REVIEW ARTICLE A quick glance at selected topics in this issue Pradeep Bhambhvani, MD,a Fadi G. Hage, MD, FASNC,b,c and Ami E. Iskandrian, MD, MASNCb a
b c
Division of Molecular Imaging and Therapeutics, Department of Radiology, The University of Alabama at Birmingham, Birmingham, AL Division of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL Section of Cardiology, Birmingham Veterans Affairs Medical Center, Birmingham, AL
Received Aug 4, 2017; accepted Aug 7, 2017 doi:10.1007/s12350-017-1039-0
‘‘A quick glance at selected topics in this issue’’ aims to highlight contents of the Journal and provide a quick review to the readers. We realize that many of you do not have time to read all journals or attend all national meetings. For that reason, every issue of the JNC includes 2 types of literature reviews. One, summarizing recent key nuclear cardiology articles that have been published in journals other than ours, while the second outlines select publications in the general cardiovascular disease literature that have relevance to our field. The current issue includes papers on molecular imaging (cardiac regenerative therapies; doi: 10.1007/s12350-017-0785-3), technical issues (combining exercise with regadenoson stress; doi: 10.1007/s12350-017-0903-2) and what goes on internationally (Nuclear Cardiology in China; doi: 10.1007/s12350-017-0985-x). These contributions compliment a great selection of original articles with accompanying editorials, brief reports, a CME review paper, ‘What is this image’, and ‘Images that Teach’. Many of the original articles have power point slides and some also have audio interviews. The abstract of the lead original article on standardization of time-frame sampling for 82Rb PET flow quantification by Lee and colleagues from Ottawa, Canada, has also been translated into Chinese and Spanish in response to requests from the international readership. Power point slides and an audio interview with its lead author can be found by searching doi: 10.1007/s12350-017-0899-7. The Joint SNMMI–ASNC expert consensus document on the role
Reprint requests: Pradeep Bhambhvani, MD, Division of Molecular Imaging and Therapeutics, Department of Radiology, The University of Alabama at Birmingham, 619 19th Street South, JT 777, Birmingham, AL 35249; [email protected] 1071-3581/$34.00 Copyright Ó 2017 American Society of Nuclear Cardiology.
of 18F-FDG PET/CT in cardiac sarcoid detection and therapy monitoring doi:(10.1007/s12350-017-0978-9) and debate articles with editorial on the value of neurocardiac imaging in patient management (doi’s: 10.1007/s12350-017-0948-2; 10.1007/s12350-0170948-2; 10.1007/s12350-017-0948-2) are also included in this issue. Our comments on a few selected papers noted below are therefore only the tip of the iceberg. These manuscripts were selected at random and we believe all original articles serve a purpose, provide great value, and have undergone an intense peer review. The incremental prognostic and diagnostic value of myocardial blood flow (MBF) and myocardial flow reserve (MFR) quantification over traditional myocardial perfusion imaging is well established. With presently available technologies, MBF can be easily added to a standard PET MPI study without additional cost or radiation exposure. Successful implementation of a MBF quantification program requires optimization of specific technical factors to achieve accurate and precise MBF measurements. One of these factors includes timeframe binning of the raw data to produce dynamic image sequences from which MBF is quantified. Lee and colleagues from Ottawa, Canada (doi:10.1007/s12350017-0899-7) define an optimal temporal sampling protocol for dynamic 82Rubidium MPI in modern PET systems, using real-world data from patients and healthy volunteers in addition to simulations. They identify a simple two-phase framing of dynamic 82Rubidium PET images where the blood phase has frame durations of 5 seconds and a tissue phase of 120 seconds that optimally samples the blood pool time-activity curve for modern 3D PET systems. Fughhi et al. from Chicago, IL (doi: 10.1007/s12350-016-0506-3) study the effects of aminophylline (administered to attenuate regadenoson related adverse events) on the burden of regadenosoninduced ischemia detected by SPECT MPI. The authors
Bhambhvani et al JNC Quick Glance September 2017
