- Email: [email protected]
Antimyosin Scintigraphy for Detection of Cardiac Amyloidosis
Antimyosin Scintigraphy for Detection of Cardiac Amyloidosis John Lekakis, MD, Meletios Dimopoulos, MD, John Nanas, MD, Vassilios Prassopoulos, MD, Nikos Agapitos, MD, George Alexopoulos, MD, Lakis Palazis, MD, Panos Kostamis, MD, Stamatios Stamatelopoulos, MD, and Spyridon Moulopoulos, MD ardiac amyloidosis belongs to the list of important C cardiac masqueraders; it is one of the more likely causes of restrictive cardiomyopathy, the diagnosis of which may be frequently missed.1 Infiltration of the heart muscle by amyloid is frequently found in patients with amyloidosis and is associated with very poor prognosis.2 Echocardiography and radionuclide imaging with techetium-99m pyrophosphate or iodine-123 labeled serum amyloid P component offer valuable insight to the diagnosis of cardiac amyloidosis, but for a definitive diagnosis of this condition an endomyocardial biopsy is usually required.3–5 We have recently reported a case of cardiac amyloidosis detected by indium-111 antimyosin imaging.6 In this study we prospectively investigated the diagnostic value of antimyosin scanning in a group of patients with biopsy-proven cardiac amyloidosis; this study highlights a new, noninvasive method for diagnosing cardiac amyloid deposits. •••
Seven patients with histologically confirmed primary or myeloma-related amyloidosis were studied; 3 were women and 4 men and their mean age was 56 6 9 years (range 37 to 61). Characteristics of the patients are shown in Table I. Clinically overt heart failure was present in 4 patients and all patients had left ventricular thickening on the echocardiogram and an abnormal electrocardiogram. Right ventricular endomyocardial biopsy was performed in all patients and it was successful in 6 of 7 patients; Congo red staining was positive for amyloid in the vascular wall and interstitium of all specimens. In 1 patient (patient 2), biopsy was not obtained because the patient developed ventricular tachycardia during the catheterization. However, in this patient the diagnosis of cardiac amyloidosis was confirmed by the presence of left ventricular thickening on the echocardiogram, a low voltage on the electrocardiogram, and presence of amyloid in a kidney biopsy specimen. Six patients with low probability of cardiac amyloidosis formed a control group; there were 2 women and 4 men with a mean age of 54 6 11 years (range 34 to 60). All control patients had a long-standing history of systemic hypertension and left ventricular hypertrophy on the echocardiogram (septum 1.5 6 0.4 mm, posterior wall 1.4 6 0.3 mm), but no evidence of From the Department of Clinical Therapeutics and Department of Nuclear Medicine, Alexandra University Hospital, Athens, Greece. Dr. Lekakis’ address is: 86 Alkionis Street, P. Faliron 175 62, Athens, Greece. Manuscript received March 11, 1997; revised manuscript received and accepted June 2, 1997. ©1997 by Excerpta Medica, Inc. All rights reserved.
