Coronary computed tomography angiography (CCTA) was introduced in clinical practice in the end of the last century to promote noninvasive visualization of coronary arteries. Its use proved it an appropriate option for the evaluation of coronary artery disease.
On the other hand, the routine use of CT scan could result in a greater number of invasive procedures, since it would show lesions without clinical manifestation and that would be submitted to interventional treatment.
Given the importance of myocardial ischemia detection, either by echocardiography, magnetic resonance imaging, myocardial scintigraphy, or by invasive examinations that include Fractional Flow Reserve (FFR) analysis,
Initial positive expectations were strengthened as technology progressed, including dual energy use, increased detector numbers, and improvements in spatial and temporal resolutions.
Nowadays, there are tomographs in Brazil with all characteristics necessary to ensure that such images are generated in accordance with what is described in this document. In addition, similar to what happened with the standardization of coronary angiotomography procedures by the National Agency for Supplementary Health Guidelines, the creation of a document on use is also educational and may hinder the indiscriminate use of diagnostic tests, thus avoiding the waste of resources in situations with no solid scientific evidence of the benefit these could bring.
Therefore, the purpose of this paper is to discuss in more depth the characteristics of ischemia CT research, the technological and software prerequisites, and to define which subgroups of patients would benefit from this exam.
Myocardial CTP is based on the principles of the theory of tracer-dilution, first developed by Stewart,
Thus, in the first-pass imaging approach, the concentration of iodinated contrast is ideally proportional to MBF in a wide range of blood flows. Areas with lower (darker) attenuation upon first contrast passage are classified as hypoperfused territories and are visually and quantitatively evaluated in comparison to adjacent myocardial territories.
Although recently inserted in the clinical evaluation, Miocardial CTP has been subject of research for several years. In 2006, George et al.
Promising data from single-center clinical studies prompted the study CORE320.
Data from this same study evaluated the performance of Miocardial CTP alone in the diagnosis of significant stenosis identified by catheterization alone, compared to MPC.
Although the isolated use of MDCT for myocardial ischemia detection is not the end goal of tomography use, a recent study published by Takx et al.,
The use of dynamic myocardial perfusion in the detection of myocardial ischemia has shown encouraging results validated by different reference techniques.
| Study | Year | N | Reference | Sens. | Spec. | PPV | NPV |
|---|---|---|---|---|---|---|---|
| George et al. |
2009 | 27 | ICA and MPC | 86 | 92 | 92 | 85 |
| Rocha-Filho et al. |
2010 | 35 | ICA | 96 | 100 | 100 | 91 |
| George et al. |
2012 | 50 | MPC | 72 | 91 | 81 | 85 |
| Bettencourt et al. |
2013 | 101 | FFR | 89 | 83 | 80 | 90 |
| Rochitte et al. (CORE 320) |
2014 | 381 | ICA and MPC | 80 | 74 | 65 | 86 |
| Cury et al. |
2015 | 110 | MPC | 90 | 84 | 36 | 99 |
| Takx et al. |
2015 | 2048 | FFR | 88 | 80 | - | - |
| Sørgaard et al. |
2016 | 1188 | MPC, MRI, ICA, FFR | 85 |
81 |
- | - |
| Pontone et al. |
2018 | 100 | ICA and FFR | 98 | 54 | 68 | 96 |
ICA: invasive coronary angiography; MPC: myocardial perfusion scintigraphy; Spec.: specificity; FFR: fractional flow reserve; MRI: Magnetic Resonance Imaging; Sens.: sensitivity; PPV: positive predictive value; NPV: negative predictive value.
Results of myocardial perfusion by computed tomography with MPC and MRI as reference.
Any 64-channel or more (4 cm z-axis coverage) CT scan is able to perform coronary angiography, and therefore synchronizes with the electrocardiogram (ECG) and appropriate settings, being also able to study pharmacological-stress myocardial perfusion.
A contrast infusion pump, preferably with two heads, is required for dynamic injection of high flow contrast. There is no need for an infusion pump for dipyridamole, but its presence can help optimize and ensure protocol quality. Despite the safety of dipyridamole/adenosine demonstrated in past studies, emergency care supplies regularly present in radiological clinics should be readily available, as well as qualified personnel to use them. Since dipyridamole/adenosine may induce advanced atrioventricular blocks (especially in conjunction with beta-blockers), the presence of percutaneous pacemaker can be helpful. Aminophylline should be ready for infusion after dipyridamole/adenosine administration. Continuous monitoring by ECG of satisfactory quality is indispensable during infusion.
Monitoring of coronary artery tomography images, as well as CTMP, should be conducted by a specialized professional.
