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Increased right ventricular uptake on stress SPECT myocardial perfusion images in a patient with severe coronary artery disease
NUCLEAR CARDIOLOGY BULLET Increased right ventricular uptake on stress SPECT myocardial perfusion images in a patient with severe coronary artery disease John P. Higgins, MD, MPhil Severe abnormal myocardial perfusion defects on single photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) are often related to obstructive coronary artery disease. However, falsenegative results may be encountered in patients with severe and extensive coronary artery disease if all of the myocardial territories are uniformly affected—so-called balanced ischemia. In these cases other clues to high risk on MPI should be ascertained, including increased right ventricular uptake on stress images. Our patient had relatively minor myocardial perfusion defects at rest and stress but had a striking increase in right ventricular uptake on technetium 99m tetrofosmin imaging and other features that prompted appropriate further cardiac workup and management. Case history. A 72-year-old man with chest pain was referred for exercise myocardial perfusion scintigraphy. He had hypertension, type 2 diabetes mellitus, hyperlipidemia, and peripheral vascular disease. Six weeks previously, he began to have intermittent chest pain at rest and with exertion. Thinking that this was a result of indigestion, he did not seek medical help. He describes the chest pain as 2/10 substernal nonradiating pressure, which lasts for 1 to 5 minutes and is relieved by rest. He also has had shortness of breath on several occasions while gardening. He normally rides a stationary bike without resistance for 15 minutes every morning and walks 3 miles every other day without having shortness of breath or chest pain. His wife notes that he has been more fatigued over the past 2 months and that he is sleeping more during the day. He denies palpitations, orthopnea, or diaphoresis associated with chest pain. His current medications include aspirin, fosinopril, hydrochlorothiazide, simvastatin, and glipizide.
From the Cardiac Stress Laboratory, Harvard Medical School, VA Boston Healthcare System, Boston, Mass. Reprint requests: John P. Higgins, MD, MPhil, Director, Cardiac Stress Laboratory, VA Boston Healthcare System, Nuclear Cardiology Section, Nuclear Medicine 2C-120, 1400 VFW Pkwy, Boston, MA 02132; [email protected]. J Nucl Cardiol 2006;13:725-7. 1071-3581/$32.00 Copyright © 2006 by the American Society of Nuclear Cardiology. doi:10.1016/j.nuclcard.2006.06.115
A 1-day stress/rest Tc-99m tetrofosmin perfusion study was performed, with the stress portion being performed on a treadmill via the Bruce protocol. Approximately 12 mCi Tc-99m tetrofosmin was injected at rest, and 32 mCi was injected during stress. Gated MPI was performed with attenuation correction via Vantage software (Vantage Software, Inc, Croyden, England). The patient exercised for 6 minutes 33 seconds via the Bruce protocol, stopping because of chest pain that was the same as that he had been having for the past 6 weeks. His resting standing heart rate and blood pressure were 62 beats/min and 120/68 mm Hg, respectively. His maximum heart rate and blood pressure during exercise were 133 beats/min (89% of maximal predicted heart rate for his age) and 140/80 mm Hg, respectively. His maximum workload was 7.8 metabolic equivalents. There was significant electrocardiographic evidence of ischemia during exercise with 2- to 3-mm horizontal ST depression noted in leads II, III, aVF, and V4 through V6. His Duke treadmill score was ⫺12.0 (high risk). The SPECT myocardial perfusion scan raw data showed good image quality with a normal-sized left ventricle. The lung/heart ratio on the stress images was increased at 0.50 (normal value, ⬍0.40). There was a small reversible apical/inferoapical perfusion abnormality with a moderate reduction in counts and a small fixed basal inferior wall abnormality on the perfusion scans (Figure 1). The attenuation-corrected scans showed similar findings. The quality-control indices for the stress and rest studies showed normal counts and no truncation. Poststress gated images showed a moderately reduced left ventricular ejection fraction of 32%, with global hypokinesis being present. The left ventricular enddiastolic volume was normal, at 119 mL. The ventricular cavity was larger on stress images than on rest images, with a transient ischemic dilatation ratio of 1.16. There was increased right ventricular tracer uptake on stress images, which was more apparent on the gray-scale images (Figure 2). The exercise right ventricular–left ventricular uptake ratio, determined by use of the regionof-interest method, was elevated, at 0.63 (normal value, 0.24-0.36). Because of the abnormal findings on exercise electrocardiography and the high-risk findings on MPI, the 725
726
Higgins Increased right ventricular uptake in patient with severe CAD
Figure 1. Gated SPECT findings revealed a small reversible apical/inferoapical perfusion abnormality with a moderate reduction in counts, as well as a small fixed basal inferior wall abnormality on the perfusion scans. Systolic dysfunction was present: there was global hypokinesis with a left ventricular ejection fraction of 32%; the left ventricle was of normal size. Septal wall motion was hypokinetic, with reduced thickening. In addition, the lung-heart ratio was abnormal, transient cavity dilatation was present, and right ventricular radionuclide uptake was increased.
