4

Techniques for Cardiovascular System Disorders

Broadly speaking, diagnostic testing in the cardiovascular system is used to evaluate anatomical or physiologic functions of the heart and vasculature, often in response to symptoms or signs of cardiovascular disease, which may involve atherosclerosis, ischemia, valvular dysfunction, or arrhythmia. Cardiovascular disease may manifest with symptoms of chest pain, shortness of breath, fatigue, or decreased exercise tolerance and can limit a person’s overall functioning and work capacity in multiple ways. In some individuals the heart may become too weak to pump an adequate amount of blood to provide oxygen to exercising muscle. Even when the contractility of the heart appears adequate at rest, structural and functional impairments involving the coronary circulation, cardiac muscle, valves, or electrical system may limit the heart’s response to exercise. For some individuals who are physically capable of exercise, the cardiologist may prescribe activity restriction because of a risk of sudden life-threatening arrhythmia or other physical collapse during exertion, such as can occur with some inherited genetic heart diseases, advanced hypertrophic cardiomyopathy, or critical aortic stenosis (NASEM, 2019). Cardiovascular testing varies by the suspected diagnosis and often requires the use of multiple tests to confirm a specific pathology and assess its severity.

Over the last 30 years cardiovascular diagnostic testing has changed tremendously with the innovations in imaging techniques discussed in Chapter 3. In cardiology, a combination of functional and anatomic techniques is used to interrogate for the presence and severity of disease. Noninvasive approaches to testing can include the use of exercise stress testing, echocardiography, nuclear imaging, magnetic resonance imaging (MRI),

and computed tomography (CT). While the former noninvasive approaches are commonly used as first-line testing in many clinical scenarios, invasive techniques involving the use of catheter procedures and electrophysiologic testing (of electrical currents that generate heartbeats) are also used and have undergone significant advances as well.

In this chapter the committee opted to highlight selected techniques that have, when compared to those previously and widely available in 1990, enhanced diagnostic accuracy for important cardiovascular conditions. These include disease processes commonly resulting in coronary obstruction, myocardial ischemia, valvular dysfunction, and arrhythmia, which may have an impact upon an individual’s capacity to function in his or her usual environment. Many of the techniques involve significant advances or a refinement of previously available technology, or both. For example, within echocardiography recent advances include the use of two-dimensional (2D) as well as 3D transesophageal echocardiography, Doppler imaging, and myocardial strain evaluation for improved visualization of valvular anatomy and assessment of hemodynamic impairments and myocardial mechanics, respectively. Within nuclear cardiology, advances in cardiac single-photon emission computed tomography (SPECT) include the development of high-resolution cadmium-zinc-telluride detectors and stress-first imaging protocols with reduced radiation doses for the evaluation of suspected myocardial ischemia and the repurposing of Tc-99 pyrophosphate (PYP) bone imaging for the novel noninvasive evaluation of cardiac transthyretin (TTR) amyloidosis. Also within nuclear cardiology, advances in cardiac positron emission tomography (PET) include enhanced diagnostic accuracy over cardiac SPECT; the ability to evaluate coronary blood flow and coronary flow reserve (CFR) for quantification of myocardial ischemia, including coronary microvascular dysfunction; and fluorodeoxyglucose (FDG) imaging for the evaluation of myocardial viability post infarction or cardiac inflammation in cardiac sarcoidosis. Advances in cardiac magnetic resonance (CMR) imaging have led to superior spatial resolution, which assists in the comprehensive assessment of cardiovascular structure and function, including the evaluation of late gadolinium enhancement (LGE) for the assessment of myocardial viability and investigating the etiology of cardiomyopathies. Advances in CT include being able to quantify coronary artery calcium for enhanced risk-stratification in cardiovascular prevention as well as the use of coronary CT angiography (CCTA) for the noninvasive evaluation of epicardial coronary artery disease. Finally, new methods in invasive coronary angiography have been developed in the areas of intravascular hemodynamic assessment of the coronary circulation (e.g., fractional flow reserve FFR], coronary flow reserve [CFR], index of microcirculatory resistance) and intravascular imaging (e.g., intravascular ultrasound, optical coherence

tomography of coronary lesion characteristics and atherosclerotic plaque morphology), with further advances in electrophysiologic testing.

These advances have substantially improved diagnostic accuracy for numerous cardiovascular conditions and are facilitating the use of novel and effective therapeutic approaches to reduce the burden of cardiovascular disease. Beyond this, the continued application, combination, and refinement of these techniques are expected to broaden our understanding of cardiovascular disease pathophysiology across gender and racially diverse populations, including, for example, the importance of nonobstructive atherosclerosis and coronary microvascular dysfunction in the morbidity and mortality of patients with ischemic heart disease. In the future, continued advances in multimodality imaging technology, genetics and molecular biology, and artificial intelligence may further improve the precision of diagnosis involving cardiovascular conditions. Ultimately, as discussed in Chapters 1–3, despite these technological advancements, the assessment of the functional status of an individual, including the possibility of disability, is not dependent on any single test of the cardiovascular system and requires a holistic approach integrated across organ systems and the individual’s environment.

