Chest Pain Of Recent Onset

You may skip this if you feel it’s not the same as your local guidelines. This is from NICE 2010 guideline.

1. Do not exclude ACS with a normal ECG

2. Oxygen administration routinely is not indicated, except

  • SpO2 < 94 percent, aim for SpO2 of 94-98 percent
  • COPD, aim for SpO2 of 90 percent

3. ACS symptoms do not differ between different ethnic groups.

4. Stable angina is diagnosed based on

  • Clinical symptoms alone
  • Clinical symptoms + diagnostic testing

5. What is typical angina? They define anginal pain as

  1. Constricting discomfort in chest, neck, jaw or arms
  2. Precipitated by exertion
  3. Relieved by rest or GTN within five minutes

3/3 = typical angina
2/3 = atypical angina
1/3 = not anginal pain

6. Likelihood of CAD is estimated by sex, age and risk factors

  • With age, the risk increases.
  • Men generally have higher risks than women.
  • Risk is also higher with ECG abnormalities.
  • For men > 70, the risk is >90 percent regardless of typical/atypical symptoms.
  • For women > 70, the risk is 61-90 percent, unless if there are high risk factors where a risk of > 90 percent is assumed.

Risk factors: smoking, diabetes, hyperlipidemia, hypertension, previous family history of CAD, based on these, patients are divided into high or low risk factors.


– Risk is > 90 percent: manage as stable angina, no further testing required
– Risk is 61-90 percent, offer invasive angiography
– Risk is 31-60 percent, offer functional imaging (stress imaging eg echo, MRI or perfusion imaging eg cardiac SPECT and first pass contrast enhanced MR perfusion)
– Risk is < 30 percent, offer CT calcium scoring.

  • If the calcium score is 0, consider other causes of CP.
  • 1-400: offer 64 slice or above of CT coronary angiography
  • > 400: offer invasive coronary angiography. If this is not clinically appropriate and revascularisation is not considered, offer non-invasive functional imaging.

7. Note that
– Angina is a clinical diagnosis.
– Coronary angio is anatomical diagnosis. .
– Functional imaging is functional testing for MYOCARDIAL ISCHEMIA.
– Need to emphasize that demonstrable obstructed CAD (angio) or ischemia (functional testing) is neither necessary nor sufficient for a diagnosis of angina.
(the statement here is quite confusing, but what I understand is to qualify as angina using diagnostic testing, you need to have clinical symptoms. Diagnostic testing alone is not enough for angina diagnosis. But clinical symptoms alone without any testing is enough to make the diagnosis.)

8. For people with confirmed CAD (eg previous MI, revascularisation), offer non invasive functional testing when it’s not sure whether the CP is caused by myocardial ischemia. Exercise ECG can be used instead of functional imaging.

9. If coronary angiography or CT coronary angiography shows CAD of uncertain significance, offer non-invasive functional imaging.

10. If non-invasive functional imaging results are inconclusive, offer invasive coronary angio.

11. Do not use exercise ECG to diagnose/exclude angina in a patient without known CAD.**

12. For functional imaging
– Adenosine or dipyridamole for perfusion imaging.
– Exercise or dobutamine for stress echo or MRI.

13. Make a diagnosis of angina when

  • Significant CAD obstruction is found in angio (70 percent stenosis in at least one major epicardial artery or 50 percent in LMCA) OR
  • Reversible ischemia is found in functional imaging.

14. If typical chest pain but low risk, consider
– Hyperdynamic circulation eg anemia, thyrotoxicosis

15. Syndrome X is typical anginal pain + clean arteries in angio (due to microvascular circulation dysfunction).

Above are some of the points I got. Particularly interesting points are:

  1. Risk stratification based on symptoms, risk factors and sex, age.
  2. Use of modern imaging techniques in the diagnosis of angina.
  3. This statement which is very confusing to me “Exercise ECG should not be used to diagnose or exclude stable angina without known CAD”. Exercise ECG is only recommended to be used instead of modern imaging techniques if the patient has known CAD but the CP cause is uncertain.

