Objectives　To assess the effects of long-term angiotensin-converting enzyme(ACE) inhibitor treatment with captopril on cardiac function in acute myocardial infarction (AMI).
　　Methods　One hundred and one patients with AMIwho were admitted to hospital within 72 hours of the onset of symptoms with no cardiogenic shock were randomly allocated to captopril (n=52; group Ⅰ) and conventional treatment (n=49; group Ⅱ). Left ventricular (LV) systolic performance and diastolic transmitral flow velocity profiles were assessed by Doppler echocardiography at admission (1.2±1.1 days), before discharge (27±10 days) and during follow-up (363±31 days).
　　Results　At one year follow-up, in group Ⅰ LV end-diastolic volume decreased, and ejection fraction increased due to a disproportionate decrease in end-systolic volume. The incidence of cardiac dilatation was reduced. LV early diastolic filling velocity (E)increased and late atrial filling velocity (A) decreased, resulting in an elevation of E/A ratio.However, the mean values of LV systolic and diastolic functional parameters were unchanged in group Ⅱ.
　　Conclusions　Long-term treatment with captopril exerts a beneficial effect on cardiac protection for patients with AMI.

Chin Med J 1998; 111(2):139-141

　　After acute myocardial infarction (AMI), infarct expansion and left ventricular (LV) remodeling often lead to LV dilatation and cardiac dysfunction.1,2　These changes in LV performance unfavorably affect the clinical outcome of patients with AMI.3,4　Acute angiotensin-converting enzyme (ACE) inhibitor therapy improves functional capacity and even the survival of these patients.5,6　However, the cardiac protective effects of long-term ACE inhibitor treatment after AMI remain not fully understood. The aim of this prospective study was to assess the changes in LV volumes, systolic function and diastolic filling during long-term captopril treatment in patients with AMI.

METHODS

Patients
　　This study included 101 patients withAMI,recruited from the study population in the Shanghai Second Prevention of AMI Trial reported previously.7　All patients were specially selected as they were 75 years or younger and hospitalised within 72 hours from the onset. None had severe hypotension or cardiogenic shock and severe hypertension (systolic blood pressure >26.7 kPa ［200 mmHg］ and/or diastolic blood pressure >16 kPa ［120mmHg］).

Medical therapy
　　On admission, all patients received conventional medical therapy for AMI if not contraindicated, including intravenous thrombolysis (urokinase 1.0-1.5 million IU) and oral administration of aspirin (300-325 mg/d) or metoprolol (50-100 mg, twice daily). Patients were then randomly allocated to captopril (group Ⅰ) or conventional therapy only (group Ⅱ). The therapeutic regimen captopril has been described in detail previously.7　For each patient in group Ⅰ, an appropriate maintaining of captopril dose (12.5-25 mg, three time daily) was used throughout the whole follow-up period.

Doppler echocardiographic assessment
　　All patients underwent Doppler echocardiographic examinations at admission (1.2±1.1 days), before discharge (27±10 days) and during follow-up (363±31 days). Patients were studied in the left lateral decubitus position and standard apical four-chamber view was recorded with an Acuson 128 ultrasonic imaging system. LV end-diastolic and end-systolic volumes were determined by area-length method as described previously, and ejection fraction was calculated by the standard formula. We have previously shown that this method for determining LV function has satisfactory accuracy and reproducibility.1

　　For assessing transmitral diastolic blood flow velocity profiles, the pulsed Doppler sample volume was placed at the tip of the mitral leaflets. Under the guidance of color Doppler, the angle between the sampling site and the direction of blood flow was always maintained less than 15 degree if possible, in order to obtain maximal flow velocity. All Doppler echocardiograms were recorded on a tape for further analysis. In each patient, an average of early (E) and late (A) diastolic filling velocity and E/A ratio measured from three consecutive beats was used.

Cardiac catheterization
　　Left heart catheterization was performed in 74 patients with standard Judkins technique, and LV end-diastolic pressure was determined.

Follow-up
　　ll patients were seen in a special cardiac clinic every 2-3 months. Details were elicited for cardiac events including cardiac death, heart failure, reinfarction or severe arrhythmias.

Statistical analysis
　　Data are expressed as mean±standard deviation (SD). Difference between groups is assessed by student t test and chi-square test. Relation among variables is tested by linear regression analysis.

RESULTS

　　Of the 101 patients studied, 52 received early and long-term treatment with captopril (group Ⅰ) and 49 were treated by conventional therapy only (group Ⅱ). The baseline clinical characteristics including patient's age, risk factors for coronary artery disease, infarct site and peak CPK and medications, including thrombolysis, antiplatelet and beta-blocker treatment were similar in the two groups, but the blood pressure was significantly lower in group Ⅰ (18.2±2.3/10.4±1.3 kPa ［136±17/78±10 mmHg］) than in group Ⅱ (19.2±2.5/11.1±1.5 kPa ［144±19/83±11 mmHg］, all P<0.05).