OVERVIEW OF SELECTED TECHNIQUES

Box 4-1 highlights the techniques for diagnosing cardiovascular disease selected on the basis of criteria described in Chapter 1. A main focus is on the cardiovascular disorders in SSA’s Listings of Impairments, which include chronic heart failure, ischemic heart disease, recurrent arrhythmias, symptomatic congenital heart disease, heart transplant, aneurysm of aorta or major branches, chronic venous insufficiency, and peripheral arterial disease. Following the descriptions of the selected techniques, the last section of the chapter outlines emerging techniques for cardiovascular system disorders.

Patient Reported Questionnaires and Exercise Testing

In addition to the use of non-invasive and invasive techniques such as those listed above, demonstrating functional cardiac limitation can be supported by a patient questionnaire and a medical provider’s integrated clinical assessment. The addition of exercise testing provides objective functional measurement during an exercise tolerance test. Details about cardiopulmonary exercise testing can be found in the chapters on general techniques (Chapter 3) and respiratory disease (Chapter 6).

Multiple validated patient questionnaires can be used to assess symptomatic limitation with cardiovascular disease. Two standard questionnaires

for heart failure are the Minnesota Living with Heart Failure Questionnaire (Rector et al., 2006) and the Kansas City

Cardiomyopathy Questionnaire (Joseph et al., 2013). Both have been extensively validated and show good reliability, responsiveness, performance across populations, feasibility, and interpretability (Kelkar et al., 2016). These instruments were not developed specifically to address physical function but rather to quantify the overall impact of a decrease in heart function on the life of an individual. They survey multiple domains, including physical, social, and emotional. Both questionnaires are approved by the U.S. Food and Drug Administration as valid for demonstrating the value of medical interventions, either medications or devices. Functional Assessment for Adults with Disabilities (NASEM, 2019) provides additional relevant information about these tests and others for selected cardiac and cardiovascular assessments.

IMAGING TECHNIQUES

As described in this section, advances in imaging technology have improved the precision of diagnoses involving cardiovascular conditions.

Echocardiography

Two-dimensional (2D) and 3D echocardiography are non-invasive tests that use ultrasound imaging technology to assess the structure and function

of a heart in real time. Over the past decades the use of echocardiography as an imaging method has increased, to the point that echocardiography is one of the most clinically used diagnostic tools in daily cardiology practice (Lang et al., 2006). Hemodynamic imaging through Doppler techniques is specific in evaluating the flow of blood through the heart chambers and valves and can detect abnormal blood flow in the heart’s functioning. Echo strain is evaluation of the muscle by evaluating the deformation resulting from an applied force (Lopez-Candales et al., 2017). A transesophageal echocardiogram is done by inserting the transducer down the esophagus, allowing for a clearer image, particularly of the posterior structures of the heart, such as the left atrium and left atrial appendage and the mitral valve, because the sound waves do not have to pass through skin, muscle, or bone tissue.

The responses to the items in the statement of task for echocardiography are as follows:

1. Accepted uses for echocardiography include imaging of heart structures, i.e., the pericardium, ventricles and their cavities, valves, vessels, and chambers. The American College of Cardiology, the American Heart Association, and the American Society of Echocardiography published practice guidelines (last updated in 2003) for the clinical application of echocardiography (Cheitlin et al., 2003).
2. 3D echocardiography is state of the art and provides accurate and reliable measurements of chamber size and function and improved delineation of valvular and congenital abnormalities (Lang et al., 2006). Whereas CT and MRI are capable of producing 3D images of cardiac structure by combining 2D slices of images, 3D echocardiography can acquire 3D images directly. The 3D echocardiography transducer transmits a 3D beam and receives ultrasound waves in a 3D pattern (Mansi, 2020).
3. Examples of specific impairments that can be more accurately assessed by echocardiography include pericardial effusion, ventricular hypertrophy, ventricular dilation, ventricular wall motion abnormalities, thrombi, mitral stenosis, aortic stenosis, mitral valve prolapse, congenital heart disease, and traumatic heart disease (Mansi, 2020). In addition, by using hemodynamic imaging through Doppler techniques valvular stenosis, valvular regurgitation, and diastolic and systolic dysfunctions of the heart can be detected (Mansi, 2020).
4. Research on the usefulness of 3D echocardiography in clinical practice began in the early 1990s (Lang et al., 2006).
5. Several disparities have been found in echocardiography use across patient groups, with significant age, racial, and sex disparities.

For example, in 2015 researchers reported that among Medicare beneficiaries whites were more likely than other races to receive echocardiography, although this was not found within the Veterans Administration system (Rajaei et al., 2015). Additionally, a 2021 study found that women, older adults, and non-white people were less likely to have an echocardiogram (Hyland et al., 2022).

