D.J. Coltart

Effects on coronary artery disease of lipid-lowering diet, or diet plus cholestyramine, in the St Thomas' Atherosclerosis Regression Study (STARS)

To assess the effect of dietary reduction of plasma cholesterol concentrations on coronary atherosclerosis, we set up a randomised, controlled, end-point-blinded trial based on quantitative image analysis of coronary angiograms in patients with angina or past myocardial infarction. Another intervention group received diet and cholestyramine, to determine the effect of a greater reduction in circulating cholesterol concentrations. 90 men with coronary heart disease (CHD), who had a mean (SD) plasma cholesterol of 7.23 (0.77) mmol/l were randomised to receive usual care (U, controls), dietary intervention (D), or diet plus cholestyramine (DC), with angiography at baseline and at 39 (SD 3.5) months. Mean plasma cholesterol during the trial period was 6.93 (U), 6.17 (D), and 5.56 (DC) mmol/l. The proportion of patients who showed overall progression of coronary narrowing was significantly reduced by both interventions (U 46%, D 15%, DC 12%), whereas the proportion who showed an increase in luminal diameter rose significantly (U 4%, D 38%, DC 33%). The mean absolute width of the coronary segments (MAWS) studied decreased by 0.201 mm in controls, increased by 0.003 mm in group D, and increased by 0.103 mm in group DC (p less than 0.05), with improvement also seen in the minimum width of segments, percentage diameter stenosis, and edge-irregularity index in intervention groups. The change in MAWS was independently and significantly correlated with LDL cholesterol concentration and LDL/HDL cholesterol ratio during the trial period. Both interventions significantly reduced the frequency of total cardiovascular events. Dietary change alone retarded overall progression and increased overall regression of coronary artery disease, and diet plus cholestyramine was additionally associated with a net increase in coronary lumen diameter. These findings support the use of a lipid-lowering diet, and if necessary of appropriate drug treatment, in men with CHD who have even mildly raised serum cholesterol concentrations.

Association of antibodies against phospholipids with heart valve disease in systemic lupus erythematosus

A prospective echocardiographic study was carried out on 132 consecutive patients with systemic lupus erythematosus (SLE) derived from three European university medical centres. The prevalence of valvular lesions in patients with SLE was 22.7% compared with 2.9% in a control group of 68 healthy volunteers. 50 SLE patients had antibodies against phospholipids. The prevalence of valve vegetations (8/50 [16%]) and of mitral regurgitation (19/50 [38%]) was significantly higher among the SLE patients with antiphospholipids than among those without (1 and 10/82 [1.2% and 12%], respectively). During follow-up of the patients with valvular lesions, haemodynamically significant clinical valve disease developed in 6 but surgery was required in only 1; 9 had cerebrovascular occlusions; and 7 died, although no death was due directly to the cardiac involvement. Thus, valvular heart disease, particularly affecting the mitral valve, is common in patients with SLE, and the presence of antibodies against phospholipids is associated with a higher prevalence of valvular abnormalities in these patients.

Coxsackie B Virus-Specific IgM Responses in Patients with Cardiac and Other Diseases

An enzyme-linked immunosorbent assay (ELISA) test using polyvalent antigens and antisera was developed to detect Coxsackie-B-virus-specific IgM responses. The sera of 24 of 64 (37.5%) patients with acute pericarditis and 14 of 38 (36%) with acute myocarditis were positive for Coxsackie-B-virus-specific IgM. 4 of 30 (13.3%) patients with acute ischaemic heart disease and 2 of 28 (7.1%) patients with congestive cardiomyopathy were also positive. Coxsackie-B-virus-specific IgM was detected in the sera of 21 of 57 (36.8%) patients with Bornholm disease and 2 of 4 patients with acute-onset juvenile diabetes. Coxsackie-B-virus-specific IgM responses persisted for 6-8 weeks. Sera from patients with chronic valvular heart disease, Mycoplasma pneumoniae infections, and virus infections caused by viruses other than Coxsackie-B viruses were all negative. False-positive results did not occur when sera containing high titres of rheumatoid factor were tested.

