Nonfatal Recurrent Infarction Research Articles

Primary Percutaneous Coronary Intervention Compared With Fibrinolysis for Myocardial Infarction in Diabetes Mellitus

There is growing evidence for a clinical benefit of primary percutaneous coronary intervention (PCI) compared with fibrinolysis; however, whether the treatment effect is consistent among patients with diabetes mellitus is unclear. We compared PCI with fibrinolysis for treatment of ST-segment elevation myocardial infarction in patients with diabetes mellitus. A pooled analysis of individual patient data from 19 trials comparing primary PCI with fibrinolysis for treatment of ST-segment elevation myocardial infarction was performed. Trials that enrolled at least 50 patients with ST-segment elevation myocardial infarction and randomized patients to receive either primary PCI or fibrinolysis were considered for inclusion in our study. Clinical end points were total deaths, recurrent infarction, death or nonfatal recurrent infarction, and stroke, measured 30 days after randomization. Of 6315 patients, 877 (14%) had diabetes. Thirty-day mortality (9.4% vs 5.9%; P < .001) was higher in patients with diabetes. Mortality was lower after primary PCI compared with fibrinolysis in both patients with diabetes (unadjusted odds ratio, 0.49; 95% confidence interval, 0.31-0.79; P = .004) and without diabetes (unadjusted odds ratio, 0.69; 95% confidence interval, 0.54-0.86, P = .001), with no evidence of heterogeneity of treatment effect (P = .24 for interaction). Recurrent infarction and stroke were also reduced after primary PCI in both patient groups. After multivariable analysis, primary PCI was associated with decreased 30-day mortality in patients with and without diabetes, with a point estimate of greater benefit in diabetic patients. Diabetic patients with ST-segment elevation myocardial infarction treated with reperfusion therapy have increased mortality compared with patients without diabetes. The beneficial effects of primary PCI compared with fibrinolysis in diabetic patients are consistent with effects in nondiabetic patients.

Depression as a risk factor for mortality after acute myocardial infarction

The ENRICHD clinical trial, which compared an intervention for depression and social isolation to usual care, failed to decrease the rate of mortality and recurrent acute myocardial infarction (AMI) in post-AMI patients. One explanation for this is that depression was not associated with increased mortality in these patients. The purpose of this study was to determine if depression was associated with an increased risk of mortality in a subsample of the ENRICHD trial's depressed patients compared with a group of nondepressed patients recruited for an ancillary study. Three hundred fifty-eight depressed patients with an acute AMI from the ENRICHD clinical trial and 408 nondepressed patients who met the ENRICHD medical inclusion criteria were followed for up to 30 months. There were 47 deaths (6.1%) and 57 nonfatal AMIs (7.4%). After adjusting for other risk factors, depressed patients were at higher risk for all-cause mortality (hazard ratio 2.4, 95% confidence interval 1.2 to 4.7) but not for nonfatal recurrent infarction (hazard ratio 1.2, 95% confidence interval 0.7 to 2.0) compared with nondepressed patients. In conclusion, depression was an independent risk factor for death after AMI, but it did not have a significant effect on mortality until nearly 12 months after the acute event, nor did it predict nonfatal recurrent infarction.

Anti-ischaemic therapy during the follow-up phase of acute coronary syndromes. Is there a role for calcium channel blockers?

Various pharmacological strategies are currently being sought to enhance the efficacy of thrombolysis after an acute myocardial infarction (AMI). Apart from the use of new thrombolytic agents, novel anticoagulants and antiplatelet drugs, attention has recently been focused on agents such as the calcium channel blockers (calcium antagonists) traditionally used (prior to the thrombolytic era) for secondary prevention after an AMI. In this context, although calcium channel blockers have not been definitively proven to have any benefit with regard to all-cause mortality or subsequent infarctions, diltiazem has been shown to reduce cardiac mortality, recurrent nonfatal infarction and myocardial ischaemia after non-Q-wave AMI. These benefits have been linked to the drug's effect of lowering heart rate. Since both non-Q-wave AMI and the AMI treated with thrombolytic therapy result in early reperfusion and clinical manifestations of 'incomplete infarction', and are characterised by a similar high incidence of ischaemic complications, it is plausible to hypothesise that prophylactic calcium channel blocker administration to AMI patients post-thrombolysis might decrease the cumulative occurrence of reinfarction and refractory ischaemia during long term follow-up. With this in mind, the Incomplete INfarction Trial of European Research Collaborators Evaluating Prognosis Post-Thrombolysis with Tildiem was initiated in September 1994. This represents the first prospective study to investigate the efficacy of a calcium channel blocker (long-acting diltiazem 300 mg/day) administered as adjunctive therapy with aspirin 160 mg/day in up to 920 patients with an uncomplicated first AMI receiving early thrombolytic therapy. The primary trial objective is to assess the efficacy of blinded therapy on the 6-month cumulative occurrence of a combined clinical end-point (cardiac death, recurrent non-fatal infarction, medically refractory ischaemia)-an end-point identical to that utilised in the assessment of diltiazem in non-Q-wave AMI.