6. Advances in echocardiography described here offer substantial improvements over single-dimension M mode echocardiography, which is no longer used in isolation but can be integrated into a comprehensive evaluation that includes 2D echocardiography and Doppler imaging at a minimum. Suboptimal image quality still occurs in a substantial portion of patients undergoing 2D echocardiography (Wang and Hung, 2017), which can impede a diagnosis or lead to additional testing. Suboptimal echocardiographic imaging windows are more frequent in patients with obesity or lung disease.
7. Echocardiography provides quantification of the cardiac chambers, left and right atria, and ventricles. It also measures the volume of blood blow as well as the ejection fraction, giving an indication of heart health and function. There are differences in baseline volumes between men and women (Kou et al., 2014). A “normal” ejection fraction is estimated to be between 50 and 70 percent; a measurement below 40 percent may be evidence of heart failure or cardiomyopathy (AHA, 2023).
8. Cardiologists interpret most echocardiography studies, with internists being the next most common interpreters of these studies. The equipment required for echocardiography includes an echocardiography machine, a suitable transducer, and, for intravenous contrast examinations, contrast material. Proper adjustment of the settings on the echocardiography machine is crucial.
9. One paper suggests that the complex acquisition and lengthy data analysis have been a barrier to the widespread use of 3D echocardiography in clinical practice (Wang and Hung, 2017).
10. Some limitations of echocardiography as a detection method for cardiac structure and functional evaluation are related to the complexity of the measurement and analysis of the test values, the potential for operator subjectivity, and the wide observation ranges even under standard conditions (Zhou et al., 2021). These have led to interest in applying artificial intelligence approaches to this technique, but these techniques are still under development and not widely used.

Cardiac SPECT

As discussed in the nuclear medicine overview in Chapter 3, SPECT and PET are two molecular imaging techniques used for noninvasive myocardial perfusion imaging (MPI). MPI and stress testing examine heart blood flow during rest and exertion to assess the heart’s structure and function in patients with known or suspected coronary artery disease.

The responses to the items in the statement of task for cardiac SPECT are below.

1. The accepted uses for cardiac SPECT MPI are in the diagnosis and management of patients with known or suspected coronary artery disease.
2. Advances in this area include the development of high-resolution cadmium-zinc-telluride (CZT) detectors and stress-first imaging protocols with reduced radiation doses for the evaluation of suspected myocardial ischemia. CZT radiation detectors represent a new technology that provides a higher speed and resolution compared with the conventional Anger camera (Niimi et al., 2017). In 2018 the American Society of Nuclear Cardiology published a statement on innovations and best practices of contemporary cardiac SPECT imaging (Abbott et al., 2018). Among the practice recommendations is the use of a stress-first strategy: if the results of the stress testing show normal myocardial perfusion and cardiac function, the rest-imaging protocol can be omitted, thus reducing a patient’s radiation exposure by eliminating another injection of the radiotracer (Aquino et al., 2020). In addition, another example of a major advancement involving the use of cardiac SPECT over the last 5 years is a new application of a bone-avid SPECT tracer, technetium-99m pyrophosphate (Tc-99m-PYP) in the noninvasive evaluation of amyloid transthyretin cardiac amyloidosis (ATTR-CA). Cardiac amyloidosis is a disorder caused by deposits of an abnormal protein (amyloid) in the heart tissue, which may severely impair cardiac function.
3. Impairments more accurately assessed by the technique include myocardial ischemia and ATTR-CA.
4. Nuclear cardiology techniques evolved in 1970-1980s with significant advances in the last 30 years, including the more recent advances described in this section over the last 10 years.
5. Disparities in access to cardiac SPECT follow the same patterns as the overall disparities common to the health care system, which are described in Chapter 2. In addition, emerging evidence from sex-specific research in cardiovascular disease suggests that ischemic

heart disease may manifest differently in women and men (Taqueti, 2018).

6. Earlier techniques for diagnosing myocardial ischemia from suspected coronary artery disease were limited by their lower diagnostic quality and higher radiation exposure from thallium-201 perfusion scans or by invasive catheter-based approaches. With respect to the evaluation of ATTR-CA, prior to the use of the Tc-99m-PYP protocol with SPECT the disease could only be diagnosed by biopsy, which is invasive and less accurate (Poterucha et al., 2022).
7. Outcomes: Cardiac SPECT for MPI has high diagnostic and prognostic accuracy for women and men (Taqueti, 2022a) and has reduced the need for invasive diagnostic coronary angiography. Additionally, SPECT used with the Tc-99m-PYP protocol has not only improved the diagnostic accuracy of ATTR-CA, but has also reduced the need for cardiac biopsy (Chacko, 2005). Inducible perfusion defects represent stress-induced myocardial ischemia and can be characterized in terms of size, severity, and associated coronary distribution. Fixed perfusion defects (i.e., those present at both rest and stress) are consistent with areas of myocardial scar, which may become visible following a myocardial infarction.
8. To perform cardiac SPECT for MPI, perfusion radiotracers (commonly Tc99m- sestamibi or -tetrafosmin) are administered intravenously at rest and following exercise or pharmacologic stress conditions, and the resulting myocardial perfusion images are compared. The pharmacologic stress agents for SPECT include three vasodilator agents currently approved by the Food and Drug Administration (FDA): dipyridamole, adenosine, and regadenoson (Lak). The vasodilators agents increase blood flow through the coronary arteries, but only modestly increase heart rate in most patients. The agents create differences in blood flow between coronary arteries that have high-grade blockages and normal arteries, which results in perfusion defects that can be detected using radionuclide imaging (IOM, 2010). Nuclear cardiac imaging is typically performed by licensed technologists under the supervision of cardiologists and/or radiologists, who also interpret the clinical images and report findings.
9. Although conventional SPECT for MPI is widely used throughout the United States, the high cost of replacing older conventional cameras with newer, more sophisticated medical technology may be an impediment to greater use of SPECT as described.
10. One limitation to the efficacy of cardiac SPECT scans is the presence of artifacts, commonly from soft tissue attenuation, which can be misidentified as perfusion defects (Fornell, 2008). Adding CT

imaging to SPECT may help reduce the rate of false positive results, but the additional cost may not be reimbursed through CMS.

