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Nuclear Cardiology
Review Article
NUCLEAR CARDIOLOGY Uma Ravishankar, N. Savita, M.U.Siddique and Surbhi Pande Department of Cardiology, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India. Correspondance to: Dr. Uma Ravishankar, Senior Consultant, Nuclear Cardiology, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India. The single most frequent application of Nuclear Cardiology is in the assessment of myocardial perfusion. The diagnosis of Coronary Artery Disease (CAD) remains a common application of myocardial perfusion scintigraphy, but it is increasingly being used for diagnosis of acute MI, risk stratification after infarction, and assessment of viable myocardium versus scar in patients with chronic coronary disease. Key words: Myocardial perfusion imaging, Viability, FDG-PET, Gated SPECT, Ischemia, Infarct.
INTRODUCTION
Indications and Contraindications to Stress Testing
Myocardial Perfusion Spect Imaging The most important clinical indications for performing myocardial perfusion imaging (MPI) are the detection of coronary artery disease and risk stratification of patients with the disease [1]. Myocardial perfusion imaging maps the relative distribution of coronary flow, which is normally almost uniform in the absence of prior infarction or fibrosis. In the presence of luminal narrowing, flow non uniformity corresponds to the anatomical location of the coronary stenoses and to the cumulative severity of the obstructions along the coronary arterial tree and the size of its watershed. Therefore, MPI can diagnose not only the presence of coronary artery disease, but also its extent and severity [2]. The easiest method of increasing coronary flow is physical exercise, using a motorized treadmill or a stationary bicycle. In patients who are unable to exercise adequately, pharmacological agents (adenosine, dipyridamole, dobutamine) are used for transient elevation of coronary flow [2].
Diagnosis of chest pain syndromes Evaluation of known CAD; location and extent of ischemia Assessment of medical therapy Assessment after PTCA or CABG Evaluation and prognosis post myocardial infarction Evaluation of myocardial reserve Preoperative evaluation for major noncardiac surgery Screening high risk patient populations Contraindications Acute myocardial infarction Unstable angina Life threatening cardiac arrhythmia Acute inflammatory disease of heart Critical aortic stenosis
Rationale in Exercise Testing Physical exercise increases cardiac workload: increased work increases myocardial oxygen demand.
Pulmonary edema/CHF Pulmonary embolism Excessive arterial hypertension
Normal coronary arteries dilate and flow increases. Stenotic vessels do not dilate; flow reserve is limited; myocardial ischemia is induced. Apollo Medicine, Vol. 4, No. 3, September 2007
Indications
210
Serious intercurrent non cardiac illness Inability to provide informed consent
Review Article
Patient Groups Commonly Referred for MPI
Patients followed after revascularization procedures ( CABG, PTCA, coronary stenting ) Patients evaluated prior to non cardiac surgery Patients surveyed after cardiac transplantation for presence of transplant vasculopathy
Patients with stable CAD evaluated for prognosis Patients with acute chest pain syndromes Patients after an acute myocardial infarction
Diagnostic patterns in myocardial perfusion imaging after stress testing [3] Pattern on immediate post stress images Normal
Pattern on resting delayed or reinjection images
Diagnosis
Normal
Normal
Defect(s)
Normal
Transient Ischemia
Defect(s)
Defect (unchanged)
Prior infarct with scar
Defect(s)
Some normalization with areas of persistent defect
Transient ischemia and scar
Normal
Defect
“Reverse” redistribution
Fig. 1. Stress induced reversible ischemia in apical, and infero-lateral walls of left ventricular myocardium.
Fig. 2. Apical, anterior, septal and infero-septal infarct with no scan evidence of reversible ischemia.
QUANTITATIVE ANALYSIS
The relative radiotracer uptake on SPECT images is displayed either as polar plots (bull’s eye plots) or as circumferential count distribution profiles [1].
Quantitative analysis is complementary to visual analysis. A number of validated software packages are commercially available for quantification of SPECT myocardial perfusion and function. Normalized relative radiotracer uptake in reconstructed slices is compared and quantified against normal data files.