plasma cell dyscrasia. An additional control group consisted of 10 patients with long-standing (.1 year) history of idiopathic-dilated cardiomyopathy and no evidence of myocarditis on endomyocardial biopsy; there were 4 women and 6 men and the mean age was 49 6 6 years (range 38 to 57). Left ventricular ejection fraction was 23 6 13% (range 9 to 49). All patients underwent myosin-specific monoclonal antibody imaging. Antimyosin antibody (Myoscint, Centocor, Inc., Leiden, The Netherlands) was supplied as a sterile nonpyrogenic solution containing 0.5 mg of R11 D10 Fab diethylenetramine pentaacetic acid, which is a mouse monoclonal antibody fragment that binds specifically to myosin. The antimyosin was radiolabeled by the addition of sterile indium-111 chloride. Two millicuries of indium-111 were diluted to 10 ml of volume and were administered intravenously by slow injection. Planar imaging was performed after 48 hours using a gamma camera (General Electric Maxi Camera 400, Milwaukee, Wisconsin). Three views were obtained (anterior, 45° left anterior oblique, and left anterior oblique, 70°) using a 128 3 128 matrix for 10 min/view. Both photopeaks of indium-111 were used (173 keV and 247 keV) with 20% energy windows. A heart-to-lung (H/L) ratio was used to quantify tracer uptake; the unprocessed anterior projection was used to adjust a region of interest in the myocardium and a region of interest in each lung. The average count per pixel in the myocardium was divided by the average count per pixel in each lung to obtain the H/L ratio. A ratio .1.6 was considered abnormal.7 The antimyosin antibody was administered without adverse reactions in all patients and control subjects. In the control group, all 6 patients had a normal antimyosin study; H/L ratio ranged from 1.3 to 1.6 (mean 1.43 6 0.1). In each patient with cardiac amyloidosis the antimyosin scanning was always abnormal (Figure 1); the H/L ratio ranged from 2.1 to 3.2 (mean 2.5 6 0.4) and was significantly higher than that observed in the control group (p ,0.001). Diffuse uptake of antimyosin was observed in all patients with cardiac amyloidosis. Patients with amyloidosis and congestive heart failure had a higher H/L ratio (2.76 6 0.30) compared with patients without clinically evident heart failure (2.17 6 0.06, p 5 0.04). The H/L ratio in the group of patients with idiopathic-dilated cardiomyopathy was 1.6 6 0.2 (range 1.4 to 2.1) and was significantly lower than that observed in amyloidosis patients (p ,0.001); the H/L ratio was abnormal in 4 of these patients. 0002-9149/97/$17.00 PII S0002-9149(97)00558-4
963
TABLE I Characteristics of Patients With Cardiac Amyloidosis Electrocardiogram
Patient 1 2 3 4 5 6 7
Age (yr) & Sex
Myeloma
Monoclonal Protein
57/F 56/M 37/M 66/M 58/F 61/F 60/M
1 0 0 1 0 0 1
l-Chain only l-Chain only Nonsecretory IgAl IgGl IgAl IgAl
Organs With Amyloid
Heart H C-P K PN Li Lu S Failure Voltage 1 1 1 1 1 1 1
1 0 0 0 1 1 0
0 1 1 0 0 0 1
0 1 0 1 0 0 0
0 0 0 1 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
1 0 1 0 1 1 0
1 1 0 1 0 1 1
BBB
ST
1 (R,LAH) 0 1 (R,LAH) 0 1 (LPH) 0 0
1 1 0 1 1 1 0
Poor RWave Progression Biopsy/Scan 0 1 0 1 1 0 0
1/H/L 2/H/L 1/H/L 1/H/L 1/H/L 1/H/L 1/H/L
3.2 2.2 2.64 2.2 2.34 2.85 2.1
BBB 5 bundle branch block; C-P 5 Carpal tunnel syndrome; H/L 5 heart-to-lung antimyosin ratio; IgA 5 immunoglobulin A; K 5 Kidney; LAH 5 left anterior hemiblock; Li 5 Liver; LPH 5 Left posterior hemiblock; Lu 5 Lung; PN 5 Peripheral nerves; R 5 right; S 5 skin.
FIGURE 1. Positive antimyosin scanning in a patient with biopsyproven cardiac anyloidosis.
