- Email: [email protected]
Role of BMIPP imaging for risk stratification in patients with coronary artery disease
EDITORIAL Role of BMIPP imaging for risk stratification in patients with coronary artery disease Nagara Tamaki, MD
See related article, p. 172 Myocardial energy metabolism has long been investigated in experimental models with use of Langendorff’s perfusion system and/or coronary sinus blood sampling. The introduction of a variety of radiopharmaceutical agents has made it possible to visualize myocardial energy metabolism in vivo. Although positron emission tomography (PET) has a unique character to probe myocardial energy metabolism in vivo by use of various radiolabeled physiologic compounds such as carbon 11 palmitate and C-11 acetate, it has an inherent limitation for wide application because of the use of expensive PET cameras and a cyclotron. Iodine 123–labeled fatty acids have received great attention for assessing myocardial metabolism in vivo.1,2 Among various types of iodinated fatty acid compounds, 15-(p-iodophenyl)-3-(R,S) methylpentadecanoic acid (BMIPP) is a most promising agent, which has been widely used to investigate basic kinetics and clinical implications, particularly in Japan and Europe.3-8 Methyl branching of the fatty acid chain retains the compounds in the myocardium while protecting against metabolism by -oxidation (metabolic trapping). Thus excellent myocardial images are obtained with a long acquisition time after BMIPP administration. Although BMIPP uptake may not directly reflect fatty acid oxidation, BMIPP retains some of the physiologic properties, such as fatty acid uptake and turnover rate of triglyceride pool. One of the most promising applications of this agent is detection of myocardial ischemia at rest as an area of reduced fatty acid utilization. Because persistent metabolic alterations are often seen in post–myocardial ischemia after recovery of myocardial blood flow, prior ischemic insult may be identified as areas of reduced BMIPP uptake indicating altered fatty acid metabolism From the Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan. Reprint requests: Nagara Tamaki, MD, Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, N-15, W-7, Kitaku, Sapporo, 060-8638, Japan; [email protected]. J Nucl Cardiol 2005;12:148-50. 1071-3581/$30.00 Copyright © 2005 by the American Society of Nuclear Cardiology. doi:10.1016/j.nuclcard.2005.01.007 148
despite normal myocardial perfusion (so-called ischemic memory imaging).9-11 Because such persistent metabolic alteration is often seen in severe ischemic myocardium, BMIPP at rest has been used for identifying ischemic myocardium. A number of reports from Japan showed high diagnostic accuracy of BMIPP imaging at rest for detecting patients with coronary stenosis without a history of myocardial infarction.12-17 More recently, the clinical trials of BMIPP in the United States confirmed its diagnostic value for identifying ischemic myocardium at rest after ischemia.18 The sensitivity of BMIPP imaging for detecting coronary artery lesions ranged from 55% to 89%, which might be slightly inferior to the conventional stress perfusion imaging, which provides sensitivity of 80% to 90%. On the other hand, this imaging does not require a stress test and, therefore, is quite suitable for patients with unstable angina or severe coronary artery disease. The sensitivity tended to be higher in the study of patients with unstable angina or those with associated regional wall motion abnormalities,13-16 indicating sustained alteration of myocardial metabolism after severe ischemia. Thus BMIPP imaging is considered to be the method of choice for identifying regional abnormalities as persistent metabolic alterations (“ischemic memory”) in these patients and may assist in the choice of therapeutic options in patients with chest pain. The areas with less BMIPP than perfusion may represent ischemic and jeopardized myocardium. Accordingly, combined BMIPP and thallium imaging may have potential value for risk stratification in coronary patients. This concept may come from the important prognostic findings reported on the perfusion-metabolism mismatch pattern on fluorodeoxyglucose (FDG)– positron emission tomography (PET) studies. The initial study by our group surveyed 50 consecutive patients with myocardial infarction who underwent BMIPP and thallium scanning and were followed up for a mean interval of 23 months.19 Among various clinical, angiographic, and radionuclide indices, discordant BMIPP uptake was the best predictor of future cardiac events, followed by number of coronary stenosis. In their multicenter study, Nakata et al20 indicated that the BMIPP defect score was the most powerful index for predicting future cardiac events in patients after acute myocardial infarction. Although these findings remain preliminary,
Journal of Nuclear Cardiology Volume 12, Number 2;148-50
