Showing papers in "European Heart Journal in 1994"

Paroxysmal Atrial Fibrillation: A Disorder of Autonomic Tone?

Abstract: Electrophysiological characteristics of atrial cells (action potential duration and refractoriness, conduction speed) are modulated differently by vagal and sympathetic influences. The former tends to favour macro-reentry phenomena whereas the latter favours abnormal automaticity and triggered activity. In normal hearts vagal influences are predominant, thus explaining that the clinical pattern of vagal-mediated paroxysmal atrial fibrillation is preferentially observed in the absence of detectable heart disease, in young male adults, with an ECG pattern of common flutter alternating with fibrillation. Symathetically mediated atrial fibrillation is observed in the presence of any heart disease, the first effect of which is to provoke a vagal withdrawaL The clinical history is a reliable guide for suspecting which type of physiological autonomic predominance contributes to destabilize the arrhythmogenic substrate, but observing the behaviour of sinus rate variability just preceding the onset of the arrhythmia only permits documentation of the mechanism The role of the autonomic influences should be taken into consideration every time conventional antiarrhythmic treatment is insufficient. Beta-blockers as well as digitalis may be either beneficial or detrimental, according to the causal mechanism, so that the choice of their use as a single or a combined therapy should be appropriate.

Factors associated with calcific aortic valve degeneration in the elderly

Abstract: This study aimed at identifying factors influencing aortic valve calcification in old age. Echocardiographic and Doppler characteristics of the aortic valve were compared with possible clinical and biochemical predictors in 501 people aged 75-86 years and in 76 aged 55-71. Slight calcification was seen in 222 people (40%) and severe calcification in 72 (13%); 21 people had moderate or severe aortic stenosis. Age (P = 0.000) and serum parathyroid hormone (P = 0.015) were higher and body mass index lower (P = 0.002) in the presence of aortic valve calcification. In multivariate analysis, age (P = 0.000), hypertension (P = 0.005) and body mass index (P = 0.005) were independent predictors of aortic valve calcification, and age (P = 0.022) and serum ionized calcium (P = 0.037) of valve stenosis. The odds ratio (95% confidence interval) for valve calcification was 1.89 (1.42-2.50) for a 10-year increase in age, 1.74 (1.19-2.55) in the presence of hypertension, and 1.39 (1.10-1.76) for a 5 kg.m-2 decrease in body mass index. Sex, smoking, diabetes, serum lipids and insulin were unrelated to valvular calcification. These data suggest that leanness and a history of hypertension increase the likelihood of senile aortic valve calcification. Calcium metabolism may also be of significance. The mechanisms of these associations deserve further study.

Influence of the force—frequency relationship on haemodynamics and left ventricular function in patients with non-failing hearts and in patients with dilated cardiomyopathy

Abstract: In isolated human myocardium it was shown that a positive force-frequency relationship occurs in non-failing myocardium; however, the force-frequency relationship was found to be inverse in myocardium from failing human hearts. In order to investigate the clinical relevance of these experimental findings, the influence of heart rate changes on haemodynamics and left ventricular function was studied in eight patients without heart failure and in nine with failing dilated cardiomyopathy (NYHA II-III). Right ventricular pacing was performed at a rate slightly above sinus rate and at 100, 120 and 140 beats.min-1. Haemodynamic parameters were obtained by right heart catheterization and by high-fidelity left ventricular pressure measurements. Left ventricular angiography was performed at basal pacing rate and at 100 and 140 beats.min-1. With increasing heart rate, cardiac index increased in patients with normal left ventricular function from 2.9 +/- 0.2 to 3.5 +/- 0.21.min-1.m-2 (P < 0.01) and decreased continuously in patients with dilated cardiomyopathy from 2.6 +/- 0.1 to 2.2 +/- 0.1 l.min-1. m-2 (P < 0.05). With increasing heart rate, the maximum rate of left ventricular pressure rise increased in non-failing hearts from 1388 +/- 86 to 1671 +/- 88 mmHg.s-1 (P < 0.01) and did not change in failing hearts. Ejection fraction decreased from 27 +/- 3% to 19 +/- 2% in patients with dilated cardiomyopathy (P < 0.05) when the pacing rate was changed from 84 +/- 2 beats.min-1 to 140 beats.min-1, which was associated with a significant increase in end-systolic volume without significant changes in end-diastolic volume.(ABSTRACT TRUNCATED AT 250 WORDS)

The carotid intima-media thickness as a marker of the presence of severe symptomatic coronary artery disease

Abstract: High resolution ultrasound can be used for the accurate measurement of intima-media thickness (IMT). The within-observer coefficient of variation of the IMT of two carotids measured seven times each on different days by two different observers was between 4% and 8%, and the mean absolute difference of the IMT of 68 carotids measured independently by two observers was 0.11 +/- 0.11 mm (mean value +/- SD). Seventy-five consecutive male patients who underwent coronary angiography for assessment of chest pain and 40 normal controls matched for age and sex, were examined with high resolution B-mode ultrasound. The IMT of the common carotid artery for the controls was 0.71 +/- 0.16 mm and for the patients 0.91 +/- 0.18 mm (P or = 0.85 mm was derived from the studied population of 75 patients as a criterion for the prediction of coronary artery disease (CAD).(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic congestive heart failure. Description and survival of 190 consecutive patients with a diagnosis of chronic congestive heart failure based on clinical signs and symptoms.

