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Asynergy of the Noninfarcted Left Ventricular Inferior Wall in Anterior Wall Acute Myocardial Infarction Secondary to Isolated Occlusion of the Left Anterior Descending Artery
Asynergy of the Noninfarcted Left Ventricular Inferior Wall in Anterior Wall Acute Myocardial Infarction Secondary to Isolated Occlusion of the Left Anterior Descending Artery Hideaki Yoshino, MD, Masato Taniuchi, MD, Eisei Kachi, MD, Hisashi Shimizu, Tatsuto Kajiwara, MD, Masahisa Ohguchi, MD, Michio Okada, MD, and Kyozo Ishikawa, MD
MD,
There are patients in whom left ventricular (LV) wall motion decreases in the noninfarcted region and LV systolic function declines globally despite the presence of a localized myocardial infarct attributable to narrowing or occlusion of a single coronary artery. This study examines angiographic characteristics of patients with chronic hypokinesia of noninfarcted myocardium after anterior wall acute myocardial infarction (AMI) due to narrowing of a single coronary artery, namely, the left anterior descending (LAD) artery. The LV ejection fraction, abnormalities in the motion of the noninfarcted LV inferior wall (SD/chord value by Sheehan’s technique), the angiographic characteristics of the infarct-related coronary artery, the effect of acute reperfusion therapy, and presence of coronary risk factors were examined in 85 consecutive patients. The SD/chord value in the noninfarcted region showed a positive correlation with the
LV ejection fraction (r 5 0.505, p <0.0001). By multivariate analysis, hypertension (odds ratio 5 0.53, 95% confidence interval [CI] 0.36 to 0.80), an infarct-related narrowing proximal to the origin of the first diagonal branch (odds ratio 5 0.56, 95% CI 0.38 to 0.84), and patency of the infarct-related lesion during AMI (odds ratio 5 1.56, 95% CI 1.03 to 2.30) were independent predictors of wall motion in the noninfarct region. In some patients with single-vessel anterior wall AMI, the motion of the noninfarcted inferior LV wall decreases during the chronic stage and cardiac function declines severely. In most of these patients, the infarct-related narrowing or occlusion is proximal to the origin of the first diagonal branch of the LAD artery. Q1998 by Excerpta Medica, Inc. (Am J Cardiol 1998;81:828 – 833)
n some patients with acute myocardial infarction (AMI), wall motion also decreases in the noninIfarcted left ventricular (LV) region and LV systolic
METHODS
function declines globally. These patients usually have severe left-sided heart failure despite the fact that they have had narrowing of only a single coronary artery. The inferior LV wall of the noninfarct region usually becomes hypercontractile to compensate for the decreased anterior wall motion in the infarct region.1,2 There have been no studies that closely examine the characteristics of patients with single-vessel coronary disease and AMI in which the noninfarcted myocardium shows a decline in function. In this study, we examined the relation between the presence of abnormal motion of noninfarcted LV wall during the recovery period and the angiographic characteristics of the infarct-related left anterior descending (LAD) coronary artery (i.e., length of the LAD coronary artery, residual stenosis, collateral flow, and location of the infarct-related narrowing) in patients with anterior wall AMI and single-vessel coronary disease. From the Second Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan. Manuscript received August 8, 1997; revised manuscript received and accepted December 8, 1997. Address for reprints: Kyozo Ishikawa, MD, Second Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181, Japan.
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©1998 by Excerpta Medica, Inc. All rights reserved.
Subjects: Between January 1990 and December 1994, 182 consecutive patients were admitted to our hospital within 12 hours of the onset of symptoms and were diagnosed with a first acute anterior myocardial infarction. Of these, 85 patients (70 men and 15 women; average age of 58 years; range 38 to 77), in whom single-vessel disease of the LAD coronary artery was confirmed by coronary angiography, were retrospectively studied. Anterior wall AMI was diagnosed by the presence of persistent ST-segment elevation (0.2 mV in $2 contiguous anterior chest leads (V1 to V4) on the electrocardiogram during the acute period; a compatible clinical syndrome, including severe chest pain without response to nitroglycerin or isosorbide dinitrate, lasting .30 minutes; and an increase in serum creatine phosphokinase to more than twice the upper limit of normal. Inclusion criteria were singlevessel disease of the LAD coronary artery on coronary angiography performed before discharge; age ,80 years; no history of AMI; and the absence of cardiomyopathy, severe valvular heart disease, or congenital heart disease. No patients received b blockers or angiotensin-converting enzyme inhibitors during the study. Blood samples for the measurement of creatine phosphokinase activity were collected every 3 hours until the peak value was obtained. 0002-9149/98/$19.00 PII S0002-9149(98)00015-0
In 35 of the 85 patients, acute reperfusion therapy by coronary thrombolysis (intravenous infusion of 960,000 U of urokinase or 24 million U of recombinant tissue plasminogen activator in 21 patients, and intracoronary administration of 480,000 to 600,000 U of urokinase in 14 patients) was performed within 6 hours of the onset of chest pain. In 23 patients, percutaneous transluminal coronary angioplasty was performed to achieve acute reperfusion. The other 27 patients underwent conventional conservative treatment without reperfusion therapy. In 49 of 85 patients (58%), emergency coronary angiography was performed to initiate reperfusion therapy. There were no differences in the baseline characteristics between the patients who underwent emergency coronary angiography and those who did not, except the prevalence of hyperlipidemia, which was higher in the patients who underwent emergency coronary angiography. When coronary blood flow was Thrombolysis in Myocardial Infarction (TIMI)3 flow grade $2, coronary angiography was terminated without reperfusion therapy. Cardiac catheterization: Cardiac catheterization was performed by the Seldinger technique 1 to 3 months after the onset of myocardial infarction or before discharge (mean: 49 6 20 days). Biplane left ventriculography was performed in the 30° right anterior oblique and 60° left anterior oblique projections at a rate of 60 frames/s per view. Coronary angiography with multiple views was performed in the routine manner using the Judkins’ technique. The baseline hemodynamic measurements included pulmonary capillary wedge and LV pressures. Written informed consent was obtained from each patient after an appropriate explanation of the risks and potential complications of cardiac catheterization. Analysis of coronary and ventricular angiograms:
Cine angiograms were assessed visually by 2 independent experienced observers who were unaware of the clinical data and electrocardiographic findings. The culprit lesion was determined from its angiographic characteristics (the presence of residual thrombus, ulcerated plaque, or the tightness and irregularity of the lesion) or by detection of complete obstruction of the LAD coronary artery in emergency or chronic phase coronary angiograms. The site of occlusion or residual stenosis of the LAD coronary artery was classified both by the American Heart Association (AHA) classification4 and the Coronary Artery Surgery Study (CASS) classification.5 The relation of the site of LAD coronary artery occlusion or residual stenosis to the origins of its first septal perforator and the first diagonal branch was determined. When the culprit lesion was located proximal to the origin of the first septal perforator, patients were classified into the AHA no. 6 group. When the culprit lesion was distal to the origin of the first septal perforator, patients were classified into the AHA no. 7 group. Patients with a culprit lesion proximal to the origin of the first diagonal branch were classified into the CASS no. 12 group, and patients with a culprit lesion distal to the origin of the first diagonal branch were classified into the CASS
no. 13 group. Patients in the CASS no. 13 group with a 99% stenosis of the first diagonal branch were considered equivalent to those in the CASS no. 12 group, and were transferred to that group. Collateral blood supply to the territory at risk was assessed by visual analysis of cine angiograms using the system proposed by Rentrop et al.6 Briefly, this system involves assigning 1 of 4 grades: grade 0, no visible collateral channels; grade 1, side branches of the artery perfused via collateral vessels are filled without visualization of the epicardial segment; grade 2, the epicardial segment is partly filled via collateral vessels; and grade 3, the epicardial segment is filled completely via collateral vessels. The extent of disease in the noninfarcted coronary arteries was also assessed. We evaluated the degree of stenosis by the caliper method. The degree of coronary stenosis was classified by the AHA classification, and any stenosis $75% in the noninfarcted arteries was defined as significant, for the purpose of detecting multivessel disease. Patients with multivessel disease were excluded from this study. To assess the extension of the LAD coronary artery over the apex of the heart, the following grading system was used: grade 1, the LAD coronary artery does not reach the apex; grade 2, the LAD coronary artery supplies the anterior LV wall as far as the apex, but does not supply the inferior wall; and grade 3, the LAD coronary artery continues beyond the apex onto the diaphragmatic surface of the inferior wall. Analysis of cine ventriculograms was performed with the help of a computer-based ventricular analysis system (Cathex Co, Ltd., Shibuya, Tokyo, Japan). The boundaries of 2 LV silhouettes (at end-diastole and end-systole) were traced manually with a digitizing device by a blinded observer. The end-diastolic frame was determined as the frame nearest the peak of the R wave from the electrocardiogram simultaneously recorded on the cine film. The frame showing the smallest ventricular volume was taken as the end-systolic frame. The LV volume was calculated by the biplane area-length method and was used to determine the ejection fraction, the end-diastolic volume index, and the end-systolic volume index. Regional wall motion was analyzed using the centerline method established by Sheehan et al.7 The measured motion of each chord was normalized for heart size by dividing by the length of the end-diastolic perimeter and then was expressed in terms of SD units above or below the normal mean motion of all the chords (SD/chord). Normal wall motion was determined from the ventriculograms of 30 patients with normal LV function and no coronary artery or valvular disease. To filter out noise, wall motion of noninfarcted myocardium was computed by averaging the motion of chords lying in the most abnormally contracting half of the territory for each 10 sequential chords and was expressed as the mean SD/chord value. In each patient, 3 sequences of 10 chords (chords 51 to 60, 61 to 70, and 71 to 80) were assessed, and the highest mean SD/chord value was taken to indicate the re-
CORONARY ARTERY DISEASE/INFERIOR WALL ASYNERGY AFTER ANTERIOR MI
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FIGURE 1. A, Hypokinetic wall motion in the noninfarcted inferior myocardium. LV wall motion was evaluated using Sheehan’s centerline method. Focusing on wall motion in inferior myocardium, values within 1 SD of normal were considered to be in the normal range, and wall motion of the inferior wall decreasing <1 SD than normal was considered to be hypokinetic wall motion. B, Hyperkinetic wall motion in noninfarcted inferior myocardium.Values within 1 SD of normal were determined to be in the normal range, and wall motion of the inferior myocardium >1 SD above normal was considered to be hyperkinetic wall motion.
gional wall motion of the noninfarcted inferior myocardium perfused by the normal right coronary artery and was expressed as the SD/chord in the noninfarct region (Figure 1). The severity of hypokinesia in the infarcted anterior wall was expressed as the SD/chord value in the infarct region, which was the mean SD/ chord value of chords 31 to 40. Multivariate analysis: The effects of various factors on the SD/chord in the noninfarct region were examined by multivariate analysis using the stepwise increment method. Covariates in the analysis included the following 13 items: age, gender, presence of type II diabetes mellitus or hypertension (systolic pressure 830 THE AMERICAN JOURNAL OF CARDIOLOGYT
VOL. 81
.160 mm Hg, diastolic .95 mm Hg), cigarette smoking ($10 cigarettes/day), hyperlipidemia (serum cholesterol .240 mg/dl or fasting serum triglycerides .200 mg/dl), reperfusion therapy, patency during the acute phase, infarct-related lesion in AHA no. 6 group, infarct-related lesion in CASS no. 12 group, length of LAD coronary artery, stenosis on chronic phase coronary angiograms, and chronic collateral flow grade. Patency during the acute phase was confirmed by emergency coronary angiography, and the patients with “patency during the acute phase” included patients with TIMI-2 or better flow at the initial coronary angiography, patients with TIMI-2 or better APRIL 1, 1998
TABLE I Multivariate Analysis for SD/Chord in the Noninfarct Region
Hypertension Patency during the acute phase IRL:CASS#12 IRL 5 infarct-related lesion.