they indicate that BMIPP in combination with perfusion imaging may hold promise for identifying high-risk subgroups among patients with coronary artery disease. On the other hand, it remains uncertain whether BMIPP imaging may have a role for risk stratification in coronary patients without a history of myocardial infarction. The multicenter study published in this issue of the Journal is one of the first few reports indicating that BMIPP imaging may play a clinical role in selecting a high-risk subgroup among patients with suspected coronary artery disease.21 During a median follow-up of 3.9 years, the Kaplan-Meier survival estimate showed a hard event-free survival rate of 98% at 3 years in patients with a BMIPP defect score of less than 5 but 93% in those with a defect score of 5 or greater (P ⫽ .03). With regard to total cardiac events, the study demonstrated an eventfree survival rate of 92% at 3 years in those with a BMIPP defect score of less than 5, as compared with 80% in those with a defect score of 5 or greater (P ⫽ .0003). The study was well designed, collecting data from many patients from several different centers to demonstrate that those with reduced BMIPP uptake may be likely to have future cardiac events, as compared with those with normal BMIPP uptake. The authors concluded that BMIPP imaging at rest has a potential role for risk stratification in patients with known or suspected coronary artery disease. Despite the retrospective nature of risk analysis by searching the existing databases of 4 institutions, the current study nicely demonstrates, for the first time, the prognostic value of BMIPP imaging in patients with coronary artery disease. Another important finding is that BMIPP imaging successfully stratified diabetic and nondiabetic patients into low- and high-risk subgroups, as many other reports have indicated. Metabolic imaging, such as FDG-PET, may demonstrate some difficulties in acquiring high-quality studies because of the significant differences in metabolic substrates in patients with diabetes. On the other hand, BMIPP uptake in the myocardium is not influenced by blood substrate levels,22 and therefore BMIPP imaging is feasible for diabetic patients without any need for plasma substrate control. However, there are 2 major issues that were not fully addressed in the current study. The study included a heterogeneous population with quite a number of severely ill patients, such as those with New York Heart Association class III/IV. Some patients may have had severely reduced left ventricular function, and they may have a naturally poor prognosis on follow-up. Perhaps a left ventricular functional parameter such as ejection fraction could modify the conclusion of this study. Unfortunately, such left ventricular functional parameters were not included in this study.
Tamaki Role of BMIPP imaging for risk stratification
149
Another issue concerns when and how to use BMIPP imaging in the clinical setting. Although the current study nicely showed the potential prognostic value of BMIPP imaging at rest, it remains unclear whether BMIPP imaging should be applied to all patients with known or suspected coronary artery disease and also whether BMIPP imaging might have a complementary role with stress myocardial perfusion imaging. On the basis of increasing recognition of its strong prognostic value, stress myocardial perfusion imaging has become a central guide in decision making in patients with coronary artery disease. In each study the results of stress myocardial perfusion imaging were found to be the single-most important variable in risk stratification. Previous reports indicated that BMIPP distribution may be slightly different from myocardial perfusion imaging with thallium or technetium 99m perfusion agents.23-27 However, other reports indicated that BMIPP reduction was closely related to the areas of perfusion abnormalities on stress myocardial perfusion studies.28,29 Several important clinical questions may arise. What is the relationship between BMIPP imaging at rest and stress MPI studies with regard to risk stratification in these populations? Did BMIPP imaging provide independent and additional prognostic value? In the study of stable patients, which was the first choice—a stress myocardial perfusion study or resting BMIPP imaging? What about those patients who could not achieve adequate exercise? Would a pharmacologic stress perfusion study or resting BMIPP imaging be useful? Our recent report from a prospective study may respond to these important questions.30 When 167 consecutive patients with angina who underwent both stress myocardial perfusion imaging and resting BMIPP imaging were followed up for 48 months, BMIPP defect score at rest, stress perfusion score, diabetes, and left ventricular ejection fraction were independent predictors on multivariate Cox analysis. No hard event was observed with normal BMIPP uptake, whereas 2 patients with nearly normal stress perfusion with abnormal BMIPP uptake had hard events.30 Despite a relatively limited number of patients enrolled, this preliminary study may suggest that BMIPP imaging at rest may provide important prognostic power independent from stress myocardial perfusion imaging. Again, BMIPP imaging is a promising technique by which to identify ischemic myocardium at rest. In addition, these new reports indicate the prognostic value of BMIPP imaging in patients with coronary artery disease. I believe that these clinical experiences with BMIPP in terms of diagnosis and prognosis of patients with coronary artery disease will contribute new evidence for applying this imaging modality for clinical use.
