Abstract

Arq Bras Cardiol

abc

Arquivos Brasileiros de Cardiologia

Arq. Bras. Cardiol.

0066-782X 1678-4170

Sociedade Brasileira de Cardiologia - SBC

KwYKNNTjW7Gcr6NShrNjWtt

S0066-782X2016004300365

S0066-782X2016005020102

10.5935/abc.20160104

Review Article

Relationship between Calcium Score and Myocardial Scintigraphy in the Diagnosis of Coronary Disease

Siqueira

Fabio Paiva Rossini

1 Mesquita

Claudio Tinoco

1 2 Santos

Alair Augusto Sarmet M. Damas dos

3 4 Nacif

Marcelo Souto

1 3 4

1 Universidade Federal Fluminense Programa de Pós-graduação em Ciências Cardiovasculares

Niterói

Brazil Programa de Pós-graduação em Ciências Cardiovasculares da Universidade Federal Fluminense (UFF) Niterói, RJ - Brazil Universidade Federal Fluminense 2 Universidade Federal Fluminense Hospital Universitário Antônio Pedro Setor de Medicina Nuclear

Niterói

Brazil Setor de Medicina Nuclear, Hospital Universitário Antônio Pedro (HUAP), Universidade Federal Fluminense (UFF) Niterói, RJ - Brazil Universidade Federal Fluminense 3 Universidade Federal Fluminense Faculdade de Medicina Departamento de Radiologia Brazil Departamento de Radiologia, Faculdade de Medicina, Universidade Federal Fluminense (UFF) Niterói, RJ - Brazil Universidade Federal Fluminense 4 Universidade Federal Fluminense Hospital Universitário Antônio Pedro Serviço de Radiologia

Niterói

Brazil Serviço de Radiologia, Hospital Universitário Antônio Pedro (HUAP), Universidade Federal Fluminense (UFF) Niterói, RJ - Brazil Universidade Federal Fluminense

Mailing Address: Fabio Paiva Rossini de Siqueira, Universidade Federal Fluminense. Alameda Carolina 18/601, Icaraí. Postal Code 24230-140, Niterói, RJ - Brazil. E-mail: fabioprs@gmail.com, fabioprs@outlook.com

Author contributions

Conception and design of the research, Acquisition of data, Analysis and interpretation of the data and Critical revision of the manuscript for intellectual content: Siqueira FPR, Mesquita CT, Santos AASMD, NacifMS; Writing of the manuscript: Siqueira FPR.

Potential Conflict of Interest

No potential conflict of interest relevant to this article was reported.

18 07 2016

10 2016

107 4 365 374 07 11 2015 12 04 2016 13 04 2016

This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Half the patients with coronary artery disease present with sudden death - or acute infarction as first symptom, making early diagnosis pivotal. Myocardial perfusion scintigraphy is frequently used in the assessment of these patients, but it does not detect the disease without flow restriction, exposes the patient to high levels of radiation and is costly. On the other hand, with less radiological exposure, calcium score is directly correlated to the presence and extension of coronary atherosclerosis, and also to the risk of cardiovascular events. Even though calcium score is a tried-and-true method for stratification of asymptomatic patients, its use is still reduced in this context, since current guidelines are contradictory to its use on symptomatic diseases. The aim of this review is to identify, on patients under investigation for coronary artery disease, the main evidence of the use of calcium score associated with functional evaluation and scintigraphy.

Keywords Coronary Artery Disease / diagnoses Scintigraphy Calcium Signaling Tomography, Emission Computed

Introduction

Cardiovascular diseases (CVDs) remain the primary cause of death in Brazil and in the world, accounting for over 30% of total deaths on the planet - of which 50% are related to coronary artery disease (CAD). According to the World Health Organization, in 2008, approximately 17 million deaths were related to cardiovascular system disorders and, though some regions showed a drop in these rates, absolute numbers are still alarming.1

According to the American Heart Association, in 2009, one in every six hospital admissions in the United States was due to cardiovascular diseases, amounting to 6 million patients. It is estimated that, only in USA, 15 million people suffer from coronary disorders, and data from 2004 show that admissions and procedures related to coronary artery disease account for over 44 billion dollars.2

Over the last decades, it has been observed that the progression of CVDs was greater in developing countries in comparison to developed ones.1 A large portion of deaths happens in underdeveloped regions, being four to five times more frequent. This shows that, in Latin America, the epidemiologic transition of cardiovascular diseases is in a different stage than in North America or Western Europe.3

In Brazil, statistics point in the same direction. CVDs are still the main cause of death, in men and women, accounting for around 20% of all deaths in the country. According to the Brazilian Ministry of Health, in 2009, over 139,000 deaths were caused by disorders related to atherosclerosis.4 Incidence of cerebrovascular disease is still superior to that of coronary disease, which suggests that CAD, over the next few decades, may become more frequent in our population and be the main cause of death, if the epidemiologic transition follows the same path as in developed nations.5

Pathophysiology of atherosclerosis

The main cause of coronary insufficiency is atherosclerotic disease, defined as an inflammatory disorder. Plaque formation begins with early accumulation of low density lipoprotein particles (LDL) in the arterial intima.6 Oxidation of lipid material is one of the factors responsible for the attack on the endothelium, altering its permeability and increasing the expression of adhesion molecules, integrins and selectins, which participate in the migration of monocytes as part of the innate inflammatory response.7

Macrophages initiate LDL phagocytosis, which results in the formation of foam cells that produce cytokines and metalloproteinases, amplifies inflammatory response and recruits platelets and T lymphocytes.6^,7 Platelets adhere to the lesion and release prostaglandins and leukotrienes, as well as growth factors that induce monocytes and smooth muscle cell multiplication.7 T lymphocytes are presented to lesion antigens by dendritic cells, start producing cytokines, and modulate adaptive immune response.6

Deposition of extracellular matrix produced by the differentiated smooth muscle, cell proliferation, necrosis, and angiogenesis promote expansion of the plaque.8 The progression of atherosclerotic disease, however, does not obstruct vascular light in the same proportion due to positive remodeling of vessel size which does not compromise the luminal diameter.8^,9 When maximum capacity is reached, we see negative remodeling and plaque progression to the interior of the artery which, by gradually compromising the flow, may cause myocardial ischemia.8

Migration and proliferation of poorly differentiated smooth muscle cells in the intima promotes atherosclerotic plaque mineralization.9 These cells are able to differentiate into osteoblasts, produce mineralized extracellular matrix, and deposit hydroxyapatite crystals by accumulating calcium in the interior of the lesion9,10 in an osteogenesis-like process. Microcalcifications and calcified deposits may lead to plaque cavitation, erosion and rupture, increasing the risk of coronary thrombosis.10