Odds Ratio
95% CI
0.53 1.56 0.56
0.36–0.80 1.03–2.30 0.38–0.84
showed 3 independent factors, including hypertension, patency during the acute phase, and an infarct-related lesion in CASS no. 12 group (Table I). An infarctrelated lesion in AHA no. 6 group was not an independent factor. In Figure 2, the SD/chord in the noninfarct region showed a positive correlation with the LV ejection fraction (p ,0.0001). However, no significant correlation was observed between the SD/ chord in the noninfarct region and that in the infarct region (p 5 0.0564) or between the SD/chord in the noninfarct region and peak creatine phosphokinase activity (p 5 0.1295).
Effect of LAD artery occlusion proximal to the first diagonal branch on LV function: Various factors were com-
pared between the patients with CASS no. 12 lesions and those with CASS no. 13 lesions (Table II). There was no difference between the 2 groups with respect to age, gender, coronary risk factors, LAD coronary artery length, percent stenosis on the initial coronary angiograms, percent stenosis on chronic phase coronary angiograms, collateral flow on chronic phase coronary angiograms, reperfusion therapy, and patency during the acute phase. LV function was compared between the CASS no. 12 and CASS no. 13 groups. As shown in Table III, indexes such as LV ejection fraction (p ,0.0001), LV end-systolic volFIGURE 2. Comparison of SD/chord in the noninfarct region and LV function. A positive correlation between SD/chord values in the noninfarct region and LV ejection ume index (p 5 0.0003), LV endfraction are shown. The y-axis corresponds to SD/chord in noninfarct region, and the diastolic volume index (p 5 0.0319), x-axis corresponds to LV ejection fraction. chrLVEF 5 chronic left ventricular ejection SD/chord in the infarct region (p 5 fraction; nonSD/C 5 SD/Chord in noninfarct region. 0.0008), SD/chord in the noninfarct region (p 5 0.0214), and peak creatine phosphokinase value (p 5 flow obtained by intravenous coronary thrombolysis 0.0466) were more abnormal in the CASS no. 12 or intracoronary thrombolysis, and patients with suc- group than in the CASS no. 13 group. When LV function was compared, according to the AHA clascessful reperfusion by angioplasty. Statistical analysis: Statistical analysis was per- sification, between the AHA no. 6 group, with infarctformed using StatView 4.11 (Abacus Concepts, Inc., related lesions proximal to the first septal branch, and Berkeley, California). Data are expressed as the mean the AHA no. 7 group, with lesions distal to this value 6 SD. Comparisons between the 2 groups were branch, significant differences were observed with performed using the unpaired Student’s t test. Statis- respect to the LV ejection fraction and LV end-systically significant differences among the 3 groups tolic volume index. However, LV end-diastolic volwere determined by 1-way analysis of variance, fol- ume index, SD/chord in the infarct region, and SD/ lowed by the Bonferroni method in cases where the chord in the noninfarct region did not differ signifi1-way analysis of variance p value was ,0.05. The cantly. chi-square test was used for comparisons of categorical data. Results were considered statistically signif- DISCUSSION LV dysfunction and hypokinesia of noninfarcted icant when the p value was ,0.05. The odds ratios, 95% confidence intervals, and p values reported are myocardium: In this study, the study group was rethose for the final model (i.e., adjusted for all other stricted to patients having their first AMI and with single-vessel coronary disease of the LAD coronary significant covariates). artery. Increased contractile function in the noninfarct region is usually expected to compensate for deRESULTS Motion of noninfarcted inferior myocardium and fac- creased wall motion in the infarct region.1,2 However, tors affecting LV function: Multivariate analysis of the in this study, wall motion in the noninfarct region factors affecting SD/chord in the noninfarct region actually declined in patients with poor LV function. CORONARY ARTERY DISEASE/INFERIOR WALL ASYNERGY AFTER ANTERIOR MI
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TABLE II Baseline Clinical and Angiographic Characteristics According to the Infarct-Related Lesion CASS No. 12 (n 5 39) Men/women Age (yrs) Hypertension Hyperlipidemia Diabetes mellitus Smoker Stenosis on initial coronary angiography (%)* Emergency coronary angiography Residual stenosis on chronic phase coronary angiography (%) LAD length score Chronic collateral flow grade Reperfusion therapy Conservative treatment IV thrombolysis Intracoronary thrombolysis/coronary angioplasty Peak creatine phosphokinase activity (IU/L)†
29/10 60 6 9 13 (33%) 5 (13%) 9 (23%) 22 (56%) 97.2 6 4.2
CASS No. 13 (n 5 46)
p Value
41/5 57 6 9 21 (46%) 8 (17%) 8 (17%) 34 (76%) 97.7 6 4.0
0.08 0.12 0.24 0.28 0.51 0.09 0.67
24 (62%) 78.0 6 27.7
25 (54%) 75.1 6 26.3
0.50 0.63
2.8 6 0.6 0.6 6 1.0
2.7 6 0.8 0.5 6 0.9
0.29 0.49 0.23
13 (33%) 9 (23%) 17 (44%)
14 (30%) 13 (28%) 19 (42%)
5,821 6 3,114
4,149 6 3,028
0.0466
*Data on stenosis in the acute phase were available for 24 patients with CASS No. 12 and 25 patients with CASS No. 13 lesions. † Peak creatine phosphokinase activity data were available for 27 patients with CASS No. 12 and 29 patients with CASS No. 13 lesions.
