Ten things to know about ten imaging studies: A preventive cardiology perspective (“ASPC top ten imaging”)





Abstract


Knowing the patient’s current cardiovascular disease (CVD) status, as well as the patient’s current and future CVD risk, helps the clinician make more informed patient-centered management recommendations towards the goal of preventing future CVD events. Imaging tests that can assist the clinician with the diagnosis and prognosis of CVD include imaging studies of the heart and vascular system, as well as imaging studies of other body organs applicable to CVD risk. The American Society for Preventive Cardiology (ASPC) has published “Ten Things to Know About Ten Cardiovascular Disease Risk Factors.” Similarly, this “ASPC Top Ten Imaging” summarizes ten things to know about ten imaging studies related to assessing CVD and CVD risk, listed in tabular form. The ten imaging studies herein include: (1) coronary artery calcium imaging (CAC), (2) coronary computed tomography angiography (CCTA), (3) cardiac ultrasound (echocardiography), (4) nuclear myocardial perfusion imaging (MPI), (5) cardiac magnetic resonance (CMR), (6) cardiac catheterization [with or without intravascular ultrasound (IVUS) or coronary optical coherence tomography (OCT)], (7) dual x-ray absorptiometry (DXA) body composition, (8) hepatic imaging [ultrasound of liver, vibration-controlled transient elastography (VCTE), CT, MRI proton density fat fraction (PDFF), magnetic resonance spectroscopy (MRS)], (9) peripheral artery / endothelial function imaging (e.g., carotid ultrasound, peripheral doppler imaging, ultrasound flow-mediated dilation, other tests of endothelial function and peripheral vascular imaging) and (10) images of other body organs applicable to preventive cardiology (brain, kidney, ovary). Many cardiologists perform cardiovascular-related imaging. Many non-cardiologists perform applicable non-cardiovascular imaging. Cardiologists and non-cardiologists alike may benefit from a working knowledge of imaging studies applicable to the diagnosis and prognosis of CVD and CVD risk – both important in preventive cardiology.


What is already known about this subject?




  • The American Society for Preventive Cardiology (ASPC) has published “Ten Things to Know About Ten Cardiovascular Disease (CVD) Risk Factors,” [ , ] which summarizes major CVD risk factors, accompanied by sentinel reviews or guidelines relative to ten important CVD risk factors.



  • Assessing existing CVD and CVD risk through imaging is commonly used to stratify CVD risk and influence CVD prevention management. Diagnostic and prognostic imaging studies of the heart and other body organs help clinicians with management decisions to prevent future CVD events.



What are the new findings in this manuscript?




  • The “ASPC Top Ten Imaging” summarizes ten things to know about ten important CVD-related imaging studies (listed in a tabular format).



  • Non-cardiologists (e.g., primary care physicians, nurse practitioners, physician assistants, gynecologists, endocrinologists, obesity medicine specialists, lipidologists, diabetologists etc.) may benefit from an overview of CVD-related imaging studies commonly performed by cardiologists. Cardiologists may benefit from an overview of imaging studies beyond the heart, but applicable to global preventive cardiology – which are imaging studies often performed by non-cardiologists.



  • In addition to the “Top Ten” things to know about CVD imaging studies, citations are listed in the applicable tables to provide the reader more in-depth resources (e.g., illustrative guidelines and other references) pertaining to each imaging category.




Introduction


The intent of the “American Society for Preventive Cardiology (ASPC) Top Ten Imaging” is to help primary care clinicians and cardiology specialists keep up with the ever-increasing pace of diagnostic and prognostic imaging studies applicable to preventive cardiology. Imaging studies focused on the heart are often performed by cardiologists and/or radiologists and help with diagnosis and prognosis. Other imaging studies may also help in CVD risk stratification, and include imaging studies of the peripheral vasculature, body fat, liver, brain, kidney, and ovary. The “ASPC Top Ten Imaging” summarizes ten things to know about ten CVD-related imaging studies, listed in tabular formats. These ten imaging studies include: (1) coronary artery calcium (CAC) imaging and scoring, (2) coronary computed tomography angiography (CCTA), (3) cardiac ultrasound (echocardiography), (4) nuclear myocardial perfusion imaging (MPI), (5) cardiac magnetic resonance (CMR), (6) cardiac catheterization [with or without intravascular ultrasound (IVUS) or coronary optical coherence tomography (OCT)], (7) dual x-ray absorptiometry (DXA) body composition, (8) hepatic imaging [ultrasound of liver, vibration-controlled transient elastography (VCTE), CT, MRI proton density fat fraction (PDFF), magnetic resonance spectroscopy (MRS)], (9) peripheral artery / endothelial function imaging (e.g., carotid ultrasound, peripheral doppler imaging, ultrasound flow-mediated dilation, other tests of endothelial function and peripheral vascular imaging) and (10) images of other body organs applicable to preventive cardiology (brain, kidney, ovary). ( Fig. 1 )




Fig. 1


Cardiac and other organ imaging relevant to preventive cardiology.


The intent is not to create a comprehensive discussion of all imaging studies applicable to CVD assessment. Nor is this document intended to be a comprehensive discussion of each imaging study. Rather, the intent is to focus on common imaging studies having implications for preventive cardiology. For a more in-depth discussion of these CVD imaging studies, this “ASPC Top Ten Imaging” provides updated guidelines and other selected references in the applicable tables.



