Medical and surgical management of early Q wave myocardial infarction. II. Effects on mortality and global and regional left ventricular function at 10 or more years of follow-up

To determine the long-term effect of surgical reperfusion on survival and left ventricular function of patients with anterior and inferior Q wave myocardial infarction, 387 patients were followed up for greater than or equal to 10 years after early Q wave infarction. In the anterior infarction group, 102 received conventional therapy and 101 underwent surgical reperfusion. The overall hospital mortality rate in the medically and surgically treated patients was different (16.7% [17 of 102] versus 6.9% [7 of 101], p less than 0.05). The cumulative 13 year actuarial mortality rate widened between the anterior medical and surgical groups (54% versus 31%, p = 0.0003) by the adjusted Cox proportional hazards model. The hospital mortality rate with early reperfusion (that is, less than or equal to 6 h of symptom onset) was 2% (1 of 51), whereas the mortality rate with late reperfusion was 12% (6 of 50). The 13 year actuarial cumulative mortality rate was significantly lower in both the early and late reperfusion groups (30% and 33%, respectively) than in the conventional therapy group (54%, p = 0.0006). The mortality rate in patients receiving surgery after surviving initial medical therapy was 50% (15 of 30). In the survivors of anterior Q wave myocardial infarction, improved global ejection fraction was seen in the patients undergoing early (54 +/- 13%) and late (50 +/- 10%) surgery relative to those receiving conventional therapy (43 +/- 11%, p less than 0.05). Only the early reperfusion group had better regional function of the anterior wall than that of the conventional therapy group. Thus, ventricular function correlated with improved long-term survival. In the patients with inferior Q wave myocardial infarction, the overall hospital mortality rate in the medical and surgical groups was not different (6.1% [6 of 98] versus 4.6% [6 of 86], p = NS). Likewise, the 13 year actuarial cumulative mortality rate was not different between the medical and surgical groups overall (32% versus 30%, p = 0.29) by the adjusted Cox proportional hazards model. The hospital mortality rate in the early reperfusion group was lower than that in the late reperfusion group (2.0% [1 of 49] versus 8.1% [3 of 37], p = NS). The 13 year actuarial cumulative mortality rate was lower in the early surgical group compared with that in the medical group (19% versus 32%, p = 0.04). The late surgical group had a similar 13 year actuarial cumulative mortality rate to that of the medical group (47% versus 32%, respectively, p = 0.47).(ABSTRACT TRUNCATED AT 400 WORDS)     

Long-term follow-up after recovery from acute myocardial infarction. Observations on survival, ventricular arrhythmias, and sudden death

A long-term 12-year follow-up of 248 patients surviving acute myocardial infarction indicated a cumulative survival of 89%, 68%, 53%, and 45% for 1, 5, 10, and 12 years, respectively. When patients were assessed with five routinely obtained clinical factors, significant prognostic stratification of high- and low-risk survival groups extended throughout the follow-up period. Sudden cardiac death was found to be twice as frequent as nonsudden cardiac death, but a significant relationship between sudden death and complex ventricular ectopic beats could not be defined. The extent of complex features of ventricular ectopic beats such as pairs, multiform, repetitive, and R-on-T was inversely related to survival. During the first year after acute myocardial infarction, frequency of ventricular ectopic beats was also inversely related to survival. A long-term effect of frequency on survival, however, could not be demonstrated.     

Plasma concentrations of fibrinolytic factors in the subacute phase of myocardial infarction predict recurrent myocardial infarction or sudden cardiac death

