Left ventricular wall motion at rest in patients with organic coronary artery disease vs coronary spasm

Left vents ic coro8Mwy with or coronary spasm

at Ireat ia

s vs

Left ventricular ejection fractions and regional ejection changes obtained from left ventriculograms at rert were analyzed in 15 normai subjects, in 17 pattents wlth isolated, organic left anterior descending coronary artery disease, and in 11 patients wtth isolated left anterior descending coronary artery spasm. Patknts with coronary artery spasm dkl not have signhkant organic lesions at the site of spasm. All patients with organic coronary artery disease and coronary artery spasm had a history of angtna pectorfo wlthout myocardlal Infarction. No slgnifkant differences in ejection fraction were observed among the three groups. The regional ejectlon change of the anterolateral and apkal wail suppthad by the IOft ante&W descending coronary artery was slgnifkantly decreased In patknts with organic coronary artery lsease compared wlth those in normal subjects (anterolateral 39.5 + 10.3% vs 48.4 + 7.7%, p < 0.05; apical 48.4 rl: 8.8% vs 55.6 + 7.8%, p < 0.05). However, the anterolaterai and apkal wall motion was not impaired in patlents with coronary artery spasm. Thus, patients with organk coronary artery disease had impairment of left ventrkular watl motion, white those wtth coronary artery spasm did not, although both groups of pattents had symptoms of angtna. These results suggest that patients with organic coronary artery disease may have had coronary blood flow disturbances through stenosed vessels and chronic acthe ischemir that produced left ventricular impairment. (AM HEART J 1987;113:684.)

Yasuo Matsuda, M.D., Kohshiro Moritani, M.D., Hiroshi Ogawa, M.D., Masako Matsuda, M.D., Michihiro Kohno, M.D., Toshiro Miura, M.D., Shinya Kohtoku, M.D., Takafumi Hiro, M.D., Masafumi Yano, M.D., and Reizo Kusukawa, M.D. Yumaguchi, Japan

The pathogenesis of angina pectorie is precipitated mainly by either a coronary artery spasm, which causes angina by abruptly decreasing blood flow to the myocardium, or a fixed organic lesion, which causes angina when the flow requirement of the myocardium exceeds the flow capacity of the diseased ~essel.‘~~ Patients with severe organic coronary artery disease without a history of myocardial infarction have been reported to have impaired left ventricular wall motion.6v7 However, the effect of angina on left ventricular wall motion has not been investigated in patients with coronary artery spasm. In the present study, patients with clinical manifestations of angina were divided into two groups: From the Department of Internal Medicine, Yamaguchi University School of Medicine. Received for publication March 31, 1986; accepted July 18, 1986. Reprint requests Yasuo Matauda, M.D., Department of Internal Medicine, Yamaguchi University School of Medicine, 1144 Kogushi, Ube, Yamaguchi 155, Japan.

684

those with coronary artery spasm without significant organic lesions and those with significant organic coronary artery disease. Left ventricular wall motion was observed in patients with coronary artery spasm and organic coronary artery disease. METHODS Pattsnt

selectton.

Left ventriculograrns were analyzed

in 17 consecutive patients with organic lumen diameter reduction of more than 75% (group 0) and in 11 consecutive patients with coronary artery spasm(group S) in the proximal left anterior descending coronary artery. Patients were selected retrospectively from a review of cardiac catheterization data. None of the patienta in group 0 had more than 70% organic lumen diameter reduction in the right coronary artery, left circumflex coronary artery, or any branches of the major coronary artery. In group S, no organic lesionswere found at the site of spasm or in any major coronary arteries or their branches. Coronary artery spasm was documented by ergonovine malaatetesti& at the time of cardiac catheterization, and total or subtotal spastic occlusion was seen with angina and an ECG changesimilar to that seenin angina1attack

Veluma Number

113 3

Silent

ischemia

and resting

LV wall motion

585

Table I. Clinical characteristics of angina in patients with

organic coronary artery disease(group 0) and coronary artery spasm(group S) Clinical characteristics No. of patients Men Women Age

(yr)

Initial AP-Cath (mo) Last AP-Cath (days) Type of AP Exercise Rest Both Duration of AP 55 min >5 min Frequency of AP 3/wk ECG changes SW

Group 0

Group S

17 14 3 52 f 8 6*7 11 IT 18

11 10 51 2 7 8+7 2*2

11 1 5

0 5 6

15 2

8 3

ST4 Abbreviations: depression;

STt

AP = angina pectoris; = ST elevation.