Gated SPECT Imaging This evaluates ventricular function at rest during a myocardial perfusion study. It gives an appreciation of wall thickening, wall motion and left ventricular volumes.
211
In patients with perfusion defects, gated SPECT Apollo Medicine, Vol. 4, No. 3, September 2007
Review Article
to hospital admission. Others perform stress testing, with or without MPI, 6-12 hours after a negative work up for an acute MI. Based on the results of MPI, a patients short term prognosis can be determined . Safety of early stress testing has been well documented. In several cost analyses, up to a 50% decrease in hospital charges and a 50% shorter hospital stay can potentially be realized [2]. MPI after an Acute Myocardial Infarction The purposes of early pre discharge MPI evaluation after an acute myocardial infarction are:
Fig. 3. Gated SPECT
imaging is helpful in detecting myocardial viability and differentiating withy attenuation artifacts.
•
To assess the extent of sustained damage, including determination of ejection fraction,
•
To detect residual ischemia, both in the infarct related territory and in the other vascular territories using either exercise MPI or pharmacological stress.
A perfusion defect still showing wall thickening and/ or wall motion can be identified as a viable region. Wall motion and photon activity are the basis for viability [4].
Patients with a limited amount of ischemia after an acute myocardial infarction can be risk stratified non invasively and, if found to have a low risk profile, treated medically with the same results as treated with interventions [2].
CLINICAL UTILITY OF MYOCARDIAL PERFUSION IMAGING
MPI in Patients After Revascularization Procedures
Coronary Artery Disease
Successful surgery or angioplasty results in the elimination of transient defects caused by exerciseinduced ischemia but have no effect on scarred areas , and fixed defects should appear unchanged.
Risk stratification in stable CAD •
Multiple defects in two or more coronary artery territories
•
Large stress induced defects
•
Large stress induced reversibility
•
Increased pulmonary radiotracer uptake after stress
•
Transient dilatation of left ventricle after stress
•
Transient visualization of right ventricle after stress
•
Depressed resting LVEF
Imaging should be delayed 6 weeks or more because some pre intervention defects may persist if the scan is done too soon [3].
High risk patterns on either planar or SPECT imaging are highly specific (approximately 95%) for multivessel coronary disease; however, the sensitivity is only about 70% (1). Acute Chest Pain Syndromes Only 40% of the visits of chest pain in emergency department (ED) the pain is of cardiac origin. Many medical centers have recently established dedicated chest pain evaluation units, usually adjacent to ED. Some centers perform MPI at rest. Abnormal results lead Apollo Medicine, Vol. 4, No. 3, September 2007
If a patient has an infarction as a result of the therapeutic intervention, a previously transient defect may be converted into a fixed defect or an entirely new defect may occur as a result of the injury.
At approximately 4 weeks after the intervention , a good correlation has been demonstrated between stress induced myocardial perfusion abnormalities and the presence or absence of restonoses, independent of clinical symptoms [1]. When symptoms recur, the early post therapy study serves as a useful baseline. The development of new or recurrent disease is readily detected on repeat stress imaging. MPI Prior to Noncardiac Surgery
212
The American Heart Association and the American
Review Article
College of Cardiology (AHA/ACC) published extensive guidelines for preoperative cardiac stress testing in patients scheduled for noncardiac surgery in which the type of surgery and clinical risk factors are weighted. If testing is indicated, in most patients pharmacologic vasodilation myocardial perfusion imaging with adenosine or dipyridamole is the most appropriate test. Short term prognosis is determined by the presence of evidence of ischemia, i.e., reversible myocardial perfusion defects, whereas long term prognosis is determined by the presence of fixed defects [1]. MPI After Cardiac Transplantation MPI (and perhaps stress echocardiography) are emerging as surveillance methods for detection of asymptomatic myocardial ischemia [2]. CONGESTIVE HEART FAILURE Myocardial stress perfusion SPECT imaging is very useful for prognostic risk stratification. The value of stress and rest imaging lies in establishing : •
LV vs RV dysfunction.
•
In the presence of normal LV function or only mild to moderate LV dysfunction , the presence of extensive stress induced ischemia, which clinically presents as heart failure, a high risk combination that indicates need for CABG.
