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Thrombolytic therapy reduces mortality in patients with acute myocardial infarction (AMI) and left bundle branch block (LBBB). The difficulty in accurately diagnosing AMI in patients with LBBB, however, might result in their undertreatment. Among 3,890 patients hospitalized with chest pain, 241 (6.2%) had LBBB at presentation. The only variable independently associated with AMI among patients with LBBB was in-hospital left ventricular failure (odds ratio [OR]: 4.32, 95% confidence interval [CI]: 1.95-9.57, p < 0.0005). Only 16 (29%) of the LBBB patients with AMI received thrombolytic therapy compared with 583 (78%) of the 747 patients with ST-elevation AMI (p < 0.0005). A further 19 (10%) LBBB patients without AMI also received thrombolysis. Difficulty in making an accurate early diagnosis in patients with LBBB ensures that the majority of those with AMI fail to receive thrombolytic therapy while others without AMI are treated inappropriately. Improved diagnostic and therapeutic strategies are needed for patients with acute coronary syndromes and LBBB., (Copyright (c) 2010 Wiley Periodicals, Inc.)

Aims: To determine the clinical utility of 24 hour Holter monitoring by measuring the frequency of candidate arrhythmias recorded during the investigation of palpitations and altered consciousness., Methods: Of 9,729 Holter recordings, reports were available in 8,973 (92.2%) performed in the 7394 patients who comprise the study group. The mean age of the study group was 66 +/- 19 years and 56.4% were women., Results: The most common indications were altered consciousness (41.7%) and palpitations (36.2%). Among patients with palpitations and sinus rhythm (n=2688), recordings were normal in 2247 (83.6%). Abnormalities included paroxysmal atrial fibrillation (PAF, 6.6%), narrow complex tachycardia (NCT, 2.8%) nonsustained or sustained ventricular tachycardia (NSVT/VT, 2.6%). Among patients with altered consciousness (n=3075), recordings were normal in 2589 (84.2%). Abnormalities included PAF (9.5%), NCT (2.6%), NSV/VT (0.2%), pause >2.8s (2.2%) and high degree AV block (1.3%). The diagnostic yield of Holter monitoring was particularly low in patients aged < or =50 years, of whom 93.1% had palpitations and 95.3% had altered consciousness had normal recordings., Conclusions: The diagnostic utility of Holter monitoring in patients being investigated for palpitations and altered consciousness is very limited, particularly in young patients for whom alternative diagnostic methods should be considered.

Background: Anemia is an important determinant of heart failure and death after ST elevation myocardial infarction (STEMI). The frequency of anemia and its impact on these outcomes across the range of acute coronary syndromes (ACS), however, have not been defined., Methods: This is a cohort study of 2310 patients with ACS stratified by quartiles of admission hemoglobin concentration [Hb]): Q1, <12.5 g/dL; Q2, 12.5-13.6 g/dL; Q3, 13.7-14.7 g/dL; Q4, >14.7 g/dL., Results: There were 29.7% of women and 23.2% of men who were anemic. Rates of STEMI increased across [Hb] quartile groups from 25.0% (Q1) to 35.5% (Q4) as rates of unstable angina decreased from 52.0% (Q1) to 40.7% (Q4) (P < .0005). Despite this, rates of left ventricular failure (LVF) were inversely related to [Hb] in all diagnostic groups, patients with unstable angina (Q1, 14.2%; Q4, 4.4%; P < .0005) showing a similar trend to patients with non-STEMI (Q1, 26.8%; Q4, 10.4%; P < .0005) and STEMI (Q1, 33.8%; Q4, 20.6%; P < .0005). The age-adjusted odds of LVF in Q4 compared with Q1 were 0.64 (95% confidence interval, 0.45-0.90). Inhospital cardiac mortality was 3.0% and was not influenced by [Hb]., Conclusions: Anemia is a common comorbidity in patients presenting with ACS, and it is a powerful independent determinant of LVF. The association with LVF occurs not only in STEMI but also in less severe diagnostic groups.

Objectives: To determine whether case fatality rates in South Asian (Bangladeshi, Indian and Pakistani) patients with acute myocardial infarction have shown similar declines to those reported for white patients during the past 15 years., Design: Cross-sectional, observational study., Setting: Coronary care unit in east London., Patients: 2640 patients-29% South Asian-admitted with acute myocardial infarction between January 1988 and December 2002., Main Outcome Measures: Differences over time in rates of in-hospital death, ventricular fibrillation and left ventricular failure., Results: The proportion of South Asians increased from 22% in 1988-92 to 37% in 1998-2002. Indices of infarct severity were similar in South Asian and white patients, with declining frequencies of ST elevation infarction (88.2% to 77.5%, p < 0.0001), Q wave development (78.1% to 56.9%, p < 0.0001) and mean (interquartile range) peak serum creatine kinase concentrations (1250 (567-2078) to 1007 (538-1758) IU/l, p < 0.0001) between 1988-92 and 1998-2002. Rates of in-hospital death (13.0% to 9.4%, p < 0.01), ventricular fibrillation (9.2% to 6.0%, p < 0.001) and left ventricular failure (33.2% to 26.5%, p < 0.0001) all declined; these changes did not interact significantly with ethnicity. Odds ratios for the effect of time on risk of death increased from 0.81 (95% CI 0.70 to 0.93) to 1.02 (95% CI 0.87 to 1.21) after adjustment for ethnicity and indices of infarct severity (ST elevation, peak creatine kinase, Q wave development and treatment with a thrombolytic)., Conclusions: In the past 15 years, death from acute myocardial infarction among South Asians has declined at a rate similar to that seen in white patients. This is largely caused by reductions in indices of infarct severity.

Objectives: To evaluate the impact the National Service Framework (NSF) for coronary heart disease has had on emergency treatment and outcomes in patients presenting with acute coronary syndromes., Design: Retrospective cohort study., Setting: Coronary care units of two district general hospitals., Results: Data from 3371 patients were recorded, 1993 patients in the 27 months before the introduction of the NSF and 1378 patients in the 24 months afterwards. After the introduction of the NSF in-hospital mortality was significantly reduced (95 patients (4.8%) v 43 (3.2%), p = 0.02). This was associated with a reduction in the development of Q wave myocardial infarction (40.6% v 33.3%, p < 0.0001) and in the incidence of left ventricular failure (15.9% v 12.3%, p = 0.003). The proportion of patients receiving thrombolysis increased (69.4% v 84.7%, p < 0.0001) with a decrease in the time taken to receive it (proportion thrombolysed within 20 minutes 12.1% v 26.6%, p < 0.0001). The prescription of beta blockers (51.9% v 65.8%, p < 0.0001), angiotensin converting enzyme inhibitors (37% v 66.4%, p < 0.0001), and statins (55.2% v 72.7%, p < 0.0001) improved and the proportion of patients referred for invasive investigation increased (18.3% v 27.0%, p < 0.0001). Trend analysis showed that improvements in mortality and thrombolysis were directly associated with publication of the NSF, whereas the improvements seen in prescription of beta blockers and statins were the continuation of pre-existing trends., Conclusions: In the two years that followed publication of the NSF the initial treatment and outcome of patients presenting with acute coronary syndromes improved. Some of the improvements can be attributed to the NSF but others are continuations of pre-existing trends.

Background: Heart failure has a poor prognosis, yet drugs known to improve outcomes are either not prescribed, or prescribed at sub-therapeutic doses. The National Service Framework (NSF) for coronary heart disease recommended specialist heart failure clinics to address this problem but their efficacy has not been evaluated., Objectives: To determine the effectiveness of a protocol-driven heart failure clinic staffed by nurse and pharmacist specialists for improving symptoms and optimising treatment with key therapeutic agents, without adversely affecting renal function., Results: Of the 234 patients with at least one follow-up visit, 127 (57%) were receiving none or only one key therapeutic agent when first seen, this was reduced to 25 patients (11%) at most recent follow-up. The improvement in prescription rates was accompanied by significant up-titration of dose, the proportion of patients on "medium" or "high" doses rising from 43 (18%) to 134 (57%) for beta-blockers, and from 129 (55%) to 201 (86%) for ACE-inhibitors/angiotensin receptor blockers. Clinical improvement was reflected in reductions in patients with NYHA functional classes III and IV (93 (40%) to 53 (23%)), and in patients with moderate or severe symptoms. Significant reductions in alcohol consumption and cigarette smoking were recorded. Up-titration of treatment was associated with reductions in heart rate and systolic blood pressure; increases in serum potassium and creatinine concentrations were small., Conclusion: In a heart failure clinic staffed by nurse and pharmacist specialists, it is possible to achieve target doses of key therapeutic agents and improve symptoms without adversely affecting electrolytes or renal function.

