- Email: [email protected]
Estimation of inferobasal myocardial infarct size by late activation abnormalities of the QRS complex
Estimation of Inferobasal Myocardial Infarct Size by Late Activation Abnormalities of the QRS Complex MARIE J. COWAN, PhD, ROBERT A. BRUCE, MD, and DENNIS D. REICHENBACH, MD
This report describes the relation of myocardial infarct (MI) size in the left ventricular inferobasal wall, measured at necropsy, to late activation abnormalities of the QRS complex, measured by computerized spatial vectorcardiography. Fifteen patients with single inferobasal MIs and 10 patients with no evidence of heart disease were studied. The percentage of MI in the inferobasal wall was significantly related to the vectorcardiographic abnormalities noted late (i.e., 31 -I- 13 ms before the end of the QRS waveform) (r = 0.96, p <0.00001). The integral of the vector magnitudes during late
abnormal activation significantly predicted the amount of MI in the basal inferior wall (r = 0.88) and in the basal inferior wall plus the outer, subepicardial half of the transmural middle inferior, lateral and inferoseptal walls (r = 0.91). The additional information obtained from late activation of the QRS complex contributed more significance to the estimation of the left ventricular inferobasal MI size than the abnormalities commonly noted during early activation (i.e., during the Q wave).
Whether late activation abnormalities of the QRS complex can be used to estimate inferobasal myocardial infarct (MI) size is not known. Using spatial vectorcardiography (VCG), the percent volume of MI of the left ventricular (LV) wall for single or multiple MIs in all locations can be estimated by the integral of the magnitudes of the spatial vectors during the initial abnormal depolarization period (IAD) (r = 0.90, p <0.001). 1 However, this early activation index slightly underestimates the size of transmural inferobasal MIs measured at necropsy. This study describes the relation between the integral of the sequential vector spatial magnitudes during late activation and the pathologic measurement of MI in each of the basal inferior, middle inferior, inferoseptal and posterolateral LV regions. The latter vectorcardiographic index was defined by an alteration in the first derivative of the spatial vector magnitudes waveform during late activation. This study also analyzes the relation of inferobasal MI size to 2 predictive variables using abnormalities in early and late activation. The significance of the additional information obtained from late activation to that of early activation in estimation of inferobasal MI size is reported.
Methods
(Am J Cardiol 1984;54:726-732)
Twenty-five persons were studied: 15 patients with evidence of single inferobasal MIs documented at necropsy (MI group) and 10 control subjects who did not have MI. Autopsy permits were obtained for 35 patients with inferobasal MIs; 20 of 35 had 2 or more MIs of differing ages and LV locations. All patients with single inferobasal MIs were included in the sample. Five persons in the control group died from cancer, and the absence of heart disease was confirmed at necropsy. The absence of heart disease was confirmed in the other 5 by a negative history, a negative maximal treadmill exercise test response and a 5-year follow-up of yearly questionnaires indicating no morbidity. These 5 persons had been enrolled in the Seattle Heart Watch Program. The MI group had 9 men and 6 women, mean age 70 + 7 years. The control group had 7 men and 3 women, mean age 67 + 13 years. Only the VCGs taken within 24 hours of death were used for analysis. No patient had electrocardiograms that indicated left or right bundle branch block, left anterior or posterior fascicular block, or left or right ventricular hypertrophy. Electrocardiographic analyses: The computerized, high-frequency VCGs were recorded using the corrected Frank orthogonal lead system. 1,2 Data were quantitatively reproducible within 5% differences of the vector spatial magnitude values and 0 differences of the onset of the Q wave. All computer records were overread by 2 persons; I reader was consistently blinded to the autopsy findings. The predictive variable was the integral of vector magnitudes during late abnormal depolarization. It was calculated by the integration of the magnitudes of the spatial vectors every 2.5 ms (]~ ~¢/X2 -}- y2 + Z 2) for a variable duration during late ventricular depolarization. This variable was first suspected to be related to inferobasal MIs because patients
From the Departments of Physiological Nursing, Pathology, and Medicine, Division of Cardiology, University of Washington, Seattle, Washington. This study was supported in part by Grant HL27257 from the National Institutes of Health, Bethesda, Maryland. Manuscript received February 13, 1984; revised manuscript received May 31, 1984, accepted June 5, 1984. Address for reprints: Marie J. Cowan, PhD, Department of Pathology, SM-28, University of Washington, Seattle, Washington 98195. 726
October 1, 1984 THE AMERICAN JOURNAL OF CARDIOLOGY Volume54
with inferobasal MIs had VCGs with notches or slurs during the late activation period on the graphic display of the vector spatial magnitudes. Correct determination of the integral of late activation vectors depended on defining the correct period for integration. This was done by analyses of the first derivative of the vector spatial magnitudes (dm/dt = A v/X2 + y2 + Z2/At). The algorithm defined the onset of abnormal depolarization by a notch or slur in the time courses of the graphic display of the first derivative after the peak of R. A notch was defined as a local maximum and minimum in the derivative for at least 5 ms. If there was more than 1 notch, only the first detected notch was used. A slur was defined when the rate of change of the derivative was relatively slower. The minimal amount of change required for a slur to be identified was a value of the derivative <0.04 mV/ms for any 2.5-ms sampling point. 1 The end of the period was defined at the end of the QRS when the derivative was equal to 0. In the control group, the notches or slurs of the derivative during late depolarization were analogous to and approximately coincident with the change of direction commonly observed by the S wave. The S wave in leads X, Y and Z could begin at different points in time; therefore, the spatial designation by the derivative (dm/dt) was used to indicate notches or slurs in the control group (Fig. 1). The other predictive variable was the integral of the vector spatial magnitudes every 2.5 ms for a variable duration during IAD. 1 The period of IAD was determined by analyses of the first derivative from the beginning of depolarization to the time at the end of the "notch". This period was analogous to the Q-wave duration when the latter was evident in the X, Y, Z tracings (Fig. 1). Pathologic analyses: The pathologic methods used to analyze the heart have been described. 1 Transverse sections of the left ventricle were incubated in a solution of nitroblue tetrazolium followed by the addition of sodium succinate to detect dehydrogenase enzyme depletion. Volume displacement was done on each transverse section. Histologic examination of 25 to 50 tissue blocks were done for each left ventricle. MI size was quantified by computer-assisted planimetry, z MI volumes were calculated as a percentage of the volume of the left ventricle. All planimetry was performed twice for reproducibility, and the error was less than 1%. The transverse LV myocardial sections were divided longitudinally into 3 sectors and 5 circumferential segments (Fig. 2). The histologic ages of MI, the distribution of MI by LV segment, and the extent of transmural MI involvement are listed in Table I. The dependent variables were the total percentage of MI (%MI) in the inferobasal LV wall as well as the %MI in each of the following LV wall segments: basal inferior, middle inferior, inferoseptal, lateral, outer subepicardial 50% of the transmural wall, and inner subendocardia150% of the transmural wall. The total %MI in all the basal inferior segment plus the %MI in the subepicardial 50% of the transmural middle inferior, lateral and inferoseptal walls were summed to be used as another dependent variable. Statistical analyses: The relation of inferobasal MI size to electrocardiographic abnormalities during late activation was analyzed by simple linear regression. The relation of inferobasal MI size to 2 predictive variables, vectorcardiographic abnormalities during early and late activation, were analyzed by multivariate stepwise regression. Comparison of mean values were analyzed by 2-tailed, nonpaired Student t tests. Results
Relation of inferobasal infarct size to late activation abnormalities: T h e total p e r c e n t of inferobasal
727
M I was significantly related (r = 0.92, p <0.00001) to late activation abnormalities in the QRS waveform (Fig. 3). T h e integral of vector m a g n i t u d e s during late abn o r m a l activation ( L A T E ) h a d the highest correlation (r = 0.91) with the % M I in the basal inferior L V wall plus the epicardial half of the t r a n s m u r a l wall of t h e middle inferior, lateral, and inferoseptal L V walls (Fig. 4). Specifically, L A T E was significantly related to t h e a m o u n t of M I in the epicardial h a l f of the t r a n s m u r a l middle inferior, lateral, a n d inferoseptal left ventricle (r = 0.87) and the transmural basal inferior left ventricle (r = 0.88). T h e s e positive linear relations are illustrated in Figures 5 a n d 6. T h e late activation a b n o r m a l i t i e s were not as closely related to M I size in the inferior s e p t u m (r = 0.65), the t r a n s m u r a l middle inferior wall (r = 0.55), or the t r a n s m u r a l lateral wall (r = 0.45). T h e relations of late activation a b n o r m a l i t i e s a n d the distribution of %MI b y s e g m e n t in the inferobasal L V wall Spatial
Magnitude
First Derivative B
Control
D
C
Inferobalal MI
F
v,-
IAD~
--~v.J
Inferobasal MI
LATE
FIGURE 1. Representative time courses from the computer graph of the sequential spatial magnitudes of vector (~/X 2 -I- y2 -I- Z2) and the derivatives of the vector spatial magnitudes (A ~/X 2 + y2 -t- Z2/At) during a 16-beat averaged QRS complex for a patient without heart disease (control, A and B) and 2 patients with inferobasal myocardial infarctions (MIs) (C and D, E and F). The dotted area under the curve of the time course of the spatial magnitudes of vectors (C and E) indicates the summation of the vector magnitudes (LATE) during late abnormal depolarization (C and D). Note the slur (C) commonly observed on the spatial magnitude time course during late activation. The double arrows during late activation in the first derivative (D and F) indicate
the period defined by the notches for integration of LATE. The slur on the derivative (B) of the control during late activation indicates a short duration and a small value of the integral of the vector magnitudes. The darkened area under the curve of the time course of the vector spatial magnitudes (C and E) indicates the summation of the vector magnitudes during initial abnormal depolarization (lAD). The single arrow during initial activation in the first derivative (D and F) represents the period defined by the notch for integration of lAD.