Cath

1

5

1

7 5

3 7

2

9

15

2

= catheterization;

ST4 = ST

before catheterization. No concomitant occurrence of coronary artery spasmwas seenin the right coronary artery, left circumflex coronary artery, or any branches of the major coronary arteries. All patients in groups 0 and S had a history of angina before cardiac catheterization. None of the patients had a history of unstable angina or myocardial infarction, and none had pathogenic Q waves on ECG. The control group (group C) comprised 15 consecutive patients with qualitatively normal left ventricular wall motion. These patients had normal coronary arteries or only minimal luminal irregularities on selective coronary angiography, as well as normal hemodynamics. None of the patients had stenotic or incompetent valvular lesions. Cardiac catheterlzatlon. Cardiac catheterization was performed after an overnight fast. Cardiac medications were discontinued for at least 2 days prior to the study, except for sublingual nitroglycerin which wasallowed for anginal attack. Informed consentwas obtained from each patient before the study. After pressure measurements were obtained, left ventriculography wasperformed in the 30-degreeright anterior oblique and 60-degreeleft anterior oblique projections. Left ventriculography was performed with the injection of 40 ml of Renografin 76 % over 3 seconds.Left ve&+icuIogrti were not obtained at the time patients were actively having angina. Selective coronary arteriography was performed by the Sones technique.@ Films wereexposedat a speedof 60 frames/set in a 35 mm camera mounted on a SiemensCardoskop U, 17 to 25 cm dual-fields image intensifier.

Fig. 1. Regional wall motion of left ventricle. Outline of left ventricle in 30-degreeright anterior oblique projection, showing the five regions used to calculate regional ejection fraction change.R,-anterobasal, R,-anterolateral; R,-apical; R,-diaphragmatic; R,-posterolateral. Films were reviewed on a Vanguard projector. Regional wall motion was assessed from the left ventriculogram in the 30-degreeright anterior oblique projection, according to the method of Gelberg et allo Briefly, five areas of interestanterobasal, anterolateral, apical, diaphragmatic, and posterobasal-were constructed by drawing a longitudinal axis from the midpoint of the aortic valve to the apex and trisecting it by two equidistant chords (Fig. 1). The two apical areaswere combined and treated as a single region. The systolic change for each region was measured as the segmental ejection fraction: (diastolic regional area - systolic regional area) / diastolic regional area X 100. Statistical analysis. All valuesare expressedasmean +standard deviation. Analysis of variance was used to compare groupsC, 0, and S. A p value lessthan 0.05 was consideredsignificant. RESULTS Patient characteristics. The mean age was 51 & 6 years in group C, 52 sf: 8 years in group 0, and 51 * 7 years in group S. There were six men and nine women in group C, 14 men and three women in group 0, and 10 men and one woman in group S. The clinical characteristics of angina in groups 0 and S are listed in Table I. The mean interval from the initial episode of angina to cardiac catheterization was not different in group 0 and group S. The mean interval from the last episode of angina to cardiac catheteriiation in group S was shorter than that in group 0. Most of the patients in group 0 had exertional angina, whereas those in group S had

March

606

Matsuda

et al.

Table

II. Left ventricular ejection fraction and regional ejection change

American

1987

Heart Journal

Group

Ejection fraction (%o)

R,

R2

R3

R,

R.5

C 0 S

61.8 f 6.1 56.4 + 5.7 61.5 + 4.8

58.2 + 6.3 52.7 rt 9.1 57.0 t 10.6

48.4 + 7.7 39.5 t 10.3* 50.0 + 14.6*

55.6 zk 7.8* 48.8 ? 8.8 52.5 k 9.7

53.8 + 6.6 50.1 + 4.4 51.6 k 6.3

36.2 + 9.5 31.8 k 7.5 30.0 + 7.9

Regional ejection change (%)

*p < 0.05.

