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To evaluate a system of prehospital thrombolysis, delivered by paramedics, in meeting the national service framework's targets for the management of acute myocardial infarction.Prospective observational cohort study comparing patients with suspected acute myocardial infarction considered for thrombolysis in the prehospital environment with patients treated in hospital.The catchment area of a large teaching hospital, including urban and rural areas.201 patients presenting concurrently over a 12 month period who had changes to the electrocardiogram that were diagnostic of acute myocardial infarction or who received thrombolysis for suspected acute myocardial infarction.Time from first medical contact to initiation of thrombolysis (call to needle time), number of patients given thrombolysis appropriately, and all cause mortality in hospital.The median call to needle time for patients treated before arriving in hospital (n=28) was 52 (95% confidence interval 41 to 62) minutes. Patients from similar rural areas who were treated in hospital (n=43) had a median time of 125 (104 to 140) minutes. This represents a median time saved of 73 minutes (P0.001). Sixty minutes after medical contact 64% of patients (18/28) treated before arrival in hospital had received thrombolysis; this compares with 4% of patients (2/43) in a cohort from similar areas. Median call to needle time for patients from urban areas (n=107) was 80 (78 to 93) minutes. Myocardial infarction was confirmed in 89% of patients (25/28) who had received prehospital thrombolysis; this compares with 92% (138/150) in the two groups of patients receiving thrombolysis in hospital.Thrombolysis delivered by paramedics with support from the base hospital can meet the national targets for early thrombolysis. The system has been shown to work well and can be introduced without delay.

Aims—To determine the sensitivity and specificity of each ICD9 code for a diagnosis of definite or possible myocardial infarction (MI) from the perspective of the Myocardial Infarction Causality Study (MICA) and to use these data to estimate the likely number of MICA cases in Scotland that would be undetected were these codes omitted from the study. Setting—Women resident and registered with general practitioners in the Tayside region of Scotland between October 1993 and October 1995. Method—All SMR1 records of Tayside hospitalizations containing ICD9 (International Classification of Diseases, ninth revision) codes for myocardial infarction (410) or possible myocardial infarction (411, 412, 413, 414, 427.4, 427.5, 786.5) were identified for women aged between 16 and 44 years between 1 October 1993 and 15 October 1995. Original case records were sought and each episode abstracted using a predefined form. Records were independently scrutinized by two consultant cardiologists blinded to the SMR1 code. Cases were categorized as definite MI, possible MI or unlikely MI. Where there was disagreement between the two cardiologists, the profiles for such events were examined by a third cardiologist who acted as the final adjudicator. The adjudicator's verdict was, in this study, considered dominant. The sensitivity, specificity and positive predictive value of each ICD9 code was determined. Results—Two hundred and fifty-three women fulfilled the SMR1 search criteria. Case records of 204 (81%) were retrieved but four case records contained no data on the admission of interest and were classified as invalid. Forty-six of the 200 remaining patients were ineligible for the MICA study leaving 154 records for evaluation. There were 12 patients who had a discharge code for MI (ICD9 410). Of these, 11 were judged as a definite MI by both cardiologists. One event (discharge code ICD9 410) was judged as ‘possible’ by one cardiologist and ‘unlikely’ by the other. The adjudicator subsequently judged this event as ‘definite’. Another six events were subsequently judged as ‘possible’. Thus, after adjudication, 12 cases of definite MI and six cases of ‘possible’ MI were identified. The sensitivity and specificity of ICD9 code 410 was 67% and 100% respectively. The positive predictive value was 100%. The sensitivity of code 411 was 5·6%. The specificity was 99% and the positive predictive value was 50%. Code 413 had a sensitivity of 5·6% with a specificity of 94% and a positive predictive value of 9·1%. Code 414 also had a sensitivity of 5·6%. The specificity was 86% and the positive predictive value was 4·5%. Code 786·5 had a sensitivity of 17%, a specificity of 23% and a positive predictive value of 2·5%. Code 427·5 failed to identify any definite or possible cases. Conclusions—In the MICA Study, ICD9 code 410 was found to be the most robust. All 12 patients judged to have had a definite MI had the appropriate discharge code (ICD9 410). The six patients judged to have had a possible MI all had discharge codes other than that for MI (410). However, identifying these six patients required the validation of a further 160 events—giving a combined sensitivity of 33%, a specificity of 0% and a positive predictive value of only 3·8%. The use of ICD9 codes 411, 413, 414, 427·5 and 786·5 must, therefore, only be employed when circumstances fully justify the additional workload. Copyright © 1998 John Wiley & Sons, Ltd.