728
INFEROBASALINFARCT SIZE BY LATE ACTIVATION QRS
TABLE I
Case
Distribution of Percent of Infarct by Segment and Involvement of Transmural Myocardlum Age of MI (days)
1
21
2 3 4 5 6 7 8 9 i0 11 12 13 14 15 Mean 4- SD
7-14 old 7 old 5 3 old. 7-14 7-14 old old old 3 old
%MI Total
%MI B Subepi
%MI Subepi
%MI NT
%MI Basal
%MI IMI
%MI IS
%MI LAT
%MI AP
30
19
19
11
4
10
3
7
R
24 12 24 2 31 39 17 21 16 16 10 ,7 46 9 20 4-12
16 7 8 1 22 22 4 9 10 5 3 6 25 5 11 -I-8
14 4 12 1 15 17 1 6 8 7 3 2 21 7 9 -I-7
10 8 12 1 i6 22 16 15 8 9 6 5 25 2 11 4-7
8 2 1 0.5 10 7 2 6 3 3 3 0.5 12 0 4 -I-4
3 7 11 1 14 15 3 5 9 6 5 6 6 .3 7 4-4
5 2 (AS) 11 2 1 0 6 11 2 2 3 1 1 0.5 4 3 3 ,4-4
0 0 10 0.5 1 2 3 6 0 5 0 0 17 2 3 4-5
2 1 1
R R LOM R R R R LC R R R R R R
0 4 7 2 1 1 1 0 7 1 2 4-2
Occ CA
Seven of i5 patiehts had ."old" myoc.ardial infarcts (MIs) (i.e., scars) and died from complications of this single inferobasal MI. No patient had right ventricular MI by chance alone. The group was not selected to exclude right ventricular involvement. L --- left c rcumflex arteryi LOM = left obtuse'marginal artery; %MI AP = percent of myocardial infarction in apex;, %MI AS = %MI in anterior two-thirds of the septum; %MI Basal = %MI in basal inferior left ventricular (LV) wall; %MI B Subepi = total %MI in the transmural basal inferior segment plus MI in subepicardial 50% of transmural middle inferior, lateral and inferoseptal LV walls (does not include apex); %MI IMI = %MI in middle inferior (diaphragmatic)LV wall; % MINT = % MI in subendocardia150 % of transmural LV wall; % MI IS-- % MI in inferior third of septal wall (only ! of 15 patients rl~atient 1] had MI that extended into middle third of septum); %MI total = total %MI in LV wall; Occ CA = occluded coronary arteries; R = right coronary artery.
are listed in Table II. In general, the greater the amount of MI, the larger the sum of the vector spatial magnitudes over the period of late activation. Comparison of late depolarization in t h e i n f a r c t group and the control group: The mean value of the integral of spatial vectors during late activation was significantly (p <0.0001) greater for the MI group (12 4- 6 mV.ms) than for the control group (2 4- 1 mV-ms). The mean duration of late activation abnormalities for the MI group commenced 31 ± 13 ms before the end of
Left
Ventricle
Right
the QRS, which was significantly longer than the 11 ± 3 ms period for the control group (p <0.0001). The rate of change of vector spatiaI magnitude with time (dm/dt) was measured every 2.5 ms, and these values were averaged over the duration of the integration of vector magnitudes during late activation for each group. The mean of the averaged dm/dt of the MI group was 0.03 + 0.01 mV/ms and was not significantly different from the control group, 0.02 4- 0.02 mV/ms (p = 0.498).
Ventricle
: Inferobasal
~
2 cm ; ~,~'~-_~'~\ Basal ~ Sections I L a~t~e^ra/u^ , ~ (Posterior: ECG, ECHO)
Infarction .
Middle
"Sections _ . 3 cm • ; Apical Sections
Subendocardial Transmural Wall
Inferior Septum (1/3) Basal Inferior
Middle Inferior (Diaphragmatic)
Apex
Epicardial Outer 50% Transmural Wall
FIGURE 2. Designation of inferobasal segments of the left ventricular (LV) wall. The LV wall was divided longitudinally into basal, middle, and apical sectors, and circumferentially into inferior, inferoseptal (one-third of septum), anteroseptal (two-thirds of septum), lateral and anterior LV walls. The inferior LV wall extended from the junction Of the ventricular septum and the right ventricular and LV walls to the posterolateral ventricular curvature, including the posterior papillary muscle. The boundaries of the lateral wall were ventral to the anterior papillary muscle and dorsal to the postero!ateral ventricular curvature. To communicate the anatomy and infarct changes more systematically, the electrocardiographic (ECG) and echocardiographic (ECHO) nomenclature of "posterior" refers approximately to that LV wall designated as lateral in this study. The intramural ventricular wall was divided in half. MIs that involved the subendocardial 50% were defined as nontransmural and those that extended beyond 50% were transmural; the volume of MI in the outer 50% of the wall was defined as subepicardial.
October 1, 1984 THE AMERICANJOURNAL OF CARDIOLOGY Volume54 50
729
12-
r = .92
11-
n.=
15
/
10
4O
r = .88
•
/
/
9
~> ..I i
-~ 30
iio
O
~_e-
I--
IE
•
-~ 20 43"
10
1.
0
t 5 10 15 20 25 I n t e g r a l of t h e S p a t i a l V e c t o r M a g n i t u d e s During Late Abnormal Depolarization
0
f
!
I
!
5 10 15 20 Integral of the Spatial Vector Magnitudes During Late Abnormal Oepolarlzetlon
(mv.msec)
I
25
(mv.msec)
FIGURE 3, Least-squaresfitted regression line of the relation of the total percent volume of inferobasal myocardial infarction (% MI) in the left ventricular walls and the integral of the sequential spatial vector magnitudes during late abnormal depolarization (LATE) (% MI -- --0.87 + 1.83 LATE; p <0.00001).
FIGURE 5. Least-squaresfitted regression line of the relation of percent volume of myocardial infarct (%MI) in the epicardial half of the transmural middle inferior, lateral and inferoseptal left ventricular walls and the integral of the sequential spatial vector magnitudes during late abnormal depolarization (LATE)(%MI = --1.83 -I- 0.94 LATE; r = 0.87, n = 15).
26 24
r
= .91
20
r = .87
A
18
18
16
16
•
./
"10 k,. (J
"3.
LU 1 4 =¢l 12 0=
0~
tn
• /
10 8 6 4
."