Purpose of cardiac imaging





  • Cardiac imaging helps assess the degree of CVD, which is important in stratifying current CVD risk and determining management strategies toward preventing future CVD events. CVD risk factor management is often more aggressive and often prioritized to patients most likely to benefit, which often includes those with diagnosed CVD or otherwise at increased CVD risk.



  • Cardiac imaging may help further stratify patients at intermediate CVD risk, as otherwise determined by coronary heart disease (CHD) risk scores [ , ].



  • Cardiac imaging results may help decide who to treat, what to treat, and when to treat, as well as how aggressively to treat atherosclerotic lesions (e.g., revascularization) and/or CVD risk factors (e.g., dyslipidemia, hypertension, hyperglycemia) – all for the purpose of helping prevent future CVD events.



  • Extracardiac images of other body organs such as body composition (android and visceral fat) liver (hepatic fat), brain (cerebral vascular disease), kidney (vascular abnormalities), ovary (polycystic ovarian syndrome) and peripheral vasculature (endothelial dysfunction) can also provide insight regarding other CVD risk factors and need for potential treatment of these CVD risk factors.




Appropriate use [ , ]





  • The choice of cardiac imaging studies should be based upon established “Appropriate Use” criteria, [ , ] and individual patient presentation.



  • Appropriate imaging studies are those where the clinical benefits and value in an individual patient exceed the risk ( Reference Chart 1 ) and cost, through providing clinically meaningful information about CVD and CVD risk, beyond clinical judgment alone.



    Reference Chart 1

    Invasiveness and patient radiation exposure regarding various imaging procedures. Radiation exposure for some procedures may be less than listed via use of ultra-low dose radiation protocols involving stress-only imaging. Some common diagnostic procedures are listed at the bottom of the table for reference/illustrative purposes. [ , ].






















































































    Procedure Invasiveness Patient radiation exposure *
    Contemporary coronary artery calcium CT (CAC) Noninvasive, no contrast ~ 1 mSv [ , , ]
    Contemporary coronary CT angiography (CCTA) Requires injection of contrast material (i.e., iodine) 1.0 – 5 mSv ⁎⁎ [ , , , ]
    Cardiac ultrasound / echocardiogram Noninvasive. If unable to physically exercise, then dobutamine may be injected to mimic exercise. May include contrast (i.e., agitated saline or commercial ultrasound contrast agents). 0.00 mSv (no radiation)
    Nuclear myocardial perfusion imaging (MPI)
    • SPECT perfusion imaging Intravenous administration of nuclear contrast with imaging at rest, followed by walking on a treadmill with another injection afterwards of nuclear contrast. If unable to physically exercise, then an A2A adenosine receptor agonists (i.e., regadenoson coronary vasodilator for cardiolite stress test) can be injected to mimic exercise 10 -15 mSv with technetium-99 25 – 30 mSv with thallium-201 (seldom used in current clinical practice)
    • PET perfusion imaging Requires injection of radiotracer (e.g., 50 mCi of 82 rubidium or 20 mCi of 13 ammonia for rest and stress perfusion). If unable to physically exercise, then pharmacologic stress testing can be achieved via the vasodilators regadenoson, adenosine, dipyridamole, or inotropic/chronotropic agents such as dobutamine with or without atropine 4 mSv with 82 rubidium or 13 ammonia (older reports suggest higher radiation exposure) [ , ]
    • MUGA ventricular imaging (seldom use in current clinical practice) Requires injection of radiotracer 5 – 10 mSv with technetium-99m-pertechnetate
    CMR Most cardiac protocols involve injection of contrast (i.e., gadolinium) 0.00 mSv (no radiation)
    Cardiac catheterization Cardiac catheterization involves insertion of a catheter tube into the artery or vein in the groin, neck, or arm, which is then threaded into the heart. 2 – 7 mSv for diagnostic cardiac catheterization 10 mSv or higher for interventional catheterization [ , ]
    DXA total body composition scan Noninvasive ≤ 0.001mSv for typical body composition (minimal radiation; technicians not required to wear garments to protect from radiation)
    Hepatic imaging• Ultrasound of liver• VCTE/fibroscan• CT• MRI-PDFF• MRS
    NoninvasiveNoninvasiveMay involve injection of contrast (e.g., iohexol)May involve injection of contrast (i.e., gadolinium)May involve injection of contrast (i.e., gadolinium)

    0.00 mSv (no radiation)0.00 mSv (no radiation)3.0 mSv0.00 mSv (no radiation)0.00 mSv (no radiation)
    Carotid ultrasound, peripheral doppler imaging, ultrasound flow-mediated dilation, and pulse amplitude tonometry Fingertip infrared light transmission photoplethysmograpy for endothelial function Noninvasive 0.00 mSv (no radiation)
    Daily background radiation 0.007 mSv
    Yearly background radiation 3.0 mSv
    Roundtrip Transatlantic Flight 0.100 mSv
    Chest X-ray 0.02 – 0.1 mSv
    Mammogram 0.40 mSv
    DXA AP spine scan 0.001 – 0.004 mSv
    Older body PET / CT scans 15 – 25.0 mSv
    Older whole body CT scans 10 – 20 mSv

    The standard measure of radiation is Sievert (Sv) or millisievert (mSv) or microsievert (uSv) units where 1 Sv = 1000 mSv = 1,000,000 uSv. Humans have natural daily radiation exposure of about 0.007 mSv from soil, rocks, radon, and outer space.