Aims Resting plasma levels of atrial natriuretic peptide and B-type natriuretic peptide rise with left ventricular dysfunction, but little is known about effects of cardiac ischaemia on atrial natriuretic peptide and B-type natriuretic peptide levels during exercise. We investigated exercise levels of atrial natriuretic peptide and B-type natriuretic peptide in patients with suspected angina to determine whether these measurements could improve non-invasive assessment of coronary disease severity. Methods and results One hundred patients performed an exercise test (Bruce protocol) within 2 weeks of coronary angiography. Plasma levels of atrial natriuretic peptide and B-type natriuretic peptide were measured at rest and at peak exercise. Multivariate regression analysis was used to assess effects of age, sex, coronary anatomy, exercise time and ventricular function on atrial natriuretic peptide and B-type natriuretic peptide levels. Increasing age and female sex were significantly associated with higher resting atrial natriuretic peptide levels; age alone was associated with higher exercise atrial natriuretic peptide levels. As expected, left ventricular end-diastolic pressure and disease of left anterior descending and circumflex coronary arteries were associated with increased resting B-type natriuretic peptide levels. However, the usual rise in B-type natriuretic peptide levels during exercise was independently reduced by disease of the right coronary artery. Conclusion This paradoxical effect of right coronary artery disease limits the value of natriuretic peptide measurements as predictors of coronary disease severity. Impaired release of B-type natriuretic peptide may reduce exercise tolerance in patients with right coronary artery disease.

Concomitant coronary artery disease often occurs in patients with peripheral vascular disease, but it may be asymptomatic. Despite being asymptomatic, cardiovascular events are the main source of morbidity and mortality in this group of patients. Dipyridamole thallium scintigraphy has been shown to be of prognostic value in patients with peripheral vascular disease and symptomatic coronary artery disease, but its effect on the long-term outcome in the asymptomatic group of patients is less defined. Eighty-four consecutive patients with peripheral vascular disease and no symptoms of coronary artery disease were therefore evaluated by clinical assessment, dipyridamole thallium imaging, radionuclide ventriculography, and cardiac catheterization and followed for a mean of 66 months. Abnormal perfusion patterns were found on thallium scintigraphy in 48 patients (57%); fixed, mixed, and reversible defects were present in 14 (17%), 11 (13%), and 23 (27%) patients, respectively. Significant coronary artery disease was present in 52 patients (69%) and mean left ventricular ejection fraction was 44%. During the followup period, 23 patients had a cardiac event (nonfatal myocardial infarction or cardiac death). Univariate analysis of 15 clinical, scintigraphic, radionuclide, and angiographic variables revealed that age, angiographic extent of coronary artery disease, and an abnormal thallium scan were significant predictors of subsequent cardiac events. Multivariate stepwise logistic regression analyses selected fixed and mixed thallium defects and diffuse coronary artery disease as the only significant independent predictors of outcome. Thus, the present study shows the value of dipyridamole thallium scintigraphy as a valuable prognostic indicator for long-term event-free survival in a cohort of patients with peripheral vascular disease and no history or symptoms of coronary artery disease.

OBJECTIVES--To determine whether plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor antigen, and prostacyclin stimulating factor and plasminogen activator inhibitor activity show circadian variation in men with ischaemic heart disease. DESIGN--Blood samples were obtained every four hours for 24 hours from 10 men with ischaemic heart disease. The men were ambulant from 08:10 until 00:00 when they went to bed and they remained in bed until 08:00 the following morning. PATIENTS--Ten men with positive diagnostic exercise tolerance tests with no significant past history, who were not regularly taking any medical treatment except for glyceryl trinitrate. RESULTS--There was significant circadian variation in plasminogen activator inhibitor activity (p = 0.001) (peak value 04:00 and trough value 20:00), but not in plasma concentrations of tissue plasminogen activator antigen, von Willebrand factor, or prostacyclin stimulating factor. CONCLUSION--Men with ischaemic heart disease showed a significant circadian variation in fibrinolysis. The combination of peak values of plasminogen activator inhibitor activity and failure of plasma concentrations of tissue plasminogen activator antigen to increase in the early morning must predispose to thrombosis at this time. The circadian variation in fibrinolysis may contribute to the increased incidence of myocardial infarction in the morning.

Clinical studies have demonstrated that patients with coronary artery disease (CAD) have markers suggestive of increased free radical (FR) activity when compared with normal subjects; however, the relationship between the extent of CAD and level of FR markers is not known. The following indices of FR activity, plasma malondialdehyde (MDA), plasma thiols (PSH), red blood cell (RBC) glutathione (GSH), and RBC superoxide dismutase (SOD) were measured in 58 patients admitted for coronary angiography and in 50 matched controls. Regression analysis demonstrated no significant correlation between MDA, PSH, GSH, or SOD, and the angiographic grade which indicated the severity of the CAD. Patients with angiographically proven CAD (median 7.9 nmol/ml IQR 6.9-9.2) and patients with a history suggestive of angina pectoris but normal coronary angiograms (median 8.4 nmol/ml IQR 7.4-9.9) had significantly raised MDA levels compared with the controls (median 6.85 nmol/ml IQR 6.1-7.4), p less than 0.001 and p less than 0.005, respectively. The patients with angiographically proven CAD had significantly lower GSH levels (median 1461 microM IQR 1348-1709, p less than 0.002) compared with the controls (median 1754 microM IQR 1492-1930). Significantly raised SOD levels also were detected in patients with angiographically proven CAD (median 121.8 U/ml RBC, IQR 113.8-143.9) and in patients with a history of suggestive of angina pectoris but normal coronary angiograms (median 146 U/ml RBC, IQR 96.8-156.7) when compared with controls (median 96.3 U/ml RBC, IQR 82.4-115.6), p less than 0.001 and p less than 0.02, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of atenolol on dipyridamole 201Tl myocardial perfusion tomography was evaluated in 12 patients with angiographically proven coronary artery disease. The patients had dipyridamole 201Tl tomography performed after 7 days treatment with 50 mg atenolol and then repeated after a further 7 days treatment with placebo. The images were interpreted qualitatively by two experienced observers and quantitatively using the Bullseye technique. Qualitative analysis of the images revealed that four of the 12 patients had larger defects on their scans whilst receiving atenolol compared to placebo. The remaining eight patients had defects which were the same size on both treatments. The severity of defects assessed qualitatively was not significantly influenced by atenolol therapy (P = 0.13, McNemera's test). The results obtained with the Bullseye method did not demonstrate significant statistical differences for defect size, degree of reversibility or percentage reversibility whilst the patients were receiving atenolol or placebo (Wilcoxon Rank Sum Test). Atenolol increased the size of perfusion defects on dipyridamole 201Tl tomography qualitatively and quantitatively for four patients in this group of 12 with proven coronary artery disease. Although this did not achieve a high level of statistical significance physicians should be aware that atenolol can influence the images obtained at dipyridamole 201Tl tomography.