Cardiac PET

As with cardiac SPECT above, positron emission tomography (PET) is a nuclear imaging technique that has over the last two decades contributed significantly to an understanding of cardiac and coronary pathophysiology. Below are the responses to the items in the statement of task for cardiac PET.

1. Cardiac PET is commonly used to assess myocardial perfusion, residual myocardial viability after large myocardial infarction, and the presence of active cardiac inflammation.
2. Cardiac PET for myocardial perfusion imaging offers distinct advantages as compared with other noninvasive techniques for the evaluation of known or suspected coronary artery disease, namely: (1) improved diagnostic accuracy, including in the presence of breast or adipose tissue and small left ventricular cavity size; (2) decreased radiation exposure through the use of short-lived radiopharmaceuticals (82-rubidium and 13N-ammonia); and (3) the ability to quantify myocardial blood flow and coronary flow reserve to diagnose myocardial ischemia and coronary microvascular dysfunction even in the absence of obstructive coronary artery disease (Gulati et al., 2021; Taqueti and Di Carli, 2016; Taqueti et al., 2017). PET is the gold standard for the noninvasive evaluation of coronary flow reserve and coronary microvascular dysfunction. Largely as a result of advances in cardiac PET imaging, coronary microvascular dysfunction is now increasingly recognized as an important cardiovascular condition that is associated with serious adverse cardiovascular outcomes, including cardiac death (Taqueti and Di Carli, 2018). The advantages of cardiac PET are especially useful in the evaluation of diverse patient populations with a high prevalence of women and obese individuals.

   Additionally, cardiac PET with the use of F-18-fluorodeoxyglycose (FDG), a type of metabolic radiotracer, is able to identify metabolic activity in the myocardium and can be used to assess myocardial viability after a large myocardial infarction (Ahmed and Devulapally, 2022). In selected patients with an adequate pretest dietary preparation (involving high-fat, low-carbohydrate meals and a period of fasting), FDG-PET can also provide improved diagnostic accuracy in assessing suspected cardiac sarcoidosis, an autoimmune disorder that results in myocardial inflammation and may lead to dilated cardiomyopathy and heart failure (Bokhari et al., 2017).

3. The specific impairments more accurately assessed by the perfusion and metabolic images taken by PET scan include myocardial ischemia, coronary microvascular dysfunction, reduced coronary flow reserve, and cardiac sarcoidosis.
4. Advances in cardiac PET have occurred over the past two decades.
5. Disparities in access to cardiac PET follow the same patterns as the overall disparities common to the health care system, which are described in Chapter 2. In addition, emerging evidence from sex-specific research in cardiovascular disease suggests that ischemic heart disease may manifest differently in women and men (Taqueti, 2018).
6. Specific drawbacks or limitations of the previously used techniques include insufficient diagnostic accuracy, particularly in the presence of breast or adipose tissue and small left ventricular cavity size; concerning levels of radiation exposure; and an inability to quantify myocardial blood flow and coronary flow reserve.
7. Cardiac PET can identify reduced myocardial blood flow and coronary flow reserve, which can indicate myocardial ischemia or coronary microvascular dysfunction. With the use of FDG, cardiac PET can identify reduced metabolic activity in the myocardium, which can indicate reduced myocardial viability after a large myocardial infarction.
8. In cardiac PET for MPI, the pharmacologic stress agents administered intravenously are the same as those identified for cardiac SPECT above. Nuclear cardiac imaging is typically performed by licensed technologists under the supervision of cardiologists and/or radiologists, who also interpret the clinical images and report findings.
9. The high cost and limited availability of highly sophisticated medical technology and PET perfusion radiotracers may be impediments to greater use of PET in the applications described. However, PET is considered cost-effective due to its high accuracy, which can lead to early diagnosis and treatment of disease (Ahmed).
10. PET provides superior diagnostic accuracy and is almost always performed in conjunction with CT for attenuation correction. CT can provide complementary diagnostic and prognostic information, such as the assessment of coronary artery calcification in selected patients during the time of cardiac PET testing. Comprehensive knowledge of these imaging techniques among physicians is essential for the selection of an appropriate diagnostic test.

Cardiac MRI

Cardiac magnetic resonance (CMR) imaging is an imaging adjunct to echocardiography in the evaluation of advanced cardiac disease, as it provides information that is important in both diagnosing and stratifying risk in patients with cardiac disease (DiGeorge et al., 2020). Late-gadolinium-enhancement (LGE) CMR is an effective and reproducible method for assessing myocardial fibrosis and has demonstrated prognostic use in patients with cardiomyopathy. LGE is a technique used for cardiac tissue characterization and can assess for the presence of myocardial scar (Nojiri et al., 2011).

