Correlative Study of Regional Left Ventricular Histology And Contractile Function
EDWARD B. STINSON, MD, FACC" MARGARET E. BILLINGHAM, MD Stanford, Cafifornia
From the Departmentsof CardiovascularSurgery and Pathology,StanfordUniversityMedicalCenter, Stanford, California. Manuscript received December 23, 1975; revised manuscript received August 17, 1976, accepted September 10, 1976. ° Established Investigator of the American Heart Association. Address for reprints: Edward B. Stinson, MD, Department of CardiovascularSurgery, Stanford University Medical Center, Stanford, California 94305.
378
In 110 patients with documented coronary artery disease, transmural biopsy of the anteroapical region of the left ventricle was performed during aortocoronary bypass grafting. Biopsy specimens were semiquantitatively graded microscopically for myocardial fibrosis as an indicator of chronic ischemic damage. Preoperatively, systolic wall motion of the region from which the biopsy specimen was taken was semiquanUtatively graded as showing normal motion, hypokinesia, akinesia or dyskinesia on ventriculography. Wall motion-histologic correlations, taking into account both electrocardiographic evidence of anterior infarction and ST-T abnormalities, were then established. Overall, there was fair agreement (72 percent) between functional and histologic assessment of the left yentricular region evaluated, both qualitatively (normal versus abnormal, 72 percent agreement) and quantitatively (degree of abnormality, correlation coefficient 0.66, P = 0.005). The 22 patients with electrocardiographic evidence of anterior infarction had various degrees of abnormal regional motion and myocardial fibrosis. Discordance between wall motion and histologic findings was most common (50 percent of instances) in the 34 patients with anterior ST-T changes without infarction and generally was manifest as abnormal motion with normal histologic features. By contrast, normal motion and abnormal histologic features represented the most common type of discordance (22 percent of instances) in the 54 patients without either anterior infarction or ST-T deviation. These data provide a basis for inference of myocardial morphologic features (fibrosis) from assessment of ventricuIographic wall motion and the electrocardiogram. They may thus be useful in predicting the potential functional benefits of bypass grafting of coronary arteries supplying abnormally contractile segments of the left ventricle.
Regional disorders of left ventricular contraction, as assessed with cineradiographic techniques, are common in patients with coronary artery disease; the reported frequency generally ranges from 40 to 70 percent. 1-12 When contractile abnormalities coexist with electrocardiographic evidence of transmural infarction in the appropriate region, one can reasonably assume the presence of pathologic changes--acute, chronic or both--characteristic of myocardial necrosis. Alternately, it has been presumed that reversibility of regional dyssynergy in the left ventricle under the influence of agents such as inotropic drugs or nitroglycerin connotes the persistence of viable myocardium.13-16 However, the correlative relation of wall motion disorders with regional histologic abnormalities has not been well defined except in cases of left ventricular aneurysm with total or nearly total fibrous replacement of the myocardium. 17,1s Furthermore, the apparent discrepancy between locally abnormal contraction and the absence of Q waves diagnostic of infarction in the corresponding region ("false negative electrocardiogram") in
March1977 The American Journal of CARDIOLOGY Volume39
LEFT VENTRICULARMOTION-HISTOLOGIC CORRELATIONS--STINSONAND BILLINGHAM
p a t i e n t s with c o r o n a r y a r t e r y disease has not been analyzed with regard to microscopic m y o c a r d i a l structure. In order to correlate m o r e a c c u r a t e l y regional left v e n t r i c u l a r systolic m e c h a n i c a l p e r f o r m a n c e a n d elect r o c a r d i o g r a p h i c findings with m y o c a r d i a l histologic findings, we p e r f o r m e d t r a n s m u r a l left v e n t r i c u l a r needle biopsy in 110 patients undergoing aortocoronary b y p a s s grafting. Biopsy s p e c i m e n s were serniquantitatively evaluated for myocardial fibrosis as an indication of chronic ischemic damage. Patients
REGION
and Methods
~',,',~
