Care to Care White Paper Hybrid Cardiac PET-MRI

HYBRID CARDIAC PET/MRI: ASSESSING COVERAGE FOR A NEW TECHNOLOGY By: Julian Safir, MD, Chief Medical Officer Care to Care, LLC March 2015

Hybrid Cardiac PET/MRI: Assessing Coverage For A New Technology Introduction Cardiovascular diseases are the leading cause of death in the world, underscoring the importance of further development of both novel diagnostic and therapeutic strategies in this field. Medical imaging, comprised of echocardiography, nuclear cardiology, cardiac computed tomography (CT), cardiac magnetic resonance imaging (MRI), and positron emission tomography (PET), plays an important role in the clinical management of patients with cardiac diseases. When properly integrated into clinical practice, cardiovascular imaging promotes prompt, efficient, and cost- effective patient care. Efforts to ensure appropriate imaging while containing health care costs include developing evidence-based guidelines. To ensure the appropriateness of such guidelines a solid body of clinical and economic evidence is required. Care to Care aims to enable its clients to make sure that their members with cardiac disease receive the right test at the right time to achieve the best outcomes through the use of evidence-based medicine. Coronary artery disease (CAD) is still largely perceived as a consequence of the incremental occlusion of coronary arteries through progressive vascular stenosis, classically diagnosed by coronary angiography and treated by percutaneous or surgical coronary revascularization. This approach has led to an unreasonably large number of symptomatic, and asymptomatic at- risk, patients with suspected CAD who undergo coronary angiography with normal findings. Also, recent large randomized trials have emphasized the limitations of coronary arteriography studies that lead to therapeutic interventions based only on the morphologic severity of epicardial coronary stenosis; these trials advocate for additional proof of hemodynamically significant stress-induced reduction in coronary flow before any therapeutic interventions are undertaken.Care to Care, LLC -2 - www.caretocare.com

Hybrid Cardiac PET/MRI: Assessing Coverage For A New Technology Cardiac PET Myocardial perfusion imaging with single photon emission computed tomography (SPECT) is a widely established method for non-invasive evaluation of coronary artery stenosis. The most important applications of SPECT are in the diagnosis of CAD, prediction of disease progression, selection of patients for revascularization and assessment of acute coronary syndromes. The diagnostic accuracy of myocardial perfusion by PET in the assessment of CAD has been reported to be superior to SPECT, particularly in patients with mutivessel disease, and in heavier patients due to PET’s ability to correct for attenuation artifacts. PET remains the reference technique that has been extensively validated for the accurate detection of hemodynamically significant coronary stenosis as compared with invasive coronary angiography. PET also provides accurate and reproducible evaluation of absolute myocardial blood flow at rest and under stress conditions, as well as an accurate estimate of coronary flow reserve. The introduction of hybrid PET/CT technology offers the possibility of assessing the extent of anatomic CAD through CT angiography. Care to Care covers pre-authorization of PET exams using the FDA-approved radiopharmaceuticals Rubidium 82 or Ammonia N-13 to assess myocardial perfusion in place of, but not in addition to SPECT scan or following an inconclusive SPECT scan. The identification of patients with partial loss of heart muscle movement or hibernating myocardium is important in selecting candidates with compromised ventricular function to determine appropriateness for revascularization. Diagnostic tests such as Positron Emission Tomography (PET) distinguish between dysfunctional but viable myocardial tissue and scar tissue in order to affect management decisions in patients with ischemic cardiomyopathy and left ventricular dysfunction. Care to Care covers FDG-PET to assess myocardial viability following anCare to Care, LLC -3 - www.caretocare.com