The responses to the items in the statement of task for cardiac MRI are below:

1. CMR provides superior spatial resolution for the comprehensive assessment of cardiovascular structure and function, including LGE evaluation for the assessment of myocardial viability and diagnosis of cardiomyopathies. CMR is the imaging method of choice for cardiomyopathies, for shunts, and for use in patients with congenital heart disease (DiGeorge et al., 2020).
2. As an advance, CMR provides anatomic and functional assessment that is radiation free as well as flow measurements and a degree of tissue characterization that cannot be performed with cardiac CT angiography or echocardiography, which are also discussed in this chapter (DiGeorge et al., 2020). MRI provides high soft-tissue contrast for myocardial and vascular wall characterization for scarring, fibrosis, and edema (Amsallem et al., 2016; DiGeorge et al., 2020). CMR is also useful in the quantification of valve regurgitation. It makes routine functional assessment feasible and can be performed without IV contrast medium (DiGeorge et al., 2020).
3. In terms of specific impairments that are more accurately assessed, CMR is the gold standard for assessing left ventricular function, volumes, mass, and ejection fraction (Amsallem et al., 2016). It is useful in the assessment of multiple aspects of the inflammatory process, including edema, molecular imaging, necrosis, and fibrosis (Amsallem et al., 2016). In addition, CMR plays a central role in the diagnosis and management of pulmonary hypertension (PH). While Doppler echocardiography is essential in the evaluation of PH, it is limited by its 2D planar capabilities. CMR is capable of determining the etiology and pathophysiology of PH using 4D flow assessment. CMR can yield accurate measures of right ventricular size and function, stroke volume, myocardial mass, and ejection fraction (Freed et al., 2016).

4. CMR has been used clinically since the 1980s, but the field continues to see additional new and emerging techniques.
5. Regarding access, one study among patients who were referred for CMR found that 86 percent of those with commercial insurance completed the exam, compared with just 3 percent of those with Medicaid or Medicare coverage (Cavallo et al., 2017).
6. Whereas echocardiography represents the first-line diagnostic test for the assessment of cardiac structure and function due to its widespread availability and low cost, CMR is commonly used as an imaging adjunct to echocardiography in the evaluation of advanced cardiac disease because of its increased accuracy and versatility. It can recognize milder hypertrophy (Valente et al., 2013). Echo-cardiograms are also typically operator-dependent with sometimes limited reproducibility and accuracy in certain patient populations, including those who are obese or have chronic pulmonary disease (Marwick et al., 2013).
7. Regarding the range of outcomes, there are five CMR sequences of clinical significance: spin-echo imaging, T1-weighted contrast-enhanced imaging, balanced steady-state free precession (SSFP), MR tagging, and flow velocity encoding (phase contrast) (Aldweibe et al., 2018). Spin echo imaging uses blood as a contrast. T1-weighted contrast-enhanced imaging uses intravenous administration of a paramagnetic contrast agent, gadolinium. SSFP provides high spatial and temporal resolution and is a workhorse imaging sequence. MR radio-frequency tissue-tagging techniques are useful in detecting fibrotic adhesion of pericardial layers and myocardial involvement in constrictive pericarditis. Phase velocity mapping is a technique that non-invasively measures and depicts blood flow while accurately quantifying blood flow velocities (Aldweibe et al., 2018).
8. The requirements for administering cardiac MRI in terms of equipment and specialized expertise are similar to those described under imaging techniques in Chapter 3. Cardiac MRI is typically performed by licensed technologists under the supervision of cardiologists and/or radiologists, who also interpret the clinical images and report findings. Cardiac MRIs have not been widely adopted because they can be time consuming and require specialized technical expertise (Freed et al., 2016) and also have high cost.
9. In terms of limitations, cardiac MRI is relatively contraindicated for patients with pacemakers or implanted medical devices and defibrillators (Amsallem et al., 2016). In pediatric patients, sedation may be required. (DiGeorge et al., 2020). Newer acquisition techniques and abbreviated imaging protocols may help to mitigate

need for sedation in pediatric patients (Ahmad et al., 2018). Overall, its cost is higher than the cost of echocardiography, and the total cost is dependent on the type of MRI used and on whether or not contrast is used (Freed et al., 2016).

Coronary Computed Tomography Angiography

Coronary computed tomography angiography (CCTA) is a noninvasive imaging technique that produces 3D images of the arteries to detect abnormalities in how blood flows through the heart. CCTA is used in the assessment of coronary artery disease (CAD). During the procedure an iodinated contrast dye is injected through a peripheral vein and images of the coronary arteries are taken using a CT system (IOM, 2010).