Patients: The study group comprised 110 patients referred from various hospitals for surgical treatment of symptomatic coronary artery disease. Ninety-two were men, and the average age of all patients was 53 years (range 37 to 71 years). In 95 percent of patients angina pectoris refractory to medical control was the primary indication for operation. Twentyeight patients (25 percent) presented with a clinical syndrome of unstable angina pectoris, defined as recent and new (within 8 weeks of operation) development of angina pectoris at rest (daytime or nocturnal). Forty-four patients (40 percent) had had an electrocardiographically documented myocardial infarction (anterior in 15, inferior in 22 and both anterior and inferior in 7). Eight patients presented symptoms of left ventricular failure. All patients had been studied with selective coronary arteriography and left ventriculography performed in a right anterior oblique projection. No patient had a new myocardial infarction between ventriculographic study and operation. Standard electrocardiograms obtained before, but as close as possible to the time of left ventriculography were reviewed and interpreted according to the modified criteria of the Minnesota code 19 for evidence of anterior myocardial infarction or anterior ST-T segment deviations consistent with myocardial ischemia. Patterns of anterior infarction were initially distinguished as anteroseptal or anterolateral but were subsequently combined into an "anterior infarction" category because subdivision did not correlate separately with further analysis of regional wall motion or myocardial histologic features (see later). S-T segment and T wave changes were not specifically subclassified. Ventricular wall motion: Left ventricular systolic motion at the endocardial border in the region of the anterolateral left ventricle near the apex was assessed preoperatively from review of the left ventriculogram (Fig. 1). In all cases this region was supplied by the distal distribution of the left anterior descending coronary artery, as is usual. 2° Contractile motion in this area was semiquantitatively graded as showing eukinesia (normal motion), hypokinesia, akinesia or dyskinesia (paradoxical systolic movement). Only sinus conducted beats not occurring within five cycles of a premature ventricular contraction were analyzed. Patients with defects of intraventricular conduction were excluded. The maximal extent of inward systolic movement, not asynchrony of contraction, was assessed.
A semiquantitative grading system for systolic motion was chosen because contractile movement of the anteroapical portion of the normal left ventricle (in the area of biopsy) is not accurately portrayed by measured percent shortening of either the traditional longitudinal or short (hemiaxial) axis; total or nearly total obliteration of the diastolic ventriculographic silhouette during systole normally occurs in this reg!on, indicating an oblique mean inward movement of the
FIGURE 1. Left ventricular (L.V.) silhouette as visualized with ventriculography in the right anterior oblique projection. The region of biopsy of the anteroapical segment is indicated in A. B illustrates grading of systolic inward movement of endocardial border: Displacement into area 1 was graded as normal (eukinesia) and into area 2 as hypokinesia; lack of contractile movement was graded as akinesia (3), and paradoxical motion as dyskinesia (4).
endocardial surface toward the geometrical center of the ventricle, in contrast to the more perpendicular motion of central and basal portions of the ventricle (as visualized in the right anterior projection). Furthermore, considerable variation in the extent of fiber shortening in the apical region exists in normal ventricles (reported percent anterior hemiaxial shortening near the apex ranges from 25 to more than 50 percent). 1,4,9,2]-23 For this reason, only clearly discernible abnormalities of contraction were distinguished. Surgery and ventricular biopsy: Operation was performed with the patient on cardiopulmonary bypass, utilizing a disposable bubble-type oxygenator. After institution of bypass and induction of ventricular fibrillation by transient alternating current stimulation, a transmural biopsy specimen measuring 1.5 mm in diameter was obtained with a Tru-Cut biopsy needle (Travenol Laboratories) from the anterolateral left ventricle near the apex, that is, the region in which systolic movement had previously been assessed on left ventriculography. A routine vent for left ventricular decompression was then inserted through this area; subsequently, the vent site was closed by a purse-string suture. Biopsy specimens, preserved in buffered formaldehyde, were examined microscopically after staining with hematoxylin-eosin and Masson's trichrome stain to facilitate recognition of fibrous tissue. The degree of myocardial fibrosis in specimens identified only by code was graded as follows (Fig. 2): Grade I, normal myocardial histologic features; grade II, mild to moderate myocardial fibrosis with preservation or only mild disruption of basic morphologic architecture (for example, fascicular bundles); grade III, moderate to severe myocardial fibrosis with disruption of architecture and loss of muscle mass; and grade IV, total fibrous replacement. Only full thickness specimens, exhibiting both endocardium and epicardium, were assessed, and the histologic features of the entire transmural region were taken into account (isolated subendocardial scarring was not encountered).