BACKGROUND: The prognostic value of plasma concentrations of tissue type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and C-reactive protein has been reported in patients with coronary artery disease. However, the association between cardiac events and these factors during the acute and subacute phases of myocardial infarction (MI) is unknown. The purpose of this study was to determine whether elevated plasma concentrations of t-PA, PAI-1, and C-reactive protein in patients with MI are associated with future recurrent MI or sudden cardiac death. METHODS: We studied 106 consecutive patients who survived a confirmed first MI between 1993 and 1998 in our hospital. The control group consisted of 50 patients who had no significant coronary artery stenosis. Blood samples were obtained at the time of admission for acute MI and on the 28th day after admission. Patients were followed for a mean of 50 months after these measurements. The primary end points were sudden cardiac death and fatal or nonfatal acute MI. RESULTS: Of the 92 patients who were available for follow-up, 10 had cardiac events. Both the plasma t-PA and PAI-1 concentrations were elevated on day 1 of acute MI compared to the control group and decreased by day 28, but remained higher than those in the controls. Plasma C-reactive protein concentration was also elevated on day 1 and decreased by day 28. Using a stepwise variable choice model of Cox proportional hazards analysis including these fibrinolytic factors and C-reactive protein, only the t-PA concentration in the subacute phase was a significant predictor of cardiac events (relative risk per S.D. 3.20, P<0.01). We further found that independent of other risk factors, an elevated t-PA concentration was predictive of cardiac events. CONCLUSIONS: This study reveals that a rise in endogenous t-PA concentration during the subacute phase of MI could predict recurrent MI or sudden cardiac death.     

Sustained benefit at 10-14 years follow-up after thrombolytic therapy in myocardial infarction.

AIMS: To investigate whether the benefit of thrombolytic therapy was sustained beyond the first decade. We report the 10-14 year outcome of 533 patients who were randomized to treatment with intracoronary streptokinase or to conventional therapy during the years 1980-1985. METHODS AND RESULTS: Details of survival and cardiac events were obtained from the civil registry, from medical records or from the patient's physician. At follow-up, 158 patients (59%) of the 269 patients allocated to thrombolytic treatment and only 129 patients (49%) of the 264 conventionally treated patients were alive. The cumulative 1-, 5- and 10-year survival rates were 91%, 81% and 69% in patients treated with streptokinase and 84%, 71% and 59% in the control group, respectively (P=0.02). Reinfarction during 10-years of follow-up was more frequent after thrombolytic therapy, particularly during the first year. Coronary bypass surgery and coronary angioplasty were more frequently performed after thrombolytic therapy. At 10 years approximately 30% of the patients were free from subsequent cardiac events.Independent determinants of mortality were elderly age, indicators of impaired residual left ventricular function, multivessel disease and an inability to perform an exercise test at the time of hospital discharge. CONCLUSION: Improved survival after thrombolytic therapy is maintained beyond the first decade. Age, left ventricular function, multivessel disease and an inability to perform an exercise test were independent predictors for long-term mortality, as they are predictors for early mortality.     

Predictors of sudden death up to 18 years after a first attack of unstable angina or myocardial infarction.

Factors related to the occurrence of sudden death were examined in 551 men aged less than 60 years who survived a first attack of unstable angina or myocardial infarction by at least 28 days. There were 301 deaths over an average follow up period of 9.4 years and 138 (46%) of these were sudden. Life table techniques permitted the estimation of mortality up to 18 years after the index event. The proportion of sudden deaths showed a decrease with length of follow up. In those who were non-smokers and in those aged less than 45 years on admission sudden deaths in the first two years were very common (80% (95% confidence interval: 69%-91%) and 79% (95% confidence interval: 68%-90%) respectively). The proportion of sudden deaths in the remaining 16 years of follow up was related inversely to age at initial attack. After the first two years of follow up sudden death rates were similar in those who continued to smoke and those who stopped smoking, although those who continued to smoke had a significantly higher overall mortality. The risk of sudden death should be borne in mind when planning the investigation and rehabilitation of young and non-smoking subjects presenting with a first coronary event.     

Dobutamine- vs exercise-induced ST segment elevation early after Q wave myocardial infarction. Prediction of functional recovery after revascularization.

