REVIEW ARTICLE Proceedings of the ASNC Cardiac PET Summit, 12 May 2014, Baltimore, MD 1: The value of PET: Integrating cardiovascular PET into the care continuum Rob Beanlands, MD,a and Gary V. Heller, MD, PhDb a b
Department of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada Gagnon Cardiovascular Institite, Morristown Medical Center, Morristown, NJ
Received Jan 30, 2015; accepted Mar 10, 2015 doi:10.1007/s12350-015-0129-0
INTRODUCTION Cardiac nuclear imaging includes widely applied and accurate methods for detection and risk stratification of patients with known or suspected coronary artery disease. Nuclear myocardial perfusion imaging (MPI) methods include SPECT and PET MPI. SPECT MPI is widely applied and accompanied by a wealth of data to support its routine use. Cardiac PET including PET MPI has not been as widely applied but has been recognized for many years as an accurate imaging modality with particular advantages over other functional imaging approaches. Its implementation has lagged due to logistics, cost issues, as well as misunderstandings of the value of cardiac PET. As medical imaging moves from volume-to-value-based strategies, the true importance of cardiac PET imaging in the Nuclear Cardiology arena is expected to become more important. This document summarizes a presentation made at the ASNC Cardiac PET Summit meeting, Baltimore MD, on 12 May 2014 and will highlight the clinical value of cardiac PET as it is currently performed. Data supporting its use will include both MPI strategies and assessment of myocardial viability.
Reprint requests: Gary V. Heller, MD, PhD, Gagnon Cardiovascular Institite, Morristown Medical Center, Morristown, NJ; [email protected] J Nucl Cardiol 2015;22:557–62. 1071-3581/$34.00 Copyright Ó 2015 American Society of Nuclear Cardiology.
STRENGTHS OF CARDIAC PET PERFUSION IMAGING Diagnostic Accuracy Current literature supports a high diagnostic accuracy for cardiac PET perfusion imaging. The reasons for this are multiple and include robust attenuation correction, high count densities for excellent image quality and interpretation as well as tracers that follow myocardial blood flow (MBF) in a more linear fashion than current SPECT tracers. Evidence has been accumulating for both a high sensitivity and specificity for cardiac PET.1-4 A meta-analysis of the cardiac PET literature performed by Nandalur and colleagues demonstrated a sensitivity (92%) and specificity (85%) for the detection of coronary artery disease, which was based upon data from both rubidium-82 and ammonia N-13.1 Two recent metaanalyses comparing both rubidium-82 and ammonia N-13 PET data to SPECT (primarily technetium-99m based SPECT) confirmed the diagnostic accuracy. Both demonstrated higher diagnostic accuracy for PET with a 3-5% increase in specificity and 4-5% increase in sensitivity, see Figures 1 and 2.2,3 that were statistically significant. Data from Bateman and colleagues, in a clinical comparison between rubidium-82 PET and technetium-99m sestamibi SPECT in patients undergoing cardiac catheterization, suggested that the high accuracy was independent of both gender and body habitus.4 Risk Stratification A recognized strength of cardiac SPECT imaging is the wealth of data regarding risk stratification in over 100,000 patients and the ability to assist physicians in decision-making. Data are now accumulating for cardiac 557
558
Beanlands and Heller The value of PET
Journal of Nuclear CardiologyÒ May/June 2015
Figure 1. Systematic review and meta-analysis comparison of diagnostic accuracy between gated technetium-99m-based SPECT with attenuation correction and rubidium-82 PET (with permission from McArdle et al.2).
Myocardial Blood Flow Quantitation
Figure 2. Meta-analysis comparison of diagnostic accuracy between SPECT and rubidium-82/Ammonia-NH-13 PET (with permission from Parker et al.3).
PET risk stratification as well, demonstrating that the size and severity of perfusion abnormalities are important as well as decreased ejection fraction at stress and overall ventricular function in identifying high-risk patients.5-9 A recent study from multiple institutions has confirmed the prognostic value of PET imaging results in the largest accumulation of patients to date (over 7000).9 This study demonstrated abnormal PET perfusion defect size and severity predicts outcomes for both cardiac death and allcause mortality in both genders, see Figure 3.
