Cardiovascular Positron Emission Tomography: A State of the Art and Into the Future

The cost of cardiovascular disease in the U.S. is estimated at $315.4 billion for the year 2010 alone.1 This high cost is partly attributable to diagnostic tests, as well as pharmaceutical and medical interventions. With the advent of accountable care organizations (ACOs), there is now an important shift from high volume to high value in the care delivery model. The purpose is to encourage change in patient care so as to accelerate progress toward a three-part aim: better care for individuals, better health for populations, and slower growth in costs through improvements in care.2 An important but costly part of cardiovascular medicine includes the utilization of imaging technology to make appropriate diagnoses. In this new environment, high diagnostic accuracy and cost-effective imaging will take on greater importance. Cardiac positron emission tomography (PET) is becoming a popular method of imaging the heart for a variety of conditions. Its role in cardiology has expanded with the increased availability of radiopharmaceuticals and PET camera systems and has the proven potential to deliver both high diagnostic accuracy and better utilization. This summary will describe the benefits of cardiovascular PET imaging, which could supersede the benefits of SPECT because of superior diagnostic accuracy leading to less downstream testing, improved spatial and temporal resolution, and the advantage of measuring regional blood flow, all while exposing the patient to less radiation.

In order for a noninvasive cardiac study to be effective, there should be confidence in the test because clinical decisions are based upon the results. Several studies have demonstrated a reduced rate of referral for diagnostic coronary imaging following PET as compared to SPECT. A study by Merhige and colleagues examined the cost effectiveness of Rb – 82 PET in terms of downstream angiography and revascularization utilization as compared to a SPECT patient matched group. In this study, the false positive rate at catheterization was reduced by 67%, the coronary artery bypass graft (CABG) utilization was reduced by 50%, and the treatment costs were reduced by 52%.3 Similar findings have been reported by Blankenstein and colleagues. In their analysis of their own referrals, there was decreased procedure utilization after diagnostic PET as compared to SPECT.4 Thus, although the initial test of PET may be more expensive than SPECT, it subsequently reduces overall health care costs by fewer retesting procedures. Beyond downstream testing, the authors of this Expert Analysis article believe that cardiac PET will continue to grow as the patient care model shifts from high volume to high value in the care delivery model. This will be elucidated through discussions of the role of cardiovascular PET imaging, diagnostic accuracy, patient safety via radiation reduction, and other uses of the procedure:

  • One of the advantages of PET imaging is its high temporal and spatial resolution. This is gained because of high-energy gamma rays (511 kEV vs. 140 for technetium) emitted at 180° angles from each other; the rays are absorbed by the detectors. The result is a superior diagnostic accuracy and risk stratification of obstructive coronary disease when compared to SPECT perfusion imaging. This has been demonstrated in several publications including a systematic review by Mc Ardle and colleagues, which demonstrated that the sensitivity and specificity utilizing Rb–82 was 90% and 88%, respectively, higher for comparable SPECT data.5 In a meta-analysis of 11,862 patients by Parker et al., PET myocardial perfusion imaging (MPI) demonstrated a higher sensitivity for coronary artery disease (CAD) than SPECT MPI.6 Additionally, PET has an important role in risk stratification. In a recent report by Dorbala et al., it was found that the extent and severity of ischemia and scar on PET MPI provided powerful and incremental risk estimates of cardiac death and all-cause death compared with traditional coronary risk factors.7

  • PET also has the ability to accurately evaluate regional and global myocardial blood flow and blood flow reserve. This is achieved by quantification of myocardial blood flow during the stress and the rest portion of the test, which offers an enhanced ability to delineate the extent and severity of CAD to the level of coronary circulation.8 The ability to quantify myocardial blood flow has been shown to have an incremental prognostic value for predicting adverse cardiac events.9 A study by Taqueti and colleagues found that myocardial blood flow was associated with outcomes independent of documented angiographic CAD, and in this study, myocardial blood flow modified the effect of early revascularization.10 In fact, those with normal blood flow and normal perfusion have extremely low risk for CAD. Furthermore, a recent study by Majmudar et al., demonstrated that those with impaired coronary vascular function as quantified by myocardial blood flow irrespective of ischemic versus non-ischemic cardiomyopathy have an increased incidence of major adverse cardiovascular events.11

  • Ionizing radiation exposure is an important consideration when ordering a diagnostic test. This has been a concern raised by both the American Society of Nuclear Cardiology (ASNC),12 as well as the American College of Cardiology. A think tank held on February 28, 2011 and led by Pamela S. Douglas, MD, MACC reported a consensus on several issues, including the need for collaboration amongst stakeholders and a better understanding of the relationship between medical radiation and stochastic events.13 Additionally, there was discussion of fostering a culture of safety by educating staff and physicians who utilize testing that requires radiation. One of the important advantages of PET in this context is the reduction in radiation dose compared to standard SPECT procedures. In a recent paper by the SPARC investigators, the level of radiation exposure was reported to be 6 mSv for PET versus 11.6 for mSv SPECT.14 Data from the Hopkins group demonstrates radiation exposure for Rubidium PET to be 0.9 mSv per 20 mCi, or approximately 3-5 mSv per patient.15,16 Lastly, a more recent review by Einstein17 reported PET perfusion imaging to be 2-3mSv. These data demonstrate that current PET imaging meets the goals reestablished by ASNC of less than 9 mSv per patient.12 This is clearly an important advantage of PET and should be emphasized when considering imaging that requires ionizing radiation.

