Coronary Artery Disease: Diagnostic Tests

Medical device diagnostics are based on the patient’s history, any symptoms, and the results of laboratory diagnostics

Mandatory Diagnostics

  • Resting electrocardiogram (resting ECG with 12 leads) – Indications:

    [Myocardial infarction/heart attack: new pathologic Q-spikes? ST-segment elevation? ; complex ventricular arrhythmias?]Wg. transient ST-segment elevation see below “Further notes”.

  • Exercise ECG (electrocardiogram during exercise, that is, under physical activity/exercise ergometry) – Indications: For intermediate pretest probability (VTW; 15-85%) of coronary artery disease (CAD) based on sex, age, and clinical symptoms; before starting a fitness program; do not use the procedure if VTW for the presence of stenosing CAD exceeds 65%Contraindications: patients with WPW syndrome, pacemaker pacing (VVI /DDD), ST-segment depression at rest > 1 mm, or left bundle branch block (due tolimited assessability of ST segments) → perform imaging here[evidence of coronary artery disease (CAD) in exercise ECG:
    • ST-segment:
      • Newly occurring descending or horizontal ST dips (≥ 0.1 mV, 80 msec after the J-point).
      • Ascending ST segment (depression ≥ 0.15 mV, 80 msec after the J point).
    • Clinical symptoms of CHD: angina (chest tightness, heart pain) and/or dyspnea (shortness of breath).

    Duration of the examination: depending on the level of stress up to 15 minutes.

  • Echocardiography (echo; cardiac ultrasound) – indications:
    • Evidence of left ventricular hypertrophy (class IIb).
    • Pathological resting ECG
    • Vitium suspicious heart murmur (heart defect)
    • Indication of heart failure (cardiac insufficiency)

    [CHD: evidence of exercise-inducible, reversible regional wall motion abnormality secondary to myocardial ischemia/poor perfusion of the myocardium]Duration of examination: 20 to 30 minutes.

Optional diagnostics (according to symptomatology or pre-test probability).

  • CT coronary angiography (radiologic procedure that uses contrast agents to visualize the lumen (interior) of the coronary arteries (arteries that surround the heart in a wreath shape and supply blood to the heart muscle)), MR angiography if necessary – to assess regional and global cardiac function and fractional flow reserve (FFR). FFR indicates the ratio of the mean blood pressure distal to the stenosis to the mean aortic pressure; considered a metric that provides an indication of how much a stenosis (narrowing) restricts blood flow in the coronary vessel (heart vessel); gold standard for analyzing coronary stenosis; measured using an intracoronary pressure-measuring wire; grade of recommendation: class 1a); indications:
    • Pretest probability: stable CAD/stenosing CAD (intermediate).
    • Patients who have developed an acute coronary syndrome.
    • Patients who have persistent angina under guideline-directed drug therapy
    • Patients with pathological results of noninvasive examinations.
    • Patients who have survived sudden cardiac arrest or life-threatening ventricular arrhythmia
    • Patients with symptoms of chronic heart failure (heart failure) with unknown coronary status or V.a. progression (progression) of CHD.

    Note: The number of purely diagnostic coronary angiographies can be greatly reduced by means of estimation of fractional flow reserve (FFR; gold standard for analysis of coronary stenosis/cardiac vasoconstriction) using multislice CT scans (FFR-CT). The procedure can also be used for noninvasive functional imaging, assessing myocardial perfusion.The National Institute for Clinical Excellence (NICE) in the United Kingdom declares the procedure to be the first-line CHD diagnostic test for clinically typical or even atypical angina symptoms, as well as for angina-typical ECG changes. According to the ESC guideline, the procedure has the highest sensitivity (percentage of diseased patients in whom the disease is detected by the use of the test, i.e. a positive test result occurs) with 95-99%.Duration of the examination: less than 5 minutes.

