Contemporary management of coronary heart disease.

Coronary heart disease remains the leading cause of mortality in the UK. This review focuses on the contemporary management of patients with acute coronary syndromes and those with stable angina, including the role of primary percutaneous coronary intervention versus fibrinolytic therapy in a UK setting, current and emerging antiplatelet and anticoagulant therapies and the latest guidance on secondary prevention/lifestyle modification.

A timely diagnosis of myocardial infarction.

The diagnosis of acute myocardial infarction currently rests on the measurement of troponin, a biomarker of myocardial necrosis. Unfortunately, the current generation troponin assays detect troponin only 6-9 h after symptom onset. This can lead to a delay in diagnosis and also excessive resource utilization when triaging patients who, ultimately, have noncardiac causes of acute chest pain. For these reasons, there has been extensive research interest in biomarkers that can detect and rule out myocardial infarction early after symptom onset. These include markers of myocardial injury, such as myoglobin, heart-type fatty acid binding protein, glycogen phosphorylase BB; hemostatic markers, such as D-dimer; and finally, inflammatory markers, such as matrix metalloproteinase 9. Recently, highly sensitive troponin assays have reported an early sensitivity for myocardial infarction of greater than 95%, although at a cost of reduced specificity. The optimal strategy with which to use these novel biomarkers and highly sensitive troponins has yet to be determined, and interpretation of their results in light of thorough clinical assessment remains essential.

Is there a Failure to Optimize theRapy in anGina pEcToris (FORGET) study?

BACKGROUND: In the management of chronic stable angina, percutaneous coronary intervention (PCI) provides symptomatic relief of angina rather than improvement of prognosis. Current guidelines recommend optimization of medical therapy prior to elective PCI. It is not clear if these guidelines are adhered to in clinical practice. AIM: The aim of this multi-centre study was to determine the extent to which these treatment guidelines are being implemented in the UK. DESIGN: This was a multi-centre study involving six hospitals in the UK. METHODS: The medical treatment and extent of risk factor modification was recorded for consecutive patients undergoing elective PCI for chronic stable angina at each site. Data collected included anti-anginal drug therapy, lipid levels and blood pressure (BP). Data on heart rate (HR) control were also collected, since this represents a fundamental part of medical anti-anginal therapy. Target HR is <60 b.p.m. for symptomatic angina. RESULTS: A total of 500 patients [74% male; mean age +/- SD (64.4 +/- 10.1 years)] were included. When considering secondary prevention, 85% were receiving a statin and 76% were on an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker. In terms of medical anti-ischaemic therapy, 78% were receiving beta-blockers [mean equivalent dose of bisoprolol 3.1 mg (range 1.25-20 mg)], 11% a rate limiting calcium antagonist, 35% a nitrate or nicorandil and one patient was receiving ivabradine. The mean total cholesterol (95% confidence interval) was 4.3 mmol/l (4.2-4.4), mean systolic BP of 130 +/- 24 mmHg and mean diastolic BP of 69 +/- 13 mmHg. Serum cholesterol was <5 mmol/l in 77% and <4 mmol/l in 42% of the patients, 62% of the patients had systolic BP < 140 mmHg and 92% had diastolic BP < 90 mmHg. Considering European Society of Cardiology targets, 50% had systolic BP < 130 mmHg and 76% had diastolic BP < 80 mmHg. A large proportion of patients did not achieve target resting HR; 27% of patients had a resting HR of >or=70 b.p.m., 40% had a resting HR between 60 and 69 b.p.m. and 26% had a resting HR between 50 and 59 b.p.m. The resting HR was not related to the dose of beta-blocker. CONCLUSION: A significant proportion of the patients with chronic stable angina undergoing elective PCI did not achieve therapeutic targets for lipid, BP and HR control. Over 50% of patients did not receive adequate HR lowering anti-anginal therapy to achieve recommended target resting HR.

Dyslipidemia therapy update: the importance of full lipid profile assessment.

Lipid guidelines typically focus on total cholesterol +/- low-density lipoprotein cholesterol levels with less emphasis on high-density lipoprotein cholesterol (HDL-C) or triglyceride assessment, thus potentially underestimating cardiovascular (CV) risk and the need for lifestyle or treatment optimization. In this article, we highlight how reliance on isolated total cholesterol assessment may miss prognostically relevant lipid abnormalities; we describe from the European Systematic COronary Risk Evaluation (SCORE) data set how incorporation of HDL-C may improve estimation of CV risk; and, finally, we critically evaluate the evidence base surrounding triglycerides and CV risk.