TABLE III Comparison of Left Ventricular Function According to the Infarct-related Lesion by the CASS and AHA Classifications CASS No. 12 (n 5 39) SD/chord in the noninfarct region SD/chord in the infarct region Ejection fraction (%) End-systolic volume index (ml/m2) End-diastolic volume index (ml/m2) Peak creatine phosphokinase activity (IU/L)
20.4 23.0 46 53 94 5,821
6 6 6 6 6 6
1.0 0.6 12 31 35 3,114
AHA No. 6 (n 5 47) SD/chord in the noninfarct region SD/chord in the infarct region Ejection fraction (%) End-systolic volume index (ml/m2) End-diastolic volume index (ml/m2) Peak creatine phosphokinase activity (IU/L)
20.1 22.8 50 48 90 5,406
6 6 6 6 6 6
1.0 0.8 14 30 34 2,877
CASS No. 13 (n 5 46) 10.1 22.3 60 33 80 4,149
6 6 6 6 6 6
AHA No. 7 (n 5 38) 20.0 22.4 59 35 81 4,354
6 6 6 6 6 6
Depressed wall motion in the noninfarct region was not related to wall motion in the infarct region, but was correlated with overall LV function, although whether this was a cause or effect is not clear. Importance of an infarct-related LAD coronary artery narrowing for LV function: In the present study, multi-
variate analysis showed that the location of the infarctrelated lesion, according to the CASS classification (i.e., proximal or distal to the origin of the first diagonal branch), affected wall motion in the noninfarct region. No difference in the LAD coronary artery length, grade of collateral flow to the LAD coronary artery, or degree of LAD coronary artery residual 832 THE AMERICAN JOURNAL OF CARDIOLOGYT
0.9 1.2 13 17 25 3,028
VOL. 81
1.0 1.2 13 16 24 3,465
p Value 0.0214 0.0008 ,0.0001 0.0003 0.0319 0.0466
p Value
0.67 0.07 0.0024 0.0163 0.18 0.22
stenosis was observed between the patients with CASS no. 12 lesions and low contractility in the noninfarct region and patients with CASS no. 13 lesions and good contractility in the noninfarct region. It is unclear why there are patients with depressed LV function and impaired wall motion in the noninfarct region among those with infarct-related lesions proximal to the origin of the first diagonal branch. Angiographically, it is clear that CASS no. 12 patients have a larger perfused area than the CASS no. 13 patients. The extent of infarction alone may not provide an explanation, because there was no difference with respect to the LAD coronary artery length. The peak creatine phosphokinase value in the CASS no. 12 group was higher than that in the CASS no. 13 group, but was not the independent factor affecting the noninfarct inferior wall motion by multivariate analysis. In AHA no. 6 patients, a greater area of the ventricular septum was affected and the LV ejection fraction was lower than in AHA no. 7 patients, but no difference in LV wall motion of the noninfarct region was noted between AHA no. 6 patients and AHA no. 7 patients. Therefore, the impaired wall motion in the noninfarct inferior region may be due to the fact that the infarct region is extensive and involves the first diagonal branch territory. Many factors such as geometric changes, infarct size, extent of dilation, remodeling, changes in shape or radius of curvature may be the causes of a change in wall motion. Future studies are needed to explain the mechanisms of the results. Effect of reperfusion and residual infarct-related stenosis on LV function:
The benefits of reperfusion therapies such as thrombolytic therapy and primary coronary angioplasty for AMI have been well established. Acute reperfusion therapy improves both prognosis8 and LV function.9,10 In this study, multivariate analysis revealed that patency during the acute phase was an independent predictor of wall motion in the noninfarct region. Patients who obtain coronary artery patency by reperfusion therapy appear to have better LV function than those in whom patency is not maintained.11–14 Few studies have clearly shown a relation between the degree of residual stenosis and LV function during the chronic stage in patients with patent infarct-related APRIL 1, 1998
arteries. Leung et al15 demonstrated that the degree of residual stenosis during the chronic stage is an important factor predicting depressed LV systolic function and chronic LV dilation. However, in our study, the degree of residual stenosis did not have a significant influence on wall motion in the noninfarct region. 1. Theroux P, Ross J, Franklin D, Covell JW, Bloor CM, Sasayama S. Regional
myocardial function and dimensions early and late after myocardial infarction in the unanesthetized dog. Circ Res 1977;40:158 –165. 2. Sasayama S, Gallagher KP, Kemper WS, Franklin D, Ross J. Regional left ventricular wall thickness early and late after coronary occlusion in the conscious dog. Am J Physiol 1988;240: H293–H299. 3. Chesebro JH, Knatterud G, Roberts R, Borer J, Cohen LS, Dalen J, Dodge HT, Francis CK, Hillis D, Ludbrook P, et al. Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Circulation 1987;76:142–154. 4. AHA Committee Report. A reporting system on patients evaluated for coronary artery disease. Report of the Ad Hoc Committee for grading of coronary artery disease, Council on Cardiovascular Surgery, American Heart Association. News from the American Heart Association. Circulation 1975;51:5– 40. 5. The Principal Investigators of CASS and The Associates. The National Heart, Lung and Blood Institute Coronary Artery Surgery Study (CASS). Circulation 1981;63 (Suppl I):I-1– 88. 6. Rentrop KP, Feit F, Sherman W, Thornton JC. Serial angiographic assessment of coronary artery obstruction and collateral flow in acute myocardial infarction. Circulation 1989;80:1166 –1175.