150
Tamaki Role of BMIPP imaging for risk stratification
Acknowledgment The author has indicated he has no financial conflicts of interest.
References 1. Machulla HJ, Marsmann M, Dutschka K. Biochemical synthesis of a radioiodinated phenyl fatty acid for in vivo metabolic studies of the myocardium. Eur J Nucl Med 1980;5:171-3. 2. Knapp FF Jr, Goodman MM, Callahan AP, Kirsch G. Radioiodinated 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid: a useful new agent to evaluate myocardial fatty acid uptake. J Nucl Med 1986;27:521-31. 3. Fujibayashi Y, Nohara R, Hosokawa R, Okuda K, Yonekura Y, Tamaki N, et al. Metabolism and kinetics of iodine-123-BMIPP in canine myocardium. J Nucl Med 1996;37:757-61. 4. Morishita S, Kusuoka H, Yamamichi Y, Suzuki N, Kurami M, Nishimura T. Kinetics of radioiodinated species in subcellular fractions from rat hearts following administration of iodine-123-labelled 15-(p-iodophenyl)-3-(R,S) methylpentadecanoic acid (123I-BMIPP). Eur J Nucl Med 1996;23:383-9. 5. Yamamichi Y, Kusuoka H, Morishita K, Shirakami Y, Kurami M, Okano K, et al. Metabolism of 123I-labeled 15-p-iodophenyl-3(R,S)-methyl-pentadecanoic acid (BMIPP) in perfused rat heart. J Nucl Med 1995;36:1043-50. 6. Hosokawa R, Nohara R, Fujibayashi Y, Okuda K, Ogino M, Hata T, et al. Metabolic fate of iodine-123-BMIPP in canine myocardium after administration of etomoxir. J Nucl Med 1996;37:1836-40. 7. Fujibayashi Y, Yonekura Y, Takemura Y, Wada K, Matsumoto K, Tamaki N, et al. Myocardial accumulation of iodinated beta-methylbranched fatty acid analogue, iodine-125-15-(p-iodophenyl)-3-(R,S) methylpentadecanoic acid (BMIPP), in relation to ATP concentration. J Nucl Med 1990;31:1818-22. 8. Nohara R, Okuda K, Ogino M, Hosokawa R, Tamaki N, Konishi J, et al. Evaluation of myocardial viability with iodine-123-BMIPP in a canine model. J Nucl Med 1996;37:1403-7. 9. Tamaki N, Morita K, Kuge Y, Tsukamoto E. The role of fatty acids in cardiac imaging. J Nucl Med 2000;41:1525-34. 10. Mochizuki T, Murase K, Higashino H, et al. Ischemic “memory image” in acute myocardial infarction of 123I-BMIPP after reperfusion therapy: a comparison with 99mTc-pyrophosphate and 201Tl dual-isotope SPECT. Ann Nucl Med 2002;8:563-8. 11. Tanaka R, Nakamura T, Kumamoto H, Miura M, Hirabayashi K, Okamato N, et al. Detection of stunned myocardium in postreperfusion cases of acute myocardial infarction. Ann Nucl Med 2003;1:53-60. 12. Takeishi Y, Fujiwara S, Atsumi H, et al. Clinical significance of decreased myocardial uptake of 123 I-BMIPP in patients with stable effort angina pectoris. Nucl Med Commun 1995;16:1002-8. 13. Takeishi Y, Sukekawa H, Saito H, Nishimura S, Shibu T, Sasaki Y, et al. Impaired myocardial fatty acid metabolism detected by 123 I-BMIPP in patients with unstable angina pectoris: comparison with perfusion imaging by 99mTc-sestamibi. Ann Nucl Med 1995;9:125-30. 14. Tateno M, Tamaki N, Yukihiro M, Kudoh T, Hattori N, Tadamura E, et al. Assessment of fatty acid uptake in patients with ischemic heart disease without myocardial infarction. J Nucl Med 1996;37: 1981-5. 15. Suzuki A, Takada Y, Nagasaka M, Kato R, Watanabe T, Shimokata K, et al. Comparison of resting -methyl-iodophenyl pentadecanoic acid (BMIPP) and thallium-201 tomography using quantitative polar maps in patients with unstable angina. Jpn Circ J 1997;61:133-8.
