECG NSST
• Trop-0.13, Cr-250
• CCU resident (not fellow) says his trop is just
  up cuz of his Cr can go to the hospitalist.
• What do you think?

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• Over 7000 pts enrolled in GUSTO IV trial
• These were all patients that were suspected of
  having an ACS required gt5 min of angina at
  least 0.5mm STD or ve trop (gt0.1)
• Looked at short-term outcomes (death or MI at 30
  days) based on 1) Trop gt0.1 and trop gt0.03, 2)
  Quartiles of Creatinine Clearance

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Conclusion

• 581 pts had outcome (renal failure, elevated trop
  MI or death)
• 305 had non-fatal MI
• 71 had fatal MI
• 205 died w/o evidence of MI
• Regardless of degree of renal failure, elevated
  troponins predict short term mortality and MIs
  in RF pts

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Case 8

• 74F. HTN, high chol, ex-smoker. RSCP x 3 days,
  LBBB (old).
• Told to come in by FP on call b/c trop 0.38.
• Waited in the WR for 6 hours b/c she did not
  mention her CP simply said she was to come in
  b/c of abnormal blood test. Repeat trop 0.39.
• How do you want to treat her?

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Cardiology Trials Generalizations

• All pts receive ASA heparin
• Nitrates, ß-blockers, CCBs use at discretion of
  treating physicians
• UA/NSTEMI definitions require at least one
  objective finding (ECG changes, elevated cardiac
  markers) therefore most studies on relatively
  high risk pts
• Often use composite E.P. (re-infarction, death,
  need for urgent re-vascularization)
• Renal failure often an exclusion criteria

Thanks Moritz
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Treatment

• Prior to current medical management, MR rate and
  re-infarction rate were 17 and 47 at 3 months
• Now, 3month MR are in the range of 10-12 post MI

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Treatment Strategies

• Anti-ischemic
• Increase supply Oxygen, nitrates
• Decrease demand ß-Bs, morphine, ACE-Is
• Anti-platelet
• ASA, clopidogrel, GPIIb/IIIa inhibitors
• Anti-thrombotic
• Medical UFH, LMWH, thrombolytics
• Invasive PTCA, CABG
• Anti-inflammatory
• Statins

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Oxygen

• Give it
• Definitely if sats lt90, likely to everyone
• Animal data shows that it decreased infarct
  size(110)
• Small human study that showed it resulted in ECG
  changes(111)
• According to AHA - give it

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Nitrates

• Two major studies (GISSI-3 and ISIS-4)
• no reduction in MR
• Meta-analysis of more than 80,000 patients showed
  a MR of 7.7 in the control group, versus 7.4 in
  the nitrate group not s.s.
• Use for Tx of Sx, but if BP low save the BP for
  mortality reducing interventions

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ASA

• Eight RCTs showing a decrease in MR with ASA
• 4 RCTs also showed better to be given early,
  including out-of-hospital
• To prevent outcome (death, MI, ischemic event-
  systematic review) ARR 6.1, NNT-16
• To prevent 1 death(ISIS-2) ARR 2.3, NNT 43

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• In the setting of ACS what dose do we give and
  why?
• 160mg dose came from ISIS-2 but others studies
  have shown that no difference between 75 and
  1300mg
• GI bleeding risks where less with 160 v 325
• Two studies showed that chewed or soluble ASA
  resulted in more rapid bioavailability

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Clopidogrel

• Clopidogrel is a thienopyridine derivative that
  works by inhibiting ADP action on platelet
  receptors
• This then blocks platelet activation and
  aggregation
• Ticlopidine is a similar agent but not used b/c
  of potential severe s/e - agranulocytosis
• Dose 600mg achieves platelet inhibition by 2H,
  300mg by 4-6H, 75mg 3-5 days

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The studies

• CURE
• RCT of plavix(300mg-gt75) ASA vs ASA in NSTEMI
• High risk ACS/NSTEMIs (ECG changes or ve enz)
• Composite EP (cardiac death, non-fatal MI or
  stroke)
• 11.4 in ASA group 9.3 in plavix/ASA group
• ARR 2.1 , NNT 48
• Death alone as an EP - not s.s. decrease(not
  powered)
• More major bleeds with plavix 3.7 vs 2.7 , NNH
  100
• The higher the TIMI score, the more more pts
  benefited from plavix

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• COMMIT
• 45,000pts, RCT, plavix/ASA v ASA
• ARR 0.9 and NNT 111 for composite E.P.
• PCI-CURE
• NSTEMI who underwent PCI
• benefit of early treatment with clopidogrel prior
  to PCI resulted in an ARR of 3.8, NNT-26 of
  composite EP (CV death, MI, need for re-vasc)

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When to give Plavix?

