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Hemodynamic and prognostic value of thallium-201 myocardial imaging in patients with dilated cardiomyopathy
International Elsevier
CARD10
Journal of Cardiology,
219
24 (1989) 219-224
00898
Hemodynamic and prognostic value of thallium-201 myocardial imaging in patients with dilated cardiomyopathy Jun Tamai,
Se&i Nagata,
Tsunehiko
Hiroshi Cardiology Division of Medicine,
Nishimura,
Sakakibara National
Chikao
and Yasuharu
Cardiovascular
Yutani,
Kunio
Miyatake,
Nimura
Center, 5-7-1, Fujishirodai,
Suita, Osaka, Japan
(Received 30 September 1988; revision accepted 7 March 1989)
Tamai J, Nagata S, Nishimura T, Yutani C, Miyatake K, Sakakibara H, Nimura Y. Hemodynamic and prognostic value of thallium-201 myocardial imaging in patients with dilated cardiomyopathy. Int J Cardiol 1989;24:219-224. We studied 70 patients with dilated cardiomyopathy to determine whether extent of perfusion defect on thallium imaging could be related to the hemodynamics and prognosis of the patients. Patients were divided into three groups according to the extent of perfusion defect, i.e., Grade I: no perfusion defect (n = 19), Grade II: apical perfusion defect (n = 22), and Grade III: extensive perfusion defect (n = 29). The patients of Grade III demonstrated marked hemodynamic deterioration compared with those of Grade I and II. Three-year survival rate showed lower value in proportion to the extent of perfusion defect (P -c 0.05). Death from progressive heart failure tended to occur in patients with extensive perfusion defect (P -z0.05). In patients of Grade III, the perfusion defect extended mainly to the posterolateral segment. Although autopsy studies showed increased fibrosis in the left ventricular wall in these patients, the extension of the fibrosis was not related to that of fibrosis. Moreover, the perfusion defect had regressed in three of 18 patients in the follow-up examination. These results indicate that the extent of perfusion defect on thallium imaging may be of value in non-invasive evaluation and prediction of the prognosis in patients with dilated cardiomyopathy. Distribution of the perfusion defect was, however, not related to that of myocardial fibrosis. Key words: Thallium scanning; Dilated cardiomyopathy; Introduction Dilated cardiomyopathy is characterized as a cardiac enlargement due to degenerative changes in the myocardium [l]. The late stage of this
Correspondence to: Seiki Nagata, M.D., National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka, 565, Japan. This study was supported in part by a “Research grant for Research on Idiopathic Cardiomyopathy” from the Ministry of Health and Welfare, Japan, 1987. 0167-5273/89/$03.50
Myocardial
fibrosis
disease results in refractory congestive heart failure associated with impairment of cardiac function [2]. Some investigators studied myocardial thallium imaging in patients with dilated cardiomyopathy to determine the diagnostic values to distinguish these patients from those with ischemic heart disease [3-51. Although they reported that some patients with dilated cardiomyopathy showed apical or extensive perfusion defect on thallium imaging [3,4], they have not extensively studied the value of thallium imaging for non-invasive evaluation and management of the patients with dilated cardiomyopathy.
0 1989 Elsevier Science Publishers B.V. (Biomedical Division)
220
The aims of the present study are to determine whether the extent of perfusion defect on the thallium imaging is related to hemodynamic deterioration and prognosis of the patients with dilated cardiomyopathy. Materials
and Methods
Subjects Subjects of this study were 70 patients with dilated cardiomyopathy referred to cardiac catheterization from 1 February 1978 to 15 February 1986 in our laboratory. There were 48 men and 22 women, aged 11 to 66 years (mean 46). These patients had ventricular arrhythmia and/or symptomatic left ventricular failure (New York Heart Association functional classes II-IV). The diagnoses were based on the results of cardiac catheterization, which in each case involved left ventriculography, coronary angiography and endomyocardial biopsy. All subjects had impaired left ventricular function (ejection fraction g-51’%) with normal coronary arteriograms. In addition, biopsy studies showed increased fibrosis between muscle fibers without cellular infiltration in all patients. Informed consent was obtained from each patient for cardiac catheterization, scintigraphic
ANT
Grade
LA0300
examination and follow-up study. Medication given on discharge included digitalis, diuretics, vasodilators and antiarrhythmic drugs. Thallium-201
scanning
Myocardial images were recorded by scinticamera (Shimazu LFOV) with a high resolution parallel hole collimator connected to data analyzing computer system (Shimazu scintipac 2400). Thallium-201 (2-3 mCi) was injected during resting condition and thallium scanning was performed lo-20 minutes after the injection. Myocardial images were obtained in 5 projections, i.e., anterior. 30 O, 45 o and 60” left anterior oblique with the patient supine and left lateral with the patient in the right decubitus position. In each view, 500000 counts were collected. In 18 patients, the thallium scanning was again performed at least one year after the initial procedure to examine the changes in scintigraphic findings. The perfusion defect was defined as an area with a count density smaller than 75% of the maximum. In order to assess the size and site of the perfusion defect, the 75% contour line was superimposed on the outer planimeter of the left ventricular myocardium. The percentage of the perfusion defect to the outer left ventricular cirLA0450
LA0600
L-LAT
I
Fig. 1. Representative thallium imagings in patients with dilated cardiomyopathy. Grade I: no perfusion defect. Grade II: apical perfusion defect. Grade III: extensive perfusion defect.