12
.m Q.
10
LU
./.
14
"lO i,.
.
8
ae
6 4 •
° •
•
2
2 0
:.
I
I
!
I
I
5 10 15 20 25 Integral of the Spatial Vector Magnitudes During Late Abnormal Depolarization
(mv.msec) FIGURE 4, Least-squaresfitted regression line of the relation of percent volume of myocardial infarct (%MI) in the transmural basal inferior myocardium plus the epicardial half of the transmural middle inferior, lateral and inferoseptal left ventricular wall and the integral of the sequential spatial vector magnitudes during late abnormal depolarization (LATE) (%MI = -2.51 -F 1.17 LATE; p <0.00001, n -- 15).
0 5
10
15
20
25
Integral of the Spatial Vector Magnitudes During Late Abnormal Depolarization (mv.msec) FIGURE 6. Least-squaresfitted regression line of the relation of percent volume of myocardial infarct (%MI) in the transmural basal inferior left ventrlcular wall and the integral of the sequential spatial vector megnitudes during late abnormal depolarization (LATE) (% MI = --1.88 -t0.51 LATE; p <0.00001, n = 15).
INFEROBASAL INFARCT SIZE BY LATE ACTIVATION QRS
730
TABLE II
Linear Relations of Late Activation Abnormalities and the Distribution of Percent of Infarct Size by Segment In the Inferobasal Left Ventricle
LV MI Segment
Correlation Fitted Regression Line (%MI =)
r
p Value
- 0 . 8 7 -I- 1.83 --2.51 -F 1.17
0.92 0.91
<0.00001 <0.00001
--1.88 -1.83 -0.80 2.68 --0.67
0.88 0.87 0.65 0.55 0.45
<0.00001 <0.00001 0.004 0.016 0.047
Total inferobasal Basal inferior subepicard Basal inferior Subepicardial Inferior septal Middle inferior Lateral
Jr 0.51 -t- 0.94 -I- 0.37 Jr 0.37 -I- 0.34
Number of cases includes 15 in the myocardial infarction (MI) group. Basal inferior -I- subepicard = total percent of MI (% MI) in all basal inferior segment plus MI in subepicardial 50% of transmural middle inferior, lateral, and inferior septal walls; LV = left ventricular; Subepicardial = %MI in subepicardial 50% of transmural wall.
The mean value of the integral of spatial vector magnitudes during IAD was 6 ± 4 mV-ms for the MI group and was significantly larger (p = 0.003) than the integral for the control group, 2 ± 1 mV-ms. The difference in mean duration of IAD, analogous to Q-wave duration, between patients with inferobasal MIs and the control group was only marginally significant (p = 0.063) (24 ± 10 vs 17 ± 5 ms). Contribution of additional late activation to early activation abnormalities: The equation for the fitted regression line for the total percent inferobasal MI and the integral of vector magnitudes during late activation (LATE) including both groups was %MI = -2.44 + 1.92
r : .96 4O
n=
25
35 >
3O
/
"~ 2 5 -
•
~- 2 0 "
v
~
15-
"
"
.
105-
o
Z,
•
1 '0 1 '5 2 0' 2'5 Integral of the Spatial Vector Magnitudes During Late Abnormal Depolarization (mv.msec) FIGURE 7. Least-squares fitted regression line of the relation of total percent volume of inferobasal myocardial infarction (% MI) in the left ventricular (LV) wall and the integral of the sequential spatial vector magnitudes during late abnormal depolarization (LATE) (%MI = --2.44 + 1.92 LATE; p <0.00001, n = 25).
LATE, r = 0.96, p <0.00001. The correlation coefficient and the probability level improved with the addition of the control group because the small values of the integral of the latter were clustered with little variance {Fig. 7). The 95% confidence intervals for prediction of a future observation of MI size based on measurement of LATE was ±2% MI. The predictive variable measuring LATE was more significant in estimating inferobasal MI size than the predictor measuring IAD, as shown in the analysis of variance in Table III. The equation for the regression line using multivariate analysis was %MI = -2.54 + 0.095 IAD + 1.88 LATE. The addition of the late activation information to the early activation information changed the multiple correlation coefficient from r = 0.83 with only IAD as a predictor to R = 0.96 when LATE was added. The correlation coefficient matrix in Table IV illustrates the contribution of duration and rate of changes of LATE as compared to the integration of vector spatial magnitudes for prediction of MI size in specific segments in the inferobasal LV walls. In general, duration of late abnormalities can be used, but duration is not as significant a predictor as the integral of the late vectors (LATE). Similarly, the integral of the initial vectors (IAD) remains a good predictor, but LATE is a better predictor of inferobasal MI size. Discussion
Late activation abnormalities and inferobasal infarct size: This study demonstrates that the size of transmural infarcts located in the basal inferior, middle inferior, lateral and inferoseptal LV walls can be estimated by an electrocardiographic index, the integral of the spatial magnitudes of sequential vectors during late activation. The additional information obtained from late activation contributed more significance to estimation of inferobasal MI size than the abnormalities often noted during early activation (i.e., during the Q wave). The results from this study are theoretically supported by earlier studies by several investigators,3-1° which indicated that changes in the late portions of depolarization could be used as complementary or additive to the conventional criteria of Q-wave duration or Q-wave negativity to diagnose infarction. Early studies on the pathway of ventricular depolarization by Scher et al3 and Durrer et al4 revealed that the basal inferior, basal inferior septum, and outer epicardial transmural wall of the middle inferior and posterolateral walls were the latest LV areas to be activated. Abildskov and Boyle5 produced chemical lesions in the subepicardial half of the ventricular wall and in the basal inferior region. Eight of the 11 subepicardial lesions altered only terminal portions of the QRS complex. The other 3 lesions were located near the interventricular septum and altered early as well as late portions of the QRS complex. The 2 lesions of the basal inferior LV altered only terminal portions of the QRS complex. Flowers et al6 reported a correlation between the site of infarction determined at autopsy, and the occurrence
October 1, 1984 THE AMERICAN JOURNAL OF CARDIOLOGY Volume54 TABLE III
731
Multivariate Analysis of Variance Table for Early (lAD) and Late Activation (LATE) Abnormalities
Source of Variation
D.F.
Sum of Squares
Mean Square
F Ratio
p Value
Total Regression Residual
24 2 22
4524.3661 4151.7945 372.5716
188.5153 2075.8971 16.93507
122.5796
0.0001
Summary Table
Stepwise Variables lAD LATE
F to Enter
Multiple R
R2
R2 Change
Overall F
p Value
51.9815 59.9491
0.83 0.96
0.69 0.92
-0.23
51.98 122.6
0.01 0,001
D.F. = degrees of freedom.
