Diagnosing Paroxysmal Atrial Fibrillation: Are Biomarkers the Solution to This Elusive Arrhythmia?

Atrial fibrillation (AF) is the commonest sustained arrhythmia globally and results in significantly increased morbidity and mortality including a fivefold risk of stroke. Paroxysmal atrial fibrillation (PAF) constitutes approximately half of all AF cases and is thought to represent an early stage of the disease. This intermittent form of atrial arrhythmia can be a challenge to identify and as a result many affected individuals are not prescribed appropriate antithrombotic therapy and hence are at risk of stroke and thromboembolism. Despite these adverse outcomes there have been relatively few diagnostic advances in the field since the introduction of the Holter monitor in 1949. This review aims to establish the available evidence for electrophysiological, molecular, and morphological biomarkers to improve the detection of PAF with reference to the underlying mechanisms for the condition.

Early administration of thrombolysis can prevent myocardial necrosis: time is myocardium.

A case is presented in which a 66-year-old man received thrombolysis for an acute ST elevation myocardial infarction (STEMI) within 6 minutes of developing chest pain. An ECG performed 10 minutes after thrombolysis showed complete resolution of the ST segment elevation and showed no other abnormality. An echocardiogram showed normal left ventricular function and there was no detectable myocardial necrosis, as evidenced by two negative troponin assays. The case clearly reinforces the benefits of the rapid delivery of thrombolysis when appropriate for patients with STEMI. Clinicians need to be aware of the benefits of early thrombolysis as laid out in the national service framework. Evidence for the early administration of thrombolysis, data from the Myocardial Infarction National Audit Project and the future with regard to improving thrombolysis times are discussed.

Coronary angiography using a portable super-C-arm imaging system in a district general hospital.

BACKGROUND: New generation portable super-C-arm imaging systems may offer an alternative means of performing coronary angiography at a lower cost compared with a fixed laboratory. We evaluated the use of one such system (GE-OEC 9800) in a district hospital setting. METHODS: The demographics, procedure and screening times, emitted radiation dose and diagnoses of the first 200 consecutive patients were obtained from a prospective database. Comparison between the portable and fixed systems were made by analysing results from similar cohorts of patients who underwent angiography by the same operators. Image quality was assessed in 23 patients, by an independent cardiologist, comparing the GE-OEC 9800 angiograms with repeat images using a fixed laboratory Philips (HM 3000) system within 3 months of the first study. RESULTS: The procedure time (mean (S.D.)) was 18.9 (0.8) min for the 200 cases. The screening time was 255 (15) s with an emitted radiation of 22.8 (1.4) Gy/cm(2). Comparison between the C-arm and fixed systems revealed significantly longer screening time (230.6 (14.6) vs. 157 (12.9) s, p<0.001), whilst the total radiation doses were not significantly different (21.1 (1.5) vs. 18.6 (1.11) Gy/cm(2)). Independently assessed image quality was satisfactory. The main variance in 57 lesions seen in the 23 patients using the angiograms obtained from the fixed laboratory as reference included overestimated stenosis (two lesions), underestimated stenosis (or subsequent disease progression) (four lesions), lack of appreciation of side-branch ostial involvement (two lesions) and vessel calcification (one lesion). CONCLUSIONS: Portable imaging systems can offer a reliable and cost-effective diagnostic coronary angiography service in a district hospital.

Monocyte expression of tissue factor and adhesion molecules: the link with accelerated coronary artery disease in patients with chronic renal failure.

OBJECTIVE: To investigate the expression of monocyte tissue factor (MTF) and adhesion molecules in patients with chronic renal failure (CRF) and to look for any correlation with thrombin generation and Lp(a) lipoprotein. DESIGN: A study of MTF expression and adhesion molecules, prothrombin fragments 1+2 (PTf1+2), an index of thrombin generation, and lipoproteins in patients with CRF and in normal control subjects. BACKGROUND: Patients with end stage renal failure have an increased risk of coronary artery disease despite advances in therapy. Stimulated monocytes are potent activators of blood coagulation through the generation of MTF, which was recently implicated in the aetiology of acute coronary ischaemic syndromes. METHODS: MTF expression and adhesion molecules were measured in whole blood using immunofluorescence of monocytes labelled with anti-tissue factor antibody and CD11b and c by flow cytometry. PTf1+2 and Lp(a) lipoprotein in plasma were measured by enzyme linked immunosorbent assay (ELISA). PATIENTS: 70 patients with CRF without documented coronary artery disease (30 patients with CRF undialysed, 20 patients undergoing chronic ambulatory peritoneal dialysis (CAPD), and 20 undergoing haemodialysis (HD)), together with 20 normal controls, were studied. RESULTS: The (mean (SD)) increased MTF of CRF (48.0 (29) v 33.3 (7.2) mesf unit/100 monocytes in controls, p = 0.04) was more pronounced in patients undergoing dialysis (HD 73.1 (32.8) (p < 0.003) and CAPD 62.8 (28.9) mesf unit/100 monocytes, p < 0.04). MTF activity showed a positive correlation with both PTf1+2 and serum creatinine (p < 0.003) but not with Lp(a) lipoprotein. Lp(a) lipoprotein was significantly increased in both dialysis groups compared with controls (p < 0.005) and non-dialysis CRF groups (p < 0.02). Monocyte adhesion molecule (CD11b) was significantly higher in all three CRF groups than in the controls (p = 0.006). CONCLUSION: This study has demonstrated a hypercoagulable state in patients with CRF. This was especially pronounced in the dialysis patients. These findings provide a possible explanation for the increased cardiovascular and cerebrovascular morbidity and mortality in these patients.