Journal of Nuclear Cardiology March/April 2005
16. Yamabe H, Fujiwara S, Rin K, Ando M, Yokoyama M, Sakamoro T, et al. Resting 123I-BMIPP scintigraphy for detection of organic coronary stenosis and therapeutic outcome in patients with chest pain. Ann Nucl Med 2000;14:187-92. 17. Kawai Y, Tsukamoto E, Nozaki Y, Morita K, Sakurai M, Tamaki N. Significance of reduced uptake of iodinated fatty acid analogue for the evaluation of patients with acute chest pain. J Am Coll Cardiol 2001;38:1888-94. 18. Udelson JE, Bateman TM, Bergmann SR, et al. Proof of principle study of beta-methyl-p-[123I]-iodophenyl-pentadecanoic acid (BMIPP) for ischemic memory following demand ischemia [abstract]. Circulation 2003;108:IV405. 19. Tamaki N, Tadamura E, Kudoh T, Hattori N, Yonekura Y, Nohara R, et al. Prognostic value of iodine-123 labelled BMIPP fatty acid analogue imaging in patients with myocardial infarction. Eur J Nucl Med 1996;23:272-9. 20. Nakata T, Kobayashi T, Tamaki N, Kobayashi H, Wakabayashi T, Shimoshige S, et al. Prognosis value of impaired myocardial fatty acid uptake in patients with acute myocardial infarction. Nucl Med Commun 2000;21:897-906. 21. Chikamori T, Fujita H, Nakasato M, Toba M, Nishimura T. Prognostic value of I-123 15-(p-iodophenyl)-3-(R,S) methylpentadecanoic acid myocardial imaging in patients with known or suspected coronary artery disease. J Nucl Cardiol 2005;12:172-8. 22. Kurata C, Wakabayashi Y, Shouda S, Mikami T, Takei Y, Tawarahara K, et al. Influence of blood substrate levels on myocardial kinetics of iodine-123-BMIPP. J Nucl Med 1997;38: 1079-84. 23. Tamaki N, Kawamoto M, Yonekura Y, Fujibayashi Y, Takahashi N, Konishi J, et al. Regional metabolic abnormality in relation to perfusion and wall motion in patients with myocardial infarction: assessment with emission tomography using an iodinated branched fatty acid. J Nucl Med 1992;33:659-67. 24. De Geeter F, Franken P, Knapp FF Jr, Bossuyt A. Relationship between blood flow and fatty acid metabolism in subacute myocardial infarction: a study by means of Tc-99m sestamibi and iodine-123-beta-methyl iodophenyl pentadecanoic acid. Eur J Nucl Med 1994;21:283-91. 25. Franken P, De Geeter F, Dendale P, Demoor D, Block P, Bossuyt A. Abnormal free fatty acid uptake in subacute myocardial infarction after coronary thrombolysis: correlation with wall motion and inotropic reserve. J Nucl Med 1994;35:1758-65. 26. Furutani Y, Shiigi T, Nakamura Y, Nakamura H, Harada M, Yamamoto T, et al. Quantification of area at risk in acute myocardial infarction by tomographic imaging. J Nucl Med 1997; 38:1875-82. 27. Kawai Y, Tsukamoto E, Nozaki Y, Kishino K, Kohya T, Tamaki N. Use of 123I-BMIPP single-photon emission tomography to estimate areas at risk following successful revascularization in patients with acute myocardial infarction Eur J Nucl Med 1998; 25:1390-5. 28. Matsunari I, Saga T, Taki J, Akashi Y, Hirai J, Wakasugi T, et al. Kinetics of iodine-123-BMIPP in patients with prior myocardial infarction: assessment with dynamic rest and stress images compared with stress thallium-201 SPECT. J Nucl Med 1994;35:1279-85. 29. Kawamoto M, Tamaki N, Yonekura Y, Tadamura E, Fujibayashi Y, Magata Y, et al. Combined study with I-123 fatty acid and thallium-201 to assess ischemic myocardium. Ann Nucl Med 1994;8:47-54. 30. Matsuki T, Tamaki N, Nakata T, Doi A, Takahashi H, Iwata M, et al. Prognostic value of fatty acid aimaging in patients with angina pectoris without prior myocardial infarction: comparison with stress thallium imaging. Eur J Nucl Med Mol Imaging 2004; 31:1585-91.