Abstract: The prognosis, and clinical findings related to prognosis, were examined in a consecutive series of 190 patients under 76 years of age (mean 64 years) with congestive heart failure (CHF). The aetiology of CHF was ischaemic heart disease in 66%, hypertension in 11% and cardiomyopathy in 23%. The 2-year mortality was 32%. Median left ventricular ejection fraction (LVEF) was 0.30, range 0.06 to 0.74. Eight per cent were in New York Heart Association (NYHA) class I, 46% in II, 44% in III and 2% in IV. Multivariate analysis, excluding exercise test variables, revealed seven variables with independent, significant prognostic information, (hazard ratios for death in brackets): ln (natural logarithm) (LVEF) (3.19), NYHA class III+IV (2.72), plasma urea > 7.6 mmol.l-1 (2.22), serum creatinine > 121 mumol.l-1 (2.05), serum sodium 65 years (1.86). Multivariate analysis, including exercise testing, showed the following variables to contain independent, significant prognostic information: increase in heart rate during maximal exercise 121 mumol.l-1 (2.9), maximal exercise time 7.6 mmol.l-1 (1.9). In conclusion, patients with CHF have a high risk of death despite intensive medical treatment. LVEF is a strong predictor of mortality. Both NYHA class and exercise variables have strong independent prognostic information as regards mortality in combination with LVEF, but are mutually exclusive.

Insulin resistance in chronic heart failure

Abstract: The objective of this study was to investigate the existence of abnormalities of insulin sensitivity in patients with chronic heart failure. Glucose metabolism and insulin resistance were assessed in 10 male patients with severe, chronic heart failure and in 10 matched control subjects. Glucose, insulin and C-peptide concentration profiles were measured following a 0.5 g.kg-1 intravenous glucose tolerance test. Insulin sensitivity (inversely related to insulin resistance) was estimated by minimal modelling analysis of the glucose and insulin profiles. Heart failure patients had similar mean fasting plasma glucose concentration to controls but a significantly greater mean fasting plasma insulin concentration (P = 0.002) and C-peptide concentration (P = 0.02). Plasma glucose response profile was similar in the two groups but the incremental plasma insulin response profile of the heart failure group was significantly greater (P = 0.004). Mean insulin sensitivity was 73% lower in the heart failure patients (P = 0.003). These findings show that patients with severe chronic heart failure are hyperinsulinaemic and insulin resistant compared with a matched health group. This insulin resistance and hyperinsulinaemia may contribute to the progressive deterioration in myocardial function and associated clinical features of fatigue and reduced exercise tolerance seen in heart failure. Interventions designed to overcome or reduce insulin resistance warrant further investigation.

Predictors of exercise capacity in chronic heart failure

Abstract: Abnormalities of skeletal muscle rather than of haemodynamics may be important determinants of exercise capacity in chronic heart failure. We investigated an array of indicators of central haemodynamics and peripheral muscle function to establish which resting measurements predicted exercise performance. In 20 patients quadriceps strength, resting and peak leg blood flow and leg muscle cross sectional area were measured. In 18 patients average daytime blood pressure and pulse rate, haemodynamic variables at rest and during exercise, and autonomic activity were measured. There were correlations between peak oxygen consumption and quadriceps strength (0.65; P = 0.007), thigh muscle cross sectional area (r = 0.63; P = 0.004), and average daytime systolic blood pressure (r = 0.66; P < 0.01). There were no correlations with indices of peripheral blood flow, measures of haemodynamic function, or autonomic function. Quadriceps strength was the most important individual correlate of exercise tolerance (r = 0.73). With total muscle cross sectional area and left quadriceps strength also taken into consideration, 82% of the variation in peak oxygen consumption was explained. Of the haemodynamic variables, only average daytime systolic blood pressure predicted exercise performance. The resting variables that best predict exercise performance in chronic heart failure are measures of skeletal muscle function and bulk, and average daytime systolic blood pressure. These findings suggest that abnormalities in the periphery largely determine exercise performance in chronic heart failure, and that the ability of the heart to generate an adequate blood pressure response to daily activities is also predictive of functional status.

An echocardiographic method for selecting high risk patients shortly after acute myocardial infarction, for inclusion in multi-centre studies (as used in the TRACE study)