221
cumference was calculated in each view and the largest one was used in the study. These procedures were performed by an experienced observer and technical assistants who had no information about the patients. All patients were classified into three grades according to the extent of the perfusion defect. Definitions of three grades were as follows: Grade I: no perfusion defect, i.e., only left ventricular dilatation was seen; Grade II: apical perfusion defect, i.e., perfusion defect < 20% of outer left ventricular circumference was seen in the apical segment; Grade III: extensive perfusion defect, i.e., perfusion defect was extended > 20% of outer left ventricular circumference. Fig. 1 shows the representative thallium imagings of three grades. Of the 70 patients examined, 19 showed only left ventricular dilatation without perfusion defect (Grade I), 22 showed apical perfusion defect (Grade II), and 29 showed extensive perfusion defect (Grade III). In patients of Grade III, the perfusion defect extended from the apical to the posterolateral segment rather than the anteroseptal segment. However, five of those 29 patients demonstrated the perfusion defect in posterolateral or anteroseptal segment without apical defect. There were no statistically significant differences in age and sex among the three groups of patients. Cardiac catheterization
of death, sudden death (presumed arrhythmia) or progressive heart failure was noted in patients who died during the follow-up period. Autopsy study We studied 10 of 22 patients who died during the follow-up period, at autopsy. The heart was sectioned transversely to the long axis of the left ventricle at one-third from the apex. After fixation with formaldehyde, the slice was stained with hematoxylin-eosin and masson-trichrome. To evaluate the fibrotic changes in the myocardium, the left ventricular wall was divided into anterior, septal, inferior and lateral segments on the specimen, and the percentage of fibrosis of each segment was determined by a planimeter. Statistical analysis Survival rates of the patients were plotted using a Kaplan-Meier graph. A &i-square analysis was made on survival after three years, at the end of follow-up and the cause of death using a 3 x 2 contingency table. Comparison of hemodynamic data was performed by analysis of variance (ANOVA) and unpaired r-test. P < 0.05 was considered significant. Results Thallium scanning and hemodynamics
Cardiac catheterization was performed within a month of the day of the scintigraphic examination in all patients. Cardiac output was measured by the thermodilution method with using a 7 Fr. Swan-Ganz catheter. Selective coronary angiograms were obtained by a 5 or 7 Fr. Judkins catheter. A pig-tail catheter (5 or 7 Fr.) was used for left ventricular pressure measurements and the ventriculography. The left ventricular end-systolic and end-diastolic volume were obtained from the left ventriculograms by the area-length method, and ejection fraction was calculated.
Hemodynamic parameters appeared to be deteriorated with the extension of perfusion defect (Table 1). Ejection fraction in Grade III was significantly lower than that in Grade I (P -c0.05). Cardiac index in Grade III was significantly lower than that in I (P < 0.05) and II (P < 0.05). Left ventricular end-systolic and diastolic volume index in Grade III was significantly greater than that in Grade I (P -c0.01). Left ventricular enddiastolic pressure was significantly higher in Grade III than that in I (P -c0.01) and II (P < 0.05).
