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Natural History of Left Ventricular Function in Patients With Uncomplicated Acute Myocardial Infarction
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clinical investigations- - - - - - • ....---Natural History of Left Ventricular Function in Patients With Uncomplicated Acute Myocardiallnfarction* Seishi Nakamura, M.D.; Toshiji Iwasaka, M.D., F.C.C.R; Tetsuro Sugiura, M.D., F.C.C.R; Naohiko Ohkubo, M.D.; Hisako Tsuji, M.D.; and Mitsuo Inada, M.D.
To investigate the serial changes of the infarcted and the noninfarcted areas, first-pass radionuclide angiocardiography was performed in 16 patients with uncomplicated anterior myocardial infarction (MI) at four weeks, one year, and two years after the onset of MI. Global ejection fraction (EF) and regional EF of the infarcted area improved significantly from four weeks to one year after MI (from 39 ± 16 to 44 ± 16 percent, 23 ± 3 to 29 ± 5 percent, both p
relation in the direction of the changes of global EF and regional EF of the infarcted area during the first year after MI, whereas no relation was observed between the changes of global EF and regional EF of the noninfarcted area. A greater improvement in regional EF of the infarcted area was observed in seven patients who had spontaneous recanalization compared with nine patients with totally occluded coronary arteries. Thus, a signi6cant improvement in cardiac function, mainly due to the increase in regional EF of the infarcted area, was observed during the first year after MI, which was related to patency of coronary artery. (Chest 1993; 103:1320-24)
T eft ventricular function has been shown to be the
from 27 to 75 years) fulfilled the following criteria: (1) no prior MI; (2) in Killip I at the time of hospital admission; (3) no major complications such as congestive heart failure; post-MI angina, or uncontrolled arrhythmias in the observation period; and (4) cornpleted exercise test (~85 percent of age-predicted maximal heart rate) without ischemic STchange or chest pain. None of the patients had thrombolytic or revascularization therapy in their hospitalization due to delayed arrival (more than 6 h from onset) and/or absence of symptoms and ST changes su~esting ongoin~ ischemia and followup period. The diagnosis of acute MI was made when the following criteria were present: (1) prolonged chest pain consistent with myocardial ischemia: (2) characteristic evolutionary electrocardiographic changes of MI; and (3) elevation of total serum creatinine kinase value with detection of the MB isoenzyme.
L
major determinant of morbidity and mortality after acute myocardial infarction (MI).l Radionuclide angiocardiography is a useful method to evaluate left ventricular function.v' and determines not only global but also regional left ventricular ejection fraction (EF).4-7 Global EF is influenced by abnormalities in both infarcted and noninfarcted regions of the left ventricle. Although several investigators have reported the serial change in left ventricular function after acute MI,8-12 little is known about the long-term evolution of ventricular function that may be dependent on the patency of infarct related coronary artery. Moreover, the wall motion abnormality of the infarcted area seems to have a different course from the noninfarcted area after MI. The purpose of this study was to investigate the serial change of left ventricular global and regional EF for two years after acute MI in patients with uncomplicated anterior MI. METHODS
Patients Among 79 consecutive patients admitted to the hospital with acute Q wave anterior MI, 16 men (mean age of 55 years ranging *From the Second Department of Internal Medicine, Kansai Medical University, Osaka, Japan. Manuscript received July 6; revision accepted October 13. Reprint requests: Dr. Nakamura, CCU, Kansai Medical University, l-Fumizono-cho. Morieuch! City, Osaka 570, ]llpan
1320
Radionuclide Angiocardiography First-pass radionuclide angiocardiography was performed at four weeks, one year, and two years after the onset of M I. In preparation for the procedure, each patient had a short 18-gau~e Teflon catheter placed percutaneously into an external vein. For each radionuclide acquisition, 15 mCi of !J9mTc pertechnetate was injected as a bolus, and counts were recorded at 25-ms intervals with a rnulticrystal gamma camera (Baird Atomic System 77).13-15 After correction for background activity and electric dead tirne, data frorn three to six individual beats were comhined to produce an average of representative cardiac cycle. Left ventricular EF was determined from the background-corrected representative cardiac cycle as follows: (enddiastolic counts rnin us end-systolic counts)/end-diastolic counts X 100. Left ventricular end-diastolic and end-systolic volume were calculated by the area-length method of Dodge and associates," with the ellipse of revolution modified for the single anterior plane projection as 0.85 x A2/L, where A is the area obtained by planimetry, and L is the longest diameter measured from the aortic Natural History of LV Function (Nakamura et al)
non infarcted area was found to be 0 .03, and for differ ences in three observers of measurements 0 .03 . Therefore, the difference in three estimates required to ach ieve 95 percent probability is 0 .07 . Treatment with all medication was discontinued for 24 h before the radionuclide angiograph ic study. None of the pat ients received 13blockers and angiotensin-converting enzyme inhibitors during this study period.