Abstract: The aim of our study was to examine if echocardiography can reproducibly be used in a multicentre study to select high risk patients with reduced left ventricular function early after an acute myocardial infarction (MI). In the TRAndolapril Cardiac Evaluation Study (TRACE) patients with reduced left ventricular systolic function were randomized 3–7 days post MI to receive either the ACE inhibitor trandolapril, or placebo. Twenty-seven Danish centres participated and 7001 consecutive MI patients were screened for entry. Local doctors and technicians who had received a brief but thorough training course recorded a two-dimensional echocardiographic examination on videotape 2–6 days after MI. Within 24 h, wall motion index (WMI) was visually assessed by one of two cardiologists (examiners) with considerable experience in echocardiography. A WMl of ≤l.2 (corresponding to a left ventricular ejection fraction (LVEF) ≤0.35) meant that the patient was eligible for randomization in the TRACE study. Two other experienced cardiologists with substantial experience in echocardiography (controllers) performed blind reassessment of 155 randomly chosen videotapes. We showed that 93% of the 7001 screened Mis had an assessable echocardiogram. WMl was ≤1.2 in 37% of patients. The one-year mortality was inversely related to WMl, being 60%, 30%, 14% and 11% in patients with a WMI l.6, respectively. In the random sample of 155 videorecordings that were reevaluated, 97% were found to be technically adequate for analysis both by the examiners and the controllers. Comparing the examiners with the controllers, the reproducibility analysis showed 95% confidence limits for a single estimate of LVEF of ± 0.13. Comparison between the two examiners showed corresponding confidence limits of ±0.10. Using WMl of 12 (LVEF∼0.35) as a discriminative value the concordance between examiners and controllers was 80%. Thus, evaluation by experienced cardiologists of videotaped echocardiographic examinations recorded by briefly but thoroughly trained investigators appears to be a reliable and reproducible method for the selection of high risk patients shortly after MI in multicentre studies.

Spinal electrical stimulation for intractable angina--long-term clinical outcome and safety.

Abstract: Spinal cord electrical stimulation is an alternative therapy for patients with chronic pain syndromes including angina. Although it has been shown to produce symptomatic relief and reduce ischaemia, doubts remain about its long-term safety. We report here for the first time the results of a follow-up study over a period of 62 months, mean 45 months (range 21–62), of 23 patients who had stimulator units implanted for intractable angina unresponsive to standard therapy. Symptomatic improvement was good and persisted in the majority with a mean (SD) change of NYHA grade from 3.1 (0.8) pre-operatively to 2.0 (0.9) (P<0.01) immediately after operation and 2.1 (1.07) at the latest follow-up. GTN consumption fell markedly. Mean (SEM) treadmill exercise time increased from 407 (45) s with the stimulator off to 499 (46) s with the stimulator on (P<0.01). Forty-eight hour ST segment monitoring in those with bipolar leads showed a reduction of total number and duration of ischaemic episodes. There were three deaths, none of which were sudden or unexplained and this mortality rate is acceptable for such a group of patients. Two patients had a myocardial infarction, which was associated with typical pain and not masked by the treatment. Complications related to earlier lead designs were frequent. This study confirms that spinal electrical stimulation is an effective and safe form of alternative therapy for the occasional patient whose angina is unresponsive to standard therapies.

Serum ferritin and ceruloplasmin as coronary risk factors

Abstract: Iron and copper catalyze lipid peroxidation in vitro, and recent epidemiological data suggest that these metal ions might also be involved in human coronary heart disease. We tested the hypothesis by investigating whether the storage proteins ferritin and ceruloplasmin were coronary risk factors. A nested case-control study was set up in middle-aged dyslipidaemic participants of the Helsinki Heart Study: a placebo-controlled coronary primary prevention trial with gemfibrozil. Of the 140 subjects with cardiac end-points (non-fatal myocardial infarction or cardiac death) 136 were matched with controls for geographical area and drug treatment (gemfibrozil-placebo). Frozen baseline serum samples were used in the analyses of ferritin and ceruloplasmin. Using logistic regression analyses no increment in coronary risk was detected with increasing ferritin levels (P = 0.8 for trend). Ceruloplasmin was higher 349 +/- 86 vs 317 +/- 77 mg.l-1 (P < 0.001) in cases than in controls and the risk in the highest tertile was two-fold (odds ratio 2.1; 95% CI 1.1-4.2) compared to the lowest (P < 0.005 for trend). The risk of high ceruloplasmin was influenced by lipoprotein cholesterol concentrations, with an odds ratio of 2.4 (95% CI 1.3-4.4) in subjects with high low density lipoprotein cholesterol and of 11.3 (95% CI 2.5-52.2) in subjects with low high density lipoprotein cholesterol. It was concluded that ferritin was not associated with coronary heart disease in dyslipidaemic, middle-aged men, while there was a continuous and graded increment in coronary risk with elevating ceruloplasmin level.

Coronary heart disease risk factors in women

Abstract: Coronary heart disease is the leading cause of death among women. Reported risk factors for women are smoking, use of oral contraceptives, diabetes, elevated blood pressure, elevated blood lipids, low socio-economic status, low educational attainment, Type A behaviour and chronic troubling emotions. Via an on-line literature search (Medline and Psychlit) all case-control and prospective studies of coronary heart disease risk factors in women have been collected from 1978 to 1993. Smoking remains the most prominent risk factor for myocardial infarction in young women, the risk increasing significantly with the amount of cigarettes smoked Use of modern low-dose oral contraceptives in healthy, non-smoking women does not increase the risk. Oestrogen replacement therapy seems to protect against coronary heart disease, although the reduction in risk may have been over-estimated. Elevated cholesterol and elevated blood pressure are major risk factors, and diabetes seems to have a stronger impact on risk in women than in men. Low socio-economic class is a stronger risk factor for women than for men and the double loads of career and family seem to increase risk for women.