•
•
In the presence of severe LV dysfunction the presence of stress induced ischemia that helps clarify vague symptoms or document silent ischemia. It also helps to distinguish ischemic from non ischemic heart disease.
ASSESSMENT OF VIABILITY Nonfunctional but viable myocardium includes stunned and hibernation myocardium: 1. Stunned myocardium shows decreased contractility after an episode of prolonged ischemia, but intact blood flow at the time of observation. Stunned myocardium generally improves without further intervention. 2. Hibernation occurs in myocardium that has undergone a down-regulation of contractile function, in response to chronic ischemia. Hibernation by definition requires the restoration of blood flow in order to improve function [2].
Important clinical issue is that viable but dysfunctional myocardium in patients with coronary artery disease will improve in function only if identified and revascularized. In the setting of hibernating myocardium, by definition, indexes of regional perfusion and systolic function (regional wall motion and wall thickening) will be severely reduced or absent despite maintenance of tissue viability. Thus these three indexes are imprecise in differentiating hibernating myocardium from myocardial scar [1]. Low dose dobutamine (LDDE) and high dose dobutamine echocardiography showed that both a biphasic response (improvement at low dose and deterioration at high dose) and sustained improvement of wall motion (improvement at both low dose and high dose) in dysfunctional segments were highly predictive of reversible dysfunction with a combined sensitivity of 84% and specificity of 81% [2]. Simple stress-redistribution with T l-201 has been shown to underestimate the presence of viability. Augmentation with late (12-24h) imaging and/or resting reinjection was found to increase sensitivity for viability. The latter approach yielded a combined mean sensitivity of 86% but a specificity of 47% [2]. Rest-redistribution T l-201 imaging has shown combined sensitivity of 90% and specificity of 54% [2]. Myocardial perfusion imaging with Tc99msestamibi has yielded a slightly lower sensitivity of 83% but higher specificity of 69%. Tc99m sestamibi imaging combined with nitrate administration has yielded an improved sensitivity of 91% and specificity of 88%. Gated Tc99m sestamibi imaging with nitroglycerin (NTG) administration can be used successfully as an alternative to rest-redistribution Th-201 SPECT imaging. Tc99m tetrofosmine showed performance similar to that of Th-201 stress-redistribution imaging and slightly lower sensitivity than rest-late redistribution Th-201 imaging [2]. It is evident that neither myocardial perfusion imaging or LDDE imaging can supply both high sensitivity and high specificity. Another strategy is the addition of metabolic imaging to perfusion imaging using analogues of either free fatty acids or glucose imaging. Injured myocardium frequently demonstrates impaired oxidative metabolism,
213
Apollo Medicine, Vol. 4, No. 3, September 2007
Review Article
impaired free fatty acid utilization and an excess of glucose utilization relative to flow. F-18 fleurodeoxyglucose ( FDG ) is an analogue of glucose , which is transported into cells via a specific glucose membrane transport and is phosphorylated by hexo-kinase. Unlike glucose , FDG is trapped and is not metabolized further. Its accumulation is and index of glucose utilization. Myocardial flow can be imaged with F-18 FDG, N-13 ammonia or Rb-82 with PET imaging, or Th-201 or Tc99m-sestamibi using SPECT. POSITRON EMISSION TOMOGRAPHY OF THE HEART PET imaging with FDG yielded a combined 88% sensitivity and 73% specificity for viability [2]. The reported sensitivity of PET in the diagnosis of CAD is on the order of 95%. The specificity reported in the early literature is also 95% or better [3]. Diagnosis of CAD
Fig. 4a. The SPECT study indicated multiple fixed perfusion defects in the anterior wall, apex and inferior wall, consistent with scar.