•••
Indium-111 labeled antimyosin antibodies have been shown to bind specifically to areas of myocardial necrosis; on postmortem imaging, tracer uptake matched the triphenyltetrazolium chloride staining, confirming that myosin-specific antibodies bind specifically to damaged myocardial cells.8 Previous studies reported antimyosin uptake in patients with myocardial infarction, myocarditis, cardiac transplant rejection, and adriamycin cardiotoxicity.7,9 This study confirms our previous observation of antimyosin uptake in a case of cardiac amyloidosis.6 The pattern of uptake is a diffuse one, indicating a global effect of amyloid deposit on myocyte membranes. It is unlikely that diffuse uptake in these patients is a false-positive result from residual bloodpool activity; imaging 48 hours after antibody administration minimizes this uncertainty. By this time there is only negligible blood pool activity that is not visualized.10 Rupture of the myocardial cell membrane and exposure of myosin is necessary for antimyosin to bind to the myocardium and to show a positive scintigraphic result. In addition, although no data are available, the possibility of antimyosin binding to amyloid cannot be excluded. The association of antimyosin uptake to congestive heart failure in our amyloidosis patients is interesting; 964
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VOL. 80
a close correlation between antibody uptake and the mass of necrotic myocardium has been found in both animals and humans.11 An early consequence of extracellular myocardial amyloid deposition is impaired mid-diastolic ventricular filling. With progression of the disease, more extensive amyloid deposits cause extensive damage to the myocardial cells with attendant reduction of systolic function and marked heart failure. The more intense antimyosin uptake in heart failure patients apparently highlights the more extensive damage of myocardial cells in those patients. Abnormal antimyosin uptake was seen in 4 of the 10 patients with idiopathic-dilated cardiomyopathy. Myocardial uptake of antimyosin in these patients probably reflects the presence of active myocyte damage, despite the negative endomyocardial biopsy and has been previously reported.12 It should be noted that antimyosin uptake in dilated cardiomyopathy is usually faint, whereas in cardiac amyloidosis uptake is intense and the H/L ratio is .2.1. Thickening of left ventricular myocardium may be seen in both cardiac amyloidosis and hypertrophy secondary to various causes. On the basis of our observations we conclude that left ventricular thickening with diffuse myocardial antimyosin uptake is highly suggestive of amyloid heart disease. In such patients the diagnosis of amyloidosis can be confirmed with less invasive methods (subcutaneous fat tissue aspiration or rectal biopsy). Furthermore, in patients with known amyloidosis, the antimyosin scanning could be used to screen for possible cardiac involvement.
1. Roberts WC, Waller BF. Cardiac amyloidosis causing cardiac dysfunction: analysis of 54 necropsy patients. Am J Cardiol 1983;52:137–146. 2. Kyle RA, Greipp PR, O’Fallon M. Primary systemic amyloidosis: Multivariate analysis for prognostic factors in 168 cases. Blood 1986;68:220 –224. 3. Sigueira-Filho AG, Gunha CLP, Tajik AJ, Seward JB, Schattenberg TT, Giulani ER. M-mode and two-dimensional echocardiographic fearutes in cardiac amyloidosis. Circulation 1982;66:790 –799. 4. Wizenberg TA, Muz J, Sohn YH, Samlowski W, Weissler AM. Value of positive myocardial technetium-99m-pyrophosphate scintigraphy in the noninvasive diagnosis of cardiac amyloidosis. Am Heart J 1982;103:468 – 473. 5. Hawkins PN, Lavender JP, Pepys MB. Evaluation of systemic amyloidosis by scintigraphy with I123-labeled serum amyloid P component. N Engl J Med 1990;328:508 –513. 6. Lekakis J, Nanas J, Moustafellou C, Darsinos J, Germanidis J, Agapitos N,
OCTOBER 1, 1997
Kostamis P, Moulopoulos S. Cardiac amyloidosis detected by indium-111 antimyosin imaging. Am Heart J 1992;124:1630 –1631. 7. Carrio I, Berna L, Ballester M, Estorch M, Obrador D, Cladellas M, Abadal L, Ginjanme M. Indium-111 antimyosin scintigraphy to assess myocardial damage in patients with suspected myocarditis and cardiac rejection. J Nucl Med 1988;1983–1900. 8. Jain D, Crawly JC, Lahiri A, Rafley EB. Indium-111 antimyosin images compared with triphenyltetrazolium chloride staining in a patient six days after myocardial infarction. J Nucl Med 1990;31:231–233. 9. Lekakis J, Vassilopoulos N, Psichoyiou H, Athanassiadis P, Gerali S, Kostamis P, Moulopoulos S. Doxorubicin cardiotoxicity detected by indium-111 myosin specific imaging. Eur J Nucl Med 1991;18:225–226.