7. Sheehan FH, Bolson EL, Dodge HT, Mathey DG, Schofer J, Woo H-W. Advantages and applications of the centerline method for characterizing regional ventricular function. Circulation 1986;74:293–305. 8. Wilcox RG, Olsson CG, Skene AM, Lippe GV, Jensen G, Hampton JR. Trial of tissue plasminogen activator for mortality reduction in acute myocardial infarction: Anglo-Scandinavian Study of Early Thrombolysis (ASSET). Lancet 1988;2:525–530. 9. National Heart Foundation of Australia Coronary Thrombolysis Group. Coronary thrombolysis and myocardial salvage by tissue plasminogen activator given up to 4 hours after onset of myocardial infarction. Lancet 1988;1:203–207. 10. O’Rourke M, Baron D, Keogh A, Nelson G, Barnes C, Raftos J, Graham K, Hillman K, Newman H, Healey J, Woolridge J, River J, White H, Whitlok R. Limitation of myocardial infarction by early infusion of recombinant tissue-type plasminogen activator. Circulation 1988; 77:1311–1315. 11. Topol EJ, Califf RM, Vandormael M, Grines CL, George BS, Sanz ML, Wall T, Brien MO, Schwaiger M, Aguirre FV, Popma JJ, Sigmon KN, Lee KL, Ellis SG.A randomized trial of late reperfusion therapy for acute myocardial infarction. Circulation 1992;85:2090 –2099. 12. Nidorf SM, Siu SC, Galambos G, Weyman AE, Picard MH. Benefit of late coronary reperfusion on ventricular morphology and function after myocardial infarction. J Am Coll Cardiol 1993;21:683– 691. 13. Jeremy RW, Hackworthy RA, Bautovich G, Hutton BF, Harris PJ. Infarct artery perfusion and changes in left ventricular volume in the month after acute myocardial infarction. J Am Coll Cardiol 1987;9:989 –995. 14. Marino P, Destro G, Barbieri R, Bicego D. Reperfusion of the infarct-related coronary artery limits left ventricular expansion beyond myocardial salvage. Am Heart J 1992;123:1157–1165. 15. Leung W-H, Lau C-P. Effects of severity of the residual stenosis of the infarct-related coronary artery on left ventricular dilation and function after acute myocardial infarction. J Am Coll Cardiol 1992;20:307–313.
CORONARY ARTERY DISEASE/INFERIOR WALL ASYNERGY AFTER ANTERIOR MI
833
MD,
There are patients in whom left ventricular (LV) wall motion decreases in the noninfarcted region and LV systolic function declines globally despite the presence of a localized myocardial infarct attributable to narrowing or occlusion of a single coronary artery. This study examines angiographic characteristics of patients with chronic hypokinesia of noninfarcted myocardium after anterior wall acute myocardial infarction (AMI) due to narrowing of a single coronary artery, namely, the left anterior descending (LAD) artery. The LV ejection fraction, abnormalities in the motion of the noninfarcted LV inferior wall (SD/chord value by Sheehan’s technique), the angiographic characteristics of the infarct-related coronary artery, the effect of acute reperfusion therapy, and presence of coronary risk factors were examined in 85 consecutive patients. The SD/chord value in the noninfarcted region showed a positive correlation with the
LV ejection fraction (r 5 0.505, p <0.0001). By multivariate analysis, hypertension (odds ratio 5 0.53, 95% confidence interval [CI] 0.36 to 0.80), an infarct-related narrowing proximal to the origin of the first diagonal branch (odds ratio 5 0.56, 95% CI 0.38 to 0.84), and patency of the infarct-related lesion during AMI (odds ratio 5 1.56, 95% CI 1.03 to 2.30) were independent predictors of wall motion in the noninfarct region. In some patients with single-vessel anterior wall AMI, the motion of the noninfarcted inferior LV wall decreases during the chronic stage and cardiac function declines severely. In most of these patients, the infarct-related narrowing or occlusion is proximal to the origin of the first diagonal branch of the LAD artery. Q1998 by Excerpta Medica, Inc. (Am J Cardiol 1998;81:828 – 833)
n some patients with acute myocardial infarction (AMI), wall motion also decreases in the noninIfarcted left ventricular (LV) region and LV systolic
METHODS
function declines globally. These patients usually have severe left-sided heart failure despite the fact that they have had narrowing of only a single coronary artery. The inferior LV wall of the noninfarct region usually becomes hypercontractile to compensate for the decreased anterior wall motion in the infarct region.1,2 There have been no studies that closely examine the characteristics of patients with single-vessel coronary disease and AMI in which the noninfarcted myocardium shows a decline in function. In this study, we examined the relation between the presence of abnormal motion of noninfarcted LV wall during the recovery period and the angiographic characteristics of the infarct-related left anterior descending (LAD) coronary artery (i.e., length of the LAD coronary artery, residual stenosis, collateral flow, and location of the infarct-related narrowing) in patients with anterior wall AMI and single-vessel coronary disease. From the Second Department of Internal Medicine, Kyorin University School of Medicine, Tokyo, Japan. Manuscript received August 8, 1997; revised manuscript received and accepted December 8, 1997. Address for reprints: Kyozo Ishikawa, MD, Second Department of Internal Medicine, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181, Japan.
828
©1998 by Excerpta Medica, Inc. All rights reserved.