Coronary Arteriography and Left Ventriculography
45 56 48 56 61 43 51 2
58 60
36 44 53 59 59 32 39 49 55 58 30 37 45 51 55 59 34 38 44 51 58 65 33 34 36 39 47 55 65 37 33 34 38 44 53 62 31
38 30 31 35 42 51 59 37 25 27 32 38 47 56 22 27 34 43 FI(;UIIE 1. Upper: Left ventricular r e~ional ejection fraction (REF) image . Lmc cr: Digital display of left ventricular regional ejection fraction image . Crystals within the lined-off area constitute the infarct ed ar ea defined at four weeks and the remainder of the non infarcted area . Left ventricular ejection fraction and REF of infarcte d and noninfarcted area wer e calculated as 37 percent , 29 percent and 53 percent, respectively. valve to the ap ex of th e left ventricle. There was a good correlation between left ventricular end-diastolic volume measured with radionuclide anglocardiogruphy compared with contrast angiography in our laboratory (r = 0.9, 1'<0.01; y = 0 .9 x + 0.01). Regional wall motion was asse ssed with static image s of the end-d iastolic and endsystolic perimeters that were outlined by computer program at the 23 percent isoco unt contour of the end-diastol ic image .":!" In additio n, regional function was evaluate d with a regional EF image that was generated by subtracting end-systolic counts from enddiastol ic counts for each of th e 21 x 14 crystals in th e left ventricular image . Differences in regional function were displayed with a lfi-color cod ed image , each color representing a 6.25 percent d ifference in th e EF. Ik·" From this left ventricular region al EF image, wall motion was subjectively cate gorized as normal, hypokinetic, akinetic, or d yskinetic by three experienced observers. Akinetic and dyskinetic zon es were defined as infarcted areas, and the remaining categories wer e defined as noninfarcted areas at filllr weeks afte r MI. Th e same areas th at were defined as infarcted and noninfarcted at four weeks were used to calculate th e mean regional EF at one and two years after on set of MI (Fif.( 1). We have m easured th e precision of the method by assessment of th e same data by three observers blinded with respect to prior values . The standard dev iation for a smgle measurement of left ventricular regional EF of infarcted and
Diagnostic coronary arteriography was performed within three days of first radionuclide angiographie study, and ~75 percent reduction of luminal diameter was considered to be signiflcuntly obstructed . After measuring left ventricular end-diastolic pressure, contrast ventriculography was performed in th e 30° right anterior oblique projection lind recorded at 50 or 60 frames per second.a.. The end-diastolic and end-systolic endocardial contours were projected and traced from the frames with maximal and minimal volumes, from a norm al, nonpostprernature sinus heat. Wall motion was measured by the centerline method along 100 chords eon structed perpendicular to a centerline drawn midway between the end-diastolic and end-systolic contours and nor malized by the enddiastolic perimeter. The circumferential extent of akin esi s and dyskin esis was calculated as the number of chords with absolute motion of 0 or less.
Statistical Analysis Results are reported as the mean ± SD . Two-way layout analysis of variance was used for quantitative data . A p value below 0.05 was considered signlficant. RESULTS
Serial Changes in Global EF and Left Ventricular End-Diastolic and End-Systolic Volume Changes in global EF, left ventricular end-diastolic, and end-systolic volume are shown in Table 1. Global EF improved significantly from four weeks to one year after MI, but global EF did not change significantly from one year to two years after MI. Left ventricular end-diastolic and end-systolic volume did not change during the study period (four weeks, one year, and two years).
Serial Changes in Regional EF of the Infarcted and the Noninfarcted Area Regional EF of the infarcted area increased significantly from four weeks to one year (p
I' Value
EF EDV ESV
4w
IY
2Y
4w vs IY
IY vs 2Y
39±I6 I62±5I 101 ±55
44±I6 164±42 94±48
44± 16 168±52 97±54
< 0.01 NS NS
NS NS NS
*EDV = left ventricular end-diastolic volume (ml); EF = left ventricular ejection fraction (percent); ESV = left ventricular endsystolic volume (rnl) : NS = not signtfican t : 4w = four we eks; 1Y = one year ; 2Y = two years . CHEST I 103 I 5 I MAY, 1993
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Table I-Changes in Regional Ejection Fraction of the lnfiwcted and the Noninfarcted Area·
~
"'"
I
p Value
IREF NREF
4w
lY
2Y
4w vs 1Y
1Y vs 2Y
23±3 57±10
29±5 58±10
29±6 59±10
<0.001
NS NS
NS
farcted area did not change during the study period (four weeks, one year, and two years). Relationship Between Changes in Global EF and Regional EF
There was a significant relation in the direction of the changes of global EF and regional EF of the infarcted area during the first year after MI, whereas there was no significant relation between changes of global EF and regional EF of the noninfarcted area in the same period (Figs 2 and 3). Coronary Arteriography and left Ventriculography
All patients had single-vessel coronary disease in the left anterior descending coronary artery (Table 3). Nine patients had totally occluded left anterior descending coronary arteries, but seven patients had less than 75 percent reduction of luminal diameter. There were no significant differences in the circumferential extent of akinesis and dyskinesis (15± 15 vs 11 + 14 chords), left ventricular end-diastolic pressure (18 ± 4 vs 17±2 mm Hg), and global EF (36±17 vs 41±17 20 ~
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20
n = 16 NS
-10
Change in Global EF (,,)
3. Relationship between changes in global and regional ejection fraction (EF) of the nonfarcted area from four weeks to one year after myocardial infarction. There was no relation in the direction of the changes of global and regional EF of the noninfarcted area during the first year after myocardial infarction. FIGURE
percent) between patients with totally occluded and with partially patent arteries. When the changes in global and regional EF were compared between patients with totally occluded and partially patent coronary arteries, patients with partially patent coronary arteries had greater improvement in global and regional EF of infarcted area from four weeks to one year compared with those patients with totally occluded arteries. On the other hand, there was no significant difference in the change of regional EF of the noninfarcted area between the two groups. There were no significant differences in the changes of regional and global EF between the two groups from one to two years.