Acute intervention with captopril during thrombolysis in patients with 1st anterior myocardial-infarction - results from the captopril and thrombolysis study (cats)

Abstract: The study was designed to examine the safety and efficacy of acute interventional use of captopril on left ventricular volumes, ventricular arrhythmias and neurohormones during thrombolysis in patients with a first anterior myocardial infarction, within 6 h of onset of symptoms. Left ventricular dysfunction and prognosis after myocardial infarction can be improved by angiotensin converting enzyme inhibition started after the ischaemic phase. Experimental evidence suggests that intervention during thrombolysis may lead to even further benefit. In a randomized, double-blind placebo-controlled trial, 298 patients with a first anterior myocardial infarction, eligible for thrombolytic therapy were treated with captopril 6.25 mg or placebo, started immediately upon streptokinase infusion and titrated to 2.5 mg t.i.d.. The efficacy of captopril by an intention-to-treat-analysis to reduce left ventricular volumes, ventricular arrhythmias, neurohumoral activation and enzymatic infarct size was measured. During dose titration, mean blood pressure and heart rate were similar in both groups. However, hypotension after the first dose was reported in 18 patients on placebo and 31 patients on captopril (P<0.05). At discharge, 80% of patients were on study medication. Left ventricular volumes were significantly increased in both groups at 3 months, but they tended to be lower in the captopril group; however, the differences were not statistically significant. The incidence of accelerated idioventricular rhythm and non-sustained ventricular tachycardia in captopril patients was lower than in placebo patients (P<0.05), parallelled by transiently lower norepinephrine levels (P<0.05) upon thrombolysis. In addition, enzymatic infarct size was smaller in captopril patients, especially in larger infarcts (P<0.05), and a 34% (95% confidence interval; 0–56%) lower incidence of heart failure during 3 months follow-up was reported in the captopril group. Captopril is well tolerated, although hypotension after the first dose was more common than in patients on placebo. In agreement with experimental studies, captopril reduces repetitive ventricular arrhythmias and catecholamine levels in the acute thrombolytic phase of myocardial infarction. Although left ventricular volumes were not significantly smaller in captopril patients, in the chronic phase, these patients showed a reduced incidence of heart failure. This study was carried out under auspices of the Interuniversity Institute of the Netherlands (ICIN) and the Working Group of Cardiovascular Research the Netherlands (WCN). Financial support was received from Bristol-Myers Squibb, Pharmaceutical Research Institute, Princeton, N.J., U.S.A.

Peri-operative complications following surgical closure of atrial septal defect type II in 232 patients—a baseline study

Abstract: This study intends to provide a detailed overview of the types and rates of peri-operative complications after surgical correction of an isolated ASD II. The transvenous approach to the occlusion of atrial septal defects has yielded promising results during its first 5 years of clinical trials, but before it can be established as a routine measure, definite proof is needed to demonstrate that its rate of serious complications does at least not exceed that of the surgical closure. Between 1985 and 1992, 232 consecutive patients underwent surgical closure of a secundum atrial septal defect. Among the patients 118 were children (< 18 years; 79 girls and 39 boys) with a mean age of 8.9 +/- 5.2 years (4 months-17 years) and 114 adults (74 women and 40 men) with a mean age of 28.5 +/- 10.8 years (18-69 years). Pre-operatively eight children (6.8%) and eight adults (7%) were treated for right heart failure. Mean pulmonary artery pressure was 20.4 +/- 10.4 mmHg for the children and 19.3 +/- 7 mmHg for the adults. The average pulmonary artery to systemic flow ratios were 2.9:1 and 3:1 for children and adults, respectively. Thirty children (25.4%) and 15 adults (13.2%) underwent patch closure while direct suture was the method used for the remaining patients. Average cardiopulmonary bypass time was 35.7 +/- 17.9 min for the children and 41.5 +/- 19.9 min for the adults. The length of the procedure (skin to skin) was a mean of 116 min in the young group, and 141 min in the adult group.(ABSTRACT TRUNCATED AT 250 WORDS)

Atropine increases the accuracy of dobutamine stress echocardiography in patients taking beta-blockers.

Abstract: Dobutamine-atropine stress echocardiography is used for the non-invasive diagnosis of coronary artery disease, but stress test results may be influenced by beta-blockers. The aim of this study was to assess if the addition of atropine can compensate for the presence of beta-blockers in dobutamine stress echocardiography. Twenty-six patients referred for evaluation of chest pain were studied twice, on and off metoprolol 100 mg b.i.d (in random order sequence) with a wash-out period of at least 48 h. Dobuta,nine stress echocardiography was performed using up to 40 μg. kg−1 min−1, followed, if necessary, by the addition of atropine to achieve 85% of the age-predicted maximal heart rate, unless symptoms or markers of ischaemia appeared. Atropine was given to patients on beta-blockers more often [ (22126)vs(6126) ] than to those off beta-blockers (P<0·001). Heart rate at every stage of the test was lower on beta-blockers. Chest pain occurred in patients on beta-blockers significantly less than in those off beta-blockers (8% vs 46%), and the addition of atropine made no significant difference (31% vs 46%). During dobuta stress, new wall motion abnormalities occurred in three patients on beta-blockers (12%); this number increased to 15 after the addition of atropine (57%). New or worsened wall motion abnormalities occurred in 12 patients (46%) off beta-blockers with dobutamine alone and in 14 patients after adding atropine (53%). We conclude that (1) beta-blockers decrease the chronotropic effect and reduce the incidence of myocardial ischaemia during dobutamine stress, (2) the addition of atropine to dobutamine increases heart rate and equalizes the detection of ischaemia in patients on and off beta-blockers.