Coronary artery disease assessment

Despite the slow progression of atherosclerotic disease in the intima of the coronary arteries (it takes years for precursor lesions to become a plaque that causes luminal obstruction), the possibility of becoming unstable and rupturing the plaque makes atherosclerosis, even in its subclinical form, a risk factor for the occurrence of acute coronary events.11

Approximately 50% of patients with CAD present with sudden death or acute myocardial infarction (AMI), making early diagnosis a pivotal factor. Early detection through joint evaluation of clinical and lab data and risk factors, associated to non-invasive imaging tests in selected patients, allows the applications of the best prevention and risk stratification strategies.12

Multiple risk factors have traditionally been associated to the occurrence of acute events in patients with CAD, and may be clinically evaluated through cardiovascular risk scores. However, this exclusively clinical approach, has proved limited in the diagnosis and prediction of events such as AMI and sudden death, when compared to risk prediction through associated supplementary methods.13

In the last few decades, several diagnostic methods to estimate cardiovascular risk and diagnose subclinical atherosclerosis in asymptomatic patients have been studied. Among them, coronary calcium score (CS) has shown excellent accuracy in the prediction of future risk events and detection of early disease that may be isolated or associated to clinical scores.14

Calcium score capacity for cardiovascular risk stratification has also been compared to the so-called new risk factor, capable of estimating subclinical atherosclerosis, such as carotid intimal-medial layer thickening measurement, ankle-brachial index, and C-reactive protein. However, coronary calcification was more effective in the process of re-rating patient groups' risk by clinical score, even when used alone.15^-17

On the other hand, non-invasive stratification of symptomatic patients relies on more advanced methods for anatomic and functional studies. Even though there are several proven accurate methods of coronary disease detection, myocardial perfusion scintigraphy (MPS) is the most frequently requested for diagnostic and prognostic evaluation of these patients in clinical practice.18

Myocardial perfusion scintigraphy

Myocardial perfusion scintigraphy was introduced in the 70's for cardiac perfusion and ventricular function assessment.19 Through the years, due to vast literature of accuracy evidence, its diagnostic and prognostic value and its cost-effectiveness, this technique has evolved into an important risk stratification tool and cardiovascular event predictor, and become one of the most utilized non-invasive methods in cardiology.19^-21

Scintigraphy is a method based on image formation through the acquisition of photons emitted by radiopharmaceuticals and captured by detectors located in a structure called gamma-chamber, with technetium-99m and thallium chloride -20122^,23 as the main radioactive substances (radioisotopes) used to provide images of the heart. Myocardial perfusion data are reconstructed into multiplanar images, through specific software, which correspond to cardiac tissue perfusion at the moment of medication administration.24

The exam is performed in two distinct moments: at rest and during effort - in one or two-day protocols. The effort may be physical or pharmacological through the use of vasodilating substances or inotropic agents. Such exam is able to assess myocardial perfusion by comparing the acquired images at rest and during effort and detect reversible perfusion defects, suggestive of ischemia. Moreover, it provides information on myocardial viability, cardiac function, ejection fraction, cavity volumes, and ventricular synchronicity.23^-25

Over the last few decades, a lot of effort has been put into the technique development for optimization and patient safety improvement. Chambers with cadmium zinc telluride (CZT) detectors have shown improvements in image quality, less exposure to radiation, and reduced time for acquisition, showing great progress in relation to traditional chambers. Other than gamma-chamber advancements, electronic image-treatment programs, iterative reconstruction in particular, also yield better quality exams using lower doses of radiotracers.26^,27

Myocardial perfusion scintigraphy is an established and consolidated technique in ischemia detection and prognostic evaluation. The exam shows great ability in the detection of lesions with flow restriction.28^,29 The same method is also able to determine patient prognosis - a regular exam is usually associated with less than 1% of adverse cardiovascular events per year, whereas exams with evidence of ischemia indicate increased risk, proportionate to defect extension.30

Coronary calcium score

Calcium presence in coronary arteries is a strong indicator of CAD. It has thus arisen great interest in its possibilities of diagnostic and prognostic application since it was described and used as a coronary disease detection technique, initially through fluoroscopy and electron beam CT in the 70's.31^-33

Since the introduction of computerized multiple detector CT in the 80's, it has been adapted for these new machines, yielding similar results and showing superior results in some cases, when systems with 64 detectors or more are available.32^-34

Calcium score is obtained from the acquisition of axial chest images, synchronized to the electrocardiogram, with 3 mm thick slices, without the use of iodinated contrast. In general, the effective dose of radiation is reduced and may vary with the characteristics of the scanner and technique used.32^-35

Hyperattenuating lesions with signal strength above 130 Hounsfield units and area equal to or greater than 3 contiguous pixels are quantified. Total volume, mass and Agatston score-weighted sum may be provided. The technique described by Agatston et al. is the most used in literature and the one presenting the most evidence.32^-35

Patients may be divided into groups according to the extension of the disease: Absence of calcification; minimal calcification (1-10); mild (11-100); moderate (101-400); severe (401-1000); and extensive (more than 1000). Patients may also be divided according to percentile of age, gender, and ethnicity.35

Initially, a series of studies addressed the calcium score's ability to predict the presence of significant anatomical lesions in invasive coronary angiography and its role in acute coronary syndromes as triage for catheterization.31^,32^,36 Throughout the years, the focus switched to prognostic power and cardiovascular event occurrence prediction ability.33_,37^-40

Several studies have shown that, as an indicator of atherosclerosis and cardiovascular risk, that is independent and superior to other methods and clinical scores,33^,37^-40 the presence of coronary calcification is correlated to cardiovascular events.

Risk of patients with CS above 1000 can be 12 times greater, and even minimal calcification presents an increased risk of 2 to 3 fold.39

On the other hand, in the presence of a score of zero, there is a small probability of disease in patients with low to intermediate risk, even in those showing symptoms.37^,38 Moreover, it denotes that the disease does not show great extent, which is a good prognostic indicator. The absence of calcium in the coronary determines an annual risk close to 0.1%.40

MPS is an excellent method to assess obstructive disease and indicates a good prognosis when negative; however, it fails to identify lesions without flow restriction.27 Moreover, it is costly, uses larger doses of ionizing radiation than calcium scores, requires specific technological apparatus, specialized staff, and supply of radiological material.24

Conversely, SC is directly related to the presence and extension of coronary atherosclerosis. Furthermore, it is potentially more widely available and has a lower cost in relation to scintigraphy, as well as a smaller effective radiation dose. However, it is not capable of identifying coronary stenosis and its role remains undefined in the symptomatic disease.37

Information provided by the methods are possibly complementary, which allows a joint approach. However, the correlation between the results, the influence of population characteristics on the findings and the sequential use of methods are not definitely established.38^-40 Therefore, so far there is no consensus of clinical guidelines on the joint application of calcium score and scintigraphy.