The correlations of graded wall motion and histologic features were analyzed by means of a general correlation test,
March 1977
The American Journal of CARDIOLOGY
Volume 39
379
LEFT VENTRICULAR MOTION-HISTOLOGIC CORRELATIONS--STINSON
AND BILLINGHAM
I
II
[ ,'-Iq,,
i ~ : . - ' ~ ' : ~ ~ ' _ . ~ ' ~ .
" ". " ~ . " :
-
.'~.r
-~""
"~,: : . ~ w
•
. ,., , . . .:
.'~.".c
:':, .~';
- " F
iK"
~ "
"'~
FIGURE 2. Grades of myocardial fibrosis (see text). F indicates fibrous tissue. Specimens graded I and II were stained with trichrome, producing dark staining of fibrous tissue. Grade III and IV specimens were stained with hematoxylin-eosin, producing light staining of fibrous tissue. All X 30.
assigning values of 1 through 4 to each grade; the resulting coefficients of correlation were then compared with zero for test of significance. In addition, chi-square tests were used for analysis of differences between dichotomized groups (see Results). The relations between ventriculographic wall motion and myocardial histologic features in terms of sensitivity, specificity, false positive and false negative rates and percent agreement were analyzed according to methods outlined by Holt et al. 24
dial histologic features in 30 of 42 instances (71 percent) (Table IB). D i s c o r d a n t relations b e t w e e n m o t i o n a n d histologic features in this group of p a t i e n t s were largely a c c o u n t e d for b y n o r m a l or only m o d e r a t e l y d e p r e s s e d contractile m o v e m e n t in the presence of mild m y o c a r dial fibrosis.
Results
Correlations between graded regional motion and myocardial histologic features: T h e s e correlations, taking into account b o t h electrocardiographic evidence of anterior infarction (Q waves) and a n t e r i o r S T - T changes, are s u m m a r i z e d for the entire series in T a b l e I. Overall, the regional contraction p a t t e r n correlated highly with the degree of myocardial fibrosis (r = 0.66, P = 0.005) despite a s u b s t a n t i a l n u m b e r of disc o r d a n t relations between wall m o t i o n and histologic features in patients without myocardial infarction. Most of the discordant relations with a.bnormal m o t i o n a n d n o r m a l histologic features occurred in p a t i e n t s with ischemic S T - T abnormalities without evidence for infarction (Table IA). However, even these p a t i e n t s exhibited an abnormal contraction pattern associated with myocardial fibrosis in 50 p e r c e n t of instances. Sixtyseven percent of such patients with severe abnormalities of contraction (akinesia or dyskinesia) h a d m y o c a r d i a l fibrosis, b u t none had total scar r e p l a c e m e n t (grade
TABLE I Wall Motion-Histologic Relations in Subgroups Classified According to Anterior Electrocardiographic Findings* Regional Wall M o t i o n
Histologic
IV).
In patients without either anterior S T - T changes or myocardial infarction, n o r m a l regional motion on left ventriculography was associated with n o r m a l m y o c a r -
380
March 1977
The American Journal of CARDIOLOGY
Volume 39
Grade
Eukinesia
Hypokinesia Akinesia
Dyskinesia
A. Infarction Absent, ST-T Changes Present
I II ill Iv
11 3 0 0
6 2 0 0
3 3 3 0
1 2 0 0
B. Infarction Absent, ST-T Changes Absent
I I, III IV
30 10 2 0
6 3 2 0
0 0 1 0
0 0 0 0
I
o
II
0
o
o
o
0
3
III
0
2
2
6
5
c. Infarction Present
IV
0
0
0
* Numbers indicate number of patients in each category.