Hybrid Cardiac PET/MRI: Assessing Coverage For A New Technology inconclusive nuclear imaging SPECT scan or as a primary or initial diagnostic study prior to revascularization. Cardiac MRI Cardiovascular magnetic resonance imaging (MRI) is established in clinical practice for the diagnosis and management of disease of the heart. Evaluation of patients with congenital heart disease (CHD) is a significant strength of MRI because 3D contiguous data sets are very effective for the complete depiction of the pathological anatomy of both simple and complex CHD. Moreover, the lack of ionizing radiation is an important consideration when performing sequential studies in children and young adults. MRI is well-established for evaluation of a wide variety of acquired cardiovascular diseases, including aneurysm and dissection of the thoracic aorta. MRI has opened new avenues for assessing coronary artery disease (CAD) and its consequences. It provides valuable information which may not be available from other diagnostic tools such as echocardiography and nuclear cardiology which currently dominate non-invasive diagnosis in patients with CAD. Cardiac MRI has proven to be useful for the cardiomyopathies, which include a variety of diseases where the primary pathology directly involves the myocardium excluding CAD. Both MRI and CT are well suited to define anatomic abnormalities of the pericardium including pericardial thickening and effusions. MRI has the advantage of being able to depict and quantify the functional abnormalities which may be associated with pericardial disease. Transthoracic echocardiography is the usual technique which detects intracardiac tumors. However, in many cases the characterization is incomplete, and MRI is particularly helpful in determining the relationship to normal intracardiac structures and tumor extension to adjacent vascular and mediastinal structures, infiltration into the pericardium, and surgical planning. Additional cardiac MRI applications includeCare to Care, LLC -4 - www.caretocare.com

Hybrid Cardiac PET/MRI: Assessing Coverage For A New Technology evaluation of sarcoidosis, myocarditis, valvular heart disease, and heart transplantation. The major advantages of cardiac MRI versus computed tomography (CT) as an adjunct to PET are the higher soft tissue contrast for morphologic information and the lack of radiation exposure. Despite the disadvantage of ionizing radiation, however, CT has become the most commonly used technique for noninvasive coronary angiography (CTA). For the assessment of left ventricular (LV) function, MRI represents the gold standard and has been extensively validated. MRI shows great accuracy in the determination of functional parameters such as LV volumes, mass, ejection fraction, regional wall motion, and myocardial thickening. Furthermore, most patients tolerate MRI contrast agents well. Severe adverse reactions occur more frequently under the application of CT contrast medium. Care to care provides evidence-based guidelines and pre – authorization for cardiac MRI, including the following indications: aortic dissection; arrhythmogenic right ventricular dysplasia; cardiac tumor; coarctation of the aorta; evaluation of left ventricular function if echocardiography is not adequate; distinguishing between ischemic, hypertrophic or restrictive cardiomyopathy; documented myocardial ischemia, revascularization contemplated; evaluation of congenital heart disease; Marfan’s syndrome; myocardial viability assessment of planned revascularization; myocarditis; pericarditis or other pericardial pathology; valvular heart disease; and venous mapping for planned ablation or atrial fibrillation. Hybrid Cardiac PET/MRI Traditionally, stand-alone imaging methods have been used to gain insight into various aspects of cardiac pathophysiology. The recent invention of devices combining PET with MRI (PET/MRI) opens up potential for new opportunities. Sensitivity and specificity in coronary artery disease detection is about 90% for PET imaging,Care to Care, LLC -5 - www.caretocare.com

Hybrid Cardiac PET/MRI: Assessing Coverage For A New Technology and 91% and 81% respectively for MRI. Combined PET/MRI offers a number of potential advantages in the investigation of cardiac disease, including complementary assessment of wall motion abnormalities and identification of regional and segmental hypokinesis, as well as thinning and scar tissue. As a result, PET can identify hibernating myocardium, while MRI can assess acute myocardial infarction or scarring at the site of prior infarction. Although cardiac MR imaging has gained wider adoption for routine clinical applications, PET images remain the reference in many applications for which objective analysis of metabolic and physiologic parameters is needed. In particular, in coronary artery disease, the use of quantitative and measurable parameters in a reproducible way is essential for the management of therapeutic decisions and patient follow-up. Functional MR images and dynamic assessment of myocardial perfusion from transit of intravascular contrast medium can provide useful criteria for identifying areas of decreased myocardial perfusion or for assessing tissue viability from late contrast enhancement of scar tissue. PET images, however, will provide more quantitative data on true tissue perfusion and metabolism. Quantitative myocardial flow can also lead to accurate assessment of coronary flow reserve. The combination of both modalities will therefore provide complementary data that can be expected to improve the accuracy and reproducibility of diagnostic procedures. The potential of hybrid PET/MR imaging may also reside in applications beyond the domain of coronary artery disease, such as sarcoidosis and other systemic diseases. It is also predicted that the two modalities combined could help characterize atherosclerotic plaques and differentiate plaques with a high risk of rupture from stable plaques. The fusion of two potentially competing modalities can offer the best of each modality in a single procedure. However, given the scarcity of such devices in actual use the clinical and economic impact of such advanced technology in routine clinical practice has not yet been demonstrated.Care to Care, LLC -6 - www.caretocare.com