Correlation between methods

A few decades ago, a special interest arose on the accuracy of non-invasive methods for the detection of coronary artery atherosclerosis, with an attempt to establish a parallel between the numerous forms of coronary approach. The ability of CS to identify patients at risk of ischemia using myocardial scintigraphy has been addressed by several studies in literature.41^,50

Results suggest a correlation between total coronary calcium and scintigraphy, showing that higher calcium scores mean more frequent perfusion defects and more severe ischemia in the area.41^,42 The opposite applies, with a lessened incidence of ischemia in patients with a lower calcium score.41^-43

In general, the increase of coronary calcification is correlated to a greater occurrence of ischemia. Patients with metabolic disorders and presence of coronary calcium are also more likely to have perfusion abnormalities than patients without comorbidities.44 In the diabetic population, the calcium score shows correlation to the presence of alterations in scintigraphy in a manner superior to traditional risk factors.45

Despite the described evidence, the correlation between calcium scores and myocardial perfusion may vary according to populational characteristics and symptoms.47 Clinical presentation shows great significance in the correlation between methods. In patients at high risk for CAD, occurrence of alterations in the functional exam, even with reduced calcification, was more frequent in relation to those at low or intermediate risk.47^,48

A coronary layer analysis shows that, in low calcium score coronaries, the presence of ischemia in its territories was significantly lower, with similar predictive values to CT angiography.49^,50 Even though calcium score is related to the extension of the disease and not to the stenosis level, it showed similar ability to CT angiography in the prediction of myocardial perfusion alterations.49

Calcium score zero

Calcium score, besides adding supplementary information to scintigraphy, is a powerful tool in the assessment of coronary disease. However, some situations stand out, as calcium score zero.36^-40 Absence of calcium in the coronary arteries does not mean absence of atherosclerosis, as there may be non-calcified plaques. However, this situation correlates to a disease of lower extension.39^,40

Although the use of CS in asymptomatic patients is included in more recent guidelines, that is not the case for symptomatic patients.16^-18 However, in exams like scintigraphy,51 literature indicates that, in low or intermediate symptoms and risk of coronary disease, a score of zero is able to deviate the presence of perfusion alterations.

As from initial studies, there has been particular interest in calcium score ability to deviate CAD and correlate with normal myocardial perfusion. In a normal functional examination, the absence of coronary calcification is a strong indication of the absence of atherosclerotic disease. When compared to coronary angiography, the presence of significant lesions, the need for intervention, or the occurrence of AMI are unlikely.47^,51^-54

The absence of coronary calcium has been shown to ward off ischemia caused by CAD in patients with low or intermediate symptoms and probability of significant diseases, and CS, when used in conjunction with scintigraphy, shows increase in specificity and positive predictive value of the diagnostic strategy (Figure 1).51^,55^,56

Figure 1 Patient with calcium score zero. (A) Absence of calcified plaques. Risk of coronary disease below 5% and low risk of cardiovascular events (0,1% per year). (B) Normal myocardial scintigraphy.

However, in the acute presentation of symptoms in the emergency room or in high-risk patients for CAD, the use of CS is limited, since atherothrombotic phenomena of acute coronary syndromes may be present without calcification. Absence of calcium in symptomatic patients with coronary angiography indication does not exclude the presence of significant lesions.57 In such cases, CS does not add diagnostic and prognostic information, and has lower event prediction power than scintigraphy.58^-60

Elevated coronary calcification

Severe coronary calcification has proven to be an independent risk predictor and it is complementary to virtually all other forms of coronary artery disease evaluation, be it clinical - through risk scores - or complementary - via other non-invasive methods and functional tests - as exercise stress test and scintigraphy.61^-68

High calcium score is an indicator of increased risk for cardiovascular events such as heart attack and cardiac death, with higher accuracy, alone or in joint assessments, than clinical risk scores (Figure 2 and 3). Its presence indicates a poor prognosis in these patients, reclassifying them to high-risk groups, regardless of population characteristics.36^-40

Figure 2 Patient with calcium score 1-10. (A) Minimal quantity of calcified plaques in the territory of the anterior descending artery. Probable risk (obstructive coronary disease below 10%). (B) Normal myocardial scintigraphy.

Figure 3 Patient with calcium score 11-100. (A) Discreet quantity of calcified plaques in the territory of the right coronary. Definite coronary artery disease, though discreet. (B) Myocardial scintigraphy shows ischemia in the inferior wall in region with attenuation by soft tissue.

The presence of a severely high calcium score is also related to a higher frequency of significant lesions, even in patients with normal scintigraphy.61 In persistently symptomatic patients with no perfusion alterations, extensive coronary calcification is correlated to the presence of significant lesions and may indicate the need for coronary angiography and percutaneous or surgical intervention.62

The presence of extensive coronary calcification is also associated to a higher incidence of significant obstructive disease and revascularization, even when the result of the provocative test is normal.63^-65 Similarly, patients with altered scintigraphy have higher calcium score values compared to patients with normal perfusion exams.41^-43

Increased coronary calcification is therefore able to correlate to the presence of obstructive lesion, even when the provocative test is normal, minimizing false-negative results with the combined use of both methods.66 This joint strategy is also able to refer patients who would benefit from additional investigation or invasive approaches (Figure 4 and 5).69

Figure 4 Patient with calcium score 101-400. (A) Moderate quantity of calcified plaque in the territories of the anterior descending and circumflex arteries. Moderate coronary arterial disease. (B) Myocardial scintigraphy with the presence of inferolateral ischemia.

Figure 5 Patient with calcium score above 400. (A) Large quantity of calcified plaques in the territory of the anterior descending artery. Significant coronary artery disease. (B) Myocardial scintigraphy with presence of anterior and anteroseptal ischemia.