Investigation of a multimarker approach to the initial assessment of patients with acute chest pain.

Early identification of acute coronary syndrome (ACS) is important to guide therapy at a time when it is most likely to be of value. In addition, predicting future risk helps identify those most likely to benefit from ongoing therapy. Cardiac troponin T (cTnT) is useful for both purposes although cannot reliably rule out ACS until 12 hours after pain onset and does not fully define future risk. In this review article we summarize our previously published research, which assessed the value of myocyte injury, vascular inflammation, hemostatic, and neurohormonal markers in the early diagnosis of ACS and risk stratification of patients with ACS. In addition to cTnT, we measured heart fatty acid binding protein (H-FABP), glycogen phosphorylase-BB, high-sensitivity C-reactive protein, myeloperoxidase, matrix metalloproteinase 9, pregnancy-associated plasma protein-A, D-dimer, soluble CD40 ligand, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Of the 664 patients enrolled, 415 met inclusion criteria for the early diagnosis of acute myocardial infarction (MI) analysis; 555 were included in the risk stratification analysis and were followed for 1 year from admission. In patients presenting <4 hours from pain onset, initial H-FABP had higher sensitivity for acute MI than cTnT (73% vs. 55%; P=0.043) but was of no benefit beyond 4 hours when compared to cTnT. On multivariate analysis, H-FABP, NT-proBNP, and peak cTnT were independent predictors of 1-year death/MI. Our research demonstrated that, in patients presenting within 4 hours from pain onset, H-FABP may improve detection of ACS. Measuring H-FABP and proBNP may help improve long-term risk stratification.

Body surface mapping improves early diagnosis of acute myocardial infarction in patients with chest pain and left bundle branch block.

OBJECTIVE: To test prospectively depolarisation and repolarisation body surface maps (BSMs) for mirror image reversal, which is less susceptible to artefact, in patients with acute ischaemic-type chest pain, and to compare these BSM criteria with previously published 12 lead ECG criteria. METHODS: An 80 lead portable BSM system was used to map patients presenting with acute ischaemic-type chest pain and a 12 lead ECG with left bundle branch block (LBBB). Acute myocardial infarction (AMI) was defined by serial cardiac enzymes. Each 12 lead ECG was assessed by the criteria of Sgarbossa et al and Hands et al for diagnosis of AMI. Depolarisation and repolarisation BSMs were assessed for loss of mirror image reversal of QRS with ST-T isointegral map patterns and a change in vector angle from QRS to ST-T outside 180+/-15 degrees -findings typically seen in LBBB with AMI. RESULTS: Of 56 patients with chest pain and LBBB, 18 had enzymatically confirmed AMI. Patients with loss of BSM image reversal were significantly more likely to have AMI (odds ratio 4.9, 95% confidence interval 1.5 to 16.4, p = 0.007). Loss of BSM image reversal was significantly more sensitive (67%) for AMI than either 12 lead ECG method (17%, 33%) albeit with some loss in specificity (BSM 71%, 12 lead ECG 87%, 97%). Patients with AMI compared with those without AMI had a greater mean change in vector angle outside the normal range (180+/-15 degrees ), particularly between QRS isointegral and ST60 isopotential (the potential 60 ms after the J point at each electrode site) BSMs (19 degrees v 9 degrees, p = 0.038). Loss of image reversal and QRS-ST60 vector change outside 180+/-15 degrees had 61% sensitivity and 82% specificity for AMI (odds ratio 7.0, 95% confidence interval 2.0 to 24.4, p = 0.001). CONCLUSIONS: BSM compared with the 12 lead ECG improved the early diagnosis of AMI in the presence of LBBB.

Impact of pre-hospital care in patients with acute myocardial infarction compared with those first managed in-hospital.