10. Khaw BA, Yasuda T, Gold HK, Leinbach RC, Johns JA, Kanke M, Barlai-Kovach M, Strauss HW, Haber E. Acute myocardial infarct imaging with indium-111-labeled monoclonal antimyosin Fab. J Nucl Med 1987;28: 1671–1678. 11. Khaw BA, Scott J, Fallon JT, Cahill SL, Haber E, Homicy C. Myocardial injury quantification by cell sorting initiated with antimyosin fluorescent spheres. Science 1982;217:1050 –1053. 12. Obrador D, Ballester M, Carrio I, Berna L, Pons-Llado G. High prevalence of myocardial monoclonal antimyosin antibody uptake in patients with chronic idiopathic dilated cardiomyopathy. J Am Coll Cardiol 1989;13:1289 – 1293.
Influence of Right Ventricular Volume and Pressure Overloads on Assessment of Left Ventricular Volume Using Two-Dimensional Echocardiography in Infants and Children With Congenital Heart Diseases Mika Matsumori,
MD,
Tadahiko Ito, MD, Manatomo Toyono, and Goro Takada, MD
valuation of left ventricular (LV) volume in chilE dren with congenital heart disease is essential for the determination of therapy. LV angiography has long been used for this purpose. For a noninvasive method using 2-dimensional echocardiography, either the biplane Simpson’s rule using apical 4-chamber and apical long-axis views or the modified Simpson’s rule using short-axis views have been used.1– 4 Most infants and children with complex congenital heart disease have LV distortion due to right ventricular (RV) volume or pressure overload. However, in these patients, it has never been investigated how the LV distortion influences the accuracy of these 2 methods. We designed this study to determine the influence of LV distortion on the 2 algorithms. •••
Eighty-five patients ranging in age from 5 days to 15 years were divided into 3 groups as follows: group A: patients without RV volume or pressure overload (n 5 38); 15 cases with ventricular septal defect, 9 with history of Kawasaki disease, and 14 with other diseases; group B: patients with RV volume overload due to atrial septal defect (n 5 14); and group C: patients with RV pressure overload (n 5 33); 8 cases with ventricular septal defect and pulmonary hypertension, 14 with tetralogy of Fallot, 7 with pulmonary stenosis, 2 with pulmonary atresia, and 2 with transposition of the main arteries. Two-dimensional echocardiography was performed with an Aloka SSD 870 ultrasonoscope (Tokyo, Japan). The images were recorded with standard video techniques for later playback. Biplane Simpson’s rule3: The apical 4-chamber view and apical long-axis view were used. End-systole and end-diastole were defined by advancing the From the Department of Pediatrics, Akita University School of Medicine, Akita, Japan. Dr. Ito’s address is: Department of Pediatrics, Akita University School of Medicine, 1-1-1 Hondo, Akita 010, Japan. Manuscript received March 28, 1997; revised manuscript received and accepted June 2, 1997. ©1997 by Excerpta Medica, Inc. All rights reserved.