Hybrid Cardiac PET/MRI: Assessing Coverage For A New Technology The general limitations of patients who cannot be imaged with a PET/MR imaging device are the same as those with known contraindications to MRI, including patients who have claustrophobia; patients with a pacemaker, metallic clips, or mechanical valves; and large patients because of the small scanner aperture. Another challenge of clinical cardiac PET-MR pertains to the interpretation of the PET and MR studies. The interpretation of PET/MRI scans requires a new generation of well-trained specialists in both PET and MRI expertise. Finally, cost remains a major limitation that has hindered the widespread use of PET/MR (Table 1). Hospitals and imaging facilities face substantial costs to acquire hybrid PET/MRI technology, including construction required to accommodate the combined system’s physical requirements and to install MRI-compatible ancillary medical equipment needed during imaging procedures. Therefore, hybrid PET/MRI has not reached routine clinical use and additional targeted clinical studies need to be done to better understand the clinical scenarios where PET/MRI will impact patient management and identify the real potential of this technology. A novel imaging technology like hybrid PET/MRI cannot enter routine clinical practice before technical feasibility, diagnostic accuracy, influence on therapeutic management, and economic factors have been carefully considered and evidenced by clinical studies. Care to Care uses evidence-based medicine to assess impact of a new technology on health care through a thorough search of major bibliographic and evidence based medicine databases, Health Technology Assessment websites, and clinical trials. Care to Care considers the use of combined hybrid PET/MRI imaging technology to be investigational and not medically necessary, and there is no CPT code provided by CMS. In the future, value may be achieved by providing a single, noninvasive test that assesses all aspects of the heart, and hybrid PET/MRI has the potential to provide this comprehensive examination. If the ongoing studies confirm the usefulness of PET/MRI in performing an early and detailed cardiac assessment, this new technology may overcome the limitations of availableCare to Care, LLC -7 - www.caretocare.com

Hybrid Cardiac PET/MRI: Assessing Coverage For A New Technology diagnostic imaging methods by helping prevent unnecessary clinical and surgical procedures that contribute to rising healthcare costs and negatively impact patient outcomes. Table 1. Average Cost of Cardiac Imaging Modalities Echocardiography Average Cost CT 1.0 SPECT 3.1 MRI 3.3 PET 5.5 Hybrid PET/MRI 14.0 Right and Left Heart ? Catheterization 20.0 Echocardiography is the cost comparator where costs of other modalities are a ratio of x-fold higher costs. Note: Costs are unit operating costs (not charges).Care to Care, LLC -8 - www.caretocare.com

Hybrid Cardiac PET/MRI: Assessing Coverage For A New Technology References Care to Care Criteria for Imaging Version 2014E. Nappi C, El Fakhri G. State of the Art in Cardiac Hybrid Technology: PET/MRI. Curr Cardiovasc Imaging Rep. 2013 Aug 1;6(4):338-345. Ratib O, Nkoulou R. Potential Applications of PET/MRI Imaging in Cardiology. J Nucl Med. 2014 Apr 24;55(Supplement 2):40S- 46S. Nensa F, Schlosser T. Cardiovascular Hybrid Imaging using PET/MRI. Rofo. 2014 Dec;186(12):1094-101. Wehrl H, Sauter A, Divine M. Combined PET/MR: A Technology Becomes Mature.J Nucl Med 2015; 56:165-158. Rischpler C, et al. Hybrid PET/MR Imaging of the Heart: Potential, Initial Experiences, and Future Prospects. J Nucl Med. 2013;54(3):402–15. Ratib O, N.R. Cardiovascular clinical applications of PET/MRI. Clinical Translational Imaging. 2013. O'Meara C, White SK, Elliott P. Inital experience of imaging cardiac sarcoidosis using hybrid PET-MR - a technologist's case study. J Cardiovasc Magn Reson. 2013. Catana C, Guimaraes AR, Rosen BR. PET and MR Imaging: the odd couple or a match made in heaven? J Nucl Med. 2013 Mar 14. Moudi A, Sun Z, Lenzo N. Diagnostic value of SPECT, PET, and PET/CT in the diagnosis of coronary artery disease: a systematic review. Biomed Imaging INterv J 2011: 7(2).Care to Care, LLC -9 - www.caretocare.com