So I went to do some research for point 3.

– Probably this recommendation originates from previous meta-analyses which have not included patients without known CAD.

– In a meta-analysis by A.Banerjee et al,

  1. Stress test is bad in excluding or diagnosing CAD in low risk patients (wide confidence interval). Low risk patients shouldn’t even be tested at all in my opinion unless there are high risk features eg ECG changes.
  2. Intermediate risk patients? They should probably get a stress test. A patient with negative test still has decreased likelihood (although very small) of getting CAD. A frequent follow up will be needed.
  3. Echo is better than ECG in excluding and diagnosing CAD.

1 2

– Bad of stress test

  1. MI happens when the plaque ruptures. But the ruptured plaque does not always occlude the artery > 70 percent (which is what stress tests detect)..
  2. Stress tests do not detect microvascular occlusion. But MI can happen from that.

Exercise threadmill test is bad test.  50% of women and 25% of males with reversible perfusion defects detected by nuclear stress tests had a normal ETT ((Hoilund- Carlsen, P.F., et al, Am J Card 95:96, January 1, 2005). Also, sulfonylureas attenuate the ST segment, producing false negatives.

  • But there is good too. ETT predicts cardiac events within 30 days. A low risk patients with negative ETT would not likely to have cardiac events within a month. The keyword here is LOW RISK (= minimal risk factors). A known CAD patient with negative ETT is NOT LOW RISK PATIENT. He may have a non-occlusive CAD and a plaque waiting to rupture.

Nuclear perfusion scans? They are good for acute MI, but not so for ACS if the patients are not in acute ischemia. However, the negative predictive value is important.

  • A large meta-analysis, J Am Coll Cardiol. 2007 Jan 16;49(2):227-37, reported the negative predictive value for AMI and cardiac death was 98.8% for the three years following the study (95% confidence interval [CI] 98.5 to 99.0).

So further googling led me to DIAD study:

The original DIAD study (Diabetes Care, 2004)  randomized 50-75 yo diabetic (mean HbA1c 7%) patients without known CAD ( a group considered to be intermediate-high risk) to

  1. Screened & 5 years follow up
  2. Non-screened group (only follow up)

The screening method was adenosine-stress MPI.

What they found?
– 22% of the patients had silent ischemia,

Cardiac outcomes of the patients in DIAD study were also investigated (JAMA 2009):

  1. Same percentage of patients from screened and non-screened groups have non fatal MIs and cardiac death (3 percent each).
  2. 23/32 events in male population -> 4 percent from 601 male participants
    9/32 events in female population -> 1.7 percent from 522 female participants
  3. Positive predictive value of positive MPI is not high (12 percent in the study). However, those with normal MPI or small defects had significantly lower event rate than those with moderate or large defects.

Lessons learnt:

  • Silent ischemia can happen in diabetics without known CAD.
  • However, MPI screening did not reduce CV events, probably because the cardiac event rates were low in the studied patients.
  • Thus, asymptomatic patients, regardless of risk, should probably not be screened by stress tests.
  • Patients with normal MPI are less likely to have cardiac events compared to those with moderate/large defects. (note that this is a population with moderate-high risk of CAD)

Learning points about stress testing:

  1. ETT is good only at predicting events at 30 days. However, in high risk patients, a normal ETT means nothing.
  2. MPI is good at excluding but not diagnosing MI.

So why is the recommendation from NICE “Exercise ECG should not be used in patients without known CAD to exclude/diagnose angina”? Note, NICE is referring to patients with symptoms:

  1. Exercise ECG with its poor sensitivity will probably miss many with non-obstructive CAD.
  2. A normal MPI means that risk of MI and cardiac death over the next 3 years is significantly reduced.

Low risk patients: shouldn’t had any stress test.
Intermediate risk patients:

  • Open to debate. Guidelines said yes, but many studies said stress test doesn’t mater.
  • Need to understand that a negative stress test = you do not have a fixed stenosis, but it does not predict the instability of your plaque (plaque rupture is the cause of MI).

