Multimodality Approach to Cardiovascular Disorders

Introduction

Multimodality cardiovascular imaging has come a long way since the time of 2D echocardiography and thallium stress testing. The development and increased adoption of novel techniques, namely cardiac computed tomography (CCT), cardiac magnetic resonance (CMR), single-photon emission computed tomography (SPECT) with new generation of cameras, and positron emission tomography with CT attenuation correction (PET/CT) have enhanced our capabilities to evaluate many forms of cardiovascular disease. With respect to coronary artery disease (which is the most prevalent form of cardiovascular disease) imaging can now evaluate a wide spectrum of disease, ranging from the detection of preclinical atherosclerosis to advanced assessment of myocardial blood flow and viability. However, due to the availability of multiple testing options, it is now also more challenging for clinicians to select the best test for a given patient. This chapter will focus on the application of multimodality imaging in the assessment of patients with known or suspected coronary artery disease and will offer a conceptual framework on how to select between various imaging tests.

Assessment of Patients With Suspected Coronary Artery Disease

The initial approach in patients without previously diagnosed coronary artery disease (CAD) relies primarily on whether they have symptoms of possible ischemic heart disease and how the results of the test may impact their management.

Asymptomatic Patients

In asymptomatic patients who do not have known CAD, routine testing is not recommended irrespective of the type of test being considered. In those who are not on any medical therapies, selective use of coronary artery calcium (CAC) testing may be considered, particularly if there is uncertainty regarding a patient’s risk or the role of stain therapy. Studies have shown that the detection of coronary plaque by CAC testing is associated with intensification of both lifestyle and medical therapies.

In selected high-risk asymptomatic patients, silent ischemia may be present; however, it is unclear if the detection of ischemia in such patients leads to any improvement in outcomes. Risk factors for silent ischemia include older age and longstanding diabetes.

Symptomatic Patients

In low-risk symptomatic patients, exercise treadmill testing, stress echocardiography, or CAC testing can all be considered if there is a need for further testing. However, there are also various emerging studies that suggest that it may be safe to defer testing in low-risk patients who have stable symptoms, especially if these are nonanginal symptoms, where the likelihood of finding any significant disease is low.

In intermediate- to high-risk patients, either anatomic testing with coronary CTA or functional testing approaches may be selected. The choice of testing will depend on local availability and expertise, the likelihood of obtaining diagnostic image quality with each test, and the anticipated impact of the test result on patient management. Patients who are not on any medical therapies may benefit from coronary CTA (or hybrid PET/CT or SPECT/CT) since the diagnosis of plaque may impact the use of downstream medical therapies and subsequently outcomes. On the other hand, patients who have contraindications to CTA (e.g., GFR < 30, severe contrast reaction) should be evaluated with a functional imaging test. In patients who are already on medical therapy, functional testing may also be preferred if the main clinical question is whether there is a role for invasive angiography or coronary revascularization. In such cases, information regarding exercise capacity and exercise-induced symptoms may also be helpful in determining the potential benefit of coronary revascularization.

Assessment of Patients With Known CAD

In patients with known CAD, the main clinical question is often whether they require coronary revascularization procedures. There is data [albeit mostly from retrospective studies or from invasive studies using fractional flow reserve (FFR)] that patients who have moderate to severe ischemia may benefit more from coronary revascularization procedures. Nevertheless, the ISCHMIA trial may provide further guidance regarding how aggressive medial therapy and revascularization compare.

For patients who are being evaluated for possible coronary revascularization, we recommend the use of a functional test that can quantify the amount of ischemia. A few tips may help select between different testing options, as detailed below.