Patent (n=7)
20
n = 16
r =0.78
p< 0.01
-10
Change in Global EF (,,) FIGURE 2. Relationship between changes in global and regional ejection fraction (EF) of the infarcted area from four weeks to one year after myocardial infarction. There was a significant relation in the direction of the changes of global and regional EF of the infarcted area during the first year after myocardial infarction.
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5
Table 3-Diffenmca in Global and Regional Ejection Fraction Between PatientB With PartitJlly Patent and Totally Occluded Coronary Arteries·
• •
- 5
,.1 '0
Previous studies demonstrated radionuclide angio-
•
10
10
DISCUSSION
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10
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15
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15
t
*IREF = regional ejection fraction of the infarcted area (percent); NREF =regional ejection fraction of the noninfarcted area (percent); other abbreviations as in Table 1.
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20
~
aEF
MREF aNREF aEF
MREF aNREF
Occluded (n=9)
4 wk to 1 yr 8.9±3.7 1.4±6.4 6.2± 1.7 3.7± 1.6 0.5 ± 1.2 0.4 ± 1.4 1 yr to 2 yr -2.8±2.0 1.1±5.0 -3.1±2.2 2.1±2.5 0.2 ± 2.3 1.3 ± 1.6
p Value
<0.05 <0.05
NS
NS NS NS
*aEF = change in left ventricular ejection fraction; dIREF = change in regional ejection fraction of the infarcted area; aNREF =change
in regional ejection fraction of the noninfarcted area. Other abbreviations as in Tables 1 and 2. NaturalHistoryof LV Function (Nakamura st aJ)
cardiography permitted accurate and reproducible determinations of left ventricular EF in patients with coronary artery disease with and without regional left ventricular dysfunction.vl-? Serial changes of ventricular function after acute MI have been reported by many investigators to provide the important prognostic information.v'" The changes in left ventricular function during the follow-up period depend on several factors such as the effect of thrombolytic therapy," EF soon after the onset of MI, and the severity of complications in the late hospital phase. Schelbert and associates" reported the improvement in left ventricular EF in 55 percent of patients from 2 to 39 months after the onset of acute MI and indicated that left ventricular performance in patients without persistent cardiomegaly can improve during long-term follow-up. Borer and colleagues'? reported that the normal exercise response in the radionuclide study at the time of hospital predicted the capacity for improvement of global EF during the year after acute MI. Although global EF is influenced by the motion of the infarcted and the noninfarcted regions of the left ventricle, the functional changes of the noninfarcted and infarcted regions were not investigated in these studies. In our selected patients, there was a significant improvement in global left ventricular EF from four weeks to one year after MI that was mainly due to the recovery of the regional EF in the infarcted area, but both global and regional EF did not improve from one to two years during the follow-up period. In a canine study, Preuss et al22 showed that left ventricular function in the border zone could require up to several weeks to return to normal after a 2-h period of occlusion. In a clinical study, Stack and colleagues" reported a significant improvement in the regional wall motion abnormalities 16 days after reperfusion in patients with acute MI. From these studies, the delayed functional recovery after reperfusion is attributed to the ischemia-induced disruption of metabolic process, and this phenomenon depends on the duration of ischemia. 22-24 Although there were no differences in the extent of akinesis and dyskinesis, left ventricular end-diastolic pressure, and global EF at four weeks, a greater improvement in regional EF of the infarcted area was observed in 7 of 16 patients who had spontaneous recanalization compared with those with totally occluded coronary arteries. This indicates that patency of a coronary artery plays an important role for the improvement of EF in the infarcted area. Recent evidence suggests that the tensile strength of unperfused and reperfused infarct scars is different, and that reperfusion prevents the process of myocyte slippage and infarct thinning during the healing stage. 25 These histologic differences could cause the differences in the healing process of the infarcted area.