analyzed the pooled database of the ASSUAGE and ASSUAGE-chronic kidney disease trials (n = 548). In these double-blinded, placebo-controlled, randomized clinical trials, 75 mg of aminophylline or placebo was administered intravenously 90 seconds following 99mTctetrofosmin injection. The authors found no interaction between aminophylline use and summed difference score as a determinant of the composite endpoint of cardiac death or MI or the composite endpoint of cardiac death, MI, or coronary revascularization. They conclude that aminophylline administration does not appear to attenuate the burden of myocardial ischemia. Recent trials (e.g., COURAGE trial) comparing medical therapy vs coronary revascularization in stable CAD have questioned the rationale of routine revascularization. Using serial myocardial perfusion scintigraphy, Nudi and colleagues from Italy (10.1007/s12350-016-0504-5) evaluate the impact of revascularization vs medical therapy alone, on changes in ischemia in 3631 patients. They find that revascularization was superior to medical therapy in reducing ischemic burden or normalizing myocardial perfusion among subjects with moderate or severe ischemia at baseline. There was no apparent benefit of revascularization (percutaneous or surgical) among patients without ischemia at baseline, or among subjects with only minimal or mild baseline ischemia. In fact, revascularization tended to be detrimental in those without baseline ischemia. Fukuoka and colleagues from Japan (doi: 10.1007/s12350-016-0526-z) study coronary microvascular function with 18F- FDG PET and adenosine stress 13 N-ammonia PET in 18 acute myocardial infarction patients who were successfully revascularized via percutaneous coronary intervention with bare metal stents within 24 hours of the onset of symptoms. They find that myocardial flow reserve in the mismatched segments (defined as reduced resting myocardial blood flow with preserved myocardial FDG uptake) was decreased despite successful reperfusion of the epicardial coronary artery reflecting coronary microvascular dysfunction. Furthermore, functional recovery assessed with wall motion scores in the mismatched segments was incomplete. Zeltser et al. from New York (doi: 10.1007/s12350-016-0464-9) retrospectively evaluate the association of age and gender with downstream resource utilization (i.e., invasive coronary angiography) following SPECT MPI. In a cohort of 3824 patients at a tertiary referral center, younger patients were more likely to undergo an angiogram as compared to octogenarians (77% more likely if \55 years old, 69% if 5569 years old, and 52% if 70-79 years old). Surprisingly no effect/bias was found for gender.
Journal of Nuclear CardiologyÒ
Gomez and colleagues from Chicago, IL (doi: 10.1007/s12350-016-0497-0) investigate whether integrating heart rate response (HRR) to regadenoson with myocardial perfusion imaging (MPI) analysis can enhance risk prediction in end stage renal disease (ESRD) patients (n = 303). Normal HRR to regadenoson was defined as C28% increase from baseline. They noted a step-wise increase in the risk of primary endpoint of all-cause death and the composite secondary endpoint of cardiac death or myocardial infarction. Patients with Normal MPI/Normal HRR had the lowest event rates (thus were truly low risk), and those with Abnormal MPI/Abnormal HRR had the highest event rates, whereas subjects with Abnormal MPI/Normal HRR and Normal MPI/Abnormal HRR had intermediate event rates. Interventricular mechanical dyssynchrony is an important variable for the consideration of cardiac resynchronization therapy (CRT) in patients with heart failure. Zhou et al. (doi:10.1007/s12350-016-0503-6) develop a new RV phase analysis tool and coupled with their LV phase analysis tool, measure interventricular mechanical dyssynchrony from gated SPECT MPI and validate it against electrocardiograms (ECG) derived interventricular conduction delays in 61 patients with ischemic or non-ischemic dilated cardiomyopathy. In total, a high agreement/concordance rate of 86.9% was achieved between SPECT and ECG. Technical advances in CT and specifically the development of multi-detector CT (MDCT) scanners have made possible assessment of not only coronary artery anatomy but also regional myocardial perfusion and estimation of coronary flow reserve (CFR). Marini and colleagues from Genoa, Italy, (doi: 10.1007/s12350-016-0492-5) compared regional CFR quantified by dynamic SPECT MPI and by dynamic multi-detector computed tomography (MDCT) in patients with suspected or known coronary artery disease (CAD). Although overall mean CFR values estimated by SPECT and MDCT were not different, MDCT tended to underestimate high CFR values compared to SPECT. Importantly, both techniques revealed significantly decreased CFR values in segments supplied by atherosclerotic coronary arteries compared to segments served by normal ones. Transient ischemic dilation (TID) of the left ventricle during stress and rest MPI is a proven diagnostic and prognostic marker of severe and extensive CAD. The cut-off value for a ‘‘significant’’ TID ratio varies depending on the stress modality, imaging protocol, radioisotope used, patient position, normal population definition, statistical threshold definition, and software used for TID computation. Jameria and colleagues (doi: 10.1007/s12350-016-0515-2) derive a threshold value