of notching in high-frequency orthogonal vectorcardiographic leads. Inferobasal MIs had a predominance of notching in the downslope of the Y lead. The study by Flowers et al6 supports our findings of the slower rate of change of the sequential vector spatial magnitudes during late depolarization. Later studies, 7-9 using surface potential maps, described late activation changes in the QRS complex after an acute inferobasal MI. Most recently, Recke 1° used discriminant analysis to classify inferobasal MIs by vectorcardiography, and 3 of the 5 best discriminating variables were the sum of the spatial magnitudes of the 3 terminal vectors at 0.01-second intervals, the spatial magnitude of the -0.03-second terminal vector, and the spatial magnitude of the -0.04-second terminal vector. These studies are important in that they demonstrated that the diagnosis of inferobasal MIs is no longer bound to the early part of the QRS complex or Q-wave period for evidence of MI. In fact, the sensitivity of diagnosis of inferobasal MIs can be increased by using late activation abnormalities8 instead of the standard initial abnormal QRS changes. 11-15 Roark et aP 6 reported a correlation (r = 0.74) between the percent of inferior MI and a QRS score, calculated from the standard 12-lead electrocardiogram. The regression line was %MI = 2.5 × points + 2.9. The electrocardiographic scoring system used changes during late (i.e., R/S ratio and S-wave changes), as well as the more traditional early Q-wave changes as their predictive variables. The regression line was similar to that in our study, and their results contributed to the validity of estimation of infarct size by electrocardiographic changes in the QRS complex. 1,16-21 Mechanisms of late activation abnormalities: Conclusions regarding the electrophysiologic mechanisms of the observed early and late activation abnormalities in inferobasal MIs is beyond the scope of the results of this study. However, the following considerations might be suggested for a partial explanation. The abnormalities that occur in the first half of activation may be related to an increased magnitude of the spatial vectors from the anterior septum, anterior wall and apex, because of the loss of opposing forces primarily from the subendocardial half of the middle inferior and posterolateral LV walls. Thus, the larger the MI, the
TABLE IV
Correlation Coefficient Matrix for Different Vectorcardlographic Predictive Variables of Infarct Size by Segment in the Inferobasal Left Ventricle Predictive ECG Variables
%MI Total Basal-I- subepicard Subepicardial Basal inferior Nontransmural Middle inferior Inferoseptal Lateral
lAD
lAD Duration
0.83 0.90 0.84 0.85 0.75 0.77 0.80 0.31
0.65 0.72 0.70 0.73 0.54 0.54 0.54 0.33
LATE L A T E Duration
LATE dm/dt
0.96 0.95 0.93 0.91 0.90 0.79 0.78 0.58
-0.08 --0.01 -0.09 -0.04 --0.06 --0.05 0.10 --0.26
0.90 0.82 0.84 0.83 0.88 0.71 0.55 0.75
Number of cases includes 15 in the myocardial infarction (MI) group and 10 in the control group. Basal -t- subepicard = total percent of infarcted myocardium (%MI) in transmural basal inferior segment plus MI in subepicardial 50% of transmural middle inferior, lateral and inferior septal left ventricular walls; lAD = integral of the magnitudes of spatial vectors during initial abnormal depolarization of the QRS; lAD Duration = duration of early activation abnormalities (analogous to Q-wave duration); LATE = integral of the magnitudes of spatial vectors during late abnormal depolarization of the QRS; LATE dm/dt = rate of change of spatial vector magnitude during the period of LATE; LATE Duration = duration of late activation abnormalities; Subepicardial = % MI in subepicardia150 % of transmural wall; Total = total %MI in left ventricular wall of all locations.
larger the magnitude of the uncanceled forces and the greater their integral (IAD). During late activation, the potentials are probably a reflection of a delayed activation of residual viable myocardium within the necrotic regions in the basal inferior region and middle inferior and posterolateral subepicardium since most of the other LV regions have already been activated. Theoretically, however, the larger the MI, the smaller the magnitude of the spatial vectors that might be anticipated during late activation, 1°,24but this is contrary to the results observed in the present study. The positive linear relation suggests that the activation of any viable myocardium may have been postponed by the nonactivation of the necrotic zone, thus, the observed vector magnitudes were increased relative to the lower magnitudes normally expected at that phase of the QRS interval. Whatever the mechanism, the preliminary results of this study appear valid. Nevertheless, interpretation of
732
INFEROBASAL INFARCT SIZE BY LATE ACTIVATION QRS
the results should be cautious because the sample size is relatively small; a second "test" series with another independent sample is needed for validation of VCG estimation of inferobasal MI size using late activation abnormalities; and the electrical events late in ventricular activation have multiple confounding variables, such as delayed conduction and alterations in conduction pathways that may distort estimation of MI size. References 1. Cowan MJ, Relchenbach DO, Bruce RA, Fisher L. Estimationof myocardial size by digital computer analysis of the VCG. J Electrocardiol 1982;15: 307-316. 2. Cowan MJ, Bruce RA, Van Winkle D, Davldson L, KIIIpack A. Comparative accuracy' of computerized spatial vectorcardiography and standard electrocardiography for detection of myocardial infarction. J Electrocardiol. in press. 3. Scher AM, Young AC~The pathway of vantricular depolarization in the dog. Ciro Res 1956;4:461-469. 4. Durrer D, van Dam RTh, Freud GE, Janso MJ, MelJler FL, Arzbaecher RC. Total excitation of the isolated human heart. Circulation 1970;41:899912. 5. Aldldskov JA, Boyle RS. Further studies of the electrocardiographiceffects of experimental myocardial lesions. Am Heart J 1965;69:49-55. 6. Flowers NC, Horan LG, Tolleson WJ, Thomas JR. Localization of the site of myocardial scarring in man by high-frequency components. Circulation 1969;60:927-934. 7. Flowers NC, Htoran LG, Sohl GS, Hand RC, Johnson JC. New evidence for inferoposterior myocardial infarction on surface potential maps. Am J Cardiol 1976;38:576-581. 8. Suglyama S, Sngenoya J, Wada M, NIIml N, Toyama J, Yamada K. Diagnosis of high posterior infarction: experimentalstudythrough the use of body surface isopotential maps. J Electrocardiol 1977;10:251-256. 9. Ishlkawa T, OkaJlmaM, NIIml N, Kolke Y, Toyama J, Yamada K. The body surface isopotential maps of the non-transmural infarctions. Jpn Circ J, in press. 10. Recke S. Contribution of Frank ECG measurements to the quantitative estimation of old posterodiaphragmaticmyocardial infarction. Int J Cardiol
1984;5:49-58. 11. Gunnar R, Pletras R, Blackaller J, Dadmun SE, Szanto PB, Tobln JR. Correlation of vectorcardiographic criteria for myocardial infarction with autopsy findings. Circulation 1967;35:158-171. 12. Dwyer E, Salvldor C, Greenberg H, Plnkernell B. Inferior myocardial infarction and right coronary artery occlusive disease a correlative study. Br Heart J 1975;37:464-470. 13. Savage RM, Wagner OS, Ideker RE, Podolsky SA, Hackel DB. Correlation of postmortem anatomic findings with electrocardiographic changes in patients with myocardial infarction. Circulation 1977;55:279-285. 14. Sheltlgar UR, Hultgren HN, Pfelfer JF, Lipton MJ. Diagnostic value of Qwaves in inferior myocardial infarction. Am Heart J 1974;88:170-175. 15. Hurd liP, Slarllng MR, Crawford MH, Dlabal PW, O'Roud(e RA. Comparative accuracy of electrocardiographic and vectorcardiographic criteria for inferior myocardial infarction. Circulation 1981;63:1025-1029. 16. Road( SF, Ideker RE, Wagner GS, Alonso DR, Bishop SP, Bloor CM, Bramlet DA, Edwards JE, Fallen JT, Gottlleb GJ, Hackel DB, Phillips HR, Relmer KA, Rogers WJ, Ruth WK, Savage RM, White RD, Selvester RH. Evaluation of a QRS scoring system for estimating myocardial infarct size. III. Correlation with quantitative anatomic findings for inferior infarcts. Am J Cardiol 1983;51:382-389. 17. Selvester RH, Solomon JC. Infarct size and QRS changes. (QRS criteria applicable to computer diagnostic programs.) in: Tolan GD, Pryor TA, eds. Computerized Interpretation of the ElecVocardi0gram.Proceedingsof the 1980 Engineering Foundation Conference. New York: Engineering Foundation, 1980:69-77. 19. Wagner GS, Freye CJ, Palmerl ST, Road( SF, Stack NC, Ideker RE, Harrell FE, Selvester RH. Evaluation of a QRS scoring system for estimating myocardial infarct size. I. Specificity and observer agreement. Circulation 1982;65:342-347. 19. Ideker RE, Wagner GS, Ruth WK, Alonso DR, Bishop SP, Bloor CM, Fallen JT, Goltlleb GJ, Hackel DB, Phillips HR, Relmer KA, Road( SF, Rogers WJ, Savage RM, White RD, Selvester RH. Evaluation of a QRS scoring system for estimatingmyocardial infarct size. II. Correlationwith quantitative anatomic findings for anterior infarcts. Am J Cardiol 1982;49:16041614. 20. Wlekllne SA, McNamara JJ. Vectorcardiographic quantification of infarct size in baboons. Circulation 1978;57:910-920. 21. Flowers NC, Hand RC, Srldharan MR, Horan LG, Sohl GS. Surface reflections of cardiac excitation and the assessmentof infarct volume in dogs. Circ Res 1978;43:406-413. 22. Jacobson ED, Rush S, Zlnberg S, Ablldskov JA. The effect of infarction on magnitude and orientation of electrical events in the heart. Am Heart J 1959;58:863-872.