Independent complementary information

Intermediate calcium score values are also important in the evaluation of coronary artery disease. CS proved complementary to MPS, regardless of the presence or absence of ischemia.70 In patients with normal scintigraphy, the presence of an altered score indicates higher risk, despite the good prognosis of normal scintigraphy; in turn, perfusion defect patients show greater risk of events and worse prognosis.71

The association of methods has greater diagnostic accuracy in detecting and warding off coronary disease and it more peremptorily determines the prognosis of these patients. Moreover, the presence of tests results, in parallel, allows better interpretation of the results by minimizing mistakes and improving method performance.72^,73

In patients with normal scintigraphy, calcium score indicates subclinical disease and may assist in the exclusion of CAD or infer the presence of significant obstructive lesions.74 In persistently symptomatic patients, high calcium score was a significant coronary stenosis predictor despite scintigraphy results.64

The combined use of calcium score and scintigraphy becomes even more interesting if we take into account the prognostic value of methods for CAD. The occurrence of mortality and cardiac events is related to the severity of coronary calcification, regardless of scintigraphy results.74^-76

However, the scintigraphy-established prognosis is characteristically short to medium term, in which a normal result is a predictor of good prognosis in this period, even in groups with elevated CS.75^,76 On the other hand, calcium score can estimate the risk of longer-term periods -10 to 15 years - as noted recently, in which case, elevated coronary calcification overlaps the absence of perfusion defects.39^,40^,74^,76

Moreover, an important aspect of the correlation between calcium score and MPS is the impact that the outcome of one method has on the interpretation of the other. Additional information and increased pre-test probability provided by coronary calcification exert positive influence on the interpretation of scintigraphy, improving accuracy and reducing the amount of equivocal results on the joint analysis of these two methods.77

Exposure to radiation

With regards to radiation, calcium scoring method has a clear advantage by exposing the patient to lower doses than scintigraphy. Multicenter studies have shown that the average scintigraphy dose of radiation was higher than 10 millisieverts (mSv), with even higher averages in regions such as Latin America and Asia (15 mSv).78^,79

Importantly, recent technological advances in scintigraphy, both in detectors and in image reconstruction software, enable these tests to be carried out with a much lower exposure to radiation compared to traditional techniques. The use of these advances allows examinations with an effective dose below 5 mSv with the use of ultra-low dose radiotracer protocols.26^,27^,80^,81

On the other hand, calcium score has a low radiation dose, and in patients referred for scintigraphy, such dose is not too high as to impede the examination strategy. In studies evaluating the effective dose of the calcium score, the average was 2.5 mSv.82^,83 Thus, calcium score is in a safe range for cancer risk.84

Conclusion

Literature review shows that both calcium score and scintigraphy play an important role in the diagnostic evaluation of atherosclerotic heart disease. The possibility of removing extensive coronary disease by means of a calcium score zero, or indicating the presence of an extensive disease when it is severely increased, justifies the use of this method in the initial or joint evaluation, in asymptomatic patients with suspected CAD and in cardiovascular risk stratification. The evaluation of symptomatic low-risk patients, despite suggestive evidence, should be re-evaluated in upcoming guidelines.

Confirmation of the disease with the application of more specific methods and positive predictive value as myocardial perfusion scintigraphy is still fundamental in certain patients. Thus, although literature suggests that sequential or joint use of both methods is advantageous, more data are needed to establish a cost-effective strategy for diagnostic evaluation. It seems justifiable, therefore, from the standpoint of quality and accuracy of assessment and economic context of public health, that new studies continue researching the role of these important tools.

Sources of Funding

There were no external funding sources for this study.

Study Association

This article is part of the thesis of master submitted by Fabio Paiva Rossini Siqueira, from Universidade Federal Fluminense.

Acknoledgements

The authors would like to thank the Hospital Universitário Antônio Pedro (HUAP) da Universidade Federal Fluminense (UFF) for the support in the performance of coronary angiography and nuclear medicine.

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Siqueira

Fabio Paiva Rossini

1 Mesquita

Claudio Tinoco

1 2 Santos

Alair Augusto Sarmet M. Damas dos

3 4 Nacif

Marcelo Souto

1 3 4

1 Programa de Pós-graduação em Ciências Cardiovasculares da Universidade Federal Fluminense (UFF) Niterói, RJ - Brasil 2 Setor de Medicina Nuclear, Hospital Universitário Antônio Pedro (HUAP), Universidade Federal Fluminense (UFF) Niterói, RJ - Brasil 3 Departamento de Radiologia, Faculdade de Medicina, Universidade Federal Fluminense (UFF) Niterói, RJ - Brasil 4 Serviço de Radiologia, Hospital Universitário Antônio Pedro (HUAP), Universidade Federal Fluminense (UFF) Niterói, RJ - Brasil

Correspondência: Fabio Paiva Rossini de Siqueira, Universidade Federal Fluminense. Alameda Carolina 18/601, Icaraí. CEP 24230-140, Niterói, RJ – Brasil. E-mail: fabioprs@gmail.com, fabioprs@outlook.com

Contribuição dos autores

Concepção e desenho da pesquisa, Obtenção de dados, Análise e interpretação dos dados e Revisão crítica do manuscrito quanto ao conteúdo intelectual importante: Siqueira FPR, Mesquita CT, Santos AASMD, NacifMS; Redação do manuscrito: Siqueira FPR.

Potencial conflito de interesse

Declaro não haver conflito de interesses pertinentes.

Resumo

Metade dos pacientes com doença arterial coronariana apresenta, como primeiro sintoma, morte súbita ou infarto agudo, tornando o diagnóstico precoce fundamental. A cintilografia de perfusão miocárdica é utilizada, com frequência, na avaliação desses pacientes, porém, não detecta a doença sem restrição de fluxo, expõe o paciente a uma maior radiação e seu custo é alto. Por outro lado, com menor exposição radiológica, o escore de cálcio se correlaciona diretamente com a presença e a extensão da aterosclerose coronariana e, também, com o risco de eventos cardiovasculares. Apesar do escore de cálcio ser um método estabelecido e comprovado para a estratificação de pacientes assintomáticos, sua utilização ainda é reduzida nesse contexto uma vez que as diretrizes atuais são contraditórias em relação a sua utilização na doença sintomática. Essa revisão tem como objetivo identificar, nos pacientes em investigação para doença arterial coronariana, as principais evidências em relação ao uso do escore de cálcio associado à avaliação funcional com a cintilografia.