Summary Thirty eight relatives of a patient with Marfan syndrome were screened for the presence of this disorder. Marfan syndrome was newly diagnosed in living members of 4 generations in this family without evidence of ocular abnormality in any. After screening, 10 relatives were newly diagnosed as having definite, and 5 relatives as having possible, Marfan syndrome. Family screening has drawbacks as well as benefits for the patients. The main benefit is the identification and treatment of previously undiagnosed patients at risk of cardiac complications which are the major cause of mortality. The drawbacks include employment problems created for patients with Marfan syndrome as a direct consequence of our screening programme and the anxiety induced in previously asymptomatic family members who did not realize that they could be at risk. Also, the 4 adult patients with possible Marfan syndrome found it difficult to accept that a definite diagnosis could not be reached after they had been invited to attend a screening programme for a serious genetic disorder. This report illustrates the importance of screening all the relatives of a patient with Marfan syndrome to identify previously undiagnosed cases. However, before screening a family, the physician should be aware that a clear diagnosis may not be reached in all patients, and financial, psychological or social problems may arise as a result of the screening programme.

REFERENCES 1. Mazzu A, Di Tano G, Cogode R, Lo Presti G. Myocardial bridging involving more than one site of the left anterior descending coronary artery: an uncommon cause of acute ischemic syndrome. Cathet Cardiovasc Diagn 1995;34:329-32. 2. Manakata K, Sate N, Sasaki Y, Yasutake M, Kusama Y, Takayama M, et al. Two cases of variant form angina pectoris associated with myocardial bridge--a possible relationship among coronary vasospasm. Jpn Circ J 1992;56:1248-52. 3. Bestetti RB, Finzi LA, Amaral FT, Secches AL, Oliveira JS. Myocardial bridging of coronary arteries associated with an impending acute myocardial infarction. Clin Cardiol 1987;10:129-31. 4. Bestetti RB, Costa RS, Zucolotto S, Oliveira JS. Fatal outcome associated with autopsy proven myocardial bridging of the left anterior descending coronary artery. Eur Heart J 1989;10:573-6. 5. Chee TP, Jensen DP, Padnick MB, Cornell WP, Desser KB. Myocardial bridging of the left anterior descending coronary artery resultresulting in subendocardial infarction. Arch Intern Med 1981;141: 1703-4. 6. Bestetti RB, Costa RS, Kazava DK, Oliveira JS. Can isolated myocardial bridging of the left anterior descending coronary artery be associated with sudden death during exercise? Acta Cardiol 1991;46:27-30. 7. Feld H, Guadanino V, Hollander G, Greengart A, Lichstein E, Shani J. Exercise-induced ventricular tachycardia in association with a myocardial bridge. Chest 1991;99:1295-6. 8. Laifer LI, Weiner BH. Percutaneous transluminal coronary angioplasty of a coronary artery stenosis at the site of myocardial bridging. Cardiology 1991;79:245-8. 9. Chaimer KS, Bukis E, Hartnell G, Ress JR. Myocardial bridging of the coronary arteries. Clin Radiol 1989;40:355-9. 10. Julliere Y, Berder V, Suty-Selten C, Buffet P, Danchin N, Cherrier F. Isolated myocardial bridges with angiographic milking of the left anterior descending coronary artery: a long-term follow-up study. Am Heart J 1995;129:663-5. 11. Ramos SG, Montenegro AP, Felix PR, Kazawa DK, Rossi MA. Occlusive thrombosis in myocardial bridging. Am Heart J 1993;125:1771~3. 12. Nair CK, Dang B, Heintz MH, Sketch MH. Myocardial bridges: effect of propranolol on systolic Compression. Can J Cardiol 1986;2:218-21. 13. Iversen S, Hake U, Mayer E, Erbel R, Diefenbach C, Oelert H. Surgical treatment of myocardial bridging causing coronary artery obstruction. Scand J Thorac Cardiovasc Surg 1992;26:107-11.

The effects of beta-adrenoceptor antagonists, calcium channel blockers and long acting nitrates on white blood cell (WBC) aggregation were studied in patients with ischaemic heart disease. WBC aggregation was significantly increased by beta-adrenoceptor antagonists (P = 0.011) but was unaffected by either calcium channel blockers or long acting nitrates. Enhanced WBC aggregation promotes microvascular occlusion and damage.