The ability to non-invasively assess regional and global changes in MBF is currently unique to cardiac PET. Measurement of MBF is available for both rubidium-82 and ammonia-NH-13 tracers in North America (water-O-15 is also used in Europe). Software for evaluating MBF has moved into the clinical nuclear cardiology laboratory and is providing physicians with important diagnostic and prognostic information.10,11 High accuracy compared to fractional flow reserve (FFR) has also been reported.12 Studies reported on large databases indicate the following: best prognosis is in patients with normal blood flow and flow reserve, while the worst outcomes from a cardiovascular endpoint perspective are those with severe reduction in blood flow and flow reserve.10,11 Data from Murthy and colleagues11 demonstrate that blood flow abnormality places patients in higher-risk categories for cardiac events, including those with normal perfusion. These data, as well as other studies imply that a patient with normal perfusion and normal blood flow reserve have a very low likelihood of obstructive CAD and cardiovascular events. More detailed discussion of flow quantification is considered in paper 2 in this Summit Series.
Journal of Nuclear CardiologyÒ Volume 22, Number 3;557–62
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Figure 3. Prognostic value of stress myocardial perfusion positron emission tomography: Results from a multicenter observational registry (with permission from Dorbala et al.9).
Radiation Exposure Radiation exposure has become an important aspect of all procedures which utilize ionizing radiation, including x-ray, CT, and nuclear imaging. Efforts are being made on a national level to encourage reduction of radiation exposure in individual patients by reducing the number of repeat studies, reducing the dose of radiotracers administered and using new imaging technologies to accomplish those goals. An information statement from ASNC has recommended at least 50 % of patients in a given laboratory receive \9 mSv for a routine study.13 This recommendation can be accomplished in the SPECT laboratory using newer camera technologies, processing procedures, and stress-only protocols. The radiation exposure for both available PET flow tracers has been examined and has demonstrated that patient exposure is below that recommended by ASNC.13 In a series of studies with rubidium-82, Senthamizhchelvan et al determined the radiation dose to be 0.9 mSv per 20 mCi.14,15 For an individual patient, radiation exposure for rest/stress rubidium-82 ranges from 2 to 5.4 mSv, depending upon camera systems and tracer dose. Recent trends from 2D to 3D imaging promise further radiation reduction. Radiation exposure for NH-13 ammonia is 46 mSv, and for FDG-PET studies 5-7 mSv.16 Hunter and colleagues also compared radiation exposure in an average 75 kg person.17 They found significant reductions using rubidium-82 PET in their laboratory compared with reported radiation exposure for traditional
thallium-201 and Tc-99m SPECT.17 In summary, all available PET tracers are associated with low radiation exposure that is within ASNC recommendations.13 Downstream Testing Confidence Recognized strengths of cardiac PET are superior image quality, greater count density, and robust attenuation correction. This has provided greater confidence in the interpretation of normal/abnormal scans and predicting the presence of CAD vs attenuation artifact as demonstrated by Bateman et al.4 In turn, this has resulted in greater referring physician confidence in the interpretations. The downstream effect is referral to catheterization for consideration for potential revascularization rather than to confirm diagnosis. Studies have demonstrated fewer catheterizations following PET compared to SPECT studies, but a higher percentage of those who do undergo the procedure are referred for CABG/PCI, see Figure 4.17,18
Patient Satisfaction/Protocols Because of greater count density and shorter halflives, rapid protocols are routinely available for PET MPI. Rest/stress rubidium-82 protocols can be accomplished in 30-45 minutes, while with ammonia-NH-13 within an hour. Although standard rest/stress SPECT protocols generally require 3-4 hours for completion, using newer SPECT cameras (CZT) and protocols such as stress-only imaging in selected patients can also
560
Beanlands and Heller The value of PET
Journal of Nuclear CardiologyÒ May/June 2015
Figure 4. Cardiac catherization and revascularization following SPECT or PET imaging (with permission from Merhige et al.18).
