Late streptokinase infusion and antithrombotic treatment in myocardial infarction reduce subsequent myocardial ischemia

Volume

121

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3, Part

1

plasty in patients with unstable angina pectoris: is there a role f’or thrombolysis? .I Am Coil Cardiol 1988;lZ(suppl A):69A77.4 :N. T~pol Ed, Califf RM, George HS. et al. A randomized trial of immediate versus delayed elective angioplasty after intravenous tissue plasminogen activator in acute myocardial infarction. Ii Engl .I Med 1987::317:5til-8.

:39. Simoons ML. Arnold AER, Betriu A, et al. ‘I’hromholysis with rt-PA in acute myocardiat infarction: no beneficial effects of immediate P’I’CA. Lancet 1988;1:197-?(l:i. 40. TIM1 Research Group. Immediate \‘erhus delayed cathetertherap,v f’~,r ization and anyioplasty followin g thromholgt.ic acute my~cardial inf’arct.ion. .JAMA lSXX:~ti0:~X-lit-58,

Late streptokinase infusion and antithrombotic treatment in myocardial infarction reduce subsequent myocardial ischemia Of 255 consecutive patients with acute myocardial infarction, 111 were eligible for attempted late thrombolysis. They were randomly assigned to either thrombolytic and antithrombotic treatment (treatment group) or routine treatment (control group). Patients in the treatment group received streptokinase initiated late (mean 32 hours; range 12 to 49) after the onset of symptoms, followed by heparin infusion for at least 5 days and warfarin and dipyridamole for at least 3 months. Patients were examined clinically and by bicycle ergometry on discharge from the hospital and after 3 and 12 months. The two groups did not differ with respect to deaths or reinfarctions. There was a trend toward a lower incidence of angina pectoris in the treatment group. Exercise tolerance in this group was significantly higher than in the control group (at 3 months 124 t 39 W vs 107 ? 41 W; p < 0.05). The difference was entirely accounted for by patients with no previous history of infarction or angina pectoris (at 3 months 142 ? 37 W vs 112 ? 45 W; p = 0.01). ECG signs of myocardial ischemia, silent or symptomatic, occurred at significantly lower levels of exercise among patients in the control group compared with patients in the treatment group. The results support the notion that thrombolytic therapy given as late as 12 to 49 hours after the onset of symptoms may reduce the incidence of residual ischemia during the postinfarction period. (AM HEART J 1991;121:737.)

Lars Grip, MD, and Lars Ryden,

MD, PhD. Stochholm,

It is well established that early thrombolysis reduces the number of in-hospital deaths resulting from myocardial infarction. There is a general consensus that thrombolytic treatment is effective if given within the first 4 to 6 hours after the onset of symptoms suggestive of myocardial infarcti0n.l This is based on the theory that a decrease in infarct size is reponsible for the lower mortality and that the infarction Frclm the Divisi~ln 01’Cardic~luyy. Ikpartment ot Internal Medicine, liar,,linska H~spiial. Supported hy grants from the Swedish Heart and Lung Foundaticm and the Vlaes (;roshinsky Foundation, Stockholm. Sweden. Kecei\ed t;~r publication July 16, 1990; accepted Sept. 1. 1990. &print requests Lars Grip, MD, Division of Cardi&)gy. Department ot Internal Merdicinr, Karolinska Hospital, S-104 01 Stockholm. Sweden. 511126480

Sweden

process usually is completed within 6 hours after coronary artery occlusion. Results of several studies call this theory into question. A decrease in mortality has also been achieved in studies in which thrombolysis was instituted fairly late. ‘3~ For instance, the results of the recent ISIS-2 trial4 favor effective therapy up to 24 hours after the onset of symptoms. Accordingly the time span within which thrombolysis may be effective is less well defined. Results of intracoronary thrombolysis in a small group of patients indicate the possibility of reestablishing antegrade Aow in the infarct-related artery, favorably affecting postinfarction angina even days after the infarct.5 The aim of this study was to investigate the effects of thrombolysis with streptokinase 12 to 48 hours after the onset 737

March

738

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Rydkn

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anticoagulants or antlplatelets SK-contraindications Dlagnosls establrshed ,’ 48 hours Other admtnlstratlve reasons Death before randomlzatlon

Heart

1991 Journal

On

L-l Eilglble 111

/

Fig.