On the other hand, there was no significant change in the regional EF of the noninfarcted area for four weeks to two years. The dilatation of the left ventricle after MI, "left ventricular remodeling," causes changes in both the infarcted (infarct expansion) and the noninfarcted region (volume-overload hypertrophy).26.27 The remodeling process is a compensatory mechanism aiming to restore a reduced stroke volume, and the magnitude of these remodeling changes is inversely related to increased wall stress due to decreased left ventricular pump function." Although Pfeffer et al29 have shown remodeling in a population of patients with lower left ventricular EF of30 percent by radionuclide angiocardiography, considering our sample of patients (no clinical heart failure, negative exercise test), it is not surprising to find no increase in left ventricular end-diastolic and end-systolic volumes, because MI in our patients was not large enough to cause significant ventricular remodeling and hence, regional EF of the noninfarcted area was maintained during the second year after MI. Limitation Two limitations of our study should be addressed. First, serial left ventriculography was not performed because our patients did not have thrombolytic interventions and were free of complications during the follow-up period. Nevertheless, our results provide the information about natural history of left ventricular function by a noninvasive tool. Second, as the patient population in this study was a highly selected group with a small sample size who had good EF, negative stress test, and single-vessel disease, another population with larger infarct size is necessary to evaluate that our conclusion about the time course of global and regional left ventricular function can be generalized to these patients. CONCLUSION
The recovery of left ventricular function could occur in the infarcted area within one year after the onset of MI, which was related to patency of the coronary artery. REFERENCES
1 Weber KTt Ratshin RAt Janicki TS t Rackley CE t Russell RO. Left ventricular dysfunction following acute myocardial infarction. Am J Med 1973; 54:697-705 2 Marshall RC t Berger 8Ft Reduto LA t Gottschalk At Zaret BL. Variability in sequential measures of left: ventricular performance assessed with radionuclide angiocardiography. Am J Cardiol 1978; 41:531-36 3 Marshall RC t Berger HJt Costin JC t Freedman GS t Wolberg It Cohen LS t et aI. Assessment of cardiac performance with quantitative radionuclide angiocardiography: sequential left: ventricular ejection fraction, normalized left ventricular ejection rate t and regional wall motion. Circulation 1977; 56:820-24 4 Borer JSt Bacharach SL t Green M~ Kent KM t Ebstein SEt CHEST I 103 I 5 I MA'f, 1993
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Johnston GS. Real-time radionuclide cineangiography in the noninvasive evaluation of global and regional left ventricular function at rest and during exercise in patients with coronaryartery disease. N Engl J Moo 1977; 296:839-44 5 Maddox DE, Holman BL, Wynne J, Parker JA, Cohn PF. Ejection fraction image: a noninvasive index of regional left ventricular wall motion. Am J Cardioll978; 41:1230-38 6 Maddox DE, Wynne J, Uren R, Parker JA, Idoine J, Siegel LC, et ale Regional ejection fraction: a quantitative radionuclide index of regional left ventricular performance. Circulation 1979; 59:1001-09 7 Wynne J, Sayres M, Maddox DE, Idoine J, Alpert JS, Neill J, et ale Regional left ventricular function in acute myocardial infarction: evaluation with quantitative radionuclide ventriculography. Am J Cardioll980; 45:203-09 8 Schelbelt HR, Henning H, Ashburn WL, Verba ~ Karliner JS, O'Rourke RA. Serial measurements of left ventricular ejection fraction by radionuclide angiography early and late after myocardial infarction. Am J Cardio11976; 38:407-15 9 Reduto LA, Berger HJ, Cohen LS, Gottschalk A, Zaret BL. Sequential radionuclide assessment of left and right ventricular performance after acute transmural myocardial infarction. Ann Intern Med 1978; 89:441-47 10 Borer JS, Rosing DR, Miller RH. Natural history of left ventricular function during one year after acute myocardial infarction: comparison with clinical, electrocardiographic and biochemical determinations. Am J Cardiol198O; 46: 1-12 11 Silberberg J, Haiehin R, Stewart S, Lisbona R, Sniderman A. Long-term stepwise sustained improvement in left ventricular ejection fraction after myocardial infarction. Am Heart J 1989; 117:532-37 12 Nemerovaski M, Shah PK, Pichler M, Berman DS, Shellock F, Swan HJC. Radionuclide assessment of sequential changes in left and right ventricular function following first acute transmural myocardial infarction. Am Heart J 1982; 104:709-17 13 Jones RH, McEwan ~ Newman GE, Port S, Rerych SK, Sholtz PM, et ale Accuracy of diagnosis of coronary artery disease by radionuclide measurement of left ventricular function during rest and exercise. Circulation 1981; 64:586-601 14 Schelbelt HR, Verba.JW: Ashburn WL, Johnson AD, Brock G~ Alazraki N~ et ale Nontraumatic determination of left ventricular ejection fraction by radionuclide angiography. Circulation 1975; 51:902-09 15 Upton MT, Rerych SK, Newman E~ Bounous EP Jr, Jones RH. The reproducibility of radionuclide angiocardiographic measurements of left ventricular infarction in normal subjects at rest and during exercise. Circulation 1980; 62:126-32 16 Dodge HT, Sandler H, Ballow D~ Lord JD Jr. The use of biplane angiocardiography for the measurement of left ventricular volume in man. Am Heart J 1960; 60:762-76 17 Matsumoto K, Natsuzami S, Shiraishi L Examination of left