Follow-up study
Thallium scanning and prognosis
After scintigraphic evaluation, patients were followed until death, or until May 1987. The cause
Survival curves for the three groups are shown using a Kaplan-Meier graph in Fig. 2. No patients
222 TABLE
1
Grading of thallium scanning and hemodynamic parameters in patients with dilated cardiomyopathy. Grading of scan
No. of patients
CI (l/min/m2)
LVESVI
LVEDVI
LVEDP
(8)
W/m*)
(mWn2)
(mm Hg)
I
19 22 29
38k 8 32 f 11 29*13 *
3.3 + 0.9 3.3 + 0.8 2.6 f 0.8 *.+
77* 6 108+13 * 128*13 **
120 * 34 149 + 64 172+72 **
9*5 10 f I 16k8 **.I
II III
EF
Values are mean f SD. Grading of scan: I: no perfusion defect. II: apical perfusion defect. III: extensive perfusion defect. CI = cardiac index; EF = ejection fraction; LVEDP = left ventricular end-diastolic pressure; LVEDVI = left ventricular end-diastolic volume index; LVESVI = left ventricular end-systolic volume index. * P i 0.05, * * P < 0.01 vs Grade I; + P c 0.05vsGrade II by unpaired f-test.
died from other disease than cardiomyopathy. Low survival rate was noted in patients with Grade III. Although overall survival trends were not significantly different in the three groups of patients, the three-year mortality rate was significantly higher in proportion to the extension of perfusion defect (P -c0.05 by &i-square analysis): one in Grade I (5%) four in Grade II (18%) and 14 in Grade III (48%) died within three years. Death from progressive heart failure tended to occur more frequently in patients with extensive perfusion defect (P < 0.05 by &i-square analysis): one of two patients in Grade I, one of five in Grade II and 12 of 14 in Grade III died from
progressive denly.
heart failure while others died sud-
Follow-up thallium scanning Thallium scanning was again performed in 18 patients (Fig. 3). Mean interval between the initial and follow-up examinations was 26 months (ranging from 12 to 48 months). In the initial thallium scanning, five patients were Grade I, eight Grade II and five Grade III. In the follow-up examination, five patients showed the extension of the perfusion defect although 10 were unchanged. However, three patients showed the regression of the perfusion defect. In two of them, improvement in subjective symptoms was associated with the reduction of perfusion defect, while another patient showed no changes in clinical condition.
w
Initial
o!
0
30
I
Grade
U
Grade
RI x
BO,Month*,
60
Follow-up
Grade
Follow-Up
Period
Fig. 2. Survival rate of patients with dilated cardiomyopathy plotted in a Kaplan-Meier graph. Lower survival rate was noted in proportion to the grade of thallium scanning. Grade I: no perfusion defect, Grade II: apical perfusion defect, Grade III: extensive perfusion defect.
Grade
111
Fig. 3. Changes in the grading of thallium scanning in patients with dilated cardiomyopathy. Each line indicates the individual patient. Grade I: no perfusion defect, Grade II: apical perfusion defect, Grade III: extensive perfusion defect.
223 TABLE
2
Extension of myocardial fibrosis in left ventricular patients with dilated cardiomyopathy. Patient No. 1 2 3 4 5 6 7 8 9 10
Grading of scan III III III III III III II II II I
Grading of scan: I: defect, III: extensive subdivided into five fibrosis is < 25% of segment area; + + + + + = fibrosis is
wall in
Extension of fibrosis in left ventricle Septum
Anterior
Lateral
Posterior
+
-
_
f + +
+
+ + ++ +++ ++ + ++ +
+ ++ ++ +++ + +++ ++ ++
f +++ ++ f + ++
f + ++ ++ + ++ f +
+
f f
no perfusion defect, II: apical perfusion perfusion defect. Extension of fibrosis is ranges: - = no increase in fibrosis; f = segment area; + = fibrosis is 25-508 of = fibrosis is 50-75% of segment area; > 75% of segment area.
Thallium scanning and autopsy findings Autopsy was done in six patients of Grade III, three of Grade II and one of Grade I (Table 2). Mean interval from thallium scans to the autopsy was 4.2 years. Increased fibrosis was noted in each patient of all the three grades. Marked fibrosis (> 75% of segmental area) was noted in three patients of Grade III. In cases 2-4, fibrosis was extended into posterior and lateral segments rather than anterior and septal segments, which coincided with the findings in thallium scanning. However, in cases 1, 5 and 6, fibrosis was extended into anterior and septal segments the same as in posterior and lateral segments while perfusion defect was extended into posterior and lateral segments on thallium scanning in these patients. Discussion The present study demonstrated that extent of perfusion defect on thallium imaging was related to the hemodynamic deterioration and the threeyear prognosis of the patients with dilated cardiomyopathy.