4
LEFT VENTRICULAR MOTION-HISTOLOGIC CORRELATIONS--STINSON AND BILLINGHAM
The 22 patients with electrocardiographic evidence of transmural anterior myocardial infarction uniformly exhibited in various degrees abnormal systolic motion and myocardial fibrosis regardless of the presence or absence of ST-T changes (Table IC). Motion was graded as akinetic or dyskinetic in 20 (91 percent); 17 of the 22 patients (77 percent) had grade III or IV myocardial fibrosis. Total fibrous replacement of the myocardium (grade IV) was seen in only four patients, all of whom had a saccular ventricular aneurysm. Each of the five patients whose biopsy showed minimal fibrosis (grade II) but whose ventriculogram showed severe motion abnormalities had, in addition to infarction, ST-T segment deviations consistent with ischemia. Wall motion-histologic correlations for the entire series were further examined by classifying patients into those displaying (1) abnormal anteroapical wall motion (hypokinesia, akinesia, dyskinesia), or (2) normal contraction (Table II). This analysis showed that 38 of the 54 patients with abnormal motion (70 percent) had myocardial fibrosis of various degrees. Of the remaining 16, 10 had ST-T abnormalities consistent with myocardial ischemia; moreover, only 4 of the 16 had severe disorders of contraction (akinesia or dyskinesia). Conversely, 73 percent of the 56 patients with normal contraction had normal histologic findings; 13 of the remaining 15 patients in this group had only mild fibrosis (grade II). These differences in distribution were highly significant (P < 0.001). Thus, for the entire patient group, abnormal regional ventriculographic wall motion of any degree showed a sensitivity of 72 percent and a specificity of 72 percent if histologic assessment of myocardial fibrosis is taken as the standard of comparison. There was a false positive rate of 30 percent, mostly attributable to patients with ST-T abnormalities. Relations between contractile motion and myocardial histologic features for the 76 patients who did not exhibit isolated anterior ST-T changes (that is, ST-T changes not associated with an electrocardiographic pattern of transmural infarction) are shown in Figure 3. The overall motion-histologic correlation (r = 0.75) in such patients was highly significant (P = 0.005). Discordant relations were unusual (18 cases) and were predominantly (12 of 18) of the type with normal motion and abnormal histologic features. When these patients were classified into those showing (1) normal or hypokinetic wall motion, or (2) akinetic or dyskinetic
motion on ventriculography, the sensitivity of ventriculograms in correlation with myocardial fibrosis was 53 percent and specificity 100 percent; the false positive rate was zero, but the false negative rate remained high (48 percent) (see Fig. 3). Correlations of wall motion, histologic findings and myocardial infarction with stenosis of the left anterior descending coronary artery: Nearly all patients (88 percent) had an occlusive lesion of the left anterior descending coronary artery considered hemodynamically significant (70 percent or greater reduction of luminal diameter). As expected because of crosscorrelations, the frequency of anterior contractile, histologic and electrocardiographic abnormalities was significantly and directly related to the degree of stenosis of the left anterior descending coronary artery. Virtually all patients whose biopsy showed severe myocardial fibrosis (grades III to IV) or who manifested akinesia or dyskinesia on ventriculography had a high grade occlusive lesion. Similarly, all patients with electrocardiographic evidence of anterior infarction had a stenotic lesion greater than 70 percent; 19 of these 22 patients showed greater than 90 percent stenosis of the left anterior descending coronary artery. Six of 13 patients with less than 70 percent stenosis of the left anterior descending coronary artery had grade II or III myocardial fibrosis, but none of the 6 had abnormal anteroapical contractions. Relations to clinical status: Twenty-eight patients in this series presented for evaluation with angina pectoris defined as unstable. Nineteen had ST-T abnormalities without infarction, and 12 of the 19 had anteroapical contractile dysfunction. The presence of multiple vessel disease in the majority of patients with unstable angina precludes a valid correlation of localized anteroapical histologic findings and wall motion with clinical status, but it is of interest that 8 of the 10 patients with ST-T changes without infarction who
PATIENTS WITHOUT ISOLATED ST-T CHANGES
,,,
~oo°
~88oo
oo
~oo
EDWARD B. STINSON, MD, FACC" MARGARET E. BILLINGHAM, MD Stanford, Cafifornia
From the Departmentsof CardiovascularSurgery and Pathology,StanfordUniversityMedicalCenter, Stanford, California. Manuscript received December 23, 1975; revised manuscript received August 17, 1976, accepted September 10, 1976. ° Established Investigator of the American Heart Association. Address for reprints: Edward B. Stinson, MD, Department of CardiovascularSurgery, Stanford University Medical Center, Stanford, California 94305.