  • Recommended functional procedures by the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS) for noninvasive diagnosis for patients with intermediate probability of chronic CHD:
    • Stress echocardiography – To detect or exclude stress-induced reduced perfusion (wall motion abnormalities? ); according to the ESC guideline, the procedure has the highest specificity (probability that actually healthy individuals who do not have the disease in question will also be identified as healthy in the test) at 92-95%. Note: see below “Further therapy” comments on patients in whom the stress ECG indicates CHD (+ECG), but no wall motion abnormalities (WBS) are detected in the stress echo (-echo).
    • Myocardial scintigraphy (SPECT – Single Photon Emission Computed Tomography; Myocardial Perfusion SPECT) – assessment of myocardial perfusion (blood flow to the myocardium/cardiac muscle) and ejection fraction; Types of stress are – as in exercise ECG and stress echocardiography – physical stress via ergometry (bicycle or treadmill) or, alternatively, in case of physical limitations, pharmacological stress with the vasodilators (adenosine or regadenoson) or, in rarer cases, with dobutamine if contraindications to vasodilators existThe procedure is a suitable tool for the preliminary evaluation of patients with stable angina pectoris. It has a high sensitivity of 90-91% according to ESC guidelines.Duration of the examination: up to 4 hours, with longer breaks in between.
    • Cardiac magnetic resonance imaging (stress MRI; dobutamine MRI; stress perfusion MRI) – for intermediate pretest probability of CHD, if any of the following ECG changes are present: Ventricular rhythm due to pacing or left bundle branch block or inconclusive ergometry for early detection of patients at increased risk of infarction; stress perfusion MRI involves bolus application of MR contrast agent during infusion of a vasodilator (adenosine or regadenoson) and recording of passage through the heart with ultrafast MR sequences. [Significantly increased incidence rate for the events of myocardial infarction and cardiovascular-related death in patients with evidence of ischemia/evidence of reduced perfusion on MRI]Duration of studies:
      • Stress perfusion MRI: 20 to 30 minutes.
      • Dobutamine MRI: 40 to 60 minutes
    • Myocardial perfusion study with adenosine or dipyridamole to study perfusion or wall motion (depending on study approach).
    • Positron emission tomography (PET; myocardial perfusion PET) with the radiopharmaceutical 18F-sodium fluoride (18F-NaF) for cardiac perfusion measurement.
      • Preventive procedure for detection of atherosclerotic risk plaques of coronary arteries.
      • Particularly suitable for patients with multivessel disease
  • Long-term electrocardiogram – for better assessment of arrhythmias.
  • Cardio-computed tomography (cardio-CT) including measurement of coronary artery calcification (CAC; CAC scan) – early detection of coronary sclerosis (CAC score; calcium score for risk estimation)Indications: Patients at low to intermediate risk for CHD for risk assessment or avoidance of overtreatment of low-risk patients (favorable alternative to screening for CHD)In a long-term study, the coronary artery calcification (CAC) determined correlated with mortality within the next 15 years. Cardio-computed tomography (cardio-CT) avoided six of seven cardiac catheterization examinations in patients with chest pain or atypical angina (chest tightness, heart pain) in a randomized trial, with no increased incidence of cardiovascular disease in the first three years thereafter. There was no significant difference for a MACE event (“major adverse cardiovascular event”; defined here as apoplexy (stroke), myocardial infarction (heart attack), cardiac death, unstable angina, or revascularization) when comparing the cardio-CT group and the cardiac catheterization patients. Note: In patients with IOCA (ischemia and no obstructive coronary artery disease; “non-obstructive CHD”), some of whom have pronounced angina pectoris symptoms and a positive stress test result (echocardiogram), no relevant coronary stenoses (narrowing of the coronary arteries) are shown on cardio-CT.
  • Cardio-magnetic resonance imaging (synonyms: cardio-MRI; cardio-MRI; MRI-cardio; MRI-cardio) for targeted imaging of the heart – for diagnosis of functional disorders of the heart.
  • X-ray of the thorax (X-ray thorax / chest), in two planes – to assess the size of the heart, lung congestion, pleural effusion.
  • Transcranial Doppler sonography (ultrasound examination through the intact skull for orienting control of cerebral (“concerning the brain”) blood flow; brain ultrasound) – Doppler sonographic evidence of stenosis, plaques, or intima-media thickening/thickness (IMT; IMD) of the carotids (carotid arteries) signify increased risk of myocardial infarction (heart attack)/apoplexy (stroke)
  • Ankle-brachial index (ABI; examination method that can describe the risk of cardiovascular disease (heart and vascular disease)).

Further notes

  • Transient ST-segment elevation in acute coronary syndrome /4-24% of patients): TRANSIENT study concludes that these patients behave like NSTEMI patients; mircovascular obstruction is rare (4.2% versus 50% in STEMI patients):Patients with transient ST-segment elevation tend to be younger, frequent smokers, and majority male compared with STEMI patients.
  • Fractional flow reserve (FFR) indicates the ratio of mean blood pressure distal to the stenosis to mean aortic pressure; considered a metric that provides an indication of how much a stenosis restricts blood flow in the coronary vessel (heart vessel); gold standard for analyzing coronary stenosis; measured using an intracoronary pressure-measuring wire; grade of recommendation: Class 1a)FFR: IQWIG: Higher benefit when indicated for PCI (myocardial infarction less frequent) but not in stable CHD (neither evidence of benefit nor harm).
  • A further development of the classic FFR is the so-called “iFR” (“instantaneous wave-free ratio”). iFR is performed using high-pressure pressure wires that are passed distal to the coronary stenosis (narrowing of the coronary artery). IFR isolates a specific period in diastole, called the wave-free period, and uses the ratio of distal coronary pressure (Pd) to the pressure observed in the aorta (Pa) over this period. It has been demonstrated that iFR-guided therapy is not clinically inferior to the FFR-guided approach to revascularization