Cardiac vagal hyperactivity in adolescent anorexia nervosa

Abstract: Adolescent anorexia nervosa, a psychiatric disease with high mortality, is often associated with bradycardia. We studied the vagal control of sinus node function in anorexic subjects, to investigate the mechanism of anorexic bradycardia. Cardiac vagal tone was determined in a group of 11 adolescent anorexic girls and in 11 age- and height-matched controls. Cardiac vagal tone in the anorexic patients was measured as the change in R-R interval in response to complete cholinergic blockade; in addition, non-invasive indices of cardiac vagal tone and baroreflex sensitivity were determined in both anorexic and control subjects. Cardiac vagal tone in anorexic subjects was 465 +/- 52 (SE) ms, about 30% higher than values reported for healthy subjects. Vagal tone values were directly related to percent weight loss (R = 0.69, P = 0.017). Non-invasive indices of both cardiac vagal activity and baroreflex sensitivity were significantly higher in the anorexic group as compared to controls; the percent increase of cardiac vagal tone, however, exceeded the increase of baroreflex sensitivity. Cardiac vagal hyperactivity significantly contributes to the bradycardia of anorexic subjects. The excess vagal activity is only partly explained by enhanced baroreflex sensitivity.

Morning and Monday: critical periods for the onset of acute myocardial infarction. The GISSI 2 Study experience.

Abstract: The onset of acute myocardial infarction (AMI) is unevenly distributed over the 24 h and the week. While presence of a morning peak is generally agreed upon, contrasting results had been obtained regarding other periods of the day, probably due to differences of origin, size and composition of the populations. The 24 h and weekly distributions were studied within 6 h from the beginning of the symptoms in a population following a Latin life-style, who were enrolled in the GISSI 2 Study (n = 11472). Subgroups (smokers, the elderly (> 65 years), diabetics, hypertensives) were also considered. Six hour periods starting at midnight were tested for uniformity. Circadian non-uniformity was found. Events increased in the morning hours and reduced during the night regardless of the day of the week. The night and day difference was attenuated in smokers and diabetics. Non-uniformity of the events was also found among the days of the week. AMI significantly increased in non-smokers on Monday. We suggest that there is a night-day gradient (characterized by the short time interval between the two frequency extremes) in the time of onset of AMI. The different distribution in smokers stresses the possible unfavourable and masking effect of a heightened sympathetic tone during the day while the general protective role of the night hours is preserved. Moreover, the increased incidence of events on Monday may suggest the importance of the shift from a period of non-scheduled to scheduled activity.

Angiotensin II receptor subtypes : selective antagonists and functional correlates

Abstract: Angiotensin II (Ang II) receptor heterogeneity is currently defined by the new subtype-selective agents, losartan (AT1) and PD123177 (AT2). Although both subtypes have been cloned and sequenced, only the AT1 receptor has been shown to have an important physiological or pathophysiological role. AT1 and AT2 receptors are found in both normal and failing cardiac tissue. They are found on myocytes, endothelial cells, fibroblasts, coronary arterial smooth muscle cells, and peripheral sympathetic nerves. The AT1 receptors mediate virtually all of the effects of Ang II in myocytes even though cardiac tissue may contain over 50% AT2 sites. In endothelial cells, functional responses are predominately AT1. In fibroblasts, preliminary data suggest that AT2 receptors may be involved in collagen synthesis. In isolated tissue, Ang II has a limited positive inotropic effect in atrial, but not in ventricular tissue, which is blocked by losartan. Ang II may also have a tonic effect on coronary artery resistance as angiotensin inhibitors can increase coronary flow. Both ACE (Ang II synthesis) inhibitors and Ang II receptor antagonists produce beneficial effects in experimental models of heart failure, suggesting Ang II is an important mediator of heart failure. Because ACE inhibitors also potentiate bradykinin and are non-specific inhibitors of Ang II synthesis (availability of Ang II to both receptor subtypes) some differences can be anticipated. At the present time, however, the beneficial role of bradykinin is controversial and the predominant functional Ang II receptor in the heart and other tissues is the AT, subtype. Selective AT1 antagonists represent an important new class of potential therapeutic agents not only in hypertension, which is now firmly established, but also in cardiac failure, renal failure, and stroke.

The ‘Ermenonville’ classification of observations at coronary angioscopy—evaluation of intra- and inter-observer agreement

Abstract: A European coronary angioscopy working group has been established to create and evaluate a classification system for angioscopic observation. The 'Ermenonville' classification features items, graded in 3-5 categories, such as lumen diameter, shape of narrowing, colours of surface, atheroma, dissection, thrombus, etc. Inter- and intra-observer agreement on the interpretation of angioscopic images, using this classification system, was studied within the working group. Kappa values for chance-corrected intra-observer agreement of the diagnostic items were 0.51-0.67. The mean kappa values for inter-observer agreement were very low at 0.13-0.29. The important items, such as red thrombus and dissection were studied after recoding as either present or absent. These items proved to have a good intra-observer agreement, and an acceptable inter-observer agreement after recoding. Other angioscopic diagnoses should be made with caution. Multicentre angioscopy studies should make use of an angioscopy core laboratory. A set of definitions for coronary angioscopy is proposed, and this working group will re-evaluate observer agreements using these definitions.