PET Myocardial Perfusion Imaging (MPI)

• Offers robust attenuation correction and ability to quantify absolute myocardial blood flow (MBF)
• When compared to SPECT, PET has higher diagnostic accuracy and may be particularly useful in patients who have multivessel disease, as SPECT MPI may underestimate severity or extent of ischemia
• When PET is used, data on myocardial blood flow reserve (MBFR) adds additional prognostic value and can be used to rule out high-risk anatomy
• Specifically, normal myocardial blood flow reserve has high negative predictive value for excluding left main or 3-vessel obstructive CAD
• Notably, information on myocardial blood flow reserve can only be obtained during vasodilator testing
• Main limitation: Not widely available

Cardiac MR

• Accurately detects ischemia using dynamic first-pass perfusion imaging
• Contractile reserve can be evaluated using dobutamine MR
• Late gadolinium enhancement (LGE) can be used to evaluate for myocardial viability based on extent of scarring
• Based on patterns of LGE, cardiomyopathies can be characterized

SPECT MPI

• Widely available and can be performed during exercise or vasodilator testing
• Accuracy may be reduced in patients with multivessel disease

Coronary CTA

• Has more limited role in patients who have known CAD, particularly as native coronary arteries are more likely to have significant coronary calcifications, which may limit ability to visualize vessel lumen
• Select role in evaluating proximal large stents (≥ 3 mm in diameter)
• In patients who have undergone prior revascularization, 2 potential indications for coronary CTA exist: Evaluating proximal large stents (≥ 3 mm in diameter) and evaluating bypass grafts

Exercise Treadmill Testing (ETT)

• Limited by low accuracy to detect ischemia and not useful in quantifying amount of ischemia
• However, advantages include useful prognostic information, providing data on patient’s functional capacity, as well as whether they develop any significant symptoms during exercise

Additional Considerations for Various Testing Strategies

Below are more specific details on various testing options, which may be useful to understand when selecting among different choices

Exercise Testing

• ETT, stress echocardiography, SPECT MPI, and some forms of PET can be performed with exercise
• Advantages: Provide data on exercise capacity, blood pressure, and heart rate response to exercise and development of symptoms and electrocardiographic (ECG) changes with exercise
• Information on exercise capacity and symptoms may be useful when deciding on role of coronary revascularization, and thus combining data from ETT with other tests that are not performed during exercise may be beneficial
• e.g., may be useful to combined data from CTA or CAC with ETT, or in some cases PET or CMR with ETT

SPECT/PET

• Data derived from MPI include extent and severity of ischemia and size of infarction
• Left ventricular volumes and function can also be calculated
• Added benefit of improved spatial resolution and improved sensitivity compared to SPECT
• Furthermore, since most PET cameras also have hybrid CT, coronary calcium score can be calculated, thus providing information on burden of atherosclerotic disease
• Finally, quantification of myocardial blood flow at peak stress and rest and their ratio (myocardial blood flow reserve) can be derived from PET/CT

Coronary CTA (CCTA)

• Utilization in initial assessment of patients with suspected CAD should be considered for patients at intermediate to high risk with adequate renal function who can follow breath-holding instructions
• Advantages include fast acquisition of images delineating not only anatomy of coronary tree, but also location, extent, and severity of coronary plaque
• Combination of CCTA with functional evaluation of moderate severity stenoses using CT-based fractional flow reserve (CT-FFR) has been validated in a few clinical trials and registries
• Use of CT-FFR may increase in future, and several large comparative effectiveness studies are underway
• Functional evaluation can also be performed by using CT perfusion, which involves acquisition of images at rest and after pharmacological stress

Stress CMR

• May be compelling in young patients in whom there is desire to avoid radiation, e.g., premenopausal women
• Usually done in combination with vasodilator or dobutamine stress testing
• MR-compatible ergometers are available in selected institutions
• In addition to assessing for presence and extent of perfusion defects, stress CMR can also provide information on left and right ventricular size and function, as well as presence of myocardial edema (via T2 imaging or T2 mapping), or myocardial fibrosis, infiltration or scar (via LGE and parametric mapping, which can quantify myocardial T1 and extracellular volume)
• Abnormalities on LGE can help identify and differentiate ischemic from nonischemic cardiomyopathies based on pattern and distribution of LGE
• Thus, stress CMR may be particularly attractive in patients who have left ventricular systolic dysfunction with possible nonischemic cardiomyopathy
• Overall, stress CMR has been shown to be of comparable diagnostic accuracy to nuclear MPI techniques
• From prognostic standpoint, negative stress CMR is associated with excellent event-free survival
• Quantification of global MBFR can also be performed using stress CMR although this is not widely performed clinically and is less validated than blood flow quantification techniques used by PET MPI

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