1.

treatment

I. Baseline

Table

Randomization group.

characteristics

\

scheme showing

reasons for exclusion

9 26 9

from study. SK, streptokinase;

SK-group,

at randomization Control group

Characteristics Age (mean 2 SD) Sex (M/F) Previous history Myocardial infarction Hypertension Diabetes Claudication Effort angina Smoking Previous therapy $-blockers Ca++ antagonists Location of index infarct Q anterior Q inferior NON-Q

Maximum CK (Fkat/L) Admission status Systolic blood pressure (mm Hg) Heart rate (beats/min) Coronary care unit course Left-heart failure Hypotension (blood pressure <90 mm Hg) NS, Not

32 68

(n = 57)

Treatment group (n = 54)

63 LIZ 9 40117

60 + 9 44/10

17 (30°C’)

NS NS

25 (44’, ) 24 142”;m)

12 14 7 6 21 “5

) ) ) ) ) )

NS NS NS NS NS NS

15 (26”, 9 (16”;

) )

12 (32°C ) 6 (ll”, )

NS NS

14 (24°C ) 17 (30”; ) 26 (46 (‘Cl)

12 (22’, ) 15 (28°C ) 27 (5O’f )

NS NS NS

.32 It 2.5

29 + 23

NS

149 i- “6 66 z!z 14

157 i 31 70 + 16

NS NY

16 128’1s 1 8 (14rc,)

16 (30’rm) 5 (9°C 1

NS NS

“1 (37f’c )

5 (9”,8) 3 (51, )

(22’,’ (26”~ (13°C (ll’, (39’r (46’~

Zliffprrnce

significant.

of symptoms, followed by antithrombotic treatment, on residual ischemia after myocardial infarction. METHODS Patients. From February 1985 to August 1986, patients admitted to the coronary care unit of Karolinska Hospital (serving a population of 160,000) within 48 hours after the onset of symptoms suggestive of acute myocardial infarc-

tion were consecutively and prospectively assessed for inelusion in our study. A patient was included if the diagnosis of myocardial infarction was made on the basis of at least two of three diagnostic criteria: (1) chest pain suggestive of myocardial ischemia and lasting longer than 15 minutes, (2) development of new Q waves, or (3) an increase in creatinine kinase or aspartate aminotransferase levels by two values above the upper limit of normal. Elec-

Volume Number

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trocardiographic ST changeswere not required for inclusion. Exclusion criteria were age more than 75 years, contraindications to streptokinase treatment, and indications or contraindications for antithrombotic treatment, including heparin, coumarin, and dipyridamole. The study was approved by the local ethics committee and all patients gave informed consent. Eligible patients were stratified for Q wave and non-Q wave infarctions and then randomly assignedto either the treatment or control group. Patients in the treatment group were given 100mg of hydrocortisone intravenously followed by 1,500,OOO units of streptokinaseintravenously for 1 hour. Immediately afterward a continuous intravenous infusion of heparin was begun, initially at 1000U/hr and later adjusted according to activated partial thromboplastin time (APTT) levels, aiming for a therapeutic level of 60 to 90 seconds.Heparin therapy wascontinued for at least 5 days. Simultaneously with heparin, dipyridamole, 75 mg three times a day, was begun and continued for 3 months. In addition, warfarin wasgiven in dosesadjusted accordingto the thrombotest levels, aiming for 6% to 12% (correspondingto international normalized ratio 4.0to 2.4). Warfarin therapy was continued for 3 months. Subsequently patients wererandomly assignedeither to continue warfarin therapy for up to 12 months or to stop receiving therapy. Patients in the control group were handled without the preceding regimen. Patients in both groups were given beta blockersfrom the secondor third day onward if ,there were no contraindications. All other medications,including antiarrhythmic agents, calcium channel antagonists,and nitrates, were given only when deemednecessary by the patients’ clinical status. Aspirin was not used as routine secondaryprophylaxis. Follow-up. All patients wereseenafter 6 weeksand 3 and 12 months, respectively. Casehistories were taken, with particular emphasison the occurrence of effort angina. This was defined as chest pain provoked by exercise and relieved within a few minutes by rest or by sublingual nitroglycerin. Recordsfrom rehospitalizations were studied, including those from other hospitalsto which patients had beenadmitted. Death certificates and autopsy reports were studied to establish the cause of death. An ECG was obtained to detect changesindicative of silent reinfarction. It was also noted whether patients younger than the retirement ageof 65 years had been able to resumework. Exercise testing. On discharge from the hospital, the exercise tests were submaximum, whereas at 3 and 12 months, respectively, the tests proceeded to a symptomlimited maximum. Exercise testing was performed on an electrically braked bicycle ergometer with a 10 W/min stepwise increment of the work load.6 The ECG was recorded continuously, heart rate was monitored every minute, and systolic blood pressure every 2 minutes. Alternatively the submaximum predischargetest wasterminated if the heart rate exceededa previously determined maximum asfollows: amongpatients receiving beta blockers, 110 beats/min for those lessthan 60 years of ageand 100 beats/min for those more than 60 years of age, and amongpatients not receiving beta blockers, 130beats/min

