Chest pain and troponins on the acute take J N Townend Queen Elizabeth Hospital Birmingham
3 rd 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) Macrophages Large lipid core Spotty calcification Intra-coronary imaging with OCT 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 stenosis may be delayed until the lesion occupies 40 percent of the internal elastic lamina area The preservation of a nearly normal lumen crosssectional area despite the presence of a large plaque should be taken into account lumen plaque 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
QEHB: With permission ACS Management at QEHB
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 sensitivity Time Course Detects myocardial injury and necrosis, not specific to type 1 MI Upper limit - 99 th 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 16 14 aspirin placebo 12 % 10 8 6 4 2 0 VA Cairns Theroux RISC Verheugt Lancet 1999
Cumulative Hazard Rate Clopidogrel in ACS: The CURE Study Primary End Point - MI/Stroke/CV Death 0.14 0.12 0.10 Placebo + ASA* 11.4% 9.3% 0.08 0.06 Clopidogrel + ASA* 0.04 0.02 0.00 20% RRR P < 0.001 N = 12,562 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
Cumulative incidence (%) K-M estimate of time to first primary efficacy event (composite of CV death, MI or stroke) 13 12 11 10 9 8 7 6 5 4 3 2 1 0 Clopidogrel Ticagrelor HR 0.84 (95% CI 0.77 0.92), p=0.0003 11.7 9.8 0 60 120 180 240 300 360 No. at risk Days after randomisation 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 Reduce to avoid bleeding? Increase to prevent thrombotic events? DAPT trial 2014: Do we still need aspirin or will ticagrelor alone suffice? Global Leaders Twilight 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
K-M estimated rate (% per year) Time to major bleeding primary safety event 15 HR 1.04 (95% CI 0.95 1.13), p=0.434 10 Ticagrelor Clopidogrel 11.58 11.20 5 Non-CABG related bleeding 4.5% vs 3.8%, HR 1.19, p<0.03) 0 0 60 120 180 240 300 360 No. at risk Days from first IP dose 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 eg AF amyloid SAH hypovolaemia Brady-arrhythmia myocarditis sepsis severe anaemia acute heart failure pulmonary embolism acute exacerbation COPD critical illness / ITU admission AKI / CKD hypoxia major trauma heavy exercise 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