substantially reduce procedure time, often to less than 1 hours. These shorter protocols are of benefit to both patients and laboratory efficiency. VALUE PROPOSITION FOR CARDIAC PET A major issue confronting the implementation of wide scale use and acceptance of cardiac PET is appropriate payment for the procedures. While CMS has consistently paid for rest/stress rubidium-82 studies, many insurance companies do not. The two most common cardiac PET reimbursements (and sometimes the only) are for obese patients ([30 BMI) and inconclusive SPECT studies. This excludes many commonly accepted indications for SPECT, such as chest pain, preoperative evaluation and others, unless the patient either first has a SPECT study or meets body habitus requirement. The reasons for such restrictions seems to be a limited understanding of the benefits of cardiac PET and the fact that the individual PET procedures are more costly than SPECT, and stress echo. Similarly, in Canada, efforts have been made to adjust the funding for perfusion imaging using PET to meet the added costs to deliver the value-added features of higher accuracy, prognostic value, low radiation exposure, and improved patient experience. In the province of Ontario a proposal has been submitted to the Ontario Ministry of Health and Long Term Care for a payment structure that would enable greater access to cardiac PET in this Province. This proposal has been
reviewed and is supported by the PET Steering Committee of Cancer Care Ontario, the Cardiac Care Network of Ontario, the Ontario Medical Association Nuclear Medicine Section and the Ontario Association of Nuclear Medicine. It is also proposed that the use of PET would be part of a broader strategy for all nuclear imaging to improve appropriate use, quality, radiation reduction, and accuracy of nuclear imaging. The arguments in support of cardiac PET included reduced inconclusive results reduced false-positive and falsenegative results, low radiation exposure, and patient convenience. STRENGTHS OF CARDIAC PET MYOCARDIAL VIABILITY ASSESSMENT Myocardial viability assessment for patients being considered, particularly for CABG, has been a mainstay in the decision to proceed with the intervention. However, this approach recently came under scrutiny based on data from the STICH trial.19 In this prospective trial, while viability was predictive of outcome, it was not independent of other parameters and it was not dependent on revascularization. Myocardial viability determination methods included thallium-201 or technetium-99m based SPECT.19 Myocardial viability assessment with PET, in the form of FDG imaging, is unique in the nuclear realm in view of the fact that it measures metabolism, not perfusion. The best predictor from FDG imaging is a ‘‘mismatch’’ in which perfusion assessment does not
Journal of Nuclear CardiologyÒ Volume 22, Number 3;557–62
show viability, but glucose uptake in the same area does, indicating myocardial hibernation. FDG imaging was not part of the STICH trial, and because of its mechanism, may demonstrate added value not seen with perfusion agents alone. As well, the STICH trial included patients with good vessel targets that were candidates for surgery. The patients in STICH also had low rates of some comorbidities such as renal dysfunction and prior CABG compared to trials such as PARR-2.20-22 However, myocardial viability is most appropriate in patients where decisions for revascularization are difficult such as those with mediocre targets and co-morbidities such as r renal dysfunction, and prior CABG. Several prospective studies conducted in a multicenter format have demonstrated the value of FDG-PET imaging for viability assessment.21-23 These data suggest that FDG-PET imaging is a very useful tool for assessment of myocardial viability and is currently being used in several centers in the United States, Canada and Europe. Data from ongoing trials such as IMAGE HF will further define its role.23 SUMMARY: WHAT IS NEEDED NOW? The application and acceptance of Cardiac PET imaging has been increasing in North America. This presentation outlined several reasons for this including: high diagnostic accuracy, excellent image quality, short protocols, low radiation exposure, and potentially more effective use of downstream testing. In spite of these value adds, the adoption may be slower than one may expect and there are some jurisdictions reluctant for broader adoption. So, what is needed for wider translation of cardiac PET into clinical practice? (i) Broad based initiatives that will emphasize quality and value add for patients, appropriate use of all nuclear testing and adopting strategies which improve accuracy, interpretative certainty, lower radiation, and the patient experience Such strategies should include greater implementation of PET as well as newer SPECT technologies. (ii) Defining the full clinical value of flow quantification to enable its broad clinical use and determine: a. Its role in microvascular disease detection with or without obstructive CAD. b. Its role in guiding treatment and responses to therapies. (iii) Determination of whether exercise PET is possible with F-18 agents such as F-18-Flurpiridaz, BFPET. (iv) Enhanced Guidelines and Standardization that integrate imaging approaches for clinical decisions, supported by best evidence and new indications such as flow quantification and inflammation imaging.