Palavras-chave Doença Arterial Coronariana / diagnóstico Cintilografia Sinalização do Cálcio Tomografia Computadorizada de Emissão

Introdução

As doenças cardiovasculares (DCV) permanecem como a principal causa de mortalidade no Brasil e no mundo, sendo responsáveis por mais de 30% do total de mortes em todo o planeta e a doença arterial coronariana (DAC) está relacionada com metade desses casos. De acordo com a Organização Mundial da Saúde, no ano de 2008, cerca de 17 milhões de mortes foram relacionadas a distúrbios do sistema cardiovascular e, apesar de algumas regiões apresentarem reduções dos índices, os números absolutos ainda são alarmantes.1

Segundo a American Heart Association, em 2009, uma em cada seis internações hospitalares nos Estados Unidos da América deveu-se a doenças cardiovasculares, totalizando 6 milhões de pacientes. Estima-se que, somente nos EUA, 15 milhões de pessoas sofram de distúrbios coronarianos, e dados de 2004 apontam que as internações e procedimentos relacionados à doença arterial coronariana resultaram em gastos superiores a 44 bilhões de dólares.2

Nas últimas décadas, observou-se que nos países em desenvolvimento, o avanço das DCV foi maior em relação aos países desenvolvidos.1 Grande parte das mortes se concentram em regiões não-desenvolvidas chegando a ser de quatro a cinco vezes mais frequentes. Isso demonstra que, na América Latina, a transição epidemiológica das doenças cardiovasculares encontra-se em diferente fase daquela dos países da América do Norte e Europa Ocidental.3

No Brasil, as estatísticas apontam para o mesmo sentido. As DCV ainda permanecem como a principal causa de mortalidade, tanto em homens, quanto em mulheres, representando cerca de vinte por cento de todas as mortes no país. Segundo o Ministério da Saúde, em 2009, mais de 193 mil mortes foram causadas por distúrbios relacionados à aterosclerose.4 A incidência de doença cerebrovascular ainda é superior à de doença coronariana, o que pode indicar que a DAC, nas próximas décadas, venha a se tornar mais frequente na nossa população e se torne a maior causa de mortes, se a transição epidemiológica seguir o mesmo caminho dos países desenvolvidos.5

Fisiopatologia da aterosclerose

A insuficiência coronariana tem como causa principal a doença aterosclerótica, definida como distúrbio inflamatório. A formação da placa se inicia com o acúmulo precoce de partículas de lipoproteína de baixa densidade (LDL) na camada íntima arterial.6 A oxidação do material lipídico é um dos fatores responsáveis pela agressão ao endotélio, alterando sua permeabilidade e aumentando a expressão de moléculas de adesão, integrinas e selectinas, que participam da migração de monócitos como parte da resposta inflamatória inata.7

Os macrófagos iniciam a fagocitose do LDL, resultando na formação de células espumosas que produzem citocinas e metaloproteinases, amplificam a resposta inflamatória e recrutam plaquetas e linfócitos T.6^,7 As plaquetas aderem à lesão e liberam prostaglandinas e leucotrienos, além de fatores de crescimento que induzem a multiplicação de monócitos e células de músculo liso.7 Os linfócitos T são apresentados a antígenos da lesão por células dendríticas, passam a produzir citocinas e modulam a resposta imune adaptativa.6

A deposição da matriz extracelular produzida pelo músculo liso diferenciado, a multiplicação celular, necrose e angiogênese promovem a expansão da placa.8 A progressão da doença aterosclerótica, no entanto, não obstrui a luz vascular na mesma proporção, devido ao remodelamento positivo dos vasos que não compromete o diâmetro luminal.8^,9 Ao atingir o máximo da capacidade, ocorrem o remodelamento negativo e o avanço da placa para o interior da artéria que, comprometendo gradativamente o fluxo, pode causar isquemia miocárdica.8

A migração e multiplicação de células de músculo liso pouco diferenciadas na camada íntima promove a mineralização da placa aterosclerótica.9 Essas células são capazes de se diferenciar em osteoblastos, produzir matriz extracelular mineralizada e depositar cristais de hidroxiapatita, acumulando cálcio no interior da lesão9^,10 em processo semelhante à osteogênese. As microcalcificações e os depósitos calcíficos podem levar à cavitação, erosão e ruptura da placa, aumentando o risco de trombose coronariana.10

Avaliação da doença arterial coronariana

Apesar da lenta progressão da doença aterosclerótica na camada íntima das artérias coronárias (demora anos para as lesões precursoras tornarem-se uma placa causando a obstrução luminal), a possibilidade de se tornar instável e causar ruptura da placa fazem da aterosclerose, mesmo subclínica, um risco para a ocorrência de eventos coronarianos agudos.11

Aproximadamente metade dos pacientes com DAC apresenta, como primeiro sintoma, a morte súbita ou o infarto agudo do miocárdio (IAM), tornando, fundamental, o diagnóstico precoce. A detecção precoce por meio de avaliação conjunta dos dados clínicos, laboratoriais e fatores de risco, associados a métodos de imagem não-invasivos em pacientes selecionados, permite a aplicação de melhores estratégias de prevenção e de estratificação de risco.12

Múltiplos fatores de risco estão classicamente associados à ocorrência de eventos agudos em pacientes com DAC e podem ser clinicamente avaliados por meio de escores de risco cardiovascular. No entanto, essa abordagem, exclusivamente clínica, se mostrou limitada no diagnóstico e na predição de eventos como IAM e morte cardíaca, quando comparadas à predição de risco com utilização de métodos complementares associados.13

Nas últimas décadas, diversos métodos diagnósticos têm sido estudados para estimar o risco cardiovascular e diagnosticar a aterosclerose subclínica em pacientes assintomáticos. Dentre eles, o escore de cálcio (EC) coronariano mostrou excelente acurácia em estimar o risco de eventos futuros e detectar a doença precoce de forma isolada ou associada aos escores clínicos.14

A capacidade do EC de estratificação do risco cardiovascular também foi comparada aos chamados novos fatores de risco capazes de estimar a aterosclerose subclínica, como a medida do espessamento da camada médio-intimal carotídea, o índice tornozelo-braquial e a proteína C-reativa. Entretanto, a calcificação coronariana foi melhor na reclassificação de risco de grupos de pacientes estimado por escores clínicos, com grande poder, ainda que utilizada de forma isolada.15^-17

Por outro lado, a estratificação não-invasiva do paciente sintomático se utiliza de métodos mais avançados para o estudo anatômico ou funcional. Apesar de diversos métodos terem comprovada acurácia na detecção da doença coronariana, a cintilografia de perfusão miocárdica (CPM) é, na prática clínica, o mais frequentemente solicitado para avaliação diagnóstica e prognóstica desses pacientes.18

