Long-term excess mortality associated with diabetes following acute myocardial infarction: a population-based cohort study.

BACKGROUND: The long-term excess risk of death associated with diabetes following acute myocardial infarction is unknown. We determined the excess risk of death associated with diabetes among patients with ST-elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) after adjustment for comorbidity, risk factors and cardiovascular treatments. METHODS: Nationwide population-based cohort (STEMI n=281 259 and NSTEMI n=422 661) using data from the UK acute myocardial infarction registry, MINAP, between 1 January 2003 and 30 June 2013. Age, sex, calendar year and country-specific mortality rates for the populace of England and Wales (n=56.9 million) were matched to cases of STEMI and NSTEMI. Flexible parametric survival models were used to calculate excess mortality rate ratios (EMRR) after multivariable adjustment. This study is registered at ClinicalTrials.gov (NCT02591576). RESULTS: Over 1.94 million person-years follow-up including 120 568 (17.1%) patients with diabetes, there were 187 875 (26.7%) deaths. Overall, unadjusted (all cause) mortality was higher among patients with than without diabetes (35.8% vs 25.3%). After adjustment for age, sex and year of acute myocardial infarction, diabetes was associated with a 72% and 67% excess risk of death following STEMI (EMRR 1.72, 95% CI 1.66 to 1.79) and NSTEMI (1.67, 1.63 to 1.71). Diabetes remained significantly associated with substantial excess mortality despite cumulative adjustment for comorbidity (EMRR 1.52, 95% CI 1.46 to 1.58 vs 1.45, 1.42 to 1.49), risk factors (1.50, 1.44 to 1.57 vs 1.33, 1.30 to 1.36) and cardiovascular treatments (1.56, 1.49 to 1.63 vs 1.39, 1.36 to 1.43). CONCLUSIONS: At index acute myocardial infarction, diabetes was common and associated with significant long-term excess mortality, over and above the effects of comorbidities, risk factors and cardiovascular treatments.

Geographic variation in the treatment of non-ST-segment myocardial infarction in the English National Health Service: a cohort study.

OBJECTIVES: To investigate geographic variation in guideline-indicated treatments for non-ST-elevation myocardial infarction (NSTEMI) in the English National Health Service (NHS). DESIGN: Cohort study using registry data from the Myocardial Ischaemia National Audit Project. SETTING: All Clinical Commissioning Groups (CCGs) (n=211) in the English NHS. PARTICIPANTS: 357 228 patients with NSTEMI between 1 January 2003 and 30 June 2013. MAIN OUTCOME MEASURE: Proportion of eligible NSTEMI who received all eligible guideline-indicated treatments (optimal care) according to the date of guideline publication. RESULTS: The proportion of NSTEMI who received optimal care was low (48 257/357 228; 13.5%) and varied between CCGs (median 12.8%, IQR 0.7-18.1%). The greatest geographic variation was for aldosterone antagonists (16.7%, 0.0-40.0%) and least for use of an ECG (96.7%, 92.5-98.7%). The highest rates of care were for acute aspirin (median 92.8%, IQR 88.6-97.1%), and aspirin (90.1%, 85.1-93.3%) and statins (86.4%, 82.3-91.2%) at hospital discharge. The lowest rates were for smoking cessation advice (median 11.6%, IQR 8.7-16.6%), dietary advice (32.4%, 23.9-41.7%) and the prescription of P2Y12 inhibitors (39.7%, 32.4-46.9%). After adjustment for case mix, nearly all (99.6%) of the variation was due to between-hospital differences (median 64.7%, IQR 57.4-70.0%; between-hospital variance: 1.92, 95% CI 1.51 to 2.44; interclass correlation 0.996, 95% CI 0.976 to 0.999). CONCLUSIONS: Across the English NHS, the optimal use of guideline-indicated treatments for NSTEMI was low. Variation in the use of specific treatments for NSTEMI was mostly explained by between-hospital differences in care. Performance-based commissioning may increase the use of NSTEMI treatments and, therefore, reduce premature cardiovascular deaths. TRIAL REGISTRATION NUMBER: NCT02436187.

Mortality and missed opportunities along the pathway of care for ST-elevation myocardial infarction: a national cohort study.

