Patients with new-onset stable chest pain syndromes

Introduction

Chest pain remains one of the most common patient complaints both at the primary care level and in the specialized cardiology clinic. According to the American Heart Association’s heart disease and stroke statistics, 635,000 Americans have a new coronary event every year, of which 20% are silent myocardial infarction. Chest pain is also the most frequent chief complaint in the emergency room, causing more than 8 million visits a year (see discussion in Chapter 11 ). The evaluation of patients with chest pain is important and requires a detailed approach that takes into account multiple considerations, including the typicality of symptoms, pretest likelihood of coronary artery disease (CAD), and strengths and limitations of the ancillary tests used in the diagnostic workup. In this chapter, we discuss the role of radionuclide imaging in the assessment of patients with new-onset stable chest pain. We will focus on the role of single photon emission computed tomography (SPECT) and positron emission tomography (PET) in the evaluation of these patients. The value of alternative approaches to diagnosis, especially exercise treadmill testing (ETT) and cardiac computed tomography (CT), will also be discussed.

Initial assessment of patients with new-onset chest pain

The aim of the management of patients with stable chest pain in the clinic is to determine the likelihood of CAD and confirm the diagnosis via further testing. Thus the initial evaluation of these patients would include a history and physical examination to identify signs and symptoms of obstructive CAD.

In addition, an electrocardiogram (ECG) may guide the disposition of these patients. For example, the presence of ischemic changes or abnormal Q waves on the ECG would increase the likelihood of CAD and may prompt referral for noninvasive testing and, sometimes, direct coronary angiography.

The analysis of probability as an aid to the diagnosis of obstructive CAD in stable symptomatic patients has been standard practice in cardiology for many decades. Multiple CAD probability scores integrating age, sex, chest pain characteristics, and coronary risk factors have been proposed for the assessment of patients with stable chest pain syndromes. A strong evidence base has demonstrated that noninvasive imaging testing for obstructive CAD is most cost effective when applied to patients with an intermediate likelihood of CAD and is recommended by guidelines. These include the Diamond-Forrester risk score, the CONFIRM (COroNary CT Angiography Evaluation For Clinical Outcomes: An InteRnational Multicenter Registry) risk score, and the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) risk score. Nevertheless, the predictive value of these scores is often dependent on the population the score is derived from, as well as the population it is applied to. Recent data suggest that CAD probability scores overestimate the risk and prevalence of CAD. For example, in the PROMISE trial, the prevalence of CAD as determined by coronary CT angiography or abnormal myocardial perfusion imaging (MPI) was significantly lower than predicted by the pretest score. Similarly, a study from the CONFIRM registry also showed that the prevalence of CAD was overestimated by the Diamond-Forrester risk score compared with the prevalence of CAD by coronary CT angiography. Part of the problem is that these scores have been validated in cohorts of patients referred for invasive coronary angiography or coronary computed tomography angiography (CCTA), which overestimates the prevalence of CAD, thereby increasing the sensitivity and decreasing the specificity of CAD probability scores. This overestimation of CAD probability may explain the relatively lower frequency of abnormal studies in recent reports. ^, It is important to keep in mind that as the prevalence of disease in the studied population decreases, the negative predictive value increases and the positive predictive value decreases (because of an increase in false-positives). This applies to both the CAD probability scores and imaging tests.

Incremental value of imaging tests

Exercise ECG remains an important test in the assessment of patients with stable chest pain syndrome, especially those with a normal baseline ECG. It is the initial modality recommended by the American College of Cardiology and American Heart Association guidelines for assessing patients with stable ischemic heart disease. It provides valuable information regarding exercise capacity and cardiorespiratory fitness, ^, thus providing important diagnostic and prognostic information that is useful in guiding management. More notably, the presence of chronotropic incompetence has been associated with a worse long-term outcome and hypertensive response during exercise has been associated with increased incidence of future comorbidities, including new incident hypertension. The Duke treadmill score can also be calculated using data gathered from the stress test and has widely recognized prognostic value. Nevertheless, exercise ECG has lower overall accuracy compared with functional and anatomic imaging tests. A meta-analysis including more than 24,000 patients with 22 years of follow-up has shown that stress ECGs have a sensitivity of 68% and specificity of 77% for the diagnosis of obstructive CAD.

Given the limitations of exercise ECG, further testing with imaging is often needed in different clinical scenarios including patients with

• Equivocal exercise electrocardiography;

• Abnormal resting ECGs, including left bundle branch block (LBBB) and left ventricular (LV) hypertrophy with repolarization abnormalities; and

• Certain populations where ECG ischemic changes may be falsely positive rather than indicative of obstructive CAD, such as in young women.

Diagnostic value of radionuclide imaging

SPECT imaging is the most commonly used stress imaging test for CAD diagnosis in the United States. Overall, the sensitivity and specificity for detection of obstructive CAD ranges between 75% and 85%. A limitation of SPECT MPI is that the test often uncovers only myocardial regions supplied by the most severe coronary stenosis. This can lead to underestimation of the extent of CAD, especially in high-risk patients with multivessel CAD. An important advantage of PET MPI is its unique ability to provide absolute measures of myocardial blood flow and flow reserve, which allows for improved delineation of flow-limiting CAD and also microvascular dysfunction. Recent meta-analyses ^, and the prospective multicenter EVINCI (Evaluation of Integrated CAD Imaging in Ischemic Heart Disease) study support the diagnostic advantage of PET. Furthermore, a recent meta-analysis using fractional flow reserve (FFR) as the gold standard for flow-limiting CAD demonstrated higher diagnostic accuracy for PET compared with SPECT MPI. Finally, the results of the PACIFIC (Prospective Comparison of Cardiac PET/CT, SPECT/CT Perfusion Imaging and CT Coronary Angiography With Invasive Coronary Angiography) study confirmed the superiority of quantitative PET MPI for the detection of flow-limiting CAD, including the combination of CCTA with and FFR derived from standard coronary CT angiography (FFR _CT ).

A detailed discussion of stress testing and imaging protocols used with SPECT and PET imaging can be found in Chapter 4 , and common artifacts that may challenge image interpretation can be found in Chapter 5 .