Subjects: Between January 1990 and December 1994, 182 consecutive patients were admitted to our hospital within 12 hours of the onset of symptoms and were diagnosed with a first acute anterior myocardial infarction. Of these, 85 patients (70 men and 15 women; average age of 58 years; range 38 to 77), in whom single-vessel disease of the LAD coronary artery was confirmed by coronary angiography, were retrospectively studied. Anterior wall AMI was diagnosed by the presence of persistent ST-segment elevation (0.2 mV in $2 contiguous anterior chest leads (V1 to V4) on the electrocardiogram during the acute period; a compatible clinical syndrome, including severe chest pain without response to nitroglycerin or isosorbide dinitrate, lasting .30 minutes; and an increase in serum creatine phosphokinase to more than twice the upper limit of normal. Inclusion criteria were singlevessel disease of the LAD coronary artery on coronary angiography performed before discharge; age ,80 years; no history of AMI; and the absence of cardiomyopathy, severe valvular heart disease, or congenital heart disease. No patients received b blockers or angiotensin-converting enzyme inhibitors during the study. Blood samples for the measurement of creatine phosphokinase activity were collected every 3 hours until the peak value was obtained. 0002-9149/98/$19.00 PII S0002-9149(98)00015-0
In 35 of the 85 patients, acute reperfusion therapy by coronary thrombolysis (intravenous infusion of 960,000 U of urokinase or 24 million U of recombinant tissue plasminogen activator in 21 patients, and intracoronary administration of 480,000 to 600,000 U of urokinase in 14 patients) was performed within 6 hours of the onset of chest pain. In 23 patients, percutaneous transluminal coronary angioplasty was performed to achieve acute reperfusion. The other 27 patients underwent conventional conservative treatment without reperfusion therapy. In 49 of 85 patients (58%), emergency coronary angiography was performed to initiate reperfusion therapy. There were no differences in the baseline characteristics between the patients who underwent emergency coronary angiography and those who did not, except the prevalence of hyperlipidemia, which was higher in the patients who underwent emergency coronary angiography. When coronary blood flow was Thrombolysis in Myocardial Infarction (TIMI)3 flow grade $2, coronary angiography was terminated without reperfusion therapy. Cardiac catheterization: Cardiac catheterization was performed by the Seldinger technique 1 to 3 months after the onset of myocardial infarction or before discharge (mean: 49 6 20 days). Biplane left ventriculography was performed in the 30° right anterior oblique and 60° left anterior oblique projections at a rate of 60 frames/s per view. Coronary angiography with multiple views was performed in the routine manner using the Judkins’ technique. The baseline hemodynamic measurements included pulmonary capillary wedge and LV pressures. Written informed consent was obtained from each patient after an appropriate explanation of the risks and potential complications of cardiac catheterization. Analysis of coronary and ventricular angiograms:
Cine angiograms were assessed visually by 2 independent experienced observers who were unaware of the clinical data and electrocardiographic findings. The culprit lesion was determined from its angiographic characteristics (the presence of residual thrombus, ulcerated plaque, or the tightness and irregularity of the lesion) or by detection of complete obstruction of the LAD coronary artery in emergency or chronic phase coronary angiograms. The site of occlusion or residual stenosis of the LAD coronary artery was classified both by the American Heart Association (AHA) classification4 and the Coronary Artery Surgery Study (CASS) classification.5 The relation of the site of LAD coronary artery occlusion or residual stenosis to the origins of its first septal perforator and the first diagonal branch was determined. When the culprit lesion was located proximal to the origin of the first septal perforator, patients were classified into the AHA no. 6 group. When the culprit lesion was distal to the origin of the first septal perforator, patients were classified into the AHA no. 7 group. Patients with a culprit lesion proximal to the origin of the first diagonal branch were classified into the CASS no. 12 group, and patients with a culprit lesion distal to the origin of the first diagonal branch were classified into the CASS
no. 13 group. Patients in the CASS no. 13 group with a 99% stenosis of the first diagonal branch were considered equivalent to those in the CASS no. 12 group, and were transferred to that group. Collateral blood supply to the territory at risk was assessed by visual analysis of cine angiograms using the system proposed by Rentrop et al.6 Briefly, this system involves assigning 1 of 4 grades: grade 0, no visible collateral channels; grade 1, side branches of the artery perfused via collateral vessels are filled without visualization of the epicardial segment; grade 2, the epicardial segment is partly filled via collateral vessels; and grade 3, the epicardial segment is filled completely via collateral vessels. The extent of disease in the noninfarcted coronary arteries was also assessed. We evaluated the degree of stenosis by the caliper method. The degree of coronary stenosis was classified by the AHA classification, and any stenosis $75% in the noninfarcted arteries was defined as significant, for the purpose of detecting multivessel disease. Patients with multivessel disease were excluded from this study. To assess the extension of the LAD coronary artery over the apex of the heart, the following grading system was used: grade 1, the LAD coronary artery does not reach the apex; grade 2, the LAD coronary artery supplies the anterior LV wall as far as the apex, but does not supply the inferior wall; and grade 3, the LAD coronary artery continues beyond the apex onto the diaphragmatic surface of the inferior wall. Analysis of cine ventriculograms was performed with the help of a computer-based ventricular analysis system (Cathex Co, Ltd., Shibuya, Tokyo, Japan). The boundaries of 2 LV silhouettes (at end-diastole and end-systole) were traced manually with a digitizing device by a blinded observer. The end-diastolic frame was determined as the frame nearest the peak of the R wave from the electrocardiogram simultaneously recorded on the cine film. The frame showing the smallest ventricular volume was taken as the end-systolic frame. The LV volume was calculated by the biplane area-length method and was used to determine the ejection fraction, the end-diastolic volume index, and the end-systolic volume index. Regional wall motion was analyzed using the centerline method established by Sheehan et al.7 The measured motion of each chord was normalized for heart size by dividing by the length of the end-diastolic perimeter and then was expressed in terms of SD units above or below the normal mean motion of all the chords (SD/chord). Normal wall motion was determined from the ventriculograms of 30 patients with normal LV function and no coronary artery or valvular disease. To filter out noise, wall motion of noninfarcted myocardium was computed by averaging the motion of chords lying in the most abnormally contracting half of the territory for each 10 sequential chords and was expressed as the mean SD/chord value. In each patient, 3 sequences of 10 chords (chords 51 to 60, 61 to 70, and 71 to 80) were assessed, and the highest mean SD/chord value was taken to indicate the re-
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FIGURE 1. A, Hypokinetic wall motion in the noninfarcted inferior myocardium. LV wall motion was evaluated using Sheehan’s centerline method. Focusing on wall motion in inferior myocardium, values within 1 SD of normal were considered to be in the normal range, and wall motion of the inferior wall decreasing <1 SD than normal was considered to be hypokinetic wall motion. B, Hyperkinetic wall motion in noninfarcted inferior myocardium.Values within 1 SD of normal were determined to be in the normal range, and wall motion of the inferior myocardium >1 SD above normal was considered to be hyperkinetic wall motion.