Journal of Nuclear CardiologyÒ
for the TID ratio using upright imaging on a Cadmium Zinc Telluride (CZT) SPECT camera and evaluate its capability to differentiate extensive from non-extensive CAD. With treadmill exercise, an upright TID ratio C1.16 provided a positive predictive value of 50% and a negative predictive value of 85.4% for the identification of extensive CAD. In the regadenoson group, an upright TID ratio of C1.29 provided a positive predictive value of 20% and a negative predictive value of 75.9%. Although not an independent predictor of extensive CAD in all subjects, in subjects with a normal upright LVEF, the TID ratio provided a predictive value by receiver operating characteristics comparable to the summed stress score. Thus the authors suggest that upright TID ratio can serve in an adjunctive role to summed stress score, and may be most effective in patients with a normal upright exercise LVEF. In a comprehensive review article, Jamali et al. from the University of Cincinnati College of Medicine, Cincinnati, OH, (doi:10.1007/s12350-016-0725-7)
Bhambhvani et al JNC Quick Glance September 2017
summarize basic anatomy, physiology, and pathophysiology of the cardiac autonomic nervous system including adrenergic receptors and discuss various imaging modalities (including 123I-mIBG) that can aid in diagnosis of cardiac autonomic dysfunction and autonomic modulation techniques including pharmacologic and device-based therapies of ventricular arrhythmias. We encourage the readers to read the several other original articles in the Journal as well the accompanying scholarly and informative editorials that not only put the findings in perspectives but also outline future directions. We would like to hear your comments as we strive to gain knowledge and in the process, improve patient care. Disclosure There are no COI with this work.
b c
Division of Molecular Imaging and Therapeutics, Department of Radiology, The University of Alabama at Birmingham, Birmingham, AL Division of Cardiovascular Disease, The University of Alabama at Birmingham, Birmingham, AL Section of Cardiology, Birmingham Veterans Affairs Medical Center, Birmingham, AL
Received Aug 4, 2017; accepted Aug 7, 2017 doi:10.1007/s12350-017-1039-0
‘‘A quick glance at selected topics in this issue’’ aims to highlight contents of the Journal and provide a quick review to the readers. We realize that many of you do not have time to read all journals or attend all national meetings. For that reason, every issue of the JNC includes 2 types of literature reviews. One, summarizing recent key nuclear cardiology articles that have been published in journals other than ours, while the second outlines select publications in the general cardiovascular disease literature that have relevance to our field. The current issue includes papers on molecular imaging (cardiac regenerative therapies; doi: 10.1007/s12350-017-0785-3), technical issues (combining exercise with regadenoson stress; doi: 10.1007/s12350-017-0903-2) and what goes on internationally (Nuclear Cardiology in China; doi: 10.1007/s12350-017-0985-x). These contributions compliment a great selection of original articles with accompanying editorials, brief reports, a CME review paper, ‘What is this image’, and ‘Images that Teach’. Many of the original articles have power point slides and some also have audio interviews. The abstract of the lead original article on standardization of time-frame sampling for 82Rb PET flow quantification by Lee and colleagues from Ottawa, Canada, has also been translated into Chinese and Spanish in response to requests from the international readership. Power point slides and an audio interview with its lead author can be found by searching doi: 10.1007/s12350-017-0899-7. The Joint SNMMI–ASNC expert consensus document on the role
Reprint requests: Pradeep Bhambhvani, MD, Division of Molecular Imaging and Therapeutics, Department of Radiology, The University of Alabama at Birmingham, 619 19th Street South, JT 777, Birmingham, AL 35249; [email protected] 1071-3581/$34.00 Copyright Ó 2017 American Society of Nuclear Cardiology.