MD,
Kenji Harada,
MD,
videotape frame by frame to obtain the maximum and minimum ventricular sizes. In the 2 apical views, we traced the LV endocardial surfaces, including the planes of the apposed mitral leaflets with exclusion of the papillary muscles. LV volumes were calculated by biplane Simpson’s rule with the aid of a computerinterfaced digitizer pad (Cardio 500; Kontron Instrument, Tokyo, Japan). Modified Simpson’s rule1: The short-axis crosssectional areas of LV cavity at the mitral valve (Am) and papillary muscle (Ap) levels were traced and planimetered with exclusion of the papillary muscle. The long-axis length of the LV cavity was measured from the apical 4-chamber view as the distance from the LV apical endocardium to the midpoint of the mitral annulus. The LV volumes (V) were calculated from the formula: V 5 ~Am! 3 L/3 1 {~Am 1 Ap!/ 2} 3 L/3 1 Ap/3 3 L/3. The left ventricle in the right anterior and axial left anterior oblique projections was recorded as biplane cine angiograms, and the cavity borders were manually traced at the end-diastole and end-systole. Then, LV volumes were calculated with area–length methods.5 Each set of echocardiographic measurement was compared with that derived from angiography. The LV volumes measured from echocardiography varied up to 8% among 3 observers. When retraced by 1 observer, the volumes varied up to 7%. The maximum intraobserver and interobserver errors from angiography were 4% and 6%, respectively. Linear regression analysis was performed (Y axis, values obtained from angiography; X axis, values from echocardiography). Patients without RV volume or pressure overload (group A) are shown in Figure 1. The LV end-diastolic and end-systolic volumes obtained from the 2 methods using echocardiography correlated closely with those counterparts from angiography in group A. There were no significant differences in the slopes of 0002-9149/97/$17.00 PII S0002-9149(97)00559-6
965
Seven patients with histologically confirmed primary or myeloma-related amyloidosis were studied; 3 were women and 4 men and their mean age was 56 6 9 years (range 37 to 61). Characteristics of the patients are shown in Table I. Clinically overt heart failure was present in 4 patients and all patients had left ventricular thickening on the echocardiogram and an abnormal electrocardiogram. Right ventricular endomyocardial biopsy was performed in all patients and it was successful in 6 of 7 patients; Congo red staining was positive for amyloid in the vascular wall and interstitium of all specimens. In 1 patient (patient 2), biopsy was not obtained because the patient developed ventricular tachycardia during the catheterization. However, in this patient the diagnosis of cardiac amyloidosis was confirmed by the presence of left ventricular thickening on the echocardiogram, a low voltage on the electrocardiogram, and presence of amyloid in a kidney biopsy specimen. Six patients with low probability of cardiac amyloidosis formed a control group; there were 2 women and 4 men with a mean age of 54 6 11 years (range 34 to 60). All control patients had a long-standing history of systemic hypertension and left ventricular hypertrophy on the echocardiogram (septum 1.5 6 0.4 mm, posterior wall 1.4 6 0.3 mm), but no evidence of From the Department of Clinical Therapeutics and Department of Nuclear Medicine, Alexandra University Hospital, Athens, Greece. Dr. Lekakis’ address is: 86 Alkionis Street, P. Faliron 175 62, Athens, Greece. Manuscript received March 11, 1997; revised manuscript received and accepted June 2, 1997. ©1997 by Excerpta Medica, Inc. All rights reserved.
plasma cell dyscrasia. An additional control group consisted of 10 patients with long-standing (.1 year) history of idiopathic-dilated cardiomyopathy and no evidence of myocarditis on endomyocardial biopsy; there were 4 women and 6 men and the mean age was 49 6 6 years (range 38 to 57). Left ventricular ejection fraction was 23 6 13% (range 9 to 49). All patients underwent myosin-specific monoclonal antibody imaging. Antimyosin antibody (Myoscint, Centocor, Inc., Leiden, The Netherlands) was supplied as a sterile nonpyrogenic solution containing 0.5 mg of R11 D10 Fab diethylenetramine pentaacetic acid, which is a mouse monoclonal antibody fragment that binds specifically to myosin. The antimyosin was radiolabeled by the addition of sterile indium-111 chloride. Two millicuries of indium-111 were diluted to 10 ml of volume and were administered intravenously by slow injection. Planar imaging was performed after 48 hours using a gamma camera (General Electric Maxi Camera 400, Milwaukee, Wisconsin). Three views were obtained (anterior, 45° left anterior oblique, and left anterior oblique, 70°) using a 128 3 128 matrix for 10 min/view. Both photopeaks of indium-111 were used (173 keV and 247 keV) with 20% energy windows. A heart-to-lung (H/L) ratio was used to quantify tracer uptake; the unprocessed anterior projection was used to adjust a region of interest in the myocardium and a region of interest in each lung. The average count