The diagnosis of coronary heart disease (CHD) is a major cost driver in the healthcare system, due to the frequency of CHD and the frequent residual uncertainty after a diagnostic test has been performed. It is therefore important to be aware of the benefits, limitations, costs and risks of the various methods and not to add these assessment modalities together, but to select them specifically.
The diagnosis of coronary heart disease (CHD) is a major cost driver in the healthcare system, due to the frequency of CHD and the frequent residual uncertainty after a diagnostic test has been performed. It is therefore important to be aware of the benefits, limitations, costs and risks of the various methods such as electrocardiogram (ECG), ergometry, stress echocardiography, magnetic resonance imaging (MR), computed tomography (CT), myocardial perfusion radionuclide imaging (single-photon emission tomography [SPECT] or positron emission tomography [PET]) and coronary angiography and to select these diagnostic modalities in a targeted manner rather than adding them together. The aim is, on the one hand, to make the most accurate diagnosis possible and, on the other hand, to monitor therapy and ideally make a prognostic statement. While ergometry has become less important in the diagnosis of CHD, cardiac CT has become increasingly important and is probably the most comprehensive diagnostic and prognostic method alongside coronary angiography. Stress MR heart and stress echocardiography as well as myocardial perfusion SPECT/PET are the most important methods for ischemia imaging and quantification today. In addition to the patient’s pre-test probability, factors such as local availability and expertise as well as individual patient characteristics must also be taken into account when selecting the appropriate clarification method.
CHD and its consequences continue to be one of the most important causes of death worldwide. A precise diagnosis is therefore important. If you suspect CHD, you need to know the exact definition. According to the guidelines of the ESC (European Society of Cardiology), CHD is a pathological process characterized by an accumulation of atherosclerotic plaques in the epicardial arteries, obstructive and non-obstructive [1]. This definition already shows that a diagnosis of CHD is difficult, as it should cover obstructive and non-obstructive changes. In the following, we will limit ourselves to the diagnostic tests for the assessment of obstructive CHD. When investigating suspected CHD, we have anatomical tests such as computed tomography (CT) of the coronaries or coronary angiography as well as functional tests such as magnetic resonance imaging (MRI) of the heart and stress echocardiography, myocardial perfusion scintigraphy (SPECT), positron emission tomography (PET) examination or coronary angiography with measurement of the intravascular flow reserve. Each of these methods has its advantages and disadvantages. Healthcare costs are becoming increasingly limited, which forces us not to add up the available clarification methods, but to select them in a targeted manner. The aim would be to reach the goal as quickly as possible in a way that is less stressful for the patient and meaningful in terms of diagnosis and prognosis. In the following, we will try to explain the clarification steps recommended today.
Suspicion of coronary heart disease
Nowadays, the guidelines for investigating suspected CHD have changed in that symptoms, electrocardiogram (ECG) and laboratory tests are recorded first and ergometry is no longer recommended as a first-line test. According to current guidelines, a 12-lead ECG and resting echocardiography for risk stratification and diagnosis are part of the work-up [1]. The ECG may be normal in CHD, but may also show Q waves or conduction disturbances such as left bundle branch block or AV block and/or dynamic changes in repolarization. In addition to a reduction in the ejection fraction and/or regional wall motility disorders, echocardiography can also assess diastolic function and heart valve function. Ergometry is still very important for assessing exercise capacity, clarifying symptoms, arrhythmias, blood pressure behavior and risk in certain patients (class I indication). For the assessment of ischemia in known CHD as well as for the initial diagnosis of CHD, ergometry is a class IIb indication and is only recommended if other non-invasive or invasive imaging procedures are not available. If the quality of the echocardiography is poor and/or the findings are unclear, an MR heart can be used to assess the global and regional function of the left ventricle.