The two PET perfusion agents, Rb-82 and N-13 ammonia are used most commonly for the diagnosis of CAD. After baseline studies are obtained under resting conditions, one of the pharmacological agents is administered to challenge coronary flow reserve. Normal patients should have homogenous uptake of tracer throughout both the right and left ventricular myocardium. Patients with hemodynamically significant coronary artery disease but no ischemia at rest demonstrate normal visualization of myocardium at rest with the appearance of perfusion defects after pharmacological stress. Patients with resting ischemia (hibernating myocardium) demonstrate perfusion defects, even on baseline studies, that may become worse after pharmacological stress. Areas of prior myocardial infarction appear cold on both baseline and post stress images. Combined Perfusion and F-18 FDG Imaging The combination of a photon deficient area by perfusion imaging that demonstrates FDG uptake is the scintigraphic hallmark of severely ischemic or hibernating myocardium. The presence of FDG indicates myocardial viability. Completely infracted or scarred areas do no accumulate FDG. Apollo Medicine, Vol. 4, No. 3, September 2007
Fig. 4b. The PET perfusion study is arranged as short axis (stress over rest), vertical long axis (stress over rest), and horizontal long axis (stress over rest). Note the clear reversibility in portions of the anterior wall, apex and inferior wall.
Patients with viable but severely ischemic myocardium have better survival and event outcomes from surgical revascularization tham from medical management. Patients with only myocardial scarring and no ischemia do not benefit from revascularization surgery.
214
Review Article
option than cardiac transplantation. On the other hand if there is just diffuse abnormality without evidence of hibernating myocardium in the face of extremely poor global function, CABG is unlikely to improve pump function.
Diagnostic patterns for combined and FDG imaging [3] Perfusion
Glucose (NH3, Rb)
Glucose metabolism (FDG)
Normal myocardium
Present
Present
Ischemic myocardium ( severe, chronic)
Absent or decreased
Present
Necrotic myocardium or scar
Absent
Absent
A
B
C
FDG PET
Perfusion
Fig. 6. FDG PET (resting) left with 99mTc tetrofosmin study in same patient displayed in short axis (A), vertical long axis (B) and horizontal long axis (C) note FDG uptake with corresponding reduction in perfusion in the interventricular septum (arrows) indicating compromised, but viable myocardium. There is no perfusion or viable myocardium at the apex suggesting old infarction. Fig. 5. PET cardiac imaging - comparison of FDG and NH3 studies.
Combined Tc99m sestamibi and FDG imaging Areas demonstrating diminished Tc99m activity with normal or increased FDG represent ischemic but viable tissue and have a high likelihood of functional recovery after revascularization. Areas of matched perfusion and metabolic abnormality are unlikely to improve. If the poor function of the heart can be shown to result from multiple areas of chronically ischemic but viable (hibernating) tissue CABG is probably a better
OTHER RADIONUCLIDES FOR STUDYING THE HEART Radionuclide metaiodobenzylguanidine (MIBG) has been used to study the adrenergic status of the heart. Decreased uptake is seen after MI and in diabetic patients with denervated hearts. Some patients with cardiomyopathy also have diminished or absent uptake. Neuroendocrine imaging techniques remain investigative, although it is being used to assess reinnervation after cardiac transplantation and to help determine prognosis in patients with dilated cardiomyopathy.
215
A recently approved agent is radiolabeled antimyosin Apollo Medicine, Vol. 4, No. 3, September 2007
Review Article
antibody. The tracer localizes in areas of acute MI. The sensitivity for detecting acute MI is quite high, over 85% in reported cases [3].
2. Elgazzar Abdelhamid.H. The Pathologic Basis of Nuclear Medicine; 2001 print; Springer Publishers, Heidelberg, Germany; pp 221-257.
REFERENCES
3. Thrall James.H, Ziessman Harvey.A. Nuclera Medicine The requisites; 2nd edition; 2001; Mosby Publishers, Missouri, USA, pp 65-109.
1. Sandler Martin P, Coleman R. Edward, Patton A. James, Wackers Frans J. TH., Gotschalk Alexander. Diagnostic Nuclear Medicine; 4th edition;2003; Lippincott Williams & Wilkins Publishers, Philadelphia, USA; pp 273-332.
Apollo Medicine, Vol. 4, No. 3, September 2007
216
4. Mesotten L, Maes A, Hambye A Sophie, Everaert Hhendrik, Muegdenbergh V V, Franken P, Mortelman L. Nuclear Cardiology, Part IV. Viability. J Nucl Med Techno 1999; 27(2): 93-102.
