Preventing myocardial infarction: use and limitation of non-invasive imaging modalities

Abstract

Identifying patients at high risk of coronary events is the main focus of cardiovascular prevention. For primary prevention score and risk cards are very low cost solutions, but only of limited efficacy, thus justifying the use of non-invasive imaging testing for the purpose of increasing the ‘diagnostic gain’. Considering all the diagnostic tests employed, only few demonstrated significant additional contribution to the risk score stratification. Coronary imaging with high speed volumetric computed tomography can provide essential information in ruling out and/or definition of coronary artery disease but also has limitations as far as the biological risk, the costs, and the difficulties of putting into perspective the results obtained in asymptomatic patients.

Introduction

Prevention of acute coronary syndromes (ACS) and coronary artery disease (CAD) is an important public health goal. In fact, mortality and morbidity for ACS and CAD and/or their sequelae is very high, constituting the leading cause of death in the Western world.¹ Numerous studies have also shown that the appropriate use of treatments able to influence the progression of coronary heart disease and to affect its stabilization (statins, anti-platelet, effective anti-hypertensive treatment) reduces acute coronary events, hospitalizations, as well as immediate and long-term mortality.^2–4

The strategies commonly used in primary prevention are basically two:

• The population strategy, extended to the whole population and focused on the adoption of appropriate lifestyles;

• The personalized intervention strategy based on the risk of individual events, usually focused on the estimation of the individual risk of events established on the basis of ‘Scores’ or ‘risk tables’.

The strategy of personalized intervention is certainly cost-effective but has its main limitation in the correct identification of subjects at intermediate or medium-low risk. For the latter, it may be useful to add an additional test to the initial stratification that can bring an additional contribution and facilitate the identification of those individuals at higher risk.

Several non-invasive imaging tests have been investigated in the risk assessment of ACS in addition to the risk scores. The most frequently used non-invasive tests are those that explore the presence of preclinical vascular damage in peripheral districts (carotids, arteries of the lower limbs) or in the coronary district.

Non-invasive imaging of the carotid district and lower limbs

Several population studies have shown that atherothrombotic involvement is multi-district and consequently the uncovering of subclinical atherosclerosis in peripheral districts, that can be evaluated with non-invasive methods, can improve the risk stratification performance of coronary events in subjects who do not reach the risk threshold for ‘intensive’ drug treatment.

The study of the carotid district has traditionally been based on the intima-media thickness complex (IMT), a predictor of events more in women than in men and in a non-linear manner. The lack of well-defined standardization criteria and the lack of ability to improve the predictive capacity of some algorithms such as Framingham have effectively excluded the utility of this test in the last European Society of Cardiology (ESC) 2016 guidelines.¹

Greater usefulness would seem to have the presence of carotid plaques responding to diagnostic criteria based on thickness (IMT > 1.5) and on the percentage of vessel stenosis (>50%), but predictability is greater for cerebrovascular events than for coronary ones.

The ABI (Ankle/Brachial Index) is closely correlated to the frequency of major cardiac and cardiovascular events (MACE) but its usefulness in the redistributing of patients at intermediate risk is questioned in the ESC guidelines on cardiovascular prevention and rating of recommendation of the method is rather low (IIb).

The search for a peripheral vascular disease is also useful in patients who have undergone an acute coronary event, in secondary prevention, to establish which patients should be treated more intensively for the reduction of MACE and also of mortality with dual long-term platelet anti-aggregation² or with lipid-lowering agents.³

The calcium score

Calcium score (CAC) quantification with electron beam or multi-slice CT (computed tomography) is based on the assumption that the extent of coronary calcifications correlates with plaque burden and therefore with the probability of coronary events. Although the presence of calcium indicates ‘stable’ plaques, there is a discrete correlation between Agatston score and the probability of coronary events. An Agatston score >300 or more than 75% predicted for age and sex indicates an increased risk and is helpful in re-structuring low-risk subjects. Furthermore, a negative CAC is usually associated with a low probability of coronary events (!).