Beanlands and Heller The value of PET
561
While PET cannot and should not be expected to replace SPECT and other techniques, it is reasonable, given its value add, to enable it to be part of strategies in Nuclear Cardiology to improve quality, radiation reduction and accuracy (for disease and ischemia detection and risk stratification) toward patient-centered care. Wider implementation of PET (and also newer SPECT imaging approaches) will enable nuclear imaging to achieve the value that patients, clinicians and payers seek to achieve for the best decision-making possible to direct patients to the best treatments and achieve the best outcomes and quality of life.
References 1. Nandular KR, Dwamena BA, Choudhri AF, Nandalur SR, Reddy P, Carlos RC. Diagnostic performance of positron emission tomography in the detection of coronary artery disease: A metaanalysis. Acad Radiol. 2008;15:444-51. 2. McArdle BA, Dowsley TF, deKemp RA, Wells GA, Beanlands RS. Does Rubidium-82 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. 3. Parker MW, Iskandar A, Limone B, Perugini A, Kim H, Jones C, 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. 4. Bateman T, Heller GV, McGhie I, Friedman JD, Case JA, Bryngelson JR, et al. Diagnostic accuracy of rest/stress ECG-gated rubidium-82 myocardial perfusion PET: Comparison with ECGgated Tc-99m-sestamibi SPECT. J Nucl Cardiol. 2006;12:24-33. 5. Yoshinaga K, Chow BJW, Williams K, Chen L, de Kemp RA, Garrard L, et al. What is the prognostic value of myocardial perfusion imaging using rubidium-82 positron emission tomography? J Am Coll Cardiol. 2006;48:1029-39. 6. Dorbala S, Dorbala H, Hachamovitch R, Cunillova Z, Thomas D, Vangala D, et al. Incremental prognostic value of gated Rb-82 positron emission tomography myocardial perfusion imaging over clinical variables and rest LVEF. J Am Coll Cardiol Imaging. 2009;2:846-54. 7. Marwick TH, Shan K, Patel S, Go RT, Lauer MS. Incremental value of rubidium-82 positron emission tomography for prognostic assessment of known or suspected coronary artery disease. Am J Cardiol. 1997;80:865-70. 8. Lertsburapa K, Ahlberg AW, Bateman TM, Katten D, Volker L, Cullom SJ, et al. Independent and incremental prognostic value of left ventricular ejection fraction determined by stress gated rubidium 82 PET imaging in patients with known or suspected coronary artery disease. J Nucl Cardiol. 2008;15:745-53. 9. Dorbala S, DiCarli MF, Beanlands RS, Merhige ME, Williams BA, Veledar E, et al. Prognostic value of stress myocardial perfusion positron emission tomography. J Am Coll Cardiol. 2013;61:176-84. 10. Ziadi MC, deKemp RA, Williams KA, Guo A, Chow BJ, Renaud JM, 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.
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11. Murthy VL, Naya M, Foster CR, Hainer J, Gaber M, Di Carli G, et al. Improved cardiac risk assessment with noninvasive measures of coronary flow reserve. Circulation. 2011;124:2215-24. 12. Kajander S, Joutsiniemi E, Saraste M, Pietila M, Ukkonen H, Saraste A, et al. Cardiac positron emission tomography/computed tomography imaging accurately detects anatomically and functionally significant coronary artery disease. Circulation. 2010;122:603-13. 13. Cerqueira MD, Allman KC, Ficaro EP, Hansen CL, Nichols KJ, Thompson RC. Recommendations for reducing radiation exposure in myocardial perfusion imaging. J Nucl Cardiol. 2010;17:709-18. 14. Senthamizhchelvan S, Bravo PE, Esaias C, Lodge MA, Merrill J, Hobbs RF, et al. Human biodistribution and radiation dosimetry of 82 Rb. J Nucl Med. 2010;51:1592-9. 15. Senthamizhchelvan S, Bravo PE, Lodge MA, Merrill J, Bengel FM, Sgouros G, et al. Radiation dosimetry of 82Rb in humans under pharmacologic stress. J Nucl Med. 2011;52:485-91. 16. Einstein AJ. Effects of radiation exposure from cardiac imaging: How good are the data? J Am Coll Cardiol. 2012;59:553-65. 17. Hunter CRRN, Hill J, Ziadi MC, Beanlands RSB, deKemp RA. Biodistribution and radiation dosimetry of 82Rb at rest and during peak pharmacological stress in patients referred for myocardial perfusion imaging. Eur J Nucl Med Mol Imaging. 2015. doi: 10.1007/s00259-015-3028-3. 18. 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.