gional wall motion of the noninfarcted inferior myocardium perfused by the normal right coronary artery and was expressed as the SD/chord in the noninfarct region (Figure 1). The severity of hypokinesia in the infarcted anterior wall was expressed as the SD/chord value in the infarct region, which was the mean SD/ chord value of chords 31 to 40. Multivariate analysis: The effects of various factors on the SD/chord in the noninfarct region were examined by multivariate analysis using the stepwise increment method. Covariates in the analysis included the following 13 items: age, gender, presence of type II diabetes mellitus or hypertension (systolic pressure 830 THE AMERICAN JOURNAL OF CARDIOLOGYT
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.160 mm Hg, diastolic .95 mm Hg), cigarette smoking ($10 cigarettes/day), hyperlipidemia (serum cholesterol .240 mg/dl or fasting serum triglycerides .200 mg/dl), reperfusion therapy, patency during the acute phase, infarct-related lesion in AHA no. 6 group, infarct-related lesion in CASS no. 12 group, length of LAD coronary artery, stenosis on chronic phase coronary angiograms, and chronic collateral flow grade. Patency during the acute phase was confirmed by emergency coronary angiography, and the patients with “patency during the acute phase” included patients with TIMI-2 or better flow at the initial coronary angiography, patients with TIMI-2 or better APRIL 1, 1998
TABLE I Multivariate Analysis for SD/Chord in the Noninfarct Region
Hypertension Patency during the acute phase IRL:CASS#12 IRL 5 infarct-related lesion.
Odds Ratio
95% CI
0.53 1.56 0.56
0.36–0.80 1.03–2.30 0.38–0.84
showed 3 independent factors, including hypertension, patency during the acute phase, and an infarct-related lesion in CASS no. 12 group (Table I). An infarctrelated lesion in AHA no. 6 group was not an independent factor. In Figure 2, the SD/chord in the noninfarct region showed a positive correlation with the LV ejection fraction (p ,0.0001). However, no significant correlation was observed between the SD/ chord in the noninfarct region and that in the infarct region (p 5 0.0564) or between the SD/chord in the noninfarct region and peak creatine phosphokinase activity (p 5 0.1295).
Effect of LAD artery occlusion proximal to the first diagonal branch on LV function: Various factors were com-
pared between the patients with CASS no. 12 lesions and those with CASS no. 13 lesions (Table II). There was no difference between the 2 groups with respect to age, gender, coronary risk factors, LAD coronary artery length, percent stenosis on the initial coronary angiograms, percent stenosis on chronic phase coronary angiograms, collateral flow on chronic phase coronary angiograms, reperfusion therapy, and patency during the acute phase. LV function was compared between the CASS no. 12 and CASS no. 13 groups. As shown in Table III, indexes such as LV ejection fraction (p ,0.0001), LV end-systolic volFIGURE 2. Comparison of SD/chord in the noninfarct region and LV function. A positive correlation between SD/chord values in the noninfarct region and LV ejection ume index (p 5 0.0003), LV endfraction are shown. The y-axis corresponds to SD/chord in noninfarct region, and the diastolic volume index (p 5 0.0319), x-axis corresponds to LV ejection fraction. chrLVEF 5 chronic left ventricular ejection SD/chord in the infarct region (p 5 fraction; nonSD/C 5 SD/Chord in noninfarct region. 0.0008), SD/chord in the noninfarct region (p 5 0.0214), and peak creatine phosphokinase value (p 5 flow obtained by intravenous coronary thrombolysis 0.0466) were more abnormal in the CASS no. 12 or intracoronary thrombolysis, and patients with suc- group than in the CASS no. 13 group. When LV function was compared, according to the AHA clascessful reperfusion by angioplasty. Statistical analysis: Statistical analysis was per- sification, between the AHA no. 6 group, with infarctformed using StatView 4.11 (Abacus Concepts, Inc., related lesions proximal to the first septal branch, and Berkeley, California). Data are expressed as the mean the AHA no. 7 group, with lesions distal to this value 6 SD. Comparisons between the 2 groups were branch, significant differences were observed with performed using the unpaired Student’s t test. Statis- respect to the LV ejection fraction and LV end-systically significant differences among the 3 groups tolic volume index. However, LV end-diastolic volwere determined by 1-way analysis of variance, fol- ume index, SD/chord in the infarct region, and SD/ lowed by the Bonferroni method in cases where the chord in the noninfarct region did not differ signifi1-way analysis of variance p value was ,0.05. The cantly. chi-square test was used for comparisons of categorical data. Results were considered statistically signif- DISCUSSION LV dysfunction and hypokinesia of noninfarcted icant when the p value was ,0.05. The odds ratios, 95% confidence intervals, and p values reported are myocardium: In this study, the study group was rethose for the final model (i.e., adjusted for all other stricted to patients having their first AMI and with single-vessel coronary disease of the LAD coronary significant covariates). artery. Increased contractile function in the noninfarct region is usually expected to compensate for deRESULTS Motion of noninfarcted inferior myocardium and fac- creased wall motion in the infarct region.1,2 However, tors affecting LV function: Multivariate analysis of the in this study, wall motion in the noninfarct region factors affecting SD/chord in the noninfarct region actually declined in patients with poor LV function. CORONARY ARTERY DISEASE/INFERIOR WALL ASYNERGY AFTER ANTERIOR MI
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TABLE II Baseline Clinical and Angiographic Characteristics According to the Infarct-Related Lesion CASS No. 12 (n 5 39) Men/women Age (yrs) Hypertension Hyperlipidemia Diabetes mellitus Smoker Stenosis on initial coronary angiography (%)* Emergency coronary angiography Residual stenosis on chronic phase coronary angiography (%) LAD length score Chronic collateral flow grade Reperfusion therapy Conservative treatment IV thrombolysis Intracoronary thrombolysis/coronary angioplasty Peak creatine phosphokinase activity (IU/L)†
29/10 60 6 9 13 (33%) 5 (13%) 9 (23%) 22 (56%) 97.2 6 4.2
CASS No. 13 (n 5 46)
p Value
41/5 57 6 9 21 (46%) 8 (17%) 8 (17%) 34 (76%) 97.7 6 4.0
0.08 0.12 0.24 0.28 0.51 0.09 0.67
24 (62%) 78.0 6 27.7
25 (54%) 75.1 6 26.3
0.50 0.63
2.8 6 0.6 0.6 6 1.0
2.7 6 0.8 0.5 6 0.9
0.29 0.49 0.23
13 (33%) 9 (23%) 17 (44%)
14 (30%) 13 (28%) 19 (42%)
5,821 6 3,114
4,149 6 3,028
0.0466
*Data on stenosis in the acute phase were available for 24 patients with CASS No. 12 and 25 patients with CASS No. 13 lesions. † Peak creatine phosphokinase activity data were available for 27 patients with CASS No. 12 and 29 patients with CASS No. 13 lesions.