AIMS: To compare prospectively the impact of pre-hospital care by a physician-staffed mobile coronary care unit with patients managed initially in-hospital, all with acute myocardial infarction. METHODS AND RESULTS: This was a single centre registry of consecutive patients (n=750) admitted with acute myocardial infarction to the coronary care unit and cardiology wards of the Royal Victoria Hospital, Belfast between 1998 and 2001. For the 750 patients, in-hospital mortality was 11% and was significantly lower for those managed pre-hospital (8% vs 13%, P=0.04): patients who received fibrinolytic therapy (n=474), the in-hospital mortality was significantly lower in the pre-hospital group (7% vs 13%, P=0.02). Those managed pre-hospital had significant reduction in the median delay times (25th, 75th percentiles) from onset of symptoms to call for help 1.0 (0.5, 2.2) vs 2.0 (0.9, 6.0) h, P<0.001, from call for help to receiving fibrinolytic therapy 1.0 (0.8, 1.5) vs 1.8 (1.2, 2.5) h, P<0.001 resulting in a shorter pain-to-needle time for fibrinolytic therapy 2.3 (1.5, 3.8) vs 4.0 (2.6, 7.2) h, P<0.001. For all patients, older age, haemodynamic indicators on admission (hypotension, higher heart rate, heart failure) and managed by the in-hospital route were significant independent variables for an adverse in-hospital mortality. Although for patients aged >or=75 years no statistical significant reduction in mortality occurred for those managed pre-hospital (P=0.051), nevertheless patients in this age group first treated pre-hospital who received fibrinolytic therapy had a significantly lower mortality than those first treated in-hospital (21% vs 43%, P=0.02). CONCLUSIONS: Consecutive patients with acute myocardial infarction seen and managed initially out-of-hospital by a physician-staffed mobile coronary care unit had significantly lower in-hospital mortality.

Randomized comparison of enoxaparin with unfractionated heparin following fibrinolytic therapy for acute myocardial infarction.

AIMS: To compare the efficacy and safety of low molecular weight heparin with unfractionated heparin following fibrinolytic therapy for acute myocardial infarction. METHODS AND RESULTS: Three-hundred patients receiving fibrinolytic therapy following acute myocardial infarction were randomly assigned to low molecular weight heparin as enoxaparin (40 mg intravenous bolus, then 40 mg subcutaneously every 8 h, n=149) or unfractionated heparin (5000 U intravenous bolus, then 30 000 U. 24 h(-1), adjusted to an activated partial thromboplastin time 2-2.5x normal, n=151) for 4 days in conjunction with routine therapy. Clinical and therapeutic variables were analysed, in addition to use of enoxaparin or unfractionated heparin, to determine independent predictors of the 90-day composite triple end-point (death, non-fatal reinfarction, or readmission with unstable angina). The triple end-point occurred more frequently in patients receiving unfractionated heparin rather than enoxaparin (36% vs. 26%; P=0.04). Logistic regression modelling of baseline and clinical variables identified the only independent risk factors for recurrent events as left ventricular failure, hypertension, and use of unfractionated heparin rather than enoxaparin. There was no difference in major haemorrhage between those receiving enoxaparin (3%) and unfractionated heparin (4%). CONCLUSION: Use of enoxaparin compared with unfractionated heparin in patients receiving fibrinolytic therapy for acute myocardial infarction was associated with fewer recurrent cardiac events at 90 days. This benefit was independent of other important clinical and therapeutic factors.

Suspected angina pectoris: a rapid-access chest pain clinic.

We prospectively evaluated a rapid-access chest pain clinic in terms of clinical diagnoses, outcomes, morbidity and mortality at 3 months follow-up in patients, and cost-effectiveness. All patients seen at the clinic from February 1999 to December 2000 were assessed. Referring doctors indicated the management they would have provided had the clinic been unavailable, to allow a cost-effectiveness analysis. Overall, 709 patients were referred, 471 (66%) from General Practitioners, 212 (30%) from Accident and Emergency doctors and 26 (4%) from other sources. All had recent onset, or increasing frequency of ischaemic-type chest pain (excluding those with suspected myocardial infarction or rest chest pain angina). Fifty-one (7%) had acute coronary syndromes, 119 (17%) had stable ischaemic heart disease, 144 (20%) had possible ischaemic heart disease, and 395 (56%) were considered to have non-ischaemic symptoms. Some 70% of patients were seen within 24 h. Only 57 patients (8%) were admitted. Had the clinic been unavailable, 160 patients would have been admitted. Out-patient cardiology appointments were arranged for 116 patients (16%), and 429 patients (60%) were discharged directly. Follow-up data at 3 months were obtained from 565/567 eligible patients (99.6%). No major cardiac events (death/myocardial infarction) occurred in those with non-ischaemic chest pain. There were five deaths (including one due to cancer) and three patients had a myocardial infarction (event rate 1%). There were eleven readmissions for angina: six were in patients with acute coronary syndromes, and four of these six were awaiting revascularization. The estimated net saving was pound 58/patient. A rapid-access chest pain clinic offers a prompt, safe and cost-effective service in a challenging group of patients.