Journal of Nuclear Cardiology September/October 2006
Figure 3. Coronary angiogram of left coronary artery system (right anterior oblique caudal view). There was a 99% long left main coronary artery stenosis (arrow) with intimal disease of the left anterior descending and left circumflex coronary arteries.
Figure 4. Coronary angiogram of right coronary artery system (left anterior oblique straight view). The right coronary artery was a small-caliber vessel with a small posterior descending artery.
Figure 2. Gated SPECT findings (gray scale) revealed a small reversible apical/inferoapical perfusion abnormality with a moderate reduction in counts, as well as a small fixed basal inferior wall abnormality on the perfusion scans. The increased right ventricular radionuclide uptake may be easier to observe via a monochrome color scale.
patient was referred for cardiac evaluation. Coronary angiography revealed a 99% long left main coronary artery stenosis with intimal disease of the left anterior descending and left circumflex coronary arteries (Figure 3). The right coronary artery was a small-caliber vessel with a small posterior descending artery (Figure 4). After surgical consultation, the patient underwent successful coronary artery bypass grafting.
Discussion. MPI variables that portend high risk include the following: severe and reversible perfusion defect(s),1 increased pulmonary radiotracer uptake,2 transient cavity dilatation of the left ventricle,3 increased right ventricular tracer uptake on stress images,4 and decreased poststress left ventricular ejection fraction (stunning).5 This case illustrates several of these highrisk features, including increased pulmonary radiotracer uptake, transient cavity dilatation, and increased right ventricular uptake on stress images. As illustrated in Figure 2, it is important to view the images both with a monochrome scale (eg, gray scale) and with another multicolor scale (eg, cool), as these findings may be subtle. Increased right ventricular activity with stress is highly sensitive (90%-93%) but less specific (30%-49%)
Journal of Nuclear Cardiology Volume 13, Number 5;725-7
for severe left main or multivessel coronary artery disease.4 Its low specificity is due to the fact that it is observed in other conditions that result in right ventricular pressure or volume overload.4,6 Such conditions include chronic obstructive pulmonary disease, acute right ventricular strain, pulmonary hypertension, right ventricular hypertrophy, significant valvular heart disease, congenital heart disease (eg, atrial septal defects), and exercise-induced pulmonary hypertension, edema, or bronchospasm.4,7,8 However, in most of these latter cases patients have abnormally increased right ventricular activity on both the rest and stress images. The criterion for increased right ventricular tracer uptake on stress images is as follows4: exercise right ventricular–left ventricular uptake ratio greater than 0.42 (normal value, 0.24-0.36) or exercise right ventricular– rest right ventricular uptake ratio greater than 1.20 (ie, ⬎20% increase from rest to exercise) (or both). The pathophysiology of this increased right ventricular activity in patients with severe coronary artery disease likely involves the following4,7: a) a global reduction in left ventricular tracer uptake at stress (because MPI delineates relative myocardial blood flow, patients with global left ventricular hypoperfusion but preserved right ventricular perfusion at stress may have a relative increase in right ventricular tracer uptake on stress images), and b) an acute rise in right ventricular wall stress due to exercise-induced ischemic left ventricular diastolic dysfunction or systolic dysfunction (or both) (which, in turn, may result in an increase in right ventricular wall stress and a secondary increase in myocardial blood flow and thus increased tracer delivery to the right ventricle). This report highlights the importance of SPECT MPI in helping to risk-stratify patients who present with chest pain. Correct interpretation of SPECT MPI studies requires both a systematic approach to quality-control
Higgins Increased right ventricular uptake in patient with severe CAD
727
issues and thorough image review. Furthermore, we suggest viewing images both with a monochrome scale and with a multicolor scale to aid in the detection of ancillary high-risk findings.