NUCLEAR CARDIOLOGY Uma Ravishankar, N. Savita, M.U.Siddique and Surbhi Pande Department of Cardiology, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India. Correspondance to: Dr. Uma Ravishankar, Senior Consultant, Nuclear Cardiology, Indraprastha Apollo Hospitals, Sarita Vihar, New Delhi 110 076, India. The single most frequent application of Nuclear Cardiology is in the assessment of myocardial perfusion. The diagnosis of Coronary Artery Disease (CAD) remains a common application of myocardial perfusion scintigraphy, but it is increasingly being used for diagnosis of acute MI, risk stratification after infarction, and assessment of viable myocardium versus scar in patients with chronic coronary disease. Key words: Myocardial perfusion imaging, Viability, FDG-PET, Gated SPECT, Ischemia, Infarct.
INTRODUCTION
Indications and Contraindications to Stress Testing
Myocardial Perfusion Spect Imaging The most important clinical indications for performing myocardial perfusion imaging (MPI) are the detection of coronary artery disease and risk stratification of patients with the disease [1]. Myocardial perfusion imaging maps the relative distribution of coronary flow, which is normally almost uniform in the absence of prior infarction or fibrosis. In the presence of luminal narrowing, flow non uniformity corresponds to the anatomical location of the coronary stenoses and to the cumulative severity of the obstructions along the coronary arterial tree and the size of its watershed. Therefore, MPI can diagnose not only the presence of coronary artery disease, but also its extent and severity [2]. The easiest method of increasing coronary flow is physical exercise, using a motorized treadmill or a stationary bicycle. In patients who are unable to exercise adequately, pharmacological agents (adenosine, dipyridamole, dobutamine) are used for transient elevation of coronary flow [2].
Diagnosis of chest pain syndromes Evaluation of known CAD; location and extent of ischemia Assessment of medical therapy Assessment after PTCA or CABG Evaluation and prognosis post myocardial infarction Evaluation of myocardial reserve Preoperative evaluation for major noncardiac surgery Screening high risk patient populations Contraindications Acute myocardial infarction Unstable angina Life threatening cardiac arrhythmia Acute inflammatory disease of heart Critical aortic stenosis
Rationale in Exercise Testing Physical exercise increases cardiac workload: increased work increases myocardial oxygen demand.
Pulmonary edema/CHF Pulmonary embolism Excessive arterial hypertension
Normal coronary arteries dilate and flow increases. Stenotic vessels do not dilate; flow reserve is limited; myocardial ischemia is induced. Apollo Medicine, Vol. 4, No. 3, September 2007
Indications
210
Serious intercurrent non cardiac illness Inability to provide informed consent
Review Article
Patient Groups Commonly Referred for MPI
Patients followed after revascularization procedures ( CABG, PTCA, coronary stenting ) Patients evaluated prior to non cardiac surgery Patients surveyed after cardiac transplantation for presence of transplant vasculopathy
Patients with stable CAD evaluated for prognosis Patients with acute chest pain syndromes Patients after an acute myocardial infarction
Diagnostic patterns in myocardial perfusion imaging after stress testing [3] Pattern on immediate post stress images Normal
Pattern on resting delayed or reinjection images
Diagnosis
Normal
Normal
Defect(s)
Normal
Transient Ischemia
Defect(s)
Defect (unchanged)
Prior infarct with scar
Defect(s)
Some normalization with areas of persistent defect
Transient ischemia and scar
Normal
Defect
“Reverse” redistribution
Fig. 1. Stress induced reversible ischemia in apical, and infero-lateral walls of left ventricular myocardium.
Fig. 2. Apical, anterior, septal and infero-septal infarct with no scan evidence of reversible ischemia.
QUANTITATIVE ANALYSIS
The relative radiotracer uptake on SPECT images is displayed either as polar plots (bull’s eye plots) or as circumferential count distribution profiles [1].
Quantitative analysis is complementary to visual analysis. A number of validated software packages are commercially available for quantification of SPECT myocardial perfusion and function. Normalized relative radiotracer uptake in reconstructed slices is compared and quantified against normal data files.