378
In 110 patients with documented coronary artery disease, transmural biopsy of the anteroapical region of the left ventricle was performed during aortocoronary bypass grafting. Biopsy specimens were semiquantitatively graded microscopically for myocardial fibrosis as an indicator of chronic ischemic damage. Preoperatively, systolic wall motion of the region from which the biopsy specimen was taken was semiquanUtatively graded as showing normal motion, hypokinesia, akinesia or dyskinesia on ventriculography. Wall motion-histologic correlations, taking into account both electrocardiographic evidence of anterior infarction and ST-T abnormalities, were then established. Overall, there was fair agreement (72 percent) between functional and histologic assessment of the left yentricular region evaluated, both qualitatively (normal versus abnormal, 72 percent agreement) and quantitatively (degree of abnormality, correlation coefficient 0.66, P = 0.005). The 22 patients with electrocardiographic evidence of anterior infarction had various degrees of abnormal regional motion and myocardial fibrosis. Discordance between wall motion and histologic findings was most common (50 percent of instances) in the 34 patients with anterior ST-T changes without infarction and generally was manifest as abnormal motion with normal histologic features. By contrast, normal motion and abnormal histologic features represented the most common type of discordance (22 percent of instances) in the 54 patients without either anterior infarction or ST-T deviation. These data provide a basis for inference of myocardial morphologic features (fibrosis) from assessment of ventricuIographic wall motion and the electrocardiogram. They may thus be useful in predicting the potential functional benefits of bypass grafting of coronary arteries supplying abnormally contractile segments of the left ventricle.
Regional disorders of left ventricular contraction, as assessed with cineradiographic techniques, are common in patients with coronary artery disease; the reported frequency generally ranges from 40 to 70 percent. 1-12 When contractile abnormalities coexist with electrocardiographic evidence of transmural infarction in the appropriate region, one can reasonably assume the presence of pathologic changes--acute, chronic or both--characteristic of myocardial necrosis. Alternately, it has been presumed that reversibility of regional dyssynergy in the left ventricle under the influence of agents such as inotropic drugs or nitroglycerin connotes the persistence of viable myocardium.13-16 However, the correlative relation of wall motion disorders with regional histologic abnormalities has not been well defined except in cases of left ventricular aneurysm with total or nearly total fibrous replacement of the myocardium. 17,1s Furthermore, the apparent discrepancy between locally abnormal contraction and the absence of Q waves diagnostic of infarction in the corresponding region ("false negative electrocardiogram") in
March1977 The American Journal of CARDIOLOGY Volume39
LEFT VENTRICULARMOTION-HISTOLOGIC CORRELATIONS--STINSONAND BILLINGHAM
p a t i e n t s with c o r o n a r y a r t e r y disease has not been analyzed with regard to microscopic m y o c a r d i a l structure. In order to correlate m o r e a c c u r a t e l y regional left v e n t r i c u l a r systolic m e c h a n i c a l p e r f o r m a n c e a n d elect r o c a r d i o g r a p h i c findings with m y o c a r d i a l histologic findings, we p e r f o r m e d t r a n s m u r a l left v e n t r i c u l a r needle biopsy in 110 patients undergoing aortocoronary b y p a s s grafting. Biopsy s p e c i m e n s were serniquantitatively evaluated for myocardial fibrosis as an indication of chronic ischemic damage. Patients
REGION
and Methods
~',,',~
Patients: The study group comprised 110 patients referred from various hospitals for surgical treatment of symptomatic coronary artery disease. Ninety-two were men, and the average age of all patients was 53 years (range 37 to 71 years). In 95 percent of patients angina pectoris refractory to medical control was the primary indication for operation. Twentyeight patients (25 percent) presented with a clinical syndrome of unstable angina pectoris, defined as recent and new (within 8 weeks of operation) development of angina pectoris at rest (daytime or nocturnal). Forty-four patients (40 percent) had had an electrocardiographically documented myocardial infarction (anterior in 15, inferior in 22 and both anterior and inferior in 7). Eight patients presented symptoms of left ventricular failure. All patients had been studied with selective coronary arteriography