Aims: To compare major determinants of myocardial oxygen demand (heart rate, blood pressure and rate pressure product) in patients with and without diabetes admitted with acute coronary syndromes., Methods: A cross-sectional study of the relation between diabetes and haemodynamic indices of myocardial oxygen demand in 2542 patients with acute coronary syndromes, of whom 1041 (41.0%) had acute myocardial infarction and 1501 (59.0%) unstable angina., Results: Of the 2542 patients, 701 (27.6%) had diabetes. Major haemodynamic determinants of myocardial oxygen demand were higher in patients with than without diabetes: heart rate 80.0 +/- 20.4 vs. 75.2 +/- 19.2 beats/minute (P < 0.0001); systolic blood pressure 147.3 +/- 30.3 vs. 143.2 +/- 28.5 mmHg (P = 0.002); rate-pressure product 11533 +/- 4198 vs. 10541 +/- 3689 beats/minute x mmHg (P < 0.0001). Multiple regression analysis confirmed diabetes as a significant determinant of presenting heart rate [multiplicative coefficient (MC) 1.05; 95% confidence interval (CI) 1.03-1.07; P < 0.0001], rate pressure product (MC 1.09; CI 1.05-1.12; P < 0.0001) and systolic blood pressure, which was estimated to be 3.9 mmHg higher than in patients without diabetes (P=0.003). These effects of diabetes were independent of a range of baseline variables including acute left ventricular failure and mode of presentation (unstable angina or myocardial infarction)., Conclusions: In acute coronary syndromes, heart rate and other determinants of myocardial oxygen demand are higher in patients with than without diabetes, providing a potential contributory mechanism of exaggerated regional ischaemia in this high-risk group.

In this prospective cohort study we analyzed the impact of admission renal function on the hospital course of 2,503 patients with unstable angina pectoris (UAP) and acute myocardial infarction (AMI). The patients were stratified into quartile groups (Q1 to Q4) defined by baseline corrected creatinine clearance (cCrCl) values of 51.4, 63.8, and 76.8 mg/min/72 kg. The proportions of patients with a discharge diagnosis of AMI increased with declining cCrCl, from 35.5% in Q4 to 46.0% in Q1 (p <0.0001). The frequency of left ventricular (LV) failure (Q4 4.5%, Q1 31.0%, p <0.0001) and cardiac death (Q4 0.5%, Q1 9.5%, p <0.0001) also increased linearly with decreasing cCrCl, with no evidence that the prognostic impact of renal dysfunction was different in AMI or UAP (p for interaction 0.15). Logistic regression analysis confirmed the independent effects of cCrCl on outcome, with odds of LV failure and cardiac death for patients in Q4 being 0.34 (95% confidence intervals 0.16 to 0.72) and 0.14 (95% confidence intervals 0.03 to 0.74), respectively, relative to patients in Q1. No threshold was detected for the adverse effects of renal dysfunction on outcomes; the log odds of LV failure and cardiac death against quartiles of cCrCl both showed significant linear trends (p <0.0001) with each change in quartile, resulting in risk reductions of 55% (odds [SE] 0.45 [0.03]) and 65% (odds [SE]: 0.35 [0.05]), respectively. In conclusion, renal function showed a graded association with LV failure and hospital death that was independent of diagnosis (UAP or AMI) and other baseline variables. There was no detectable threshold of renal dysfunction for these adverse prognostic effects.

Objectives: To analyse the relation between serum glucose concentration and hospital outcome across the whole spectrum of acute coronary syndromes., Methods: This was a prospective cohort study of 2127 patients presenting with acute coronary syndromes. The patients were stratified into quartile groups (Q1 to Q4) defined by serum glucose concentrations of 5.8, 7.2, and 10.0 mmol/l. The relation between quartile group and major in-hospital complications was analysed., Results: The proportion of patients with acute myocardial infarction increased incrementally across the quartile groups, from 21.4% in Q1 to 47.9% in Q4 (p < 0.0001). The trend for frequency of in-hospital major complications was similar, particularly left ventricular failure (LVF) (Q1 6.4%, Q4 25.2%, p < 0.0001) and cardiac death (Q1 0.7%, Q4 6.1%, p < 0.0001). The relations were linear, each glucose quartile increment being associated with an odds ratio of 1.46 (95% confidence interval (CI) 1.27 to 1.70) for LVF and 1.52 (95% CI 1.17 to 1.97) for cardiac death. Although complication rates were higher for a discharge diagnosis of acute myocardial infarction than for unstable angina, there was no evidence that the effects of serum glucose concentration were different for the two groups, there being no significant interaction with discharge diagnosis in the associations between glucose quartile and LVF (p = 0.69) or cardiac death (p = 0.17). Similarly there was no significant interaction with diabetic status in the associations between glucose quartile and LVF (p = 0.08) or cardiac death (p = 0.09)., Conclusion: Admission glycaemia stratified patients with acute coronary syndromes according to their risk of in-hospital LVF and cardiac mortality. There was no detectable glycaemic threshold for these adverse effects. The prognostic correlates of admission glycaemia were unaffected by diabetic status and did not differ significantly between patients with acute myocardial infarction and those with unstable angina.

Objectives: To compare serum potassium concentrations in diabetic and non-diabetic patients in the early phase of acute coronary syndromes., Background: Acute phase hypokalaemia occurs in response to adrenergic activation, which stimulates membrane bound sodium-potassium-ATPase and drives potassium into the cells. It is not known whether the hypokalaemia is attenuated in patients with diabetes because of the high prevalence of sympathetic nerve dysfunction., Methods: Prospective cohort study of 2428 patients presenting with acute coronary syndromes. Patients were stratified by duration of chest pain, diabetic status, and pretreatment with beta blockers., Results: The mean (SD) serum potassium concentration was significantly higher in diabetic than in non-diabetic patients (4.3 (0.5) v 4.1 (0.5) mmol/l, p < 0.0001). Multivariate analysis identified diabetes as an independent predictor of a serum potassium concentration in the upper half of the distribution (odds ratio 1.66, 95% confidence interval 1.38 to 2.00). In patients presenting within 6 hours of symptom onset, there was a progressive increase in plasma potassium concentrations from 4.08 (0.46) mmol/l in patients presenting within 2 hours, to 4.20 (0.47) mmol/l in patients presenting between 2-4 hours, to 4.24 (0.52) mmol/l in patients presenting between 4-6 hours (p = 0.0007). This pattern of increasing serum potassium concentration with duration of chest pain was attenuated in patients with diabetes, particularly those with unstable angina. Similar attenuation occurred in patients pretreated with beta blockers., Conclusion: In acute coronary syndromes, patients with diabetes have significantly higher serum potassium concentrations and do not exhibit the early dip seen in non-diabetics. This may reflect sympathetic nerve dysfunction that commonly complicates diabetes.

Background: Shortening prehospital delay has been identified as an important means of improving responses to reperfusion treatment. If this increases the risk profile of the population delivered to hospital, it may paradoxically cause a deterioration in hospital mortality., Objective: To examine the interaction between arrival time (time from onset of chest pain to arrival at hospital) and thrombolytic treatment in determining the early outcome of acute myocardial infarction., Methods: Prospective cohort study of 1723 patients with acute myocardial infarction who were potentially eligible for thrombolytic treatment (ST elevation on ECG; arrival time < or = 12 hours)., Results: All patients were eligible for thrombolysis but only 1098 (80%) received it. Patients who did not receive thrombolytic treatment were older (66 (58-73) v 61 (53-70) years, p < 0.001), more commonly female (32.1% v 24.8%, p < 0.01), and had higher frequencies of previous infarction (28.6% v 15.6%, p < 0.001) and left ventricular failure (37.5% v 26.9%, p < 0.01) than patients who received thrombolytic treatment. For the group as a whole, 30 day mortality was 11.7% and was unaffected by arrival time, but in patients who did not receive thrombolysis an arrival time of < or = 6 hours was associated with significantly higher 30 day mortality than an arrival time of 6-12 hours (24.3% v 2.6%, p = 0.002). Conversely, in patients who did receive thrombolysis an arrival time of < or = 6 hours was associated with a lower 30 day mortality than an arrival time of 6-12 hours (8.5% v 14.5%, p < 0.02)., Conclusions: Shortening prehospital delay in acute myocardial infarction will tend to increase the risk profile of patients presenting to emergency departments. The data presented here indicate that this may increase hospital mortality if underutilisation of thrombolytic treatment among high risk groups is not diminished.