Large-scale trials of angiotensin converting enzyme (ACE) inhibitors after acute myocardial infarction (AMI) suggest that the benefits are greatest in patients with left ventricular (LV) dysfunction. However, early evaluation of LV function in all patients after AMI by current methods can be difficult due to a lack of resources and skilled personnel. Thus a clinical algorithm that could be used at the bedside to reliably identify patients with a left ventricular ejection fraction (LVEF)or = 40% would be helpful as an occasional alternative to echocardiography. We have devised such an algorithm based on the presence of one of: (i) clinical signs of heart failure; (ii) an index Q-wave anterior myocardial infarction; (iii) lack of thrombolytic therapy when there is a history of two or more previous myocardial infarctions and a CK rise1000 U/l. We tested this new algorithm prospectively in the coronary care units of two hospitals (one UK and one USA). In the UK centre, the sensitivity and specificity of the algorithm at identifying patients with a LVEFor = 40% were 82% and 72%, respectively. In the US centre, the sensitivity of the algorithm was 91% and the specificity 78% at identifying patients with LV dysfunction. We have validated a simple clinical algorithm which can be used at the bedside for identifying patients who would benefit from an ACE inhibitor after AMI.

Although elevations of plasma atrial natriuretic peptide (ANP) concentrations have been shown to have prognostic significance in patients after acute myocardial infarction (AMI), the relation between plasma levels of B-type natriuretic peptide (BNP) and cardiovascular mortality remains unknown. To test the prognostic value of plasma ANP and BNP after AMI, plasma concentrations were measured a mean of 3 days after infarction in 75 patients. During a median follow-up of 19.7 months, 14 patients (18.4%) died of cardiovascular causes. On univariate analysis, plasma ANP and BNP, Killip class, modified Peel index, left ventricular ejection fraction, and presence of left ventricular failure were all associated with cardiovascular mortality. In contrast, plasma ANP was the only variable that correlated with the development of symptomatic heart failure and hospitalization. For the combined end point of cardiovascular mortality, symptomatic heart failure, and hospitalization, plasma neurohormones were the only variables of predictive value. By stepwise regression analysis, plasma BNP was the only significant independent predictor of cardiovascular mortality (p = 0.001), whereas plasma ANP identified patients at risk of symptomatic heart failure and hospitalization (p = 0.002 and 0.019, respectively). This study indicates that plasma BNP measured after AMI is a powerful neurohormonal predictor of subsequent cardiovascular mortality, whereas plasma ANP correlates better with the development of symptomatic heart failure and hospitalization. Routine measurement of both of these peptides in the period immediately after an AMI may provide a simple means of risk stratification with different information gained from each peptide.

Objective : To determine whether QTc dispersion, which is easily obtained from a standard electrocardiogram, can predict those patients with peripheral vascular disease who will subsequently suffer a cardiac death, despite having no cardiac symptoms or signs. Design : Patients with peripheral vascular disease were followed up for five years after they had had coronary angiography, radionuclide ventriculography, and their QTc dispersion calculated from their 12 lead electrocardiogram. Subjects : 49 such patients were then divided into three groups: survivors (34), cardiac death (12), and non-cardiac death (3). Main outcome measure : Survival. Results : The mean (SD; range) ejection fractions were similar in all three groups: survivors 45.9 (11.0; 27.0-52.0), cardiac death 44.0 (7.90; 28.5-59.0), and non-cardiac death 45.3 (4.55; 39.0-50.0). QTc dispersion was significantly prolonged in the cardiac death group compared with in the survivors (86.3 (23.9; 41.0-139) v 56.5 (25.4; 25.0-164); P=0.002). A QTc dispersion >/=60 ms had a 92% sensitivity and 81% specificity in predicting cardiac death. QTc dispersion in patients with diffuse coronary artery disease was significantly (P

The mechanism(s) causing high levels of plasma atrial natriuretic factor (ANF) in cardiac allograft recipients is(are) unclear. The kidney is important for the clearance of ANF and renal function may decline with cyclosporin A therapy in these patients. The relationship between plasma ANF level and renal function and also the pharmacokinetics of a continuous infusion of ANF (15.5 ng.kg-1.min-1 for 60 min) was examined in 6 cardiac allograft recipients on cyclosporin A therapy. Resting plasma ANF levels were significantly higher in these patients than in 8 healthy subjects (71 vs. 21 ng.l-1). Both effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) were significantly lower in these patients than in healthy subjects (215 vs. 617 ml.min-1 and 55 vs. 102 ml.min-1 respectively). There was a significant inverse correlation between plasma ANF and ERPF (r = -0.86) and between plasma ANF and GFR (r = -0.81). During the period of ANF infusion, steady state plasma ANF levels were significantly higher in cardiac allograft recipients. Total body clearance of ANF was marginally lower in these patients than in healthy subjects (60 vs. 10.0 l.min-1) although this difference did not reach statistical significance. Derived endogenous secretion rate of ANF was threefold higher in patients when compared to healthy subjects (633 vs. 208 ng.min-1). We have therefore shown that cardiac allograft recipients on cyclosporin A have elevated plasma ANF levels and also decreased renal function. Pharmacokinetic analysis have shown that this increase in plasma ANF levels is due more to increased ANF secretion than to decreased ANF clearance in these patients.