in AMI

739

Table II. Side effects associatedwith streptokinaseinfusion

in 51 patients Patients

Type

of side effect

Hypotension(systolic

blood pressure <90 mm Hg) Systolic blood pressure decrease 220 mm Hg Flush/itching Asthmatic reaction Shivering Bursitis Acute back pain Minor bleeding Treated without reactions

With side effects 5

With interrupted infusions 1

12 5 1 3 1 2 7 20

1

2

for those lessthan 60 years of age and 120 beats/min for thosemore than 60years of age.Tests werealsoterminated in the event of intolerable chest pain, dyspnea, or exhaustion or if there was a decreasein systolic blood pressure exceeding 10 mm Hg. At 3 and 12 months patients exercised until the occurrence of severechest pain, dyspnea, exhaustion, or a decreasein systolic blood pressure exceeding 10 mm Hg. A standard 12-lead ECG was obtained before and immediately after the test. During the predischargetest the ECG from the six chest-headleads, CH l-6, was recorded during the last 15 secondsof each minute. In the 3- and 12-month exercisetests the ECG signal wasaveragedby a computerized ECG-processingtechnique permitting both chest and extremity leadsto be recordedduring the completetest. This technique, which has beendescribedin detail elsewhere,7permits very accurate determination of ST segmentshifts during maximum work load and afterward. The ST segmentamplitude was measured 60 msecafter the end of the QRS complex (ST 60), with the PQ interval as the isoelectric reference.The presenceof a myocardial ischemicresponsewasdefined asST60 depressionof 1 mm in relation to the resting level in any of the ECG leads.ECG analysiswas not performed if the resting ECG showedbundle branch block. All exercisetests weresupervisedby a physician who wasnot involved in the ongoing study. Statistical methods. Summary data are expressed as mean ( ? ) standard deviations. Statistical significancewas determined with the two-tailed t test for continuous variables.Results of exercisetests were also evaluated with a Mann-Whitney test. For dichotomous variables, the chisquaretest or Fisher’sexact test (if numbersin any cell of the table fell below five) wasapplied. To evaluate trends in ECG changesor in incidence of chest pain with different exercise loads,a log-rank test (similar to life-table analysis) was applied. All data concerning exercise tests were analyzed according to the intention to treat principle.

740

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and

Rydbn

American

30

PC0

March 1991 Heart Journal

05

280 260 240

i

0 ’ C ”

53

hospital

t

C

t

C

t

44

50

44

44

37

discharge

three

12 months

months

Exercise

tests

Fig. 2. Maximum exercise tolerance in exercise tests at discharge from hospital and at 3- and 12-month follow-up tests, given as means (k) standard deviation, and as presentation of exact distribution of results. C, control group; t, treatment group.

