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Biomedical subjects

A D Timmis

Publications and source records attributed to A D Timmis.

At least 19 recordsLinked to original sources

How effective are rapid access chest pain clinics? Prognosis of incident angina and non-cardiac chest pain in 8762 consecutive patients.

OBJECTIVE: To determine whether rapid access chest pain clinics are clinically effective by comparison of coronary event rates in patients diagnosed with angina with rates in patients diagnosed with non-cardiac chest pain and the general population. DESIGN: Multicentre cohort study of consecutive patients with chest pain attending the rapid access chest pain clinics (RACPCs) of six hospitals in England. PARTICIPANTS: 8762 patients diagnosed with either non-cardiac chest pain (n = 6396) or incident angina without prior myocardial infarction (n = 2366) at first cardiological assessment, followed up for a median of 2.57 (interquartile range 1.96-4.15) years. MAIN OUTCOME MEASURES: Primary end point--death due to coronary heart disease (International Classification of Diseases (ICD)10 I20-I25) or acute coronary syndrome (non-fatal myocardial infarction (ICD10 I21-I23), hospital admission with unstable angina (I24.0, I24.8, I24.9)). Secondary end points--all-cause mortality (ICD I20), cardiovascular death (ICD10 I00-I99), or non-fatal myocardial infarction or non-fatal stroke (I60-I69). RESULTS: The cumulative probability of the primary end point in patients diagnosed with angina was 16.52% (95% confidence interval (CI) 14.88% to 18.32%) after 3 years compared with 2.73% (95% CI 2.29% to 3.25%) in patients with non-cardiac chest pain. Coronary standardised mortality ratios for men and women with angina aged <65 years were 3.52 (95% CI 1.98 to 5.07) and 4.39 (95% CI 1.14 to 7.64). Of the 599 patients who had the primary end point, 194 (32.4%) had been diagnosed with non-cardiac chest pain. These patients were younger, less likely to have typical symptoms, more likely to be south Asian and more likely to have a normal resting electrocardiogram than patients with angina who had the primary end point. CONCLUSION: RACPCs are successful in identifying patients with incident angina who are at high coronary risk, but there is a need to reduce misdiagnosis and improve outcomes in patients diagnosed with non-cardiac chest pain who accounted for nearly one third of cardiac events during follow-up.

Angina Pectoris↗

Rapid-access chest pain clinics and the traditional cardiology out-patient clinic.

BACKGROUND: The National Service Framework for coronary heart disease recommends rapid-access chest pain clinics (RACPCs) for cardiological assessment of new-onset chest pain within 2 weeks of referral. AIM: To measure the extent to which an RACPC successfully substituted for an out-patient cardiology clinic (OPCC) at a general hospital, in assessing new-onset chest pain referrals. METHODS: Prospective measurement of attendance and waiting times for consecutive patients at the RACPC and OPCC, and multivariate analysis of factors associated with referral for angiography. RESULTS: From September 2002 to August 2004, 1382 patients with chest pain attended the RACPC, and 228 patients, the OPCC. All RACPC patients were seen within 24 h of referral, except those referred on Friday afternoons, or the day before national holidays. The mean +/- SD waiting time for OPCC appointments was 97 +/- 43 days. Of 208 OPCC patients, 30 (14%) fulfilled the RACPC referral criterion of recent onset chest pain (<4 weeks duration) vs. 926/1382 (67%) RACPC patients. Thus the RACPC substituted for the OPCC in 926/956 (97%) new chest pain referrals. Patients from the OPCC were 3.82 (95%CI 1.85-7.90) more likely to be referred for a coronary angiogram. compared to those attending the RACPC. DISCUSSION: The RACPC has provided efficient and effective substitution for the OPCC in the assessment of new chest pain referrals according to pre-defined referral criteria. Broadening the referral criterion of the RACPC to patients with chest pain of >4 weeks duration would result in more referrals.

Ambulatory Care Facilities↗

Ivabradine -- the first selective sinus node I(f) channel inhibitor in the treatment of stable angina.

Heart rate, a major determinant of angina in coronary disease, is also an important predictor of cardiovascular mortality. Lowering heart rate is therefore one of the most important therapeutic approaches in the treatment of stable angina pectoris. To date, beta-blockers and some calcium-channel antagonists reduce heart rate, but their use may be limited by adverse reactions or contraindications. Heart rate is determined by spontaneous electrical pacemaker activity in the sinoatrial node controlled by the I(f) current. Ivabradine is the first specific heart rate-lowering agent that has completed clinical development for stable angina pectoris. It is selective for the I(f) current, lowering heart rate at concentrations that do not affect other cardiac ionic currents. Specific heart-rate lowering with ivabradine reduces myocardial oxygen demand, simultaneously improving oxygen supply. Ivabradine has no negative inotropic or lusitropic effects, preserving ventricular contractility, and does not change any major electrophysiological parameters unrelated to heart rate. Randomised clinical studies in patients with stable angina show that ivabradine effectively reduces heart rate, improves exercise capacity and reduces the number of angina attacks. It has superior anti-anginal and anti-ischaemic activity to placebo and is non-inferior to atenolol and amlodipine. Ivabradine therefore offers a valuable approach to lowering heart rate exclusively and provides an attractive alternative to conventional treatment for a wide range of patients with confirmed stable angina.