    ⁎⁎ Quality CCTA images with ~ 1 mSv radiation exposure can sometimes be obtained in younger patients without overweight/obesity, or when utilizing low-dose CCTA protocols. [ , , ] CMR = Cardiac magnetic resonance, CT = computerized tomography, DXA = Dual x-ray absorptiometry, FFR = Fractional flow reserve, IVUS = Intravascular ultrasound, MRI = Magnetic resonance imaging, MRI-PDFF = MRI proton density fat fraction, MRS = Magnetic resonance spectroscopy, MUGA = Multiple-gated acquisition scan, OCT = Optical coherence tomography, PET = Positron emission tomography, SPECT = Single-photon emission computerized tomography, VCTE = Vibration-controlled transient elastography.




  • Appropriate use of imaging studies includes procedures most likely to provide safe and definitive answers to the diagnostic questions raised, and least likely to prompt further imaging studies and invasive downstream procedures, irrespective of the initial imaging study results. In other words, in the interest of limiting the risks and costs of multiple imaging procedures, the choice of cardiac imaging procedure should focus on which procedure is likely to provide the greatest amount of actionable information applicable to the individual patient, in the safest manner possible.



  • Clinicians should be cautious and judicious in cardiac imaging studies in patients at low CVD risk, especially for imaging studies that have low specificity in patients at low CVD risk. Low specificity cardiac imaging in low CVD risk patients may often lead to false positive results. False positive findings on cardiac imaging may needlessly prompt more invasive, more costly, and potentially unnecessary additional testing and/or procedures, resulting in more health risk than benefit.



  • Selecting the most appropriate imaging test should take into consideration whether the patient is symptomatic or asymptomatic. Performing cardiac imaging studies with low selectivity in asymptomatic patients at low CVD risk has a higher risk of false positive findings than cardiac imaging studies with high selectivity in symptomatic patients at high CVD risk ( Reference Chart 2 ).



    Reference Chart 2

    Sensitivity and Specificity of Cardiac Imaging Studies [ , , ].






























































    Imaging Test Sensitivity Specificity
    Anatomically significant coronary artery disease *
    Coronary Calcium Imaging/Score 98% 40%
    Exercise electrocardiogram 58% 62%
    Stress echocardiogram (Echo) 85% 82%
    Coronary computed tomography angiography (CCTA) 96% 82%
    Single-photon emission computed tomography (SPECT) 87% 70%
    Positron emission tomography (PET) 90% 85%
    Stress cardiac magnetic resonance (CMR) 90% 80%
    Functionally significant coronary artery disease ⁎⁎
    Coronary computed tomography angiography (CCTA) 93% 53%
    CCTA with fractional flow reserve (FFR) 85% 78%
    Single-photon emission computed tomography (SPECT) 73% 83%
    Positron emission tomography (PET) 89% 85%
    Stress cardiac magnetic resonance (CMR) 89% 87%

    Anatomically significant CAD is sometimes defined as > 50% stenosis of the left main coronary artery, 70% stenosis of any major coronary vessel, or 30 – 70% stenosis with fractional flow reserve of ≤ 0.8.


    ⁎⁎ Heart function imaging involves assessing blood flow within coronary arteries. The significance of a coronary artery obstruction can be assessed by measuring (directly or virtually) the pressure differential before and after a coronary artery stenosis (fractional flow reserve). The cut-off point for functionally significant CAD is often reported as ≤ 0.8, with other flow coronary blood flow metrics being dependent on the individual imaging technique. [ , , ].




  • Procedures having the most robust evidence to support use in screening for coronary artery disease in asymptomatic individuals include family history assessment for premature CVD, CVD risk factor assessment, and CVD and CHD risk scores. [ , ] Additional diagnostic procedures having evidenced-based support in screening asymptomatic individuals include CAC scoring, with some suggestion that carotid artery ultrasound can assist with CVD risk stratification. Little evidence supports the routine clinical use of cardiac resting or stress imaging testing in asymptomatic patients. Possible exceptions (albeit with lower level evidence as noted per guidelines) include coronary CTA among selected, asymptomatic individuals at high CVD risk, or stress electrocardiogram in physically inactive patients at higher CVD risk who plan to start a rigorous physical exercise program.



  • The selection of the most appropriate imaging test should be based upon the patient presentation. A common clinical scenario that directly impacts management directed at CVD prevention is the evaluation of chest pain, which typically involves various disease endotypes: (1) angina due to obstructive coronary artery disease (CAD) with fractional flow reserve ≤0.80; (2) microvascular angina with coronary flow reserve <2.0 and/or index of microvascular resistance >25); (3) microvascular angina due to small vessel spasm (which can be assessed by intracoronary acetylcholine administration); (4) vasospastic angina due to epicardial coronary spasm (which can be assessed by intracoronary acetylcholine administration); and (5) noncoronary etiology (i.e., patients found to have normal coronary anatomy and normal function via cardiac imaging).



  • While “ischemia and no obstructive coronary artery” (INOCA) disease can be assessed by the invasive coronary reactivity tests described above, common noninvasive cardiac imaging studies applicable to coronary microvascular disease include PET, CMR, and echocardiography, with invasive imaging studies including coronary flow reserve via coronary angiography. Similarly, causes of “myocardial infarction with nonobstructive coronary arteries” (MINOCA) include cardiac microvascular disease (i.e., microvascular plaque, thrombosis), coronary vasospasm, and coronary artery dissection. Imaging studies to assess MINOCA include coronary angiography with or without intravascular ultrasound or optical coherence tomography, as well as possibly intracoronary acetylcholine if coronary spasm is suspected. [ , , ] Yet other cardiac imaging studies to help assess MINOCA include echocardiography, with PET and CMR useful to assess coronary microvascular dysfunction. [ , ]



  • Most instances of coronary artery disease involve macrovascular disease leading to obstruction and often clinically manifest by angina and myocardial infarction. Even among patients with coronary microvascular disease, most such patients also have macrovessel atherosclerosis. However, a sole focus on coronary macrovascular disease may underdiagnose cardiac disease in patients with coronary microvascular disease as often occurs in women. Therefore, selecting the most appropriate imaging study is best determined by the patient presentation, and the information reasonably derived by the imaging study performed on an individual patient.