Table

III. Clinical

outcome

after 12 months Intention Controls in = 57)

Outcome

CABG, *None

Coronary artery of the differences

RESULTS Patient

to treat Treatment (n =

Receiving group

n

c;,

6

10

10

19

6

5

9

1 10 4

2 19 7

5 20 2

“9

54

23

20

35 4 42

2 24

bypass grafting. between groups

reached

statistical

and randomization.

n

continuous

treatment Treatment group (n = ‘1.1)

“;

n

I

6

14

11 9 35

0 9

4 41

4 25

0 20 9 :,7

significance

Of 255 consecutive patients admitted to the coronary care unit, 111 were eligible for late treatment with streptokinase according to our criteria. Fifty-four of these patients were randomly assigned to treatment with streptokinase and subsequent antithrombotic drugs, and 57 were assigned to the control group (Fig. 1). The groups were well matched with respect to a number of baseline characteristics (Table I). Thrombolytic and antithrombotic treatment. Strepselection

Controls (n = 56)

54)

0;

n

Mortality Nonfatal reinfarction Effort angina CABG None of above

of follow-up*

tokinase treatment was initiated 12 to 49 hours (mean 32 hours) after the onset of symptoms. The complications seen after treatment with streptokinase are noted in Table II. The streptokinase infusion had to be stopped prematurely in four patients, because of a drop in blood pressure in one, an asthmatic reaction in one, and severe back pain in two. Warfarin therapy was associated with bleeding complications, necessitating interruption of therapy in two patients, one with hemarthrosis and one with rectal bleeding. In a third patient, warfarin was dis-

Volume Number

121 3. Part

1

Late streptokinase

n q

Controls Treated

40

in AMZ

741

p
80 100 Work load in watts

%

n q m -6

.c -za % .-6 r 8 2

Controls Treated

35 30 25 20 15 10 5

B

o 40

60

80 Work

100 load in

120

140

watts

Cumulative frequency of patients with ST segmentdepressionsof 1 mm (A) or 2 mm (B) at different work loadsduring exercisetest at 3-month follow-up. Analysis was basedon 40 and 51 patients in treatment and control groups,respectively. Four treated patients were excluded becauseof bundle branch block on resting ECG. Filled bars, control group; hatched bars, treatment group; NS, difference not statistically significant. Fig.

3.

continued because of alcohol abuse. Three of the patients randomly assigned to active treatment refused to participate. Thus a total of 44 patients in the treatment group completed the scheduled therapy with streptokinase and antithrombotic drugs. One

patient in the control group received intravenous heparin infusion from the second day on because of left ventricular mural thrombosis. Clinical outcome. The study was not designed for statistical evaluation of clinical outcome, There were

742

Grip and Rydkn

American

n q

March 1991 Heart Journal

Controls Treated

40

60

80 Work

100 load in watts

Fig. 4. Cumulative frequency of patients with chest pain at different work loads during exercise test at 3-month follow-up. Analysis was based on all 44 and 51 patients who performed test in treatment and control groups, respectively. Filled bum, control group; hatched bars, treatment group; NS, difference not statistically significant.

no statistically significant differences between the two groups with respect to deaths or reinfarctions, and the beta error was high (>O.lO). Figures for mortality,

nonfatal

reinfarctions,

the number

of patients

referred for bypass surgery, and the incidence of angina pectoris during a 12-month follow-up period are given in Table III. No patients underwent. percutaneous transluminal coronary angioplasty during the follow-up period. Included in the numbers reported are the hospital deaths of seven patients in the treatment group and two patients in the control group. Patients with Q wave and non-Q wave infarctions did not differ in these respects. The median duration of hospitalization was 8 days in each group (range 6 to 18 days in the treatment group vs 5 to 39 days in the control group; not significant [NS]). Of patients who were gainfully employed and had at least 1 year left before retirement before the infarction, 21 of 25 in the treatment group and 12 of 21 in the control group (NS) went back to work within the first year after the infarction. Exercise testing. All analyses of exercise test results were conducted under the principle of intention to treat. Before hospital discharge, patients in the treatment group exercised to a significantly higher work load than those in the control group (97 -t 30 vs 82 i 26 W; p < 0.05). Results of the symptom-limited maximum exercise tests at 3 and 12 months

showed that patients in the treatment group had a higher exercise tolerance than those in the control group (p < 0.05) (Fig. 2). At the 3-month test, 45 of 54 patients in the treatment group had survived; however, one was unable to perform a bicycle exercise test because of poor physical condition. In the control group 53 of 57 patients had survived, but one refused to take the test and another was disabled because of hemiparesis on the basis of a cerebral vascular lesion after reinfarction. Thus a total of 44 treated and 51 control patients performed the 3-month test,. Signs of ischemia reported as chest pain and/or ST segment depression on ECG appeared at lower work loads among patients in the control group compared with those treated with thrombolytic and antithrombotic agents (Figs. 3 to 5). Further analysis showed that the entire difference in exercise tolerance was found in the subgroup of patients without any previous history of coronary heart disease (Table IV). The length of warfarin therapy did not influence exercise tolerance after 1 year. DISCUSSION