Interaction of ischaemia and encainide/flecainide treatment: a proposed mechanism for the increased mortality in CAST I.

To determine whether an interaction between encainide or flecainide and intercurrent ischaemia could account for the observed increase in cardiac and sudden deaths in the study group in the Cardiac Arrhythmia Suppression Trial (CAST) I. CAST I was a randomised, double blind, placebo controlled study in which patients received the drug which suppressed at least 6 premature ventricular contractions per minute by 80% or episodes of non-sustained ventricular tachycardia by 90%. Arrhythmic sudden death or aborted sudden death were the study end points. Measured secondary end points included recurrent myocardial infarction, new or increasing angina pectoris, congestive heart failure, and syncope. The CAST I database was analysed to determine which of three end points occurred first--cardiac death or cardiac arrest, angina pectoris, or non-fatal recurrent infarction. They were regarded as mutually exclusive end points. The triad of cardiac or sudden arrhythmic death plus congestive heart failure and syncope was similarly analysed. It was assumed that recurrent non-fatal infarction and new or increasing angina pectoris were ischaemic in origin. The sum of these non-fatal ischaemic end points and sudden death were nearly identical in the placebo group (N = 129) and the treatment group (N = 131). The one year event rate in each group was 21%. However, the treatment group had a much greater fatality rate (55 v 17; P < 0.0001) than the placebo group. The same relation was found when the data were examined on the basis of drug exposure rather than intention to treat. The temporal and circadian events were similar in each group and were consistent with an ischaemic pattern. No such patterns emerged from analysis of the presumed non-ischaemic end points of congestive heart failure and syncope. These data suggest that the interaction between active ischaemia and treatment with encainide or flecainide may have been responsible for the increased mortality seen in the treatment group in CAST I. This conversion of a non-fatal to a fatal event emphasises the need for future antiarrhythmic drugs to be screened in ischaemic models.

Design of a placebo-controlled clinical trial of long-acting diltiazem and aspirin versus aspirin alone in patients receiving thrombolysis with a first acute myocardial infarction

Several pharmacologic forms of adjunctive therapy, designed to enhance the efficacy of thrombolysis following acute myocardial infarction (AMI), are being explored. However, few studies have assessed the use of standard secondary prevention therapies (beta-blockers, angiotensin-converting enzyme inhibitors, magnesium, calcium antagonists, etc.) for antecedent thrombolysis. Although calcium antagonists have not been shown to alter post-AMI mortality, diltiazem has been shown to reduce recurrent nonfatal infarction and myocardial ischemia following non-Q-wave AMI. Because both non-Q-wave AMI and AMI treated with thrombolytic therapy result in early reperfusion and clinical manifestations of “incomplete infarction” (i.e., aborted transmural infarction), we hypothesize that prophylactic administration of diltiazem to AMI patients who receive thrombolysis before other therapies might decrease ischemic complications. We have initiated a multicenter, randomized, placebo-controlled, double-blind, parallel-group comparison of long-acting diltiazem 300 mg/day and aspirin 160 mg/day versus aspirin 160 mg/day alone in up to 920 patients with an uncomplicated first AMI (no heart failure or left ventricular dysfunction) within 36 to 96 hours of receiving thrombolysis. Active enrollment is under way at 46 centers in the United Kingdom, Belgium, The Netherlands, and Denmark. This trial (known as the Incomplete I Nfarction Trial of European Research Collaborators Evaluating Prognosis Post- Thrombolysis [diltiazem], or INTERCEPT) represents the first long-term, large-scale, prospective study of a calcium antagonist administered post-thrombolysis as adjunctive therapy to AMI patients in which the primary trial objective is to assess the effect of blinded therapy on the 6-month cumulative occurrence of a combined clinical end point (cardiac death, recurrent nonfatal AMI, and medically refractory ischemia).