Journal of Nuclear CardiologyÒ May/June 2015
19. Bonow RO, Maurer G, Lee KL, Holly TA, Binkley RF, DesvigneNickens P, et al. Myocardial viability and survival in ischemic left ventricular dysfunction. N Engl J Med. 2011;364:1617-25. 20. Mielniczuk LM, Beanlands RS. Does imaging-guided selection of patients with ischemic heart failure for high risk revascularization improve identification of those with the highest clinical benefit? Imaging-guided selection of patients with ischemic heart failure for high-risk revascularization improves identification of those with the highest clinical benefit. Circ Cardiovasc Imaging. 2012;5:262-70. 21. Beanlands RSB, Nichol G, Huszti E, Humen D, Racine N, Freeman M, et al. F-18-fluorodeoxyglucose positron emission tomography imaging-assisted management of patients with severe left ventricular dysfunction and suspected coronary disease. A randomized controlled trial (PARR-2). J Am Coll Cardiol. 2007;50:2002-12. 22. Ling LF, Marwick TH, Flores DR, Jaber WA, Brunken RC, Cerqueira MD, et al. Identification of therapeutic benefit from revascularization in patients with left ventricular systolic dysfunction: Inducible ischemia versus hibernating myocardium. Circ Cardiovasc Imaging. 2013;6:363-72. 23. O’Meara E, Mielniczuk LM, Wells GA, deKemp RA, Klein R, Coyle D, et al. Alternative imaging modalities in ischemic heart failure (AIMI-HF) IMAGE HF Project I-A: Study protocol for a randomized controlled trial. Trials. 2013;14:218.
Department of Cardiology, University of Ottawa Heart Institute, Ottawa, ON, Canada Gagnon Cardiovascular Institite, Morristown Medical Center, Morristown, NJ
Received Jan 30, 2015; accepted Mar 10, 2015 doi:10.1007/s12350-015-0129-0
INTRODUCTION Cardiac nuclear imaging includes widely applied and accurate methods for detection and risk stratification of patients with known or suspected coronary artery disease. Nuclear myocardial perfusion imaging (MPI) methods include SPECT and PET MPI. SPECT MPI is widely applied and accompanied by a wealth of data to support its routine use. Cardiac PET including PET MPI has not been as widely applied but has been recognized for many years as an accurate imaging modality with particular advantages over other functional imaging approaches. Its implementation has lagged due to logistics, cost issues, as well as misunderstandings of the value of cardiac PET. As medical imaging moves from volume-to-value-based strategies, the true importance of cardiac PET imaging in the Nuclear Cardiology arena is expected to become more important. This document summarizes a presentation made at the ASNC Cardiac PET Summit meeting, Baltimore MD, on 12 May 2014 and will highlight the clinical value of cardiac PET as it is currently performed. Data supporting its use will include both MPI strategies and assessment of myocardial viability.
Reprint requests: Gary V. Heller, MD, PhD, Gagnon Cardiovascular Institite, Morristown Medical Center, Morristown, NJ; [email protected] J Nucl Cardiol 2015;22:557–62. 1071-3581/$34.00 Copyright Ó 2015 American Society of Nuclear Cardiology.