per pixel in the myocardium was divided by the average count per pixel in each lung to obtain the H/L ratio. A ratio .1.6 was considered abnormal.7 The antimyosin antibody was administered without adverse reactions in all patients and control subjects. In the control group, all 6 patients had a normal antimyosin study; H/L ratio ranged from 1.3 to 1.6 (mean 1.43 6 0.1). In each patient with cardiac amyloidosis the antimyosin scanning was always abnormal (Figure 1); the H/L ratio ranged from 2.1 to 3.2 (mean 2.5 6 0.4) and was significantly higher than that observed in the control group (p ,0.001). Diffuse uptake of antimyosin was observed in all patients with cardiac amyloidosis. Patients with amyloidosis and congestive heart failure had a higher H/L ratio (2.76 6 0.30) compared with patients without clinically evident heart failure (2.17 6 0.06, p 5 0.04). The H/L ratio in the group of patients with idiopathic-dilated cardiomyopathy was 1.6 6 0.2 (range 1.4 to 2.1) and was significantly lower than that observed in amyloidosis patients (p ,0.001); the H/L ratio was abnormal in 4 of these patients. 0002-9149/97/$17.00 PII S0002-9149(97)00558-4
963
TABLE I Characteristics of Patients With Cardiac Amyloidosis Electrocardiogram
Patient 1 2 3 4 5 6 7
Age (yr) & Sex
Myeloma
Monoclonal Protein
57/F 56/M 37/M 66/M 58/F 61/F 60/M
1 0 0 1 0 0 1
l-Chain only l-Chain only Nonsecretory IgAl IgGl IgAl IgAl
Organs With Amyloid
Heart H C-P K PN Li Lu S Failure Voltage 1 1 1 1 1 1 1
1 0 0 0 1 1 0
0 1 1 0 0 0 1
0 1 0 1 0 0 0
0 0 0 1 1 1 0 0 0 0 0 0 0 0 0 0 0 0 0 0 0
1 0 1 0 1 1 0
1 1 0 1 0 1 1
BBB
ST
1 (R,LAH) 0 1 (R,LAH) 0 1 (LPH) 0 0
1 1 0 1 1 1 0
Poor RWave Progression Biopsy/Scan 0 1 0 1 1 0 0
1/H/L 2/H/L 1/H/L 1/H/L 1/H/L 1/H/L 1/H/L
3.2 2.2 2.64 2.2 2.34 2.85 2.1
BBB 5 bundle branch block; C-P 5 Carpal tunnel syndrome; H/L 5 heart-to-lung antimyosin ratio; IgA 5 immunoglobulin A; K 5 Kidney; LAH 5 left anterior hemiblock; Li 5 Liver; LPH 5 Left posterior hemiblock; Lu 5 Lung; PN 5 Peripheral nerves; R 5 right; S 5 skin.
FIGURE 1. Positive antimyosin scanning in a patient with biopsyproven cardiac anyloidosis.
•••
Indium-111 labeled antimyosin antibodies have been shown to bind specifically to areas of myocardial necrosis; on postmortem imaging, tracer uptake matched the triphenyltetrazolium chloride staining, confirming that myosin-specific antibodies bind specifically to damaged myocardial cells.8 Previous studies reported antimyosin uptake in patients with myocardial infarction, myocarditis, cardiac transplant rejection, and adriamycin cardiotoxicity.7,9 This study confirms our previous observation of antimyosin uptake in a case of cardiac amyloidosis.6 The pattern of uptake is a diffuse one, indicating a global effect of amyloid deposit on myocyte membranes. It is unlikely that diffuse uptake in these patients is a false-positive result from residual bloodpool activity; imaging 48 hours after antibody administration minimizes this uncertainty. By this time there is only negligible blood pool activity that is not visualized.10 Rupture of the myocardial cell membrane and exposure of myosin is necessary for antimyosin to bind to the myocardium and to show a positive scintigraphic result. In addition, although no data are available, the possibility of antimyosin binding to amyloid cannot be excluded. The association of antimyosin uptake to congestive heart failure in our amyloidosis patients is interesting; 964
THE AMERICAN JOURNAL OF CARDIOLOGYT
VOL. 80
a close correlation between antibody uptake and the mass of necrotic myocardium has been found in both animals and humans.11 An early consequence of extracellular myocardial amyloid deposition is impaired mid-diastolic ventricular filling. With progression of the disease, more extensive amyloid deposits cause extensive damage to the myocardial cells with attendant reduction of systolic function and marked heart failure. The more intense antimyosin uptake in heart failure patients apparently highlights the more extensive damage of myocardial cells in those patients. Abnormal antimyosin uptake was seen in 4 of the 10 patients with idiopathic-dilated cardiomyopathy. Myocardial uptake of antimyosin in these patients probably reflects the presence of active myocyte damage, despite the negative endomyocardial biopsy and has been previously reported.12 It should be noted that antimyosin uptake in dilated cardiomyopathy is usually faint, whereas in cardiac amyloidosis uptake is intense and the H/L ratio is .2.1. Thickening of left ventricular myocardium may be seen in both cardiac amyloidosis and hypertrophy secondary to various causes. On the basis of our observations we conclude that left ventricular thickening with diffuse myocardial antimyosin uptake is highly suggestive of amyloid heart disease. In such patients the diagnosis of amyloidosis can be confirmed with less invasive methods (subcutaneous fat tissue aspiration or rectal biopsy). Furthermore, in patients with known amyloidosis, the antimyosin scanning could be used to screen for possible cardiac involvement.