Free radicals (FR) are a highly reactive chemical species which have been implicated in the pathogenesis of reperfusion injury. Experimental models of reperfusion injury have demonstrated that FR scavengers improve myocardial salvage and thus it has been postulated that they may be of benefit in acute myocardial infarct (MI) patients treated with thrombolysis. Previous studies of FR activity post MI have focused on the immediate post reperfusion period; the present study investigates FR activity in post MI patients over a longer time span. Free radicals have a very short half-life and in clinical studies their activity is usually assessed indirectly by measuring either the level of FR reaction products such as malondialdehyde (MDA) or FR scavengers such as plasma thiols (PSH). In the presence of increased FR activity MDA levels increase and PSH levels decrease. Twenty-two acute MI patients had blood samples taken on admission, day 7 and day 21 post MI for measurement of MDA and PSH levels. On day 7 post MI a significant increase in MDA was detected P= θ0.0001 (Sign test) (median change + θ2.1 μmol. I) and a significant decrease was detected in PSH P = θ 0.04 (Sign test) (median change, − θ 38 μmol. l− θ1). No significant differences were detected between admission and day 21 levels of MDA and PSH. This study demonstrates the presence of enhanced FR activity at a later time point than has previously been recognised. White blood cells utilise FRs during phagocytosis and the late rise in FR activity detected in this study may reflect white blood cell removal of necrotic myocardium.

OBJECTIVE--The SAVE study showed that captopril improves mortality in patients with left ventricular dysfunction after myocardial infarction and that this benefit occurred even in patients with no clinically overt heart failure. On the basis of this, it seems important to identify correctly which patients have left ventricular dysfunction after a myocardial infarction. The objective was to compare various methods of identifying patients with left ventricular dysfunction (left ventricular ejection fraction, LVEF, < or = 40%) after acute myocardial infarction. The methods compared were echocardiography (quantitative and qualitative visual assessment), clinical evaluation (subjective assessment and three clinical score methods), and measurement of plasma concentrations of cardiac natriuretic peptide hormones (atrial and brain natriuretic peptides, ANP and BNP). DESIGN--Cross sectional study of left ventricular function in patients two to eight days after acute myocardial infarction. SETTING--Coronary care unit of a teaching hospital. PATIENTS--75 survivors of a recent myocardial infarction aged 40 to 88 with no history of cardiac failure and without cardiogenic shock at the time of entry to the study. MAIN OUTCOME MEASURES--Sensitivities and specificities of the various methods of detecting left ventricular dysfunction were calculated by comparing them with a cross sectional echocardiographic algorithm for LVEF. RESULTS--Clinical impression was poor at identifying LVEF < 40% (sensitivity 46%). Clinical scoring improved this figure somewhat (modified Peel index sensitivity 64%). Qualitative visual assessment echocardiography was a more sensitive method (sensitivity 82%) for detecting LVEF < 40%. Plasma BNP concentration was also a sensitive measure for detecting left ventricular dysfunction (sensitivity 84%) but plasma ANP concentration was much poorer (sensitivity 64%). CONCLUSION--Left ventricular dysfunction is easily and reliably detected by echocardiographic measurement of LVEF and also by a quick qualitative echocardiographic assessment but is likely to be missed by clinical assessment alone. High concentrations of plasma BNP maybe another useful indicator of left ventricular dysfunction, particularly in hospitals where not all patients can be screened by echocardiography or radionuclide ventriculography after myocardial infarction.

The effect of the injection of additional thallium after a redistribution study and prior to a further resting study was evaluated in 21 patients with angiographically proven coronary artery disease. Using dipyridamole as the stress mechanism, the studies were carried out tomographically and the results analysed quantitatively with the Bull's-eye technique. Two patients had normal scans. Of the remaining 19, 11 patients had a perfusion defect which appeared irreversible on redistribution imaging. However, six of these patients demonstrated improved or normal uptake after the second injection of thallium. Of the eight patients with a reversible defect, two revealed considerably greater reversibility after reinjection. These results indicate that the reinjection of thallium prior to the resting study significantly (P < 0.02) improves the detection rate of ischaemia during dipyridamole thallium tomography.

Summary Fourteen patients with Marfan syndrome, defined according to present criteria, had bone mineral content of the distal forearm measured by single photon absorptiometry. Patients were matched for age and sex with a large local group of healthy volunteers. While further work is needed with other methods of densitometry with measurements at other sites, our results provide no evidence that there is an increased incidence of osteoporosis in Marfan syndrome. Previous reports of an association were probably due to incorrect clinical diagnosis or confusion with clinically similar syndromes known to cause osteoporosis.

Markers suggestive of enhanced free radical (FR) activity have been demonstrated in patients with chest pain and normal coronary angiograms. This may be of pathogenetic importance because FRs impair vascular relaxation and are generated following episodes of myocardial ischaemia/reperfusion. Fifteen patients with angina pectoris, normal coronary angiograms and either a positive exercise tolerance test and/or abnormal dipyridamole thallium tomogram were studied along with 15 age-, sex- and smoking-matched controls. A peripheral venous blood sample was obtained to measure the following FR markers: malondialdehyde, plasma thiols, red blood cell glutathione and superoxide dismutase. No significant differences were detected in the levels of any of the FR markers between either the group of 15 patients with chest pain and normal angiograms or the subgroup with positive exercise tolerance tests when compared to the controls. There is therefore no evidence of enhanced FR activity in patients with chest pain and normal coronary angiograms in peripheral venous blood samples.