  • Sarcoidosis is a systemic disease; its morbidity and mortality substantially increases when cardiac structures are affected. Approximately one quarter of sarcoidosis patients will have cardiac involvement. This can result in heart block, ventricular arrhythmias, and heart failure. Systemic steroid therapy is an important pharmacologic intervention in treating cardiac sarcoidosis by decreasing the progression of left ventricular dysfunction and potentially preventing fatal arrhythmias. Therefore, it behooves the provider to recognize cardiac sarcoidosis as quickly as possible. Until recently, this diagnosis was difficult to make non-invasively, and especially in the identification of active inflammation. Fluorine–18 fluorodexoglucose (FDG) PET is an important newer tool for the identification of cardiac sarcoidosis and inflammation. By demonstrating abnormal uptake of FDG, one can identify those patients at higher risk of cardiac death and ventricular arrhythmias. Patients with right ventricular involvement are at particular risk18 and, hence, have worse outcome.19 Exciting new studies also suggest that monitoring with FDG PET imaging can assess whether treatment strategies are successful.20

  • Heart failure is a growing health concern with a growing older population and improved rescue therapy for those with heart failure. In recent years, it has been demonstrated that hibernating and stunned myocardium may be improved through revascularization resulting in improved left ventricular function. PET myocardial viability is an important tool used to identify patients with hibernating and/or stunned myocardium that may benefit from undergoing cardiac revascularization. Utilizing PET FDG, metabolic active areas can be identified and, thus, direct the revascularization team to the appropriate patient and area of salvageable myocardium. By identifying appropriate areas for revascularization, there is an 80-85% chance of improved function following revascularization.21,22

  • Cardiac infections remain a diagnostic challenge. Although echocardiography remains the cornerstone in the diagnostic work-up, imaging using PET cameras is gaining use for the evaluation of infection and inflammation related to prosthetic valves or device implantation. In fact, adding abnormal FDG uptake to the modified Duke criteria increases the sensitivity from 70 to 97%.23 Similarly, several studies have demonstrated increased FDG uptake in patients who have infected implantable devices.24 Thus, one important new utility of PET may be the evaluation of implantable cardioverter-defibrillator infections, prosthetic valve infections or even graft infections for patients who have undergone CABG.

In summary, cardiac PET offers a wide diagnostic spectrum and utility with proven reduced downstream testing as well as reduced radiation exposure, making this test very appealing as a first line for the diagnosis of obstructive CAD and other conditions.