    • Coronary anatomy can be assessed by CAC, CCTA, CMR and cardiac catheterization.



    • Cardiac diastolic dysfunction can be evaluated by echocardiogram and CMR. [ , ]



    • Myocardial perfusion can be assessed by SPECT, PET, and CMR. [ , ]



    • Cardiomyocyte injury and fibrosis can be evaluated by CMR and CTA. [ , ]



    • Microvascular dysfunction can be evaluated by PET and CMR.



    • Hybrid imaging includes:




      • PET/CT and PET/MRI: Assesses perfusion, cardiac viability, and atherosclerosis [ , ]



      • CT- Fractional Flow Reserve (FFR): Provides anatomic (i.e. luminal and plaque) and physiologic/functional imaging data to assess obstructive CAD [ , ]



      • Cardiac catheterization and FFR: Provides (invasive) anatomic and functional assessment of CAD





  • CAC added to SPECT or PET may help further identify coronary artery plaque and better stratify risk [ , ]



  • CCTA added to CAC scoring may help improve the assessment of total plaque burden and better discriminate risk of death and/or myocardial infarction among symptomatic patients with suspected coronary artery disease. [ , ]



  • Although it may have low specificity, CAC scoring is illustrative of a cardiac imaging study of high sensitivity, limited invasiveness, and low radiation exposure ( Reference Charts 1 & 2 ). CAC is often performed in asymptomatic patients to help stratify CVD risk (see Section 1 and Table 1 below). [ , ]



    Table 1

    Ten things to know about computerized tomography coronary artery calcium (CAC) measurements.









    • (1)

      For most patients, the higher the CAC score, the higher the atherosclerotic burden and the higher the risk of a subsequent CVD event.


    • (2)

      The Multi-Ethnic Study of Atherosclerosis Risk Score ( www.mesa-nhlbi.org/MESACHDRisk/MesaRiskScore/RiskScore.aspx ) assesses CHD risk based upon sex, age, race/ethnicity (e.g., Caucasian, Chinese, African American, and Hispanic), diabetes, smoking, family history of myocardial infarction, total cholesterol, high density lipoprotein cholesterol, systolic blood pressure, lipid lowering medications, hypertension medications and CAC scoring . [ , , ] The Astronaut Cardiovascular Health and Risk Modification (Astro-CHARM) Coronary Calcium Atherosclerotic Cardiovascular Risk Calculator ( astrocharm.org/ ) is an ASCVD risk calculator that incorporates multiple ASCVD risk factors, including age, sex, systolic blood pressure, hypertension treatment, total and high density lipoprotein cholesterol, smoking, diabetes mellitus, family history of myocardial infarction, high sensitivity C-reactive protein and CAC scores .


    • (3)

      Patients most likely to benefit from CAC testing include asymptomatic individuals not known to have CVD, but who are 40 years and older without diabetes mellitus, individuals in whom primary CVD prevention therapeutics are being considered (e.g., statins), and/or individuals having borderline to intermediate 10-year ASCVD risk estimate of 5 – 20% (i.e., borderline risk = 5 – 7.5% and intermediate risk = 7.5 – 20%). [ , , ]


    • (4)

      CAC scoring is generally not recommended for patients at low, < 5% 10-year ASCVD risk or patients with known CVD or patients at high, greater than 20% 10-year ASCVD risk.


    • (5)

      Generally, a CAC score of > 0 – 400 AU identifies individuals at minimal to mild to moderate CVD risk. An individual with a CAC score of 1 – 99 may have a risk of CVD death, myocardial infarction, or unstable angina of 2 % in ~ 2 years. An individual with a CAC score of 100 – 400 may have a risk of CVD death, myocardial infarction, or unstable angina of 4% in ~ 2 years. In appropriate individuals, statin therapy is strongly indicated when the CAC score is > 100 AU, or ≥ 75 th percentile.


    • (6)

      A CAC score of zero AU suggests a low risk of subsequent CVD event (i.e., acute myocardial infarction, coronary death, stroke, revascularization) over at least the next 8 years. Individuals with an initial CAC score of zero may consider a second scan 3-7 or more years later. Unless the patient has intervening onset or worsening of CVD risk factors or diminished adherence to healthful nutrition and physical activities, individuals with double-zero CAC may not need an additional scan in the near future afterwards, because their risk of a CVD is ≤ 2% within 8-years after the repeat CAC score.


    • (7)

      A CAC score of ≥ 1000 AU represent a unique very high-risk phenotype of extreme coronary atherosclerosis with mortality outcomes commensurate with high-risk secondary prevention patients. Such patients are at very high risk for a CVD event. Similarly, patients with high baseline CAC scores of ≥ 400 AU are also at high CHD/ASCVD risk* (10 – 15% ten-year ASCVD risk); repeat CAC scoring is not appropriate for patients with CAC scores ≥ 400 AU, especially if treated with statins. Patients with baseline CAC scores of 100 – 399 AU may have a > 5% 10-year ASCVD risk and be candidates for statin therapy. If statin therapy is implemented, then repeat CAC scoring may provide little additional benefit. Patients with CAC scores of 1 – 100 AU who elect to defer statin therapy or other preventive measures may benefit from repeat CAC in 5 years. Especially if statin therapy is implemented, once a CAC score is found to be ≥ 100, then it is unclear that repeat CAC scores provide additional, clinically meaningful information.