ST depression only on the initial 12-lead ECG: early diagnosis of acute myocardial infarction.

AIMS: To compare the diagnostic ability of the 12-lead ECG with body surface mapping for early detection of acute myocardial infarction in patients presenting with ST depression only on the 12-lead ECG. METHODS AND RESULTS: Fifty-four consecutive patients with chest pain <24 h and ST depression were recruited. A 12-lead ECG and 80-lead body surface map were recorded at presentation from which univariate and multivariate prediction models of acute myocardial infarction were developed. Patients were randomly divided into a training-set and a validation-set. Acute myocardial infarction occurred in 16/30 training-set and 8/24 validation-set patients. Univariate prediction of acute myocardial infarction by the 12-lead ECG, based on the depth or numbers of leads with ST depression, was not improved by assessment of ST elevation outside the conventional 12 leads using body surface mapping. The optimum multivariate 12-lead ECG model developed in training-set patients (six ST depression variables) had poor sensitivity (38%) although good specificity (81%) for acute myocardial infarction when tested prospectively in validation-set patients. In contrast, the optimum body surface mapping model developed in training-set patients (three isointegral or isopotential variables) achieved high sensitivity (88%) whilst maintaining good specificity (75%) for acute myocardial infarction when tested prospectively in validation-set patients. CONCLUSION: Body surface mapping, when compared with the 12-lead ECG, may improve the early diagnosis of acute myocardial infarction in patients presenting with chest pain and ST depression only on the 12-lead ECG.

Noninvasive assessment of reperfusion after fibrinolytic therapy for acute myocardial infarction.

Assessment of reperfusion by the 12-lead electrocardiogram (ECG) or biochemical markers is limited by suboptimal sensitivity and/or specificity. Body surface mapping (BSM) improves the spatial sampling of the 12-lead ECG. Serial 12-lead ECGs and 64-lead anterior BSMs were recorded from 67 patients with acute myocardial infarction undergoing coronary angiography 90 minutes after fibrinolytic therapy. ECG-1 and BSM-1 were recorded before/shortly after therapy (median 18 minutes). ECG-2 and BSM-2 were recorded after the 90-minute angiogram (median 30 minutes). The maximum ST elevation on ECG-1 was noted and > or = 30% ST resolution on ECG-2 was taken to represent partial/complete reperfusion. Patients were randomly divided into a training set and validation set. Isointegral and isopotential ST-T variables from BSMs of training-set patients were compared with Thrombolysis In Myocardial Infarction (TIMI) trial flow using discriminant analysis to identify which variables best classified reperfusion. Reperfusion (TIMI 2/3 flow) occurred in 32 of 34 training-set patients and in 29 of 33 validation-set patients. In the training set, > or = 30% ST resolution correctly classified reperfusion with 72% sensitivity (23 of 32) and 50% specificity (1 of 2). In the validation set, > or = 30% ST resolution classified reperfusion with 59% sensitivity (17 of 29) and 50% specificity (2 of 4). In comparison, a model containing 24 BSM variables correctly classified all training-set patients, and when prospectively tested in the validation-set, correctly classified 28 of 29 patients who achieved reperfusion (97% sensitivity) and all 4 patients who failed to reperfuse (p = 0.035). In conclusion, BSM is more useful than the 12-lead ECG for noninvasive assessment of reperfusion after fibrinolytic therapy for acute myocardial infarction.

Improving the ECG classification of inferior and lateral myocardial infarction by inversion of lead aVR.

OBJECTIVE: To assess whether the use of inverted lead aVR (-aVR) would improve the classification of acute inferior or lateral myocardial infarction presenting with ST elevation. DESIGN: Observational study. The presence of >/= 1 mm ST elevation in lead -aVR (derived by manual assessment of ST depression in conventional lead aVR) was determined by a single investigator, blinded to patient outcome. PATIENTS: 173 consecutive patients with chest pain for /= 1 mm in inferior leads (II, III, aVF) or lateral leads (I, aVL, V5, V6), excluding those with anterolateral ST elevation. MAIN OUTCOME MEASURE: Incidence of ST elevation in lead -aVR in patients with inferior or lateral ST elevation, or both. RESULTS: ST elevation in lead -aVR was present in 25 of 136 patients (18%) with inferior but no lateral ST elevation (indicating greater superior involvement) and in three of 11 patients (27%) with lateral but no inferior ST elevation (indicating greater inferior involvement). ST elevation in lead -aVR bridged the gap between inferior and lateral ST elevation in 15 of 25 (60%) patients with inferior and lateral chest lead (V5/V6) ST elevation, and in all patients with inferior and lateral limb lead (I/aVL) ST elevation. The presence of ST elevation in lead -aVR was associated with a larger infarct size as defined by median peak creatine kinase on serial sampling: 1780 v 987 mmol/l; p = 0.021. CONCLUSIONS: Use of lead -aVR improves the ECG classification of acute inferior or lateral acute myocardial infarction and thus may be useful as part of the routine 12 lead ECG assessment of such patients.