Gated SPECT Imaging This evaluates ventricular function at rest during a myocardial perfusion study. It gives an appreciation of wall thickening, wall motion and left ventricular volumes.
211
In patients with perfusion defects, gated SPECT Apollo Medicine, Vol. 4, No. 3, September 2007
Review Article
to hospital admission. Others perform stress testing, with or without MPI, 6-12 hours after a negative work up for an acute MI. Based on the results of MPI, a patients short term prognosis can be determined . Safety of early stress testing has been well documented. In several cost analyses, up to a 50% decrease in hospital charges and a 50% shorter hospital stay can potentially be realized [2]. MPI after an Acute Myocardial Infarction The purposes of early pre discharge MPI evaluation after an acute myocardial infarction are:
Fig. 3. Gated SPECT
imaging is helpful in detecting myocardial viability and differentiating withy attenuation artifacts.
•
To assess the extent of sustained damage, including determination of ejection fraction,
•
To detect residual ischemia, both in the infarct related territory and in the other vascular territories using either exercise MPI or pharmacological stress.
A perfusion defect still showing wall thickening and/ or wall motion can be identified as a viable region. Wall motion and photon activity are the basis for viability [4].
Patients with a limited amount of ischemia after an acute myocardial infarction can be risk stratified non invasively and, if found to have a low risk profile, treated medically with the same results as treated with interventions [2].
CLINICAL UTILITY OF MYOCARDIAL PERFUSION IMAGING
MPI in Patients After Revascularization Procedures
Coronary Artery Disease
Successful surgery or angioplasty results in the elimination of transient defects caused by exerciseinduced ischemia but have no effect on scarred areas , and fixed defects should appear unchanged.
Risk stratification in stable CAD •
Multiple defects in two or more coronary artery territories
•
Large stress induced defects
•
Large stress induced reversibility
•
Increased pulmonary radiotracer uptake after stress
•
Transient dilatation of left ventricle after stress
•
Transient visualization of right ventricle after stress
•
Depressed resting LVEF
Imaging should be delayed 6 weeks or more because some pre intervention defects may persist if the scan is done too soon [3].
High risk patterns on either planar or SPECT imaging are highly specific (approximately 95%) for multivessel coronary disease; however, the sensitivity is only about 70% (1). Acute Chest Pain Syndromes Only 40% of the visits of chest pain in emergency department (ED) the pain is of cardiac origin. Many medical centers have recently established dedicated chest pain evaluation units, usually adjacent to ED. Some centers perform MPI at rest. Abnormal results lead Apollo Medicine, Vol. 4, No. 3, September 2007
If a patient has an infarction as a result of the therapeutic intervention, a previously transient defect may be converted into a fixed defect or an entirely new defect may occur as a result of the injury.
At approximately 4 weeks after the intervention , a good correlation has been demonstrated between stress induced myocardial perfusion abnormalities and the presence or absence of restonoses, independent of clinical symptoms [1]. When symptoms recur, the early post therapy study serves as a useful baseline. The development of new or recurrent disease is readily detected on repeat stress imaging. MPI Prior to Noncardiac Surgery
212
The American Heart Association and the American
Review Article
College of Cardiology (AHA/ACC) published extensive guidelines for preoperative cardiac stress testing in patients scheduled for noncardiac surgery in which the type of surgery and clinical risk factors are weighted. If testing is indicated, in most patients pharmacologic vasodilation myocardial perfusion imaging with adenosine or dipyridamole is the most appropriate test. Short term prognosis is determined by the presence of evidence of ischemia, i.e., reversible myocardial perfusion defects, whereas long term prognosis is determined by the presence of fixed defects [1]. MPI After Cardiac Transplantation MPI (and perhaps stress echocardiography) are emerging as surveillance methods for detection of asymptomatic myocardial ischemia [2]. CONGESTIVE HEART FAILURE Myocardial stress perfusion SPECT imaging is very useful for prognostic risk stratification. The value of stress and rest imaging lies in establishing : •
LV vs RV dysfunction.
•
In the presence of normal LV function or only mild to moderate LV dysfunction , the presence of extensive stress induced ischemia, which clinically presents as heart failure, a high risk combination that indicates need for CABG.