This report describes the relation of myocardial infarct (MI) size in the left ventricular inferobasal wall, measured at necropsy, to late activation abnormalities of the QRS complex, measured by computerized spatial vectorcardiography. Fifteen patients with single inferobasal MIs and 10 patients with no evidence of heart disease were studied. The percentage of MI in the inferobasal wall was significantly related to the vectorcardiographic abnormalities noted late (i.e., 31 -I- 13 ms before the end of the QRS waveform) (r = 0.96, p <0.00001). The integral of the vector magnitudes during late
abnormal activation significantly predicted the amount of MI in the basal inferior wall (r = 0.88) and in the basal inferior wall plus the outer, subepicardial half of the transmural middle inferior, lateral and inferoseptal walls (r = 0.91). The additional information obtained from late activation of the QRS complex contributed more significance to the estimation of the left ventricular inferobasal MI size than the abnormalities commonly noted during early activation (i.e., during the Q wave).
Whether late activation abnormalities of the QRS complex can be used to estimate inferobasal myocardial infarct (MI) size is not known. Using spatial vectorcardiography (VCG), the percent volume of MI of the left ventricular (LV) wall for single or multiple MIs in all locations can be estimated by the integral of the magnitudes of the spatial vectors during the initial abnormal depolarization period (IAD) (r = 0.90, p <0.001). 1 However, this early activation index slightly underestimates the size of transmural inferobasal MIs measured at necropsy. This study describes the relation between the integral of the sequential vector spatial magnitudes during late activation and the pathologic measurement of MI in each of the basal inferior, middle inferior, inferoseptal and posterolateral LV regions. The latter vectorcardiographic index was defined by an alteration in the first derivative of the spatial vector magnitudes waveform during late activation. This study also analyzes the relation of inferobasal MI size to 2 predictive variables using abnormalities in early and late activation. The significance of the additional information obtained from late activation to that of early activation in estimation of inferobasal MI size is reported.
Methods
(Am J Cardiol 1984;54:726-732)
Twenty-five persons were studied: 15 patients with evidence of single inferobasal MIs documented at necropsy (MI group) and 10 control subjects who did not have MI. Autopsy permits were obtained for 35 patients with inferobasal MIs; 20 of 35 had 2 or more MIs of differing ages and LV locations. All patients with single inferobasal MIs were included in the sample. Five persons in the control group died from cancer, and the absence of heart disease was confirmed at necropsy. The absence of heart disease was confirmed in the other 5 by a negative history, a negative maximal treadmill exercise test response and a 5-year follow-up of yearly questionnaires indicating no morbidity. These 5 persons had been enrolled in the Seattle Heart Watch Program. The MI group had 9 men and 6 women, mean age 70 + 7 years. The control group had 7 men and 3 women, mean age 67 + 13 years. Only the VCGs taken within 24 hours of death were used for analysis. No patient had electrocardiograms that indicated left or right bundle branch block, left anterior or posterior fascicular block, or left or right ventricular hypertrophy. Electrocardiographic analyses: The computerized, high-frequency VCGs were recorded using the corrected Frank orthogonal lead system. 1,2 Data were quantitatively reproducible within 5% differences of the vector spatial magnitude values and 0 differences of the onset of the Q wave. All computer records were overread by 2 persons; I reader was consistently blinded to the autopsy findings. The predictive variable was the integral of vector magnitudes during late abnormal depolarization. It was calculated by the integration of the magnitudes of the spatial vectors every 2.5 ms (]~ ~¢/X2 -}- y2 + Z 2) for a variable duration during late ventricular depolarization. This variable was first suspected to be related to inferobasal MIs because patients
From the Departments of Physiological Nursing, Pathology, and Medicine, Division of Cardiology, University of Washington, Seattle, Washington. This study was supported in part by Grant HL27257 from the National Institutes of Health, Bethesda, Maryland. Manuscript received February 13, 1984; revised manuscript received May 31, 1984, accepted June 5, 1984. Address for reprints: Marie J. Cowan, PhD, Department of Pathology, SM-28, University of Washington, Seattle, Washington 98195. 726
October 1, 1984 THE AMERICAN JOURNAL OF CARDIOLOGY Volume54
with inferobasal MIs had VCGs with notches or slurs during the late activation period on the graphic display of the vector spatial magnitudes. Correct determination of the integral of late activation vectors depended on defining the correct period for integration. This was done by analyses of the first derivative of the vector spatial magnitudes (dm/dt = A v/X2 + y2 + Z2/At). The algorithm defined the onset of abnormal depolarization by a notch or slur in the time courses of the graphic display of the first derivative after the peak of R. A notch was defined as a local maximum and minimum in the derivative for at least 5 ms. If there was more than 1 notch, only the first detected notch was used. A slur was defined when the rate of change of the derivative was relatively slower. The minimal amount of change required for a slur to be identified was a value of the derivative <0.04 mV/ms for any 2.5-ms sampling point. 1 The end of the period was defined at the end of the QRS when the derivative was equal to 0. In the control group, the notches or slurs of the derivative during late depolarization were analogous to and approximately coincident with the change of direction commonly observed by the S wave. The S wave in leads X, Y and Z could begin at different points in time; therefore, the spatial designation by the derivative (dm/dt) was used to indicate notches or slurs in the control group (Fig. 1). The other predictive variable was the integral of the vector spatial magnitudes every 2.5 ms for a variable duration during IAD. 1 The period of IAD was determined by analyses of the first derivative from the beginning of depolarization to the time at the end of the "notch". This period was analogous to the Q-wave duration when the latter was evident in the X, Y, Z tracings (Fig. 1). Pathologic analyses: The pathologic methods used to analyze the heart have been described. 1 Transverse sections of the left ventricle were incubated in a solution of nitroblue tetrazolium followed by the addition of sodium succinate to detect dehydrogenase enzyme depletion. Volume displacement was done on each transverse section. Histologic examination of 25 to 50 tissue blocks were done for each left ventricle. MI size was quantified by computer-assisted planimetry, z MI volumes were calculated as a percentage of the volume of the left ventricle. All planimetry was performed twice for reproducibility, and the error was less than 1%. The transverse LV myocardial sections were divided longitudinally into 3 sectors and 5 circumferential segments (Fig. 2). The histologic ages of MI, the distribution of MI by LV segment, and the extent of transmural MI involvement are listed in Table I. The dependent variables were the total percentage of MI (%MI) in the inferobasal LV wall as well as the %MI in each of the following LV wall segments: basal inferior, middle inferior, inferoseptal, lateral, outer subepicardial 50% of the transmural wall, and inner subendocardia150% of the transmural wall. The total %MI in all the basal inferior segment plus the %MI in the subepicardial 50% of the transmural middle inferior, lateral and inferoseptal walls were summed to be used as another dependent variable. Statistical analyses: The relation of inferobasal MI size to electrocardiographic abnormalities during late activation was analyzed by simple linear regression. The relation of inferobasal MI size to 2 predictive variables, vectorcardiographic abnormalities during early and late activation, were analyzed by multivariate stepwise regression. Comparison of mean values were analyzed by 2-tailed, nonpaired Student t tests. Results
Relation of inferobasal infarct size to late activation abnormalities: T h e total p e r c e n t of inferobasal
727
M I was significantly related (r = 0.92, p <0.00001) to late activation abnormalities in the QRS waveform (Fig. 3). T h e integral of vector m a g n i t u d e s during late abn o r m a l activation ( L A T E ) h a d the highest correlation (r = 0.91) with the % M I in the basal inferior L V wall plus the epicardial half of the t r a n s m u r a l wall of t h e middle inferior, lateral, and inferoseptal L V walls (Fig. 4). Specifically, L A T E was significantly related to t h e a m o u n t of M I in the epicardial h a l f of the t r a n s m u r a l middle inferior, lateral, a n d inferoseptal left ventricle (r = 0.87) and the transmural basal inferior left ventricle (r = 0.88). T h e s e positive linear relations are illustrated in Figures 5 a n d 6. T h e late activation a b n o r m a l i t i e s were not as closely related to M I size in the inferior s e p t u m (r = 0.65), the t r a n s m u r a l middle inferior wall (r = 0.55), or the t r a n s m u r a l lateral wall (r = 0.45). T h e relations of late activation a b n o r m a l i t i e s a n d the distribution of %MI b y s e g m e n t in the inferobasal L V wall Spatial
Magnitude
First Derivative B
Control
D
C
Inferobalal MI
F
v,-
IAD~
--~v.J
Inferobasal MI
LATE
FIGURE 1. Representative time courses from the computer graph of the sequential spatial magnitudes of vector (~/X 2 -I- y2 -I- Z2) and the derivatives of the vector spatial magnitudes (A ~/X 2 + y2 -t- Z2/At) during a 16-beat averaged QRS complex for a patient without heart disease (control, A and B) and 2 patients with inferobasal myocardial infarctions (MIs) (C and D, E and F). The dotted area under the curve of the time course of the spatial magnitudes of vectors (C and E) indicates the summation of the vector magnitudes (LATE) during late abnormal depolarization (C and D). Note the slur (C) commonly observed on the spatial magnitude time course during late activation. The double arrows during late activation in the first derivative (D and F) indicate
the period defined by the notches for integration of LATE. The slur on the derivative (B) of the control during late activation indicates a short duration and a small value of the integral of the vector magnitudes. The darkened area under the curve of the time course of the vector spatial magnitudes (C and E) indicates the summation of the vector magnitudes during initial abnormal depolarization (lAD). The single arrow during initial activation in the first derivative (D and F) represents the period defined by the notch for integration of lAD.