See related article, p. 172 Myocardial energy metabolism has long been investigated in experimental models with use of Langendorff’s perfusion system and/or coronary sinus blood sampling. The introduction of a variety of radiopharmaceutical agents has made it possible to visualize myocardial energy metabolism in vivo. Although positron emission tomography (PET) has a unique character to probe myocardial energy metabolism in vivo by use of various radiolabeled physiologic compounds such as carbon 11 palmitate and C-11 acetate, it has an inherent limitation for wide application because of the use of expensive PET cameras and a cyclotron. Iodine 123–labeled fatty acids have received great attention for assessing myocardial metabolism in vivo.1,2 Among various types of iodinated fatty acid compounds, 15-(p-iodophenyl)-3-(R,S) methylpentadecanoic acid (BMIPP) is a most promising agent, which has been widely used to investigate basic kinetics and clinical implications, particularly in Japan and Europe.3-8 Methyl branching of the fatty acid chain retains the compounds in the myocardium while protecting against metabolism by -oxidation (metabolic trapping). Thus excellent myocardial images are obtained with a long acquisition time after BMIPP administration. Although BMIPP uptake may not directly reflect fatty acid oxidation, BMIPP retains some of the physiologic properties, such as fatty acid uptake and turnover rate of triglyceride pool. One of the most promising applications of this agent is detection of myocardial ischemia at rest as an area of reduced fatty acid utilization. Because persistent metabolic alterations are often seen in post–myocardial ischemia after recovery of myocardial blood flow, prior ischemic insult may be identified as areas of reduced BMIPP uptake indicating altered fatty acid metabolism From the Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan. Reprint requests: Nagara Tamaki, MD, Department of Nuclear Medicine, Hokkaido University Graduate School of Medicine, N-15, W-7, Kitaku, Sapporo, 060-8638, Japan; [email protected]. J Nucl Cardiol 2005;12:148-50. 1071-3581/$30.00 Copyright © 2005 by the American Society of Nuclear Cardiology. doi:10.1016/j.nuclcard.2005.01.007 148
despite normal myocardial perfusion (so-called ischemic memory imaging).9-11 Because such persistent metabolic alteration is often seen in severe ischemic myocardium, BMIPP at rest has been used for identifying ischemic myocardium. A number of reports from Japan showed high diagnostic accuracy of BMIPP imaging at rest for detecting patients with coronary stenosis without a history of myocardial infarction.12-17 More recently, the clinical trials of BMIPP in the United States confirmed its diagnostic value for identifying ischemic myocardium at rest after ischemia.18 The sensitivity of BMIPP imaging for detecting coronary artery lesions ranged from 55% to 89%, which might be slightly inferior to the conventional stress perfusion imaging, which provides sensitivity of 80% to 90%. On the other hand, this imaging does not require a stress test and, therefore, is quite suitable for patients with unstable angina or severe coronary artery disease. The sensitivity tended to be higher in the study of patients with unstable angina or those with associated regional wall motion abnormalities,13-16 indicating sustained alteration of myocardial metabolism after severe ischemia. Thus BMIPP imaging is considered to be the method of choice for identifying regional abnormalities as persistent metabolic alterations (“ischemic memory”) in these patients and may assist in the choice of therapeutic options in patients with chest pain. The areas with less BMIPP than perfusion may represent ischemic and jeopardized myocardium. Accordingly, combined BMIPP and thallium imaging may have potential value for risk stratification in coronary patients. This concept may come from the important prognostic findings reported on the perfusion-metabolism mismatch pattern on fluorodeoxyglucose (FDG)– positron emission tomography (PET) studies. The initial study by our group surveyed 50 consecutive patients with myocardial infarction who underwent BMIPP and thallium scanning and were followed up for a mean interval of 23 months.19 Among various clinical, angiographic, and radionuclide indices, discordant BMIPP uptake was the best predictor of future cardiac events, followed by number of coronary stenosis. In their multicenter study, Nakata et al20 indicated that the BMIPP defect score was the most powerful index for predicting future cardiac events in patients after acute myocardial infarction. Although these findings remain preliminary,
Journal of Nuclear Cardiology Volume 12, Number 2;148-50