of 18F-FDG PET/CT in cardiac sarcoid detection and therapy monitoring doi:(10.1007/s12350-017-0978-9) and debate articles with editorial on the value of neurocardiac imaging in patient management (doi’s: 10.1007/s12350-017-0948-2; 10.1007/s12350-0170948-2; 10.1007/s12350-017-0948-2) are also included in this issue. Our comments on a few selected papers noted below are therefore only the tip of the iceberg. These manuscripts were selected at random and we believe all original articles serve a purpose, provide great value, and have undergone an intense peer review. The incremental prognostic and diagnostic value of myocardial blood flow (MBF) and myocardial flow reserve (MFR) quantification over traditional myocardial perfusion imaging is well established. With presently available technologies, MBF can be easily added to a standard PET MPI study without additional cost or radiation exposure. Successful implementation of a MBF quantification program requires optimization of specific technical factors to achieve accurate and precise MBF measurements. One of these factors includes timeframe binning of the raw data to produce dynamic image sequences from which MBF is quantified. Lee and colleagues from Ottawa, Canada (doi:10.1007/s12350017-0899-7) define an optimal temporal sampling protocol for dynamic 82Rubidium MPI in modern PET systems, using real-world data from patients and healthy volunteers in addition to simulations. They identify a simple two-phase framing of dynamic 82Rubidium PET images where the blood phase has frame durations of 5 seconds and a tissue phase of 120 seconds that optimally samples the blood pool time-activity curve for modern 3D PET systems. Fughhi et al. from Chicago, IL (doi: 10.1007/s12350-016-0506-3) study the effects of aminophylline (administered to attenuate regadenoson related adverse events) on the burden of regadenosoninduced ischemia detected by SPECT MPI. The authors
Bhambhvani et al JNC Quick Glance September 2017
analyzed the pooled database of the ASSUAGE and ASSUAGE-chronic kidney disease trials (n = 548). In these double-blinded, placebo-controlled, randomized clinical trials, 75 mg of aminophylline or placebo was administered intravenously 90 seconds following 99mTctetrofosmin injection. The authors found no interaction between aminophylline use and summed difference score as a determinant of the composite endpoint of cardiac death or MI or the composite endpoint of cardiac death, MI, or coronary revascularization. They conclude that aminophylline administration does not appear to attenuate the burden of myocardial ischemia. Recent trials (e.g., COURAGE trial) comparing medical therapy vs coronary revascularization in stable CAD have questioned the rationale of routine revascularization. Using serial myocardial perfusion scintigraphy, Nudi and colleagues from Italy (10.1007/s12350-016-0504-5) evaluate the impact of revascularization vs medical therapy alone, on changes in ischemia in 3631 patients. They find that revascularization was superior to medical therapy in reducing ischemic burden or normalizing myocardial perfusion among subjects with moderate or severe ischemia at baseline. There was no apparent benefit of revascularization (percutaneous or surgical) among patients without ischemia at baseline, or among subjects with only minimal or mild baseline ischemia. In fact, revascularization tended to be detrimental in those without baseline ischemia. Fukuoka and colleagues from Japan (doi: 10.1007/s12350-016-0526-z) study coronary microvascular function with 18F- FDG PET and adenosine stress 13 N-ammonia PET in 18 acute myocardial infarction patients who were successfully revascularized via percutaneous coronary intervention with bare metal stents within 24 hours of the onset of symptoms. They find that myocardial flow reserve in the mismatched segments (defined as reduced resting myocardial blood flow with preserved myocardial FDG uptake) was decreased despite successful reperfusion of the epicardial coronary artery reflecting coronary microvascular dysfunction. Furthermore, functional recovery assessed with wall motion scores in the mismatched segments was incomplete. Zeltser et al. from New York (doi: 10.1007/s12350-016-0464-9) retrospectively evaluate the association of age and gender with downstream resource utilization (i.e., invasive coronary angiography) following SPECT MPI. In a cohort of 3824 patients at a tertiary referral center, younger patients were more likely to undergo an angiogram as compared to octogenarians (77% more likely if \55 years old, 69% if 5569 years old, and 52% if 70-79 years old). Surprisingly no effect/bias was found for gender.