Early diagnosis of right ventricular or posterior infarction associated with inferior wall left ventricular acute myocardial infarction.

Right ventricular (RV) or posterior infarction associated with inferior wall left ventricular acute myocardial infarction (AMI) has important therapeutic and prognostic implications. However, RV and posterior chest leads in addition to the 12-lead electrocardiogram are required for accurate detection. Body surface mapping (BSM) has greater spatial sampling and may further improve inferior wall AMI classification. Consecutive patients with chest pain lasting <12 hours were assessed to identify those with AMI and > or =0.1 mV ST elevation in > or =2 contiguous inferior leads of the 12-lead electrocardiogram (bundle branch block or left ventricular hypertrophy excluded). A 12-lead electrocardiogram, RV leads (V(2)R, V(4)R), posterior chest leads (V(7), V(9)), and a BSM were recorded. From each BSM, the 12 electrodes overlying the RV region (regional RV map) and 10 electrodes overlying the posterior wall (regional posterior map) were assessed for ST elevation. Infarct size was estimated by serial cardiac enzymes. AMI occurred in 173 of 479 patients. Of the 62 patients with inferior wall AMI, ST elevation > or =0.1 mV occurred in 26 patients (42 in V(2)R or V(4)R compared with 36 patients (58%) in > or =1 electrode on the regional RV map (p = 0.0019). ST elevation > or =0.1 mV occurred in 1 patient (2%) in V(7) or V(9) compared with 17 patients (27%) in > or =1 electrode on the regional posterior map (p = 0.00003). ST elevation > or =0.05 mV occurred in 6 patients (10%) in V(7) or V(9) compared with 22 patients (36%) in > or =1 electrode on the regional posterior map (p = 0.00003). Patients with ST elevation on regional RV and/or posterior maps had a trend toward larger infarct size (mean peak creatine kinase 1,789+/-226 vs. 1,546+/-392 mmol/L; p = NS). Thus, BSM, when compared with RV or posterior chest leads, provides improved classification of patients with inferior wall AMI and RV or posterior wall involvement.

Optimizing the initial 12-lead electrocardiographic diagnosis of acute myocardial infarction.

AIMS: The optimum definition of ST elevation for diagnosis of acute myocardial infarction, with respect to both the minimum height and the minimum numbers of leads, is unknown. Furthermore, only 50% of patients with acute myocardial infarction present with ST elevation. We thus quantified the sensitivity and specificity of different ST elevation criteria for diagnosis of acute myocardial infarction, and determined whether models incorporating multiple QRST features in addition to ST elevation, could improve detection of acute myocardial infarction. METHODS AND RESULTS: The study population comprised 1190 subjects: 1041 consecutive patients presenting with chest pain (335 with acute myocardial infarction) and 149 controls without chest pain. Subjects were randomly divided into a training set (587) and a validation set (603). ECG prediction models for acute myocardial infarction incorporating different ST elevation criteria and/or additional QRST features (Q waves, ST depression, T wave inversion, bundle branch block, axes deviations, and left ventricular hypertrophy) were developed in training set patients using forward stepwise multiple logistic regression. Models were then prospectively tested in the validation set patients. The optimum ST elevation model (based on > or =1 mm ST elevation in > or = 1 inferior/lateral leads, or > or =2 mm ST elevation in > or =1 anteroseptal leads) correctly classified 83.1% of subjects (55.8% sensitivity, 94. 0% specificity). The choice of ST elevation definition had marked influence on the sensitivity (45.4-68.6%) and specificity (81.2-98. 1%) for diagnosis of acute myocardial infarction. The addition of multiple QRST variables only marginally improved overall classification but did result in high specificity (92.6-96.1%). CONCLUSION: Different definitions of 'significant' ST elevation led to marked variations in sensitivity and specificity for diagnosis of acute myocardial infarction. Multiple QRST features in addition to ST elevation only marginally improved overall classification.