The responses to the items in the statement of task for CCTA are as follows:

1. CCTA is a generally accepted means of testing for the presence and severity of coronary artery stenosis in patients with suspected acute or chronic coronary disorders. CCTA is most useful in patients with low to intermediate risk of coronary heart disease. It is also extremely useful in the evaluation of anomalous coronary arteries (Ramjattan et al., 2022).
2. Noninvasive CCTA has dramatically increased test sensitivity for the diagnosis of CAD and also enabled early characterization of plaque morphology compared with previous techniques (Taqueti and Shaw, 2021). Current-generation multi-detector row-computed tomography scanners allow rapid coverage of anatomic structures, including diagnostic imaging resolutions that are clear enough for the small cardiovascular structures of pediatric patients (DiGeorge et al., 2020). In pediatric patients, one of the main advantages of CCTA, especially compared with cardiac MRI, is that it is fast and requires little or no sedation (DiGeorge et al., 2020).
3. As for specific impairments accurately diagnosed, a major strength of CCTA lies in its high negative predictive value for exclusion of obstructive coronary artery disease. In patients with extensive calcium deposits or prior coronary artery stents, accurate detection of stenosis is difficult (Budoff et al., 2006).
4. CCTA generally became available in the 2000s (IOM, 2010).
5. CCTA is not as widely available as echocardiography (Freed et al., 2016) and may not be accessible to all patients who would benefit from the test.
6. Prior to the emergence of CCTA, invasive coronary angiography was used to assess and diagnose CAD. In the latter procedure, a catheter

is inserted into an artery in the groin or wrist and advanced to the coronary arteries using X-ray images as a guide. Relative to CCTA, the drawbacks to invasive coronary angiography include the more inherent risks of complications because of its invasive nature as well as high cost and relatively high radiation exposure (Knaapen, 2019).

7. The increasing use of CCTA has underscored the importance of nonobstructive CAD in cardiovascular prognosis. Observational data demonstrate that the presence of any atherosclerotic plaque, obstructive or not, indicates increased risk for future adverse events and that the higher the overall plaque burden that is present, the higher the risk (Taqueti, 2022b). The improved ability to detect subclinical atherosclerosis increases the chance for earlier initiation of preventive medical therapy and fewer cardiac events (Alalawi and Budoff, 2022)
8. CCTA is typically performed by licensed technologists under the supervision of cardiologists and/or radiologists, who also interpret the clinical images and report findings.
9. Widespread use of CCTA may be limited by difficulty in reimbursement as many insurers tried to curb overuse of medical imaging (Dowe, 2010), but it has experienced rapid growth over the past 5 years.
10. CCTA can overestimate the severity of coronary stenosis as compared with invasive coronary angiography and may increase downstream testing in patients found to have intermediate or severe anatomical stenoses. The frame rate of CT is lower than that of 2D echocardiography; high frame rates enable the viewing of rapidly moving structures (such as heart valves) without motion artifacts as well as the performance of velocity and deformation analysis (i.e., tissue Doppler) (Freed et al., 2016). Unlike cardiac MRI, CCTA has a limited ability to characterize tissue and exposes patients to ionizing radiation. However, modern techniques using newer multislice scanners, iterative reconstruction, dual energy acquisition, and prospective cardiac gating techniques have decreased radiation doses while maintaining adequate diagnostic information (Freed et al., 2016; DiGeorge et al., 2020).

Intravascular Imaging

Intravascular ultrasound (IVUS) and coronary optical coherence tomography (OCT) are two types of invasive intravascular imaging tests used in interventional cardiology, which uses specialized catheter-based techniques for the comprehensive assessment of coronary artery disease. IVUS uses high-frequency sound waves to provide images from inside the

blood vessels (RadiologyInfo, 2022), while OCT uses near-infrared light to provide high-definition images of an artery, with the high precision making it possible to access lesion characteristics and plaque morphology.

The responses to the items in the statement of task for IVUS are as follows:

1. Both IVUS and OCT may be used as adjunctive techniques in the diagnosis and treatment of acute and chronic coronary artery conditions, especially those involving acute coronary syndromes such as myocardial infarction and for lesions requiring percutaneous coronary intervention (PCI) (Nagaraja et al., 2020). Both IVUS and OCT may be useful in distinguishing the between mechanisms of acute coronary syndromes, including plaque rupture versus erosion, or spontaneous coronary artery dissection. IVUS may be used to help characterize lesion morphology, quantify plaque burden, guide stent sizing, assess stent expansion, and identify procedural complications (Parviz et al., 2018; Shlofmitz et al., 2022). OCT provides automated, accurate measurements to help guide stent selection, placement, and deployment (Fujino et al., 2018).
2. IVUS is an advance in that it provides a tomographic (three-dimensional) high-resolution view and precise vessel and plaque dimensions; this is helpful, for instance, in identifying diffuse disease in arteries that appear “normal” through angiographies. For further detailed assessment of coronary arteries, OCT has demonstrated even greater spatial resolution than IVUS and more detail on the microstructure of the vessel wall (Rathod et al., 2015).
3. The specific impairments more accurately assessed by intravascular imaging are acute and chronic coronary artery conditions, including plaque rupture, spontaneous coronary artery dissection, and diffuse disease that appears “normal” in an angiography.
4. IVUS was first developed in the late 1980s (Ono et al., 2020), and in the last 25 years IVUS has become the most commonly used intravascular imaging device (Rathod et al., 2015). OCT was first developed in 1991 (Rathod et al., 2015), but it was not studied in humans until 2002 (Ono et al., 2020).
5. Disparities in access reported by one study include higher IVUS (and OCT) use in Asian/Pacific Islander populations as well as within urban teaching and western region hospitals in the United States (Desai et al., 2019).
6. Previous techniques using coronary angiography are limited by 2D images, limited spatial resolution, and an inability to fully characterize the appearance of plaque (Shah and Cohen, 2021) and details about the coronary wall (Rathod et al., 2015).