Angina Pectoris↗

Declining case fatality rates for acute myocardial infarction in South Asian and white patients in the past 15 years.

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.

Asian People↗

Women in cardiology: a UK perspective.

Women are particularly under-represented in cardiology in the UK, even though women outnumber men in admissions to medical school. Could this disparity be detrimental to the specialty in this country?

Cardiology↗

The effect of diabetes on heart rate and other determinants of myocardial oxygen demand in acute coronary syndromes.

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.

Acute Disease↗

Effect of diabetes on serum potassium concentrations in acute coronary syndromes.

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.

Acute Disease↗

Cumulative risk assessment in unstable angina: clinical, electrocardiographic, autonomic, and biochemical markers.

OBJECTIVES: To determine the incremental value of clinical data, troponin T, ST segment monitoring, and heart rate variability for predicting outcome in patients with non-ST elevation acute coronary syndromes. METHODS: Prospective cohort study of 304 consecutive patients. Baseline clinical and electrocardiographic data were recorded, serial blood samples were obtained for troponin T assay, and 48 hour Holter monitoring was performed for ST segment and heart rate variability analysis. End points were cardiac death and non-fatal myocardial infarction during 12 months' follow up. RESULTS: After 12 months, 7 patients had died and 21 had had non-fatal myocardial infarction. The risk of an event was increased by troponin T > 0.1 microg/l, T wave inversion on the presenting ECG, Holter ST shift, and a decrease in the standard deviation of 5 minute mean RR intervals. Positive predictive values of individual multivariate risk were low; however, analysis of all multivariate risk markers permitted calculation of a cumulative risk score, which increased the positive predictive value to 46.9% while retaining a negative predictive value of 96.9%. CONCLUSION: A cumulative approach to risk stratification in non-ST elevation coronary syndromes successfully identifies a group in whom the risk of cardiac death or non-fatal myocardial infarction approaches 50%.

Angina, Unstable↗

Bangladeshi patients present with non-classic features of acute myocardial infarction and are treated less aggressively in east London, UK.

OBJECTIVE: To analyse differences in the presentation and management of Bangladeshi and white patients with Q wave acute myocardial infarction (AMI). DESIGN: Prospective observational study. SETTING: East London teaching hospital. PARTICIPANTS: 263 white and 108 Bangladeshi patients admitted with Q wave AMI. MAIN OUTCOME MEASURE: Character of presenting symptoms, their interpretation by the patient, and the provision of emergency treatment. RESULTS: There were no significant differences between Bangladeshi and white patients in the time from pain onset to hospital arrival (arrival time 64.5 (117.5) minutes v 63.0 (140.3) minutes, p = 0.63), but once in hospital it took almost twice as long for Bangladeshi as for white patients to receive thrombolysis (median (interquartile range) door to needle time 42.5 (78.0) minutes v 26.0 (47.7) minutes, p = 0.012). Bangladeshis were significantly less likely than whites to complain of central chest pain (odds ratio (OR) 0.11, 95% confidence interval (CI) 0.03 to 0.38; p = 0.0006) or to offer classic descriptions of the character of the pain (OR 0.25, 95% CI 0.09 to 0.74; p = 0.0118). These differences persisted after adjustment for age, sex, and risk factor profile differences including diabetes. Proportions of Bangladeshi and whites interpreting their symptoms as "heart attack" were similar (45.2% v 46.9%; p = 0.99). CONCLUSIONS: Bangladeshi patients with AMI often present with atypical symptoms, which may lead to slower triage in the casualty department and delay in essential treatment. This needs recognition by emergency staff if mortality rates in this high risk group are to be reduced.

Age Distribution↗

A single serum glucose measurement predicts adverse outcomes across the whole range of acute coronary syndromes.

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.

Analysis of Variance↗

Management of stable angina.

Ischaemic heart disease may present as a wide variety of clinical entities including unstable or stable angina pectoris, acute myocardial infarction, and occasionally heart failure. Chronic stable angina is a common condition and results in a considerable burden for both the individual and society. The goals in management are (i) treatment of other conditions that may worsen angina; (ii) modification of risk factors and treatment with medications for coronary artery disease to improve outcome; and (iii) effective relief of anginal symptoms. There are limitations to the methods available to risk-stratify patients, and the optimal treatment strategy remains unclear. The benefits of lifestyle modification cannot be over-emphasised, and appropriate attention to modifiable risk factors is paramount. The mortality benefit of lipid lowering treatment and antiplatelet therapy is well proved. However the evidence base for anti-ischaemic therapy is less rigorous, being based mainly on extrapolations from studies of acute coronary syndromes. Angioplasty has been shown to be more effective in relief of symptoms than medical therapy alone, but provides no mortality benefit. Coronary artery bypass surgery, however, has been shown to reduce mortality in patients with severe proximal coronary disease when compared with medical management alone.

Adrenergic alpha-Antagonists↗

Restricted weekend service inappropriately delays discharge after acute myocardial infarction.

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.

Aged↗

Interaction between arrival time and thrombolytic treatment in determining early outcome of acute myocardial infarction.

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.

Aged↗