The fibrinolytic activity of blood has a circadian variation with increased thrombotic tendency in the morning. This may be a contributory factor to the circadian variation in the time of onset of thrombotic events. However, there has recently been increasing interest to the role of the white blood cells (WBC) and free radicals (FRs) in thrombosis. We have previously reported a circadian variation in WBC aggregation and FR status in normal volunteers. No one has yet studied possible circadian variations in these parameters in patients with stable ischaemic heart disease (IHD). Ten men with stable IHD had blood samples collected at four-hourly intervals from midday until midday the following day. The patients were ambulant until midnight at which time they went to bed and remained in bed until 0800 h. The following were measured on each sample: WBC aggregation, malondialdehyde (MDA) which is a product of lipid peroxidation by FRs; the FR scavengers, plasma thiol (PSH), red cell glutathione (GSH) and superoxide dismutase (SOD) which are all altered in the presence of increased FR activity. WBC aggregation and PSH had significant circadian variations, P < 0.015 and P < 0.001 respectively. The WBC aggregation peak was at 1200 h and trough at 1600 h, the PSH peak was at midnight and the trough at 0400 h. WBC behaviour and FR status influence the flow properties of blood. The largest rise in WBC aggregation occurred from 0800 h to 1200 h; such an increase in aggregation could predispose to microcirculatory occlusion.(ABSTRACT TRUNCATED AT 250 WORDS)

We report the cases of four patients with secondary left ventricular hypertrophy (three due to hypertension and one to aortic stenosis) in whom Doppler echocardiography showed dynamic left ventricular outflow tract obstruction and marked impairment of diastolic filling. Each patient derived marked symptomatic benefit from treatment with either a beta-blocker (atenolol) or calcium antagonist (verapamil). Repeat Doppler studies in three patients revealed a substantial improvement in systolic and diastolic flow abnormalities. Ventricular outflow tract obstruction should be recognized as occurring in a subgroup of patients with secondary left ventricular hypertrophy, and its presence should be sought by Doppler echocardiography before embarking on therapy. Negatively inotropic or positively lusitropic agents such as beta-blockers and rate-limiting calcium antagonists appear to be logical therapy for this condition.

The effect of atenolol on dipyridamole 201Tl myocardial perfusion tomography was evaluated in 12 patients with angiographically proven coronary artery disease. The patients had dipyridamole 201Tl tomography performed after 7 days treatment with 50 mg atenolol and then repeated after a further 7 days treatment with placebo. The images were interpreted qualitatively by two experienced observers and quantitatively using the Bullseye technique. Qualitative analysis of the images revealed that four of the 12 patients had larger defects on their scans whilst receiving atenolol compared to placebo. The remaining eight patients had defects which were the same size on both treatments. The severity of defects assessed qualitatively was not significantly influenced by atenolol therapy (P = 0.13, McNemera's test). The results obtained with the Bullseye method did not demonstrate significant statistical differences for defect size, degree of reversibility or percentage reversibility whilst the patients were receiving atenolol or placebo (Wilcoxon Rank Sum Test). Atenolol increased the size of perfusion defects on dipyridamole 201Tl tomography qualitatively and quantitatively for four patients in this group of 12 with proven coronary artery disease. Although this did not achieve a high level of statistical significance physicians should be aware that atenolol can influence the images obtained at dipyridamole 201Tl tomography.

The endothelium has a central role in the regulation of vascular tone, thrombosis, and hemostasis. Endothelial damage incurred during reperfusion injury may limit the restoration of blood flow to potentially viable ischemic myocardium. Although endothelial dysfunction after reperfusion has been demonstrated in animal models, 1, 2 patient data are limited. This study investigates endothelial dysfunction after reperfusion in acute myocardial infarction (MI) patients. Endothelial injury releases factor VIII von Willebrand factor antigen (fVIIIvWFAg), which can be measured in plasma and serves as a marker of endothelial

Brain natriuretic peptide (BNP) is a new natriuretic peptide with marked similarity to atrial natriuretic peptide (ANP) in both its amino acid sequence and its biological actions. 1 Although originally isolated from the porcine brain, subsequent studies in pigs, rats and humans have shown that BNP is also a cardiac hormone synthesized and secreted from the heart into the circulation. 2 The stimulus for BNP release in humans is unclear, although plasma levels of human BNP-like immunoreactivity have been reported to be increased in classical conditions of volume overload, such as congestive heart failure. 2 Therefore, it is likely that the release of BNP may be related to an increase in either cardiac pressure or distension. With regard to ANP, there is compelling evidence that atrial distension is the primary stimulus for its release based on observations in patients with cardiac tamponade. 3 Relief of tamponade by aspiration results in a reduction in atrial pressure, but an increase in both atrial distension and plasma ANP concentration. Therefore, we compared the plasma concentrations of human BNP-like immunoreactivity and ANP during therapeutic pericardiocentesis in patients with cardiac tamponade.