Acknowledgment The author has indicated he has no financial conflicts of interest.
References 1. Papaioannou GI, Heller GV. Risk assessment by myocardial perfusion imaging for coronary revascularization, medical therapy, and noncardiac surgery. Cardiol Rev 2003;11:60-72. 2. Leslie WD, Tully SA, Yogendran MS, Ward LM, Nour KA, Metge CJ. Prognostic value of lung sestamibi uptake in myocardial perfusion imaging of patients with known or suspected coronary artery disease. J Am Coll Cardiol 2005;45:1676-82. 3. Abidov A, Bax JJ, Hayes SW, et al. Transient ischemic dilation ratio of the left ventricle is a significant predictor of future cardiac events in patients with otherwise normal myocardial perfusion SPECT. J Am Coll Cardiol 2003;42:1818-25. 4. Williams KA, Schneider CM. Increased stress right ventricular activity on dual isotope perfusion SPECT: a sign of multivessel and/or left main coronary artery disease. J Am Coll Cardiol 1999; 34:420-7. 5. Thomas GS, Miyamoto MI, Morello AP III, et al. Technetium 99m sestamibi myocardial perfusion imaging predicts clinical outcome in the community outpatient setting. The Nuclear Utility in the Community (NUC) Study. J Am Coll Cardiol 2004;43:213-23. 6. Matoh F, Tawarahara K, Mikami N, et al. Usefulness of lung and right ventricular thallium-201 uptake during single photon emission computed tomography in exercise testing of patients with coronary artery disease [in Japanese]. J Cardiol 2005;46:131-40. 7. Mannting F, Zabrodina YV, Dass C. Significance of increased right ventricular uptake on 99mTc-sestamibi SPECT in patients with coronary artery disease. J Nucl Med 1999;40:889-94. 8. Kondo C. Myocardial perfusion imaging in pediatric cardiology. Ann Nucl Med 2004;18:551-61.