and left ventriculography performed in a right anterior oblique projection. No patient had a new myocardial infarction between ventriculographic study and operation. Standard electrocardiograms obtained before, but as close as possible to the time of left ventriculography were reviewed and interpreted according to the modified criteria of the Minnesota code 19 for evidence of anterior myocardial infarction or anterior ST-T segment deviations consistent with myocardial ischemia. Patterns of anterior infarction were initially distinguished as anteroseptal or anterolateral but were subsequently combined into an "anterior infarction" category because subdivision did not correlate separately with further analysis of regional wall motion or myocardial histologic features (see later). S-T segment and T wave changes were not specifically subclassified. Ventricular wall motion: Left ventricular systolic motion at the endocardial border in the region of the anterolateral left ventricle near the apex was assessed preoperatively from review of the left ventriculogram (Fig. 1). In all cases this region was supplied by the distal distribution of the left anterior descending coronary artery, as is usual. 2° Contractile motion in this area was semiquantitatively graded as showing eukinesia (normal motion), hypokinesia, akinesia or dyskinesia (paradoxical systolic movement). Only sinus conducted beats not occurring within five cycles of a premature ventricular contraction were analyzed. Patients with defects of intraventricular conduction were excluded. The maximal extent of inward systolic movement, not asynchrony of contraction, was assessed.
A semiquantitative grading system for systolic motion was chosen because contractile movement of the anteroapical portion of the normal left ventricle (in the area of biopsy) is not accurately portrayed by measured percent shortening of either the traditional longitudinal or short (hemiaxial) axis; total or nearly total obliteration of the diastolic ventriculographic silhouette during systole normally occurs in this reg!on, indicating an oblique mean inward movement of the
FIGURE 1. Left ventricular (L.V.) silhouette as visualized with ventriculography in the right anterior oblique projection. The region of biopsy of the anteroapical segment is indicated in A. B illustrates grading of systolic inward movement of endocardial border: Displacement into area 1 was graded as normal (eukinesia) and into area 2 as hypokinesia; lack of contractile movement was graded as akinesia (3), and paradoxical motion as dyskinesia (4).
endocardial surface toward the geometrical center of the ventricle, in contrast to the more perpendicular motion of central and basal portions of the ventricle (as visualized in the right anterior projection). Furthermore, considerable variation in the extent of fiber shortening in the apical region exists in normal ventricles (reported percent anterior hemiaxial shortening near the apex ranges from 25 to more than 50 percent). 1,4,9,2]-23 For this reason, only clearly discernible abnormalities of contraction were distinguished. Surgery and ventricular biopsy: Operation was performed with the patient on cardiopulmonary bypass, utilizing a disposable bubble-type oxygenator. After institution of bypass and induction of ventricular fibrillation by transient alternating current stimulation, a transmural biopsy specimen measuring 1.5 mm in diameter was obtained with a Tru-Cut biopsy needle (Travenol Laboratories) from the anterolateral left ventricle near the apex, that is, the region in which systolic movement had previously been assessed on left ventriculography. A routine vent for left ventricular decompression was then inserted through this area; subsequently, the vent site was closed by a purse-string suture. Biopsy specimens, preserved in buffered formaldehyde, were examined microscopically after staining with hematoxylin-eosin and Masson's trichrome stain to facilitate recognition of fibrous tissue. The degree of myocardial fibrosis in specimens identified only by code was graded as follows (Fig. 2): Grade I, normal myocardial histologic features; grade II, mild to moderate myocardial fibrosis with preservation or only mild disruption of basic morphologic architecture (for example, fascicular bundles); grade III, moderate to severe myocardial fibrosis with disruption of architecture and loss of muscle mass; and grade IV, total fibrous replacement. Only full thickness specimens, exhibiting both endocardium and epicardium, were assessed, and the histologic features of the entire transmural region were taken into account (isolated subendocardial scarring was not encountered).