Predictors of nonfetal reinfarction in survivors of myocardial infarction after thrombolysis: Results of the gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) data base

Objectives. This study was designed to reassess the prediction of recurrent nonfatal myocardial infarction in patients recovering from acute myocardial infarction after thrombolysis.Background. Recurrent nonfatal myocardial infarction is a strong and independent predictor of subsequent mortality. Current knowledge of risk factors for nonfatal reinfarction is still largely based on data gathered before the advent of thrombolysis. Thus, this prospective study was planned to identify harbingers of nonfatal reinfarction in the postinfarction patients of the multicenter Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico (GISSI-2) trial.Methods. Predictors of nonfatal reinfarction at 6 months were analyzed by multivariate technique (Cox model) in 8,907 GISSI-2 survivors of myocardial infarction with clinical follow-up, relying on a set of prespecified variables reflecting residual ischemia, left ventricular failure or dysfunction, complex ventricular arrhythmias, comorbidity as well as demographic and historical factors.Results. The postdischarge to 6-month incidence rate of nonfetal reinfarction was 2.5%. Independent predictors of nonfatal reinfarction were cardiac ineligibility for exercise test (relative risk 2.97, 95% confidence interval [CI] 1.98 to 4.45), previous myocardial infarction (relative risk 1.70, 95% CI 1.22 to 2.36) and angina at follow-up (relative risk 1.50, 95% CI 1.10 to 2.04). On further multivariate analysis, performed in 6,580 patients with both echocardiographic and electrocardiographic monitoring data available, a history of angina emerged as an additional risk predictor (relative risk 1.58, 95% CI 1.10 to 2.25).Conclusions. The 6-month incidence of nonfatal reinfarction is rather low in survivors of myocardial infarction after thrombolysis. Cardiac ineligibility for exercise testing and a history of coronary artery disease are risk predictors. Recurrent nonfatal infarction is not predictable by qualitative variables reflecting residual ischemia, except by postdischarge angina. Prediction of nonfatal reinfarction appears less accurate than prediction of mortality, as almost 50% of reinfarctions occur in patients without any of the identified risk factors.

Living Alone After Myocardial Infarction

Objective. —To determine if the presence of a disrupted marriage or living alone would be an independent prognostic risk factor for a subsequent major cardiac event following an initial myocardial infarction. Design. —Prospective evaluation in the placebo wing of a randomized, double-blind drug trial in patients with an enzyme-documented acute myocardial infarction who were admitted to a coronary care facility. Data for living alone and/or a marital disruption were entered into a Cox proportional hazards model constructed from important physiologic and nonphysiologic factors in the same database. Setting. —Multicenter trial in a mixture of community and academic hospitals in the United States and Canada. Patients. —All consenting patients who were 25 to 75 years of age and without other serious diseases were enrolled (placebo, N = 1234) within 3 to 15 days of the index infarction and followed for a period of 1 to 4 years (mean, 2.1 years). Nine hundred sixty-seven patients were followed for 1.1 years and 530 for 2.2 years. Primary Outcome Measure. —Recurrent major cardiac event (either recurrent nonfatal infarction or cardiac death). Results. —Living alone was an independent risk factor, with a hazard ratio of 1.54 (95% confidence interval, 1.04 to 2.29; P P =.001). A disrupted marriage was not an independent risk factor. Conclusion. —Living alone but not a disrupted marriage is an independent risk factor for prognosis after myocardial infarction when compared with all other known risk factors. ( JAMA . 1992;267:515-519)

Social and Economic Factors in Patients With Coronary Disease-Reply

<h3>In Reply.</h3> —In reply to the letter of Dr Burke, all conclusions and figures were based on the prestated primary end point of the occurrence of either nonfatal recurrent infarction or cardiac death, whichever came first. Data on cardiac death were included for completeness. As we stated, the lack of independent risk for cardiac death may imply either a differential effect of psychosocial factors on recurrent cardiac events, or a reduced statistical power for cardiac death (123 vs 226 events). We certainly agree with Drs Frasure-Smith, Lespérance, Hojat, Morris, and Robinson that negative emotions such as depression, loneliness, anxiety, and emotional distress may bear an important relationship to the observed increase in major recurrent events. At the same time, we are not sure of the specific mechanisms that would initiate either an acute MI or cardiac death in this group; further studies are needed to explore the mechanism. The fact