AIMS: To examine the association between cumulative missed opportunities for care (CMOC) and mortality in patients with ST-elevation myocardial infarction (STEMI). METHODS: A cohort study of 112,286 STEMI patients discharged from hospital alive between January 2007 and December 2010, using data from the Myocardial Ischaemia National Audit Project (MINAP). A CMOC score was calculated for each patient and included: pre-hospital ECG, acute use of aspirin, timely reperfusion, prescription at hospital discharge of aspirin, thienopyridine inhibitor, ACE-inhibitor (or equivalent), HMG-CoA reductase inhibitor and ß-blocker, and referral for cardiac rehabilitation. Mixed-effects logistic regression models evaluated the effect of CMOC on risk-adjusted 30-day and 1-year mortality (RAMR). RESULTS: 44.5% of patients were ineligible for ≥1 care component. Of patients eligible for all nine components, 50.6% missed ≥1 opportunity. Pre-hospital ECG and timely reperfusion were most frequently missed, predicting further missed care at discharge (pre-hospital ECG incident rate ratio [95% CI]: 1.64 [1.58-1.70]; timely reperfusion 9.94 [9.51-10.40]). Patients ineligible for care had higher RAMR than those eligible for care (30-days: 1.7% vs. 1.1%; 1-year: 8.6% vs. 5.2%), whilst those with no missed care had lower mortality than patients with ≥4 CMOC (30-days: 0.5% vs. 5.4%, adjusted OR (aOR) per CMOC group 1.22, 95% CI: 1.05-1.42; 1-year: 3.2% vs. 22.8%, aOR 1.23, 1.13-1.34). CONCLUSIONS: Opportunities for care in STEMI are commonly missed and significantly associated with early and later mortality. Thus, outcomes after STEMI may be improved by greater attention to missed opportunities to eligible care.

Prospective development and validation of a model to predict heart failure hospitalisation.

OBJECTIVE: Acute heart failure syndrome (AHFS) is a major cause of hospitalisation and imparts a substantial burden on patients and healthcare systems. Tools to define risk of AHFS hospitalisation are lacking. METHODS: A prospective cohort study (n=628) of patients with stable chronic heart failure (CHF) secondary to left ventricular systolic dysfunction was used to derive an AHFS prediction model which was then assessed in a prospectively recruited validation cohort (n=462). RESULTS: Within the derivation cohort, 44 (7%) patients were hospitalised as a result of AHFS during 1 year of follow-up. Predictors of AHFS hospitalisation included furosemide equivalent dose, the presence of type 2 diabetes mellitus, AHFS hospitalisation within the previous year and pulmonary congestion on chest radiograph, all assessed at baseline. A multivariable model containing these four variables exhibited good calibration (Hosmer-Lemeshow p=0.38) and discrimination (C-statistic 0.77; 95% CI 0.71 to 0.84). Using a 2.5% risk cut-off for predicted AHFS, the model defined 38.5% of patients as low risk, with negative predictive value of 99.1%; this low risk cohort exhibited <1% excess all-cause mortality per annum when compared with contemporaneous actuarial data. Within the validation cohort, an identically applied model derived comparable performance parameters (C-statistic 0.81 (95% CI 0.74 to 0.87), Hosmer-Lemeshow p=0.15, negative predictive value 100%). CONCLUSIONS: A prospectively derived and validated model using simply obtained clinical data can identify patients with CHF at low risk of hospitalisation due to AHFS in the year following assessment. This may guide the design of future strategies allocating resources to the management of CHF.

An evaluation of composite indicators of hospital acute myocardial infarction care: a study of 136,392 patients from the Myocardial Ischaemia National Audit Project.

BACKGROUND: Hospital acute myocardial infarction (AMI) care is increasingly evaluated using composite quality scores. We investigated the influence of three aggregation methods for an AMI indicator on mortality and hospital rank. METHODS AND RESULTS: We studied 136,392 patients discharged alive from 199 hospitals with AMI recorded in the Myocardial Ischaemia National Audit Project, between 01/01/2008 and 31/12/2009. A composite of prescription of aspirin, thienopyridine inhibitor, ß-blocker, angiotensin converting enzyme inhibitor, HMG CoA reductase enzyme inhibitor and enrolment in cardiac rehabilitation at discharge was aggregated as opportunity based (OBCS), weighted opportunity-based (WOBCS) and all-or-nothing (ANCS) scores. We quantified adjusted 30-day, 6-month and 1-year mortality rates and hospital performance rank. Median (IQR) scores were OBCS: 95.0% (3.5), WOBCS: 94.7% (0.8) and ANCS: 80.9% (11.8). The three methods affected the proportion of hospitals outside 99.8% credible limits of the national median (OBCS: 52.2%, WOBCS: 64.3% and ANCS: 37.7%) and hospital rank. Each 1% increase in composite score was significantly associated with a 1 to 3% and a 4% reduction in 6-month and 1-year mortality, respectively. However, the ANCS had fewer cases and no significant association with 30-day mortality. CONCLUSIONS: A hospital composite score, incorporating 6 aspects of AMI care, was significantly inversely associated with mortality. However, composite aggregation method influenced hospital rank, number of cases available for analysis and size of the association with all-cause mortality, with the ANCS performing least well. The use and choice of composite scores in hospital AMI quality improvement requires careful evaluation.