728
INFEROBASALINFARCT SIZE BY LATE ACTIVATION QRS
TABLE I
Case
Distribution of Percent of Infarct by Segment and Involvement of Transmural Myocardlum Age of MI (days)
1
21
2 3 4 5 6 7 8 9 i0 11 12 13 14 15 Mean 4- SD
7-14 old 7 old 5 3 old. 7-14 7-14 old old old 3 old
%MI Total
%MI B Subepi
%MI Subepi
%MI NT
%MI Basal
%MI IMI
%MI IS
%MI LAT
%MI AP
30
19
19
11
4
10
3
7
R
24 12 24 2 31 39 17 21 16 16 10 ,7 46 9 20 4-12
16 7 8 1 22 22 4 9 10 5 3 6 25 5 11 -I-8
14 4 12 1 15 17 1 6 8 7 3 2 21 7 9 -I-7
10 8 12 1 i6 22 16 15 8 9 6 5 25 2 11 4-7
8 2 1 0.5 10 7 2 6 3 3 3 0.5 12 0 4 -I-4
3 7 11 1 14 15 3 5 9 6 5 6 6 .3 7 4-4
5 2 (AS) 11 2 1 0 6 11 2 2 3 1 1 0.5 4 3 3 ,4-4
0 0 10 0.5 1 2 3 6 0 5 0 0 17 2 3 4-5
2 1 1
R R LOM R R R R LC R R R R R R
0 4 7 2 1 1 1 0 7 1 2 4-2
Occ CA
Seven of i5 patiehts had ."old" myoc.ardial infarcts (MIs) (i.e., scars) and died from complications of this single inferobasal MI. No patient had right ventricular MI by chance alone. The group was not selected to exclude right ventricular involvement. L --- left c rcumflex arteryi LOM = left obtuse'marginal artery; %MI AP = percent of myocardial infarction in apex;, %MI AS = %MI in anterior two-thirds of the septum; %MI Basal = %MI in basal inferior left ventricular (LV) wall; %MI B Subepi = total %MI in the transmural basal inferior segment plus MI in subepicardial 50% of transmural middle inferior, lateral and inferoseptal LV walls (does not include apex); %MI IMI = %MI in middle inferior (diaphragmatic)LV wall; % MINT = % MI in subendocardia150 % of transmural LV wall; % MI IS-- % MI in inferior third of septal wall (only ! of 15 patients rl~atient 1] had MI that extended into middle third of septum); %MI total = total %MI in LV wall; Occ CA = occluded coronary arteries; R = right coronary artery.
are listed in Table II. In general, the greater the amount of MI, the larger the sum of the vector spatial magnitudes over the period of late activation. Comparison of late depolarization in t h e i n f a r c t group and the control group: The mean value of the integral of spatial vectors during late activation was significantly (p <0.0001) greater for the MI group (12 4- 6 mV.ms) than for the control group (2 4- 1 mV-ms). The mean duration of late activation abnormalities for the MI group commenced 31 ± 13 ms before the end of
Left
Ventricle
Right
the QRS, which was significantly longer than the 11 ± 3 ms period for the control group (p <0.0001). The rate of change of vector spatiaI magnitude with time (dm/dt) was measured every 2.5 ms, and these values were averaged over the duration of the integration of vector magnitudes during late activation for each group. The mean of the averaged dm/dt of the MI group was 0.03 + 0.01 mV/ms and was not significantly different from the control group, 0.02 4- 0.02 mV/ms (p = 0.498).
Ventricle
: Inferobasal
~
2 cm ; ~,~'~-_~'~\ Basal ~ Sections I L a~t~e^ra/u^ , ~ (Posterior: ECG, ECHO)
Infarction .
Middle
"Sections _ . 3 cm • ; Apical Sections
Subendocardial Transmural Wall
Inferior Septum (1/3) Basal Inferior
Middle Inferior (Diaphragmatic)
Apex
Epicardial Outer 50% Transmural Wall
FIGURE 2. Designation of inferobasal segments of the left ventricular (LV) wall. The LV wall was divided longitudinally into basal, middle, and apical sectors, and circumferentially into inferior, inferoseptal (one-third of septum), anteroseptal (two-thirds of septum), lateral and anterior LV walls. The inferior LV wall extended from the junction Of the ventricular septum and the right ventricular and LV walls to the posterolateral ventricular curvature, including the posterior papillary muscle. The boundaries of the lateral wall were ventral to the anterior papillary muscle and dorsal to the postero!ateral ventricular curvature. To communicate the anatomy and infarct changes more systematically, the electrocardiographic (ECG) and echocardiographic (ECHO) nomenclature of "posterior" refers approximately to that LV wall designated as lateral in this study. The intramural ventricular wall was divided in half. MIs that involved the subendocardial 50% were defined as nontransmural and those that extended beyond 50% were transmural; the volume of MI in the outer 50% of the wall was defined as subepicardial.
October 1, 1984 THE AMERICANJOURNAL OF CARDIOLOGY Volume54 50
729
12-
r = .92
11-
n.=
15
/
10
4O
r = .88
•
/
/
9
~> ..I i
-~ 30
iio
O
~_e-
I--
IE
•
-~ 20 43"
10
1.
0
t 5 10 15 20 25 I n t e g r a l of t h e S p a t i a l V e c t o r M a g n i t u d e s During Late Abnormal Depolarization
0
f
!
I
!
5 10 15 20 Integral of the Spatial Vector Magnitudes During Late Abnormal Oepolarlzetlon
(mv.msec)
I
25
(mv.msec)
FIGURE 3, Least-squaresfitted regression line of the relation of the total percent volume of inferobasal myocardial infarction (% MI) in the left ventricular walls and the integral of the sequential spatial vector magnitudes during late abnormal depolarization (LATE) (% MI -- --0.87 + 1.83 LATE; p <0.00001).
FIGURE 5. Least-squaresfitted regression line of the relation of percent volume of myocardial infarct (%MI) in the epicardial half of the transmural middle inferior, lateral and inferoseptal left ventricular walls and the integral of the sequential spatial vector magnitudes during late abnormal depolarization (LATE)(%MI = --1.83 -I- 0.94 LATE; r = 0.87, n = 15).
26 24
r
= .91
20
r = .87
A
18
18
16
16
•
./
"10 k,. (J
"3.
LU 1 4 =¢l 12 0=
0~
tn
• /
10 8 6 4
."
12
.m Q.
10
LU
./.
14
"lO i,.
.
8
ae
6 4 •
° •
•
2
2 0
:.
I
I
!