Cintilografia de perfusão miocárdica

A cintilografia de perfusão miocárdica foi introduzida na década de 70 para avaliação da perfusão cardíaca e da função ventricular.19 Ao longo dos anos, devido à vasta literatura fornecendo evidências de sua acurácia, seu valor diagnóstico, prognóstico e seu custo-efetividade, a técnica evoluiu para uma importante ferramenta de estratificação de risco e predição de eventos cardiovasculares, tornando-se um dos métodos não-invasivos mais utilizados na cardiologia.19^-21

A cintilografia é um método baseado na formação de imagens através da aquisição de fótons emitidos por radiofármacos captados por detectores localizados em uma estrutura chamada gamma-câmara, tendo o tecnécio-99m e o cloreto de tálio-20122^,23 como principais substâncias radioativas (radioisótopos) utilizadas para fornecer imagens do coração. Os dados da perfusão miocárdica são reconstruídos em imagens multiplanares, utilizando-se softwares específicos, que correspondem à perfusão do tecido cardíaco no momento da administração da medicação.24

O exame é realizado em dois momentos distintos: repouso e esforço - em protocolos de um ou dois dias. O esforço pode ser físico ou farmacológico, utilizando-se substâncias vasodilatadoras ou inotrópicos. É capaz de avaliar a perfusão miocárdica pela comparação das imagens adquiridas no esforço e no repouso e detectar defeitos perfusionais reversíveis, sugestivos de isquemia. Além disso, fornece informações sobre a viabilidade miocárdica, a função cardíaca, a fração de ejeção, os volumes cavitários e o sincronismo ventricular.23^-25

Nas últimas décadas, foram realizados esforços no desenvolvimento de tecnologias para otimização e aumento da segurança para o paciente. Câmaras com detectores de telureto de cádmio e zinco (CZT) demonstraram melhorias na qualidade das imagens, menor exposição radiológica e tempo de aquisição reduzido, promovendo um grande salto em relação às câmaras tradicionais. Além dos avanços nas gamma-câmaras, programas eletrônicos de tratamento das imagens, notadamente a reconstrução iterativa, também permitem exames de maior qualidade, utilizando-se menores doses de radiotraçadores.26^,27

A cintilografia de perfusão miocárdica é uma técnica estabelecida e consolidada para a detecção de isquemia e avaliação prognóstica. O exame apresenta grande capacidade de detectar lesões com restrição de fluxo.28^,29 O mesmo método é, também, capaz de determinar o prognóstico do paciente, pois um exame normal está, na maioria das vezes, associado a menos de 1% de eventos cardiovasculares adversos por ano, enquanto um exame com evidência de isquemia indica um risco aumentado proporcionalmente à extensão do defeito.30

Escore de cálcio coronariano

A presença de cálcio nas artérias coronárias é um forte indício de DAC. Por isso, desde que foi descrito e passou a ser utilizado como técnica para detecção da doença coronariana, inicialmente pela fluoroscopia e pela tomografia computadorizada por feixe de elétrons na década de 70, despertou grande interesse nas possibilidades de aplicação diagnóstica e prognóstica.31^-33

A partir da introdução, na década de oitenta, da tomografia computadorizada com múltiplos detectores, a técnica foi adaptada para a realização nesses novos aparelhos, apresentando resultados semelhantes, com resultados superiores em alguns pontos, principalmente, quando disponíveis, sistemas com 64 detectores ou mais.32^-34

O escore de cálcio é obtido a partir da aquisição de imagens axiais do tórax, de forma sincronizada ao eletrocardiograma, com cortes de 3 mm de espessura, sem utilização de contraste iodado. Em geral, a dose efetiva de radiação é reduzida podendo variar com as características do tomógrafo e da técnica utilizados.32^-35

São quantificadas as lesões hiperatenuantes com intensidade de sinal acima de 130 unidades Hounsfield e área igual ou maior a 3 pixels contíguos. Pode ser fornecido o volume total, a massa ou a soma ponderada pelo escore de Agatston. A técnica descrita por Agatston et al. é a mais utilizada na literatura e a que apresenta maiores evidências.32^-35

Os pacientes podem ser divididos em grupos de acordo com a extensão da doença: ausência de calcificação, calcificação mínima (1-10), leve (11-100), moderada (101-400), severa (401-1000) e extensa (maior que 1000). Podem ainda ser classificados em grupos de acordo com o percentil para a idade, sexo e etnia.35

Inicialmente, uma série de trabalhos abordaram a capacidade do escore de cálcio predizer a presença de lesões anatômicas significativas na coronariografia invasiva e seu papel nas síndromes coronarianas agudas como triagem para a realização de cateterismo.31^,32^,36 Com o passar dos anos, o interesse se voltou para o poder prognóstico e a capacidade de predizer a ocorrência de eventos cardiovasculares.33^,37^-40

Diversos estudos demonstraram que, por ser um indicador da aterosclerose e do risco cardiovascular de forma independente e superior a outros métodos e escores clínicos,33^,37^-40 a presença de calcificação coronariana se correlaciona com eventos cardiovasculares. O risco de pacientes com EC acima de 1000 chega a ser 12 vezes superior, e mesmo a calcificação mínima confere um risco aumentado de 2 a 3 vezes.39

Por outro lado, na presença de um escore igual a zero, é pequena a probabilidade de doença em pacientes com risco baixo a intermediário, mesmo que apresentem sintomas.37^,38 Além disso, denota que a doença não demonstra grande extensão, sendo um indicador de bom prognóstico. A ausência de cálcio nas coronárias determina um risco anual próximo a 0,1%.40

A CPM é um excelente método para avaliar a doença obstrutiva e indica bom prognóstico quando negativa, contudo, tem a limitação de não identificar lesões sem restrição de fluxo.27 Além disso, tem custo elevado, utiliza maiores doses de radiação ionizante que o escore de cálcio, exige aparato tecnológico específico, pessoal especializado e fornecimento de material radiológico.24

Em contrapartida, o EC se relaciona diretamente com a presença e extensão da aterosclerose coronariana. Além disso, tem uma potencial disponibilidade maior e custo inferior em relação à cintilografia, além de menor dose efetiva de radiação. No entanto, não é capaz de quantificar a estenose coronariana e tem um papel ainda indefinido na doença sintomática.37

As informações fornecidas pelos métodos são possivelmente complementares, possibilitando uma abordagem conjunta. Entretanto, a correlação entre os resultados, a influência das características populacionais sobre os achados e a utilização dos métodos de forma sequencial não estão estabelecidas de forma definitiva.38^-40 Sendo assim, não existe, até o momento, consenso nas diretrizes clínicas em relação à forma de aplicação conjunta do escore de cálcio e da cintilografia.