Objective: To assess the comparative contribution of clinical assessment, electrocardiography, and chest radiography to the diagnosis of left ventricular systolic dysfunction in patients admitted to a general medical ward with acute dyspnoea. Design: Prospective cross sectional study. Setting: Acute medical admissions ward of a teaching hospital. Subjects: 71 randomly selected patients admitted with acute dyspnoea. Main outcome measures: Sensitivity and specificity of each investigation and logistic regression analysis of each variable in identifying left ventricular systolic dysfunction. Results: Clinical assessment in this cohort of patients with severe dyspnoea was generally sensitive (sensitivity 81%). Patients were divided into three groups on the basis of clinical assessment. In the first group (37 patients) the diagnosis of systolic dysfunction was clear, in the second (22) it was in doubt, and in the third (12) it was unlikely. The sensitivity of clinical assessment in identifying left ventricular systolic dysfunction was 81% and the specificity was 47%. The specificity of diagnosis was improved by electrocardiography (69%) and chest radiography (92%). Logistic regression analysis showed that isolated pulmonary crepitations were a comparatively poor predictor of left ventricular systolic dysfunction (2=10.215, P=0.0014) but that a full clinical examination had reasonable predictive value (2=24.82, P Conclusion: Clinical assessment in patients admitted with acute dyspnoea is comparatively accurate. Patients with abnormal results on chest radiography, electrocardiography, and clinical examination have a high likelihood of having left ventricular systolic dysfunction. Echocardiography contributes little more to the diagnosis in these patients and may be more efficiently directed towards patients in whom the diagnosis is still in doubt after clinical assessment, chest radiography, and electrocardiography. Key messages The availability of echocardiography is limited for patients admitted to hospital with acute dyspnoea The presence of isolated lung crepitations is a poor predictor of left ventricular systolic dysfunction Full clinical assessment is sensitive in detecting left ventricular systolic dysfunction, with specificity being added by either chest radiography or electrocardiography Echocardiography should be reserved for cases with the most diagnostic doubt

The pharmacokinetic and pharmacodynamic effects of the beta-adrenoceptor antagonist H-I 42 BS were examined in healthy subjects. In an open dose ranging study, H-I 42 BS 50, 100, 200 and 400 mg were given as single oral doses to four subjects. H-I 42 BS 400 mg caused maximum reduction in exercise heart rate (20.4 +/- 1.0%--mean +/- s.d.) at 4 h and still reduced exercise heart rate at 96 h (18.4 +/- 7.2%). Seven subjects received in double-blind, randomised order, single oral doses of H-I 42 BS 50, 100 and 200 mg, atenolol 50 and 100 mg and placebo. H-I 42 BS 400 mg was given in a single blind manner as the last dose of the study. Both H-I 42 BS and atenolol reduced supine and standing heart rate and systolic blood pressure (P less than 0.05) although atenolol had the more marked effect. The maximum percent reduction of exercise heart rate after H-I 42 BS 50 mg was 10.9 +/- 7.1%, after 100 mg was 18.7 +/- 5.8%, after 200 mg was 20.6 +/- 6.4% and after 400 mg was 21.9 +/- 8.2%. H-I 42 BS 400 mg still caused 11.0 +/- 3.5% reduction at 168 h. Atenolol 50 mg caused maximum percent reduction of exercise heart rate of 26.0 +/- 6.0% but did not reduce exercise heart rate after 24 h. The mean peak plasma concentrations for all doses of H-I 42 BS occurred at 5.1 +/- 1.5 h. The plasma elimination half-life was 47.6 +/- 8.1 h. There was a linear correlation between the dose and AUC0-infinity (r = 0.97). The cardioselectivity of H-I 42 BS and atenolol was compared. Six subjects received in double-blind random order H-I 42 BS 100 and 400 mg, atenolol 50 mg and placebo. After each dose, graded infusions of isoprenaline were given until the heart rate increased by 50 beats min-1. Dose-response curves for heart rate, diastolic blood pressure, forearm blood flow and finger tremor were constructed. There was no difference in the dose-response curves for forearm blood flow or finger tremor after H-I 42 BS 400 mg or atenolol 50 mg. Atenolol 50 mg caused more attenuation (P less than 0.01) of the diastolic blood pressure response. These results indicate that H-I 42 BS is a cardioselective beta-adrenoceptor antagonist with a long duration of action in man.

In 12 healthy volunteers who received orally 100, 200, 300, 400 and 600 mg mexiletine at weekly intervals, the maximum plasma concentration of mexiletine and AUC increased linearly with the dose of mexiletine. Between doses there were no significant differences in the values for clearance and volume of distribution of mexiletine but there were for plasma elimination half-life. These results indicate that the kinetics of mexiletine are linear.

In Tayside region, from 1976 to 1986, the number of permanent pacemakers implanted per year more than doubled, with the increase particularly marked over the latter five years. In order to determine the factor(s) which had caused this increase in implantation rates, a retrospective analysis of patients undergoing pacemaker implantation during the period 1981–1986 was undertaken. No change in the number of elderly in the population, age of patients, mode of referral, waiting time before insertion or clinical indications for pacing was observed to account for this change. The advent of ambulatory ECG monitoring may have contributed to this increase, but the appointment of an extra cardiologist in Tayside in 1982 was believed to have been more important. These results suggest that the number of pacemakers implanted in a region is highly dependent on the number of cardiological staff in that region available for their insertion.