• AHA-2005 Guidelines
• Give 300mg Plavix load w/i 4-6H of pt contact if
• ve cardiac markers or ECG changes consistent
  with ischemia or (high risk TIMI score (gt4)
  without these)
• STEMI (?600mg if planned PCI- ask
  interventionalist)
• Suspected ACS but pt has CI to ASA
• ? Hold if going to CABG
• CLARITY TIMI28 did not show a increase in postop
  bleeding if given plavix- therefore do not hold
  based on presumption pt may have 3VD and may need
  CABG
• If they are planned for CABG, probably best to
  hold

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Anti-thrombins UA/NSTEMI

• A number of studies have looked at the benefit of
  heparin/LMWH in addition to ASA in ACS (TIMI IIB,
  ESSENCE, SYNERGY, A to Z study, RISC, ACUTE II)
• And just as many Meta-analysis done

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• For UA/NSTEMI
• Clear that LMWH/heparin decrease MI and need for
  re-vascularization
• LMWH
• To prevent 1 MI
• ARR 0.8, NNT 125
• To prevent 1 revascularization
• ARR 2, NNT 50

Magee KD. Cochrane Database of Systematic
Reviews 2005.
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• Meta-analysis done
• No difference in death (3.0 in both groups) _at_ 30
  days consistent with findings from other
  studies
• Significant decrease in composite endpoint (death
  or MI) _at_ 30 days (10.1 to 11.0, NNT 107)
  studies only powered to for composite EPs
• Similar blood txn and major bleeding risks

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TIMI IIB ESSENCE
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• What are two contra-indications (relative) to
  LMWH as opposed to Heparin?
• Extrapolation from SYNERGY and meta-analysis
  found that changing from one form another of
  anti-thombin (i.e. from LMWH- heparin) is
  detrimental
• Some evidence from CRUSADE that there were more
  dosing errors and resultant bleeding problems
  with UFH(JAMA Dec 28, 2005, Vol.294)

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B-blockade

• Initial benefit
• Reduction in cardiac index, heart rate, and blood
  pressure
• As a result improved myocardial oxygen supply and
  demand are reflected in reductions in chest pain,
  STEMI evolution

• Long term benefit
• Reduce infarct size
• Reduce recurrent ischemia
• Decrease arrhythmias

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Evidence for B-blockers

• They decrease MR in ACS
• MIAMI, ISIS-1, TIMI IIB
• ARR 2.3, NNT42
• The reduction in mortality is not demonstrated in
  early administration of b-blockers
• TIMI IIB did demonstrate lower recurrent CP and
  re-infarction rates from acute administration
• Some recent evidence that if they are used
  indiscriminately they can increase mortality

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• RCT of metoprolol (15mg IV 200mg PO) vs placebo
• gt45,000 pts
• 93 had STE or BBB, 7 had STD (very high risk
  patients)
• E.P. death, re-infarction, cardiac arrest

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Conclusion from COMMIT

• Death, re-infarction, cardiac arrest
• 9.4 with metoprolol, 9.9 placebo, NS
• Death alone
• 7.7 with metoprolol, 7.8 placebo, NS
• Re-infarction
• 2.0 with metoprolol, 2.5 placebo, SS
• Cardiogenic shock
• 5.0 with metoprolol, 3.9 placebo, SS

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CI to b-blockers post MI

• Absolute
• Heart rate lt 60bpm
• sBP lt 100
• Mod or severe LV failure
• Shocky(Killip 3/4)
• AVB

• Relative
• Severe COPD
• History of asthma
• Severe PVD
• Insulin-dependent DM

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How to give

• 5 mg IV repeat Q5min up to 3 doses to HR ? 60,
  sBP gt100
• What then?
• Wait 15 minutes if hemodynamic stability is
  maintained give 50mg PO

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GPIIB/IIIA Inhibitors

• Potent anti-platelet agent
• Not our domain in ED
• But two studies showed a reduction in combined EP
  for high risk ACS going to PCI
• PURSUIT PRISM-PLUS
• Other studies and meta-analysis have showed no
  benefit of GP2B/3A for ACS without PCI

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ACE-Inhibitors

• Decrease MR post MI, NNT200
• Favourable effect on ventricular remodelling,
  improved hemodynamics and less CHF
• Class effect (likely doesnt matter which ACE-I)
• Dont need to be started x 24-36H
• As a result, we dont get free lunches from
  altace

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Statins

• Numerous studies done showing that they have a
  benefit in decreasing composite endpoints
• Do not need to be started until 24H.
• Not something we need to start in the ED
• NNT around 200

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When would you consider lytics?