    • (8)

      Individuals with a positive CAC score of potential unclear clinical significance include patients with extensive calcification due to older age, patients with kidney disease (vascular medial sclerosis), patients treated with statins (i.e., reports suggest statins may increase CAC in some patients), and some patients with high levels of physical activity. [ , , , ] Given that CAC scores are unlikely to regress, CAC scores do not track response to cardiovascular preventive therapy (i.e., response to statins). While alcohol drinkers in general may have increased frequency of atherosclerotic plaque in the coronary arteries despite reduced or zero CAC scores, [ , ] heavy consumption of hard liquor may sometimes increase CAC scores. [ , ]


    • (9)

      Individuals with a negative CAC score of potential unclear clinical significance include younger individuals who may have non-calcified atherosclerosis, patients with microvascular dysfunction, such as some women (and men) with non-obstructive ischemic heart disease (as may be assessed by PET).


    • (10)

      A low CAC score should not negate CVD risk factor management. For example, a low CAC score in a patient otherwise at high CVD risk should not give a false sense of security, and interpreted as negating the need for aggressive lipid management (e.g., stopping statin therapy in patients with Familial Hypercholesterolemia, who while young, may still have “soft” uncalcified plaque).

    Sentinel Guidelines and References 2021 National Lipid Association Scientific Statement on Coronary Artery Calcium Scoring 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol 2018 Coronary Calcium Score and Cardiovascular Risk 2020 Coronary Calcium StatPearls 2018 Coronary Artery Calcium: If Measuring Once Is Good, Is Twice Better?

    *CHD = coronary heart disease (e.g., myocardial infarction or death from coronary heart disease)

    *ASCVD = Atherosclerotic cardiovascular disease is often defined as acute coronary syndrome, myocardial infarction, stable or unstable angina, coronary or other arterial revascularization, stroke, transient ischemic attack, peripheral artery disease, and aortic aneurysm – all of atherosclerotic origin .




Cardiac exercise stress testing


Preventive cardiology incorporates both primary and secondary CVD prevention. Understanding the extent of CVD disease in both asymptomatic and symptomatic patients helps the clinician better recommend therapeutic interventions towards the goal of preventing future CVD events. Non-invasive cardiac imaging studies in patients with stable coronary obstructive symptoms (stable ischemic heart disease or “chronic coronary syndrome”) can help diagnose ischemic heart disease and are often performed prior to cardiac catherization. In most cases, the use of imaging studies to diagnose ischemia is performed with exercise testing, such as through use of a treadmill or bicycle. Imaging with exercise testing can enhance accuracy of the stress testing, especially in patients with non-interpretable electrocardiograms. The purpose of physical exercise coupled with imaging studies is to evoke coronary (macro and micro) blood flow, and promote other functional cardiovascular responses, during times of greater oxygen and nutrient demands of the heart (i.e., during times of “stress” such as via exercise).


Thus, stable patients suspected of myocardial ischemia who are able to exercise, and who have interpretable ECG/s, are best “stressed” via physical exercise (i.e., treadmill or bicycle). Incorporating exercise in a cardiac “stress test” allows for non-imaging assessment of hemodynamic response (i.e., heart rate, blood pressure), ST- segment analysis, and onset of dysrhythmias. Stress electrocardiography alone is reported to have sensitivity and specificity of 50 – 80%, depending on the source and patient population studied. [ , ] ( Reference Chart 2 ) In patients with ECG abnormalities (e.g., left bundle branch block, changes consistent with left ventricular hypertrophy, ST-T wave changes), the addition of heart imaging (e.g., echocardiography or MPI such as SPECT or PET) to exercise cardiac stress testing may help identify and quantify cardiac dysfunction and/or ischemia.


A patient at low to intermediate CVD risk with a negative cardiac stress test [i.e., demonstrating no chest pain and no electrocardiographic evidence of ischemia after undergoing standard exercise protocols and achieving ten metabolic equivalents (METS)] is at low risk for future CVD events and or CVD mortality. However, among patients with exercise treadmil stress tests suggesting possible ischemia, then depending on CVD risk, only 39% may subsequently have positive imaging/angiogram evidence of atherosclerosis. Thus, among patients presenting with intermediate likelihood of CVD, exercise cardiac stress testing (i.e., treadmill or bicycle) plus cardiac imaging (e.g., echocardiogram, MPI, or PET) is more specific than an exercise stress test alone. Furthermore, in patients with uninterpretable ECG’s, or in patients unable to exercise, and/or who undergo pharmacologic cardiac stress testing, concomitant heart imaging studies are often required.


Patients unable to undergo adequate exercise stress testing (e.g., relative immobility due to deconditioning, frailty, obesity, stroke, orthopedic impairments, neuropathy, lung disease) may require pharmacologic stress testing. Examples of pharmacologic stress agents include regadenoson (A2a receptor agonist), adenosine (nonselective adenosine receptor agonist), dipyridamole (nonselective vasodilator and antiplatelet agent that raises adenosine levels), and dobutamine (sympathomimetic). Regadenoson is the most common pharmacologic vasodilator used for pharmacological SPECT stress testing. [ , ]



Imaging studies


Safety considerations of imaging studies include the degree of their invasiveness and amount of radiation exposure ( Reference Chart 1 ). Invasiveness is defined here as access to the body via inserting a diagnostic device or injecting imaging media through incision or percutaneous puncture. Potential radiation exposure may be especially important in cardio-oncology.


