Chest pain and troponins on the acute

take

J N Townend
Queen Elizabeth Hospital Birmingham
 3rd Universal Definition of Myocardial Infarction

• Type 1: Spontaneous MI related to atherosclerotic plaque

rupture…

• Type 2: Myocardial injury with necrosis where a condition other

than CAD contributes to an imbalance between myocardial
oxygen supply and demand

• Type 3: Cardiac death with symptoms suggestive of myocardial

ischaemia and presumed new ischaemic ECG change

• Type 4: a. MI related to PCI b. MI related to stent thrombosis

• Type 5: MI related to CABG

European Heart Journal (2012) 33, 2551–2567

 The Vulnerable Coronary Plaque
Fibrous cap < 65 mm (TCFA) Intra-coronary imaging with
Macrophages OCT
Large lipid core
Spotty calcification

Lipid core

mod. From Ross R, N Engl J Med 340 (1999) & Falk et al., Circulation 92 (1995)
 Coronary Remodelling
• ‘Human coronary arteries
enlarge in relation to plaque
area’
• ‘Functionally important lumen
lumen stenosis may be
delayed until the lesion
occupies 40 percent of the
internal elastic lamina area’
plaque
• ‘The preservation of a nearly
normal lumen cross-
sectional area despite the
presence of a large plaque
should be taken into
account…’

Glagov et al. New England Journal of Medicine 1987

Plaque Rupture
STEMI vs. NSTEMI
Pathophysiology

STEMI

NSTEMI
Mortality at 6 months
(GRACE Registry N = 43810)

BMJ 2006
 STEMI

Emergency Treatment
– Aspirin, IV access, defibrillator
– Call the PPCI phone and transport to cath lab
– Restore coronary flow and myocardial perfusion
 Takotsubo (Stress) Cardiomyopathy
Presenting as STEMI
• 64 yr female
• Non smoker
• Recent stress due to
‘family’
• ECG ST elevation in
anterior leads
• Normal coronary
arteries
NSTEACS (NSTEMI and Unstable Angina)

1. Diagnosis – clinical, ECG and circulating markers

2. Risk Assessment – GRACE score
3. Treat
1. Anti-platelets: aspirin + clopidogrel /prasugrel / ticagrelor
2. Anti-thrombotics: LMWH/Fondaparinux
3. Anti-anginals: beta-blockers, IV nitrates
4. Plaque stabilisers: statins and ACE inhibitors
Refer to cardiology
1. Angiography in medium & high risk (GRACE predicted 6
month mortality> 3% (ECG change +/- Tn elevation)
2. Urgent revascularisation
 Diagnosis
• Chest pain is very common
– Typical pain, funny pain, funny turns, syncope, acute SOB…
– Consider risk factors (pre-test probability)

• ECG interpretation
– requires learning and continued exposure
– Fixed (non significant) ECG abnormalities are common

• Troponin interpretation
 ACS Management at QEHB

QEHB: With permission

The ECG

NB can be normal
• 1684 consecutive US
patients with MI identified
retrospectively
• Frequency of failure to
diagnose ST/T change on
presenting ECG was 12%
• In hospital mortality:
7.9% vs. 4.9%

Masoudi et al. 2006 Circulation

 HS Tn
• HS Tn improves speed and
Time Course
sensitivity
• Detects myocardial injury and
necrosis, not specific to type 1 MI
• Upper limit - 99th centile – problems
• Elevation on admission rules in
when typical chest pain
• Serial (2) negative HS cTn are
required to rule out
• Use of change in HS cTn
– 1 hour or 3 hours
– Depends on time of
presentation, may be looking for
a rise or fall
– 20% is sensitive, 50% change
quite specific
• 50% vs. 23% discharged
from ED
• LOS reduced to 18 vs.25
hours
• Higher rate of detection of
CAD 9% vs. 3.5%

New Engl J Med 2012

Risk Stratification
 Treatment of ACS
ACS is a thrombotic, platelet
driven event

– Anti-platelet agents and

anti-thrombotics
improve mortality and
morbidity

– Anti-anginals not proven

to improve prognosis
 Aspirin in ACS
Effect on Death/Recurrent MI
18
aspirin
16
placebo
14

12

10
%
8

0
VA Cairns Theroux RISC

Verheugt Lancet 1999

 Clopidogrel in ACS: The CURE Study
Primary End Point - MI/Stroke/CV Death
0.14 11.4%
Placebo
0.12 + ASA*
Cumulative Hazard Rate