they indicate that BMIPP in combination with perfusion imaging may hold promise for identifying high-risk subgroups among patients with coronary artery disease. On the other hand, it remains uncertain whether BMIPP imaging may have a role for risk stratification in coronary patients without a history of myocardial infarction. The multicenter study published in this issue of the Journal is one of the first few reports indicating that BMIPP imaging may play a clinical role in selecting a high-risk subgroup among patients with suspected coronary artery disease.21 During a median follow-up of 3.9 years, the Kaplan-Meier survival estimate showed a hard event-free survival rate of 98% at 3 years in patients with a BMIPP defect score of less than 5 but 93% in those with a defect score of 5 or greater (P ⫽ .03). With regard to total cardiac events, the study demonstrated an eventfree survival rate of 92% at 3 years in those with a BMIPP defect score of less than 5, as compared with 80% in those with a defect score of 5 or greater (P ⫽ .0003). The study was well designed, collecting data from many patients from several different centers to demonstrate that those with reduced BMIPP uptake may be likely to have future cardiac events, as compared with those with normal BMIPP uptake. The authors concluded that BMIPP imaging at rest has a potential role for risk stratification in patients with known or suspected coronary artery disease. Despite the retrospective nature of risk analysis by searching the existing databases of 4 institutions, the current study nicely demonstrates, for the first time, the prognostic value of BMIPP imaging in patients with coronary artery disease. Another important finding is that BMIPP imaging successfully stratified diabetic and nondiabetic patients into low- and high-risk subgroups, as many other reports have indicated. Metabolic imaging, such as FDG-PET, may demonstrate some difficulties in acquiring high-quality studies because of the significant differences in metabolic substrates in patients with diabetes. On the other hand, BMIPP uptake in the myocardium is not influenced by blood substrate levels,22 and therefore BMIPP imaging is feasible for diabetic patients without any need for plasma substrate control. However, there are 2 major issues that were not fully addressed in the current study. The study included a heterogeneous population with quite a number of severely ill patients, such as those with New York Heart Association class III/IV. Some patients may have had severely reduced left ventricular function, and they may have a naturally poor prognosis on follow-up. Perhaps a left ventricular functional parameter such as ejection fraction could modify the conclusion of this study. Unfortunately, such left ventricular functional parameters were not included in this study.
Tamaki Role of BMIPP imaging for risk stratification
149
Another issue concerns when and how to use BMIPP imaging in the clinical setting. Although the current study nicely showed the potential prognostic value of BMIPP imaging at rest, it remains unclear whether BMIPP imaging should be applied to all patients with known or suspected coronary artery disease and also whether BMIPP imaging might have a complementary role with stress myocardial perfusion imaging. On the basis of increasing recognition of its strong prognostic value, stress myocardial perfusion imaging has become a central guide in decision making in patients with coronary artery disease. In each study the results of stress myocardial perfusion imaging were found to be the single-most important variable in risk stratification. Previous reports indicated that BMIPP distribution may be slightly different from myocardial perfusion imaging with thallium or technetium 99m perfusion agents.23-27 However, other reports indicated that BMIPP reduction was closely related to the areas of perfusion abnormalities on stress myocardial perfusion studies.28,29 Several important clinical questions may arise. What is the relationship between BMIPP imaging at rest and stress MPI studies with regard to risk stratification in these populations? Did BMIPP imaging provide independent and additional prognostic value? In the study of stable patients, which was the first choice—a stress myocardial perfusion study or resting BMIPP imaging? What about those patients who could not achieve adequate exercise? Would a pharmacologic stress perfusion study or resting BMIPP imaging be useful? Our recent report from a prospective study may respond to these important questions.30 When 167 consecutive patients with angina who underwent both stress myocardial perfusion imaging and resting BMIPP imaging were followed up for 48 months, BMIPP defect score at rest, stress perfusion score, diabetes, and left ventricular ejection fraction were independent predictors on multivariate Cox analysis. No hard event was observed with normal BMIPP uptake, whereas 2 patients with nearly normal stress perfusion with abnormal BMIPP uptake had hard events.30 Despite a relatively limited number of patients enrolled, this preliminary study may suggest that BMIPP imaging at rest may provide important prognostic power independent from stress myocardial perfusion imaging. Again, BMIPP imaging is a promising technique by which to identify ischemic myocardium at rest. In addition, these new reports indicate the prognostic value of BMIPP imaging in patients with coronary artery disease. I believe that these clinical experiences with BMIPP in terms of diagnosis and prognosis of patients with coronary artery disease will contribute new evidence for applying this imaging modality for clinical use.