The most invasive CVD imaging study is cardiac catheterization. ( Reference Chart 1 ) Cardiac catheterization remains the initial imaging procedure of choice for patients whose history, signs, symptoms and/or CVD imaging test results suggest high risk for myocardial dysfunction (e.g., high CVD risk features on a cardiac exercise stress test). This is especially true if it is anticipated the cardiac catheterization may be accompanied by a therapeutic intervention (i.e., PCI, thrombectomy, atherectomy). Complications of cardiac catheterization include bruising/bleeding at the catheter insertion site, myocardial infarction, stroke and other thrombotic complications, vascular injury, cardiac dysrhythmias, infection, contrast induced nephropathy, or allergic reaction to the contrast dye (i.e., iodine).


The invasiveness, radiation exposure, and cost associated with cardiac catheterization have prompted development of alternative noninvasive imaging procedures, many having limited radiation exposure. Radiation exposure is important because ionizing radiation contributes to cell death, cellular injury, or cell mutation potentially leading to cancer. (Non-ionizing radiation includes electric and magnetic fields, radio waves, microwaves, infrared, ultraviolet, and visible radiation, which have insufficient energy to ionize atoms or molecules.) The degree of radiation exposure is dependent on the dose of tracer infused, length of the imaging procedure, and the number of times the procedure is performed. Examples of CVD imaging studies with limited invasiveness include CAC, CCTA, & MPI. CVD imaging studies with limited invasiveness and no or minimal radiation exposure include CMR and ultrasound. (See Reference Chart 1 )



Computerized tomography (CT) coronary artery calcium (CAC)


A coronary artery calcium (CAC) score utilizes CT to assess the amount of calcium found in coronary arteries. Arterial calcium reflects vascular injury, inflammation, and repair. Coronary calcium is a marker of plaque burden. It is not a measure of plaque vulnerability to rupture or degree of coronary stenosis. Due to vessel remodeling early in atherosclerosis, enlargement of coronary arteries may occur, mitigating signs or symptoms of stenosis, despite substantial plaque burden. This pathogenic clinical scenario is often clarified by CAC. Other cardiac imaging (i.e., with exercise stress testing) are more appropriate for patients with angina and/or obstructive CAD. However, CAC is a non-invasive cardiac procedure that can assess plaque burden, that is best used in asymptomatic patients to help guide the need for further cardiac evaluation or help determine the timing and degree of aggressiveness in managing existing CVD risk factors.


CAC scores may be increased with older age, men versus women for same age, metabolic syndrome, high blood glucose, high blood pressure, increased atherogenic lipoprotein cholesterol burden, cigarette smoking, chronic kidney disease, and elevated C-reactive protein levels. Assessment of coronary artery calcium is most often performed by multidetector computed tomography (MDCT); CAC does not require contrast. The Agatston score reflects the total area of calcium deposits in coronary arteries, and the density of the calcium.


CAC Agatston Unit (AU) scores and coronary plaque burden can be categorized as:




  • 0: No identifiable calcified coronary atherosclerosis



  • 1–100: Calcification suggestive of mild coronary atherosclerosis



  • 100 to 400: Calcification suggestive of moderate coronary atherosclerosis



  • 400 or above: Calcification suggestive of severe coronary atherosclerosis



  • 1000 or above: Calcification suggestive of extreme coronary atherosclerosis



In a Scientific Statement from the National Lipid Association, CAC scoring:




  • Informs ASCVD risk discrimination and reclassification



  • Aids in ASCVD risk prediction, regardless of race, gender, or ethnicity



  • Aids the clinician to allocate statin therapy based on ASCVD risk



  • May inform decision-making about add-on therapies to statins, especially if CAC scores are very high



  • Aids decision-making about aspirin and anti-hypertensive therapy



Reference Chart 1 describes the relative radiation exposure with CAC. Table 1 lists ten things to know about computerized tomography coronary artery calcium (CAC) measurements.



Coronary computed tomography angiography (CCTA)


Atherosclerotic progression begins with early reversible subendothelial lipid accumulation, early inflammation, and minimal fibrosis. Further atherosclerotic progression may lead to lipid plaque, chronic inflammation, fibrosis, and perivascular adipose tissue remodeling – which if untreated, may ultimately become irreversible. CCTA can measure lipid rich plaque, as well as perivascular fat and inflammation. [ , ]


Clinically, CCTA is a cardiac imaging study utilizing CT that is often used to quantify coronary atherosclerotic burden. When combined with FFR, CCTA can help determine the functional significance of stenotic lesions. With use of an iodine intravenous contrast agent, CCTA can visualize the coronary artery lumen. CCTA is sensitive for anatomically significant CAD (e.g., obstructive CAD and nonobstructive calcified plaques) and reasonably sensitive for functionally significant CAD. However, CCTA is not specific for functionally significant CHD. ( Reference Chart 2 ) Reference Chart 1 describes the relative radiation exposure with CCTA. Table 2 lists ten things to know about coronary computed tomography angiography (CCTA).



Table 2

Ten things to know about coronary computed tomography angiography (CCTA) .