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20
21
22
23
24
25
26
27
28
29
ventricular volume with spheroid phantom. Jpn J Nucl Med 1983; 20:549 Takahashi N, Iwasaka T, Sugiura T, Hasegawa T, Tarumi N, Kimura Y, et ale Left ventricular regional function after acute myocardial infarction in diabetic patients. Diabetes Care 1989; 12:630-35 Kimura Y, Iwasaka T, Onoyama H, Sugiura T, Ichibangase J, Koito H, et ale Assessment of cardiac performance by radionuelide angiocardiography in the patients with myocardial infarction: comparison between infarcted area and noninfarcted area. Jpn J Nucl Med 1987; 24:1775-83 Sheehan FH, Bolson EL, Dodge HT, Mathey DG, Schofer J, Woo HW Advantages and applications of the centerline method for characterizing regional ventricular function. Circulation 1986; 74:293-305 Schmidt WG, Sheehan FH, Essen R, Uebis R, Effert S. Evolution of left ventricular function after intracoronary thrombolysis for acute myocardial infarction. Am J Cardiol 1989; 63:497-502 Preuss KC, Gross GJ, Brooks HL, Warltier DC. Time course of recovery of"stunned' myocardium following variable episodes of ischemia in conscious and anesthetized dogs. Am Heart J 1987; 114: 696-703 Stack RS, Phillips HR, Grierson DS, Behar VS, Kong Y, Peter RH, et ale Functional improvement of jeopardized myocardium following streptokinase infusion in acute myocardial infarction. J Clin Invest 1983; 72:84-95 Ellis SG, Henschke CI, Sandor T, Wynne J, Braunwald E, Kloner RA. Tune course of functional and biochemical recovery of myocardium salvaged by reperfusion. J Am ColI Cardioll983; 1:1047-55 Connelly eM, VogelWM, Wiegner AW, Osmers EL, Bing OHL, Kloner RA, et a1. Effects of reperfusion after coronary artery occlusion on post-infarction scar tissue. Circ Res 1985; 57:56277 Rigo ~ Murray M, Strauss HW, Tayler D, Kelly D, Weisfeldt ML, et ale Left ventricular function in acute myocardial infarction evaluated by gated scintigraphy. Circulation 1974; 50:67884 Erlebacher JA, Weiss JL, Weisfeldt ML, Bulkley BH. Early dilatation of the infarcted segment in acute transmural myocardial infarction: role of infarct expansion in acute left ventricular enlargement. J Am Coil Cardioll984; 4:201-08 McKay RG, Pfeffer MA, Pastennak RC, Markis JE, Come PC, Nakao S, et ale Left ventricular remodeling after myocardial infarction: a corollary to infarct expansion. Circulation 1986; 74:639-702 Pfeffer MA, Lamas GA, Vaugham DE, Parisi AF, Brawnwald E. Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med 1988; 319:80-6
NaturalHistory of LVFunction (Nakamura at aI)
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~~II
clinical investigations- - - - - - • ....---Natural History of Left Ventricular Function in Patients With Uncomplicated Acute Myocardiallnfarction* Seishi Nakamura, M.D.; Toshiji Iwasaka, M.D., F.C.C.R; Tetsuro Sugiura, M.D., F.C.C.R; Naohiko Ohkubo, M.D.; Hisako Tsuji, M.D.; and Mitsuo Inada, M.D.
To investigate the serial changes of the infarcted and the noninfarcted areas, first-pass radionuclide angiocardiography was performed in 16 patients with uncomplicated anterior myocardial infarction (MI) at four weeks, one year, and two years after the onset of MI. Global ejection fraction (EF) and regional EF of the infarcted area improved significantly from four weeks to one year after MI (from 39 ± 16 to 44 ± 16 percent, 23 ± 3 to 29 ± 5 percent, both p
relation in the direction of the changes of global EF and regional EF of the infarcted area during the first year after MI, whereas no relation was observed between the changes of global EF and regional EF of the noninfarcted area. A greater improvement in regional EF of the infarcted area was observed in seven patients who had spontaneous recanalization compared with nine patients with totally occluded coronary arteries. Thus, a signi6cant improvement in cardiac function, mainly due to the increase in regional EF of the infarcted area, was observed during the first year after MI, which was related to patency of coronary artery. (Chest 1993; 103:1320-24)
T eft ventricular function has been shown to be the
from 27 to 75 years) fulfilled the following criteria: (1) no prior MI; (2) in Killip I at the time of hospital admission; (3) no major complications such as congestive heart failure; post-MI angina, or uncontrolled arrhythmias in the observation period; and (4) cornpleted exercise test (~85 percent of age-predicted maximal heart rate) without ischemic STchange or chest pain. None of the patients had thrombolytic or revascularization therapy in their hospitalization due to delayed arrival (more than 6 h from onset) and/or absence of symptoms and ST changes su~esting ongoin~ ischemia and followup period. The diagnosis of acute MI was made when the following criteria were present: (1) prolonged chest pain consistent with myocardial ischemia: (2) characteristic evolutionary electrocardiographic changes of MI; and (3) elevation of total serum creatinine kinase value with detection of the MB isoenzyme.