Evaluation of risk scores for risk stratification of acute coronary syndromes in the Myocardial Infarction National Audit Project (MINAP) database.

OBJECTIVE: To compare the discriminative performance of the PURSUIT, GUSTO-1, GRACE, SRI and EMMACE risk models, assess their performance among risk supergroups and evaluate the EMMACE risk model over the wider spectrum of acute coronary syndrome (ACS). DESIGN: Observational study of a national registry. SETTING: All acute hospitals in England and Wales. PATIENTS: 100 686 cases of ACS between 2003 and 2005. MAIN OUTCOME MEASURES: Model performance (C-index) in predicting the likelihood of death over the time period for which they were designed. The C-index, or area under the receiver-operating curve, range 0-1, is a measure of the discriminative performance of a model. RESULTS: The C-indexes were: PURSUIT C-index 0.79 (95% confidence interval 0.78 to 0.80); GUSTO-1 0.80 (0.79 to 0.81); GRACE in-hospital 0.80 (0.80 to 0.81); GRACE 6-month 0.80 (0.79 to 0.80); SRI 0.79 (0.78 to 0.80); and EMMACE 0.78 (0.77 to 0.78). EMMACE maintained its ability to discriminate 30-day mortality throughout different ACS diagnoses. Recalibration of the model offered no notable improvement in performance over the original risk equation. For all models the discriminative performance was reduced in patients with diabetes, chronic renal failure or angina. CONCLUSION: The five ACS risk models maintained their discriminative performance in a large unselected English and Welsh ACS population, but performed less well in higher-risk supergroups. Simpler risk models had comparable performance to more complex risk models. The EMMACE risk score performed well across the wider spectrum of ACS diagnoses.

Predictors of in-hospital mortality for patients admitted with ST-elevation myocardial infarction: a real-world study using the Myocardial Infarction National Audit Project (MINAP) database.

OBJECTIVE: Although early thrombolysis reduces the risk of death in STEMI patients, mortality remains high. We evaluated factors predicting inpatient mortality for patients with STEMI in a "real-world" population. DESIGN: Analysis of the Myocardial Infarction National Audit Project (MINAP) database using multivariate logistic regression and area under the receiver operating curve analysis. SETTING: All acute hospitals in England and Wales. PATIENTS: 34 722 patients with STEMI from 1 January 2003 to 31 March 2005. RESULTS: Inpatient mortality was 10.6%. The highest odds ratios for inpatient survival were aspirin therapy given acutely and out-of-hospital thrombolysis, independently associated with a mortality risk reduction of over half. A 10-year increase in age doubled inpatient mortality risk, whereas cerebrovascular disease increased it by 1.7. The risk model comprised 14 predictors of mortality, C index = 0.82 (95% CI 0.82 to 0.83, p<0.001). A simple model comprising age, systolic blood pressure (SBP) and heart rate (HR) offered a C index of 0.80 (0.79 to 0.80, p<0.001). CONCLUSION: The strongest predictors of in-hospital survival for STEMI were aspirin therapy given acutely and out-of-hospital thrombolysis, Previous STEMI models have focused on age, SBP and HR We have confirmed the importance of these predictors in the discrimination of death after STEMI, but also demonstrated that other potentially modifiable variables impact upon the prediction of short-term mortality.

Predicting sudden death in patients with mild to moderate chronic heart failure.