In this study of patients with myocardial infarction, attempted late thrombolysis with subsequent. anticoagulant therapy resulted in improved exercise tolerance evaluated on discharge from the hospital

Volume

121

Number

3.

Part

Late

1

streptokinase

in AMI

743

50 -

n 45 -

.

Zontrols

p
7 -rested

EA

40 35 30 25 20 15 10 -\

40

60

80 Work

100 load

in watts

Fig. 5. Analysis of trends of positive outcome at different levels of exercise, defined as ST segment depression of 1 mm in any lead or chest pain, at s-month exercise test. Analysis was based on 40 and 51 patients in treatment and control groups, respectively. Four treated patients with bundle branch block were excluded. Filled bars, control group; hatched bars, treatment group.

Table

IV.

previous

Symptom-limited maximum exercise tolerance manifestations of coronary artery disease) Control

AMI,

Acute myocardial

infarction;

group

test (subgrouped Treatment

Watts

n

112 + 45 101 I! 36

26 24

Categoq No previous AM1 or angina Previous AMI or angina

at the s-month

Watts 142 i 37 100 + 27

with reference

to history

of

group n 25 19

Difference

p = 0.01 NS

NS. not significant

and after 3 and 12 months of follow-up. The trend toward less postinfarction angina and more frequent return to preinfarction occupational activities is interesting and may be related to the lower incidence of myocardial ischemia. The study was prospective and randomized but for obvious reasons had to be open in design. This is a limitation, especially with regard to evaluation of the occurrence of angina pectoris. Results of exercise tests conducted by independent examiners, however, support the notion that functional status was favorably affected by the therapy given, The therapy studied was a combination of thrombolysis and antithrombotic drugs. Accordingly evaluation of the exact contribution of each component is impossible. However, the difference in exercise tolerance before hospital discharge makes it unlikely that the long-term result was influenced to any

great extent by the oral anticoagulation. Thus the thrombolytic part of the treatment was probably important. In this study bicycle ergometry was used to evaluate functional status and reveal signs of ischemia. Low exercise tolerance8 and the occurrence of ST segment depression9 and chest pain have been shown to be associated with poor prognosis in the post-myocardial infarction period. It has also been reported that patients with positive postinfarction exercise test results show more severe coronary lesions on coronary arteriograms than patients with negative results after myocardial infarction.lO Besides the improved exercise tolerance among patients in the treatment group in our study, it was also observed that the control patients had ST depression and chest pain at lower work loads than those given an-

744

Grip and Rydbn

tithrombotic treatment. Thus it is reasonable to assume that the lower incidence of residual postinfarction myocardial ischemia among the treated patients accounts for their superior exercise tolerance. It was also demonstrated that the difference between the two groups was more or less entirely composed of patients with no previous history of angina pectoris or myocardial infarction, who may be expected to benefit most from a restored or improved antegrade flow in the infarct-related artery. Reduced ischemia may also improve left ventricular function by reducing myocardial stunning, l1 which is frequently seen after prolonged and severe ischemia. This stunning may be one reason why it has been so difficult in some previous studies12, l3 to show beneficial effects on ventricular function after early thrombolytic therapy. More active revascularization with percutaneous transluminal coronary angioplasty in patients with postinfarction angina has been shown to improve global left ventricular systolic function considerably. l4 Recently15 a correlation has been demonstrated between vessel patency and left ventricular function, regardless of early thrombolysis or reperfusion. Left ventricular function may also improve over a period of years after transmural infarctioni focusing on the importance of remodeling of the infarct segment. A thinning and widening of the infarct segment (expansion) can often be demonstrated. In a canine model17 it was possible to reduce this infarct expansion after late coronary reperfusion, instituted at a time when actual infarct size was no longer affected. Thus it remains possible that the improved working capacity observed in this study to some extent was the result of better preserved left ventricular function. The question arises whether thrombolysis is effective after the initial 4 to 6 hours in myocardial infarction. It is well established that Q wave infarctions are caused by occlusive coronary thrombosis and that spontaneous lysis frequently occurs,18 with subsequent recanalization. Theoretically this may be augmented by exposing the thrombus to an exogenous thrombolytic agent. In non-Q wave infarction, on the other hand,lg subtotal occlusions are seen more often but with a tendency toward later complete occlusions, a process that may be arrested by the combined antithrombotic therapy used in the present study. Before the ISIS-2 trial thrombolytic therapy was ordinarily restricted to patients initially seen with symptoms suggestive of myocardial infarction usually lasting no longer than 6 hours. The results of the ISIS-2 trial clearly advocate widening of this “time window,” and findings in the present study, which