  • (1)

    CCTA has a high negative predictive value, such that if negative, then clinically meaningful CVD risk. CCTA may be especially valuable in assessing patients with chest pain or related symptoms, but without known CHD and who are at low to intermediate CVD risk. CCTA guided changes in management can improve clinical outcomes.


  • (2)

    CCTA is a potential non-invasive imaging test of choice in patients with symptoms of chest pain where obstructive CAD cannot be reasonably established by history and physical exam alone.


  • (3)

    CCTA may also be helpful to rule out left main CAD. The absence of coronary artery stenosis with CCTA imaging is associated with a favorable prognosis.


  • (4)

    Evaluation of the severity of coronary stenosis can be derived from estimating pressure differences via “virtual” fractional flow reserve derived from CCTA (FFR CT ).


  • (5)

    CCTA can assess non-obstructive coronary artery plaque, which can inform CVD preventive management. Management decisions guided by CCTA in patients with stable chest pain may reduce CHD and MI mortality at 5 years, without prompting a higher rate of coronary angiography or coronary revascularization.


  • (6)

    Poor image quality and severe calcification can overestimate CCTA coronary artery stenosis.


  • (7)

    CCTA is not recommended in patients with extensive coronary calcification (which may occur with older age and kidney failure), cardiac dysrhythmias (including tachycardia), significant obesity, and in patients unable to hold their breath – all which may adversely affect image quality.


  • (8)

    CCTA image quality may be impaired in patients with prior cardiac revascularization.


  • (9)

    The contrast with CCTA is contraindicated in patients with contrast dye allergies.


  • (10)

    Contrast (i.e., iodine) induced acute kidney injury occurs due to contrast-mediated hypoperfusion, direct tubular toxicity, and vasoconstriction. CCTA contrast should be used with caution in patients with kidney insufficiency and warrants adequate fluid intake in those receiving contrast. Additional risk factors for CCTA contrast induced nephropathy beyond renal insufficiency (i.e., estimated glomerular filtration rate <45 ml min / 1.73m 2 ) include severe heart disease, dehydration, diabetes mellitus, multiple iodinated doses in a short time interval (<24 h) and use of nephrotoxic medications, such as non-steroidal anti-inflammatory drugs and diuretics.

Sentinel Guidelines and References 2021 Epicardial fat and coronary artery disease: Role of cardiac imaging 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: Recommendations for cardiovascular imaging 2018 Coronary CT Angiography and 5-Year Risk of Myocardial Infarction 2015 Outcomes of anatomical versus functional testing for coronary artery disease 2015 Cardiac CT vs. Stress Testing in Patients with Suspected Coronary Artery Disease: Review and Expert Recommendations



Cardiac ultrasound (echocardiography)


Echocardiography utilizes ultrasound waves (sound wave range beyond that audible by humans) to provide hemodynamic information about heart function. When accompanied by stress testing, echocardiography is often used to assess myocardial ischemia (i.e., coronary artery atherosclerosis), left ventricular function (i.e. heart failure, cardiomyopathy) and structural heart disease (i.e., valvulopathy, congenital heart disease, aneurysm, cardiac tumor, pericarditis, endocarditis, aortic dissection, heart chamber thrombosis). Approaches to echocardiography include transthoracic chest wall approach or transesophageal approach. Types of echocardiography include: [ , ]




  • M-mode: “Motion mode” generates tracing images rather than picture images.



  • Doppler (previously known as B or “Brightness-mode”): Assesses blood flow and can be characterized as continuous-wave, pulsed-wave or color-flow. Continuous and pulse wave doppler echocardiography images allow for calculated flow velocity, as well as estimates for volume and pressure gradients across heart valves.



  • 2-D (two-dimensional) echocardiography: Provides cross-sectional real-time motion images of the heart



  • 3-D (three-dimensional) echocardiography: Able to view real-time motion of the heart via 3-D images



Stress echocardiography is reasonably sensitive and specific for diagnosing coronary artery disease in symptomatic patients. ( Reference Chart 2 ). However, despite its noninvasive safety, “routine” echocardiograms should not be performed in asymptomatic patients (“inappropriate use”), as this may lead to false positive or equivocal findings, resulting in unnecessary downstream consultations and procedures. Reference Chart 1 describes how cardiac ultrasound results in no radiation exposure. Table 3 lists ten things to know about echocardiography.



Table 3

Ten things to know about cardiac ultrasound (echocardiography) [ , ]









  • (1)

    Transthoracic echocardiography is the most common approach, with transesophageal echocardiography preferred in patients with conditions that compromise transthoracic imaging quality (e.g., obesity, certain lung conditions). Contrast options include agitated saline or commercial ultrasound contrast agents ( Reference Chart #1 ). Contrast echocardiography may improve diagnostic performance regarding left ventricular opacification or microvascular perfusion imaging.


  • (2)

    Transesophageal echocardiography may provide better resolution images of the left heart, evidence of potential endocarditis, mitral and aortic valves, and aorta (i.e., aortic dissection).


  • (3)

    Doppler echocardiography can assess stroke volume, heart chamber pressure gradients, valvular regurgitations, and intracardiac shunts.


  • (4)

    In patients with angina-like chest pain, echocardiography can help diagnose alternative cardiac etiologies of chest pain, identify regional wall-motion abnormalities, determine left ventricular ejection fraction, and evaluate diastolic dysfunction for stratification purposes (i.e., surgical risk based upon cardiac status).