OBJECTIVES: To explore the relation between non-invasive measures of cardiac function and sudden cardiac death, as well as the development and utility of an index integrating these variables to identify patients at increased risk of this mode of death. DESIGN: UK-HEART (United Kingdom-heart failure evaluation and assessment of risk trial) was a prospective study conducted between December 1993 and April 2000. The study was specifically designed to identify non-invasive markers of death and mode of death among patients with chronic heart failure. SETTING: 8 UK general hospitals. MAIN OUTCOME MEASURES: Death and mode of death. RESULTS: 553 patients aged a mean (SD) of 63 (10) years, in New York Heart Association functional class 2.3 (0.02), recruited prospectively. After 2365 patient-years' follow up, 201 patients had died (67 suddenly). Predictors of sudden death were greater cardiothoracic ratio, QRS dispersion, QT dispersion corrected for rate (QTc) across leads V1-V6 on the 12 lead ECG, and the presence of non-sustained ventricular tachycardia. The hazard ratio and 95% confidence intervals (CI) of sudden death for a 10% increase in cardiothoracic ratio was 1.43 (95% CI 1.20 to 1.71), for a 10% increase in QRS dispersion 1.11 (95% CI 1.04 to 1.19), for the presence of non-sustained ventricular tachycardia 2.03 (95% CI 1.27 to 3.25), and for a 10% increase in QTc dispersion across leads V1-V6 1.03 (95% CI 1.00 to 1.07) (all p < 0.04). An index derived from these four factors performed well in identifying patients specifically at increased risk of sudden death. CONCLUSIONS: Results show that an index derived from three widely available non-invasive investigations has the potential to identify ambulant patients with chronic heart failure at increased risk of sudden death. This predictive tool could be used to target more sophisticated investigations or interventions aimed at preventing sudden death.

Antiarrhythmic management and implantable defibrillator use in survivors of prehospital cardiac arrest without myocardial infarction in West Yorkshire.

OBJECTIVE: To explore the current use of secondary preventive treatment in survivors of out of hospital cardiac arrest without myocardial infarction (primary ventricular tachycardia/ventricular fibrillation (VT/VF)) in West Yorkshire, and assess the implications of recent studies on the benefits of implantable cardioverter-defibrillators (AICD) in this context. DESIGN: Retrospective analysis of an ambulance service based database of outcome after resuscitation of out of hospital cardiac arrest and the Leeds AICD implantation database. MAIN OUTCOME MEASURES: Mortality, rate of referral for specialist investigation, antiarrhythmic treatment. RESULTS: Twelve month mortality following successful discharge after primary VF arrest was 15%. Of 53 patients with primary VF/VT, 29 apparently did not see a cardiologist during the initial admission. Amiodarone was the most widely used antiarrhythmic agent. Six patients (15%) received an AICD. During the same period 22 patients from the same catchment area received an AICD following an in-hospital cardiac arrest. CONCLUSIONS: Mortality among survivors of non-infarct related prehospital cardiac arrest remains significant, with few patients being referred for specialist investigation. The implementation of recent guidelines on AICD use in cardiac arrest survivors would have resulted in an approximate 60% increase in the total numbers of defibrillators implanted in the West Yorkshire area.

The relationship between QT intervals and mortality in ambulant patients with chronic heart failure. The united kingdom heart failure evaluation and assessment of risk trial (UK-HEART)

AIMS: Mortality in patients with heart failure remains high and is difficult to predict. QT interval parameters on a 12-lead ECG have been shown to predict arrhythmic events in patients with a variety of myocardial diseases. There is some, but not consistent, evidence that QT interval parameters may act as predictors of mortality, in particular sudden death, in patients with heart failure. In an adequately powered prospective study we have studied QT interval parameters in patients with stable chronic heart failure in order to determine whether they are predictive of all-cause mortality or mode of death. METHODS AND RESULTS: Five hundred and fifty-four ambulant outpatients with chronic heart failure were recruited. A 12-lead ECG, chest radiograph, echocardiogram, 24 h ambulatory electrocardiogram and serum for biochemical analysis were obtained at baseline. Patients were followed for 471+/-168 days. QT intervals were measured in all leads blinded to patient's characteristics and outcome, were corrected for heart rate, and the maximum QT intervals, and QT dispersion (range of QT intervals) were determined. The same parameters were determined for JT intervals. The primary end-point was all-cause mortality, secondary end-points were sudden cardiac death and death due to progressive heart failure. Multivariate analysis with the Cox's proportional hazards model was used to determine which variables were independently related to outcome. Four hundred and ninety-five patients had analysable ECGs at study entry and of these 71 died during follow-up. The heart rate corrected QT dispersion and maximum QT interval were significant univariate predictors of all-cause mortality (P=0.026 and <0.0001 respectively), and also of sudden death and progressive heart failure death, but were not related to outcome in the multivariate analysis. The independent predictors of all-cause mortality were cardiothoracic ratio (P=0.0003), creatinine (P=0.0009), heart rate (P=0.007), echocardiographically derived left ventricular end-diastolic dimension (P=0.007) and ventricular couplets on 24 h electrocardiographic monitoring (P=0.015). CONCLUSION: In an adequately powered prospective study none of the QT or JT parameters were shown to be independent predictors of outcome in patients with mild to moderate congestive heart failure. These variables do not therefore add to the prognostic information which can be gained from simple radiographic, biochemical, echocardiographic and Holter data in this group of patients.