AIMS: The association between stress-induced ST elevation and functional recovery following revascularization after myocardial infarction remains unclear. We assessed the relative accuracy of dobutamine- and exercise-induced ST elevation in Q wave leads in predicting functional recovery following revascularization, and we investigated the relationship of ST elevation to different wall motion responses to dobutamine. METHODS AND RESULTS: Thirty-nine patients underwent dobutamine stress echo and exercise test 8+/-2 days after Q wave myocardial infarction. All patients underwent angiography and subsequent revascularization. Follow-up echocardiograms were obtained 7+/-4 weeks after revascularization. Functional recovery was assessed by the difference between the baseline and the follow-up asynergy index. Nineteen patients (48%) developed dobutamine- and exercise-induced ST elevation. There was significant agreement between the tests (k=0.58, P<0.001). We found a significant correlation between dobutamine and exercise-induced ST elevation with functional recovery following revascularization (r=0. 45, P<0.005 and r=0.7, P<0.001, respectively). The parameters with the highest predictive value for functional recovery were: (a) the biphasic response during dobutamine infusion, (b) the development of ST elevation in both tests, and (c) the development of exercise-induced ST elevation in more than three leads. CONCLUSION: There is a strong association between dobutamine- and exercise-induced ST elevation with functional recovery following revascularization. Exercise-induced ST elevation in more than three leads and a biphasic response during dobutamine infusion accurately predict functional recovery.     

Predictors of sudden death up to 18 years after a first attack of unstable angina or myocardial infarction

Factors related to the occurrence of sudden death were examined in 551 men aged less than 60 years who survived a first attack of unstable angina or myocardial infarction by at least 28 days. There were 301 deaths over an average follow up period of 9.4 years and 138 (46%) of these were sudden. Life table techniques permitted the estimation of mortality up to 18 years after the index event. The proportion of sudden deaths showed a decrease with length of follow up. In those who were non-smokers and in those aged less than 45 years on admission sudden deaths in the first two years were very common (80% (95% confidence interval: 69%-91%) and 79% (95% confidence interval: 68%-90%) respectively). The proportion of sudden deaths in the remaining 16 years of follow up was related inversely to age at initial attack. After the first two years of follow up sudden death rates were similar in those who continued to smoke and those who stopped smoking, although those who continued to smoke had a significantly higher overall mortality. The risk of sudden death should be borne in mind when planning the investigation and rehabilitation of young and non-smoking subjects presenting with a first coronary event.     

Occurrence of coronary ostial stenosis in a necropsy series of myocardial infarction, sudden death, and violent death.

A postmortem coronary angiography technique employing aortic injection of contrast medium and double contrast visualization of the aortic bulb and large epicardial coronary trunks was applied to the study of coronary ostia in a series of 124 deaths from acute myocardial infarction and a series of 89 sudden deaths without recent infarction and 42 violent deaths. A stenosis of 50 per cent or more of the lumen was found in the right ostium in 45 per cent and in the left ostium in 8 per cent of infarct cases. The corresponding figures in sudden deaths were 37 per cent on the right and 4.5 per cent on the left side, and in violent deaths 7 per cent in the right ostium and none in the left. Most ostial stenoses were caused by coronary atherosclerosis. In 9 patients, two with a recent infarct and 7 sudden deaths, an ostial stenosis was the only stenosed site in the coronary arterial tree. Of theses 9 patients, 7 were known to have suffered from symptomatic heart disease during life, chest pain on effort and arrhythmias being the most common complaint.     

Occurrence of coronary ostial stenosis in a necropsy series of myocardial infarction, sudden death, and violent death.

A postmortem coronary angiography technique employing aortic injection of contrast medium and double contrast visualization of the aortic bulb and large epicardial coronary trunks was applied to the study of coronary ostia in a series of 124 deaths from acute myocardial infarction and a series of 89 sudden deaths without recent infarction and 42 violent deaths. A stenosis of 50 per cent or more of the lumen was found in the right ostium in 45 per cent and in the left ostium in 8 per cent of infarct cases. The corresponding figures in sudden deaths were 37 per cent on the right and 4.5 per cent on the left side, and in violent deaths 7 per cent in the right ostium and none in the left. Most ostial stenoses were caused by coronary atherosclerosis. In 9 patients, two with a recent infarct and 7 sudden deaths, an ostial stenosis was the only stenosed site in the coronary arterial tree. Of theses 9 patients, 7 were known to have suffered from symptomatic heart disease during life, chest pain on effort and arrhythmias being the most common complaint.     

