CardioNerd Amit Goyal is joined by Dr. Erika Hutt (Cleveland Clinic general cardiology fellow), Dr. Aldo Schenone (Brigham and Women’s advanced cardiovascular imaging fellow), and Dr. Wael Jaber (Cleveland Clinic cardiovascular imaging staff and co-founder of Cardiac Imaging Agora) to discuss nuclear and complimentary multimodality cardiovascular imaging for the evaluation of coronary ischemia. Show notes were created by Dr. Hussain Khalid (University of Florida general cardiology fellow and CardioNerds Academy fellow in House Thomas). To learn more about multimodality cardiovascular imaging, check out Cardiac Imaging Agora! 

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Five Take Home Pearls

1. We can broadly differentiate non-invasive testing into two different categories—functional and anatomical. Functional tests allow us to delineate the functional consequence of coronary disease rather than directly characterizing the burden of disease. Anatomical tests such as coronary CTA, on the other hand, allow us to directly visualize obstructive epicardial disease.

2. In general PET imaging provides higher quality images than SPECT imaging for a variety of reasons, including a higher “keV” of energy in PET radiotracers

3. If using a SPECT camera, we should use cameras that have attenuation correction. Without attenuation correction, the specificity of a SPECT camera drops to 50-60%.

4. In evaluating ischemic heart disease, cardiac nuclear imaging can provide a wide range of information including myocardial perfusion (rest and stress), ejection fraction assessment (rest and stress), absolute myocardial blood flow with quantitative flow reserve in all coronary territories (PET), assessment of myocardial viability (PET), and calcium score with CT attenuation correction.

5. To select the best non-invasive test, we should consider a variety of factors such as pretest probability of obstructive epicardial disease, patient-specific factors (e.g., ability to exercise) and whether a functional or an anatomical test will provide the best answer for our clinical question.

Detailed Show Notes

1. What are the basic non-invasive testing categories for evaluation of coronary artery disease?  
   • We have a variety of different non-invasive testing modalities that can be broadly separated into functional tests and anatomical tests.  
     • The basic principle underlying functional stress testing is to induce ischemia or coronary vasodilation (discussed below), followed by a functional assessment by different techniques (e.g., EKG, echocardiography, radionuclide imaging) to detect flow-limiting obstructive coronary artery disease. These tests delineate the functional consequence of the coronary disease, rather than directly characterizing the burden of disease itself.  
     • Functional tests can also allow us to assess the nature of a patient’s symptoms. For example, by having a patient exercise on a treadmill we can evaluate whether we can reproduce a patient’s chest pain syndrome. 
     • Anatomical tests allow us to visualize the presence of obstructive epicardial disease. For example, obtaining a Coronary Computed Tomography Angiography (CCTA) for a patient with chest pain would allow you to directly visualize possible obstructive epicardial disease.  

1. How do we induce ischemia for functional stress testing?  
   • To induce ischemia (and/or coronary vasodilation), we have many different stressors that can be broadly separated into exercise stressors and pharmacologic stressors. 
     • Treadmill exercise via standardized protocols is the most common method for inducing ischemia and has the advantage of assessing functional capacity, which has prognostic information. Supine bicycle is another common exercise modality that is utilized. 
     • There are also several pharmacologic stressors that vary in their mechanisms of action. Dobutamine is a synthetic catecholamine that stimulates myocardial beta-1 and beta-2 receptors to increase heart rate, contractility, and consequently myocardial oxygen demand with a small decrease in systemic vascular resistance.   
     • Adenosine and adenosine derivatives (e.g. regadenoson) induce coronary vasodilation and take advantage of differences in coronary flow reserve. With obstructive coronary lesions, the vessels distal to the obstruction are already dilated at baseline and have little flow reserve. Adenosine (and its derivatives) induce vasodilation and increase flow in normal coronary beds, but much less so in areas supplied by an obstructive lesion. Consequently, we can see disparate radiotracer uptake that correlates with different coronary territories.  
   • Once we’ve induced ischemia, we can assess it via electrocardiogram (EKG) alone or in conjunction with an imaging modality such as echocardiography, MRI, or nuclear imaging — such as Single Photon Emission Computed Tomography (SPECT) or Positron Emission Tomography (PET).   