L
major determinant of morbidity and mortality after acute myocardial infarction (MI).l Radionuclide angiocardiography is a useful method to evaluate left ventricular function.v' and determines not only global but also regional left ventricular ejection fraction (EF).4-7 Global EF is influenced by abnormalities in both infarcted and noninfarcted regions of the left ventricle. Although several investigators have reported the serial change in left ventricular function after acute MI,8-12 little is known about the long-term evolution of ventricular function that may be dependent on the patency of infarct related coronary artery. Moreover, the wall motion abnormality of the infarcted area seems to have a different course from the noninfarcted area after MI. The purpose of this study was to investigate the serial change of left ventricular global and regional EF for two years after acute MI in patients with uncomplicated anterior MI. METHODS
Patients Among 79 consecutive patients admitted to the hospital with acute Q wave anterior MI, 16 men (mean age of 55 years ranging *From the Second Department of Internal Medicine, Kansai Medical University, Osaka, Japan. Manuscript received July 6; revision accepted October 13. Reprint requests: Dr. Nakamura, CCU, Kansai Medical University, l-Fumizono-cho. Morieuch! City, Osaka 570, ]llpan
1320
Radionuclide Angiocardiography First-pass radionuclide angiocardiography was performed at four weeks, one year, and two years after the onset of M I. In preparation for the procedure, each patient had a short 18-gau~e Teflon catheter placed percutaneously into an external vein. For each radionuclide acquisition, 15 mCi of !J9mTc pertechnetate was injected as a bolus, and counts were recorded at 25-ms intervals with a rnulticrystal gamma camera (Baird Atomic System 77).13-15 After correction for background activity and electric dead tirne, data frorn three to six individual beats were comhined to produce an average of representative cardiac cycle. Left ventricular EF was determined from the background-corrected representative cardiac cycle as follows: (enddiastolic counts rnin us end-systolic counts)/end-diastolic counts X 100. Left ventricular end-diastolic and end-systolic volume were calculated by the area-length method of Dodge and associates," with the ellipse of revolution modified for the single anterior plane projection as 0.85 x A2/L, where A is the area obtained by planimetry, and L is the longest diameter measured from the aortic Natural History of LV Function (Nakamura et al)
non infarcted area was found to be 0 .03, and for differ ences in three observers of measurements 0 .03 . Therefore, the difference in three estimates required to ach ieve 95 percent probability is 0 .07 . Treatment with all medication was discontinued for 24 h before the radionuclide angiograph ic study. None of the pat ients received 13blockers and angiotensin-converting enzyme inhibitors during this study period.
Coronary Arteriography and Left Ventriculography
45 56 48 56 61 43 51 2
58 60
36 44 53 59 59 32 39 49 55 58 30 37 45 51 55 59 34 38 44 51 58 65 33 34 36 39 47 55 65 37 33 34 38 44 53 62 31
38 30 31 35 42 51 59 37 25 27 32 38 47 56 22 27 34 43 FI(;UIIE 1. Upper: Left ventricular r e~ional ejection fraction (REF) image . Lmc cr: Digital display of left ventricular regional ejection fraction image . Crystals within the lined-off area constitute the infarct ed ar ea defined at four weeks and the remainder of the non infarcted area . Left ventricular ejection fraction and REF of infarcte d and noninfarcted area wer e calculated as 37 percent , 29 percent and 53 percent, respectively. valve to the ap ex of th e left ventricle. There was a good correlation between left ventricular end-diastolic volume measured with radionuclide anglocardiogruphy compared with contrast angiography in our laboratory (r = 0.9, 1'<0.01; y = 0 .9 x + 0.01). Regional wall motion was asse ssed with static image s of the end-d iastolic and endsystolic perimeters that were outlined by computer program at the 23 percent isoco unt contour of the end-diastol ic image .":!" In additio n, regional function was evaluate d with a regional EF image that was generated by subtracting end-systolic counts from enddiastol ic counts for each of th e 21 x 14 crystals in th e left ventricular image . Differences in regional function were displayed with a lfi-color cod ed image , each color representing a 6.25 percent d ifference in th e EF. Ik·" From this left ventricular region al EF image, wall motion was subjectively cate gorized as normal, hypokinetic, akinetic, or d yskinetic by three experienced observers. Akinetic and dyskinetic zon es were defined as infarcted areas, and the remaining categories wer e defined as noninfarcted areas at filllr weeks afte r MI. Th e same areas th at were defined as infarcted and noninfarcted at four weeks were used to calculate th e mean regional EF at one and two years after on set of MI (Fif.( 1). We have m easured th e precision of the method by assessment of th e same data by three observers blinded with respect to prior values . The standard dev iation for a smgle measurement of left ventricular regional EF of infarcted and
Diagnostic coronary arteriography was performed within three days of first radionuclide angiographie study, and ~75 percent reduction of luminal diameter was considered to be signiflcuntly obstructed . After measuring left ventricular end-diastolic pressure, contrast ventriculography was performed in th e 30° right anterior oblique projection lind recorded at 50 or 60 frames per second.a.. The end-diastolic and end-systolic endocardial contours were projected and traced from the frames with maximal and minimal volumes, from a norm al, nonpostprernature sinus heat. Wall motion was measured by the centerline method along 100 chords eon structed perpendicular to a centerline drawn midway between the end-diastolic and end-systolic contours and nor malized by the enddiastolic perimeter. The circumferential extent of akin esi s and dyskin esis was calculated as the number of chords with absolute motion of 0 or less.