The pre-test probability plays a role in all further clarification decisions. According to the calculations, the pre-test probability of CHD has nowadays decreased compared to the earlier Diamond and Forrester data [2,3]. With a pre-test probability of <5%, further tests should only be carried out if there is a high level of suspicion. Gender also plays a major role: for example, in the case of typical angina pectoris, the pre-test probability for CHD in 60- to 69-year-old men is now 44%, whereas in a woman of the same age it is only 16%. Accordingly, gender plays a significant role in the assessment of the frequency and the clarification steps. Almost every elderly person has plaques, just more or less; and this varies depending on the risk factors: especially if a patient has arterial hypertension, the prevalence of CHD increases massively and is then more than 75% in over 60-year-olds. The pre-test probability is influenced by the cardiovascular risk factors; in addition to the usual risk factors, CHD-accelerating factors such as polymyalgia, depression, psoriasis, radiotherapy, Covid-19 infection, shift work, etc. should also be taken into account in the medical history. Further routine clarification tests only make sense if the pre-test probability is over 15% [7,62]. With a pre-test probability of 5-15%, further investigations can be considered if there are particular predisposing factors (such as a high risk profile, ECG changes, wall motion abnormalities in echocardiography, pathological ergometry or coronary calcification in native CT).
After ECG and echocardiography, the following steps are recommended (Table 1). In terms of symptoms, it should be noted that other conditions besides classic coronary artery disease can cause angina pectoris or myocardial ischemia: Coronary anomalies, diffuse but not stenosing coronary sclerosis, coronary spasm, microvascular dysfunction, hypertrophy of the left ventricle/hypertrophic cardiomyopathy, aortic valve stenosis, Takotsubo syndrome, arterial hypertension (even without hypertrophy), anemia and polycythemia, for example.
Depending on the pre-test probability of coronary heart disease, a CT scan of the coronaries or an imaging ischemia test – such as a stress MR (with adenosine or dobutamine), stress echocardiography (treadmill, bicycle, dobutamine) or radionuclide imaging (SPECT/PET) – is recommended as a further clarification. The diagnostic performance of the various examination methods as a function of the individual pre-test probability is shown in Figure 1. Negative examination results have a high negative predictive value, especially in the case of cardiac CT, even with a high pre-test probability. Conversely, cardiac MR and PET show the highest positive predictive values for positive results in patients with low to medium pre-test probability. Immediate coronary angiography is recommended in the case of a very high pre-test probability, high risk or unstable symptoms. A comparison of the advantages and disadvantages of the individual clarification methods is shown in Table 2.
In ergometry, artificial intelligence appears to improve diagnostic reliability (machine learning using P, QRS and T waves [4]). However, so far there have mainly been studies on patients with a high pre-test probability.
CT Heart
The CT heart is an anatomical test: in contrast to echocardiography and MR heart, where the calcification of the coronary arteries cannot be assessed at all and the anatomy cannot be assessed optimally, both can be seen perfectly and quickly with the CT heart. However, the extent of a stenosis does not reflect the degree of ischemia, which limits the informative value of computed tomography. The presence of coronary calcification is very sensitive for a stenosis of at least. 50% in coronary angiography, but only moderately specific in patients over 60 years of age, sensitivity 91%, specificity 49% (16 studies).
The degree of coronary calcification, the diagnostic marker of arteriosclerosis, can be easily and simply determined using a native CT scan. Due to the abundance of prognostic data, the Agatston Score has become established for quantification. An Agatston Score 0 means exclusion of coronary sclerosis, Agatston Score 1-99 means mild coronary sclerosis, Agatston Score 100-399 means moderate coronary sclerosis and Agatston Score ≥400 means severe coronary sclerosis. The calcium score is an excellent risk marker for future cardiovascular events. A large number of studies confirm the prognostic value (in addition to and independent of the presence of traditional risk factors).
Contrast-enhanced CT coronary angiography enables high-resolution visualization of the coronary anatomy and any stenoses. The strength of this examination lies in the exclusion of CHD: with good image quality and completely normal coronary arteries, the negative predictive value of this examination is almost 100%. The clinical benefit of CT diagnostics was demonstrated in the SCOT-HEART study. A cardiac CT screening strategy led to a >40% reduction in the primary endpoint (death/myocardial infarction) after five years compared with a conservative screening strategy in patients with suspected CHD.