1. Roberts WC, Waller BF. Cardiac amyloidosis causing cardiac dysfunction: analysis of 54 necropsy patients. Am J Cardiol 1983;52:137–146. 2. Kyle RA, Greipp PR, O’Fallon M. Primary systemic amyloidosis: Multivariate analysis for prognostic factors in 168 cases. Blood 1986;68:220 –224. 3. Sigueira-Filho AG, Gunha CLP, Tajik AJ, Seward JB, Schattenberg TT, Giulani ER. M-mode and two-dimensional echocardiographic fearutes in cardiac amyloidosis. Circulation 1982;66:790 –799. 4. Wizenberg TA, Muz J, Sohn YH, Samlowski W, Weissler AM. Value of positive myocardial technetium-99m-pyrophosphate scintigraphy in the noninvasive diagnosis of cardiac amyloidosis. Am Heart J 1982;103:468 – 473. 5. Hawkins PN, Lavender JP, Pepys MB. Evaluation of systemic amyloidosis by scintigraphy with I123-labeled serum amyloid P component. N Engl J Med 1990;328:508 –513. 6. Lekakis J, Nanas J, Moustafellou C, Darsinos J, Germanidis J, Agapitos N,
OCTOBER 1, 1997
Kostamis P, Moulopoulos S. Cardiac amyloidosis detected by indium-111 antimyosin imaging. Am Heart J 1992;124:1630 –1631. 7. Carrio I, Berna L, Ballester M, Estorch M, Obrador D, Cladellas M, Abadal L, Ginjanme M. Indium-111 antimyosin scintigraphy to assess myocardial damage in patients with suspected myocarditis and cardiac rejection. J Nucl Med 1988;1983–1900. 8. Jain D, Crawly JC, Lahiri A, Rafley EB. Indium-111 antimyosin images compared with triphenyltetrazolium chloride staining in a patient six days after myocardial infarction. J Nucl Med 1990;31:231–233. 9. Lekakis J, Vassilopoulos N, Psichoyiou H, Athanassiadis P, Gerali S, Kostamis P, Moulopoulos S. Doxorubicin cardiotoxicity detected by indium-111 myosin specific imaging. Eur J Nucl Med 1991;18:225–226.
10. Khaw BA, Yasuda T, Gold HK, Leinbach RC, Johns JA, Kanke M, Barlai-Kovach M, Strauss HW, Haber E. Acute myocardial infarct imaging with indium-111-labeled monoclonal antimyosin Fab. J Nucl Med 1987;28: 1671–1678. 11. Khaw BA, Scott J, Fallon JT, Cahill SL, Haber E, Homicy C. Myocardial injury quantification by cell sorting initiated with antimyosin fluorescent spheres. Science 1982;217:1050 –1053. 12. Obrador D, Ballester M, Carrio I, Berna L, Pons-Llado G. High prevalence of myocardial monoclonal antimyosin antibody uptake in patients with chronic idiopathic dilated cardiomyopathy. J Am Coll Cardiol 1989;13:1289 – 1293.