•
•
In the presence of severe LV dysfunction the presence of stress induced ischemia that helps clarify vague symptoms or document silent ischemia. It also helps to distinguish ischemic from non ischemic heart disease.
ASSESSMENT OF VIABILITY Nonfunctional but viable myocardium includes stunned and hibernation myocardium: 1. Stunned myocardium shows decreased contractility after an episode of prolonged ischemia, but intact blood flow at the time of observation. Stunned myocardium generally improves without further intervention. 2. Hibernation occurs in myocardium that has undergone a down-regulation of contractile function, in response to chronic ischemia. Hibernation by definition requires the restoration of blood flow in order to improve function [2].
Important clinical issue is that viable but dysfunctional myocardium in patients with coronary artery disease will improve in function only if identified and revascularized. In the setting of hibernating myocardium, by definition, indexes of regional perfusion and systolic function (regional wall motion and wall thickening) will be severely reduced or absent despite maintenance of tissue viability. Thus these three indexes are imprecise in differentiating hibernating myocardium from myocardial scar [1]. Low dose dobutamine (LDDE) and high dose dobutamine echocardiography showed that both a biphasic response (improvement at low dose and deterioration at high dose) and sustained improvement of wall motion (improvement at both low dose and high dose) in dysfunctional segments were highly predictive of reversible dysfunction with a combined sensitivity of 84% and specificity of 81% [2]. Simple stress-redistribution with T l-201 has been shown to underestimate the presence of viability. Augmentation with late (12-24h) imaging and/or resting reinjection was found to increase sensitivity for viability. The latter approach yielded a combined mean sensitivity of 86% but a specificity of 47% [2]. Rest-redistribution T l-201 imaging has shown combined sensitivity of 90% and specificity of 54% [2]. Myocardial perfusion imaging with Tc99msestamibi has yielded a slightly lower sensitivity of 83% but higher specificity of 69%. Tc99m sestamibi imaging combined with nitrate administration has yielded an improved sensitivity of 91% and specificity of 88%. Gated Tc99m sestamibi imaging with nitroglycerin (NTG) administration can be used successfully as an alternative to rest-redistribution Th-201 SPECT imaging. Tc99m tetrofosmine showed performance similar to that of Th-201 stress-redistribution imaging and slightly lower sensitivity than rest-late redistribution Th-201 imaging [2]. It is evident that neither myocardial perfusion imaging or LDDE imaging can supply both high sensitivity and high specificity. Another strategy is the addition of metabolic imaging to perfusion imaging using analogues of either free fatty acids or glucose imaging. Injured myocardium frequently demonstrates impaired oxidative metabolism,
213
Apollo Medicine, Vol. 4, No. 3, September 2007
Review Article
impaired free fatty acid utilization and an excess of glucose utilization relative to flow. F-18 fleurodeoxyglucose ( FDG ) is an analogue of glucose , which is transported into cells via a specific glucose membrane transport and is phosphorylated by hexo-kinase. Unlike glucose , FDG is trapped and is not metabolized further. Its accumulation is and index of glucose utilization. Myocardial flow can be imaged with F-18 FDG, N-13 ammonia or Rb-82 with PET imaging, or Th-201 or Tc99m-sestamibi using SPECT. POSITRON EMISSION TOMOGRAPHY OF THE HEART PET imaging with FDG yielded a combined 88% sensitivity and 73% specificity for viability [2]. The reported sensitivity of PET in the diagnosis of CAD is on the order of 95%. The specificity reported in the early literature is also 95% or better [3]. Diagnosis of CAD
Fig. 4a. The SPECT study indicated multiple fixed perfusion defects in the anterior wall, apex and inferior wall, consistent with scar.