150
Tamaki Role of BMIPP imaging for risk stratification
Acknowledgment The author has indicated he has no financial conflicts of interest.
References 1. Machulla HJ, Marsmann M, Dutschka K. Biochemical synthesis of a radioiodinated phenyl fatty acid for in vivo metabolic studies of the myocardium. Eur J Nucl Med 1980;5:171-3. 2. Knapp FF Jr, Goodman MM, Callahan AP, Kirsch G. Radioiodinated 15-(p-iodophenyl)-3,3-dimethylpentadecanoic acid: a useful new agent to evaluate myocardial fatty acid uptake. J Nucl Med 1986;27:521-31. 3. Fujibayashi Y, Nohara R, Hosokawa R, Okuda K, Yonekura Y, Tamaki N, et al. Metabolism and kinetics of iodine-123-BMIPP in canine myocardium. J Nucl Med 1996;37:757-61. 4. Morishita S, Kusuoka H, Yamamichi Y, Suzuki N, Kurami M, Nishimura T. Kinetics of radioiodinated species in subcellular fractions from rat hearts following administration of iodine-123-labelled 15-(p-iodophenyl)-3-(R,S) methylpentadecanoic acid (123I-BMIPP). Eur J Nucl Med 1996;23:383-9. 5. Yamamichi Y, Kusuoka H, Morishita K, Shirakami Y, Kurami M, Okano K, et al. Metabolism of 123I-labeled 15-p-iodophenyl-3(R,S)-methyl-pentadecanoic acid (BMIPP) in perfused rat heart. J Nucl Med 1995;36:1043-50. 6. Hosokawa R, Nohara R, Fujibayashi Y, Okuda K, Ogino M, Hata T, et al. Metabolic fate of iodine-123-BMIPP in canine myocardium after administration of etomoxir. J Nucl Med 1996;37:1836-40. 7. Fujibayashi Y, Yonekura Y, Takemura Y, Wada K, Matsumoto K, Tamaki N, et al. Myocardial accumulation of iodinated beta-methylbranched fatty acid analogue, iodine-125-15-(p-iodophenyl)-3-(R,S) methylpentadecanoic acid (BMIPP), in relation to ATP concentration. J Nucl Med 1990;31:1818-22. 8. Nohara R, Okuda K, Ogino M, Hosokawa R, Tamaki N, Konishi J, et al. Evaluation of myocardial viability with iodine-123-BMIPP in a canine model. J Nucl Med 1996;37:1403-7. 9. Tamaki N, Morita K, Kuge Y, Tsukamoto E. The role of fatty acids in cardiac imaging. J Nucl Med 2000;41:1525-34. 10. Mochizuki T, Murase K, Higashino H, et al. Ischemic “memory image” in acute myocardial infarction of 123I-BMIPP after reperfusion therapy: a comparison with 99mTc-pyrophosphate and 201Tl dual-isotope SPECT. Ann Nucl Med 2002;8:563-8. 11. Tanaka R, Nakamura T, Kumamoto H, Miura M, Hirabayashi K, Okamato N, et al. Detection of stunned myocardium in postreperfusion cases of acute myocardial infarction. Ann Nucl Med 2003;1:53-60. 12. Takeishi Y, Fujiwara S, Atsumi H, et al. Clinical significance of decreased myocardial uptake of 123 I-BMIPP in patients with stable effort angina pectoris. Nucl Med Commun 1995;16:1002-8. 13. Takeishi Y, Sukekawa H, Saito H, Nishimura S, Shibu T, Sasaki Y, et al. Impaired myocardial fatty acid metabolism detected by 123 I-BMIPP in patients with unstable angina pectoris: comparison with perfusion imaging by 99mTc-sestamibi. Ann Nucl Med 1995;9:125-30. 14. Tateno M, Tamaki N, Yukihiro M, Kudoh T, Hattori N, Tadamura E, et al. Assessment of fatty acid uptake in patients with ischemic heart disease without myocardial infarction. J Nucl Med 1996;37: 1981-5. 15. Suzuki A, Takada Y, Nagasaka M, Kato R, Watanabe T, Shimokata K, et al. Comparison of resting -methyl-iodophenyl pentadecanoic acid (BMIPP) and thallium-201 tomography using quantitative polar maps in patients with unstable angina. Jpn Circ J 1997;61:133-8.
Journal of Nuclear Cardiology March/April 2005
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