Background: Early discharge after myocardial infarction is safe and feasible. Factors that delay discharge need to be identified in order to improve care and reduce bed occupancy., Objective: To investigate the potential of the restricted weekend service that operates in most hospitals to delay patient discharge., Design: Prospective cohort study., Subjects and Setting: 2541 consecutive patients with acute myocardial infarction admitted to the coronary care unit of three local district hospitals over a 12 year period., Results: Clinical factors affecting the duration of stay were age, sex, and severity of infarction. Thus older patients and women stayed significantly longer, as did patients with enzymatically large infarcts. Day of week also had an important influence on duration of stay. Discharge occurred most often on a Friday (p = 0.006) and least often over the weekend (p = 0.0001). Patients were preferentially discharged on a Friday if the length of stay was more than 72 hours. Thus patients admitted on a Sunday or Monday were usually discharged the following Friday, corresponding to a median duration of stay of five or four days, respectively. For patients admitted on Tuesday to Saturday, weekend discharge was avoided and the median duration of stay was six to eight days., Conclusions: For patients with acute myocardial infarction, discharge decisions were influenced appropriately by clinical indicators of risk, but inappropriately by the day of the week. Thus weekend discharge was generally avoided, leading to variations in length of stay that were largely determined by the day of the week on which admission occurred rather than clinical need.

Objectives: The goal of this study was to determine the interaction between smoking and the glycoprotein IIIa P1(A2) polymorphism in patients admitted with non-ST-elevation acute coronary syndromes (ACS)., Background: An increased incidence of the P1(A2) polymorphism in smokers presenting with ST-elevation acute myocardial infarction (AMI) has recently been reported. We, therefore, postulated that, as a consequence of this interaction, fewer smokers with the P1(A2) polymorphism would present with non-ST-elevation ACS., Methods: We performed a prospective cohort analysis of 220 white Caucasoid patients admitted with non-ST-elevation ACS fulfilling Braunwald class IIIb criteria for unstable angina who were stratified by smoking status., Results: There were twice as many nonsmokers as smokers. Nonsmokers compared with smokers were older (mean [SD]; 63.9 [11.2] vs. 57.6 [10.3]; p < 0.0001), more likely to have had a previous admission with unstable angina (24.3% vs. 13.2%; p = 0.051) and AMI (45.8% vs. 30.3%; p < 0.026), more likely to have undergone revascularization (24.3% vs. 1.8%; p = 0.028) and were more likely to be on aspirin on admission (60.4% vs. 44.7%; p = 0.026). The proportion of nonsmokers positive for the P1(A2) polymorphism was equivalent to that expected for this population but was significantly reduced in smokers (28.7% vs. 10%; Pearson chi-square = 9.09, p = 0.0026). In a logistic regression model, the odds ratio (OR) for being positive for the P1(A2) polymorphism was significantly reduced by smoking (OR [interquartile range]: 0.26 [0.11 to 0.62]; p = 0.0026)., Conclusions: There is a significant reduction in the P1(A2) polymorphism in smokers admitted with non-ST-elevation ACS compared with nonsmokers, which suggests an interaction between smoking and this polymorphism.

Objectives: This study was done to determine the effects of angiotensin-converting enzyme (ACE) inhibition and other clinical factors on troponin release in non-ST-elevation acute coronary syndrome (ACS)., Background: Troponin is now widely used as a marker of risk in ACS, but determinants of its release have not been defined., Methods: This was a prospective cohort study of 301 consecutive patients admitted with non-ST-elevation ACS. Baseline clinical data were recorded, ACE gene polymorphism was determined and serial blood samples were obtained for troponin-I assay., Results: Significant troponin-I release (>0.1 microg/l) was detected in 93 (31%) patients. Pretreatment with ACE inhibitors, recorded in 53 patients (17.6%), independently reduced the odds of troponin-I release (odds ratio 0.25; 95% confidence intervals 0.10 to 0.64) and was associated with lower maximum troponin-I concentrations (median [interquartile range]) compared with patients not pretreated with ACE inhibitors (0.44 microg/l [0.19 to 2.65 microg/l] vs. 4.18 microg/l [0.91 to 12.41 microg/l], p = 0.01). Pretreatment with aspirin, recorded in 173 patients (57.5%), did not significantly reduce the odds of troponin-I release after adjustment but was associated with lower maximum troponin-I concentrations compared with patients not pretreated with aspirin (2.31 microg/l [0.72 to 8.02 microg/l] vs. 5.85 microg/l [1.19 to 12.79 microg/l], p = 0.05). The ACE genotyping (n = 268) showed 81 patients (30%) DD homozygous and 77 (29%) II homozygous. There was no association between ACE genotype and troponin release., Conclusions: We conclude that ACE inhibition reduces troponin release in non-ST-elevation ACS. This is likely to be mediated by the beneficial effects of treatment on vascular reactivity and the coagulation system.

Objective: To examine the influence of socioeconomic deprivation on case fatality following acute myocardial infarction., Design: Prospective cohort observational study., Setting: General hospital., Patients: 1417 white and south Asian patients admitted with acute myocardial infarction between January 1988 and December 1996, and classified by the Carstairs socioeconomic deprivation score of the enumeration district of residence., Main Outcome Measures: 30 day and one year survival., Results: There was little variation across deprivation groups in age, sex, or smoking status, though a higher proportion of patients from more deprived enumeration districts were diabetic and of south Asian origin, and a higher proportion of them developed Q wave infarction and left ventricular failure. There was no appreciable variation in clinical treatment with deprivation. Patients from more deprived enumeration districts had a higher risk of recurrent ischaemic events (death, recurrent myocardial infarction, or unstable angina) over the first 30 days: event free survival (95% confidence interval (CI)) of the most deprived quartile was 0.79 (95% CI 0.74 to 0.83) compared with 0.85 (95% CI 0.80 to 0.88) in the least deprived quartile. The unadjusted hazard ratio corresponding to an increase from the 5th to 95th centile of the deprivation distribution was 1.54 (95% CI 1.02 to 2.32), and 1.59 (95% CI 1.03 to 2.44) after adjustment for age, sex, racial group, diabetes, acute treatment with thrombolysis and aspirin, and left ventricular failure. Survival from 30 days to one year, however, did not show a socioeconomic gradient (hazard ratio adjusted for the same variables was 1.07 (95% CI 0.68 to 1.70))., Conclusions: In patients hospitalised with acute myocardial infarction, there is a strong association between early recurrent ischaemic events and socioeconomic deprivation that is not accounted for by clinical presentation or treatment. This association appears to be attenuated over time.

Objectives: This study was designed to assess the interaction between aspirin and C-reactive protein (CRP) release in unstable angina., Background: C-reactive protein release in acute coronary syndromes may be a response to myocardial necrosis or may reflect the inflammatory process that drives atherogenesis. Aspirin has the potential to influence CRP release, either by its anti-inflammatory activity or by reducing myocardial necrosis. The clinical significance of this potential interaction has not previously been tested., Methods: We conducted a prospective cohort study of 304 consecutive patients admitted with non-ST-elevation acute coronary syndromes. Serial blood samples were obtained for CRP and troponin I assay. End points were cardiac death and nonfatal myocardial infarction during follow-up for 12 months., Results: A total of 174 patients (57%) were taking aspirin before admission. Patients taking aspirin had lower troponin I concentrations throughout the sampling period, only 45 (26.0%) having concentrations >0.1 mg/l compared with 48 (37.8%) patients not taking aspirin (p = 0.03). Maximum CRP concentrations were also lower in patients taking aspirin (8.16 mg/l [3.24 to 24.5]) than in patients not taking aspirin (11.3 mg/l [4.15 to 26.1]), although the difference was not significant. However, there was significant interaction (p = 0.04) between prior aspirin therapy and the predictive value of CRP concentrations for death and myocardial infarction at 12 months. Thus, odds ratios (95% confidence intervals) for events associated with an increase of 1 standard deviation in maximum CRP concentration were 2.64 (1.22-5.72) in patients not pretreated with aspirin compared with 0.98 (0.60-1.62) in patients pretreated with aspirin., Conclusions: The association between CRP and cardiac events in patients with unstable angina is influenced by pretreatment with aspirin. Modification of the acute-phase inflammatory responses to myocardial injury is the major mechanism of this interaction.

Aims: To define the trends in management and outcome of acute myocardial infarction over the first decade since the widespread adoption of thrombolytic therapy., Methods: Prospective cohort study of 1737 consecutive patients with acute myocardial infarction admitted for coronary care between January 1988 and December 1997., Results: Trend analysis with comparison of early (1988-1992) and late (1993-1997) cohorts showed significant increments in median age (interquartile range) from 62 (54-70) to 64 (55-72) years (P < 0.01) but the proportion of smokers fell from 72.7% to 65.8% (P < 0.01). The proportion of patients receiving thrombolytic therapy increased from 70% to 78.1% (P < 0.01) as median door-to-needle times fell significantly from 92 (60-145) to 68 (45-123) minutes (P < 0.01). The proportion of patients discharged on aspirin increased from 88.2% to 95.9% (P < 0.01), -blockers increased from 37.4% to 45.8% (P < 0.01), and angiotensin converting enzyme inhibitors increased from 12.4% to 35.7% (P < 0.01). Median hospital stay fell from 9 (7-11) to 6 (5-9) days (P < 0.0001). Although the severity of infarction declined, judged by reductions in the frequency of Q-wave development from 78.1% to 73.9% (P = 0.01) and peak CK from 1250 (569-2085) to 1004 (511-1722) IU/l, survival (95% confidence intervals) for the early and late cohorts did not change significantly either at 30 days [0.86 (0.83-0.88) vs. 0.85 (0.83-0.88)] or at 1 year [0.79 (0.76-0.81) vs 0.78 (0.76-0.81)]., Conclusion: The decade from 1988-1997 saw significant changes in the demographic characteristics and risk factor profiles of patients with acute myocardial infarction admitted for coronary care. We observed trends towards increasingly aggressive antithrombotic treatment and early discharge policies, with more patients being prescribed drugs for secondary prevention. The combined effects of these complex changes on the outcome of infarction defy simple analysis and there was no palpable change in short- and longer-term.