Living Alone After Myocardial Infarction

To determine if the presence of a disrupted marriage or living alone would be an independent prognostic risk factor for a subsequent major cardiac event following an initial myocardial infarction. Prospective evaluation in the placebo wing of a randomized, double-blind drug trial in patients with an enzyme-documented acute myocardial infarction who were admitted to a coronary care facility. Data for living alone and/or a marital disruption were entered into a Cox proportional hazards model constructed from important physiologic and nonphysiologic factors in the same database. Multicenter trial in a mixture of community and academic hospitals in the United States and Canada. All consenting patients who were 25 to 75 years of age and without other serious diseases were enrolled (placebo, N = 1234) within 3 to 15 days of the index infarction and followed for a period of 1 to 4 years (mean, 2.1 years). Nine hundred sixty-seven patients were followed for 1.1 years and 530 for 2.2 years. Recurrent major cardiac event (either recurrent nonfatal infarction or cardiac death). Living alone was an independent risk factor, with a hazard ratio of 1.54 (95% confidence interval, 1.04 to 2.29; P less than .03). Using the Kaplan-Meier statistical method for calculation, the recurrent cardiac event rate at 6 months was 15.8% in the group living alone vs 8.8% in the group not living alone. Risk remained significant throughout the follow-up period (P = .001). A disrupted marriage was not an independent risk factor. Living alone but not a disrupted marriage is an independent risk factor for prognosis after myocardial infarction when compared with all other known risk factors.

Safety and efficacy of a new regimen of intravenous recombinant tissue-type plasminogen activator potentially suitable for either prehospital or in-hospital administration

The safety and efficacy of a new regimen of intravenous recombinant tissue-type plasminogen activator (rt-PA) potentially suitable for either pre- or in-hospital administration were assessed in 60 patients with acute myocardial infarction in an open label coronary angiographic study. The regimen consisted of a 20-mg bolus dose followed 30 min later by a delayed infusion of 80 mg over 2 h. This regimen was designed to facilitate prehospital administration of rt-PA.Infarct-related artery patency (Thrombolysis in Myocardial Infarction [TIMI] grade 2 or 3 How) was observed in 40 of 53 patients at 60 min (75.5%, 95% confidence intervals [CI] 61% to 84%) and in 55 of 60 patients at 90 min (91.7%, 95% CI 80% to 95%) after the rt-PA bolus. By 90 min the majority of patients (55%) exhibited TIMI grade 3 flow; infarct artery patency at 120 min was 84.9%.During hospitalization definite recurrent ischemia occurred in nine patients (15%); nonfatal recurrent infarction was noted in one (1.7%). Four patients (6.7%) experienced major bleeding, including one with intracranial bleeding. There were seven deaths (11.7%). Mortality was significantly influenced by the occurrence of cardiogenic shock, which was present in five patients at the time of enrollment.Blood fibrinogen levels were obtained before and during rt-PA infusion. At baseline and 30 and 150 min after the bolus dose, the mean fibrinogen level (±SD) was 284.83 ± 77.39, 237.96 ± 76.92 and 192.04 ± 57.82 mg/dl, respectively. Compared with the baseline value, there was a significant (p < 0.05) decrease in fibrinogen at both 30 and 150 min.Thus, a new regimen of intravenous rt-PA has been identified that is logistically well suited for both pre- and in-hospital treatment of patients with acute myocardial infarction. The regimen features an initial 20-mg bolus dose and is capable of achieving infarct artery patency rates in excess of 90%, 90 min after initiation of therapy. Clinical use of this regimen should be deferred until the incidence of associated major adverse events is determined in a prospective large scale controlled trial.