Ventricular dilatation in the absence of ACE inhibitors: influence of haemodynamic and neurohormonal variables following myocardial infarction.

OBJECTIVE: To examine the relation between patterns of ventricular remodelling and haemodynamic and neurohormonal variables, at rest and during symptom limited exercise, in the year following acute myocardial infarction in patients not receiving angiotensin converting enzyme (ACE) inhibitors. DESIGN: A prospective observational study. PATIENTS: 65 patients recruited following hospital admission with a transmural anterior myocardial infarction. METHODS: Central haemodynamics and neurohormonal activation at rest and during symptom limited treadmill exercise were measured at baseline before hospital discharge, one month later, and at three monthly intervals thereafter. PATIENTS were classified according to individual patterns of change in left ventricular end diastolic volumes at rest, assessed at each visit using transthoracic echocardiography. RESULTS: In most patients (n = 43, 66%) ventricular volumes were unchanged or reduced. Mean (SEM) treadmill exercise capacity and peak exercise cardiac index increased at month 12 by 200 (24) seconds (p < 0.001 v baseline) and by 0.8 (0.4) l/min/m2 (p<0.05 v baseline), respectively, in this group. In patients with limited ventricular dilatation (n = 11, 17%) exercise capacity increased by 259 (52) seconds (p < 0.001 v baseline) and peak exercise cardiac index improved by 0.8 (0.7) l/min/m2 (NS). In the remaining 11 patients with progressive left ventricular dilatation, exercise capacity increased by 308 (53) seconds (p< 0. 001 v baseline) and peak exercise cardiac index similarly improved by 1.3 (0.7) l/min/m2 (NS). There were trends towards increased atrial natriuretic factor (ANF) secretion at rest and at peak exercise in this group. CONCLUSIONS: Ventricular dilatation after acute myocardial infarction is a heterogeneous process that is progressive in only a minority of patients. Compensatory mechanisms, including ANF release, appear capable of maintaining and improving exercise capacity in most patients for at least 12 months, even in those with a progressive increase in ventricular size.

Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart).

BACKGROUND: Patients with chronic heart failure (CHF) have a continuing high mortality. Autonomic dysfunction may play an important role in the pathophysiology of cardiac death in CHF. UK-HEART examined the value of heart rate variability (HRV) measures as independent predictors of death in CHF. METHODS AND RESULTS: In a prospective study powered for mortality, we recruited 433 outpatients 62+/-9.6 years old with CHF (NYHA functional class I to III; mean ejection fraction, 0.41+/-0.17). Time-domain HRV indices and conventional prognostic indicators were related to death by multivariate analysis. During 482+/-161 days of follow-up, cardiothoracic ratio, SDNN, left ventricular end-systolic diameter, and serum sodium were significant predictors of all-cause mortality. The risk ratio for a 41.2-ms decrease in SDNN was 1.62 (95% CI, 1.16 to 2.44). The annual mortality rate for the study population in SDNN subgroups was 5.5% for >100 ms, 12.7% for 50 to 100 ms, and 51.4% for <50 ms. SDNN, creatinine, and serum sodium were related to progressive heart failure death. Cardiothoracic ratio, left ventricular end-diastolic diameter, the presence of nonsustained ventricular tachycardia, and serum potassium were related to sudden cardiac death. A reduction in SDNN was the most powerful predictor of the risk of death due to progressive heart failure. CONCLUSIONS: CHF is associated with autonomic dysfunction, which can be quantified by measuring HRV. A reduction in SDNN identifies patients at high risk of death and is a better predictor of death due to progressive heart failure than other conventional clinical measurements. High-risk subgroups identified by this measurement are candidates for additional therapy after prescription of an ACE inhibitor.

Junior doctors and clinical audit.