  • (5)

    As with stress SPECT, stress PET, and stress CMR, stress echocardiography provides cardiac functional assessment.


  • (6)

    Echocardiography is commonly used to assess left ventricular ejection fraction, which is “normally” ~ 50 – 70%. Heart failure with reduced ejection fraction (HFrEF) is defined as heart failure with ejection fraction < 50%.


  • (7)

    While heart failure can occur with reduced ejection fraction, symptomatic heart failure can also occur with preserved ejection fraction (HFpEF) (i.e., ejection fraction ≥ 50%).


  • (8)

    Echocardiography may provide helpful information regarding microcirculatory dysfunction that may contribute to angina without obstructive lesions in major coronary arteries. Angina and ischemia-like electrocardiographic changes without wall motion abnormalities on echocardiography may suggest microvascular dysfunction. [ , ]


  • (9)

    In many patients, echocardiogram assessment of heart function and anatomy can provide peri-operative risk stratification.


  • (10)

    Echocardiogram assessment can provide cross-sectional and longitudinal cardiac assessment in patients undergoing chemotherapy, helping to monitor for potential adverse effects of chemotherapy on cardiac structure and function. Evidence of echocardiographic left ventricular global longitudinal strain may be reflective of subclinical ventricular dysfunction and provide prognostic information in patients receiving cardiotoxic chemotherapy.

Sentinel Guidelines and References 2021 Novelties in 3D Transthoracic Echocardiography 2021 Usefulness of Stress Echocardiography in the Management of Patients Treated with Anticancer Drugs 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes: Recommendations for cardiovascular imaging 2020 Echocardiography update for primary care physicians: a review 2004 Understanding the echocardiogram



Nuclear myocardial perfusion imaging (MPI)


Nuclear myocardial perfusion imaging through Single Photon Emission Computed Tomography (SPECT) utilizes small amounts of nuclear tracer (i.e., the isotope technetium-99 or thallium-201) injected into the blood to assess myocardial segments that do not take up the tracer (i.e., damaged myocardium) or areas with delayed uptake of the tracer (i.e., ischemic myocardium). SPECT can also help assess the patency of grafted blood vessels after coronary bypass. Techetium-99 is a radiotracer often attached to a small protein (sestamibi). Thallium-201 is typically supplied as thallous chloride. Technetium-99 has lower radiation exposure and is preferred; Thallium-201 is rarely used in current clinical practice. ( Reference Chart 1 ) The radiotracers are generally injected into the blood with imaging occurring at rest, or with exercise (e.g., “ nuclear stress test ,” “ exercise thallium scan ,” “ exercise technetium-99 sestamibe scan ”), or both. For patients unable to physically exercise, then an A2A adenosine receptor agonist (i.e., regadenoson coronary vasodilator for cardiolite stress test) can be injected as an alternative to exercise.


A positron emission tomography (PET) scan of the heart utilizes a radiotracer (i.e., often 82 rubidium or 13 ammonia for rest and stress perfusion). Uptake of the radiotracer by the myocardium is proportional to myocardial blood flow. Thus, coronary flow reserve can be added to PET to improve CVD risk assessment. Strengths of PET MPI include high diagnostic accuracy, safety with low radiation exposure (lower than SPECT), efficient with 5-min image acquisition times (may take only 30 minutes to perform), ability to accommodate ill or higher-risk patients, ability to assess patients with large body habitus, and ability to assess non-obstructive coronary microvascular dysfunction. PET is often used as a noninvasive imaging test to assess coronary flow reserve ( Table 5 ), that may assist with diagnosis, prognosis, and management of patients with a range of ASCVD, including both multivessel obstructive CAD and diffuse coronary microvascular dysfunction. Cardiac microvascular dysfunction may be especially clinically relevant in women, patients with heart failure with preserved ejection fraction, metabolic syndrome, diabetes mellitus, cardio-oncologic complications, and inflammatory-related disease. [ , ] Patients with stable ischemic heart disease (SIHD) vary in their cardiac anatomy and function. In addition to obstructive coronary lesions, it is estimated that 3 – 4 million men and women in the US have symptoms of myocardial ischemia with no evidence of obstructive CAD. Along with heart failure with preserved ejection fraction, other cardiac conditions that may occur more often in women include Takotsubo cardiomyopathy, cerebral small-vessel disease, preeclampsia, pulmonary arterial hypertension, endothelial dysfunction in diabetes, diabetes cardiomyopathy, rheumatoid arthritis, systemic lupus erythematosus and systemic sclerosis, and small vessel cardiac disease – which suggests a common etiologic linkage of these cardiac conditions. An illustrative strategy that may help balance safety and diagnostic yield would be to employ ultra-low dose radiation protocols involving stress-only imaging, with SPECT or PET used when possible for patients undergoing MPI.


A multiple-gated acquisition (MUGA) scan involves utilizes a radiotracer (e.g., technetium-99m-pertechnetate) attached to red blood cells to evaluate the size of the chamber of the heart. MUGA was historically among the most common cardiac imaging studies for measuring left ventricular ejection fraction (LVEF) MUGA scans are currently seldom used in favor of other imaging studies such as echocardiography and CMR.


Reference Charts 1 & 2 describe the radiation exposure using MPI techniques, as well as their sensitivity and selectivity. Table 4 lists ten things to know about nuclear myocardial perfusion imaging.


Jul 16, 2021 | Posted by in CARDIOLOGY | Comments Off on Ten things to know about ten imaging studies: A preventive cardiology perspective (“ASPC top ten imaging”)
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