I
I
5 10 15 20 25 Integral of the Spatial Vector Magnitudes During Late Abnormal Depolarization
(mv.msec) FIGURE 4, Least-squaresfitted regression line of the relation of percent volume of myocardial infarct (%MI) in the transmural basal inferior myocardium plus the epicardial half of the transmural middle inferior, lateral and inferoseptal left ventricular wall and the integral of the sequential spatial vector magnitudes during late abnormal depolarization (LATE) (%MI = -2.51 -F 1.17 LATE; p <0.00001, n -- 15).
0 5
10
15
20
25
Integral of the Spatial Vector Magnitudes During Late Abnormal Depolarization (mv.msec) FIGURE 6. Least-squaresfitted regression line of the relation of percent volume of myocardial infarct (%MI) in the transmural basal inferior left ventrlcular wall and the integral of the sequential spatial vector megnitudes during late abnormal depolarization (LATE) (% MI = --1.88 -t0.51 LATE; p <0.00001, n = 15).
INFEROBASAL INFARCT SIZE BY LATE ACTIVATION QRS
730
TABLE II
Linear Relations of Late Activation Abnormalities and the Distribution of Percent of Infarct Size by Segment In the Inferobasal Left Ventricle
LV MI Segment
Correlation Fitted Regression Line (%MI =)
r
p Value
- 0 . 8 7 -I- 1.83 --2.51 -F 1.17
0.92 0.91
<0.00001 <0.00001
--1.88 -1.83 -0.80 2.68 --0.67
0.88 0.87 0.65 0.55 0.45
<0.00001 <0.00001 0.004 0.016 0.047
Total inferobasal Basal inferior subepicard Basal inferior Subepicardial Inferior septal Middle inferior Lateral
Jr 0.51 -t- 0.94 -I- 0.37 Jr 0.37 -I- 0.34
Number of cases includes 15 in the myocardial infarction (MI) group. Basal inferior -I- subepicard = total percent of MI (% MI) in all basal inferior segment plus MI in subepicardial 50% of transmural middle inferior, lateral, and inferior septal walls; LV = left ventricular; Subepicardial = %MI in subepicardial 50% of transmural wall.
The mean value of the integral of spatial vector magnitudes during IAD was 6 ± 4 mV-ms for the MI group and was significantly larger (p = 0.003) than the integral for the control group, 2 ± 1 mV-ms. The difference in mean duration of IAD, analogous to Q-wave duration, between patients with inferobasal MIs and the control group was only marginally significant (p = 0.063) (24 ± 10 vs 17 ± 5 ms). Contribution of additional late activation to early activation abnormalities: The equation for the fitted regression line for the total percent inferobasal MI and the integral of vector magnitudes during late activation (LATE) including both groups was %MI = -2.44 + 1.92
r : .96 4O
n=
25
35 >
3O
/
"~ 2 5 -
•
~- 2 0 "
v
~
15-
"
"
.
105-
o
Z,
•
1 '0 1 '5 2 0' 2'5 Integral of the Spatial Vector Magnitudes During Late Abnormal Depolarization (mv.msec) FIGURE 7. Least-squares fitted regression line of the relation of total percent volume of inferobasal myocardial infarction (% MI) in the left ventricular (LV) wall and the integral of the sequential spatial vector magnitudes during late abnormal depolarization (LATE) (%MI = --2.44 + 1.92 LATE; p <0.00001, n = 25).
LATE, r = 0.96, p <0.00001. The correlation coefficient and the probability level improved with the addition of the control group because the small values of the integral of the latter were clustered with little variance {Fig. 7). The 95% confidence intervals for prediction of a future observation of MI size based on measurement of LATE was ±2% MI. The predictive variable measuring LATE was more significant in estimating inferobasal MI size than the predictor measuring IAD, as shown in the analysis of variance in Table III. The equation for the regression line using multivariate analysis was %MI = -2.54 + 0.095 IAD + 1.88 LATE. The addition of the late activation information to the early activation information changed the multiple correlation coefficient from r = 0.83 with only IAD as a predictor to R = 0.96 when LATE was added. The correlation coefficient matrix in Table IV illustrates the contribution of duration and rate of changes of LATE as compared to the integration of vector spatial magnitudes for prediction of MI size in specific segments in the inferobasal LV walls. In general, duration of late abnormalities can be used, but duration is not as significant a predictor as the integral of the late vectors (LATE). Similarly, the integral of the initial vectors (IAD) remains a good predictor, but LATE is a better predictor of inferobasal MI size. Discussion
Late activation abnormalities and inferobasal infarct size: This study demonstrates that the size of transmural infarcts located in the basal inferior, middle inferior, lateral and inferoseptal LV walls can be estimated by an electrocardiographic index, the integral of the spatial magnitudes of sequential vectors during late activation. The additional information obtained from late activation contributed more significance to estimation of inferobasal MI size than the abnormalities often noted during early activation (i.e., during the Q wave). The results from this study are theoretically supported by earlier studies by several investigators,3-1° which indicated that changes in the late portions of depolarization could be used as complementary or additive to the conventional criteria of Q-wave duration or Q-wave negativity to diagnose infarction. Early studies on the pathway of ventricular depolarization by Scher et al3 and Durrer et al4 revealed that the basal inferior, basal inferior septum, and outer epicardial transmural wall of the middle inferior and posterolateral walls were the latest LV areas to be activated. Abildskov and Boyle5 produced chemical lesions in the subepicardial half of the ventricular wall and in the basal inferior region. Eight of the 11 subepicardial lesions altered only terminal portions of the QRS complex. The other 3 lesions were located near the interventricular septum and altered early as well as late portions of the QRS complex. The 2 lesions of the basal inferior LV altered only terminal portions of the QRS complex. Flowers et al6 reported a correlation between the site of infarction determined at autopsy, and the occurrence
October 1, 1984 THE AMERICAN JOURNAL OF CARDIOLOGY Volume54 TABLE III
731
Multivariate Analysis of Variance Table for Early (lAD) and Late Activation (LATE) Abnormalities
Source of Variation
D.F.
Sum of Squares
Mean Square
F Ratio
p Value
Total Regression Residual
24 2 22
4524.3661 4151.7945 372.5716
188.5153 2075.8971 16.93507
122.5796
0.0001
Summary Table
Stepwise Variables lAD LATE
F to Enter
Multiple R
R2
R2 Change
Overall F
p Value
51.9815 59.9491
0.83 0.96
0.69 0.92
-0.23
51.98 122.6
0.01 0,001
D.F. = degrees of freedom.