As preparation for the exam, all patients should be fasting for at least four hours and not have caffeinated beverages in the last 24 hours.
Patients should be punctured with 18-20 gauge Jelco intravenous catheter in the antecubital vein of the right arm for administration of iodinated contrast. Another IV line in the left arm should be made for infusion of the stressor agent (dipyridamole/adenosine/regadenoson) and aminophylline as dipyridamole antagonist when necessary.
ECG, heart rate and blood pressure should be monitored by the attending physician throughout the examination. Patients with blood pressure above 100 mmHg may receive sublingual nitrate (isosorbide dinitrate [5mg] or propatylnitrate [10mg]), with a minimum interval of 20 minutes for subsequent pharmacological stress, as validated in previous safety profile studies.
Patients may receive intravenous or oral metoprolol prior to examination. Although there is no formal guideline for this purpose, the proposal is to use the following scheme used in a previous multicenter study:
Regardless of the mode of image acquisition or equipment available, fixed stressor administration protocols are used. In Brazil, stress protocols use mainly dipyridamole (0.56 to 0.84 mg/kg) in 4 minutes, with acquisition in the 6th minute of the beginning of injection or possibly adenosine (140 µg/kg/min for 4 minutes, with acquisition at the end of the last minute). Regadenoson can be used as a stressor at a single dose of 0.4 mg intravenous (IV) in a bolus, with stress imaging acquired within 1-2 minutes after injection.
The assessment of myocardial perfusion at rest and stress by tomography, as well as the coronary anatomical evaluation, should always be performed in a single protocol. Aiming at a low radiation dose, we always suggest performing resting perfusion study (CCTA study itself) with the usual low-dose protocols available on the device (preferably with dose modulation and/or prospective acquisition), and the protocol under pharmacological stress whenever possible, with a slightly lower radiation dose, but diagnostic quality, always prioritizing prospective acquisition.
We encourage the option of the protocol to be used (stress/rest or rest/stress) according to the experience of each center and particular characteristics of each patient or the CT scanner used.
As an example, we can describe the following acquisition parameters for first-generation 64-channel scanners:
Resting study - Retrospective Gating, 70-90 ml of contrast at 5 ml/s injection pump infusion after metoprolol (max. 20 mg), 64 x 0.5 mm or 32 x 0.6 mm collimation, mAs up to 850 depending on gender and weight and Kv of 100 (preferred). Study under pharmacological stress - Retrospective Gating, 60ml contrast at 3ml/s injection pump infusion, peak pharmacological stress acquisition, 32x1.0 mm collimation, 100 mA and 100 Kv (preferred).
Devices with latest hardware and state-of-the-art software can take advantage of available technological advances (e.g. prospective acquisition) and be based on a protocol with less radiation and the same diagnostic capability.
After iodinated contrast infusion, imaging acquisition can be performed manually as soon as the contrast is visually detected in the left atrium.
The rest protocol will simultaneously acquire anatomical image (coronary angiography) and myocardial perfusion. The start and end of acquisition should be programmed based on previously acquired calcium score images, trying to minimize the radiation dose. Acquisition parameters used include 240-320 0.5 mm detectors with 100-120 kV voltage probe, gantry rotation from 0.280 to 0.375 seconds, with prospective ECG trigger.
Intravenous contrast will be infused by pump injection in a biphasic or three-phase protocol: 100% contrast in the first phase, 30% contrast plus 70% saline in the second phase, and 100% saline in the third phase. The contrast dose will be adjusted according to the patient’s weight (see
| weight (Kg) | First phase: 100% Contrast (ml) | Second phase: 30% contrast and 70% Serum (ml) | Third phase: 100% serum (ml) | Flow (ml/s) |
|---|---|---|---|---|
| < 60 | 44 | 20 | 50 | 4 |
| 60-70 | 54 | 20 | 50 | 4.5 |
| 71-100 | 54 | 20 | 50 | 5 |
| > 100 | 64 | 20 | 50 | 5 |
Modified table from George et al.
Contrast injection monitoring must be performed by rapid real-time acquisitions initiated 5 seconds after the start of infusion. An apnea command is to be performed 14 seconds after the start of intravenous contrast infusion. When the contrast density peak reaches 300 UH in the descending aorta, acquisition of resting myocardial perfusion images and coronary angiography by CT will be initiated.
The pharmacological stress protocol will focus on stress myocardial perfusion image. Again, the beginning and end of the acquisition should be programmed based on previously acquired images, calcium score and rest perfusion. Acquisition parameters used include 240-320 0.5 mm detectors with 100-120 kV tube voltage, gantry rotation from 0.280 to 0.375 seconds with a prospective ECG trigger.