Effect of magnesium sulphate in patients with unstable angina. A double blind, randomized, placebo-controlled study.

AIMS: Administration of intravenous magnesium sulphate has been shown to be protective during acute myocardial ischaemia and it may therefore have beneficial effects in unstable angina. The purpose of this study was to assess the effects of a 24-h infusion of magnesium in patients with unstable angina. METHODS AND RESULTS: Patients who presented with unstable angina with electrocardiographic changes were randomized to receive a 24-h intravenous infusion of magnesium or placebo within 12 h of admission. The primary endpoint was myocardial ischaemia, as assessed by 48 h Holter monitoring. Resting 12-lead ECGs, creatine kinase-MB release and urinary catecholamines were also assessed. Patients were followed for 1 month. Thirty-one patients received magnesium sulphate and 31 placebo. Baseline characteristics and extent of coronary disease were similar in both groups. On 48 h Holter monitoring, 14 patients (50%) had transient ST segment shifts in the magnesium group vs 12 patients (46%) in the placebo group. However, there were fewer ischaemic episodes in the magnesium group (51 vs 101, P < 0.001) and there was a trend towards an increase in the total duration of ischaemia in the placebo group compared to the magnesium group in the second 24 h (2176 min vs 719 min respectively, P = 0.08). Regression of T wave changes on the 24 h ECG occurred more frequently in patients who received magnesium compared to those treated with placebo (11 patients vs 0 patients respectively, P < 0.005). Creatine kinase-MB release was significantly less at 6 and 24 h in patients who received magnesium compared to those treated with placebo. Catecholamine excretion was lower in patients treated with magnesium than in those treated with placebo (adrenaline: 1.05 +/- 0.16 vs 1.61 +/- 0.32 ng.mmol-1 creatinine; noradrenaline: 9.99 +/- 1.82 vs 18.48 +/- 2.41 ng.mmol-1 creatinine respectively in the first 12 h sample, P < 0.05). CONCLUSIONS: Intravenous magnesium reduces ischaemic ECG changes, creatine kinase-MB release and urinary catecholamine excretion in the acute phase of unstable angina. Thus, magnesium may be a beneficial additional therapy for these patients. Further studies are required to confirm these finding.

Elevated Chlamydia pneumoniae antibodies, cardiovascular events, and azithromycin in male survivors of myocardial infarction.

BACKGROUND: The clinical significance of the association between elevated anti-Chlamydia pneumoniae (Cp) antibody titres and coronary heart disease (CHD) is unclear. We explored the relationship between antibodies against Cp and future cardiovascular events in male survivors of myocardial infarction (MI). The effect of azithromycin antibiotic therapy was assessed in a subgroup of post-MI patients. METHODS AND RESULTS: We screened 220 consecutive male survivors of MI for anti-Cp antibodies. Of these, 213 patients were stratified into three groups: group Cp-ve (n=59), no detectable Cp antibodies; group Cp-I (n=74), intermediate titres of 1/8 to 1/32 dilution; and group Cp+ve (n=80), seropositive at > or = 1/64 dilution. Patients with persisting seropositivity of > or = 1/64 were randomized to either oral azithromycin (Cp+ve-A, 500 mg/d for 3 days [n=28] or 500 mg/d for 6 days [n=12]) or placebo (Cp+ve-P, n=20). Cp+ve-NR (n=20) represented patients not recruited into the antibiotic trial. The incidence of adverse cardiovascular events (over a mean follow-up period of 18+/-4 months) was recorded and shown to increase with increasing anti-Cp titre: Cp-ve, n=4 (7%); Cp-I, n=11 (15%); Cp+ve-NR, n=6 (30%); and Cp+ve-P, n=5 (25%). Cp+ve-NR and Cp+ve-P groups had a fourfold-increased risk for adverse cardiovascular events compared with the Cp-ve group (odds ratio [OR], 4.2; 95% confidence interval [CI], 1.2 to 15.5; P=.03). In contrast, the OR for cardiovascular events in patients receiving azithromycin (Cp+ve-A, single or double course) was the same as in the Cp-ve group (OR, 0.9; 95% CI, 0.2 to 4.6, P=NS). Patients receiving azithromycin were more likely to experience a decrease in IgG anti-Cp titres than were those in the placebo group (P=.02). CONCLUSIONS: An increased anti-Cp antibody titre may be a predictor for further adverse cardiovascular events in post-MI patients. Taking a short course of azithromycin may lower this risk, possibly by acting against Cp.