One of the problems with CT heart is that the presence of large calcifications can lead to the severity of coronary stenoses being difficult to assess or overestimated. Calcium has a high X-ray density and can therefore lead to partial volume effects and so-called “blooming artifacts”, which make the lesions appear larger than they actually are. In addition, the heart rate is also important when acquiring CT images. With current methods, a heart rate of under 70/min and ideally under 60/min is ideal. At higher heart rates, the quality and sharpness of the images are significantly worse. It is therefore often necessary to administer beta-blockers intravenously or orally. Finally, breathing is also important. Even if the breathing pauses are very short, patients are sometimes unable to hold their breath for this short period of a few seconds due to anxiety and a lack of compliance, which can lead to interference signals in the images.
A CT heart is ideal for ruling out relevant CHD, for non-diagnostic stress imaging tests, for abnormal coronaries or if imaging of the aorta is required at the same time. The spatial resolution in the CT heart is effectively 0.3-0.4 mm with today’s devices.
The radiation exposure of cardiac CT has decreased massively over the last 15 years due to technical advances and improved protocols. While the radiation exposure in the early days of 64-line devices (spiral acquisition without tube current modulation) was a good 15 mSv, this has been reduced to the sub-milliSievert range through tube current modulation, prospective step-and-shoot protocols, fast-pitch acquisition, BMI-adapted tube voltage algorithms and iterative image reconstruction algorithms (most recently also AI-based): In comparison, the radiation exposure for SPECT is 8-9 mSv. On average, the natural radiation exposure is around 3 mSv per year, the radiation exposure of a diagnostic coronary angiography is around 2-7 mSv. The younger the patient, the more the risks of radiation exposure should be carefully weighed against the potential benefits of an examination [5].
Stress MRI heart and stress echocardiography
In the case of an intermediate to high risk of CHD and an age of more than 65 years, stress imaging, i.e. an imaging procedure combined with physical or drug stress, is recommended if coronary heart disease is suspected.
Stress echocardiography and stress MR heart with questions about global and regional wall motility, scar/fibrosis and extent of ischemia are ideal for the assessment of existing CHD.
Cardiac MRI is usually performed to assess cardiac perfusion and coronary reserve. Maximum coronary dilatation is induced in the MR heart with drugs such as regadenoson or adenosine. Coronary arteries that already exhibit vasodilation to compensate for the presence of a stenosis are not able to increase blood flow under pharmacologic stress. The first passage of the contrast agent (gadobutrol) into the heart muscle is evaluated. The areas of the heart that receive less contrast are those where coronary blood flow is likely to be reduced due to coronary stenosis. In general, ischemia affecting at least two of the 16 heart segments according to the American Heart Association segmentation is considered relevant. A study published in 2019 showed that patients who underwent revascularization using cardiac MRI had a similar prognosis to patients who underwent coronarography and revascularization directly, with the advantage, of course, that the method is less invasive and fewer coronarographies were performed [6]. The advantage of the MR heart is that, in addition to transmural scars, small scars or fibrosis foci that can be missed by echocardiography can also be detected. Like stress echocardiography, MR Heart has no radiation exposure. However, the MR heart for ischemia detection is quite complex: two lines are required (adenosine and gadolinium should not be administered with the same infusion) and the duration is at least an hour, which is particularly difficult for patients with claustrophobia.
The cheapest and simplest method for ischemia detection is stress echocardiography, which can be performed using a treadmill, bicycle or dobutamine (or adenosine) infusion. Stress echocardiography is also probably the best method for arrhythmic pulse or claustrophobia.
In addition, stress echocardiography, especially if performed on a treadmill or bicycle, can identify other causes of symptoms such as dyspnea, diastolic dysfunction, pulmonary hypertension, obstruction in the left ventricular outflow tract, and the effect of stress on hemodynamics in valvular heart disease (mitral and aortic stenosis, mitral and aortic regurgitation).