Since dilated cardiomyopathy is characterized as the dilatation of the left ventricle because of the myocardial fibrosis, increase in left ventricular volume may be the primary change in hemodynamic parameters and decrease in cardiac output and ejection fraction and increase in left ventricular end-diastolic pressure may be followed. Although these hemodynamic parameters demonstrate the cardiac function of the patients, the invasive technique was required to obtain them. In the present study, thallium imaging showed that the extent of perfusion defect was related to hemodynamic parameters, suggesting the value of this method in the noninvasive evaluation of the patients with dilated cardiomyopathy. Several factors had been proposed to predict the prognosis of dilated cardiomyopathy, i.e., ventricular function [6-91, pulmonary capillary wedge pressure [lo], left ventricular end-diastolic diameter and wall thickness [ll-131 and ventricular conduction delay [14-161. The present study demonstrated that the patients with extensive perfusion defect had a higher three-year mortality rate and high risk of death from progressive heart failure, suggesting that the extent of perfusion defect on thallium scanning was important in relation not only to the prognosis but also the cause of death in patients with dilated cardiomyopathy. Autopsy studies demonstrated the marked fibrosis in patients with Grade III. In some patients, the increased fibrosis was equally seen in the anteroseptal and posterolateral area, although the perfusion defect of the thallium scanning was predominantly extended to the posterolateral segment. This discrepancy may be in part explained by the long interval from thallium scanning to autopsy. However, some factors other than myocardial fibrosis may influence the thallium imaging because the regression of the perfusion defect was seen in three patients in the follow-up examination (Fig. 3). Dunn et al. and Bulkley et al. reported that the perfusion defect was associated with the thinning of left ventricular wall although they examined only few cases [3,4]. In 10 autopsied cases in the present study, although thinning of the ventricular wall was associated with marked fibrosis, there was no close correlation of the perfusion defect
224
with increased fibrosis, and hence wall thinning. Gewirtz et al. suggested the influence of left ventricular volume on myocardial images using partial aortic occlusion in dogs [17]. In the present study, patients in Grade III (extensive perfusion defect) had greater left ventricular volume than those in Grade I (Table 1). These data indicate that left ventricular volume may influence the myocardial images of thallium scanning in the patients with dilated cardiomyopathy. In conclusion, the extent of the perfusion defect on thallium imaging was related to the hemodynamic deterioration and the prognosis of the patients, which indicated the value of thallium imaging in the evaluation and management of the patients with dilated cardiomyopathy. Although increased fibrosis in the left ventricular wall was noted in these patients, the distribution of the perfusion defect was not related to that of fibrosis.
References 1 Unverferth DV. Etiologic factors, pathogenesis, and prognosis of dilated cardiomyopathy. J Lab Clin Med 1985; 106:349-359. 2 Stern TN. Dilated cardiomyopathy: current concepts. Compr Ther 1986;12:57-62. 3 Dunn RF, Uren RF, Sadick N, et al. Comparison of thallium-201 scanning in idiopathic dilated cardiomyopathy and severe coronary artery disease. Circulation 1982;66:804-810. 4 Bulkley BH. Hutchins GM, Bailey I, Strauss HW, Pitt B. Thallium 201 imaging and gated cardiac blood pool scans in patients with ischemic and idiopathic congestive cardiomyopathy. Circulation 1977;55:753-760.