Influence of Right Ventricular Volume and Pressure Overloads on Assessment of Left Ventricular Volume Using Two-Dimensional Echocardiography in Infants and Children With Congenital Heart Diseases Mika Matsumori,
MD,
Tadahiko Ito, MD, Manatomo Toyono, and Goro Takada, MD
valuation of left ventricular (LV) volume in chilE dren with congenital heart disease is essential for the determination of therapy. LV angiography has long been used for this purpose. For a noninvasive method using 2-dimensional echocardiography, either the biplane Simpson’s rule using apical 4-chamber and apical long-axis views or the modified Simpson’s rule using short-axis views have been used.1– 4 Most infants and children with complex congenital heart disease have LV distortion due to right ventricular (RV) volume or pressure overload. However, in these patients, it has never been investigated how the LV distortion influences the accuracy of these 2 methods. We designed this study to determine the influence of LV distortion on the 2 algorithms. •••
Eighty-five patients ranging in age from 5 days to 15 years were divided into 3 groups as follows: group A: patients without RV volume or pressure overload (n 5 38); 15 cases with ventricular septal defect, 9 with history of Kawasaki disease, and 14 with other diseases; group B: patients with RV volume overload due to atrial septal defect (n 5 14); and group C: patients with RV pressure overload (n 5 33); 8 cases with ventricular septal defect and pulmonary hypertension, 14 with tetralogy of Fallot, 7 with pulmonary stenosis, 2 with pulmonary atresia, and 2 with transposition of the main arteries. Two-dimensional echocardiography was performed with an Aloka SSD 870 ultrasonoscope (Tokyo, Japan). The images were recorded with standard video techniques for later playback. Biplane Simpson’s rule3: The apical 4-chamber view and apical long-axis view were used. End-systole and end-diastole were defined by advancing the From the Department of Pediatrics, Akita University School of Medicine, Akita, Japan. Dr. Ito’s address is: Department of Pediatrics, Akita University School of Medicine, 1-1-1 Hondo, Akita 010, Japan. Manuscript received March 28, 1997; revised manuscript received and accepted June 2, 1997. ©1997 by Excerpta Medica, Inc. All rights reserved.
MD,
Kenji Harada,
MD,
videotape frame by frame to obtain the maximum and minimum ventricular sizes. In the 2 apical views, we traced the LV endocardial surfaces, including the planes of the apposed mitral leaflets with exclusion of the papillary muscles. LV volumes were calculated by biplane Simpson’s rule with the aid of a computerinterfaced digitizer pad (Cardio 500; Kontron Instrument, Tokyo, Japan). Modified Simpson’s rule1: The short-axis crosssectional areas of LV cavity at the mitral valve (Am) and papillary muscle (Ap) levels were traced and planimetered with exclusion of the papillary muscle. The long-axis length of the LV cavity was measured from the apical 4-chamber view as the distance from the LV apical endocardium to the midpoint of the mitral annulus. The LV volumes (V) were calculated from the formula: V 5 ~Am! 3 L/3 1 {~Am 1 Ap!/ 2} 3 L/3 1 Ap/3 3 L/3. The left ventricle in the right anterior and axial left anterior oblique projections was recorded as biplane cine angiograms, and the cavity borders were manually traced at the end-diastole and end-systole. Then, LV volumes were calculated with area–length methods.5 Each set of echocardiographic measurement was compared with that derived from angiography. The LV volumes measured from echocardiography varied up to 8% among 3 observers. When retraced by 1 observer, the volumes varied up to 7%. The maximum intraobserver and interobserver errors from angiography were 4% and 6%, respectively. Linear regression analysis was performed (Y axis, values obtained from angiography; X axis, values from echocardiography). Patients without RV volume or pressure overload (group A) are shown in Figure 1. The LV end-diastolic and end-systolic volumes obtained from the 2 methods using echocardiography correlated closely with those counterparts from angiography in group A. There were no significant differences in the slopes of 0002-9149/97/$17.00 PII S0002-9149(97)00559-6
965