Statistical Analysis Results are reported as the mean ± SD . Two-way layout analysis of variance was used for quantitative data . A p value below 0.05 was considered signlficant. RESULTS
Serial Changes in Global EF and Left Ventricular End-Diastolic and End-Systolic Volume Changes in global EF, left ventricular end-diastolic, and end-systolic volume are shown in Table 1. Global EF improved significantly from four weeks to one year after MI, but global EF did not change significantly from one year to two years after MI. Left ventricular end-diastolic and end-systolic volume did not change during the study period (four weeks, one year, and two years).
Serial Changes in Regional EF of the Infarcted and the Noninfarcted Area Regional EF of the infarcted area increased significantly from four weeks to one year (p
I' Value
EF EDV ESV
4w
IY
2Y
4w vs IY
IY vs 2Y
39±I6 I62±5I 101 ±55
44±I6 164±42 94±48
44± 16 168±52 97±54
< 0.01 NS NS
NS NS NS
*EDV = left ventricular end-diastolic volume (ml); EF = left ventricular ejection fraction (percent); ESV = left ventricular endsystolic volume (rnl) : NS = not signtfican t : 4w = four we eks; 1Y = one year ; 2Y = two years . CHEST I 103 I 5 I MAY, 1993
1321
Table I-Changes in Regional Ejection Fraction of the lnfiwcted and the Noninfarcted Area·
~
"'"
I
p Value
IREF NREF
4w
lY
2Y
4w vs 1Y
1Y vs 2Y
23±3 57±10
29±5 58±10
29±6 59±10
<0.001
NS NS
NS
farcted area did not change during the study period (four weeks, one year, and two years). Relationship Between Changes in Global EF and Regional EF
There was a significant relation in the direction of the changes of global EF and regional EF of the infarcted area during the first year after MI, whereas there was no significant relation between changes of global EF and regional EF of the noninfarcted area in the same period (Figs 2 and 3). Coronary Arteriography and left Ventriculography
All patients had single-vessel coronary disease in the left anterior descending coronary artery (Table 3). Nine patients had totally occluded left anterior descending coronary arteries, but seven patients had less than 75 percent reduction of luminal diameter. There were no significant differences in the circumferential extent of akinesis and dyskinesis (15± 15 vs 11 + 14 chords), left ventricular end-diastolic pressure (18 ± 4 vs 17±2 mm Hg), and global EF (36±17 vs 41±17 20 ~
~
I
J
•
,
5
Ib
J .Iii
• -10
-5
• •
• • 0
5
15
•
Ib
•Iii
!
o
-5
-10
•
• ••
• • 5
•• • 10
- 5
•
•
• 15
20
n = 16 NS
-10
Change in Global EF (,,)
3. Relationship between changes in global and regional ejection fraction (EF) of the nonfarcted area from four weeks to one year after myocardial infarction. There was no relation in the direction of the changes of global and regional EF of the noninfarcted area during the first year after myocardial infarction. FIGURE
percent) between patients with totally occluded and with partially patent arteries. When the changes in global and regional EF were compared between patients with totally occluded and partially patent coronary arteries, patients with partially patent coronary arteries had greater improvement in global and regional EF of infarcted area from four weeks to one year compared with those patients with totally occluded arteries. On the other hand, there was no significant difference in the change of regional EF of the noninfarcted area between the two groups. There were no significant differences in the changes of regional and global EF between the two groups from one to two years.
Patent (n=7)
20
n = 16
r =0.78
p< 0.01
-10
Change in Global EF (,,) FIGURE 2. Relationship between changes in global and regional ejection fraction (EF) of the infarcted area from four weeks to one year after myocardial infarction. There was a significant relation in the direction of the changes of global and regional EF of the infarcted area during the first year after myocardial infarction.