Background: Women have excessive mortality rates after acute myocardial infarction compared with men. The extent to which this increased risk can be attributed to differences in treatment is not well-understood., Methods: This was an observational follow-up study of 1737 patients admitted with acute myocardial infarction for coronary care between January 1, 1988, and December 31, 1997., Results: Compared with men, women took longer to arrive at the hospital (132.5 minutes [range 76 to 291 minutes] vs 120 minutes [range 60 to 240 minutes]; P =.006), were less likely to receive aspirin acutely (87.8% vs 91.3%; P =.03), had longer door-to-needle times (90 minutes [range 60 to 143.5 minutes] vs 78 minutes [range 50 to 131 minutes]; P =.004), and were less likely to be given beta-blockers at hospital discharge (31.6% vs 44.9%; P <.0001). Estimated survival (95% confidence interval [CI]) at 30 days was only 78.4% (range 74.4% to 81.9%) for women compared with 88.0% (range 86.1% to 89.7%) for men. Women were older and more often white, but their excess risk (hazard ratio 2.09; 95% CI, 1.59-2.75) persisted after adjustment for age, racial group, and diabetes (hazard ratio 1.52; 95% CI, 1.15-2.01). Additional adjustment for emergency thrombolytic and aspirin therapy caused a further small reduction in the excess risk for women (hazard ratio 1.46; 95% CI, 1. 09-1.98), but with adjustment for aspirin and beta-blockers prescribed at discharge, the excess risk attributable to being female disappeared as the hazard ratio fell to 0.75 (95% CI, 0.31-1. 84). Estimated 30-day survival free of reinfarction and unstable angina was also lower for women than for men (75% [range 71% to 79%] vs 86% [range 84% to 88%]); again, the excess risk for women persisted despite adjustment for age and racial group before disappearing as treatment variables were introduced into the model. The influence of treatment variables on the differential risks for women and men disappeared at 12 months., Conclusions: This study has shown that women with acute myocardial infarction arrived later at the hospital, were less likely to be given aspirin therapy acutely, had longer door-to-needle times, and, on discharge from the hospital, were less likely to be prescribed beta-blockers for secondary prevention. The data suggest that the failure to treat women as vigorously as men made a significant contribution to their worse outcome.

Objective: To determine the changing risk of ventricular fibrillation, the prognostic implications, and the potential long term prognostic benefit of earlier hospital admission, after acute myocardial infarction., Design: Prospective observational study., Setting: A district general hospital in east London., Patients: 1225 consecutive patients admitted to a coronary care unit with acute myocardial infarction., Main Outcome Measures: Time of onset of pain and ventricular fibrillation, and long term survival of patients admitted with acute myocardial infarction., Results: The rate of ventricular fibrillation in these hospital inpatients was high in the first hour from onset of pain (118 events/1000 persons/h; 95% confidence interval (CI) 50.7 to 231) and fell rapidly to an almost constant low level by six hours; 27.4% of patients with early ventricular fibrillation died in hospital, compared with 11.6% of those without (p < 0.0001), but mortality in patients who survived to hospital discharge was not altered by early ventricular fibrillation (five year survival: 75.0% (95% CI 60.0% to 84.8%) with ventricular fibrillation v 73.3% (95% CI 69.6% to 76.6%) without ventricular fibrillation)., Conclusions: Patients successfully resuscitated from early ventricular fibrillation have the same prognosis as those without ventricular fibrillation after acute myocardial infarction. Faster access to facilities for resuscitation must be achieved if major improvements in the persistently high case fatality of patients after acute myocardial infarction are to be made.

Objective: To examine demographic and clinical characteristics of patients with acute myocardial infarction in order to identify factors affecting the electrocardiographic evolution of injury., Methods: Prospective cohort study of 1399 consecutive patients with a first myocardial infarction. Baseline clinical data associated with ST elevation and Q wave development were identified and 12 month survival was estimated., Results: Smoking had complex effects on the evolution of injury, increasing the odds of ST elevation (odds ratio (OR) 1.61; 95% confidence interval (CI) 1.08 to 2.36), but reducing the odds of Q wave development (OR 0.69, 95% CI 0.49 to 0.96). The effects of previous aspirin treatment were more consistent with reductions in the odds of ST elevation (OR 0.57, 95% CI 0.35 to 0.94) and Q wave development (OR 0.53, 95% CI 0.34 to 0. 84). ST elevation and Q wave development were both associated with an adverse prognosis, with estimated 12 month survival rates of 80. 6% (95% CI 78.2% to 83.1%) and 80.0% (95% CI 77.5% to 82.5%), respectively, compared with 86.5% (95% CI 81.2% to 91.9%) and 89.9% (95% CI 86.2% to 93.7%) for patients without these ECG changes., Conclusions: The thrombogenicity of the blood may be a major determinant of infarct severity. Smoking increases thrombogenicity and the likelihood of ST elevation, but because coronary occlusion is relatively more thrombotic in smokers, responses to both endogenous and exogenous thrombolysis are better, reducing the risk of Q wave development. Previous aspirin treatment reduces thrombogenicity, protecting against ST elevation and Q wave development.

Objectives: To examine the criteria for selecting patients presenting with unstable angina for cardiac catheterisation and to assess the extent to which these criteria successfully incorporate high risk groups., Methods and Results: This was a prospective cohort study of 517 patients admitted with unstable angina with 12 months follow-up; 139 patients (26.9%) had cardiac catheterisation 32 days or longer after presentation. The odds of early catheterisation were increased by regional ST segment depression on the presenting ECG (odds ratio (OR) 1.70, 95% confidence intervals (CI) 1.01-2.87) and ongoing ischaemic chest pain more than 12 hours after admission (OR 9.72, CI 6.10-15.49), and reduced by age over 65 years (OR 0.56, 95% CI 0.35-0.90) and heart failure (OR 0.26, CI 0.11-0.64). The 12-month rates of myocardial infarction (MI) or death were 8.6% and 17.7% (p = 0.01) in patients who were and were not referred for early cardiac catheterisation, respectively. Survival analysis showed that the odds of MI and death in the first 12 months were increased substantially by heart failure (OR 2.82, 95% CI 1.53-5.20) and age over 65 (OR 1.91, 95% CI 1.13-3.23)., Conclusion: Selection for early cardiac catheterisation in this unstable angina population was largely ischaemia-driven, based on ongoing chest pain and ST segment depression. This policy was associated with a low event rate in the ischaemic group, but it failed to target elderly patients and those with heart failure who were at greatest risk of MI and death during the first year.

Background: About 75% of patients with acute myocardial infarction are older than 70 years, but patients in this age group are commonly treated less vigorously than younger patients. This differential treatment may partly reflect clinicians' misconceptions about the outlook of such patients, and the importance of age in clinical decisions. We examined how age does and should affect the management of patients and risk stratification in acute myocardial infarction., Methods: In this prospective cohort study, we recruited 1225 consecutive patients admitted with acute myocardial infarction to a district general hospital in east London. The primary endpoint was death. We used tabulation and regression methods to analyse the association between age group and clinical variables., Findings: Patients aged 70 years or older took a longer time to arrive in hospital and were less likely to receive thrombolysis or discharge beta-blockers than patients younger than 60 years: odds ratio 0.63 (95% CI 9.45-0.88) for thrombolysis and 0.25 (0.16-0.37) for beta-blockade, adjusted for sex, diabetes, previous acute myocardial infarction, Q wave infarction, and left-ventricular failure. Left-ventricular failure was the strongest independent predictor of death within 1 year of infarction with a hazard ratio of 4.76 (3.53-6.43), adjusted for age, sex, diabetes, and Q wave infarction. Patients aged 70 years or older without left-ventricular failure had significantly better survival at 1 year after acute myocardial infarction than patients under 60 years with left-ventricular failure. 70.8% (62.2-78.2) of the older patients who survived to hospital discharge were still alive 3 years later., Interpretation: Elderly patients with acute myocardial infarction were treated less vigorously than younger patients. The prognosis of acute myocardial infarction, however, was substantially affected by the development of left-ventricular failure and other clinical indices, such that many older patients had a better outlook than younger patients with adverse clinical factors. In planning risk-based management, consideration of age independently of clinical status is inappropriate.