From the Cardiac Stress Laboratory, Harvard Medical School, VA Boston Healthcare System, Boston, Mass. Reprint requests: John P. Higgins, MD, MPhil, Director, Cardiac Stress Laboratory, VA Boston Healthcare System, Nuclear Cardiology Section, Nuclear Medicine 2C-120, 1400 VFW Pkwy, Boston, MA 02132; [email protected]. J Nucl Cardiol 2006;13:725-7. 1071-3581/$32.00 Copyright © 2006 by the American Society of Nuclear Cardiology. doi:10.1016/j.nuclcard.2006.06.115
A 1-day stress/rest Tc-99m tetrofosmin perfusion study was performed, with the stress portion being performed on a treadmill via the Bruce protocol. Approximately 12 mCi Tc-99m tetrofosmin was injected at rest, and 32 mCi was injected during stress. Gated MPI was performed with attenuation correction via Vantage software (Vantage Software, Inc, Croyden, England). The patient exercised for 6 minutes 33 seconds via the Bruce protocol, stopping because of chest pain that was the same as that he had been having for the past 6 weeks. His resting standing heart rate and blood pressure were 62 beats/min and 120/68 mm Hg, respectively. His maximum heart rate and blood pressure during exercise were 133 beats/min (89% of maximal predicted heart rate for his age) and 140/80 mm Hg, respectively. His maximum workload was 7.8 metabolic equivalents. There was significant electrocardiographic evidence of ischemia during exercise with 2- to 3-mm horizontal ST depression noted in leads II, III, aVF, and V4 through V6. His Duke treadmill score was ⫺12.0 (high risk). The SPECT myocardial perfusion scan raw data showed good image quality with a normal-sized left ventricle. The lung/heart ratio on the stress images was increased at 0.50 (normal value, ⬍0.40). There was a small reversible apical/inferoapical perfusion abnormality with a moderate reduction in counts and a small fixed basal inferior wall abnormality on the perfusion scans (Figure 1). The attenuation-corrected scans showed similar findings. The quality-control indices for the stress and rest studies showed normal counts and no truncation. Poststress gated images showed a moderately reduced left ventricular ejection fraction of 32%, with global hypokinesis being present. The left ventricular enddiastolic volume was normal, at 119 mL. The ventricular cavity was larger on stress images than on rest images, with a transient ischemic dilatation ratio of 1.16. There was increased right ventricular tracer uptake on stress images, which was more apparent on the gray-scale images (Figure 2). The exercise right ventricular–left ventricular uptake ratio, determined by use of the regionof-interest method, was elevated, at 0.63 (normal value, 0.24-0.36). Because of the abnormal findings on exercise electrocardiography and the high-risk findings on MPI, the 725
726
Higgins Increased right ventricular uptake in patient with severe CAD
Figure 1. Gated SPECT findings revealed a small reversible apical/inferoapical perfusion abnormality with a moderate reduction in counts, as well as a small fixed basal inferior wall abnormality on the perfusion scans. Systolic dysfunction was present: there was global hypokinesis with a left ventricular ejection fraction of 32%; the left ventricle was of normal size. Septal wall motion was hypokinetic, with reduced thickening. In addition, the lung-heart ratio was abnormal, transient cavity dilatation was present, and right ventricular radionuclide uptake was increased.
Journal of Nuclear Cardiology September/October 2006
Figure 3. Coronary angiogram of left coronary artery system (right anterior oblique caudal view). There was a 99% long left main coronary artery stenosis (arrow) with intimal disease of the left anterior descending and left circumflex coronary arteries.
Figure 4. Coronary angiogram of right coronary artery system (left anterior oblique straight view). The right coronary artery was a small-caliber vessel with a small posterior descending artery.
Figure 2. Gated SPECT findings (gray scale) revealed a small reversible apical/inferoapical perfusion abnormality with a moderate reduction in counts, as well as a small fixed basal inferior wall abnormality on the perfusion scans. The increased right ventricular radionuclide uptake may be easier to observe via a monochrome color scale.
patient was referred for cardiac evaluation. Coronary angiography revealed a 99% long left main coronary artery stenosis with intimal disease of the left anterior descending and left circumflex coronary arteries (Figure 3). The right coronary artery was a small-caliber vessel with a small posterior descending artery (Figure 4). After surgical consultation, the patient underwent successful coronary artery bypass grafting.