ST segment shifts are poor predictors of subsequent Q wave evolution in acute myocardial infarction. A natural history study of early non-Q wave infarction

Acute ST segment elevation is regarded generally as the sine qua non of evolving Q wave myocardial infarction (MI) because such electrocardiographic (ECG) injury is believed to be a marker of transmural ischemia and a forerunner of transmural necrosis. Alternatively, ST segment depression with or without T wave inversion is viewed as the dominant ECG feature of non-Q wave MI. However, this hypothesis has not been assessed prospectively in an acute MI population. We analyzed 2,304 serial ECGs at study entry (admission), day 2, day 3, and predischarge (mean, 10.2 +/- 2 days) from 576 patients with creatine kinase MB confirmed acute non-Q wave MI to determine what percentage of patients with early ST segment elevation culminated in subsequent Q wave development. Of this group, 187 patients (32%) exhibited 1 mm or greater ST segment elevation in two or more contiguous entry ECG leads. Of those patients whose non-Q wave MI could be localized on the basis of diagnostic admission ST segment shifts, the prevalence of early ST segment elevation was 43% (187 of 439). The sum total mean (+/- SD) peak ST segment elevation by lead group (anterior, inferior, lateral) was 4.0 +/- 2.4, 4.5 +/- 2.4, and 2.5 +/- 0.6 mm, respectively. Despite this, only 20% of patients with ST segment elevation (37 of 187) developed Q waves. Of 252 patients who exhibited early ST segment depression or T wave inversion or both, 39 (15%) evolved subsequent Q waves. Thus, while the prevalence of early ST segment elevation in acute evolving non-Q wave MI was higher than previously reported, 80% of patients with and 85% of patients without ST segment elevation and absent Q waves on the admission ECG did not develop subsequent Q waves during a 2-week period of observation (p = NS). In addition, when patients with ST segment elevation were compared with patients with ST segment depression or T wave inversions or both, there were no between-group differences in log peak creatine kinase (404 vs. 383 IU), reinfarction (6% vs. 8%), postinfarction angina (50% vs. 42%), or early recurrent ischemia (49% vs. 45%), defined as postinfarction angina with transient ECG changes. Thus, in patients who present with initial acute non-Q wave MI, ST segment shifts on admission are unreliable predictors of subsequent Q wave evolution and do not discriminate significant differences in postinfarction outcome. In particular, ST segment elevation during the early hours of evolving infarction is not an invariable harbinger of subsequent Q wave development.     

Incidence of new stroke or new myocardial infarction or death at 39-month follow-up in patients with diabetes mellitus, hypertension or both with and without microalbuminuria

We investigated in 306 patients, mean age 57 +/- 10 years, with diabetes mellitus (202 patients) or hypertension (179 patients) whether microalbuminuria was a significant independent risk factor for the development of new stroke or new myocardial infarction (MI) or death. At 39-month follow-up, new stroke or new MI or death developed in 44 of 111 patients (40%) with microalbuminuria and in 38 of 195 patients (19%) without microalbuminuria (p = 0.0001). Stepwise Cox regression analysis showed that significant independent predictors of the time to development of new stroke or new MI or death were (1) diabetes (risk ratio = 1.76), (2) left ventricular (LV) mass index (risk ratio = 1.020 for each 1 g/m(2) increase), (3) prior stroke (risk ratio = 5.39), and (4) prior MI (risk ratio = 3.29). Microalbuminuria was not a significant independent predictor of new stroke or new MI or death, but LV mass index, diabetes mellitus, prior stroke, and prior MI were significant independent predictors.     

Slowed ST segment recovery despite early infarct artery patency in patients with Q waves at presentation with a first acute myocardial infarction. Implications of initial Q waves on myocyte reperfusion.