TABLE III Comparison of Left Ventricular Function According to the Infarct-related Lesion by the CASS and AHA Classifications CASS No. 12 (n 5 39) SD/chord in the noninfarct region SD/chord in the infarct region Ejection fraction (%) End-systolic volume index (ml/m2) End-diastolic volume index (ml/m2) Peak creatine phosphokinase activity (IU/L)
20.4 23.0 46 53 94 5,821
6 6 6 6 6 6
1.0 0.6 12 31 35 3,114
AHA No. 6 (n 5 47) SD/chord in the noninfarct region SD/chord in the infarct region Ejection fraction (%) End-systolic volume index (ml/m2) End-diastolic volume index (ml/m2) Peak creatine phosphokinase activity (IU/L)
20.1 22.8 50 48 90 5,406
6 6 6 6 6 6
1.0 0.8 14 30 34 2,877
CASS No. 13 (n 5 46) 10.1 22.3 60 33 80 4,149
6 6 6 6 6 6
AHA No. 7 (n 5 38) 20.0 22.4 59 35 81 4,354
6 6 6 6 6 6
Depressed wall motion in the noninfarct region was not related to wall motion in the infarct region, but was correlated with overall LV function, although whether this was a cause or effect is not clear. Importance of an infarct-related LAD coronary artery narrowing for LV function: In the present study, multi-
variate analysis showed that the location of the infarctrelated lesion, according to the CASS classification (i.e., proximal or distal to the origin of the first diagonal branch), affected wall motion in the noninfarct region. No difference in the LAD coronary artery length, grade of collateral flow to the LAD coronary artery, or degree of LAD coronary artery residual 832 THE AMERICAN JOURNAL OF CARDIOLOGYT
0.9 1.2 13 17 25 3,028
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1.0 1.2 13 16 24 3,465
p Value 0.0214 0.0008 ,0.0001 0.0003 0.0319 0.0466
p Value
0.67 0.07 0.0024 0.0163 0.18 0.22
stenosis was observed between the patients with CASS no. 12 lesions and low contractility in the noninfarct region and patients with CASS no. 13 lesions and good contractility in the noninfarct region. It is unclear why there are patients with depressed LV function and impaired wall motion in the noninfarct region among those with infarct-related lesions proximal to the origin of the first diagonal branch. Angiographically, it is clear that CASS no. 12 patients have a larger perfused area than the CASS no. 13 patients. The extent of infarction alone may not provide an explanation, because there was no difference with respect to the LAD coronary artery length. The peak creatine phosphokinase value in the CASS no. 12 group was higher than that in the CASS no. 13 group, but was not the independent factor affecting the noninfarct inferior wall motion by multivariate analysis. In AHA no. 6 patients, a greater area of the ventricular septum was affected and the LV ejection fraction was lower than in AHA no. 7 patients, but no difference in LV wall motion of the noninfarct region was noted between AHA no. 6 patients and AHA no. 7 patients. Therefore, the impaired wall motion in the noninfarct inferior region may be due to the fact that the infarct region is extensive and involves the first diagonal branch territory. Many factors such as geometric changes, infarct size, extent of dilation, remodeling, changes in shape or radius of curvature may be the causes of a change in wall motion. Future studies are needed to explain the mechanisms of the results. Effect of reperfusion and residual infarct-related stenosis on LV function:
The benefits of reperfusion therapies such as thrombolytic therapy and primary coronary angioplasty for AMI have been well established. Acute reperfusion therapy improves both prognosis8 and LV function.9,10 In this study, multivariate analysis revealed that patency during the acute phase was an independent predictor of wall motion in the noninfarct region. Patients who obtain coronary artery patency by reperfusion therapy appear to have better LV function than those in whom patency is not maintained.11–14 Few studies have clearly shown a relation between the degree of residual stenosis and LV function during the chronic stage in patients with patent infarct-related APRIL 1, 1998
arteries. Leung et al15 demonstrated that the degree of residual stenosis during the chronic stage is an important factor predicting depressed LV systolic function and chronic LV dilation. However, in our study, the degree of residual stenosis did not have a significant influence on wall motion in the noninfarct region. 1. Theroux P, Ross J, Franklin D, Covell JW, Bloor CM, Sasayama S. Regional
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