Acute intravenous beta blockade as an adjunct to thrombolytic therapy

The Thrombolysis in Myocardial Infarction Trial (TIMI) IIB was a study of adjuncts to thrombolytic therapy. During the trial, 1390 patients without contraindication to beta blockade were treated with intravenous tissue plasminogen activator (tPA) and heparin within 4 h of the onset of myocardial infarction and then were randomly assigned to metoprolol (15 mg intravenously over 6 min, followed by two 50 mg oral doses on hospital Day 1 and 100 mg b.i.d. thereafter) or matching placebo. In patients assigned to placebo, oral metoprolol therapy was initiated on hospital Day 6. Although the intravenous/oral metoprolol regimen did not reduce overall mortality, there were significant reductions in recurrent ischemia (15.4 vs. 21.2%, p=0.005) and recurrent nonfatal infarction (2.3 vs. 4.5%, p=0.02). In 631 patients treated with 100 mg of tPA and metoprolol, there were no intracranial hemorrhages, but 3 of the 617 patients treated with 100 mg of tPA and placebo had an intracranial hemorrhage (p=0.08).

Factors associated with recurrent myocardial infarction within one year after acute myocardial infarction

In a large population of patients (n = 3666) who were discharged from the hospital after acute myocardial infarction and followed up for 1 year, factors associated with recurrent nonfatal (n = 171) or fatal (n = 74) infarction were identified. Also, the effects of combining various end points (recurrent nonfatal or fatal infarction and other cardiac death) in multivariate analyses, a practice common in many small studies that evaluate the predictive value of various treatments or special tests, was examined. In univariate analyses, patients with nonfatal recurrent infarction did not differ with respect to age or gender from infarct-free survivors, but they more often had a history of previous myocardial infarction, congestive heart failure, angina pectoris, and diabetes; more severe pulmonary congestion was present on chest x-ray during the admission, and a non-Q wave index infarction was more frequent. Patients with either a fatal or nonfatal recurrent infarction had more angina pectoris during follow-up (55% to 60%) compared with 27% in event-free survivors and 31% in patients who died of other cardiac causes in whom this factor could be assessed before death. In multivariate analyses, historical and clinical prognostic factors were ranked differently for fatal or nonfatal reinfarction and other cardiac causes of death; angina pectoris at follow-up was highly related to recurrent infarction (fatal or nonfatal), along with a history of diabetes, and a non-Q wave index infarction. These factors were not independently related to other causes of cardiac death. When angina pectoris at follow-up was used in the multivariate analysis of recurrent infarction (fatal plus nonfatal), it was the most important factor. This finding supports the general practice of referring patients with angina pectoris during follow-up (34% of the population) for coronary angiography in an effort to identify those with severe disease who might benefit from revascularization, which is aimed at the prevention of recurrent myocardial infarction.

Diltiazem increases late-onset congestive heart failure in postinfarction patients with early reduction in ejection fraction. The Adverse Experience Committee; and the Multicenter Diltiazem Postinfarction Research Group.

The Multicenter Diltiazem Postinfarction Trial (MDPIT) reported no consistent diltiazem effect on new or worsened congestive heart failure (CHF) during 12-52 months' follow-up after acute myocardial infarction. This was puzzling in light of the observation that patients with findings suggesting left ventricular dysfunction (LVD) at baseline on diltiazem had more cardiac events (cardiac mortality or recurrent nonfatal infarction) than such patients on placebo. We hypothesized that diltiazem increased the frequency of late CHF as well as of cardiac events, but only in patients predisposed by LVD. Using the same characterizing variables as the primary MDPIT analysis, we found that patients with pulmonary congestion, anterolateral Q wave infarction, or reduced ejection fraction (EF) at baseline were more likely to have CHF during follow-up than those without these markers of LVD. CHF was particularly frequent in the patients with LVD who were randomized to diltiazem. Among those with a baseline EF of less than 0.40, late CHF appeared in 12% (39/326) receiving placebo and 21% (61/297) receiving diltiazem (p = 0.004). Life table analysis in patients with an EF of less than 0.40 confirmed more frequent late CHF in those taking diltiazem (p = 0.0017). In addition, the diltiazem-associated rise in the frequency of late CHF was progressively greater with increasingly severe decrements in baseline EF. This diltiazem effect was absent in patients with pulmonary congestion at baseline but an EF of 0.40 or more, suggesting a unique association between diltiazem-related late CHF and systolic LVD.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute myocardial infarction associated with single vessel coronary artery disease: An analysis of clinical outcome and the prognostic importance of vessel patency and residual ischemie myocardium