High risk: go to angio straight with revascularisation considered.

Modern imaging techniques

  1. Nuclear perfusion scan eg MPS with SPECT (blood flow through the arteries is determined by how much of the radioactive substance is seen in the heart muscle) or MUGA (radioactive tracer will attach to RBCs and pumped out of LV, can be used to estimate EF)Example of cardiac SPECT

    From Google imageExample of MUGA

    From Google image
  2. First pass contrast enhanced MR perfusion (with use of gadolinium)
    –  Gadolinium chelates are water-soluble and are able to diffuse rapidly into the extracellular space across the capillary membrane.
    – A deficient increase in signal intensity in a myocardial region indicates a myocardial perfusion defect
    – The heterogeneity of the ischemic tissue does not last long as recirculation leads to equilibration between the vascular and extracellular compartments, usually within seconds. This emphasizes the importance of first-pass imaging of the contrast agent.
    Phases of a first-pass gadolinium- enhanced myocardial perfusion study in 1 of the 3 slices in the sequence, corresponding to the mid-ventricular segment. A. Baseline, immediately before contrast injection. B. Contrast reaches the right ventricle. C. Contrast reaches the left ventricle. D. Contrast reaches the myocardium, and a uniform increase in signal intensity is observed in all the regions, indicating normal myocardial perfusion.
    A perfusion defect in myocardial wall.


  1. National Institute for Health and Clinical Excellence. Chest Pain of Recent Onset: Assessment and Diagnosis of Recent Onset Chest Pain or Discomfort of Suspected Cardiac Origin.
  2. Diagnostic Accuracy of Exercise Stress Testing for Coronary Artery Disease
    A Systematic Review and Meta-analysis of Prospective Studies
    A. Banerjee; D.R. Newman; A. Van den Bruel; C. Heneghan
    Int J Clin Pract. 2012;66(5):477-492.
  3. Detection of silent myocardial ischemia in asymptomatic diabetic subjects: the DIAD study.
    Wackers FJ1, Young LH, Inzucchi SE, Chyun DA, Davey JA, Barrett EJ, Taillefer R, Wittlin SD, Heller GV, Filipchuk N, Engel S, Ratner RE, Iskandrian AE; Detection of Ischemia in Asymptomatic Diabetics Investigators
    Diabetes Care. 2004 Aug;27(8):1954-61
  4. Cardiac Outcomes After Screening for Asymptomatic Coronary Artery Disease in Patients With Type 2 Diabetes
    The DIAD Study: A Randomized Controlled Trial FREE
    Lawrence H. Young, MD; Frans J. Th. Wackers, MD, PhD; Deborah A. Chyun, MSN, PhD; Janice A. Davey, MSN; Eugene J. Barrett, MD; Raymond Taillefer, MD; Gary V. Heller, MD, PhD; Ami E. Iskandrian, MD; Steven D. Wittlin, MD; Neil Filipchuk, MD; Robert E. Ratner, MD; Silvio E. Inzucchi, MD; for the DIAD Investigators
    JAMA. 2009;301(15):1547-1555
  5. The prognostic value of normal exercise myocardial perfusion imaging and exercise echocardiography: a meta-analysis.
    Metz LD1, Beattie M, Hom R, Redberg RF, Grady D, Fleischmann KE.
    J Am Coll Cardiol. 2007 Jan 16;49(2):227-37
  6. Assesment of Myocardial Perfusion by Cardiovascular Magnetic Resonance: Comparison With Coronary Angiography
    Guillem Pons Lladó, Francesc Carrera, Rubén Leta, Sandra Pujadas, Joan García Picart
    AOCR Article [Cardiac Imaging: Review of Cardiac MR Perfusion Imaging] [04/15/13]
  8. Stress Tests: Well Reimbursed, Rarely Helpful
    by David H. Newman, MD
  9. The Stress Test: A Good Test Often Misapplied
    by Kevin Klauer, DO
  10. Stress test vs flipping a coin: which is more accurate?
    by Carolyn Thomas 1 March 2014

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