Objectives: The purpose of this study was to examine clinical characteristics of patients with acute coronary syndromes to identify factors that influence the mode of presentation., Background: In acute coronary syndromes, presentation with myocardial infarction or unstable angina has major prognostic implications, yet clinical factors affecting the mode of presentation are not well defined., Methods: A prospective cohort study was made of 1,111 patients with acute coronary syndromes. Baseline demographic, clinical and biochemical data were compared in groups with myocardial infarction (n = 633) and unstable angina (n = 478)., Results: The risk of myocardial infarction relative to unstable angina was increased by age >70 years (odds ratio [OR] 2.21; 95% confidence interval [CI] 1.33 to 3.66), male gender (OR 1.56; CI 1.13 to 2.16) and cigarette smoking (OR 1.49; CI 1.09 to 2.03). A rise in admission creatinine from the 10th to the 90th centile of the distribution also increased the odds of myocardial infarction (OR 1.30; CI 1.05 to 1.94). Conversely, the risk of myocardial infarction relative to unstable angina was reduced by previous treatment with aspirin (OR 0.37; CI 0.27 to 0.52), hypertension (OR 0.64; CI 0.47 to 0.86) and previous acute coronary syndromes (OR 0.36; CI 0.26 to 0.51) and revascularization procedures (OR 0.36; CI 0.21 to 0.62)., Conclusions: The clinical presentation of acute coronary syndromes may be influenced by various factors that have the potential to influence the coagulability of the blood, the collateralization of the coronary circulation and myocardial mass. Myocardial infarction is favored by cigarette smoking, advanced age and renal impairment, while unstable angina is favored by treatment with aspirin, hypertension, previous revascularization and previous coronary syndromes.

Aim: To determine whether general practitioners (GPs) prefer structured computer-generated or standard dictated outpatient clinic letters., Design: Questionnaire survey of all GPs referring patients to an open-access chest pain clinic at a district general hospital in London. The GPs were asked to compare three twinned examples of structured computer-generated and unstructured dictated letters., Results: Of 93 respondents (response rate 77.5%), 75 (80.6%) preferred the computer-generated letter and 16 (17.2%) preferred the dictated letter (p < 0.0005). The preferred features of the computer-generated letter were its clear presentation, subheadings, and concise information. The computer-generated letter scored significantly higher than the dictated letter: for clarity, mean 8.2 vs 6.5 (p < 0.0005); content, mean 8.5 vs 6.9 (p < 0.0005); and readability, mean 8.2 vs 6.8 (p < 0.0005). The GPs in the survey considered a mean delay of 3.4 days to be acceptable for receiving the letter from the chest pain clinic., Conclusion: GPs prefer structured computer-generated letters to unstructured dictated letters for patients referred to an open-access chest pain clinic. Computer-generated correspondence allows rapid feedback of information to the referring GP, one of the key requirements of open-access clinics.

Objective: To document the frequency of conduction defects and their influence on prognosis in a large series of patients with acute myocardial infarction who underwent coronary care during a period when thrombolytic therapy was in common usage., Background: Conduction defects have been associated with an adverse prognosis following acute myocardial infarction, but there are few data on the incidence and outcome of conduction defects since the introduction of thrombolytic therapy., Patients and Methods: The study group comprised 1225 consecutive patients with acute myocardial infarction treated in the coronary care unit from 1 January 1988 to 31 December 1994. Conduction defects were recorded prospectively and were classified as follows: complete atrioventricular node block associated with narrow complex escape rhythms; left or right bundle branch block; bifascicular block; complete heart block involving both bundle branches., Results: Electrocardiographic data were available in 1220 patients. Complete atrioventricular node block occurred in 65 (5.3%), left and right bundle branch block in 29 (2.4%) and 44 (3.6%) bifascicular block in 36 (2.9%) and complete heart block involving both bundle branches in 20 (1.6%). The more advanced degrees of block in the bundle branches occurred more commonly in patients with diabetes, previous infarction. Q-wave infarction, anterior infarction and left ventricular failure. Survival analysis showed an increased short- and long-term cardiac mortality in patients with conduction defects, prognosis worsening as the severity of the conduction defect increased., Conclusion: Conduction defects complicated acute myocardial infarction in 16% of cases and had a graded impact on the short- and long-term prognosis, patients with advanced bundle branch involvement faring worst. The data showed a small decline in the rate of severe conduction defects compared with previous studies, possibly reflecting the beneficial effects of thrombolytic therapy on infarct size.

The discharge summary from hospital to community physician contributes importantly to patient management, but deficiencies in its preparation are well documented. We sought to determine the preferences of general practitioners for standard dictated or computer-generated discharge summaries for patients with acute coronary syndromes. The majority (68.5%) of GPs preferred the computerized summary and particularly liked its comprehensive content, concise style, ease of access to relevant information, clarity and ease of reading. Most (66.9%) thought the computer-generated summary provided the clearer management plan and 70.8% recommended its use for other specialities. In addition, its speed of generation enables GPs to receive a summary within seven days of patient discharge.

Objectives: To examine the circadian, seasonal, and weekly rhythms of acute myocardial infarction, and to identify subgroups in whom the rhythms are attenuated or absent to provide further information about the mechanisms of the rhythms and the processes responsible for triggering plaque events., Design and Setting: Prospective, observational study in a general hospital., Patients and Methods: 1225 consecutive patients admitted to a coronary care unit with acute myocardial infarction were studied. Admission rates were calculated according to the hour of the day (circadian rhythm), day of the week (weekly rhythm), and month of year (seasonal rhythm). The data were analysed for variations within the whole group and within subgroups., Results: A weekly rhythm of acute myocardial infarction could not be demonstrated but there was a trend towards higher admission rates at the beginning of the week. However, the time of onset of symptoms showed significant circadian variation for the group as a whole, peaking in the morning (P = 0.006), against an otherwise fairly constant background rate. Subgroup analysis showed complete absence of the circadian rhythm in patients who were diabetic, South Asian, or taking beta blockers or aspirin on admission. Significant seasonal variation in admission rates was also demonstrated for the group as a whole with a winter peak and a summer trough (P = 0.009). Again, no seasonal rhythm could be demonstrated in patients who were diabetic, South Asian, or taking beta blockers or aspirin on admission., Conclusions: The absence of circadian and seasonal rhythms of acute myocardial infarction in almost identical subgroups suggests that common mechanisms are involved in driving these rhythms. The autonomic nervous system is a likely candidate because the rhythms were absent in patients taking beta blockers as well as in patients in whom derangement of autonomic function commonly occurs.

Prognosis in acute myocardial infarction has been compared in patients with and without diagnostic ECGs. Of 817 patients, 89.4% had ST elevation, 2.4% had left bundle branch block, and 8.2% had no ST elevation. Patients without ST elevation had a hospital mortality rate of 3.0% compared with 14.0% and 40.0%, respectively, in patients with ST elevation and left bundle branch block (p = 0.0001). Event-free survival at 6 months in patients without ST elevation was 85.6% (74.1% to 92.3%), compared with 72.9% (69.4% to 76.0%) and 31.0% (12.0% to 52.3%) in patients with ST elevation and left bundle branch block (p < 0.001). The excess risk associated with ST elevation was largely attributable to the severity of infarction: after adjustment for Q-wave development and heart failure, the hazard ratio fell from 2.24 (1.43 to 4.38) to 1.76 (0.86 to 3.59). In conclusion, acute myocardial infarction has a considerably better prognosis when it is unassociated with ST elevation or left bundle branch block. This finding may have important implications for interventional management.

Background: Thrombolytic treatment reduces mortality in patients with acute myocardial infarction but is associated with recurrent thrombotic events after admission, and it is unclear whether current practices of early hospital discharge are safe. Timing of first major adverse events (death, reinfarction, unstable angina, secondary ventricular fibrillation) in the early post-infarction period was studied to determine the risks., Design: Follow up study., Patients: 608 consecutive patients (447 men and 161 women) with confirmed myocardial infarction who were admitted to the coronary care unit of a district general hospital between January 1989 and December 1991. Clinical details, including the development of left ventricular failure and in hospital adverse events, were recorded prospectively. Follow up for out of hospital adverse events was carried out by review of the case notes, postal questionnaire, and where necessary, by telephone contact with the patient and his general practitioner., Results: The risk (95% confidence interval) of major adverse events in the first 10 days was 32.3% (26.3 to 39.4%) in patients with heart failure and 7.3% (5.1 to 9.2%) in those without. Smoothed estimates of the event rate in patients without heart failure decreased from 5.9 events/1000 persons/day on day 6 to 3.4 events/1000 persons/day on day 10 and 0.9 events/1000 persons/day on day 21. The corresponding cumulative risk estimates suggest that about 11 in every 1000 patients suffer a major, but often unpreventable, adverse event on day 6 or 7 after admission, and 23 in every 1000 do so between days 6 and 10., Conclusions: The point at which the risk to the individual becomes acceptably low is a matter of judgement, but the risk of a major adverse event declines rapidly after a heart attack, and particularly for patients without heart failure discharge within a few days may be appropriate. Prolonging stay unnecessarily may use resources which could be more effectively used to treat cardiac disease in other ways.