1. What is the difference between SPECT and PET imaging quality? What are the advantages of using PET imaging? 
   • SPECT and PET imaging both use gamma cameras that detect gamma rays produced by the injected radionuclide tracer. SPECT utilizes a single-crystal camera to acquire multiple 2D images to be reconstructed into a 3D image, while PET imaging utilizes a multi-crystal camera which can detect more counts (e.g., quantification of radioactivity).  
   • SPECT studies usually use Technetium-based tracers which have nuclei that emit 140 keV of energy. PET studies usually use Rubidium or Ammonia which have nuclei that emit around 510 keV of energy. Either of these studies can also use Thallium which have nuclei that emit 68 keV of energy. In general, the higher the “keV”, the better the image quality. So, using thallium may result in poorer quality images and is not recommended as a first-line agent.  
     • Rubidium has a half-life of 76 seconds and Ammonia has a half-life of 10 minutes—so it is possible to do an exercise stress test if using Ammonia but not with using Rubidium! 
     • Because the radiotracers used for PET imaging have higher “keV” than those used in SPECT imaging, PET image quality is generally better with a higher resolution. 
   • If using a SPECT camera, you should use a camera that has attenuation correction. Attenuation artifact can occur when you have tissue such as breast or diaphragm that overlies the myocardium and decreases the intensity/strength of signal prior to reaching the myocardium. This can result in the false appearance of a myocardial perfusion defect in that region. Without attenuation correction, the specificity of a SPECT camera drops to 50-60%.  
   • In addition to improved spatial resolution and higher quality images resulting from using radiotracers with higher “keV”, PET cameras also do not require physical collimation. This allows for even further increase in spatial resolution and image quality.  
     • A collimator is a piece of lead with holes that absorb and stop most photons except for those that arrive almost perpendicular to the detector face. This allows the camera to accurately localize the radiotracer in the patient’s body over the organ of interest. Overall, PET has better sensitivity, specificity, and better accuracy to diagnose 50% and 70% lesions than SPECT!  
     • However, maintaining PET scanners comes at increased cost compared to SPECT. 

1. What diagnostic information can cardiac nuclear imaging provide us? What are some unique uses of nuclear imaging? 
   • In the evaluation of coronary disease, some diagnostic information provided by SPECT and PET imaging include: 
     • Assessment of myocardial perfusion and blood flow at both rest and stress 
     • Ejection fraction assessment at both rest and stress 
     • Quantitative flow reserve in all coronary territories (PET) 
     • Assessment of myocardial viability (PET) 
     • Prognostication 
     • Calcium Score with CT Attenuation Correction 
       • If using CT for attenuation correction, you should also use it for calcium score. A high coronary calcium score can change management—there is also data that shows that just showing patients the plaque on CT imaging can improve outcomes!  
   • There are many uses of nuclear imaging, and novel uses are continuously being described. In addition to its use in noninvasive stress testing and ischemic heart disease, we can also use it to assess etiology of cardiomyopathies:  
     • In patients with suspected cardiac sarcoidosis, fluorodeoxgylocse(FDG)-PET imaging with Rubidium can be utilized to detect sarcoid and prognosticate. Enjoy the upcoming discussion about sarcoidosis imaging as well as the CNCR from the University of Chicago!  
       • Nuclear scintigraphy with 99m-Technetium pyrophosphate can be used to assess for cardiac amyloidosis. Stay tuned for more on this as part of the amyloidosis imaging discussion.  
     • FDG PET and whole-body-white blood cell scan can be used to help evaluate for prosthetic valve endocarditis or LVAD-associated infections, which we will also discuss later in this imaging series! 
     • FDG-PET can help evaluate and differentiate aortopathies in patients presenting with chest pain 
   • Many novel uses of nuclear stress testing are being described for patients admitted to the cardiac intensive care unit (CICU).  
     • CT imaging and MRI require significant patient cooperation. MRI additionally is sometimes limited by patient compatibility issues. A full PET study can be done in 20-25 minutes, however, independent of renal and hepatic function.  
     • In patients admitted to the CICU with an intra-aortic balloon pump (IABP), exercise can be simulated by reducing the IABP support ratio from 1:1 to 1:3. A PET stress test can then be conducted using this “exercise” to evaluate for myocardial ischemia. 