resting angina. The duration of angina was similar in both groups. Angina was seen more frequently in group S than in group 0. Most of the patients in group 0 had ST segment depression during angina on ECG, *hereas those in group S had ST segment elevation during angina. Left ventricular wall motion. Between groups C and 0 and groups C and S, there were no significant differences in ejection fraction. Regional wall motion was analyzed in groups C, 0, and S (Table II). The regional wall motion supplied by the left anterior descending coronary artery (anterolateral and apical area) was significantly impaired in group 0 but not in group S, compared with that in group C. The remaining regional wall motion was not impaired in either group 0 or group S. DlSCliSSlON Left ventricular function in organic disease. The effects of significant

coronary

artery

organic coronary artery disease on left ventricular function have been amply investigated .6s7,11*15 The fact that patients with severe organic coronary artery disease and a history of angina pectoris without myocardial infarction often have small foci of myocardial fibrosis at autopsy suggests that anginal episodes alone may sometimes produce myocardial necrosis6 Flameng et al.’ observed the relationships between structural alterations and ventricular contraction abnormalities in patients with chronic ischemic heart disease. The histologic correlate of reduced wall motion in segments not previously infarcted was progressive loss of contractile material in otherwise viable myocardial cells. In patients with left ventricular dysfunction in coronary artery disease, Markis et al.” reported that deterioration in ejection fraction was observed without coronary angiographic changes in serial cineangiogmphic studies and suggested that recurrent ischemic episodes may result in coalescent myofibrotic changes and eventual asynergy without a frank clinical event. For many years it has been believed that the impairment of left ventricular function observed in the basal state in many patients with ischemic heart disease is

caused either by previous myocardial necrosis or by the presence of active ischemia.12In such patients, a positive inotropic intervention, such as the infusion of epinephrine,13 postextrasystolic potentiation,14 or exerciselsmay result in substantial improvement of regional function. Braunwald and Kloner12 suggested that it is likely that when the myocardium is repeatedly stunned, it may exhibit chronic postischemic left ventricular dysfunction, which may progress to myocardial scarring and ischemic cardiomyopathy. In the present study, patients with angina pectoris resulting from organic coronary artery disease had impairment of left ventricular wall motion. These results were consistent with those of previous studies. However, in this study, it is difficult to determine whether the impairment of left ventricular wall motion in patients with organic coronary artery disease is the result of small areas of fibrosis or a chronic ischemic state whereby myocardial cells are alive but not functioning normally. Left ventricular

function

in coronary

artery

spasm.

The effect of coronary artery spasm on left ventricular function has not been reported clinically. In recent experimental studies, the ,effect of repeated coronary occlusion on left ventricular function has been investigated .16, ” Geft et all6 reported observing distinct areas of subendocardial necrosis and evidence of irreversible ultrastructural damage in 3 of 32 dogs subjected to 18 occlusions lasting 5 minutes and in 7 of 24 dogs subjected to 18 occlusions lasting 15 minutes, followed by Xi-minute periods of reperfusion. In contrast, Lange et all7 reported that three consecutive 5- and 15-minute occlusions with intermittent 30-minute periods of reperfusion led to depression of endccardial contractile function in the reperfused xone, but that these alterations were not cuminulative after three repetitive coronary artery occlusions. Although these experimental models may not always be analogous to the mechanism of akgina caused by coronary artery spasm, our patients with coronary artery spasm without significant organic coronary artery disease did not have impairment of left ventricular wall motion. Dtfferent

influences

of organic

coronary

artery

dis-

Volume Number

113 3

ease and coronary artery spasm function. It has been documented

Silent on left

ventricular

that the severity and duration of postischemic changes depend on the length and intensity of the ischemia, as well as on the condition of the myocardium at the onset of the ischemic episode.‘* The pathophysiology of angina is different between patients with organic coronary artery disease and those with coronary artery spasm, and the degree of angina may not be equivalent between each group of patients. Patients with significant organic coronary artery disease had angina, when the flow requirement of the myocardium exceeded the flow capacity of the diseased vessel? On the other hand, patients with coronary artery spasm without significant organic coronary artery disease had angina resulting from acute dynamic occlusion of the coronary artery.3-5 It has been documented that coronary artery spasm with ST segment elevation seen on EGG resulted in transmural ischemia and organic coronary artery disease often associated with ST segment depression related to subendocardial ischemia.16 In the present study, the degree of angina, that is, the frequency of angina, interval since the last anginal attack to cardiac catheterization, and ST segment changes, seems to be severe in patients with coronary artery spasm (Table I). Nevertheless, patients with organic coronary artery disease had impairment of left ventricular wall motion, while patients with coronary artery spasm did not have left ventricular impairment. Vatner lg has shown that even small reductions in regional myocardial flow cause reductions in regional myocardial function. Patients with organic coronary artery disease had a continuous blood flow disturbance through fixed organic stenosis and might have chronic ongoing myocardial ischemia. Therefore, patients with organic coronary artery disease may have impaired left ventricular function. However, patients with coronary artery spasm should not have any myocardial ischemia when the vessels are widely patent, which may explain the absence of left ventricular impairment. The different mechanisms of myocardial ischemia resulting from organic coronary artery disease and coronary artery spasm had different influences on left ventricular function. Thus therapy and prognosis in patients with organic coronary artery disease and coronary artery spasm must be different. Although the future prognosis of left ventricular impairment in patients with organic coronary artery disease is obscure, restoration of coronary blood flow