9.3%
0.10

0.08 Clopidogrel
+ ASA*
0.06

0.04 20% RRR

P < 0.001
0.02 N = 12,562
0.00

0 3 6 9 12
Months of Follow-Up
The CURE Trial Investigators. N Engl J Med. 2001;345:494-502.
Ticagrelor compared to clopidogrel:
More potent, not a pro-drug – no metabolism needed, faster onset, reversible

New Engl J Med 2009

K-M estimate of time to first primary efficacy
event (composite of CV death, MI or stroke)

13
12 Clopidogrel 11.7
11
Cumulative incidence (%)

10 9.8
9
Ticagrelor
8
7
6
5
4
3
2
1 HR 0.84 (95% CI 0.77–0.92), p=0.0003
0
0 60 120 180 240 300 360
Days after randomisation
No. at risk
Ticagrelor 9,333 8,628 8,460 8,219 6,743 5,161 4,147
Clopidogrel 9,291 8,521 8,362 8,124 6,743 5,096 4,047

K-M = Kaplan-Meier; HR = hazard ratio; CI = confidence interval

 Unresolved questions about
DAPT
• Duration • Do we still need aspirin or will
– Reduce to avoid bleeding? ticagrelor alone suffice ?
– Increase to prevent – Global Leaders
thrombotic events? – Twilight
– DAPT trial 2014:

Reduction in death/MI/CVA HR 0.71

Increase in major bleeding 2.6% vs. 1.6%
 Bleeding Risk in ACS
• Bleeding after ACS is associated with high risk of
mortality (x5 at 30 days) and MI
• Increased risk with increased efficacy of drugs
• Increased risk of both thrombosis and bleeding in
diabetes, frailty, CKD…
• Bleeding risk scores
Time to major bleeding – primary safety event

15
K-M estimated rate (% per year) HR 1.04 (95% CI 0.95–1.13), p=0.434

Ticagrelor 11.58
11.20
10 Clopidogrel

5 Non-CABG related bleeding

4.5% vs 3.8%, HR 1.19, p<0.03)

0
0 60 120 180 240 300 360
Days from first IP dose
No. at risk
Ticagrelor 9,235 7,246 6,826 6,545 5,129 3,783 3,433
Clopidogrel 9,186 7,305 6,930 6,670 5,209 3,841 3,479
OASIS-5: RCT of 20078 patients with ACS to
fondaparinux or enoxaparin

• Efficacy equal

Fondaparinux was associated

with:
• Near 50% reduced risk of major
bleeding
– (4.1 vs. 2.2%) at 9 days. P<0.001)

• Reduced mortality at 30 days

and 180 days
OASIS-5 NEJM 2006
 Timing of Angiography

< 2 hours

<24 hours (UK mean is c.60 hours)

<72 hours

Roffi M, et al. 2015.. Eur Heart J 2016:37;267–315

 Case 1
67 year old female
Collapse with chest pain and SOB
Obese, smoker
SOB ++
Direct to cath lab, delay 30 mins
Case 1
 Case 2
• 79 yr female
• Hypertension
• Multiple previous PCI
• TnT 63
• ECG
 Case 3
47 yr old male
Typical chest pain at rest x 1
No risk factors
cTn >400
Cath lab at 37 hours
myocarditis MI cardiomyopathy no cause

Assomull et al. EHJ 2007

 Case 4
• 75 yrs female
• Smoker, COPD
• SOB ‘tight’
• Tn 155
• ECG
 CTPA
mucous plugging in lower zones
 Case 5
• 77 yr female
• COPD
• SOB and chest
discomfort
• New onset AF
• Tn T 214 and 628
• Near normal
coronary arteries
Myocardial Injury (Type 2 MI)

European Heart Journal (2012) 33, 2551–2567

 Myocardial Injury (Type 2 MI) is common

Tachy-arrhythmia amyloid SAH hypovolaemia

eg AF
Brady-arrhythmia myocarditis sepsis severe anaemia

acute heart failure acute exacerbation critical illness / AKI / CKD

COPD ITU admission
pulmonary hypoxia major trauma heavy exercise
embolism
coronary spasm stroke myocarditis anthracyclines

Any sick patient…

– Commandment 3: Make the Diagnosis of Acute MI (type 1)
based on Tn and the Clinical Scenario

– Tn is checked in large numbers of low risk patients making

interpretation difficult. Typically < 10% of such patients will
have an ACS

– Determine pre-test probability of ACS before ordering Tn

– Do not consider the Tn result in isolation – type 1 MI or

myocardial injury?

Heart 2012
 How to Use Troponin

“There are no facts, only

interpretations”

Nietzsche