1322
5
Table 3-Diffenmca in Global and Regional Ejection Fraction Between PatientB With PartitJlly Patent and Totally Occluded Coronary Arteries·
• •
- 5
,.1 '0
Previous studies demonstrated radionuclide angio-
•
10
10
DISCUSSION
•
••
10
.s '0
J
•
15
Ii
15
t
*IREF = regional ejection fraction of the infarcted area (percent); NREF =regional ejection fraction of the noninfarcted area (percent); other abbreviations as in Table 1.
"'"
20
~
aEF
MREF aNREF aEF
MREF aNREF
Occluded (n=9)
4 wk to 1 yr 8.9±3.7 1.4±6.4 6.2± 1.7 3.7± 1.6 0.5 ± 1.2 0.4 ± 1.4 1 yr to 2 yr -2.8±2.0 1.1±5.0 -3.1±2.2 2.1±2.5 0.2 ± 2.3 1.3 ± 1.6
p Value
<0.05 <0.05
NS
NS NS NS
*aEF = change in left ventricular ejection fraction; dIREF = change in regional ejection fraction of the infarcted area; aNREF =change
in regional ejection fraction of the noninfarcted area. Other abbreviations as in Tables 1 and 2. NaturalHistoryof LV Function (Nakamura st aJ)
cardiography permitted accurate and reproducible determinations of left ventricular EF in patients with coronary artery disease with and without regional left ventricular dysfunction.vl-? Serial changes of ventricular function after acute MI have been reported by many investigators to provide the important prognostic information.v'" The changes in left ventricular function during the follow-up period depend on several factors such as the effect of thrombolytic therapy," EF soon after the onset of MI, and the severity of complications in the late hospital phase. Schelbert and associates" reported the improvement in left ventricular EF in 55 percent of patients from 2 to 39 months after the onset of acute MI and indicated that left ventricular performance in patients without persistent cardiomegaly can improve during long-term follow-up. Borer and colleagues'? reported that the normal exercise response in the radionuclide study at the time of hospital predicted the capacity for improvement of global EF during the year after acute MI. Although global EF is influenced by the motion of the infarcted and the noninfarcted regions of the left ventricle, the functional changes of the noninfarcted and infarcted regions were not investigated in these studies. In our selected patients, there was a significant improvement in global left ventricular EF from four weeks to one year after MI that was mainly due to the recovery of the regional EF in the infarcted area, but both global and regional EF did not improve from one to two years during the follow-up period. In a canine study, Preuss et al22 showed that left ventricular function in the border zone could require up to several weeks to return to normal after a 2-h period of occlusion. In a clinical study, Stack and colleagues" reported a significant improvement in the regional wall motion abnormalities 16 days after reperfusion in patients with acute MI. From these studies, the delayed functional recovery after reperfusion is attributed to the ischemia-induced disruption of metabolic process, and this phenomenon depends on the duration of ischemia. 22-24 Although there were no differences in the extent of akinesis and dyskinesis, left ventricular end-diastolic pressure, and global EF at four weeks, a greater improvement in regional EF of the infarcted area was observed in 7 of 16 patients who had spontaneous recanalization compared with those with totally occluded coronary arteries. This indicates that patency of a coronary artery plays an important role for the improvement of EF in the infarcted area. Recent evidence suggests that the tensile strength of unperfused and reperfused infarct scars is different, and that reperfusion prevents the process of myocyte slippage and infarct thinning during the healing stage. 25 These histologic differences could cause the differences in the healing process of the infarcted area.
On the other hand, there was no significant change in the regional EF of the noninfarcted area for four weeks to two years. The dilatation of the left ventricle after MI, "left ventricular remodeling," causes changes in both the infarcted (infarct expansion) and the noninfarcted region (volume-overload hypertrophy).26.27 The remodeling process is a compensatory mechanism aiming to restore a reduced stroke volume, and the magnitude of these remodeling changes is inversely related to increased wall stress due to decreased left ventricular pump function." Although Pfeffer et al29 have shown remodeling in a population of patients with lower left ventricular EF of30 percent by radionuclide angiocardiography, considering our sample of patients (no clinical heart failure, negative exercise test), it is not surprising to find no increase in left ventricular end-diastolic and end-systolic volumes, because MI in our patients was not large enough to cause significant ventricular remodeling and hence, regional EF of the noninfarcted area was maintained during the second year after MI. Limitation Two limitations of our study should be addressed. First, serial left ventriculography was not performed because our patients did not have thrombolytic interventions and were free of complications during the follow-up period. Nevertheless, our results provide the information about natural history of left ventricular function by a noninvasive tool. Second, as the patient population in this study was a highly selected group with a small sample size who had good EF, negative stress test, and single-vessel disease, another population with larger infarct size is necessary to evaluate that our conclusion about the time course of global and regional left ventricular function can be generalized to these patients. CONCLUSION
The recovery of left ventricular function could occur in the infarcted area within one year after the onset of MI, which was related to patency of the coronary artery. REFERENCES
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NaturalHistory of LVFunction (Nakamura at aI)