STRENGTHS OF CARDIAC PET PERFUSION IMAGING Diagnostic Accuracy Current literature supports a high diagnostic accuracy for cardiac PET perfusion imaging. The reasons for this are multiple and include robust attenuation correction, high count densities for excellent image quality and interpretation as well as tracers that follow myocardial blood flow (MBF) in a more linear fashion than current SPECT tracers. Evidence has been accumulating for both a high sensitivity and specificity for cardiac PET.1-4 A meta-analysis of the cardiac PET literature performed by Nandalur and colleagues demonstrated a sensitivity (92%) and specificity (85%) for the detection of coronary artery disease, which was based upon data from both rubidium-82 and ammonia N-13.1 Two recent metaanalyses comparing both rubidium-82 and ammonia N-13 PET data to SPECT (primarily technetium-99m based SPECT) confirmed the diagnostic accuracy. Both demonstrated higher diagnostic accuracy for PET with a 3-5% increase in specificity and 4-5% increase in sensitivity, see Figures 1 and 2.2,3 that were statistically significant. Data from Bateman and colleagues, in a clinical comparison between rubidium-82 PET and technetium-99m sestamibi SPECT in patients undergoing cardiac catheterization, suggested that the high accuracy was independent of both gender and body habitus.4 Risk Stratification A recognized strength of cardiac SPECT imaging is the wealth of data regarding risk stratification in over 100,000 patients and the ability to assist physicians in decision-making. Data are now accumulating for cardiac 557
558
Beanlands and Heller The value of PET
Journal of Nuclear CardiologyÒ May/June 2015
Figure 1. Systematic review and meta-analysis comparison of diagnostic accuracy between gated technetium-99m-based SPECT with attenuation correction and rubidium-82 PET (with permission from McArdle et al.2).
Myocardial Blood Flow Quantitation
Figure 2. Meta-analysis comparison of diagnostic accuracy between SPECT and rubidium-82/Ammonia-NH-13 PET (with permission from Parker et al.3).
PET risk stratification as well, demonstrating that the size and severity of perfusion abnormalities are important as well as decreased ejection fraction at stress and overall ventricular function in identifying high-risk patients.5-9 A recent study from multiple institutions has confirmed the prognostic value of PET imaging results in the largest accumulation of patients to date (over 7000).9 This study demonstrated abnormal PET perfusion defect size and severity predicts outcomes for both cardiac death and allcause mortality in both genders, see Figure 3.
The ability to non-invasively assess regional and global changes in MBF is currently unique to cardiac PET. Measurement of MBF is available for both rubidium-82 and ammonia-NH-13 tracers in North America (water-O-15 is also used in Europe). Software for evaluating MBF has moved into the clinical nuclear cardiology laboratory and is providing physicians with important diagnostic and prognostic information.10,11 High accuracy compared to fractional flow reserve (FFR) has also been reported.12 Studies reported on large databases indicate the following: best prognosis is in patients with normal blood flow and flow reserve, while the worst outcomes from a cardiovascular endpoint perspective are those with severe reduction in blood flow and flow reserve.10,11 Data from Murthy and colleagues11 demonstrate that blood flow abnormality places patients in higher-risk categories for cardiac events, including those with normal perfusion. These data, as well as other studies imply that a patient with normal perfusion and normal blood flow reserve have a very low likelihood of obstructive CAD and cardiovascular events. More detailed discussion of flow quantification is considered in paper 2 in this Summit Series.
Journal of Nuclear CardiologyÒ Volume 22, Number 3;557–62
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Figure 3. Prognostic value of stress myocardial perfusion positron emission tomography: Results from a multicenter observational registry (with permission from Dorbala et al.9).