American

March 1991 Heart Journal

included patients with non-Q wave and Q wave infarctions, support the therapeutic efficacy of late thrombolysis. The results may have an impact on the number of patients eligible for thrombolytic therapy in the future. Since the time span for effective thrombolysis is less well defined in vivo, this should be better explored in further studies with the use of coronary arteriography. The effects of late thrombolysis on left ventricular function also require further study. We thank Elisabeth Berg for statistical ger for preparation of the manuscript.

advice

and Helena

Kag-

REFERENCES

in myocardial in1. Italian group for the study of streptokinase farction (GISSI). Effectiveness of intravenous thrombolytic treatment in acute myocardial infarction. Lancet 1986;1:397402. 2. European cooperative study group for streptokinase treatment in acute myocardial infarction. Streptokinase in acute myocardial infarction. N Engl J Med 1979;301: 797-802. 3. Kennedy JW, Ritchie JL, Davis KB, Stadius ML, Maynard C, Fritz JK. The western Washington randomized trial of intracoronary streptokinase in acute myocardial infarction. N Engl J Med 1985;312:1073-8. 4. ISIS-2 collaborative group. Randomized trial of intravenous streptokinase, oral aspirin, both, or neither among 17,187 cases of suspected active myocardial infarction: ISIS-2. Lancet 1988;2:349-60. 5. Shapiro EP, Brinker JA, Gottlieb SO, Guzman PA, Bulkley BH. Intracoronary thrombolysis 3 to 13 davs after acute mvocardial infarction for post infarction angina pectoris. Am-J Cardiol 1985;55:1453-8. 6. Astriim H, Jonsson B. Design of exercise test, with special reference to heart patients. Br Heart J 1976;38:289-96. JE, BjurG TI. A program for the process7. Falk KJ, Angelhed ing of multiple-lead exercise ECG’s in real time. Compute Programs Biomed 1982;14:133-44. 8. Fioretti P, Brower RW, Simoons ML, et al. Relative value of clinical variables, bicycle ergometry, rest radionuclide ventriculography and 24 hour ambulatory electrocardiographic monitoring at discharge to predict 1 year survival after myocardial infarction. J Am Co11 Cardiol 1986;8:40-9. 9. Theroux P, Waters DD, Halphen C, Debaisieux J-C, Mizgala HF. Prognostic value of exercise testing soon after myocardial infarction. N Engl J Med 1979;301:341-5. 10. Griffith LSC, Varnauskas E, Wallin J, Bjurii T, Ejdeback J. Correlation of coronary arteriography after acute myocardial infarction with predischarge limited exercise test response. Am J Cardiol 1988;61:201-7. 11. Braunwald E, Kloser RA. The stunned myocardial prolonged, postischemic ventricular dysfunction. Circulation 1982;66: 1146-9. 12. Chesebro JH, Knatterud G, Roberts R, et al. Thrombolysis in myocardial infarction (TIMI) trial, phase I: a comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Circulation 1987;76:142-54. 13. Ritchie JL, Cerqueira M, Maynard C, Davis K, Kennedy JW. Ventricular function and infarct size: the Western Washineton intravenous streptokinase in myocardial infarction trial.-J Am Co11 Cardiol 1988;11:689-97. 14. Sabbah HN, Brymer JF, Gherorghiade M, Stein PD, Khaja F. Left ventricular function after successful percutaneous transluminal coronary angioplasty for postinfarction angina pectoris. Am J Cardiol 1988:62:358-62. 15. Schroder R, Neuhaus K-L, Linderer T, Briiggemann T, Tebbe