5 Saltissi S, Hockings B, Croft DN, Webb-Peploe MM. Thallium-201 myocardial imaging in patients with dilated and ischaemic cardiomyopathy. Br Heart J 1981;46:290-295. 6 Baandrup U. Florio RA, Rehahn M, Richardson PJ, Olsen EGJ. Critical analysis of endomyocardial biopsies from patients suspected of having cardiomyopathy. II. Comparison of histology and clinical/haemodynamic information. Br Heart J 1981:45:487-493. 7 Kuhn H, Breithardt G. Knieriem HJ, et al. Prognosis and possible presymptomatic manifestations of congestive cardiomyopathy (COCM). Postgrad Med J 1978;54: 451-459. 8 Shirey EK. Proudfit WL, Hawk WA. Primary myocardial disease. Correlation with clinical findings, angiographic and biopsy diagnosis. Am Heart J 1980;99:198-207. 9 Gaasch WH. Left ventricular radius to wall thickness ratio. Am J Cardiol 1979;43:1189-1194. 10 Unverferth DV, Magorien RD. Moeschberger ML, Baker PB, Fetters JK, Leier CV. Factors influencing the one-year mortality of dilated cardiomyopathy. Am J Cardiol 1984;54:147-152. 11 Convert G, Delaye J, Beaune J, Biron A, Gonin A. Prognosis of primary nonobstructive cardiomyopathies. Arch Ma1 Coeur 1980;73:227-237. 12 Feild BJ. Baxley WA, Russell RO Jr, et al. Left ventricular function and hypertrophy in cardiomyopathy with depressed ejection fraction. Circulation 1973;47:1022-1031. 13 Spodick DH. Effective management of congestive cardiomyopathy. Relation to ventricular structure and function. Arch Intern Med 1982;142:6899692. 14 Danilowicz DA. Prognostic value of the electrocardiogram in endocardial fibroelastosis. Br Heart J 1976;38:516-522. 15 Lengyel M. Kokeny M. Follow-up study in congestive (dilated) cardiomyopathy. Acta Cardiol 1981;36:35-48. 16 Dye CL, Rosenbaum D. Lowe JC, Behnke RH, Genovese PD. Primary myocardial disease. Part I. Clinical features. Ann Intern Med 1963;58:426-441. 17 Gewirtz H, Grotte GJ, Strauss HW. et al. The influence of left ventricular volume and wall motion on myocardial images. Circulation 1979;59:1172-1177.
CARD10
Journal of Cardiology,
219
24 (1989) 219-224
00898
Hemodynamic and prognostic value of thallium-201 myocardial imaging in patients with dilated cardiomyopathy Jun Tamai,
Se&i Nagata,
Tsunehiko
Hiroshi Cardiology Division of Medicine,
Nishimura,
Sakakibara National
Chikao
and Yasuharu
Cardiovascular
Yutani,
Kunio
Miyatake,
Nimura
Center, 5-7-1, Fujishirodai,
Suita, Osaka, Japan
(Received 30 September 1988; revision accepted 7 March 1989)
Tamai J, Nagata S, Nishimura T, Yutani C, Miyatake K, Sakakibara H, Nimura Y. Hemodynamic and prognostic value of thallium-201 myocardial imaging in patients with dilated cardiomyopathy. Int J Cardiol 1989;24:219-224. We studied 70 patients with dilated cardiomyopathy to determine whether extent of perfusion defect on thallium imaging could be related to the hemodynamics and prognosis of the patients. Patients were divided into three groups according to the extent of perfusion defect, i.e., Grade I: no perfusion defect (n = 19), Grade II: apical perfusion defect (n = 22), and Grade III: extensive perfusion defect (n = 29). The patients of Grade III demonstrated marked hemodynamic deterioration compared with those of Grade I and II. Three-year survival rate showed lower value in proportion to the extent of perfusion defect (P -c 0.05). Death from progressive heart failure tended to occur in patients with extensive perfusion defect (P -z0.05). In patients of Grade III, the perfusion defect extended mainly to the posterolateral segment. Although autopsy studies showed increased fibrosis in the left ventricular wall in these patients, the extension of the fibrosis was not related to that of fibrosis. Moreover, the perfusion defect had regressed in three of 18 patients in the follow-up examination. These results indicate that the extent of perfusion defect on thallium imaging may be of value in non-invasive evaluation and prediction of the prognosis in patients with dilated cardiomyopathy. Distribution of the perfusion defect was, however, not related to that of myocardial fibrosis. Key words: Thallium scanning; Dilated cardiomyopathy; Introduction Dilated cardiomyopathy is characterized as a cardiac enlargement due to degenerative changes in the myocardium [l]. The late stage of this
Correspondence to: Seiki Nagata, M.D., National Cardiovascular Center, 5-7-1, Fujishirodai, Suita, Osaka, 565, Japan. This study was supported in part by a “Research grant for Research on Idiopathic Cardiomyopathy” from the Ministry of Health and Welfare, Japan, 1987. 0167-5273/89/$03.50
Myocardial
fibrosis
disease results in refractory congestive heart failure associated with impairment of cardiac function [2]. Some investigators studied myocardial thallium imaging in patients with dilated cardiomyopathy to determine the diagnostic values to distinguish these patients from those with ischemic heart disease [3-51. Although they reported that some patients with dilated cardiomyopathy showed apical or extensive perfusion defect on thallium imaging [3,4], they have not extensively studied the value of thallium imaging for non-invasive evaluation and management of the patients with dilated cardiomyopathy.