LEFT-VENTRICULAR ENDOMYOCARDIAL BIOPSY

Abstract Experience of endomyocardial biopsy of the left ventricle in 64 patients is reported and compared with right-ventricular biopsy. Using a long-sheath technique, 310 left-ventricular biopsy specimens have been taken in 64 patients and 110 right-ventricular biopsy specimens in 31 of these patients. The microscopic left-ventricular appearance of biopsy specimens differed from that of right-ventricular specimens in 60%. In 13% no biopsy material was obtained from the right ventricle and in a further 13% the right-ventricular specimen consisted of fibrous tissue, adipose tissue, or pericardium. Complications occurred in 2% of right-ventricular biopsies and 0·3% of left-ventricular biopsies. This experience suggests that endomyocardial biopsy of the left ventricle is safer and more likely to produce a specimen that represents the pathological changes affecting the myocardium than endomyocardial biopsy of the right ventricle.

EFFECTS OF EARLY ADMINISTRATION OF A HIGHLY PURIFIED HYALURONIDASE PREPARATION (GL ENZYME) ON MYOCARDIAL INFARCT SIZE

79 patients with suspected myocardial infarction entered a randomised trial to establish the safety of early intravenous administration of a highly purified hyaluronidase preparation (GL enzyme) and to assess its effects on eventual infarct size as measured by electrocardiographic, enzymatic, and scintigraphic criteria. Of the 71 patients with infarction, 35 received GL enzyme and 36 placebo within 6 h of the onset of chest pain. GL enzyme injected into a peripheral vein produced no adverse changes in the clinical, haemodynamic, biochemical, or haematological variables studied. GL enzyme reduced precordial electrocardiographic indices of infarct size as reflected by a diminution (p less than 0.02) in the degree of both R wave loss and Q wave development. In addition, the number of leads developing pathological Q waves (N delta Q greater than or equal to 2), a sign of progression from ischaemia to necrosis, was reduced (p less than 0.05) after GL enzyme treatment. However, there were no significant differences in infarct size as measured by cumulative creatine kinase MB isoenzyme release or technetium-99m pyrophosphate scintigraphic infarct area, or in clinical outcome during the hospital stay. Interpretation of the enzymatic and scintigraphic data was complicated by chance bias in pre-treatment randomisation which resulted in more (p less than 0.05) patients with severe haemodynamic impairment (and hence probably larger infarct sizes) entering the GL enzyme group. Nonetheless, a favourable effect of GL enzyme on infarct size was demonstrated by precordial electrocardiographic QRS mapping, here each patient acts as his or her own control.

Angiotensin converting enzyme gene polymorphism and the course of angiographically defined coronary artery disease

“Depurtment of Medicine, Division of’ Cardiovascular Generics, University College London Medical School, The RaJxe Institute, 5 University Street, London, WClE 6JJ, UK hDepartment qf Endocrinology and Chemical Pathology, UMDS, St Thomas’ Hospital, London SE1 7EH. UK “Department of Cardiolog),, University of London, London. UK “Department of’ Medical Biophysics, University of Manchester Medical School, Manchester A413 9PT. UK

The Relationship between Glucose Utilization during Ischemia and Ventricular Fibrillation during Early Reperfusion

Guinea pig hearts perfused in the presence of 9 mM glucose were subjected to 30 min of ischemia (coronary flow reduced to 6%) and were then reperfused. During reperfusion, 18 of the 34 hearts studied (first subgroup) exhibited irreversible ventricular fibrillation. The remaining 16 hearts (second subgroup) exhibited serious rhythm disturbances but did not fibrillate. Attempts to identify critical factors that might precipitate fibrillation led to an observation that hearts that fibrillated during reperfusion were characterized by low rates of glucose utilization (0.6 ± 0.8 µmol/min per g dry wt. and low lactate plus pyruvate production (2.5 ± 0.32 µmol/min per g dry wt.) during ischemia. In addition, these hearts had a low calculated cytplasmic ATP-to-ADP ratio (10.0) and low residential glycogen levels (55 ± 7.0 xmol glucose equivalents/g dry wt.) at the end of the ischemic period. In contrast, in hearts that did not fibrillate (group 2), glucose utilization (2.5 ± 0.12 µmol/min per g dry wt.) was higher, lactate plus pyruvate production was higher (7.4 ± 0.03 µmol/min per g dry wt), cytoplasmic ATP-to-ADP ratio was higher (36.0), and residual glycogen levels were higher (163 ± 23 µmol glucose equivalents/g dry wt.). Thus, two distinct populations of guinea pig hearts were apparent, and comparison between the two groups indicated an association among glucose utilization, cytoplasmic energy status, and myocardial electrical stability.