Correlação entre os métodos

Há algumas décadas, surgiu especial interesse na acurácia dos métodos não-invasivos para detecção da aterosclerose das artérias coronárias, buscando-se estabelecer um paralelo entre as diversas formas de abordar a doença coronariana. Foi abordada, por diversos estudos na literatura,41^-50 a capacidade do EC de identificar, no exame de cintilografia miocárdica, pacientes sob risco de apresentar isquemia.

Os resultados apontam para uma correlação entre o cálcio coronariano total e a cintilografia, demonstrando que, em faixas superiores do escore de cálcio, defeitos de perfusão são mais frequentes e a gravidade da área isquêmica é maior.41^,42 O oposto também é verdadeiro, sendo menor a incidência de isquemia em pacientes com escore de cálcio reduzido.41^-43

O aumento da calcificação coronariana se correlaciona, de forma geral, a maior ocorrência de isquemia. Pacientes com distúrbios metabólicos e presença de cálcio coronariano têm, ainda, maior probabilidade de apresentar alterações perfusionais que pacientes sem comorbidades.44 Na população diabética, o escore de cálcio demonstra correlação com a presença de alterações na cintilografia de forma superior aos fatores de risco tradicionais.45

Apesar das evidências descritas, a correlação entre escore de cálcio e perfusão miocárdica pode variar de acordo com as características populacionais e sintomas.47 A apresentação clínica tem grande importância na correlação entre os métodos. Em pacientes sintomáticos com alto risco para DAC, a ocorrência de alterações no exame funcional, mesmo quando a calcificação era reduzida, foi mais frequente em relação aos de probabilidade baixa ou intermediária.47^,48

A análise por leito coronariano demonstra ainda que, em coronárias com escore de cálcio baixo, a presença de isquemia em seus territórios foi significativamente menor com valores preditivos semelhantes ao da angiotomografia.49^,50 Apesar do escore de cálcio se correlacionar com a extensão da doença e não com o grau de estenose, demonstrou capacidade semelhante à da angiotomografia de predizer alterações da perfusão miocárdica.49

Escore de cálcio zero

O escore de cálcio, além de adicionar informações complementares à cintilografia, mostrou-se uma poderosa ferramenta na avaliação da doença coronariana. No entanto, algumas situações se sobressaem, como o escore de cálcio zero.36^-40 A ausência de cálcio nas artérias coronárias não significa a inexistência de aterosclerose, pois pode haver placas não-calcificadas. Porém, nessa situação se correlaciona com uma doença de menor extensão.39^,40

Apesar de a utilização do EC nos pacientes assintomáticos constar nas diretrizes mais recentes, o mesmo não ocorre com os pacientes sintomáticos.16^-18 Entretanto, em exames como a cintilografia51 a literatura sinaliza que, em pacientes com sintomas e risco, baixo ou intermediário, para doença coronariana, o escore zero é capaz de afastar a presença de alterações perfusionais.

A partir de estudos iniciais, surgiu especial interesse na capacidade do escore de cálcio afastar DAC e se correlacionar com a perfusão miocárdica normal. Em um exame funcional normal, a ausência de calcificação coronariana é um forte indicativo de ausência de doença aterosclerótica. Quando comparado à cineangiocoronariografia, é improvável a presença de lesões significativas, necessidade de intervenção ou ocorrência de IAM.47^,51^-54

A ausência de cálcio coronariano se mostrou capaz de afastar a isquemia ocasionada pela DAC em pacientes com sintomas e probabilidade, baixa ou intermediária, de doença significativa, e o EC quando utilizado em conjunto com a cintilografia mostra acréscimo na especificidade e no valor preditivo positivo da estratégia diagnóstica (Figura 1).51^,55^,56

Figura 1 Paciente com Escore de Cálcio zero. (A) Ausência de placas calcificadas. Risco inferior a 5% de coronariopatia e risco baixo de eventos cardiovasculares (0,1% por ano). (B) Cintilografia miocárdica normal.

Todavia, na apresentação aguda dos sintomas na sala de emergência ou em pacientes de alto risco para DAC, a utilização do EC é limitada, uma vez que os fenômenos aterotrombóticos das síndromes coronarianas agudas podem cursar sem calcificação. A ausência de cálcio em pacientes sintomáticos com indicação de cineangiocoronariografia não é capaz de excluir a presença de lesões significativas.57 Nesses casos, o EC não adiciona informações diagnósticas e prognósticas, tendo menor poder de predição de eventos que a cintilografia.58^-60

Calcificação coronariana elevada

Por outro lado, a calcificação coronariana severa se mostrou um fator preditor de risco independente e complementar a praticamente todos as outras formas de avaliação da doença arterial coronariana, seja ela clínica - por meio de escores de risco - ou complementar - via outros métodos não-invasivos e testes funcionais -, como o teste ergométrico e a cintilografia.61^-68

O escore de cálcio elevado é um indicador de maior risco para eventos cardiovasculares como o infarto e a morte cardíaca, apresentando maior acurácia isoladamente ou em conjunto do que o escores clínicos de risco (Figura 2 e 3). Sua presença indica um pior prognóstico nesses pacientes, reclassificando-os para grupos de maior risco, independentemente das características populacionais.36^-40

Figura 2 Paciente com Escore de Cálcio 1-10. (A) Mínima quantidade de placas calcificadas no território da artéria descendente anterior. Provável risco (inferior a 10% de doença coronária obstrutiva). (B) Cintilografia miocárdica normal.

Figura 3 Paciente com Escore de Cálcio 11-100. (A) Discreta quantidade de placas calcificadas no território da coronária direita. Doença arterial coronária definitiva, porém discreta. (B) Cintilografia miocárdica apresenta isquemia na parede inferior em região com atenuação por partes moles.