0 1989 Elsevier Science Publishers B.V. (Biomedical Division)
220
The aims of the present study are to determine whether the extent of perfusion defect on the thallium imaging is related to hemodynamic deterioration and prognosis of the patients with dilated cardiomyopathy. Materials
and Methods
Subjects Subjects of this study were 70 patients with dilated cardiomyopathy referred to cardiac catheterization from 1 February 1978 to 15 February 1986 in our laboratory. There were 48 men and 22 women, aged 11 to 66 years (mean 46). These patients had ventricular arrhythmia and/or symptomatic left ventricular failure (New York Heart Association functional classes II-IV). The diagnoses were based on the results of cardiac catheterization, which in each case involved left ventriculography, coronary angiography and endomyocardial biopsy. All subjects had impaired left ventricular function (ejection fraction g-51’%) with normal coronary arteriograms. In addition, biopsy studies showed increased fibrosis between muscle fibers without cellular infiltration in all patients. Informed consent was obtained from each patient for cardiac catheterization, scintigraphic
ANT
Grade
LA0300
examination and follow-up study. Medication given on discharge included digitalis, diuretics, vasodilators and antiarrhythmic drugs. Thallium-201
scanning
Myocardial images were recorded by scinticamera (Shimazu LFOV) with a high resolution parallel hole collimator connected to data analyzing computer system (Shimazu scintipac 2400). Thallium-201 (2-3 mCi) was injected during resting condition and thallium scanning was performed lo-20 minutes after the injection. Myocardial images were obtained in 5 projections, i.e., anterior. 30 O, 45 o and 60” left anterior oblique with the patient supine and left lateral with the patient in the right decubitus position. In each view, 500000 counts were collected. In 18 patients, the thallium scanning was again performed at least one year after the initial procedure to examine the changes in scintigraphic findings. The perfusion defect was defined as an area with a count density smaller than 75% of the maximum. In order to assess the size and site of the perfusion defect, the 75% contour line was superimposed on the outer planimeter of the left ventricular myocardium. The percentage of the perfusion defect to the outer left ventricular cirLA0450
LA0600
L-LAT
I
Fig. 1. Representative thallium imagings in patients with dilated cardiomyopathy. Grade I: no perfusion defect. Grade II: apical perfusion defect. Grade III: extensive perfusion defect.
221
cumference was calculated in each view and the largest one was used in the study. These procedures were performed by an experienced observer and technical assistants who had no information about the patients. All patients were classified into three grades according to the extent of the perfusion defect. Definitions of three grades were as follows: Grade I: no perfusion defect, i.e., only left ventricular dilatation was seen; Grade II: apical perfusion defect, i.e., perfusion defect < 20% of outer left ventricular circumference was seen in the apical segment; Grade III: extensive perfusion defect, i.e., perfusion defect was extended > 20% of outer left ventricular circumference. Fig. 1 shows the representative thallium imagings of three grades. Of the 70 patients examined, 19 showed only left ventricular dilatation without perfusion defect (Grade I), 22 showed apical perfusion defect (Grade II), and 29 showed extensive perfusion defect (Grade III). In patients of Grade III, the perfusion defect extended from the apical to the posterolateral segment rather than the anteroseptal segment. However, five of those 29 patients demonstrated the perfusion defect in posterolateral or anteroseptal segment without apical defect. There were no statistically significant differences in age and sex among the three groups of patients. Cardiac catheterization
of death, sudden death (presumed arrhythmia) or progressive heart failure was noted in patients who died during the follow-up period. Autopsy study We studied 10 of 22 patients who died during the follow-up period, at autopsy. The heart was sectioned transversely to the long axis of the left ventricle at one-third from the apex. After fixation with formaldehyde, the slice was stained with hematoxylin-eosin and masson-trichrome. To evaluate the fibrotic changes in the myocardium, the left ventricular wall was divided into anterior, septal, inferior and lateral segments on the specimen, and the percentage of fibrosis of each segment was determined by a planimeter. Statistical analysis Survival rates of the patients were plotted using a Kaplan-Meier graph. A &i-square analysis was made on survival after three years, at the end of follow-up and the cause of death using a 3 x 2 contingency table. Comparison of hemodynamic data was performed by analysis of variance (ANOVA) and unpaired r-test. P < 0.05 was considered significant. Results Thallium scanning and hemodynamics
Cardiac catheterization was performed within a month of the day of the scintigraphic examination in all patients. Cardiac output was measured by the thermodilution method with using a 7 Fr. Swan-Ganz catheter. Selective coronary angiograms were obtained by a 5 or 7 Fr. Judkins catheter. A pig-tail catheter (5 or 7 Fr.) was used for left ventricular pressure measurements and the ventriculography. The left ventricular end-systolic and end-diastolic volume were obtained from the left ventriculograms by the area-length method, and ejection fraction was calculated.