Radiation Exposure Radiation exposure has become an important aspect of all procedures which utilize ionizing radiation, including x-ray, CT, and nuclear imaging. Efforts are being made on a national level to encourage reduction of radiation exposure in individual patients by reducing the number of repeat studies, reducing the dose of radiotracers administered and using new imaging technologies to accomplish those goals. An information statement from ASNC has recommended at least 50 % of patients in a given laboratory receive \9 mSv for a routine study.13 This recommendation can be accomplished in the SPECT laboratory using newer camera technologies, processing procedures, and stress-only protocols. The radiation exposure for both available PET flow tracers has been examined and has demonstrated that patient exposure is below that recommended by ASNC.13 In a series of studies with rubidium-82, Senthamizhchelvan et al determined the radiation dose to be 0.9 mSv per 20 mCi.14,15 For an individual patient, radiation exposure for rest/stress rubidium-82 ranges from 2 to 5.4 mSv, depending upon camera systems and tracer dose. Recent trends from 2D to 3D imaging promise further radiation reduction. Radiation exposure for NH-13 ammonia is 46 mSv, and for FDG-PET studies 5-7 mSv.16 Hunter and colleagues also compared radiation exposure in an average 75 kg person.17 They found significant reductions using rubidium-82 PET in their laboratory compared with reported radiation exposure for traditional
thallium-201 and Tc-99m SPECT.17 In summary, all available PET tracers are associated with low radiation exposure that is within ASNC recommendations.13 Downstream Testing Confidence Recognized strengths of cardiac PET are superior image quality, greater count density, and robust attenuation correction. This has provided greater confidence in the interpretation of normal/abnormal scans and predicting the presence of CAD vs attenuation artifact as demonstrated by Bateman et al.4 In turn, this has resulted in greater referring physician confidence in the interpretations. The downstream effect is referral to catheterization for consideration for potential revascularization rather than to confirm diagnosis. Studies have demonstrated fewer catheterizations following PET compared to SPECT studies, but a higher percentage of those who do undergo the procedure are referred for CABG/PCI, see Figure 4.17,18
Patient Satisfaction/Protocols Because of greater count density and shorter halflives, rapid protocols are routinely available for PET MPI. Rest/stress rubidium-82 protocols can be accomplished in 30-45 minutes, while with ammonia-NH-13 within an hour. Although standard rest/stress SPECT protocols generally require 3-4 hours for completion, using newer SPECT cameras (CZT) and protocols such as stress-only imaging in selected patients can also
560
Beanlands and Heller The value of PET
Journal of Nuclear CardiologyÒ May/June 2015
Figure 4. Cardiac catherization and revascularization following SPECT or PET imaging (with permission from Merhige et al.18).
substantially reduce procedure time, often to less than 1 hours. These shorter protocols are of benefit to both patients and laboratory efficiency. VALUE PROPOSITION FOR CARDIAC PET A major issue confronting the implementation of wide scale use and acceptance of cardiac PET is appropriate payment for the procedures. While CMS has consistently paid for rest/stress rubidium-82 studies, many insurance companies do not. The two most common cardiac PET reimbursements (and sometimes the only) are for obese patients ([30 BMI) and inconclusive SPECT studies. This excludes many commonly accepted indications for SPECT, such as chest pain, preoperative evaluation and others, unless the patient either first has a SPECT study or meets body habitus requirement. The reasons for such restrictions seems to be a limited understanding of the benefits of cardiac PET and the fact that the individual PET procedures are more costly than SPECT, and stress echo. Similarly, in Canada, efforts have been made to adjust the funding for perfusion imaging using PET to meet the added costs to deliver the value-added features of higher accuracy, prognostic value, low radiation exposure, and improved patient experience. In the province of Ontario a proposal has been submitted to the Ontario Ministry of Health and Long Term Care for a payment structure that would enable greater access to cardiac PET in this Province. This proposal has been
reviewed and is supported by the PET Steering Committee of Cancer Care Ontario, the Cardiac Care Network of Ontario, the Ontario Medical Association Nuclear Medicine Section and the Ontario Association of Nuclear Medicine. It is also proposed that the use of PET would be part of a broader strategy for all nuclear imaging to improve appropriate use, quality, radiation reduction, and accuracy of nuclear imaging. The arguments in support of cardiac PET included reduced inconclusive results reduced false-positive and falsenegative results, low radiation exposure, and patient convenience. STRENGTHS OF CARDIAC PET MYOCARDIAL VIABILITY ASSESSMENT Myocardial viability assessment for patients being considered, particularly for CABG, has been a mainstay in the decision to proceed with the intervention. However, this approach recently came under scrutiny based on data from the STICH trial.19 In this prospective trial, while viability was predictive of outcome, it was not independent of other parameters and it was not dependent on revascularization. Myocardial viability determination methods included thallium-201 or technetium-99m based SPECT.19 Myocardial viability assessment with PET, in the form of FDG imaging, is unique in the nuclear realm in view of the fact that it measures metabolism, not perfusion. The best predictor from FDG imaging is a ‘‘mismatch’’ in which perfusion assessment does not