Early accumulation of the terminal complement-complex in the ischaemic myocardium after reperfusion

Abstract: The terminal, membrane-damaging complement complex C5b-9 accumulates in the infarcted myocardium. In experimental myocardial infarction, we investigated the time course of C5b-9 deposition and the influence of reperfusion. In a group of 17 rabbits (group 1), the circumflex coronary artery was occluded for different time periods ranging from 0.5 to 29 h without subsequent reperfusion. A second group of 23 rabbits (group 2) underwent coronary artery occlusion for periods ranging from 0.5 to 6 h followed by reperfusion. C5b-9 was determined in transmural myocardial biopsies by immunohistochemistry and by ELISA. In group 1, C5b-9 accumulation in the ischaemic myocardium was found only after 5 to 6 h of coronary artery occlusion. In group 2 (ischaemia and reperfusion), significant C5b-9 deposition was already observed after 30 min of myocardial ischaemia. We conclude that in the absence of reperfusion C5b-9 accumulation occurs as a late event when most of the jeopardized myocardium has probably already become necrotic. In the presence of reperfusion, however, the complement system is activated rapidly and this could play a role in the pathogenesis of reperfusion injury.

A comparison of antioxidant status and free radical peroxidation of plasma lipoproteins in healthy young persons from Naples and Bristol.

Abstract: Ischaemic heart disease mortality is much lower in Southern Italy than in the U.K. and this is not entirely explained by differences in classical risk factors. Differences in antioxidant intake, affecting free radical peroxidation of plasma lipoproteins, may be relevant. Therefore, dietary intake, antioxidant status and plasma lipid peroxidation were compared in healthy young persons eating typical regional diets from Naples (22) and Bristol (26). The Naples group consumed more fresh tomatoes, more fat as monounsaturates (from olive oil) and had higher plasma levels of the lipid antioxidants vitamin E (mean (SD; 95% CI) 29.1 (4.5; 26.8 to 31.3) vs 25.1 (3.86; 23.4 to 26.8) μmol I−1, P=0.005) and beta-carotene (4.74 (1.2; 4.14 to 5.34) vs 2.85 (0.8; 2.5 to 3.2) μmol. I−1, P<0.001). Intakes of vitamin C, total uncooked fruit and vegetables, plasma vitamin A, serum selenium and copper levels were similar. All indices of plasma lipid peroxidation were significantly lower in the Naples group: conjugated dienes (median (interquartile range; non-parametric 95% CI)) 29 (21.5-39.9; 24 to 36.7) vs 41.5 (37-48.5; 38 to 44.5) μmol. I−1, P<0.001; diene conjugation index 1.38 (1.02-1.55; 1.06 to 1.49) × 10−2 vs 1.57 (1.43-1.74; 1.44 to 1.71) × 10−2, P=0.019; lipid peroxides (geometric mean (95% CI)) 1.24 (1.12 to 1.37) vs 4.58 (3.84 to 5.46) μmol. I−1, P<0.001. Low levels of free radical peroxidised lipoproteins in Southern Italians may contribute to their comparatively low incidence of ischaemic heart disease and may result from increased antioxidant protection by higher plasma vitamin E and beta-carotene levels, derived from high olive oil and tomato intakes.

Emergency angioplasty of totally occluded left main coronary artery in acute myocardial infarction and unstable angina pectoris—institutional experience and literature review

Abstract: Acute occlusion of the left main coronary artery (LMCA) is a rare angiographic finding. We report five patients with acute myocardial infarction (AMI) and one patient with unstable angina, in whom reperfusion was achieved or attempted with percutaneous transluminal coronary angioplasty (PTCA). All patients had a long history of stable angina pectoris. The indication for emergency PTCA was cardiogenic shock in the five patients with MI. PTCA was successful in five of six patients. Three patients with reperfusion survived, three died. All survivors underwent coronary artery bypass grafting (CABG) and were still alive at 23 months, 3 and 8 years respectively in NYHA functional class II or III. All patients had a dominant right coronary artery, but only the survivors had moderate or extensive collateralization. Our experience and the literature review indicate that the clinical outcome of patients with acute LMCA occlusion is strongly dependent on the presence or absence of intercoronary collaterals.