Following administration of the stressor, a 12-lead ECG should be performed, along with blood pressure and heart rate checks.
Different techniques and forms of image acquisition are available and constantly evolving, including dual energy and dynamic acquisition. Although promising, such techniques require further investigation and radiation reduction strategies. Therefore, we will not address the protocols used for such techniques in this document.
The assessment of CTMP involves a sequence of steps, which must be systematized to produce a result that reflects a physiopathological change or a state of normality. In this approach, initial assessment of CCTA is recommended (
Once the CCTA is evaluated and any coronary stenosis and non-interpretable segments (stents, calcifications, artifacts) are quantified, the next step is to assess stress and rest myocardial perfusion. At this stage, qualitative and quantitative visual analyses (below) are used to establish the severity and extent of myocardial perfusion deficit, as well as its reversibility.
The third step in the process of image interpretation is the reclassification of anatomical findings. Due to potential limitations of luminal assessment by CCTA and the existence of intermediate stenoses,
The final step in the interpretation process is anatomical-perfusion alignment based on the integration of CCTA and Myocardial CTP findings. This process is essential to define the presence of flow-limiting stenoses,
Among the methods used for quantitative evaluation we can mention transmural perfusion ratio (TPR) and summed stress score (SSS), obtained through static acquisition. MBF estimates, although likely to be performed by dynamic myocardial perfusion, will not be addressed in this document.
The TPR is calculated by the average subendocardial density (in Hounsfield Units) divided by the average of the subepicardial density of each myocardial segment. This relationship showed that Myocardial CTP can detect and quantify perfusion defects compared with SPECT,
Tomography SSS should be calculated based on the sum of perfusion defect of the 17 segments predefined by the American Heart Association, ranging from a scale of 0-4 for each segment (0 - normal; 1 - discrete; 2 - moderate; 3 - important and 4 - transmural perfusion defect). SSS values for ischemia quantification are: less than 4 normal, between 4 and 8 discrete, between 9 and 13 moderate, and greater than 13 important.
Myocardial CTP assessment should be divided into qualitative and quantitative analysis. The report must contain the examiner's visual and subjective impressions, followed by the quantitative assessment (TRP and SSS). The reversibility of perfusion defects is fundamental information and should be addressed in the report, as it reflects the myocardial ischemia itself.
The most important part of the report is the integration of anatomical and perfusion findings. The examiner should clearly define whether there is a correlation between luminal obstructions and perfusion defects, as well as the extent of perfusion defects and reversibility as they define the therapeutic approach.
The main elements of the report are expressed in
| Protocol used (rest-stress, stress-rest, dynamic perfusion or dual energy perfusion) and iodinated contrast volume |
| Scanner |
| Stressor agent, doses and reversing agent (when applicable) |
| Presence of symptoms and electrocardiographic changes in stress. |
| CCTA description (quantification of stenosis) |
| Myocardial CTP description (qualitative/quantitative analysis, artifacts) |
| Anatomic-perfusional integration |
| Conclusion |
Myocardial perfusion study is advantageous when in conjunction with the anatomical assessment of the coronary arteries, as it benefits from the combined assessment. Thus, it is a limited strategy when considered in isolation, given exposure to ionizing radiation and iodinated contrast, which can be avoided in other diagnostic methods.
Because it uses additional doses of radiation and contrast when compared to coronary tomography alone, Myocardial CTP should be used with caution in patients with renal failure or undergoing other examinations employing ionizing radiation over a short time.
The use of vasodilatory pharmacological stress should be carefully evaluated in patients with any clinical or hemodynamic instability, as well as in patients with atrioventricular blocks, chronic obstructive pulmonary disease and asthma.
As previously mentioned, the use of dynamic perfusion by tomography allows the evaluation of myocardial iodine contrast kinetics, making it possible to quantify MBF. Additionally, the use of dual energy techniques (two x-ray tubes operating simultaneously at different voltages) allows to create an “iodine map” for the quantification of perfusion defects. Although such techniques are already available, further studies are needed to assess the impact of these approaches on clinical decision-making, as well as the increased supply of equipment that allows the use of this technique, which is still scarce in Brazil.
Recently, a new approach has emerged in the functional assessment of coronary artery disease by CT, known as CT-derived FFR. Although it uses a completely different technique, it has the same purpose of Myocardial CTP, using routine coronary tomography images without the need for pharmacological stress. Usually, coronary tomography images are transferred to a dedicated computer, where simulations based on computational fluid dynamics are performed, in order to create a three-dimensional model based on the anatomical and physiological characteristics of each patient. This model identifies stenoses and quantifies changes in intracoronary pressures, reflecting the changes found in stenoses invasively assessed by FFR.