7. IVUS and OCT improve clinical outcomes in patients undergoing percutaneous coronary intervention (Maehara et al., 2017). In addition, a meta-analysis comparing clinical IVUS with OCT for percutaneous coronary intervention found no differences in outcomes (Sattar et al., 2022).
8. Intravascular imaging is performed by interventional cardiologist who are trained to perform specialized catheter-based treatments for heart disease. IVUS is performed via arterial insertion of a catheter by an interventional cardiologist. Sound waves are emitted from the probe, which receives and returns echo information that sends images to a computer (Cedars Sinai, 2022). In OCT, the clinician uses a rotating glass fiber-optic system to direct and reflect coherent infrared light within the tissue to create a detailed tissue image with extremely high resolution, and IVUS-like cross-sectional tomographic images can be obtained (Terashima et al., 2012).
9. The adoption of IVUS and OCT has been limited to date. Despite evidence of clinical benefit, IVUS is often underused in much of the world, with some estimates suggesting that it accounted for as little as just 10 percent of PCI procedures as recently as 2021 (Shah and Cohen, 2021). This could be due to its high cost as well as that it requires physicians with specialized knowledge of interventional imaging use and interpretation in cardiovascular disease. OCT has a robust evidence base in research and is being increasingly used in clinical practice. When indicated, both techniques can be used in a complementary fashion to provide a more comprehensive assessment of coronary anatomy (Rathod et al., 2015).
10. Both techniques have various clinical advantages and limitations (Rathod et al., 2015); patient factors as well as the expertise of the physician inform the choice of test to use.

INTRAVASCULAR HEMODYNAMIC ASSESSMENT

Intravascular hemodynamic (functional) assessment of the coronary circulation has re-emerged as an important adjunct to anatomic coronary imaging. Fractional flow reserve (FFR) is a diagnostic test used to assess the physiological significance of an epicardial coronary artery stenosis. FFR is the reference-standard method to define flow-limiting lesions in the epicardial coronary compartment (Corcoran et al., 2017). Instantaneous wave free ratio is a resting pressure derived index and is obtained without the need for vasodilator administration by using a ratio of distal coronary pressure and aortic pressure measured at the wave-free period during a resting state (Lee et al., 2018). Invasive coronary flow reserve (CFR) expresses the

capacity of the coronary circulation to respond to a physiological increase in oxygen demand with a corresponding increase in blood flow (Díez-Delhoyo et al., 2015). Together, the fundamental parameters of FFR and CFR are complementary and jointly could contribute to better PCI guidance and understanding of macro- and micro-circulatory function (Garcia et al., 2019).

The responses to the items in the statement of task for intravascular hemodynamic assessments are as follows:

1. FFR is used to assess the severity of stenosis in coronary arteries and is usually done when a provider is deciding whether to perform angioplasty and place a stent in one of the arteries (Cleveland Clinic, 2022). It is typically done to determine if a visually intermediate stenosis (between 30 and 70 percent narrowing of the arterial lumen) is flow-limiting and could be contributing to anginal symptoms.
2. FFR-guided PCI has been demonstrated as superior to angiography-guided PCI alone (Mangiacapra et al., 2018).
3. Coronary angiography is often insufficient in guiding percutaneous coronary intervention, so FFR has been increasingly used to estimate whether a coronary lesion will lead to myocardial ischemia (Garcia et al., 2019). Similarly, CFR denotes the myocardial reserve vasodilator capacity. FFR is seen as the gold standard for the detection of ischemia-inducing coronary stenoses (Mangiacapra et al., 2018).
4. The concept of FFR was developed and introduced in the early 1990s. In 1996 a clinical trial found the cutoff value of FFR to determine the presence of ischemia (Kim and Koo, 2012).
5. A national study in 2018 found a higher increase in FFR use for women than for men between 2010 and 2014 (Desai et al., 2018). Looking at racial differences, Asians were the most likely to have FFR-guided PCI, followed by African Americans, Native Americans, Whites, and Hispanics.
6. The FFR technique for PCI has been found to reduce adverse events by deferring unnecessary stenting procedures when compared with PCI guided by angiographic evaluation alone (Bruno et al., 2020). Overall, patients who underwent FFR also had shorter hospitalization time, more off-pump procedures, and a lower number of surgical anastomoses.
7. FFR results that are equal to or greater than 0.8 suggest no significant flow limitation across an individual coronary stenosis (Cleveland Clinic, 2022). Results between 0.75 and 0.8 represent a “grey zone” that may be managed with medication or an angioplasty and stent. FFR values below 0.75 indicate at least a 25 percent decrease in pressure across a stenosis, which may benefit from

treatment via angioplasty and a stent. For CFR, most animals and healthy humans will produce a number over 3 (Díez-Delhoyo et al., 2015). In humans with chest pain, a clinically accepted cutoff for CFR is 2.0.