The use of the test obviously clashes with the related costs and the biological risk related to radiation exposure (0.8–1 mS).

Coronary computed tomography

The possibility of obtaining non-invasive coronary imaging has necessarily aroused the interest of clinicians, especially due to the extraordinary technological innovations that have occurred in the last decades. From the computerized axial tomography, to the multi-detector ‘spiral’ CT and to the current ‘volumetric’ CT scan. Volumetric CT has today made a huge leap in cardiovascular imaging technology, thanks to the ultra-fast acquisition of the entire heart volume. These new tomograms, with a scan time of just 0.28–0.35 s, are able to cover an entire anatomical district, such as the heart, from the emergence of the great vessels at its apex: 160 mm of volumetric acquisition. The direction taken by cardio-coronary imaging with volumetric CT is the ultra-fast production of high resolution images. With very rapid times of carrying out the examination and with the reduction of more than 10 times (from 14–20 to 0.8–1.8 mSv!) of the dose of ionizing radiation absorbed by the patient. The extraordinarily fast acquisition times make it possible to reduce the amount of contrast medium, with greater safety of the examination even in patient with nephropathy. The more sophisticated imaging acquisition also allow to evaluate the ‘composition’ of the plaque in order to establish the possibility of ‘instability’ of the plaque. The negativity of the scanning study indicates the subject at low risk with extreme precision. The subjects at high risk are instead identified by the presence of non-critical multivessel coronary disease, as well as by patients in whom ‘critical’ stenoses are identified. Although the advantages of the technique are clearly evident, different limits must be considered:

• The cost of the method;

• The biological risk related to radiation exposure, however limited, and the need for contrast medium;

• The relief in asymptomatic subjects of critical stenoses in the absence of symptoms, a finding that determines further investigations and often results in revascularization whose utility has not yet been established.⁵

Non-invasive imaging for the study of ischaemia

Methods for the study of ischaemia include ECHO-stress, perfusion myocardial scintigraphy, and nuclear magnetic resonance during pharmacological stress test. The pathophysiological assumption for the use of these methods is that inducible ischaemia is usually associated with a ‘functionally significant’ coronary stenosis, but in reality it is still not clear what the risk of coronary events is in the presence of inducible ischaemia. In all the studies on the topic, some very dated and conducted in the pre-statin era,⁵ the risk of overall coronary events appears to be greater in patients with severe ischaemia (>10% of left ventricular extension). The ISCHEMIA TRIAL study is currently underway, from which there will certainly be many indications on the topic and some definitive answer on the correlation between inducible ischaemia and events or between coronary heart disease and events.

In the ischaemia trial, most of the patients were selected with image tests, especially myocardial scintigraphy and ECHO-stress. Advantages and disadvantages of these methods are known. Myocardial scintigraphy involves significant radioactive exposure, but it is certainly more precise and less operator-dependent in the evaluation and quantification of ischaemia. Echo-stress is surely the most available and least correlated to biological risk, but dependent on the acoustic window and the experience of the operator. The nuclear magnetic resonance is unfortunately not very available and certainly more complex, although it is very effective in the diagnostic evaluation in terms of sensitivity and specificity.

In assessing the risk of events in patients at intermediate risk, the search for ischaemia is not recommended, beyond what the peculiarities of the methods used are.

Conclusions

In the stratification of the risk of heart attack in primary prevention the role of non-invasive imaging is modest, despite the considerable interest that is currently receiving the non-invasive imaging of coronaries with the ultra-fast volumetric CT scan. The lower cost techniques are characterized by a very weak ‘diagnostic yield’, the exceptional diagnostic capacity of the ultra-fast volumetric CT scan for the non-invasive study of the coronaries leaves obvious doubts in the clinician for the application of an expensive method, however related to a non-negligible biological risk in asymptomatic and presumptively disease-free subjects.

The stratification of the risk of events on a clinical basis and with risk scores remains the best way to establish the appropriate treatment of these patients.

Conflict of interest: none declared.