References

  1. Go AS, Mozaffarian D, Roger VL, et al. Heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation 2014;129:e28-e292.
  2. Berwick DM. Launching accountable care organizations--the proposed rule for the Medicare Shared Savings Program. N Engl J Med 2011;364:e32.
  3. Merhige ME, Breen WJ, Shelton V, Houston T, D'Arcy BJ, Perna AF. Impact of myocardial perfusion imaging with PET and (82)Rb on downstream invasive procedure utilization, costs, and outcomes in coronary disease management. J Nucl Med 2007;48:1069-76.
  4. Blankenstein J, McArdle B, Small G, et al. Reduced rate of diagnostic coronary imaging following Rubidium PET vs Thallium SPECT, as alternatives to Technetium SPECT myocardial perfusion imaging. J Nucl Med 2013;54(Supplement 2):1735.
  5. Mc Ardle BA, Dowsley TF, deKemp RA, Wells GA, Beanlands RS. Does rubidium-82 PET have superior accuracy to SPECT perfusion imaging for the diagnosis of obstructive coronary disease?: A systematic review and meta-analysis. J Am Coll Cardiol 2012;60:1828-37.
  6. Parker MW, Iskandar A, Limone B, et al. Diagnostic accuracy of cardiac positron emission tomography versus single photon emission computed tomography for coronary artery disease: a bivariate meta-analysis. Circ Cardiovasc Imaging 2012;5:700-7.
  7. Dorbala S, Di Carli MF, Beanlands RS, et al. Prognostic value of stress myocardial perfusion positron emission tomography: results from a multicenter observational registry. J Am Coll Cardiol 2013;61:176-84.
  8. Schelbert HR. Positron emission tomography measurements of myocardial blood flow: assessing coronary circulatory function and clinical implications. Heart 2012;98:592-600.
  9. Ziadi MC, deKemp RA, Williams KA, et al. Impaired myocardial flow reserve on rubidium-82 positron emission tomography imaging predicts adverse outcomes in patients assessed for myocardial ischemia. J Am Coll Cardiol 2011;58:740-8.
  10. Taqueti VR, Hachamovitch R, Murthy VL, et al. Global coronary flow reserve is associated with adverse cardiovascular events independently of luminal angiographic severity and modifies the effect of early revascularization. Circulation 2015;131:19-27.
  11. Majmudar MD, Murthy VL, Shah RV, et al. Quantification of coronary flow reserve in patients with ischaemic and non-ischaemic cardiomyopathy and its association with clinical outcomes. Eur Heart J Cardiovasc Imaging 2015 Feb 25. [Epub ahead of print]
  12. Cerqueira MD, Allman KC, Ficaro EP, et al. Recommendations for reducing radiation exposure in myocardial perfusion imaging. J Nucl Cardiol 2010;17:709-18.
  13. Douglas PS, Carr JJ, Cerqueira MD, et al. Developing an action plan for patient radiation safety in adult cardiovascular medicine: proceedings from the Duke University Clinical Research Institute/American College of Cardiology Foundation/American Heart Association Think Tank Held on February 28, 2011. J Am Coll Cardiol 2012;59:1833-47.
  14. Hlatky MA, Shilane D, Hachamovitch R, Dicarli MF. Economic outcomes in the study of myocardial perfusion and coronary anatomy imaging roles in coronary artery disease registry: the SPARC study. J Am Coll Cardiol 2014;63:1002-8.
  15. Senthamizhchelvan S, Bravo PE, Esaias C, et al. Human biodistribution and radiation dosimetry of 82Rb. J Nucl Med 2010;51:1592-9.
  16. Senthamizhchelvan S, Bravo PE, Lodge MA, Merrill J, Bengel FM, Sgouros G. Radiation dosimetry of 82Rb in humans under pharmacologic stress. J Nucl Med 2011;52:485-91.
  17. Einstein AJ. Effects of radiation exposure from cardiac imaging: how good are the data? J Am Coll Cardiol 2012;59:553-65.
  18. Manabe O, Yoshinaga K, Ohira H, et al. Right ventricular (18)F-FDG uptake is an important indicator for cardiac involvement in patients with suspected cardiac sarcoidosis. Ann Nucl Med 2014;28:656-63.
  19. Blankstein R, Osborne M, Naya M, et al. Cardiac positron emission tomography enhances prognostic assessments of patients with suspected cardiac sarcoidosis. J Am Coll Cardiol 2014;63:329-36.
  20. Blankstein R, Osborne M, Naya M, et al. Cardiac positron emission tomography enhances prognostic assessments of patients with suspected cardiac sarcoidosis. J Am Coll Cardiol 2014;63:329-36.
  21. Lucignani G, Paolini G, Landoni C, et al. Presurgical identification of hibernating myocardium by combined use of technetium-99m hexakis 2-methoxyisobutylisonitrile single photon emission tomography and fluorine-18 fluoro-2-deoxy-D-glucose positron emission tomography in patients with coronary artery disease. Eur J Nucl Med 1992;19:874-81.
  22. Tamaki N, Kawamoto M, Tadamura E, et al. Prediction of reversible ischemia after revascularization. Perfusion and metabolic studies with positron emission tomography. Circulation 1995;91:1697-705.
  23. Saby L, Laas O, Habib G, et al. Positron emission tomography/computed tomography for diagnosis of prosthetic valve endocarditis: increased valvular 18F-fluorodeoxyglucose uptake as a novel major criterion. J Am Coll Cardiol 2013;61:2374-82.
  24. Sarrazin JF, Philippon F, Tessier M, et al. Usefulness of fluorine-18 positron emission tomography/computed tomography for identification of cardiovascular implantable electronic device infections. J Am Coll Cardiol 2012;59:1616-25.

Clinical Topics: Arrhythmias and Clinical EP, Cardiac Surgery, Heart Failure and Cardiomyopathies, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Implantable Devices, SCD/Ventricular Arrhythmias, Atrial Fibrillation/Supraventricular Arrhythmias, Cardiac Surgery and Arrhythmias, Cardiac Surgery and Heart Failure, Acute Heart Failure, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Computed Tomography, Echocardiography/Ultrasound, Nuclear Imaging

Keywords: Accountable Care Organizations, Arrhythmias, Cardiac, Cardiomyopathies, Catheterization, Cicatrix, Consensus, Cooperative Behavior, Coronary Angiography, Coronary Artery Bypass, Coronary Artery Disease, Coronary Circulation, Cost-Benefit Analysis, Defibrillators, Implantable, Diagnostic Tests, Routine, Echocardiography, Fluorine, Gamma Rays, Goals, Health Care Costs, Heart, Heart Block, Heart Failure, Incidence, Inflammation, Myocardial Perfusion Imaging, Myocardial Stunning, Myocardium, Patient Care, Patient Safety, Positron-Emission Tomography, Radiopharmaceuticals, Referral and Consultation, Regional Blood Flow, Epidemiologic Research Design, Research Personnel, Risk Factors, Rubidium, Sarcoidosis, Technetium, Tomography, Emission-Computed, Single-Photon, Ventricular Dysfunction, Left, Ventricular Function, Left, Diagnostic Imaging


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