Objective: To examine the influence that being female has on the outcome of acute myocardial infarction., Design: Observational follow up study., Setting: London district general hospital., Patients: 216 women and 607 men with acute myocardial infarction admitted to a coronary care unit from 1 January 1988 to 31 December 1992., Main Outcome Measures: All cause mortality and recurrent ischaemic events in the first six months., Results: Event free survival (95% confidence interval) at six months was 63.3% (56.3% to 69.4%) in women and 76.1% (72.4% to 79.4%) in men, P < 0.001. The difference was confined to the first 30 days but thereafter the hazard plots for women and men converged, with reduction of the hazard ratio from 2.36 (1.70 to 3.27) to 0.81 (0.44 to 1.48). Women were older, but their excess risk persisted after adjustment for age, other baseline variables, and indices of severity of infarction (hazard ratio 1.53 (1.09 to 2.15), P = 0.015). Women tended to be treated with thrombolysis less commonly than men but the difference was small. Substantially fewer women than men, however, were discharged taking beta blockers (23.3% v 41.4%, P < 0.001), and although additional adjustment for discharge treatment did not further reduce the point estimate of the hazard ratio (1.84 (0.89-3.83)), the 95% confidence interval was wide and statistical significance was lost., Conclusions: Women with acute myocardial infarction have a worse prognosis than men but the excess risk is confined to the first 30 days and is only partly explained by age and other baseline variables. The tendency for women to receive less vigorous treatment than men must be remedied before gender can be considered to be an independent determinant of risk.

The aim of this study was to compare the roles of clinical assessment, treadmill stress testing, and Holter ST analysis for postinfarction risk stratification in patients treated with thrombolysis. The study group consisted of 256 consecutive patients, all of whom underwent Holter ST monitoring early (mean 83 hours, range 48 to 180) after admission. Of these, 12 were excluded from the analysis either because Holter recordings were of insufficient quality (n = 6), or because reinfarction occurred within 24 hours of monitoring (n = 6). In the remaining 244 patients, 43 sustained a recurrent event (death, reinfarction, unstable angina) over the 8-month (range 3 to 12) follow-up period, and an additional 14 patients required revascularization. At multivariate event-free survival analysis, Killip class > or = 2 and Holter ST shift were independently predictive of the outcome. The strongest predictor was Holter ST shift at a cumulative duration of > 60 minutes. Of the 232 patients eligible for stress testing (12 sustained an event between Holter monitoring and the scheduled stress test), 196 were able to perform the test. The variable "inability to perform a stress test" was not independently predictive of outcome and did not influence the multivariate analysis. When clinical, Holter, and stress test variables were taken into account in patients who performed a stress test, Killip class was the only independent predictor of outcome (event-free survival). When revascularization was included as an end point, Holter ST shift was the only independent predictor of outcome. In conclusion, a significant proportion of recurrent events after thrombolysis occurs very early, before stress testing can be performed.(ABSTRACT TRUNCATED AT 250 WORDS)

Objective: To assess the perception of angina in the elderly and its relationship to autonomic function., Design: Prospective cohort study of patients with exertional ischemia., Setting: Medical, geriatric and cardiac outpatient clinics in two centers., Participants: All subjects had ischemic heart disease as evidenced by positive treadmill stress tests and, in some, diagnostic angiography and/or documented Q wave infarction. In the first study (I), 37 older patients (range 70-82 years) and 39 younger patients (range 42-59 years) were studied. In a subsequent study (II), a further 49 patients were divided into 2 groups: those with good perception of angina (Anginal Perception Threshold < 15 seconds, group A, 26 patients) and those with no angina despite ischemia (group B, 23 patients)., Measurements: Anginal perceptual threshold (APT), age, cardiovascular autonomic function, and blood pressure were measured. APT was defined as the time between onset of 1 mm ST depression to the onset of angina during treadmill stress testing. Autonomic function was studied using heart rate ratios before and after the valsalva maneuver, heart rate responses to deep breathing, and heart rate and blood pressure responses to standing., Results: In study I, APT in the older patients was delayed by a median value of 49 seconds [79 (range 15-188) versus 30 (-99 to 97) seconds in the younger patients, P < 0.001]. There was no significant correlation between prolonged APT and autonomic dysfunction when younger and older groups were analyzed independently or together. When, however, the high APT subgroup (APT > 30 seconds) was analyzed separately, there was a significant correlation between APT prolongation and impaired valsalva response (r = -0.4; P < 0.005). In study II, 21 of 23 patients (91.3%) with positive exercise test but with no angina (group B) had at least one abnormal autonomic function test compared with 5 of 26 (19%) patients with good anginal perception (group A). Of note, group A was significantly younger than group B [60 (53-63) years vs 66 (62-70 years, P < 0.001]., Conclusion: Elevation of APT in the elderly suggests that warning of critical myocardial ischemia is delayed. Autonomic dysfunction may be one of the underlying mechanisms.

Objective: To investigate the clinical importance of reciprocal ST depression induced by exercise testing early after acute myocardial infarction in patients treated with thrombolysis., Design: Prospective observational study., Setting: District general hospital in London., Subjects: 202 patients (170 men) aged 33-69 with acute myocardial infarction treated with thrombolysis., Main Outcome Measures: All patients underwent exercise testing and coronary arteriography. ST depression induced by exercise was classified as either reciprocal (associated with ST elevation) or isolated (occurring on its own). The relation between reciprocal ST depression and the following end points was studied: characteristics of the infarct, left ventricular ejection fraction, extent of coronary artery disease on arteriography, and presence of angina induced by exercise., Results: Reciprocal ST depression occurred almost exclusively in Q wave infarctions and was associated with a lower overall ejection fraction than isolated ST depression. It tended to be associated with persistent occlusion of the coronary artery related to the infarct and did not indicate remote ischaemia due to multivessel coronary disease. Unlike isolated ST depression, reciprocal ST depression was not associated with angina induced by exercise., Conclusions: Reciprocal ST depression induced by exercise is usually associated with extensive Q wave infarctions and persistent occlusion of the artery related to the infarct. It does not seem to indicate reversible ischaemia and should not be used as a non-invasive marker of multivessel disease in the assessment of requirements for further investigation soon after acute myocardial infarction.

Objective: To compare the circadian rhythm of myocardial ischaemia in patients with stable angina with that in patients in the early postinfarction period with particular emphasis on the role of the autonomic nervous system., Patients: 44 patients with stable angina and ischaemia on treadmill testing (group A) were compared with 131 patients in the early postinfarction period (group B). All had 48 hour ambulatory Holter monitoring., Setting: Coronary care unit and cardiology department of a district general hospital., Design: Prospective, between group, comparative study., Results: 337 ischaemic episodes occurred in 35 patients in group A and 370 ischaemic episodes occurred in 65 patients in group B. 34% of patients in group A had only silent episodes of ischaemia compared with 97% in group B (p < 0.0001). In group A ischaemic episodes showed a circadian rhythm that peaked during the daytime hours (p < 0.0001), but this was not seen in group B. Both the high (0.15-0.40 Hz) and low (0.04-0.15 Hz) frequency spectral components of heart rate variability showed a clear circadian rhythm (p < 0.0001); peak values occurred during the sleeping hours, although this pattern was less pronounced in group B. The ratio of low to high frequency variability (a measure of sympathovagal balance) showed a peak in daytime hours in group A (p < 0.002), but this was not seen in group B., Conclusion: In stable angina, myocardial ischaemia peaks during the day and is associated with a similar circadian rhythm of sympathovagal balance. In the early postinfarction period both the ischaemic and sympathovagal rhythms are severely diminished or lost altogether. Circadian changes in sympathovagal tone may explain, at least in part, the circadian rhythm of ambulatory myocardial ischaemia in patients with stable angina.

The relation between both time and frequency domain analyses of RR variability and mortality was examined in a series of 226 consecutive patients with acute myocardial infarction admitted to 3 district hospitals in London. All patients underwent 24-hour Holter monitoring early after infarction (mean 83 hours, range 48 to 180), and time and frequency domain analyses of RR variability were performed using commercially available software. During an 8-month follow-up period (range 3 to 12 months), there were 19 cardiac deaths (8.4%). Time domain analysis confirmed reduced RR variability (SDRR, SDANN, SD) among nonsurvivors compared with survivors. However, there was no difference between the groups when the percentage of absolute differences between successive RR intervals > 50 ms (pNN50) and the root-mean-square of successive differences (RMSSD)--vagal measures of RR variability--were analyzed. Frequency domain analysis demonstrated a significant difference between those who died and the survivors when the low-frequency component--modulated by both vagal and sympathetic mechanisms--was analyzed; however, this was less marked when the high-frequency component--modulated by vagal activity--was analyzed. None of these measures of RR variability was related to infarct site or left ventricular ejection fraction. In conclusion, the data confirm the association between low RR variability and mortality after acute myocardial infarction. However, the mechanism does not appear to relate exclusively to decreased parasympathetic tone. The data suggest that the increased risk of early mortality associated with reduced RR variability reflects an imbalance in sympathovagal function that is unrelated to left ventricular function.