ischemia

and resting

LV wall motion

687

either by coronary angioplasty or coronary artery bypass graft surgery has to be considered, even without an episode of angina or under medically controlled angina. REFERENCES

1. Friedberg CK. Angina pectoris. Circulation 1972;46:103?. 2. Gorlin R. Pathophvsioloav of cardiac vain. Circulation 1965: 32:138. - -3. Conti CR, Feldman RL, Pepine CJ. Coronary artery spasm: prevalence, clinical significance, and provocative testing. AM HEART J 1982;103:584. 4. Epstein SE, Talbot TL. Dynamic coronary tone in precipitation, exacerbation and relief of angina pectoris. Am J Cardiol 1981;48:797. 5. Gorlin R. Role of coronary vasospasm in the pathogenesis of myocardial ischemia and angina pectoris. AM HEART J 1982; 103:598. 6. Geer JC, Crag0 CA, Little WC, Gardner LL, Bishop SP. Subendocardial ischemic myocardial lesions associated with severe coronary atherosclerosis. Am J Cardiol 1980;98:663. 7. Flameng W, Suy R, Schwarz F, Borgers M, Piessens J, Jhones F, Van Ermen H, De Geest H. Ultrastructural correlates of left ventricular contraction abnormalities in patients with chronic ischemic heart disease: determinants of reversible segmental asynergy post revascularization surgery. AM HEART J 1981;102:846. 8. Heupler FA. Provocative testing for coronary arterial spasm: risk, method and rationale. Am J Cardiol 1980:46:335. 9. Son& FM, Shirey EK. Cine coronary arteriography. Mod Concepts Cardiovasc Dis 1962;31:735. 10. Gelberg HJ, Brundage BH, Glantz S, Parmley WW. Quantitative left ventricular wall motion analysis: a comparison of area, chord and radial methods. Circulation 1979;59:991. 11. Markis JE. Joffee CD. Roberts BH. Ransil BJ. Cohn PF. Herman MV, Gorlin R.‘Evolution of left ventricular dysfunction in coronary artery disease. Serial cineangiographic studies without surgery-Circulation 1980;62:141. 12. Braunwald E. Kloner RA. The stunned mvocardium: vrolonged, postischemic ventricular dysfunction. Circula’tion 1982;66:1146. 13. Horn HR, Teichholz LE, Cohn PF, Herman MV, Gorlin R. Augmentation of left ventricular contraction pattern in coronary artery disease by inotropic catecholamine: the epinephrine ventriculogram. Circulation 1974;49:1063. 14. Dyke SH, Cohn RF, Gorlin R, Sonnenblick EH. Detection of residual myocardial function in coronary artery disease using postextrasystolic potentiation. Circulation 1974;50:694. 15. Rozanski A, Berman D, Gray R, Diamond G, Raymond M, Prouse JA, Maddahi J, Swan HJC, Matloff J. Preoperative prediction of reversible myocardial asyneigy .by postexercise radionuclide ventriculoaravhv. N Enal J Med 1982;307:212. 16. Geft IL, Fishbein MC,-Nmomiya KY Hashida J, Chanx E, Yano J, Y-Rit J, Genor T, Shell W, Ganz W. Intermittent brief periods of ischemia have a cumulative effect and may cause myocardial necrosis. Circulation 1982;66:1150. 17. Lange R, Ware J, Kloner RA. Absence of a cumulative deterioration of regional function during three repeated 5 to 15 minute coronary occlusions. Circulation 1984;69:400. 18. Hillis LD, Braunwald E. Coronary-artery spasm. N Engl J Med 1978;299:695. 19. Vather SF. Correlation between acute reduction in myocardial blood flow and function in conscious dogs. Circ Res 1980;47:201.