A presença de um escore de cálcio severamente elevado está relacionada também a maior frequência de lesões significativas, mesmo em pacientes com a cintilografia normal.61 Em pacientes persistentemente sintomáticos sem alterações perfusionais, a calcificação coronariana extensa se correlaciona com a presença de lesões significativas e pode indicar a necessidade de cineangiocoronariografia e intervenção percutânea ou cirúrgica.62

A presença de calcificação coronariana extensa se relaciona ainda com a maior incidência de doença obstrutiva significativa e revascularização, mesmo quando o resultado do teste provocativo é normal.63^-65 Analogamente, pacientes com alterações na cintilografia apresentam maiores valores de escore de cálcio, quando comparados a pacientes com exames de perfusão normal.41^-43

A calcificação coronariana aumentada é, portanto, capaz de se correlacionar com a presença de lesão obstrutiva, mesmo quando o teste provocativo é normal, minimizando os resultados falso-negativos com a utilização conjunta dos dois métodos.66 A estratégia conjunta tem ainda a capacidade de indicar pacientes que se beneficiariam de investigação adicional ou abordagem invasiva (Figura 4 e 5).69

Figura 4 Paciente com Escore de Cálcio 101-400. (A) Moderada quantidade de placas calcificadas nos territórios das artérias descendente anterior e circunflexa. Doença arterial coronária moderada. (B) Cintilografia miocárdica com presença de isquemia ínfero-lateral.

Figura 5 Paciente com Escore de Cálcio acima de 400. (A) Grande quantidade de placas calcificadas no território da artéria descendente anterior. Doença arterial coronariana importante. (B) Cintilografia miocárdica com presença de isquemia anterior e antero septal.

Informações independentes e complementares

Os valores intermediários do escore de cálcio também são importantes na avaliação da doença coronariana. O EC se mostrou complementar à CPM, independentemente da presença ou não de isquemia.70 Em pacientes com a cintilografia normal, a presença de um escore alterado indica maior risco, apesar do bom prognóstico da cintilografia normal, e os pacientes com defeitos perfusionais apresentam ainda maior risco de eventos e pior prognóstico.71

A associação dos métodos apresenta maior acurácia diagnóstica tanto ao detectar quanto ao afastar a doença coronariana, além de determinar de forma mais contundente o prognóstico desses pacientes. Além disso, a presença dos resultados dos exames em paralelo possibilita uma melhor interpretação dos resultados, minimizando achados equívocos e melhorando o desempenho dos métodos.72^,73

Nos pacientes com cintilografia normal, o escore de cálcio informa sobre a doença subclínica e pode auxiliar na exclusão de DAC ou inferir a presença de lesões obstrutivas significativas.74 Em pacientes persistentemente sintomáticos, o escore de cálcio elevado foi um fator preditor de estenose coronariana significativa a despeito dos resultados da cintilografia.64

A utilização conjunta do escore de cálcio e da cintilografia se torna ainda mais interessante se levarmos em consideração o valor prognóstico dos métodos para DAC. A ocorrência de mortalidade e eventos cardíacos se relaciona com a severidade da calcificação coronariana, independentemente do resultado da cintilografia.74^-76

Entretanto, o prognóstico estabelecido pela cintilografia é caracteristicamente de curto a médio prazo, sendo um resultado normal preditor de bom prognóstico neste período, mesmo em grupos com EC elevado.75^,76 Por outro lado, o escore de cálcio pode estimar o risco a prazos maiores de 10 a 15 anos, como observado recentemente, situação na qual a calcificação coronariana elevada se sobrepõe à ausência de defeitos perfusionais.39^,40^,74^,76

Além disso, um importante aspecto da correlação entre o escore de cálcio e a CPM é o impacto que o resultado de um método tem sobre a interpretação do outro. As informações adicionais e o acréscimo à probabilidade pré-teste fornecidas pela calcificação coronariana exercem influência positiva na interpretação da cintilografia, melhorando a acurácia e reduzindo a quantidade de resultados equívocos na análise conjunta desses dois métodos.77

Exposição à radiação

Em relação à radiação, o método do escore de cálcio leva clara vantagem por expor o paciente a doses menores que as da cintilografia. Estudos multicêntricos demonstraram que a dose média de radiação da cintilografia foi superior a 10 milisieverts (mSv), com médias ainda maiores em regiões como América Latina e Ásia (15 mSv).78^,79

É importante ressaltar que os recentes avanços tecnológicos da cintilografia, tanto em detectores quanto em softwares de reconstrução de imagens, possibilitam que esses exames sejam realizados com exposição à radiação muito inferior em relação às técnicas tradicionais. A utilização desses avanços permite exames com dose efetiva abaixo de 5 mSv com utilização de protocolos de dose ultra-reduzida de radiotraçador.26^,27^,80^,81

Por outro lado, a realização do escore de cálcio apresenta baixa dose de radiação, e nos pacientes encaminhados para cintilografia não se torna elevada de forma impeditiva à estratégia. Nos estudos que avaliaram a dose efetiva do escore de cálcio, a média foi de 2,5 mSv.82^,83 Dessa forma, o escore de cálcio se mantém em uma faixa de risco segura para neoplasias.84

Conclusão

A revisão da literatura demonstra que tanto o escore de cálcio quanto a cintilografia exercem importante papel na avaliação diagnóstica da doença aterosclerótica do coração. A possibilidade de afastar a coronariopatia de grande extensão por meio de um escore de cálcio zero, ou ainda indicar a presença de uma doença extensa quando este estiver severamente aumentado, justifica a utilização desse método na avaliação, inicial ou conjunta, de pacientes assintomáticos com suspeita de DAC e na estratificação do risco cardiovascular. A avaliação de pacientes sintomáticos de baixo risco, apesar de indícios que apontem positivamente nessa direção, deverá ser reavaliada nas próximas diretrizes.

A confirmação da doença com aplicação de métodos de maior especificidade e valor preditivo positivo como a cintilografia de perfusão miocárdica ainda se mostra fundamental em determinados pacientes. Dessa forma, apesar de a literatura sinalizar que a utilização sequencial ou conjunta dos dois métodos é vantajosa, ainda são necessários mais dados no estabelecimento de uma estratégia custo-efetiva para a avaliação diagnóstica. Parece justificável, portanto, do ponto de vista da qualidade e acurácia da avaliação e no âmbito econômico da saúde pública, que novos estudos continuem pesquisando o papel dessas importantes ferramentas.

Fontes de financiamento

O presente estudo não teve fontes de financiamento externas.

Vinculação acadêmica

Este artigo é parte de Dissertação de Mestrado de Fabio Paiva Rossini Siqueira pela Universidade Federal Fluminense.

Agradecimentos

Os autores gostariam de agradecer ao Hospital Universitário Antônio Pedro (HUAP) da Universidade Federal Fluminense (UFF) pelo suporte na realização dos exames de angiotomografia de coronária e medicina nuclear.