Objective: To evaluate Holter and treadmill responses in patients with stable angina or recent myocardial infarction in order to compare the mechanisms of ischaemia and its symptomatic expression in these two groups., Patients: 75 patients with ischaemic ST segment depression on both a treadmill stress test and ambulatory Holter monitoring. Group A comprised 35 patients with stable angina, and group B comprised 40 patients in the early period after infarction., Setting: The coronary care unit and cardiology department of a district general hospital., Design: A prospective, between group, comparative study., Results: Treadmill test showed demand driven ischaemia in both groups. Although ST depression occurred at comparable rate-pressure products and workloads, it was associated with angina in 80% of group A compared with only 40% of group B (p < 0.005). During Holter monitoring, ST depression was associated with an attenuated increase in rate in group A and almost no increase in rate in group B (18.2% v 3.7%; p < 0.005), suggesting that reductions in myocardial oxygen delivery were contributing to the ischaemic episodes, particularly in group B. Ischaemic episodes were more commonly silent during Holter monitoring, particularly patients in group B, only two of whom experienced angina in association with ST depression. Spectral and non-spectral measures of heart rate variability were significantly reduced in group B compared with group A. Patients with silent exertional ischaemia in group A had significantly less heart rate variability than patients who experienced angina but this difference was not seen in group B., Conclusion: In stable angina, myocardial ischaemia is usually painful and demand driven, whereas in the early period after infarction silent, supply driven ischaemia predominates. The failure of myocardial ischaemia to provoke symptoms in some patients with stable angina may be related to autonomic dysfunction affecting the sensory supply to the heart. In the early period after infarction despite clear evidence of autonomic dysfunction, other mechanisms must also be important as there was no tendency for the reduction in heart rate variability to be exaggerated in the subgroup with silent exertional ischaemia.

Objective: To investigate the mechanisms of Holter ST shift in patients with acute myocardial infarction treated by thrombolysis., Design: Prospective observational study., Setting: A London district general hospital., Subjects: The study group consisted of 94 patients with acute myocardial infarction treated by thrombolysis., Interventions: All underwent early 48 hour Holter ST monitoring and elective coronary arteriography., Main Outcome Measures: Relation of Holter ST shift to multivessel coronary disease, coronary patency, collateralisation, and morphology of the infarct related lesion., Results: There was a trend towards an increased prevalence of Holter ST shift in patients with patency of the infarct related artery and those with multivessel disease. This was only significant in patients with three vessel disease, a significantly higher proportion of whom had > 3 episodes of ST shift (41% v 14%; p = 0.02) or a total duration of ST shift > 1 hour (35% v 13%; p = 0.04) than those with less extensive coronary disease. Holter ST shift occurred in a significantly higher proportion of patients with complex lesion morphology (Ambrose type 2 or 3) compared with those with lesions of Ambrose morphology type 1 or 2 (60% v 33%; p = 0.05)., Conclusion: Holter ST shift detected early after thrombolysis is an ischaemic phenomenon with a complex pathophysiology. It reflects both remote ischaemia in patients with multivessel disease, and dynamic ischaemic processes related to complex lesion morphology in those with a patent infarct related artery.

Objectives: To evaluate the role of a treadmill stress test for identifying patients at risk of recurrent ischaemic events after acute myocardial infarction treated by thrombolysis., Background: The natural history of myocardial infarction has changed with the introduction of thrombolytic treatment; there is a lower mortality but a higher incidence of recurrent thrombotic events (reinfarction, unstable angina). The treadmill stress continues to be recommended for risk stratification after acute myocardial infarction even though its value has never been formally reassessed in the thrombolytic era., Methods: Prospective observational study in which 256 consecutive patients who presented with acute myocardial infarction treated by thrombolysis underwent an early treadmill stress test and were followed up for 10 (range 6-12) months., Results: Recurrent ischaemic events occurred in 41 patients (unstable angina 15, reinfarction 21, death five) and a further 21 required revascularisation. Both ST depression at a low workload and low exercise tolerance (< 7 metabolic equivalents of the task (METS) were predictive of recurrent events, with respective hazard ratios of 1.93 (95% confidence interval (95% CI) 1.17-3.20; p < 0.01)) and 1.67 (95% CI 1.0-2.78; p < 0.05). These variables identified 50% and 70% of patients who subsequently sustained a recurrent ischaemic event, but the corresponding values for positive predictive accuracy were only 26% and 21%. Thus they are of limited value as a screening measure for identifying patients likely to benefit from invasive investigation and revascularisation. None of the other variables (ST elevation, haemodynamic responses, ventricular extrasystoles, angina) was significantly associated with recurrent ischaemic events., Conclusions: The treadmill stress test is of limited value for identifying patients at risk of recurrent ischaemic events after acute myocardial infarction treated by thrombolysis.

Objectives: To evaluate the role of Holter ST monitoring for identifying patients at risk of recurrent ischaemic events after acute myocardial infarction treated by thrombolysis., Background: The natural history of myocardial infarction has changed with the introduction of thrombolytic treatment. There is now a lower mortality but a higher incidence of recurrent thrombotic events (reinfarction, unstable angina). Preliminary evidence indicates that Holter ST monitoring may be of prognostic value in patients with acute myocardial infarction, but there are limited data available in patients treated by thrombolysis., Methods: Prospective observational study of 256 consecutive patients who presented with acute myocardial infarction treated by thrombolysis. All underwent 48 hour Holter ST monitoring early after thrombolysis (mean 83, range 48-180 hours) and were followed up for eight (range three to 12) months., Results: Recurrent ischaemic events occurred in 45 patients (fatal reinfarction 17, non-fatal reinfarction 12, unstable angina 16). Also four patients died as a result of progressive heart failure, and a further 15 patients required revascularisation. Analysis of the Holter data showed that 32% of patients had at least one episode of isolated ST depression (> or = 0.1 mV) and 41% either ST depression or elevation (> or = 0.2 mV). Ischaemic episodes were silent in 95% of cases. Event free survival analysis showed a significant association between Holter findings and recurrent ischaemic events (ST depression: p = 0.009; ST depression or elevation: p = 0.002). The association remained significant when the end point was restricted to fatal or non-fatal reinfarction (ST depression: p = 0.005; ST depression or elevation p = 0.001), the period of greatest risk for patients with an abnormal recording occurred early after investigation. An abnormal Holter recording identified patients at risk of early (within 30 days) reinfarction with 79% sensitivity and 60% specificity. Although positive predictive accuracy was low (11%), a normal Holter recording was associated with 98% negative predictive accuracy., Conclusions: In patients treated by thrombolysis, ST change on Holter monitoring may be useful for identifying patients at increased risk of recurrent ischaemic events, and in particular early reinfarction.

Objective: To record prognosis and determinants of outcome in patients with acute myocardial infarction since thrombolysis was introduced., Design: Observational study., Setting: London district general hospital., Patients: 608 consecutive patients admitted to the coronary care unit with acute myocardial infarction between 1 January 1988 and 31 December 1991., Main Outcome Measure: All cause mortality, non-fatal ischaemic events (myocardial infarction, unstable angina), and revascularisation., Results: Of the 608 patients, 89 (14.6%) died in hospital. 507 [corrected] patients were followed up after discharge from hospital. Mortality (95% confidence interval) at 30 days, one year, and three years was 16.0% (13.4% to 19.2%), 21.7% (18.6% to 25.2%), and 29.4% (25.3% to 33.9%) respectively. Event free survival (survival without a non-fatal ischaemic event) was 80.4% (77.0% to 83.4%) at 30 days, 66.8% (62.8% to 70.5%) at one year, and 56.1% (51.3% to 60.6%) at three years. Survival in patients treated with thrombolysis was considerably higher than in those not given thrombolysis (three year survival: 76.7% v 54.3%), although the incidence of non-fatal ischaemic events was the same in the two groups. Multivariate determinants of six month survival were left ventricular failure, treatment with thrombolysis and aspirin, smoking history, bundle branch block, and age. For patients who survived six months, age was the only factor related to long term survival., Conclusions: Although patients treated by thrombolysis had a relatively good prognosis, long term mortality and the incidence of non-fatal recurrent ischaemic events remained high. Effective strategies for the identification and treatment of high risk patients need to be reassessed.