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U, Wegscheider K. Impact of late coronary artery reperfusion on left ventricular function one month after acute mvocardial infarction. Am J Cardiol 1989;64:878-84. 16. Silberherg J, Haichin R, Stewart S, Lisbona R, Sniderman A. Long-term stepwise sustained improvement in left ventricular eiection fraction after mvocardial infarction. AM HEART J iy89;117:532-7. 17. Force I. Kemner A. Leavitt M. Parisi AF. Acute reduction in functional infarct expansion with late coronary reperfusion:

in AMI

assessment with quantitative two-dimensional echocardioprauhv. J Am Co11 Cardiol 1988:11:192-200. 18. be -Wbod MT, Spores J, Notski R, et al. Prevalence of total coronary occlusion during the early hours of myocardial infarction. N Engl J Med 1980;303:897-902. 19. De Wood MA, Stifter WF, Simpson CS, et al. Coronary arteriographic findings soon after non-Q-wave myocardial infarction. N Engl J Med 1986:315:417-23.

Impedance measurement of absolute blood flow using an angioplasty catheter: A validation study An angioplasty catheter was developed to allow measurement of absolute coronary blood flow during interventional procedures. This method uses electrical impedance changes induced by a 0.5 ml bolus of 5% dextrose solution and indicator-dilution principles. The indicator is injected through a port located just proximal to the dilating balloon and the resulting changes in blood impedance are measured by electrodes at the catheter tip. Excellent linear correlations were found between known flow in 2 to 4 mm to diameter plastic tubes and catheter measurements (I = 0.99) and between timed collection canine femoral artery flow and catheter measurements (r = 0.97). Final validation was performed in canine coronary arteries using electromagnetic flowmeter data as the standard (r = 0.94). Thus accurate clinical determination of absolute coronary blood flow can be accomplished using this relatively inexpensive and simple catheter technique. (AM HEART J 1991;121:745.)

Lisa W. Martin, MD, Rodney A. Johnson, MD, Helen Scott, Shawn Robinson, MD, Glenn Beauman, Mark Englehardt, MD, and Robert A. Vogel, MD. Baltimore, Md.

Despite the increasing use of coronary angioplasty for the management of acute and long-standing coronary disease, the indications for and the results of this important intervention are largely determined by means of anatomic criteria. These criteria may not adequately assess the significance of a coronary stenosis. Estimates of percent stenosis have been found to have marked interobserver and intraobserver variabilitylm3 and correlate poorly with findings at autopsy. 4, 5 Assessment of the severity of a stenosis is From

filiate Received

Reprint Iiniversity 21201. 411126528

of Cardiology, Department of Medicine, University School of Medicine. in part by the University of Maryland, and by the Maryland

the Division

Maryland Supported

of the American

Heart

for publication

requests:

Robert

of Maryland

Association,

Inc.

Dec. 26, 1989;

accepted

A. Vogel, MD, Hospital

Aug.

Division

, 22 South

Greene

of

Af-

16, 1990.

METHODS

of Cardiology/N3W77, St., Baltimore.

particularly difficult during angioplasty. Importantly, percent stenosis, as utilized clinically, correlates poorly with the functional significance of coronary stenoses.6 Direct measurements of blood flow may more accurately define the hemodynamic effects of stenoses. This report describes a new angioplasty catheter system for measuring absolute blood flow in the catheterization laboratory, which is compatible with standard angioplasty techniques. It utilizes electrical impedance changes induced by a 0.5 ml bolus of 5% dextrose solution and the indicator-dilution principle. The purpose of this investigation was to study the operating characteristics of the catheter, and to validate its ability to measure blood flow.

MD

Catheter design. The catheter system (USC1 Division of C.R. Bard, Inc., Billerica, Mass.) differed from a standard angioplasty catheter only by the addition of a third lumen 745