Spontaneous reversion to sinus rhythm from long-standing atrial fibrillation is described in 4 patients, who had undergone Starr-Edwards mitral valve replacements some years previously. The reversion to sinus rhythm was spontaneous and did not follow electrical conversion or change in drug therapy. The change to sinus rhythm did not appear to benefit the patients clinically and was not accompanied by echocardiographic evidence of left atrial contraction.

The cardiovascular effects of felodipine, a new arteriolar vasodilator, were studied in 22 patients with coronary heart disease. There were significant falls in blood pressure and systemic vascular resistance of 16 and 38% respectively (P = 0.001), thus affecting after-load. Cardiac index and stroke index increased by 35 and 12% respectively. There was reflex tachycardia--from 75 +/- 3 to 85 +/- 3 b.p.m. (P = 0.005). Coronary sinus blood flow increased from 134 +/- 9 to 191 +/- 17 ml/min (P less than 0.005) and myocardial arterio-venous oxygen difference narrowed from 12.1 +/- 0.5 to 9.0 +/- 0.4 vols% (P less than 0.001) indicating less oxygen usage. With the heart rate held constant by atrial pacing, cardiac index and stroke index increased by 30 and 26% (P less than 0.001), whilst systolic blood pressure and systemic vascular resistance fell by 20 and 29% (P less than 0.001). This would suggest that the improved haemodynamics were largely secondary to after-load reduction.

Retrospective examination of weekly electrocardiograms of 13 patients on zero calorie intake for 97 +/- 25.4 d (mean +/- standard deviation) for morbid obesity demonstrated a significant progressive reduction in QRS voltage by the seventh week. There was a significant prolongation of the QTc interval in the group during the eighth week and in seven patients the QTc had lengthened beyond normal by the end of the fast. The importance of these changes is illustrated by one patient with QTc prolongation who sustained two cardiac arrests due to torsade de pointes. We recommend regular in-patient electrocardiographic monitoring for obese patients on therapeutic starvation.

An analysis of a micro-processor-based system to detect cardiac arrest rhythms was made in a series of 84 cardiac arrests in 78 patients. The ECG was sensed using 2 external ECGjdefibrillator pads applied to the chest wall. In 5 arrests, the initial rhythm was continuous electrical pacing in addition to the cardiac arrest and these were not included in the analysis. Of the remaining 79 arrests, there were 15 in which the initial rhythm was ventricular fibrillation and 14 were correctly detected by the system (sensitivity 93%). In the remaining 64 arrests the initial rhythm was not ventricular fibrillation and 62 were correctly identified (specificity 97%). A high specificity is required in any device employing automatic detection of ventricular fibrillation. Continuous electrocardiographic recordings of the cardiac arrests were analysed every 8 to 18 s: of 223 sections showing ventricular fibrillation, 165 were correctly determined by the system, i.e. sensitivity 74%, where the rhythm was not ventricular fibrillation, of the 5002 sections 4953 were correctly detected by the system, i.e. specificity 99%. The percentage accuracy of detection of ventricular fibrillation varied from 25–100% (mean 81%) and for detection of non-ventricular fibrillation from 57–100% (mean 99%) in every 8 to 18 s section of ECG tracing per cardiac arrest episode. Thus the automatic detection of cardiac arrest rhythms is feasible with a high degree of accuracy.

The week-to-week, inter- and intraobserver variation in left ventricular echocardiographic measurements has been studied in 10 normal male volunteers and in five patients with stable valvular disease. A two-way analysis of variance showed no statistically significant variation either from week to week or between observers. Furthermore the within observer variation was minimal. Calculation of the coefficient of variation allowed confidence limits to be applied to each of the six ventricular measurements, thus providing ranges of variation in follow-up studies using M-mode echocardiography.

The detection and correction of ventricular fibrillation at the earliest time after its onset is essential to ensure long-term survival. During successive cardiac arrests the rhythms occurring were sensed by using disposable pre-gelled ECG defibrillator pads placed in the anterior-anterior position. Simultaneously with the treatment, the arrest rhythms were analyzed continually every 8 to 18 seconds by a microprocessor system. This system sampled digitally the electrocardiogram, and the algorithm looked for absence of the isoelectric segment, irregular energy density spectrum, and irregular wave shape. The analysis was displayed visually as ventricular fibrillation (VF) or non-VF, and simultaneously the ECG and system's analysis were recorded on tape. Later, the system's interpretation of the rhythm was compared with the ECG record. There were 46 males and 32 females. Their ages ranged from 14 to 85 years, with a mean of 63 years. Twenty-nine patients had sustained an acute myocardial infarction. In the remaining 49 patients, there were a variety of causes for cardiac arrest, including heart failure, vasovagal syncope, cardiomyopathy, and postoperative cases. We report in detail the process and results.

This study in north east Scotland has shown that Marfan syndrome has a minimal birth incidence of 1:9802 live births, a minimal prevalence of 1:14217, and that 8/30 (26.7%) of cases in our series are new mutations. The calculated mutation rate is 15 +/- 6.7 x 10(-6) and there is evidence of reduced reproductive fitness.