Journal of Nuclear CardiologyÒ
Gomez and colleagues from Chicago, IL (doi: 10.1007/s12350-016-0497-0) investigate whether integrating heart rate response (HRR) to regadenoson with myocardial perfusion imaging (MPI) analysis can enhance risk prediction in end stage renal disease (ESRD) patients (n = 303). Normal HRR to regadenoson was defined as C28% increase from baseline. They noted a step-wise increase in the risk of primary endpoint of all-cause death and the composite secondary endpoint of cardiac death or myocardial infarction. Patients with Normal MPI/Normal HRR had the lowest event rates (thus were truly low risk), and those with Abnormal MPI/Abnormal HRR had the highest event rates, whereas subjects with Abnormal MPI/Normal HRR and Normal MPI/Abnormal HRR had intermediate event rates. Interventricular mechanical dyssynchrony is an important variable for the consideration of cardiac resynchronization therapy (CRT) in patients with heart failure. Zhou et al. (doi:10.1007/s12350-016-0503-6) develop a new RV phase analysis tool and coupled with their LV phase analysis tool, measure interventricular mechanical dyssynchrony from gated SPECT MPI and validate it against electrocardiograms (ECG) derived interventricular conduction delays in 61 patients with ischemic or non-ischemic dilated cardiomyopathy. In total, a high agreement/concordance rate of 86.9% was achieved between SPECT and ECG. Technical advances in CT and specifically the development of multi-detector CT (MDCT) scanners have made possible assessment of not only coronary artery anatomy but also regional myocardial perfusion and estimation of coronary flow reserve (CFR). Marini and colleagues from Genoa, Italy, (doi: 10.1007/s12350-016-0492-5) compared regional CFR quantified by dynamic SPECT MPI and by dynamic multi-detector computed tomography (MDCT) in patients with suspected or known coronary artery disease (CAD). Although overall mean CFR values estimated by SPECT and MDCT were not different, MDCT tended to underestimate high CFR values compared to SPECT. Importantly, both techniques revealed significantly decreased CFR values in segments supplied by atherosclerotic coronary arteries compared to segments served by normal ones. Transient ischemic dilation (TID) of the left ventricle during stress and rest MPI is a proven diagnostic and prognostic marker of severe and extensive CAD. The cut-off value for a ‘‘significant’’ TID ratio varies depending on the stress modality, imaging protocol, radioisotope used, patient position, normal population definition, statistical threshold definition, and software used for TID computation. Jameria and colleagues (doi: 10.1007/s12350-016-0515-2) derive a threshold value
Journal of Nuclear CardiologyÒ
for the TID ratio using upright imaging on a Cadmium Zinc Telluride (CZT) SPECT camera and evaluate its capability to differentiate extensive from non-extensive CAD. With treadmill exercise, an upright TID ratio C1.16 provided a positive predictive value of 50% and a negative predictive value of 85.4% for the identification of extensive CAD. In the regadenoson group, an upright TID ratio of C1.29 provided a positive predictive value of 20% and a negative predictive value of 75.9%. Although not an independent predictor of extensive CAD in all subjects, in subjects with a normal upright LVEF, the TID ratio provided a predictive value by receiver operating characteristics comparable to the summed stress score. Thus the authors suggest that upright TID ratio can serve in an adjunctive role to summed stress score, and may be most effective in patients with a normal upright exercise LVEF. In a comprehensive review article, Jamali et al. from the University of Cincinnati College of Medicine, Cincinnati, OH, (doi:10.1007/s12350-016-0725-7)
Bhambhvani et al JNC Quick Glance September 2017
summarize basic anatomy, physiology, and pathophysiology of the cardiac autonomic nervous system including adrenergic receptors and discuss various imaging modalities (including 123I-mIBG) that can aid in diagnosis of cardiac autonomic dysfunction and autonomic modulation techniques including pharmacologic and device-based therapies of ventricular arrhythmias. We encourage the readers to read the several other original articles in the Journal as well the accompanying scholarly and informative editorials that not only put the findings in perspectives but also outline future directions. We would like to hear your comments as we strive to gain knowledge and in the process, improve patient care. Disclosure There are no COI with this work.