The two PET perfusion agents, Rb-82 and N-13 ammonia are used most commonly for the diagnosis of CAD. After baseline studies are obtained under resting conditions, one of the pharmacological agents is administered to challenge coronary flow reserve. Normal patients should have homogenous uptake of tracer throughout both the right and left ventricular myocardium. Patients with hemodynamically significant coronary artery disease but no ischemia at rest demonstrate normal visualization of myocardium at rest with the appearance of perfusion defects after pharmacological stress. Patients with resting ischemia (hibernating myocardium) demonstrate perfusion defects, even on baseline studies, that may become worse after pharmacological stress. Areas of prior myocardial infarction appear cold on both baseline and post stress images. Combined Perfusion and F-18 FDG Imaging The combination of a photon deficient area by perfusion imaging that demonstrates FDG uptake is the scintigraphic hallmark of severely ischemic or hibernating myocardium. The presence of FDG indicates myocardial viability. Completely infracted or scarred areas do no accumulate FDG. Apollo Medicine, Vol. 4, No. 3, September 2007
Fig. 4b. The PET perfusion study is arranged as short axis (stress over rest), vertical long axis (stress over rest), and horizontal long axis (stress over rest). Note the clear reversibility in portions of the anterior wall, apex and inferior wall.
Patients with viable but severely ischemic myocardium have better survival and event outcomes from surgical revascularization tham from medical management. Patients with only myocardial scarring and no ischemia do not benefit from revascularization surgery.
214
Review Article
option than cardiac transplantation. On the other hand if there is just diffuse abnormality without evidence of hibernating myocardium in the face of extremely poor global function, CABG is unlikely to improve pump function.
Diagnostic patterns for combined and FDG imaging [3] Perfusion
Glucose (NH3, Rb)
Glucose metabolism (FDG)
Normal myocardium
Present
Present
Ischemic myocardium ( severe, chronic)
Absent or decreased
Present
Necrotic myocardium or scar
Absent
Absent
A
B
C
FDG PET
Perfusion
Fig. 6. FDG PET (resting) left with 99mTc tetrofosmin study in same patient displayed in short axis (A), vertical long axis (B) and horizontal long axis (C) note FDG uptake with corresponding reduction in perfusion in the interventricular septum (arrows) indicating compromised, but viable myocardium. There is no perfusion or viable myocardium at the apex suggesting old infarction. Fig. 5. PET cardiac imaging - comparison of FDG and NH3 studies.
Combined Tc99m sestamibi and FDG imaging Areas demonstrating diminished Tc99m activity with normal or increased FDG represent ischemic but viable tissue and have a high likelihood of functional recovery after revascularization. Areas of matched perfusion and metabolic abnormality are unlikely to improve. If the poor function of the heart can be shown to result from multiple areas of chronically ischemic but viable (hibernating) tissue CABG is probably a better
OTHER RADIONUCLIDES FOR STUDYING THE HEART Radionuclide metaiodobenzylguanidine (MIBG) has been used to study the adrenergic status of the heart. Decreased uptake is seen after MI and in diabetic patients with denervated hearts. Some patients with cardiomyopathy also have diminished or absent uptake. Neuroendocrine imaging techniques remain investigative, although it is being used to assess reinnervation after cardiac transplantation and to help determine prognosis in patients with dilated cardiomyopathy.
215
A recently approved agent is radiolabeled antimyosin Apollo Medicine, Vol. 4, No. 3, September 2007
Review Article
antibody. The tracer localizes in areas of acute MI. The sensitivity for detecting acute MI is quite high, over 85% in reported cases [3].
2. Elgazzar Abdelhamid.H. The Pathologic Basis of Nuclear Medicine; 2001 print; Springer Publishers, Heidelberg, Germany; pp 221-257.
REFERENCES
3. Thrall James.H, Ziessman Harvey.A. Nuclera Medicine The requisites; 2nd edition; 2001; Mosby Publishers, Missouri, USA, pp 65-109.
1. Sandler Martin P, Coleman R. Edward, Patton A. James, Wackers Frans J. TH., Gotschalk Alexander. Diagnostic Nuclear Medicine; 4th edition;2003; Lippincott Williams & Wilkins Publishers, Philadelphia, USA; pp 273-332.
Apollo Medicine, Vol. 4, No. 3, September 2007
216
4. Mesotten L, Maes A, Hambye A Sophie, Everaert Hhendrik, Muegdenbergh V V, Franken P, Mortelman L. Nuclear Cardiology, Part IV. Viability. J Nucl Med Techno 1999; 27(2): 93-102.