BACKGROUND: The presence of Q waves at presentation with a first acute myocardial infarction reflects a more advanced stage of the infarction process. When infarct-related artery patency (Thrombolysis in Myocardial Infarction 2 or 3 flow) is restored, resolution of ST segment elevation indicating successful myocyte reperfusion may differ according to how far the infarction process has progressed. METHODS AND RESULTS: In 144 patients with a first acute myocardial infarction treated with streptokinase in the first Hirulog Early Reperfusion Occlusion trial, information was obtained from continuous ST segment monitoring, the presenting electrocardiogram and early angiography performed at a median time of 99 min after the commencement of streptokinase (interquartile range 89-108 min). We determined how many patients had 50% ST recovery within 120 min and in how many cases it was sustained over 4h. In the 109 patients with patent infarct-related arteries, 50% ST recovery occurred in 95% of patients without vs 80% of those with initial Q waves (P=0.03), and sustained ST recovery occurred in 67% of patients without vs 47% of those with initial Q waves (P=0.03). On multivariate analysis including the time from symptom onset to streptokinase therapy, the presence of Q waves at presentation was the only predictor of failure to achieve 50% ST recovery (odds ratio 5.08, 95% confidence interval 1.29-20.01, P=0.02). TIMI 2 flow, as opposed to TIMI 3 flow, was the only predictor of failure to achieve stable ST recovery (odds ratio 2.63, 95% confidence interval 1.15-5.88,P =0.02). CONCLUSION: The presence of initial Q waves predicts slower and less complete ST recovery, reflecting reduced myocyte reperfusion, even in those with early infarct artery patency. These patients may be targeted for new therapeutic strategies to improve microvascular reperfusion.     

Usefulness of either or both left and right bundle branch block at baseline or during follow-up for predicting death in patients following acute myocardial infarction

The presence or onset of bundle branch block (BBB) is associated with increased mortality in patients after acute myocardial infarction (AMI). The risk increases with age. We assessed the prognostic power of BBB patterns for predicting clinical outcomes in patients after high-risk AMI. In the OPTIMAAL trial, the effects of losartan versus captopril were compared in 5,477 patients with heart failure and/or evidence of left ventricular dysfunction after MI. The association between clinical outcomes and the presence of left or right BBB at randomization (median 3 days after AMI) or occurring during follow-up (mean 2.7 years) was assessed using Cox regression models. At randomization, 8% of patients (n = 438) showed BBB patterns; 3.7% (n = 203) showed left BBB and 4.3% (n = 235) showed right BBB patterns. In patients with left BBB, there was an increased risk of all-cause death and cardiovascular death. In patients with right BBB, there was increased risk of sudden cardiac death/resuscitated cardiac arrest. During follow-up, another 4.9% (n = 272) developed BBB patterns; 2.8% (n = 153) developed left BBB and 2.17% (n = 119) developed right BBB. Left BBB was associated with increased risk for all-cause death, cardiovascular death, and sudden cardiac death/resuscitated cardiac arrest, whereas right BBB was related to increased risk of sudden cardiac death/resuscitated cardiac arrest. In conclusion, our results confirm and quantify previous observations showing substantially increased mortality in patients with BBB patterns at baseline or occurring soon after AMI.     

High density lipoprotein cholesterol and myocardial infarction or sudden coronary death: a prospective case-control study in middle-aged men of the Oslo study.

The high density lipoprotein (HDL) cholesterol concentrations of frozen specimen obtained in 1972-73 are reported from 93 men aged 40-49 years who later developed coronary heart disease (CHD), and for 186 controls. Mean HDL cholesterol of CHD-patients was 7.9% lower than that of controls matched for smoking habits and serum concentrations of triglycerides and total cholesterol (p 0.05 for 82 men who had myocardial infarction, n.s. difference for 11 with sudden coronary death), and 10.2% lower (p 0.05) than that of controls who were not matched for the parameters mentioned. The present prospective study confirms that HDL cholesterol is inversely associated with the risk of developing CHD in middle-aged men.