Objective: To determine the circadian and seasonal variations in the incidence of acute myocardial infarction and the influence of environmental temperature., Patients: 633 consecutive patients with acute myocardial infarction admitted to a coronary care unit over four years., Setting: Coronary care unit in a district general hospital., Design: An observational study., Results: The onset of acute myocardial infarction had a circadian rhythm with a peak in the second quarter of the day. A seasonal variation was also found with a significant winter peak. There was, however, an excess of infarctions on colder days in both winter and summer indicating that the effect of environmental temperature on the onset of acute myocardial infarction is independent of the time of year., Conclusion: Acute myocardial infarction is more common in winter and more common on colder days, independent of season. Environmental temperature may play an important part in the pathogenesis of acute myocardial infarction.

Objective: To investigate the clinical significance of reciprocal ST depression on the presenting electrocardiogram in patients with acute myocardial infarction treated by thrombolysis., Design: A prospective cohort analytical study., Setting: A London district general hospital., Subjects: Two hundred and fifty eight consecutive patients with acute myocardial infarction treated with thrombolysis., Interventions: All patients underwent treadmill stress testing after a mean (SEM) of 10 (3) days; 200 patients (78%) were referred for coronary arteriography at 30 (16) days., Main Outcome Measures: Relation between reciprocal ST depression at presentation and several endpoints: time from start of chest pain to hospital presentation, electrocardiographic changes during early treadmill stress testing, presence of multivessel coronary disease, and clinical outcome in terms of recurrent ischaemic events (death, reinfarction, and unstable angina) during a 10 (range six to 12) month follow up., Results: Presentation was generally early, but in this group of patients reciprocal ST depression was significantly related to the time from the start of symptoms, those with reciprocal change presenting on average one hour earlier than those without. Although reciprocal change on the presenting electrocardiogram was weakly associated with ST depression on treadmill stress testing, it was not indicative of remote ischaemia as a result of multivessel coronary disease or high grade collateralisation of the infarct related artery. There was no association between reciprocal change and the incidence of recurrent ischaemic events., Conclusion: Reciprocal ST depression on the presenting electrocardiogram seems to be a benign electrical phenomenon related to the time from the start of symptoms. It does not necessarily predict an adverse prognosis in patients treated by thrombolysis.

Background: Experimental data suggest that reperfusion injury involving free radicals contributes to the impairment of left ventricular function after successful thrombolysis., Methods: In 72 patients presenting with acute myocardial infarction, markers of free radical activity were measured before streptokinase and two hours later. Thiobarbituric acid reactive material (TBA-RM) reflects lipid peroxidation by free radicals, and the concentration of plasma total thiols (34 patients) reflects oxidative stress. Coronary arteriography was performed at 18-72 hours after thrombolysis to determine coronary patency, and left ventricular function was assessed by ventriculography and from QRS scoring of the electrocardiogram., Results: The infarct related artery was patent (Thrombolysis In Myocardial Infarction Trial grade 2 or better) in 60 (83%) and occluded in 12. In the 60 with a patent artery, the concentration of TBA-RM increased after streptokinase by (mean (SD)) 9.2 (14.0) nmol/g albumin, whereas in the 12 with an occluded artery TBA-RM decreased by 7.0 (11.3) nmol/g albumin (p < 0.01 between groups). In those with a patent artery the rise in TBA-RM associated with thrombolysis correlated with left ventricular ejection fraction (R = -0.41, p < 0.002), and with the QRS score (R = +0.38, p = 0.003). Plasma total thiol concentrations decreased by 12.7 (31.1) mumol/l in those with a patent artery, and this decrease associated with thrombolysis correlated with left ventricular ejection fraction (R = +0.39, p < 0.02) but not with the QRS score (R = -0.2, NS)., Conclusions: These findings suggest that reperfusion injury mediated by free radicals may be of clinical importance in humans.

Objective: To evaluate laboratory markers of defibrination early after thrombolytic therapy and to determine their relation to residual stenosis and left ventricular ejection fraction measured angiographically before discharge from hospital., Design: Prospective analysis of defibrination after streptokinase measured by fibrinogen assay and thrombin time to provide a comparison of these coagulation variables for predicting angiographic responses to treatment in patients with acute myocardial infarction., Setting: The coronary care unit of a district general hospital., Patients: 44 patients with acute myocardial infarction treated by streptokinase infusion, all of whom underwent paired blood sampling before and one hour after streptokinase and cardiac catheterisation at a median of six (interquartile range 3-9) days later., Main Outcome Measures: Assay of thrombin time and plasma fibrinogen concentrations one hour after streptokinase infusion. Relations between these coagulation variables and residual stenosis in the infarct related coronary artery and left ventricular ejection fraction. Separate analyses are presented for all patients (n = 44) and those with patency of the infarct related artery (n = 35)., Results: Streptokinase infusion produced profound defibrination in every patient as shown by changes in thrombin time and circulating fibrinogen. Thrombin time after streptokinase infusion correlated significantly with both residual stenosis (r = -0.43, p < 0.005) and left ventricular ejection fraction (r = 0.38, p < 0.02). The importance of these correlations was emphasised by the interquartile group comparison which showed that a thrombin time > or = 49 seconds predicted a residual stenosis of 74% and an ejection fraction of 65%, compared with 90% and 49% for a thrombin time < or = 31 seconds (p < 0.01). When the analysis was restricted to patients with patency of the infarct related artery, the correlation between thrombin time and residual stenosis remained significant and group comparisons continued to show that patients in the highest quartile range had more widely patent arteries and better preservation of ejection fraction. Analysis of the fibrinogen data, on the other hand, showed insignificant or only marginally significant correlations with these angiographic variables., Conclusions: Early after streptokinase infusion for acute myocardial infarction, the level of defibrination measured by thrombin time has an important influence on residual coronary stenosis and left ventricular ejection fraction at discharge from hospital, values above 49 seconds being associated with the best angiographic result.

Purpose: To evaluate the impact of introducing thrombolytic and aspirin therapy into the management policy of a coronary care unit, with particular reference to its effects on the hospital course of nonselected patients with acute myocardial infarction. End points chosen were the utilization of thrombolytic and aspirin therapy, hospital mortality, discharge diuretic requirements, and the incidence of ventricular fibrillation and cardiogenic shock., Patients and Methods: A total of 336 patients with acute myocardial infarction were studied, comprising consecutive admissions to the coronary care unit over two separate 12-month periods: January to December 1986 (n = 158) and September 1989 to August 1990 (n = 178), before and after thrombolytic and aspirin therapy had been introduced into the management policy of the unit., Results: Thrombolytic and aspirin therapy was given to 87% and 93%, respectively, of all patients in the 1989/1990 cohort. This high treatment rate led to substantial improvements in morbidity and mortality. Thus, comparison of the 1986 and 1989/1990 cohorts showed reductions in hospital mortality (24% to 11%, p less than 0.005), ventricular fibrillation (22% to 13%, p = 0.05), and cardiogenic shock (20% to 6%, p less than 0.001), particularly in patients aged over 60. Reductions in the incidence of lesser degrees of heart failure are reflected in the proportions of patients discharged with diuretic requirements, which declined from 43% in 1986 to 22% in 1989/1990 (p less than 0.001). The duration of hospital stay for patients who survived showed no change between 1986 and 1989/1990, but time spent in the coronary care unit decreased from 3.1 +/- 1.8 to 2.1 +/- 1.4 days (p less than 0.001)., Conclusion: The great majority of nonselected patients with acute myocardial infarction are candidates for thrombolytic and aspirin therapy, which can be given safely, leading to profound reductions in mortality and the incidence of major complications, particularly in the older age group.

Objective: To determine the effects of age and autonomic function on the perception of angina., Design: Prospective evaluation of the relations between anginal perceptual threshold, autonomic function, and systolic blood pressure in patients with symptomatic coronary artery disease. Statistical analysis was by non-parametric techniques., Setting: Cardiology departments of a district general hospital and a post-graduate teaching centre., Subjects: 82 non-diabetic men with typical exertional angina and coronary artery disease confirmed by arteriography (n = 64) or a history of Q wave infarction (n = 18)., Main Outcome Measures: Age, anginal perceptual threshold, autonomic function, and blood pressure. Anginal perceptual threshold was defined as the time from onset of 0.1 mV ST depression to the onset of angina during treadmill stress testing. Autonomic function was measured as the ratio of peak heart rate during the Valsalva manoeuvre to the minimum rate after release., Results: Anginal perceptual threshold showed a weak but significant correlation with age, with older patients tending to have a longer interval between the onset of ST depression and the onset of angina. Comparison of patients in the upper and lower quartile age ranges showed a difference of 50 seconds between median threshold measurements. Blood pressure and heart rate responses to the Valsalva manoeuvre also correlated with age, but neither variable correlated with the anginal perceptual threshold., Conclusions: In non-diabetic men with coronary artery disease the perception of angina tends to deteriorate with advancing age. The mechanism is unclear but is not attributable solely to alterations in blood pressure or autonomic function.