Three-year follow-up of the Oxford Cholesterol Study: assessment of the efficacy and safety of simvastatin in preparation for a large mortality study

Abstract: We report the results of a randomized single-centre study designed to assess the effects of simvastatin on blood lipids, blood biochemistry, haematology and other measures of safety and tolerability in preparation for a large-scale multicentre mortality study. Six hundred and twenty-one individuals considered to be at increased risk of coronary heart disease were randomized, following a 2-month placebo 'run-in' period, to receive 40 mg daily simvastatin, 20 mg daily simvastatin or matching placebo. Their mean age was 63 years, 85% were male, 62% had a history of prior myocardial infarction (MI), and the mean baseline total cholesterol was 7.0 mmol.l-1. Median follow-up in the present report is 3.4 years. Eight weeks after randomization, 40 mg daily simvastatin had reduced non-fasting total cholesterol by 29.2% +/- 1.1 (2.03 +/- 0.08 mmol.l-1) and 20 mg daily simvastatin had reduced it by 26.8% +/- 1.0 (1.87 +/- 0.07 mmol.l-1). Almost all of the difference in total cholesterol at 8 weeks was due to the reduction in LDL cholesterol (40.8% +/- 1.6 and 38.2% +/- 1.4 among patients allocated 40 mg and 20 mg of simvastatin daily respectively), but simvastatin also reduced triglycerides substantially (19.0% and 17.3%) and produced a small increase in HDL cholesterol (6.4% and 4.8%). These effects were largely sustained over the next 3 years, with 40 mg daily simvastatin producing a slightly greater reduction in total cholesterol at 3 years (25.7% +/- 1.9 reduction) than did 20 mg daily simvastatin (22.2% +/- 1.8). There were no differences between the treatment groups in the numbers of reports of 'possible adverse effects' of treatment or of a range of different symptoms or conditions (including those related to sleep or mood) recorded at regular clinic follow-up. Mean levels of alanine aminotransferase, aspartate aminotransferase and creatine kinase were slightly increased by treatment, but there were no significant differences between the treatment groups in the numbers of patients with significantly elevated levels. A slightly lower platelet count in the simvastatin group was the only haematological difference from placebo, with no difference in the numbers of patients with low platelet counts. In summary, the simvastatin regimens studied produced large sustained reductions in total cholesterol, LDL cholesterol and triglyceride and small increases in HDL cholesterol. They were well tolerated, with no evidence of serious side-effects during the first 3 years of this study.(ABSTRACT TRUNCATED AT 400 WORDS)

Nutritional assessment and muscle energy metabolism in severe chronic congestive heart failure--effects of long-term dietary supplementation.

Abstract: In order to investigate nutritional status in relation to the metabolic state of skeletal muscle in patients with severe congestive heart failure, and to explore the influence of long-term dietary supplementation, 22 patients were randomized in a double-blind study to receive either a placebo (n = 13) or high caloric fluid (n = 9). Before treatment, the muscle content of adenosine triphosphate (ATP), creatine and glycogen was lower than in healthy individuals, and muscle biopsies revealed an excess of water. Two patients were found to be malnourished according to nutritional assessment criteria. Following study treatment, no significant changes occurred, either within or between the two subgroups. Thus, patients with severe congestive heart failure displayed metabolic derangement in skeletal muscle which did not seem to be explained by malnutrition.

Spectral components of short-term RR interval variability in healthy subjects and effects of risk factors

Abstract: Cardiac neural control can be estimated by frequency domain characterization of RR interval variations. This technique may become a clinical tool, as autonomic dysfunction is involved in the pathophysiology of sudden cardiac death. The study was designed to investigate 24-h cardiac autonomic control in 104 healthy subjects aged 40-77 years and to evaluate the impact of gender, age, smoking and physical training level. The sympathovagal balance was evaluated by spectral analysis of RR interval oscillations. The square-root of power of the high- (HF; 0.15-0.40) and low-frequency (LF; 0.04-0.15 Hz) bands were considered indexes of the vagal function and of the sympathovagal interaction, respectively. In addition, the precise centre frequency of the LF and HF oscillations was determined. The vagal mediated respiratory-dependent HF oscillation exhibited a clear circadian variation, and obtained the highest power values during sleep. The centre frequency was significantly lower during sleep (0.26 Hz vs 0.28 Hz), probably due to a slower respiratory frequency at night. Values for vagal tone were higher in physically trained subjects throughout the 24-h, and decreased by 13% for every 10-year increase in age; it was also reduced in smokers. The amplitude of the LF oscillation exhibited no clear diurnal variation. The mean LF/HF ratio was 3.1. LF power was much higher in males, was reduced by 15% per 10 year increase in age, and was lower in sedentary and smoking subjects, throughout the 24-h. The mean centre frequency of this component was reduced with advancing age (0.08 to 0.06 Hz from age 40 to 80 years). LF and HF power correlated positively, (r = 0.68), and 46% and 16% of the interindividual variation in LF and HF power, respectively, was explained by the four factors (gender, age, smoking, physical activity). Thus gender, age smoking and physical training level have a significant impact on the power and centre frequency of the HF and LF components. These effects must be addressed in investigations on autonomic balance.

Characteristics and prognosis of patients with acute myocardial infarction in relation to occurrence of congestive heart failure

Abstract: Congestive heart failure is one of the major symptoms accompanying acute myocardial infarction (AMI). The study aimed to describe the occurrence, characteristics and prognosis of congestive heart failure in AMI and to compare post-MI patients with and without congestive heart failure. The methods used included baseline characteristics, initial symptoms, electrocardiogram (ECG), mortality during hospitalization and one year follow-up in consecutive patients with AMI admitted to Sahlgrenska Hospital, Goteborg, Sweden. Congestive heart failure was observed in 51% of the cases. Patients with congestive heart failure were older, more frequently had a history of previous cardiovascular disease, and, less frequently had chest pain on admission to hospital. They had a higher occurrence of life-threatening ventricular arrhythmias during initial hospitalization, and their mortality during one year follow-up was 39% as compared to 17% in patients without congestive heart failure (P<0.001). This difference remained significant when correcting for differences at baseline. Patients with severe congestive heart failure had a one year mortality of 47% vs 31% in patients with moderate congestive heart failure (P<0.01). Signs and symptoms of congestive heart failure occur in every second patient admitted to hospital due to AMI, and indicate a bad prognosis, which is directly related to the severity of congestive heart failure.