Myocardial perfusion SPECT and PET
Single photon emission computed tomography (SPECT) is a nuclear medical examination in which a radioactively labeled substance – a so-called tracer – is administered. The basis of SPECT is scintigraphy. Myocardial perfusion scintigraphy (MPS) is widely used with and without combination with CT of the coronary arteries. The regional distribution of the tracer in the myocardium is used to assess the blood flow to the heart muscle and whether ischemia or scarring of the left ventricular myocardium is present. In the case of ischemia, the localization and scar can be recorded. The extent of ischemia is also important as this correlates closely with the patient’s prognosis: Myocardial perfusion SPECT allows the quantification of ischemia in % of the left ventricular myocardium. ECG triggering can also be used to determine left ventricular volumes and the ejection fraction.
The SPECT examination allows great flexibility in stress protocols. The examination can be performed with physical stress or pharmacological stress (vasodilatants with dipyridamole, adenosine, or regadenoson or betamimetics such as dobutamine). One advantage of SPECT over stress MR, stress echo or PET is the possibility of decoupling the stress phase from the acquisition phase. Due to the physical and biological properties of 99mTc-basedperfusion tracers, the radionuclide can be administered during maximal stress (physical or pharmacological), while uptake can often take place 60-90 min later (with the patient recovered). This is particularly advantageous for elderly or immobile patients. SPECT is also safe in the case of renal insufficiency (no iodine-containing contrast agent), atrial fibrillation or metal implants such as pacemakers. Claustrophobia is rarely a problem with today’s dedicated small-footprint cardiac SPECT devices.
The disadvantages of SPECT are the relatively high radiation exposure (8-9 mSv for a complete stress test examination with a 99mTc-basedtracer, with 201-thallium even higher radiation doses are possible). The risk/benefit ratio should therefore be carefully weighed up, especially in younger patients. Another disadvantage of SPECT is attenuation artifacts. The low photon energies of the radiotracers used make the system susceptible to non-uniform signal attenuation by attenuating structures (bone, fat, metal). Such attenuation artifacts can simulate perfusion defects. Modern systems have X-ray based methods for attenuation correction, but sufficient experience and knowledge of the typical artifact patterns is crucial for interpretation.
Myocardial perfusion imaging with PET is occasionally used in routine practice, especially in Switzerland, but not in Germany or Austria, for example. The advantages of PET technology over SPECT are the higher spatial resolution of the signal (4-5 mm for PET compared to 8-10 mm for SPECT), better CT-based attenuation correction, and the possibility of quantifying absolute myocardial blood flow (in mL/min/g myocardium) and coronary flow reserve. The radiation exposure with PET is usually is also lower than with SPECT and is approx. 3-4 mSv. The main disadvantages of PET are the limited availability of this technology and the high costs. In Switzerland, myocardial perfusion PET is available almost exclusively in tertiary centers. The reason for this is the short physical half-life of the radionuclides used, so that either a cyclotron for the production of the tracers must be available on site or a rubidium generator.) Therefore, a myocardial perfusion PET examination is usually requested in special cases, such as complex coronary anatomy, known coronary three-vessel disease (with possible balanced ischemia) or after aortocoronary bypass surgery. The ability to quantify myocardial blood flow also makes myocardial perfusion PET the method of choice for suspected microcirculatory disturbances. However, microvascular disease can also be detected by ischemia in MR.
Risk assessment
High cardiovascular risk is defined as at least 3% per year, low risk as <1% pro Jahr Bei der Risikobeurteilung gibt es Daten zur Ergometrie (>3% according to Duke Treadmill Score), SPECT/PET (at least 10% ischemia of the myocardium), stress echocardiography or stress MRI (at least three of 16 segments with induced hypo- or akinesia or perfusion defects). On CT heart or coronary angiography, coronary 3-branch disease with proximal stenosis, main stem stenosis, or proximal RIVA stenosis are considered high risk. In invasive functional testing, an FFR (fractional flow reserve) of ≤0.8 or an iwFR (instantaneous wave-free ratio) of ≤0.89 identifies a prognostically unfavorable lesion. Invasive coronary angiography remains a class I indication for the diagnosis of CHD in the case of typical symptoms with low stress or persistent symptoms despite extensive drug therapy.