Hemodynamic parameters appeared to be deteriorated with the extension of perfusion defect (Table 1). Ejection fraction in Grade III was significantly lower than that in Grade I (P -c0.05). Cardiac index in Grade III was significantly lower than that in I (P < 0.05) and II (P < 0.05). Left ventricular end-systolic and diastolic volume index in Grade III was significantly greater than that in Grade I (P -c0.01). Left ventricular enddiastolic pressure was significantly higher in Grade III than that in I (P -c0.01) and II (P < 0.05).
Follow-up study
Thallium scanning and prognosis
After scintigraphic evaluation, patients were followed until death, or until May 1987. The cause
Survival curves for the three groups are shown using a Kaplan-Meier graph in Fig. 2. No patients
222 TABLE
1
Grading of thallium scanning and hemodynamic parameters in patients with dilated cardiomyopathy. Grading of scan
No. of patients
CI (l/min/m2)
LVESVI
LVEDVI
LVEDP
(8)
W/m*)
(mWn2)
(mm Hg)
I
19 22 29
38k 8 32 f 11 29*13 *
3.3 + 0.9 3.3 + 0.8 2.6 f 0.8 *.+
77* 6 108+13 * 128*13 **
120 * 34 149 + 64 172+72 **
9*5 10 f I 16k8 **.I
II III
EF
Values are mean f SD. Grading of scan: I: no perfusion defect. II: apical perfusion defect. III: extensive perfusion defect. CI = cardiac index; EF = ejection fraction; LVEDP = left ventricular end-diastolic pressure; LVEDVI = left ventricular end-diastolic volume index; LVESVI = left ventricular end-systolic volume index. * P i 0.05, * * P < 0.01 vs Grade I; + P c 0.05vsGrade II by unpaired f-test.
died from other disease than cardiomyopathy. Low survival rate was noted in patients with Grade III. Although overall survival trends were not significantly different in the three groups of patients, the three-year mortality rate was significantly higher in proportion to the extension of perfusion defect (P -c0.05 by &i-square analysis): one in Grade I (5%) four in Grade II (18%) and 14 in Grade III (48%) died within three years. Death from progressive heart failure tended to occur more frequently in patients with extensive perfusion defect (P < 0.05 by &i-square analysis): one of two patients in Grade I, one of five in Grade II and 12 of 14 in Grade III died from
progressive denly.
heart failure while others died sud-
Follow-up thallium scanning Thallium scanning was again performed in 18 patients (Fig. 3). Mean interval between the initial and follow-up examinations was 26 months (ranging from 12 to 48 months). In the initial thallium scanning, five patients were Grade I, eight Grade II and five Grade III. In the follow-up examination, five patients showed the extension of the perfusion defect although 10 were unchanged. However, three patients showed the regression of the perfusion defect. In two of them, improvement in subjective symptoms was associated with the reduction of perfusion defect, while another patient showed no changes in clinical condition.
w
Initial
o!
0
30
I
Grade
U
Grade
RI x
BO,Month*,
60
Follow-up
Grade
Follow-Up
Period
Fig. 2. Survival rate of patients with dilated cardiomyopathy plotted in a Kaplan-Meier graph. Lower survival rate was noted in proportion to the grade of thallium scanning. Grade I: no perfusion defect, Grade II: apical perfusion defect, Grade III: extensive perfusion defect.
Grade
111
Fig. 3. Changes in the grading of thallium scanning in patients with dilated cardiomyopathy. Each line indicates the individual patient. Grade I: no perfusion defect, Grade II: apical perfusion defect, Grade III: extensive perfusion defect.