Regulation of the Structural Remodelling of the Myocardium: from Hypertrophy to Heart Failure

Abstract: The Framingham heart study has shown that arterial hypertension is the major aetiological factor for the development of heart failure. In the presence of heart failure, various regulatory systems may be operative. These include the Frank-Starling mechanism, the neurohormonal system, regulation of cardiac growth and peripheral oxygen delivery. Recently, the interrelationship of the neuroendocrine system and cardiac growth has been examined. In the pressure or volume overloaded heart, growth of the myocardium involves the enlargement of cardiac myocytes, an adaptation governed by ventricular loading. Non-myocyte cell growth, including cardiac fibroblasts, may also occur. However, the haemodynamic load does not appear to be its major physiological stimulus. Cardiac fibroblast activation is responsible for the accumulation of type I and III collagens, the major fibrillar proteins of the myocardial collagen matrix, while vascular smooth muscle cell growth accounts for medial thickening of coronary resistance vessels. This structural remodelling of the cardiac interstitium represents a major determinant of pathological hypertrophy: it accounts for abnormal myocardial stiffness and impaired coronary reserve, thereby leading to ventricular diastolic and systolic dysfunction and ultimately the appearance of symptomatic heart failure. Several lines of evidence suggest that circulating and tissue renin-angiotensin-aldosterone systems are involved in the structural remodelling of the non-myocyte compartment, including the ‘cardioprotective’ effects of angiotensin converting enzyme (ACE) inhibition or the beneficial effects of anti-aldosterone treatment that were found to prevent myocardial fibrosis in renovascular hypertension due to unilateral renal ischaemia under experimental conditions. In spontaneously hypertensive rats, i.e. the analogous model for primary hypertension in man, with either early or advanced hypertensive heart disease, the ACE inhibitor lisinopril was able to restore myocardial structure and function to normal These ‘cardioreparative’ properties of chronic ACE inhibition may be valuable in reversing left ventricular dysfunction in hypertensive heart disease by treating the structural roots of heart failure.

Uniformity of captopril benefit in the SAVE study : subgroup analysis

Abstract: The Survival and Ventricular Enlargement (SAVE) Study demonstrated that long-term administration of the angiotensin-converting enzyme inhibitor captopril to recent survivors of myocardial infarction with left ventricular dysfunction resulted in a reduction in cardiovascular mortality and morbidity. Analysis of multiple subgroups demonstrated that baseline demographics (older age) and clinical characteristics (such as prior MI, history of diabetes or hypertension), that have previously been associated with a higher risk of cardiovascular events, were associated with greater end point event rates in SAVE regardless of therapy assignment at the time of randomization. The effectiveness of captopril therapy in reducing cardiovascular mortality and morbidity was examined in multiple subgroups. Although not all subgroups provided adequate statistical power, the benefits of captopril therapy were relatively uniform in the SAVE study. This indicates that the benefits were not confined to one particular subgroup and conversely that targeting of captopril therapy should be to the broadest group, as defined by SAVE entry criteria, to result in a reduction in cardiovascular mortality and morbidity.

Association of risk factors and body iron status to carotid atherosclerosis in middle-aged Eastern Finnish men

Abstract: High body iron stores have been proposed as a risk factor for advanced atherosclerosis. We investigated the prevalence of early atherosclerotic changes, and their relation to conventional CHD risk factors and body iron status. A cross-sectional study was carried out in 206 men aged 50 to 60 years (6% random population sample). Intima-media thickness (IMT) of the carotid artery was evaluated with high-resolution B-mode ultrasonography. Statistical analyses were performed separately for men with and without cardiovascular disease (CVD). Among all the study participants, 6.6% had IMT > 1.3 mm in the common carotid artery, whereas 53.8% had IMT > 1.5 mm in the carotid bifurcation. Respective values were 4.8% and 46.8% for those without CVD, and 8.5% and 62.2% for those with CVD. Mean IMT in the carotid bifurcation, the predilection site for atherosclerosis, was 1.85 mm (95% CI 1.72; 1.98) in the men with CVD, as compared to 1.65 mm (95% CI 1.56; 1.73) in the men free of CVD. Serum LDL cholesterol (beta = 0.26), saturated fat intake (beta = 0.20), blood haemoglobin (beta = -0.29), systolic blood pressure (beta = 0.21) and smoking (beta = 0.19), jointly explained 23% of the variance in the carotid bifurcation IMT in the men without CVD. Neither serum ferritin, transferrin nor dietary iron levels were associated with carotid bifurcation atherosclerosis. On the other hand, in the men with CVD, age (beta = 0.34) and physical activity (beta = -0.25) jointly explained 16.5% of the IMT variance in the carotid bifurcation.(ABSTRACT TRUNCATED AT 250 WORDS)