Discussion. MPI variables that portend high risk include the following: severe and reversible perfusion defect(s),1 increased pulmonary radiotracer uptake,2 transient cavity dilatation of the left ventricle,3 increased right ventricular tracer uptake on stress images,4 and decreased poststress left ventricular ejection fraction (stunning).5 This case illustrates several of these highrisk features, including increased pulmonary radiotracer uptake, transient cavity dilatation, and increased right ventricular uptake on stress images. As illustrated in Figure 2, it is important to view the images both with a monochrome scale (eg, gray scale) and with another multicolor scale (eg, cool), as these findings may be subtle. Increased right ventricular activity with stress is highly sensitive (90%-93%) but less specific (30%-49%)
Journal of Nuclear Cardiology Volume 13, Number 5;725-7
for severe left main or multivessel coronary artery disease.4 Its low specificity is due to the fact that it is observed in other conditions that result in right ventricular pressure or volume overload.4,6 Such conditions include chronic obstructive pulmonary disease, acute right ventricular strain, pulmonary hypertension, right ventricular hypertrophy, significant valvular heart disease, congenital heart disease (eg, atrial septal defects), and exercise-induced pulmonary hypertension, edema, or bronchospasm.4,7,8 However, in most of these latter cases patients have abnormally increased right ventricular activity on both the rest and stress images. The criterion for increased right ventricular tracer uptake on stress images is as follows4: exercise right ventricular–left ventricular uptake ratio greater than 0.42 (normal value, 0.24-0.36) or exercise right ventricular– rest right ventricular uptake ratio greater than 1.20 (ie, ⬎20% increase from rest to exercise) (or both). The pathophysiology of this increased right ventricular activity in patients with severe coronary artery disease likely involves the following4,7: a) a global reduction in left ventricular tracer uptake at stress (because MPI delineates relative myocardial blood flow, patients with global left ventricular hypoperfusion but preserved right ventricular perfusion at stress may have a relative increase in right ventricular tracer uptake on stress images), and b) an acute rise in right ventricular wall stress due to exercise-induced ischemic left ventricular diastolic dysfunction or systolic dysfunction (or both) (which, in turn, may result in an increase in right ventricular wall stress and a secondary increase in myocardial blood flow and thus increased tracer delivery to the right ventricle). This report highlights the importance of SPECT MPI in helping to risk-stratify patients who present with chest pain. Correct interpretation of SPECT MPI studies requires both a systematic approach to quality-control
Higgins Increased right ventricular uptake in patient with severe CAD
727
issues and thorough image review. Furthermore, we suggest viewing images both with a monochrome scale and with a multicolor scale to aid in the detection of ancillary high-risk findings.
Acknowledgment The author has indicated he has no financial conflicts of interest.
References 1. Papaioannou GI, Heller GV. Risk assessment by myocardial perfusion imaging for coronary revascularization, medical therapy, and noncardiac surgery. Cardiol Rev 2003;11:60-72. 2. Leslie WD, Tully SA, Yogendran MS, Ward LM, Nour KA, Metge CJ. Prognostic value of lung sestamibi uptake in myocardial perfusion imaging of patients with known or suspected coronary artery disease. J Am Coll Cardiol 2005;45:1676-82. 3. Abidov A, Bax JJ, Hayes SW, et al. Transient ischemic dilation ratio of the left ventricle is a significant predictor of future cardiac events in patients with otherwise normal myocardial perfusion SPECT. J Am Coll Cardiol 2003;42:1818-25. 4. Williams KA, Schneider CM. Increased stress right ventricular activity on dual isotope perfusion SPECT: a sign of multivessel and/or left main coronary artery disease. J Am Coll Cardiol 1999; 34:420-7. 5. Thomas GS, Miyamoto MI, Morello AP III, et al. Technetium 99m sestamibi myocardial perfusion imaging predicts clinical outcome in the community outpatient setting. The Nuclear Utility in the Community (NUC) Study. J Am Coll Cardiol 2004;43:213-23. 6. Matoh F, Tawarahara K, Mikami N, et al. Usefulness of lung and right ventricular thallium-201 uptake during single photon emission computed tomography in exercise testing of patients with coronary artery disease [in Japanese]. J Cardiol 2005;46:131-40. 7. Mannting F, Zabrodina YV, Dass C. Significance of increased right ventricular uptake on 99mTc-sestamibi SPECT in patients with coronary artery disease. J Nucl Med 1999;40:889-94. 8. Kondo C. Myocardial perfusion imaging in pediatric cardiology. Ann Nucl Med 2004;18:551-61.