The correlations of graded wall motion and histologic features were analyzed by means of a general correlation test,
March 1977
The American Journal of CARDIOLOGY
Volume 39
379
LEFT VENTRICULAR MOTION-HISTOLOGIC CORRELATIONS--STINSON
AND BILLINGHAM
I
II
[ ,'-Iq,,
i ~ : . - ' ~ ' : ~ ~ ' _ . ~ ' ~ .
" ". " ~ . " :
-
.'~.r
-~""
"~,: : . ~ w
•
. ,., , . . .:
.'~.".c
:':, .~';
- " F
iK"
~ "
"'~
FIGURE 2. Grades of myocardial fibrosis (see text). F indicates fibrous tissue. Specimens graded I and II were stained with trichrome, producing dark staining of fibrous tissue. Grade III and IV specimens were stained with hematoxylin-eosin, producing light staining of fibrous tissue. All X 30.
assigning values of 1 through 4 to each grade; the resulting coefficients of correlation were then compared with zero for test of significance. In addition, chi-square tests were used for analysis of differences between dichotomized groups (see Results). The relations between ventriculographic wall motion and myocardial histologic features in terms of sensitivity, specificity, false positive and false negative rates and percent agreement were analyzed according to methods outlined by Holt et al. 24
dial histologic features in 30 of 42 instances (71 percent) (Table IB). D i s c o r d a n t relations b e t w e e n m o t i o n a n d histologic features in this group of p a t i e n t s were largely a c c o u n t e d for b y n o r m a l or only m o d e r a t e l y d e p r e s s e d contractile m o v e m e n t in the presence of mild m y o c a r dial fibrosis.
Results
Correlations between graded regional motion and myocardial histologic features: T h e s e correlations, taking into account b o t h electrocardiographic evidence of anterior infarction (Q waves) and a n t e r i o r S T - T changes, are s u m m a r i z e d for the entire series in T a b l e I. Overall, the regional contraction p a t t e r n correlated highly with the degree of myocardial fibrosis (r = 0.66, P = 0.005) despite a s u b s t a n t i a l n u m b e r of disc o r d a n t relations between wall m o t i o n and histologic features in patients without myocardial infarction. Most of the discordant relations with a.bnormal m o t i o n a n d n o r m a l histologic features occurred in p a t i e n t s with ischemic S T - T abnormalities without evidence for infarction (Table IA). However, even these p a t i e n t s exhibited an abnormal contraction pattern associated with myocardial fibrosis in 50 p e r c e n t of instances. Sixtyseven percent of such patients with severe abnormalities of contraction (akinesia or dyskinesia) h a d m y o c a r d i a l fibrosis, b u t none had total scar r e p l a c e m e n t (grade
TABLE I Wall Motion-Histologic Relations in Subgroups Classified According to Anterior Electrocardiographic Findings* Regional Wall M o t i o n
Histologic
IV).
In patients without either anterior S T - T changes or myocardial infarction, n o r m a l regional motion on left ventriculography was associated with n o r m a l m y o c a r -
380
March 1977
The American Journal of CARDIOLOGY
Volume 39
Grade
Eukinesia
Hypokinesia Akinesia
Dyskinesia
A. Infarction Absent, ST-T Changes Present
I II ill Iv
11 3 0 0
6 2 0 0
3 3 3 0
1 2 0 0
B. Infarction Absent, ST-T Changes Absent
I I, III IV
30 10 2 0
6 3 2 0
0 0 1 0
0 0 0 0
I
o
II
0
o
o
o
0
3
III
0
2
2
6
5
c. Infarction Present
IV
0
0
0
* Numbers indicate number of patients in each category.