OBJECTIVES: To assess the extent of junior doctor involvement in clinical audit, the degree of support from audit staff, and the perceived value of the resulting audits. DESIGN: Postal survey of National Health Service (NHS) junior doctors. SUBJECTS AND SETTINGS: 704 junior doctors in central Leeds hospitals, June 1996. RESULTS: Questionnaires were returned by 232 respondents (33%), 211 (31%) were completed; 157 respondents (74%) had personally performed audit. Mean (+/- SD) duration since last audit project was 14.9 (14.1) (range 0-84) months. Of the respondents who had personally performed audit, 88 (56%) did not use the hospital audit department, 60 (38%) received no guidance and only 19 (12%) were involved in re-auditing the same project. Mean (+/- SD) time spent per audit project was 27.8 (37.7), (range 2-212) hours. Seventy-five junior doctors (48%) were aware of subsequent change in clinical practice, 41 (26%) perceived a negative personal benefit from audit, 33 (21%) perceived a negative departmental benefit, and 42 (27%) felt that audit was a waste of time. CONCLUSIONS: A large proportion of junior doctors are involved in audit projects that do not conform to established good practice and which have a low impact on clinical behaviour. Although junior doctors feel that there is inadequate assistance and poor supervision whilst performing audit, they still support the principle of audit. There is a need to improve the quality and supervision of audit projects performed by junior doctors.

Management and health status in the first year after out-of-hospital cardiac arrest.

The one-year survival, functional and cerebral capacity and patient management following out-of-hospital cardiac arrest were examined in a follow-up study of 143 prospectively identified patients discharged from a West Yorkshire hospital between January 1987 and July 1993. One-year survival was 87%; 13 of the 18 deaths were cardiac related; 89% of survivors had no further cardiac related admissions; 98% of patients surviving to one year were capable of independent daily activities. There was low utilisation of simple drug therapy: 23% of patients were discharged taking beta-blockers and 52% aspirin; 50% of patients discharged after a primary arrhythmic event were taking antiarrhythmic therapy or were given an implantable defibrillator. Irrespective of the availability of invasive cardiac facilities, there was underutilisation of investigations: only 39% of patients were seen by a cardiologist and 54% were not evaluated for ischaemic risk. Significant improvements in patient management could probably be achieved quickly without substantial increases in resources.

Haemodynamic and hormonal response to a stream of cooled air.

Many patients with angina note that their symptoms deteriorate in cold weather, although the precise physiological mechanism that explains this remains unclear. Exposure of the face to cool winds may be a contributory factor. The cardiovascular and hormonal response to a localised stream of room (22 degrees C) and cold (4 degrees C) air during submaximal treadmill exercise was therefore studied in nine normal subjects. Cardiac output and respiratory gases were measured with a mass spectrometer, using the indirect Fick principle. Blood samples were taken for plasma noradrenaline. A localised stream of air at 5 m.s-1 produced significant cardiovascular effects at rest, some of which persisted during exercise. In response to cold air, stroke volume, cardiac output, blood pressure and oxygen uptake increased (all P < 0.05). There was a trend towards a reduction in heart rate at rest and increase in plasma noradrenaline. Room air caused a reduction in blood pressure (P = 0.01) but stroke volumes and oxygen uptake were unchanged. The results of this study demonstrate significant cardiovascular effects of a cooled air facial stimulus at rest and during exercise. They may, in part, explain the effects of cold winds on patients with angina.

Patterns of neuroendocrine activation at rest and during exercise following acute myocardial infarction.

Previous studies of neurohumoral activation following myocardial infarction have concentrated on the within-hospital phase and have only made measurements at rest. The objectives of this study were to measure neuroendocrine activity in the early convalescent phase of myocardial infarction at rest and during symptom-limited maximal exercise and to study the effects of early drug therapy. We studied 75 patients, mean age 57 (range 37-74) without evidence of overt heart failure, following Q-wave myocardial infarction. Patients were studied a mean of 17 days following myocardial infarction and compared with 11 age-matched control subjects. Plasma noradrenaline, adrenaline, atrial natriuretic peptide and plasma renin activity were measured at rest, at submaximal and symptom-limited maximal treadmill exercise. At the time of study 40 patients were taking beta-blockers, 19 diuretics and 16 no treatment. Atrial natriuretic peptide levels were higher at rest (P = 0.0001) and at symptom-limited exercise (P = 0.002) in the patient group than in the control subjects. Although there were no significant resting differences between the patient subgroups, at symptom-limited exercise plasma atrial natriuretic peptide levels were significantly higher in the patients taking beta-blockers than in the other patient groups (P = 0.001). Plasma renin activity was no different between the patients and the control subjects at rest or during exercise. Those patients taking diuretics had higher values at rest (P = 0.001) and during exercise (P = 0.005) compared with the remaining patients. There were no significant differences in resting or maximal exercise levels of plasma noradrenaline and adrenaline between the patients and the control subjects (all P > 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)