8. An invasive cardiologist performs FFR evaluation at the time of invasive coronary angiography (Cleveland Clinic, 2022).
9. FFR is an invasive procedure and requires expensive devices, highly trained providers to deliver the procedure, and pharmacologic testing (Kim and Koo, 2012).
10. While FFR has gained global recognition, without the additional measurement of CFR it may be difficult to accurately predict the outcome post-PCI (Garcia et al., 2019), particularly in the setting of coronary microvascular dysfunction. Quantification of CFR can also be performed noninvasively using cardiac PET/CT scans (described previously) and has been found to aid in the risk stratification of patients with diffuse atherosclerosis and coronary microvascular dysfunction (Ruddy et al., 2022).

ELECTROPHYSIOLOGIC TESTING

An electrophysiology (EP) study is a test used to diagnose and treat patients with certain arrhythmias. EP is an invasive procedure that uses an electrode catheter to assess an electric signal to the heart, with the resulting electrical activity of the heart recorded and analyzed (Negru and Alzahrani, 2022). It can be used to see where an arrhythmia is coming from, how well certain medicines are working, and what type of intervention is needed. There has been a notable increase in this type of testing over the past 25 years.

The responses to the items in the statement of task for EP testing are as follows:

1. Following noninvasive diagnostic assessment of cardiac arrhythmias, physicians may refer some patients for invasive testing. An EP study is indicated in patients with atrial and ventricular arrhythmias. Other indications for it use include unexplained syncope, progressive cardiac conduction disease, dilated cardiomyopathy, muscular dystrophies (Duchenne, Becker), post-antiarrhythmic surgery, sarcoidosis, congenital heart disease, and conduction disorders after transcatheter aortic valve replacement (Negru and Alzahrani, 2022).
2. Advanced mapping systems, including multielectrode mapping and 3D heart mapping, are used to identify the type and location of the arrhythmia to help determine the appropriate therapy (e.g., catheter ablation, pacemaker, or implantable cardioverter defibrillator) to

correct irregular heartbeats. There is also evidence that EP studies may be useful for risk stratification of ischemic patients with reduced LV function and that they can identify patients at high risk for future arrhythmias (Katritsis et al., 2018).

3. The impairments that the electrophysiologic testing accurately assess include certain arrhythmias, progressive cardiac conduction disease, dilated cardiomyopathy, muscular dystrophies (Duchenne, Becker), sarcoidosis, congenital heart disease, and conduction disorders after transcatheter aortic valve replacement.
4. Invasive clinical electrophysiology started in 1967 and continues to be an evolving field (Kuijpers, 2021).
5. Evidence for significant racial and ethnic disparities in cardiac electrophysiology exists. Black individuals with cardiovascular disease generally have an increased risk of adverse arrhythmia-related outcomes compared with white individuals (Thomas et al., 2022).
6. Previously used techniques did not have specific drawbacks but rather are simply not as effective as EP studies for certain disorders and ailments.
7. EP study involves the placement of multipolar electrode catheters in the heart, typically in the right side, which generates intracardiac electrograms (electrical waves recorded by surface electrodes within the heart), followed by programmed electrical stimulation to trigger a focus arrhythmia (Majeed and Stattar, 2022).
8. The test is performed in an electrophysiology laboratory by cardiologists with special training in heart rhythm disorders, a specialty called electrophysiology. Small tubes or sheaths are placed into the groin, arm, or neck into the targeted artery or vein. Within the sheath, specialized catheters are advanced toward the heart. Small electric pulses are sent through the catheters to make the heart beat at different speeds. The electrical signals produced from the heart are picked up by the special catheters and recorded through cardiac mapping so that the doctor can see where arrhythmias are stemming from (AHA, 2022). The test lasts 1 to 4 hours.
9. The test is used for very specific indications (Majeed and Stattar, 2022), which may limit its availability and widespread use.
10. EP studies have varying sensitivity and specificity and may be used with other confirmatory tests (Majeed and Stattar, 2022).

EMERGING DIAGNOSTIC TECHNIQUES

The advance described above have substantially improved diagnostic accuracy for numerous cardiovascular conditions. They are also facilitating the use of novel and effective therapeutic approaches to reduce the burden

of cardiovascular disease. In the near future the continued application, combination, and refinement of these techniques—for example, in the evaluation of nonobstructive coronary artery disease, coronary microvascular dysfunction, and heart failure with preserved ejection fraction—is poised to broaden our understanding of cardiovascular disease pathophysiology across gender and racially diverse populations. In the far future, continued advances in multimodality imaging technology, genetics and molecular biology, and artificial intelligence may further improve the precision of diagnoses involving cardiovascular conditions. Ultimately, however, despite these technological advances the assessment of the functional status of an individual, including the possibility of disability, will not be dependent on any single test of the cardiovascular system but will require a holistic approach integrated across organ systems and the individual’s environment.

REFERENCES

This page intentionally left blank.