The long-term outcome and the significance of residual ischemie myocardium, as assessed by predischarge exercise thallium scintigraphy and vessel patency, were studied in 97 patients with single vessel coronary artery disease by angiography 12 ± 4 days after uncomplicated myocardial infarction. During a mean follow-up period of 39 ± 17 months, ηρ patients died, 6 (6%) had a recurrent nonfatal infarction and 25 (26%) experienced rapidly progressive angina requiring hospitalization. Although neither exercise-induced angina nor ST segment depression was predictive of a recurrent cardiac event, the mean number of infarct zone scan segments showing thallium redistribution (1.0 ± 1.0 versus 0.5 ± 0.8, p = 0.01) and the percent of patients with infarct zone redistribution (61 versus 39%, p = 0.05) were greater in those patients who experienced a late ischemie event. Kaplan-Meier analysis demonstrated a tower event-free survival rate in patients with redistribution (n = 45) than in those without redistribution (n = 52) (p = 0.019).Although no patient received immediate ihrombolytic therapy, the infarct-related vessel was angiographically patent in 40 patients (41%). Vessel patency did not influence event-free survival, although a patent vessel, as compared with an occluded vessel, was associated with a greater prevalence of nun-Q wave infarction (58 versus 21%. p < 0.001), fewer persistent infarct zone thallium defects (1.2 ± 1.1 versus 2.0 ± 1.2, p = 0.001), more reversible infarct zone thallium defects (1.0 ± 1.0 versus 0.5 ± 0.9, p = 0.02) and a trend toward a higher left ventricular ejection fraction (53 ± 10% versus 49 ± 12%, p = 0.07).In summary, uncomplicated myocardial infarction in patients with single vessel coronary artery disease is associated with a very low incidence of subsequent death and reinfarction. The presence of infarct zone thallium redistribution), compared with its absence, is predictive of a higher cardiac eyent rate. These data should be considered when recommending prophylactic percutaneous transluminal angioplasty after uncomplicated myocardial infarction in asymptomatic patients with single vessel coronary disease. On the basis of these results, future randomized trials designed to evaluate the therapeutic efficacy of revascuiarization in asymptomatic postinfarction patients with single vessel disease should limit enrollment to those patients with residual ischemia located within the infarct zone.

Clinical course and risk stratification of myocardial infarct survivors with three-vessel disease

Prevalence of three-vessel disease was prospectively analyzed in a series of 462 consecutive infarct survivors aged 60 years or less. Eighty-seven percent (403) of the patients were catheterized within one month of the acute event, and were followed for a mean of 43 months (range 21 to 69). Three-vessel disease was present in 96 cases (24%) and these patients form the study population. The primary goals of this study were to determine the prevalence of three-vessel disease and to identify predictors of survival and new coronary events among this subset of infarct survivors. During follow-up, 15 patients died, 17 had a recurrent nonfatal infarction, and 54 developed angina (4-year probability of each cardiac event being 0.20, 0.22, and 0.59, respectively). Cox's stepwise multivariate analysis identified the ejection fraction (EF) as the only predictor of survival ( p < 0.001). No predictors for nonfatal ischemic events were found among the independent variables considered. Patients were stratified in risk categories according to the EF. Four-year probability of survival was 1.0 in participants with EF = >50% (n = 23), 0.77 for those with EF = 21% to 49% (n = 66), and 0.22 in patients with more severe left ventricular dysfunction, EF = <20% (n = 7). Probability of occurrence of nonfatal reinfarction or angina was similar in the three risk categories. Thus, our results indicate that a normal ejection fraction is found in 25% of infarct survivors with three-vessel disease, and that this subset of patients has a low incidence of early and intermediate range coronary events.

Prognostic value of exercise testing: a 6-year follow-up in post-myocardial infarction patients.

The predictive value of a symptom-limited exercise test was studied over a 6-year period in 112 men, who had survived a myocardial infarct. The test was performed within 3 months after the infarct. Among clinical variables, only a history of a previous myocardial infarct seems to bear some prognostic importance. Among the exercise parameters, the development of a ST-segment depression of greater than or equal to 2.0 mm at low effort and the maximal exercise parameters were indicative of future mortality and non-fatal recurrent infarction.