223 TABLE
2
Extension of myocardial fibrosis in left ventricular patients with dilated cardiomyopathy. Patient No. 1 2 3 4 5 6 7 8 9 10
Grading of scan III III III III III III II II II I
Grading of scan: I: defect, III: extensive subdivided into five fibrosis is < 25% of segment area; + + + + + = fibrosis is
wall in
Extension of fibrosis in left ventricle Septum
Anterior
Lateral
Posterior
+
-
_
f + +
+
+ + ++ +++ ++ + ++ +
+ ++ ++ +++ + +++ ++ ++
f +++ ++ f + ++
f + ++ ++ + ++ f +
+
f f
no perfusion defect, II: apical perfusion perfusion defect. Extension of fibrosis is ranges: - = no increase in fibrosis; f = segment area; + = fibrosis is 25-508 of = fibrosis is 50-75% of segment area; > 75% of segment area.
Thallium scanning and autopsy findings Autopsy was done in six patients of Grade III, three of Grade II and one of Grade I (Table 2). Mean interval from thallium scans to the autopsy was 4.2 years. Increased fibrosis was noted in each patient of all the three grades. Marked fibrosis (> 75% of segmental area) was noted in three patients of Grade III. In cases 2-4, fibrosis was extended into posterior and lateral segments rather than anterior and septal segments, which coincided with the findings in thallium scanning. However, in cases 1, 5 and 6, fibrosis was extended into anterior and septal segments the same as in posterior and lateral segments while perfusion defect was extended into posterior and lateral segments on thallium scanning in these patients. Discussion The present study demonstrated that extent of perfusion defect on thallium imaging was related to the hemodynamic deterioration and the threeyear prognosis of the patients with dilated cardiomyopathy.
Since dilated cardiomyopathy is characterized as the dilatation of the left ventricle because of the myocardial fibrosis, increase in left ventricular volume may be the primary change in hemodynamic parameters and decrease in cardiac output and ejection fraction and increase in left ventricular end-diastolic pressure may be followed. Although these hemodynamic parameters demonstrate the cardiac function of the patients, the invasive technique was required to obtain them. In the present study, thallium imaging showed that the extent of perfusion defect was related to hemodynamic parameters, suggesting the value of this method in the noninvasive evaluation of the patients with dilated cardiomyopathy. Several factors had been proposed to predict the prognosis of dilated cardiomyopathy, i.e., ventricular function [6-91, pulmonary capillary wedge pressure [lo], left ventricular end-diastolic diameter and wall thickness [ll-131 and ventricular conduction delay [14-161. The present study demonstrated that the patients with extensive perfusion defect had a higher three-year mortality rate and high risk of death from progressive heart failure, suggesting that the extent of perfusion defect on thallium scanning was important in relation not only to the prognosis but also the cause of death in patients with dilated cardiomyopathy. Autopsy studies demonstrated the marked fibrosis in patients with Grade III. In some patients, the increased fibrosis was equally seen in the anteroseptal and posterolateral area, although the perfusion defect of the thallium scanning was predominantly extended to the posterolateral segment. This discrepancy may be in part explained by the long interval from thallium scanning to autopsy. However, some factors other than myocardial fibrosis may influence the thallium imaging because the regression of the perfusion defect was seen in three patients in the follow-up examination (Fig. 3). Dunn et al. and Bulkley et al. reported that the perfusion defect was associated with the thinning of left ventricular wall although they examined only few cases [3,4]. In 10 autopsied cases in the present study, although thinning of the ventricular wall was associated with marked fibrosis, there was no close correlation of the perfusion defect
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with increased fibrosis, and hence wall thinning. Gewirtz et al. suggested the influence of left ventricular volume on myocardial images using partial aortic occlusion in dogs [17]. In the present study, patients in Grade III (extensive perfusion defect) had greater left ventricular volume than those in Grade I (Table 1). These data indicate that left ventricular volume may influence the myocardial images of thallium scanning in the patients with dilated cardiomyopathy. In conclusion, the extent of the perfusion defect on thallium imaging was related to the hemodynamic deterioration and the prognosis of the patients, which indicated the value of thallium imaging in the evaluation and management of the patients with dilated cardiomyopathy. Although increased fibrosis in the left ventricular wall was noted in these patients, the distribution of the perfusion defect was not related to that of fibrosis.
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