Increased monocyte tissue factor expression in coronary disease.

OBJECTIVE: To investigate whether monocyte expression of tissue factor is increased in patients with acute coronary syndromes and chronic stable angina. DESIGN: Cross sectional study of monocyte tissue factor expression in patients with ischaemic heart disease and control subjects. BACKGROUND: Unstable angina and myocardial infarction are associated with enhanced mononuclear cell procoagulant activity. Procoagulant activity of blood monocytes is principally mediated by tissue factor expression. Tissue factor initiates the coagulation cascade and monocyte tissue factor expression may therefore be increased in these syndromes. METHODS: Monocyte tissue factor expression was measured cytometrically in whole blood flow using a polyclonal rabbit antihuman tissue factor antibody. PATIENTS: 30 patients with acute myocardial infarction, 17 with unstable angina, 13 with chronic stable angina, and 11 normal control subjects. RESULTS: Increased proportions of monocytes expressing tissue factor (> 2.5%) were found in none of 11 (0%) normal subjects, five 13 (38%) patients with stable angina, 11 of 17 (64%) patients with unstable angina, and 16 of 30 (53%) patients with myocardial infarction (2P = 0.006). Blood from all subjects showed similar monocyte tissue factor expression similar monocyte tissue factor expression (46.1 (15.1)%) after lipopolysaccharide stimulation. CONCLUSION: Hypercoagulability associated with acute myocardial infarction, unstable angina, and chronic stable angina may be induced by tissue factor expressed on circulating monocytes.

Class III antiarrhythmics in overdose. Presenting features and management principles.

Class III (Vaughan-Williams classification) antiarrhythmic drugs prolong the cardiac action potential without affecting depolarisation. The 3 class III drugs currently in general use are amiodarone, sotalol and bretylium. The presenting features of acute toxicity are different for each agent and are, therefore, discussed separately. Several new class III antiarrhythmic agents are under development, including dofetilide and d-sotalol, but specific data on overdoses of these potent class III drugs are not yet available. Amiodarone toxicity following acute overdose is rare because poor bioavailability and a large volume of distribution limit the peak serum concentration. Toxicity is low even if high serum concentrations are reached. The major risks from acute overdose are hypotension (intravenous administration only) and arrhythmia if other factors, such as hypokalaemia or additional antiarrhythmic agents are present. Management is chiefly directed at reducing absorption with activated charcoal or cholestyramine, and monitoring for arrhythmia. Sotalol is a beta-blocker with additional class III activity. Oral bioavailability is high, and overdosed patients can present with bradycardia, hypotension and major haemodynamic collapse. The combination of bradycardia and prolongation of the QT interval is associated with malignant arrhythmias such as torsade de pointes. Management principles include observation and correction of bradycardia with endocardial pacing, intravenous adrenergic drugs and glucagon. The risk of arrhythmia can be substantially reduced by intravenous potassium and magnesium supplements. d-Sotalol is a potent class III drug devoid of beta-blocking activity and may be expected to share the proarrhythmic affects of the racemic mixture in overdose, without pronounced hypotension and bradycardia. Intravenous bretylium in overdose causes an initial hypertensive effect, followed by profound hypotension from systemic vasodilation. Management is directed at controlling hypotension with volume expansion and norepinephrine (noradrenaline).

The association of germ cell tumours of the testis with sarcoid-like processes.

Sarcoid-type pulmonary lymphadenopathy associated with testicular cancer is a rare condition which has been previously reported in only 14 cases. Earlier case reports have failed to distinguish between generalized sarcoidosis as opposed to a local granulomatous reaction to tumour. We describe a further 8 cases of the association and provide strong supportive evidence for systemic sarcoidosis in 5 of our patients. In 3 of our patients with systemic sarcoidosis there was coexisting testicular cancer requiring additional treatment. We therefore advise caution in the interpretation of the clinical and histological findings in these patients, and recommend thorough investigation of all such cases.