　　LV systolic and diastolic function assessed by Doppler echocardiography at admission, before discharge and during follow-up was listed in Table 1. At one year follow-up, LV end-diastolic volume decreased, ejection fraction increased due to a disproportionate decrease in end-systolic volume in group Ⅰ. Univariate linear regression analysis revealed that the changes in LV end-diastolic and end-systolic volumes and ejection fraction did not correlate with the initial values. By contrast, LV volumes and systolic performance remained unaltered in group Ⅱ.

Table. Changes in LV function (±s)

　 Group Ⅰ (n=52) Group Ⅰ n(=49)
End-diastolic volume (ml) 　 　
　Admission 153±39 152±45
　Discharge 154±48 155±51
　One year 　　132±48*+ 150±46
End-systolic volume(ml) 　 　
　Admission 95±34 94±29
　Discharge 93±40 95±46
　One year 　　 71±35**++ 93±32

Ejection fraction

 　 　
　Admission 0.39±0.05 0.39±0.05
　Discharge 0.41±0.11 0.39±0.11
　One year 　　 0.47±0.09**++ 0.39±0.10

E wave (cm/s)

 　 　
　Admission 68±17 69±16
　Discharge 72±18 69±20
　One year 　　78±16**+ 69±19

A wave (cm/s)

 　 　
　Admission 71±13 70±14
　Discharge 68±16 71±17
　One year 　　65±15**+ 73±17

E/A ratio

 　 　
　Admission 1.00±0.39 1.03±0.39
　Discharge 1.10±0.42 1.01±0.41
　One year 　　1.23±0.50**+ 0.98±0.38
　　* P<0.05, ** P<0.01 vs at admission; + P<0.05, ++ P<0.01 vs before discharge.

　　 In group Ⅰ, LV dilatation defined as end-diastolic volume of 175 ml or greater occurred in 18 patients before discharge, whereas at one year follow-up, only 7 patients had LV dilatation (P<0.05). However, the occurrence of LV dilatation was unchanged in group Ⅱ (before discharge: 17 patients; at one year follow-up: 15 patients).

　　At one year follow-up, E wave increased, A wave decreased, and E/A ratio was elevated in group Ⅰ (all P<0.05). However, these LV diastolic filling parameters were unchanged in group Ⅱ.

　　In 74 patients undergoning cardiac catheterization before discharge (26±10 days, range 9-56 days), patients who received captopril (38 patients) had significantly lower LV end-diastolic pressure (2.53±0.80 kPa ［19±6 mmHg］) than those who were treated by conventional therapy (36 patients; 3.13±0.80 kPa ［23±6 mmHg］) (P<0.05). The mean value of the number of coronary disease (≥70% luminal narrowing) was not significantly different between the two groups.

　　The overall cardiac event rate during follow-up was lower in group Ⅰ (10.2%) than in group Ⅱ (34.3%) (P<0.05).

DISCUSSION

　　A large body of evidence has demonstrated that after AMI the processes of infarct expansion and LV remodeling often result in LV dilatation and cardaic dysfunction.1,2　Long-term ACE inhibitor therapy may attenuate these processes.1,3-8　However, many previous studies did not initiate therapy with ACE inhibitors until after the immediate phase of ischemic damage. It has been demonstrated that LV dilatation begins within the first 24 hours in the course of AMI, therefore ACE inhibitor treatment should be initiated as early as possible, despite concern that this might precipite potentially hazardous decreases in blood pressure.

　　The study population were specially selected as they were 75 years or younger of age and had the first AMI without cardiogenic shock.Furthermore, Group Ⅰ patients received captopril therapy immediately after admission which persisted during long-term follow-up. All patients underwent serial Doppler echocardiographic examinations for assessing LV systolic and diastolic function. Our study has shown that LV end-diastolic volume decreased and ejection fraction increased due to a further decrease in end-systolic volume during long-term captopril treatment. In this study, the overall occurrence rate of LV dilatation was reduced significantly in group Ⅰ at one year of follow-up. We have previously shown that patients with LV dilatation after AMI often developed cardiac failure and had poor prognosis.1,7　In this regard, our present study further substantiates the observations that long-term ACE inhibitor therapy has protective effects on LV function and improves clinical outcome of these patients.7-10　Our study has shown that after long-term treatment with captopril, LV diastolic filling behavior was improved as E wave increased, A wave decreased and E/A ratio was elevated. These beneficial effects of captopril on LV function may be due to favorable alterations in cardiac loading conditions and inhibition of systemic and myocardial regional renin-angiotensin-aldosterone system during long-term treatment.

　　In conclusion, ACE inhibition with captopril initiated immediately after AMI and during long-term treatment exerts cardiac protective effects in patients with AMI.

REFERENCES

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