Journal of Nuclear CardiologyÒ Volume 22, Number 3;557–62
show viability, but glucose uptake in the same area does, indicating myocardial hibernation. FDG imaging was not part of the STICH trial, and because of its mechanism, may demonstrate added value not seen with perfusion agents alone. As well, the STICH trial included patients with good vessel targets that were candidates for surgery. The patients in STICH also had low rates of some comorbidities such as renal dysfunction and prior CABG compared to trials such as PARR-2.20-22 However, myocardial viability is most appropriate in patients where decisions for revascularization are difficult such as those with mediocre targets and co-morbidities such as r renal dysfunction, and prior CABG. Several prospective studies conducted in a multicenter format have demonstrated the value of FDG-PET imaging for viability assessment.21-23 These data suggest that FDG-PET imaging is a very useful tool for assessment of myocardial viability and is currently being used in several centers in the United States, Canada and Europe. Data from ongoing trials such as IMAGE HF will further define its role.23 SUMMARY: WHAT IS NEEDED NOW? The application and acceptance of Cardiac PET imaging has been increasing in North America. This presentation outlined several reasons for this including: high diagnostic accuracy, excellent image quality, short protocols, low radiation exposure, and potentially more effective use of downstream testing. In spite of these value adds, the adoption may be slower than one may expect and there are some jurisdictions reluctant for broader adoption. So, what is needed for wider translation of cardiac PET into clinical practice? (i) Broad based initiatives that will emphasize quality and value add for patients, appropriate use of all nuclear testing and adopting strategies which improve accuracy, interpretative certainty, lower radiation, and the patient experience Such strategies should include greater implementation of PET as well as newer SPECT technologies. (ii) Defining the full clinical value of flow quantification to enable its broad clinical use and determine: a. Its role in microvascular disease detection with or without obstructive CAD. b. Its role in guiding treatment and responses to therapies. (iii) Determination of whether exercise PET is possible with F-18 agents such as F-18-Flurpiridaz, BFPET. (iv) Enhanced Guidelines and Standardization that integrate imaging approaches for clinical decisions, supported by best evidence and new indications such as flow quantification and inflammation imaging.
Beanlands and Heller The value of PET
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While PET cannot and should not be expected to replace SPECT and other techniques, it is reasonable, given its value add, to enable it to be part of strategies in Nuclear Cardiology to improve quality, radiation reduction and accuracy (for disease and ischemia detection and risk stratification) toward patient-centered care. Wider implementation of PET (and also newer SPECT imaging approaches) will enable nuclear imaging to achieve the value that patients, clinicians and payers seek to achieve for the best decision-making possible to direct patients to the best treatments and achieve the best outcomes and quality of life.
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19. Bonow RO, Maurer G, Lee KL, Holly TA, Binkley RF, DesvigneNickens P, et al. Myocardial viability and survival in ischemic left ventricular dysfunction. N Engl J Med. 2011;364:1617-25. 20. Mielniczuk LM, Beanlands RS. Does imaging-guided selection of patients with ischemic heart failure for high risk revascularization improve identification of those with the highest clinical benefit? Imaging-guided selection of patients with ischemic heart failure for high-risk revascularization improves identification of those with the highest clinical benefit. Circ Cardiovasc Imaging. 2012;5:262-70. 21. Beanlands RSB, Nichol G, Huszti E, Humen D, Racine N, Freeman M, et al. F-18-fluorodeoxyglucose positron emission tomography imaging-assisted management of patients with severe left ventricular dysfunction and suspected coronary disease. A randomized controlled trial (PARR-2). J Am Coll Cardiol. 2007;50:2002-12. 22. Ling LF, Marwick TH, Flores DR, Jaber WA, Brunken RC, Cerqueira MD, et al. Identification of therapeutic benefit from revascularization in patients with left ventricular systolic dysfunction: Inducible ischemia versus hibernating myocardium. Circ Cardiovasc Imaging. 2013;6:363-72. 23. O’Meara E, Mielniczuk LM, Wells GA, deKemp RA, Klein R, Coyle D, et al. Alternative imaging modalities in ischemic heart failure (AIMI-HF) IMAGE HF Project I-A: Study protocol for a randomized controlled trial. Trials. 2013;14:218.