Eligibility criteria for the different noninvasive procedures

CT angiography Stress echocardiography Myocardial perfusion SPECT Stress perfusion MRI Dopamine stress MRI
Target mechanism Coronary morphology Wall movement Perfusion, function Perfusion Perfusion or wall motion (depending on investigational approach), function.
Target structure Coronary arteries Total left ventricular myocardium total left ventricular myocardium left ventricular myocardium 3 to 5 representative layers
Duration of the study <5 minutes 20-30 minutes <10 minutes load, (twice) 5 to 20 minutes camera (total time incl. breaks up to 4 hours) 20-30 minutes 40-50 minutes
Load procedure ergometric, dobutamine, adenosine* . ergometric, regadenoson,adenosine, rarely dobutamine* adenosine* , regadenoson dobutamine*
Ionizing radiation X-ray radiation none (ultrasound) Gamma radiation None none
Restriction for pacemakers None none none depending on the pacemaker system dependent on pacemaker system
Disadvantages none Possibly restricted sound windows possibly weakening artifacts (chest, diaphragm) none none
Radiation exposure* * Intra- and interobserver variability. Radiation exposure* *

* The use of these drugs is an off-label use* * Radiation doses from the examination depend on the examination protocol, procedure, and technical equipment.In general, the radiation dose in the procedure is in the low dose range i.e. below 10 mSv.

CT angiography versus conventional functional testing

The PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial recruited 10,000 patients with first-time angina symptoms whose pretest probability of presence of obstructive coronary artery disease was calculated to be 53%. For the first time, anatomic diagnostics (CT angiography) were compared with functional diagnostics (exercise ECG, stress echocardiography, myocardial scintigraphy). The median follow-up time was 25 months. The following is a comparison of CT angiography versus conventional functional testing:

  • CT angiography (CT coronary angiography):
    • Primary end point (death, myocardial infarction/heart attack, hospitalization for unstable angina): 3.3
    • Occurrence or detection of more:
      • Invasive cardiac catheters (609 [12.2%] versus 406 [8.1%]).
      • Coronary stenoses (439 versus 193)
      • Revascularizing interventions (311 versus 158).
    • Infrequent cardiac catheterizations in which no coronary stenoses were found (170 [3.4%] versus 213 [4.3%]; p=0.022)
  • Conventional functional tests
    • Primary endpoint: 3.0

CONCLUSION: CT angiography is an appropriate method to clarify angina pectoris symptomatology, but it is not better than functional diagnosis.

Criteria of risk assessment of different noninvasive imaging modalities (from, modified from)

Low risk Medium risk High risk
Dobutamine: stress echocardiography No dysfunctional segments Findings between low- and high-risk constellation ≥ 3 dysfunctional segments
Dobutamine: stress MRI No dysfunctional segments Findings between low- and high-risk constellation ≥ 3 dysfunctional segments
Adenosine/regadesonone: stress perfusion MRI. No ischemia Findings between low-risk and high-risk constellation ≥ 2/16 with perfusion defects
Perfusion SPECT No ischemia Findings between low-risk and high-risk constellation Ischemia zone ≥ 10
CT angiography* Normal arteries or plaques only Prox. Stenosis(s) in large vessels, but no high-risk constellation 3-vessel CAD with prox. stenoses, main stem stenosis, prox. LAD stenosis

* Possible overestimation of findings in patients with >50% pretest probability and/or diffuse or focal calcifications. Further notes

  • Patients in whom exercise ECG is suggestive of CHD (+ECG), in stress echo a S. o. )ber no wall motion abnormalities (WBS) are detected (-echo), serious cardiac complications occurred in 14.6% of cases during the follow-up period of a mean of 7 years:this compares with the other constellation: 8.5% (-ECG/echo); 37.4% (+ECG/+echo):The event rate for +ECG/echo compared with -ECG/echo was increased both within the first 30 days and during the long-term course. Cases of +ECG/-Echo discussed stenosis (narrowing) in the ramus circumflexus (branch of the coronary sinistra/left coronary artery), for which stress echo has the lowest sensitivity (percentage of diseased patients in whom disease is detected by use of the test, ie, a positive test result occurs).