1. How do you select the best non-invasive test? 
   • A variety of factors play a role in this decision. To begin, you can start with the picking whether a functional test or an anatomical test is best to answer your clinical question. 
     • Are you trying to identify the nature of a patient’s symptoms for a possible underlying cardiac etiology? Perhaps a functional test is best.  
     • Are you trying to rule out obstructive epicardial disease? Perhaps an anatomical test is best.  
     • In many instances functional and anatomical tests provide complimentary information. And if the patient has had multiple prior non-invasive testing of the same modality with equivocal answers to the clinical question, it may be more helpful to switch to a different modality. 
   • Many imaging and individual patient factors affect the selection for the best non-invasive test. For instance: 
     • Patient factors/comorbidities such as kidney disease, liver disease, devices, metallic implants, ability to exercise, baseline abnormal ECG or TTE, and patient cooperation issues affect the selection for the best non-invasive test. 
     • Cost-effectiveness of the study and radiation exposure should be a consideration. 
     • If the patient has a low pretest probability of obstructive CAD, perhaps testing is not needed, or you could consider an anatomical test such as a Coronary CTA 
     • If the patient has a low-intermediate pretest probability of obstructive CAD, one could consider obtaining CCTA anatomical testing in addition to an exercise tolerance test (ETT) with or without imaging as this has been shown to provide higher diagnostic ability and affects management. Rather than have premature closure when obstructive epicardial disease is ruled out, we can assess for nonobstructive plaque that warrants initiation of aggressive lifestyle and risk factor modifications. 
     • If the patient has a significant cardiovascular disease history (e.g. multiple prior stents or bypass surgery) but lower suspicion of symptomatic coronary ischemia, perhaps functional testing such as stress MRI, nuclear stress test, or stress echocardiogram is preferred. 
     • If the patient has a high pretest probability of obstructive epicardial disease, perhaps it is best to skip a non-invasive test and proceed straight to an invasive test. 
     • Do note that patients with angina who do not have obstructive epicardial stenoses on anatomical testing may have coronary microvascular disease which is still important to diagnose given important therapeutic and prognostic implications. More on this in the next episode!  
   • Below is a depiction of the how effective the different non-invasive modalities are to rule in or rule out significant coronary artery disease in stable CAD patients. It is based on follow-up invasive coronary angiography or FFR assessment, stratified by pretest probability. Notably, stress ECG requires a relatively lower pretest probability to rule out obstructive CAD and relatively higher pretest probability to rule in CAD. CCTA does not perform as well as functional imaging techniques in ability to rule-in and rule out FFR-significant CAD when comparing it to its ability to rule in and rule out significant CAD by invasive coronary angiography. 

Wael Jaber, MD, is a staff cardiologist in the Section of Cardiovascular Imaging, Robert and Suzanne Tomsich Department of Cardiovascular Medicine, at the Sydell and Arnold Miller Family Heart, Vascular & Thoracic Institute at Cleveland Clinic. Dr. Jaber specializes in cardiac imaging (both nuclear cardiology and echocardiography) and valvular heart disease. Dr. Jaber attended college at the American University in Beirut, graduating with a Bachelor of Science in biology. He then went on at the American University to receive his medical degree while making the Dean’s honor list. He completed his residency in internal medicine at the St. Luke’s-Roosevelt Hospital Center at Columbia University College of Physicians and Surgeons, where he also completed fellowships in cardiovascular medicine and nuclear cardiology. Dr. Jaber is currently is the Medical Director of the Nuclear Lab and of the Cardiovascular Imaging Core Laboratory in C5Research. He is fluent in English, French and Arabic. He is the author of Nuclear Cardiology review: A Self-Assessment Tool and cofounder of Cardiac Imaging Agora.

Dr. Aldo L Schenone is one of the current Chief Non-Invasive Cardiovascular Imaging Fellows at the Brigham and Women’s Hospital. He completed medical school at the University of Carabobo in Valencia, Venezuela, and then completed both his Internal Medicine residency and Cardiology fellowship at the Cleveland Clinic where he also served as a Chief Internal Medicine Resident.

Dr. Erika Hutt @erikahuttce is a cardiology fellow at the Cleveland Clinic. Erika was born and raised in Costa Rica, where she received her MD degree at Universidad de Costa Rica. She then decided to pursue further medical training in the United States, with the goal of becoming a cardiologist. She completed her residency training at Cleveland Clinic and went on to fellowship at the same institution. Her passions include infiltrative heart disease, atrial fibrillation, valvular heart disease and echocardiography among many. She is looking forward to a career in advanced cardiovascular imaging.

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• Wael Jaber, MD