4
LEFT VENTRICULAR MOTION-HISTOLOGIC CORRELATIONS--STINSON AND BILLINGHAM
The 22 patients with electrocardiographic evidence of transmural anterior myocardial infarction uniformly exhibited in various degrees abnormal systolic motion and myocardial fibrosis regardless of the presence or absence of ST-T changes (Table IC). Motion was graded as akinetic or dyskinetic in 20 (91 percent); 17 of the 22 patients (77 percent) had grade III or IV myocardial fibrosis. Total fibrous replacement of the myocardium (grade IV) was seen in only four patients, all of whom had a saccular ventricular aneurysm. Each of the five patients whose biopsy showed minimal fibrosis (grade II) but whose ventriculogram showed severe motion abnormalities had, in addition to infarction, ST-T segment deviations consistent with ischemia. Wall motion-histologic correlations for the entire series were further examined by classifying patients into those displaying (1) abnormal anteroapical wall motion (hypokinesia, akinesia, dyskinesia), or (2) normal contraction (Table II). This analysis showed that 38 of the 54 patients with abnormal motion (70 percent) had myocardial fibrosis of various degrees. Of the remaining 16, 10 had ST-T abnormalities consistent with myocardial ischemia; moreover, only 4 of the 16 had severe disorders of contraction (akinesia or dyskinesia). Conversely, 73 percent of the 56 patients with normal contraction had normal histologic findings; 13 of the remaining 15 patients in this group had only mild fibrosis (grade II). These differences in distribution were highly significant (P < 0.001). Thus, for the entire patient group, abnormal regional ventriculographic wall motion of any degree showed a sensitivity of 72 percent and a specificity of 72 percent if histologic assessment of myocardial fibrosis is taken as the standard of comparison. There was a false positive rate of 30 percent, mostly attributable to patients with ST-T abnormalities. Relations between contractile motion and myocardial histologic features for the 76 patients who did not exhibit isolated anterior ST-T changes (that is, ST-T changes not associated with an electrocardiographic pattern of transmural infarction) are shown in Figure 3. The overall motion-histologic correlation (r = 0.75) in such patients was highly significant (P = 0.005). Discordant relations were unusual (18 cases) and were predominantly (12 of 18) of the type with normal motion and abnormal histologic features. When these patients were classified into those showing (1) normal or hypokinetic wall motion, or (2) akinetic or dyskinetic
motion on ventriculography, the sensitivity of ventriculograms in correlation with myocardial fibrosis was 53 percent and specificity 100 percent; the false positive rate was zero, but the false negative rate remained high (48 percent) (see Fig. 3). Correlations of wall motion, histologic findings and myocardial infarction with stenosis of the left anterior descending coronary artery: Nearly all patients (88 percent) had an occlusive lesion of the left anterior descending coronary artery considered hemodynamically significant (70 percent or greater reduction of luminal diameter). As expected because of crosscorrelations, the frequency of anterior contractile, histologic and electrocardiographic abnormalities was significantly and directly related to the degree of stenosis of the left anterior descending coronary artery. Virtually all patients whose biopsy showed severe myocardial fibrosis (grades III to IV) or who manifested akinesia or dyskinesia on ventriculography had a high grade occlusive lesion. Similarly, all patients with electrocardiographic evidence of anterior infarction had a stenotic lesion greater than 70 percent; 19 of these 22 patients showed greater than 90 percent stenosis of the left anterior descending coronary artery. Six of 13 patients with less than 70 percent stenosis of the left anterior descending coronary artery had grade II or III myocardial fibrosis, but none of the 6 had abnormal anteroapical contractions. Relations to clinical status: Twenty-eight patients in this series presented for evaluation with angina pectoris defined as unstable. Nineteen had ST-T abnormalities without infarction, and 12 of the 19 had anteroapical contractile dysfunction. The presence of multiple vessel disease in the majority of patients with unstable angina precludes a valid correlation of localized anteroapical histologic findings and wall motion with clinical status, but it is of interest that 8 of the 10 patients with ST-T changes without infarction who
PATIENTS WITHOUT ISOLATED ST-T CHANGES
,,,
~oo°
~88oo
oo
~oo