of notching in high-frequency orthogonal vectorcardiographic leads. Inferobasal MIs had a predominance of notching in the downslope of the Y lead. The study by Flowers et al6 supports our findings of the slower rate of change of the sequential vector spatial magnitudes during late depolarization. Later studies, 7-9 using surface potential maps, described late activation changes in the QRS complex after an acute inferobasal MI. Most recently, Recke 1° used discriminant analysis to classify inferobasal MIs by vectorcardiography, and 3 of the 5 best discriminating variables were the sum of the spatial magnitudes of the 3 terminal vectors at 0.01-second intervals, the spatial magnitude of the -0.03-second terminal vector, and the spatial magnitude of the -0.04-second terminal vector. These studies are important in that they demonstrated that the diagnosis of inferobasal MIs is no longer bound to the early part of the QRS complex or Q-wave period for evidence of MI. In fact, the sensitivity of diagnosis of inferobasal MIs can be increased by using late activation abnormalities8 instead of the standard initial abnormal QRS changes. 11-15 Roark et aP 6 reported a correlation (r = 0.74) between the percent of inferior MI and a QRS score, calculated from the standard 12-lead electrocardiogram. The regression line was %MI = 2.5 × points + 2.9. The electrocardiographic scoring system used changes during late (i.e., R/S ratio and S-wave changes), as well as the more traditional early Q-wave changes as their predictive variables. The regression line was similar to that in our study, and their results contributed to the validity of estimation of infarct size by electrocardiographic changes in the QRS complex. 1,16-21 Mechanisms of late activation abnormalities: Conclusions regarding the electrophysiologic mechanisms of the observed early and late activation abnormalities in inferobasal MIs is beyond the scope of the results of this study. However, the following considerations might be suggested for a partial explanation. The abnormalities that occur in the first half of activation may be related to an increased magnitude of the spatial vectors from the anterior septum, anterior wall and apex, because of the loss of opposing forces primarily from the subendocardial half of the middle inferior and posterolateral LV walls. Thus, the larger the MI, the
TABLE IV
Correlation Coefficient Matrix for Different Vectorcardlographic Predictive Variables of Infarct Size by Segment in the Inferobasal Left Ventricle Predictive ECG Variables
%MI Total Basal-I- subepicard Subepicardial Basal inferior Nontransmural Middle inferior Inferoseptal Lateral
lAD
lAD Duration
0.83 0.90 0.84 0.85 0.75 0.77 0.80 0.31
0.65 0.72 0.70 0.73 0.54 0.54 0.54 0.33
LATE L A T E Duration
LATE dm/dt
0.96 0.95 0.93 0.91 0.90 0.79 0.78 0.58
-0.08 --0.01 -0.09 -0.04 --0.06 --0.05 0.10 --0.26
0.90 0.82 0.84 0.83 0.88 0.71 0.55 0.75
Number of cases includes 15 in the myocardial infarction (MI) group and 10 in the control group. Basal -t- subepicard = total percent of infarcted myocardium (%MI) in transmural basal inferior segment plus MI in subepicardial 50% of transmural middle inferior, lateral and inferior septal left ventricular walls; lAD = integral of the magnitudes of spatial vectors during initial abnormal depolarization of the QRS; lAD Duration = duration of early activation abnormalities (analogous to Q-wave duration); LATE = integral of the magnitudes of spatial vectors during late abnormal depolarization of the QRS; LATE dm/dt = rate of change of spatial vector magnitude during the period of LATE; LATE Duration = duration of late activation abnormalities; Subepicardial = % MI in subepicardia150 % of transmural wall; Total = total %MI in left ventricular wall of all locations.
larger the magnitude of the uncanceled forces and the greater their integral (IAD). During late activation, the potentials are probably a reflection of a delayed activation of residual viable myocardium within the necrotic regions in the basal inferior region and middle inferior and posterolateral subepicardium since most of the other LV regions have already been activated. Theoretically, however, the larger the MI, the smaller the magnitude of the spatial vectors that might be anticipated during late activation, 1°,24but this is contrary to the results observed in the present study. The positive linear relation suggests that the activation of any viable myocardium may have been postponed by the nonactivation of the necrotic zone, thus, the observed vector magnitudes were increased relative to the lower magnitudes normally expected at that phase of the QRS interval. Whatever the mechanism, the preliminary results of this study appear valid. Nevertheless, interpretation of
732
INFEROBASAL INFARCT SIZE BY LATE ACTIVATION QRS
the results should be cautious because the sample size is relatively small; a second "test" series with another independent sample is needed for validation of VCG estimation of inferobasal MI size using late activation abnormalities; and the electrical events late in ventricular activation have multiple confounding variables, such as delayed conduction and alterations in conduction pathways that may distort estimation of MI size. References 1. Cowan MJ, Relchenbach DO, Bruce RA, Fisher L. Estimationof myocardial size by digital computer analysis of the VCG. J Electrocardiol 1982;15: 307-316. 2. Cowan MJ, Bruce RA, Van Winkle D, Davldson L, KIIIpack A. Comparative accuracy' of computerized spatial vectorcardiography and standard electrocardiography for detection of myocardial infarction. J Electrocardiol. in press. 3. Scher AM, Young AC~The pathway of vantricular depolarization in the dog. Ciro Res 1956;4:461-469. 4. Durrer D, van Dam RTh, Freud GE, Janso MJ, MelJler FL, Arzbaecher RC. Total excitation of the isolated human heart. Circulation 1970;41:899912. 5. Aldldskov JA, Boyle RS. Further studies of the electrocardiographiceffects of experimental myocardial lesions. Am Heart J 1965;69:49-55. 6. Flowers NC, Horan LG, Tolleson WJ, Thomas JR. Localization of the site of myocardial scarring in man by high-frequency components. Circulation 1969;60:927-934. 7. Flowers NC, Htoran LG, Sohl GS, Hand RC, Johnson JC. New evidence for inferoposterior myocardial infarction on surface potential maps. Am J Cardiol 1976;38:576-581. 8. Suglyama S, Sngenoya J, Wada M, NIIml N, Toyama J, Yamada K. Diagnosis of high posterior infarction: experimentalstudythrough the use of body surface isopotential maps. J Electrocardiol 1977;10:251-256. 9. Ishlkawa T, OkaJlmaM, NIIml N, Kolke Y, Toyama J, Yamada K. The body surface isopotential maps of the non-transmural infarctions. Jpn Circ J, in press. 10. Recke S. Contribution of Frank ECG measurements to the quantitative estimation of old posterodiaphragmaticmyocardial infarction. Int J Cardiol
1984;5:49-58. 11. Gunnar R, Pletras R, Blackaller J, Dadmun SE, Szanto PB, Tobln JR. Correlation of vectorcardiographic criteria for myocardial infarction with autopsy findings. Circulation 1967;35:158-171. 12. Dwyer E, Salvldor C, Greenberg H, Plnkernell B. Inferior myocardial infarction and right coronary artery occlusive disease a correlative study. Br Heart J 1975;37:464-470. 13. Savage RM, Wagner OS, Ideker RE, Podolsky SA, Hackel DB. Correlation of postmortem anatomic findings with electrocardiographic changes in patients with myocardial infarction. Circulation 1977;55:279-285. 14. Sheltlgar UR, Hultgren HN, Pfelfer JF, Lipton MJ. Diagnostic value of Qwaves in inferior myocardial infarction. Am Heart J 1974;88:170-175. 15. Hurd liP, Slarllng MR, Crawford MH, Dlabal PW, O'Roud(e RA. Comparative accuracy of electrocardiographic and vectorcardiographic criteria for inferior myocardial infarction. Circulation 1981;63:1025-1029. 16. Road( SF, Ideker RE, Wagner GS, Alonso DR, Bishop SP, Bloor CM, Bramlet DA, Edwards JE, Fallen JT, Gottlleb GJ, Hackel DB, Phillips HR, Relmer KA, Rogers WJ, Ruth WK, Savage RM, White RD, Selvester RH. Evaluation of a QRS scoring system for estimating myocardial infarct size. III. Correlation with quantitative anatomic findings for inferior infarcts. Am J Cardiol 1983;51:382-389. 17. Selvester RH, Solomon JC. Infarct size and QRS changes. (QRS criteria applicable to computer diagnostic programs.) in: Tolan GD, Pryor TA, eds. Computerized Interpretation of the ElecVocardi0gram.Proceedingsof the 1980 Engineering Foundation Conference. New York: Engineering Foundation, 1980:69-77. 19. Wagner GS, Freye CJ, Palmerl ST, Road( SF, Stack NC, Ideker RE, Harrell FE, Selvester RH. Evaluation of a QRS scoring system for estimating myocardial infarct size. I. Specificity and observer agreement. Circulation 1982;65:342-347. 19. Ideker RE, Wagner GS, Ruth WK, Alonso DR, Bishop SP, Bloor CM, Fallen JT, Goltlleb GJ, Hackel DB, Phillips HR, Relmer KA, Road( SF, Rogers WJ, Savage RM, White RD, Selvester RH. Evaluation of a QRS scoring system for estimatingmyocardial infarct size. II. Correlationwith quantitative anatomic findings for anterior infarcts. Am J Cardiol 1982;49:16041614. 20. Wlekllne SA, McNamara JJ. Vectorcardiographic quantification of infarct size in baboons. Circulation 1978;57:910-920. 21. Flowers NC, Hand RC, Srldharan MR, Horan LG, Sohl GS. Surface reflections of cardiac excitation and the assessmentof infarct volume in dogs. Circ Res 1978;43:406-413. 22. Jacobson ED, Rush S, Zlnberg S, Ablldskov JA. The effect of infarction on magnitude and orientation of electrical events in the heart. Am Heart J 1959;58:863-872.