Summary
The probability of coronary heart disease today is lower than previously expected. If the probability is very low, further investigations should be held back. At low and intermediate probability, the cardiac CT examination plays a major role today, at higher probability functional tests/stress imaging tests. Stress echocardiography, stress MR and SPECT are frequently used in the search for ischemia and have a high diagnostic accuracy. PET of the heart is used less frequently because its availability is limited and it is also the most expensive of the methods described. Traditional ergometry has increasingly taken a back seat as a diagnostic tool due to its low sensitivity and specificity. In comparison, the diagnostic accuracy of modern imaging ischemia tests is significantly higher, with slight advantages for stress MR and PET. However, as a basic principle, the diagnostic performance of any non-invasive method is strongly dependent on the pre-test probability, so the latter must be taken into account when selecting the method. Depending on the pre-test probability, one or the other test can provide a more reliable indication of the presence of suspected CHD and should therefore be preferred (Fig. 1). Furthermore, factors such as local expertise, availability, costs, risks, additional questions and the individual suitability of the patient (renal insufficiency, pacemaker, left bundle branch block, body weight, sonicity, cardiac rhythm, claustrophobia, etc.) must also be taken into consideration when selecting the non-invasive method.
Due to the high negative predictive value and the positive results of the SCOT-HEART study, cardiac CT should be preferred as a first-line test over classic ergometry or non-invasive ischemia tests, especially in patients with a low to medium pre-test probability. The situation is different in patients with a high pre-test probability or with known CHD or after revascularization: Here, functional tests such as stress echocardiography, cardiac MRI or SPECT/PET are better than CT for the decision on reintervention/invasive clarification. Ergometry retains an important role in the assessment of symptoms, arrhythmias and/or blood pressure behavior. All in all, cardiac CT is becoming increasingly important in the diagnosis of CHD. The combination of a single CT heart (or coronary angiography) followed by a functional stress imaging test is probably optimal in patients with intermediate to higher pre-test probability.
Take-Home-Messages
- When choosing the appropriate screening method for coronary heart disease, the pre-test probability plays a major role, but factors such as local availability and expertise as well as individual patient characteristics and preferences must also be taken into account.
- A normal ergometry has a low significance for the assessment of ischemia but is still important for the assessment of exercise capacity, clarification of symptoms, arrhythmias and blood pressure ratio.
- The CT heart is particularly useful for patients with low/medium risk.
a CHD is indicated. This method allows us to obtain information about the coronary anatomy and calcifications and has a very high predictive value in ruling out CHD. - Functional examinations such as stress echocardiography, MRI, myocardial perfusion SPECT and PET are more suitable for patients
with higher risk or known coronary heart disease, whereby the extent of ischemia may be relevant for the decision regarding revascularization.
Literature:
- Knuuti J, Wijns W, Saraste A, et al.: 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes.
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- Diamond GA, Forrester JS: Analysis of probability as an aid in the clinical diagnosis of coronary-artery disease. N Engl J Med 1979; 300: 1350–1358.
- Yilmaz A, Hayiroglu MI, Salturk S, et al.: Machine Learning Approach on High Risk Treadmill Exercise Test to Predict Obstructive Coronary Artery Disease by using P, QRS, and T waves’ Features. Curr Probl Cardiol 2023; 48: 101482.
- Academies NRCotN: Health Risks from Exposure to Low Levels of Ionizing Radiation: BEIR VII Phase 2. Washington, DC. The National Academies Press 2006; 245.
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HAUSARZT PRAXIS 2023; 18(12): 14–19