• What are the indications for lytics?
• When would you consider lytics over PCI?

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Indications for lytics

• Indications
• gt30mins chest pain and
• At least 1mm STE in at least 2 limb leads or
• At least 2mm in at least 2 adjacent precordial
  leads or
• Presumably new LBBB
• (True Posterior MI new addition by AHA 2005)
• Within 12 hrs of symptoms
• Benefit extends to those 75 and older
• Thrombolysis increased MR if given for STD
  7.4 MR vs 4.9MR with conservative Tx

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Reperfusion Strategies

• Open artery better than closed artery
• Especially within 12H
• Issue becomes which strategy is best
• Thrombolysis
• OR
• PTCA
• Answer is dependent on a number of variables,
  contra-indications to lytics, Sx duration, door
  to Tx time

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• Lytics vs Placebo (n 58,600)
• Initial studies were done with streptokinase
• (GISSI, ISIS 2/3, AIMS, ASSET late 80s)
• 35 day mortality
• 9.6 in lytic group
• 11.5 in placebo group
• ARR1.9, NNT52
• Overall ICH risk 0.25-1 (NNH 100-400) (TNK,
  tPA)

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Continued

• No mortality benefit extended to pts who received
  lytics gt12H after Sx onset (but small s)
• Door to needle time 30 minutes in these study

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Time to Thrombolysis
Effect of Fibrinolytic Rx on 35 d Mortality

• The mortality benefit of fibrinolytic therapy
  diminishes as duration from symptom onset
  increases
• 0-1 h 65 lives saved per 1000 pts Rx
• 1-2 h 37 lives saved
• 2-3 h 26 lives saved
• 2-6 h 29 lives saved

Boersma et al. Lancet 1996348771
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Convenient 1 time dose
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ACC-AHA Recommendations for 2005 JACC 2004
44 E11-E211
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ACC-AHA Recommendations for 2005 JACC 2004
44 E11-E211
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Lytics vs PCI

• 6 RCTs, 3 meta-analysis, 24 other studies
• (GUSTO IIB, PRAGUE-2, SHOCK)
• Generally PCI is better
• Short term death PCI 7 lytics 9
• Non fatal MI PCI 3 lytics 7
• Combined end-points PCI 8 lytics 14

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PCI Generally Preferred for Complicated Patients

• Older than 75
• CHF, Cardiogenic Shock (SHOCK trial)
• Lytics Contraindicated
• Prior AMI, PCI, CABG
• High Risk for Bleeding (CVA, ICH, operation, etc.)

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In-Hospital Management
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Pre-Hospital Management
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Definitions

• Primary PCI
• Rescue PCI
• Facilitated PCI

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If ICH risk gt4 - PCI preferred
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?Re-perfused

• Resolution of Sx
• STE ? by 50
• What percentage of pts with lytics get TIMI 3
  flow?
• 60
• What percentage of pts with PTCA get TIMI 3 flow?
  
• 90

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Case

• 68F. Gets lytics in department for STEMI (cath
  lab busy with another patient).
• This is her ECG

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• What do you want to do
• Pt is completely stable and ASx

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Accelerated IVR

• Used to be thought that it represented
  reperfusion not necessarily the case
• Occurs as a result of increased automaticity
• Can be seen with dig toxicity, DCM
• Can progress to V-Fib Tx as such
• Can become symptomatic from bradycardia usually
  responds well to atropine

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Case

• 73M. Crushing RSCP x 3 hours. Asian gentleman
• Heres his ECG

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• VS
• HR 76, BP 90/40, RR 36, sats 86 on RA
• Diaphoretic, moribund
• Anything else you want to know on exam?
• DDx?

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MI Complications case

• Early Post-MI Complications
• arrhythmias
• cardiogenic shock
• ventricular septal rupture
• acute mitral regurgitation
• acute pulmonary oedema
• ventricular free wall rupture

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