Showing papers in "European Heart Journal in 1999"

Incidence and aetiology of heart failure; a population-based study

Abstract: Aims To determine the incidence and aetiology of heart failure in the general population. Methods and Results New cases of heart failure were identified from a population of 151000 served by 82 general practitioners in Hillingdon, West London through surveillance of acute hospital admissions and through a rapid access clinic to which general practitioners referred all new cases of suspected heart failure. On the basis of clinical assessment, electrocardiography, chest radiography and transthoracic echocardiography, a panel of three cardi-ologists decided that 220 patients met the case definition of new heart failure over a 20 month period (crude incidence rate of 1·3 cases per 1000 population per year for those aged 25 years or over). The incidence rate increased from 0·02 cases per 1000 population per year in those aged 25–34 years to 11·6 in those aged 85 years and over. The incidence was higher in males than females (age-adjusted incidence ratio 1·75 [95% confidence interval 1·34–2·29, P <0·0001]). The median age at presentation was 76 years. The primary aetiologies were coronary heart disease (36%), unknown (34%), hypertension (14%), valve disease (7%), atrial fibrillation alone (5%), and other (5%). Conclusions Within the general population, new cases of heart failure largely occur in the elderly, and the incidence is higher in men than women. The single most common aetiology is coronary heart disease, but in a third of cases the aetiology cannot be determined on the basis of non-invasive investigation alone. To be relevant to clinical practice, future clinical trials in heart failure should not exclude the elderly.

Prevalence of heart failure and left ventricular dysfunction in the general population; The Rotterdam Study.

Abstract: Aims To determine the prevalence of heart failure and symptomatic as well as asymptomatic left ventricular systolic dysfunction in the general population. Methods and Results In 5540 participants of the Rotterdam Study (age 68·9±8·7 years, 2251 men) aged 55–95 years, the presence of heart failure was determined by assessment of symptoms and signs (shortness of breath, ankle oedema and pulmonary crepitations) and use of heart failure medication. In 2267 subjects (age 65·7±7·4 years, 1028 men) fractional shortening was measured. The overall prevalence of heart failure was 3·9% (95% CI 3·0±4·7) and did not differ between men and women. The prevalence increased with age, with the exception of the highest age group in men. Fractional shortening was higher in women and did not decrease appreciably with age. The prevalence of left ventricular systolic dysfunction (fractional shortening <=25%) was approximately 2·5 times higher in men (5·5%, 95% CI 4·1–7·0) than in women (2·2%, 95% CI 1·4–3·2). Sixty percent of persons with left ventricular systolic dysfunction had no symptoms or signs of heart failure at all. Conclusions The prevalence of heart failure is appreciable and does not differ between men and women. The majority of persons with left ventricular systolic dysfunction can be regarded as having asymptomatic left ventricular systolic dysfunction.

Guidelines for the study of familial dilated cardiomyopathies

Abstract: *International Centre for Genetic Engineering and Biotechnology, and **Department of Cardiology, Ospedale Maggiore, Trieste, Italy; †Department of Internal Medicine & Cardiology, Hospitals of the Philipps-University, Marburg, Germany; ‡Department of Cardiological Sciences, St. George’s Hospital Medical School, London, U.K.; §Institut de Myologie, QDepartment of Cardiology, Q¶Lab. Génétique et Insuffisance Cardiaque, Association Claude Bernard, Groupe Hospitalier Pitié-Salpétriere, Paris, France

Effects of education and support on self-care and resource utilization in patients with heart failure

Abstract: Aims To test the eVect of education and support by a nurse on self-care and resource utilization in patients with heart failure. Methods A total of 179 patients (mean age 73, 58% male, NYHA III-IV) hospitalized with heart failure were evaluated prospectively. Patients were randomized to the study intervention or to ‘care as usual’. The supportive educative intervention consisted of intensive, systematic and planned education by a study nurse about the consequences of heart failure in daily life, using a standard nursing care plan developed by the researchers for older patients with heart failure. Education and support took place during the hospital stay and at a home visit within a week of discharge. Data were collected on self-care abilities, self-care behaviour, readmissions, visits to the emergency heart centre and use of other health care resources. Results Education and support from a nurse in a hospital setting and at home significantly increases self-care behaviour in patients with heart failure. Patients from both the intervention and the control group increased their self-care behaviour within 1 month of discharge, but the increase in the intervention group was significantly more after 1 month. Although self-care behaviour in both groups decreased during the following 8 months, the increase from baseline remained statistically significant in the intervention group, but not in the control group. No significant eVects on resource utilization were found. Conclusions Intensive, systematic, tailored and planned education and support by a nurse results in an increase in patients’ self-care behaviour. No significant eVects were found on use of health care resources. Additional organisational changes, such as longer follow-up and the availability of a heart failure specialist would probably enhance the eVects of education and support. (Eur Heart J 1999; 20: 673‐682)

Relationship between smoking and cardiovascular risk factors in the development of peripheral arterial disease and coronary artery disease: Edinburgh Artery Study.

Abstract: Aims The aim was to determine whether the effect of smoking on the development of peripheral or coronary artery disease might be mediated by other cardiovascular risk factors, including dietary antioxidant vitamin intake, serum low and high density lipoproteins, blood pressure, plasma fibrinogen, blood viscosity and markers of endothelial disturbance and fibrin turnover. Methods and Results 1592 men and women aged 55–74 years were selected at random from 11 general practices in Edinburgh, Scotland and followed-up for 5 years. The incidences of peripheral arterial disease and coronary artery disease were 5·1% and 11·1%, respectively. Both conditions were more common in moderate and heavy smokers than in never smokers; cigarette smoking was a stronger risk factor for peripheral arterial disease than for coronary artery disease. Smoking was associated with reduced dietary antioxidant vitamin intake, serum high density lipoprotein cholesterol and diastolic blood pressure and with increased alcohol intake, serum triglycerides, blood viscosity, plasma fibrinogen, and markers of endothelial disturbance (tissue plasminogen activator and von Willebrand factor antigens). Simultaneous adjustment for these risk factors reduced the relative risk of peripheral arterial disease only slightly, from 3·94 (95% CI 2·04, 7·62) to 2·72 (95% CI 1·13, 6·53) in heavy smokers and from 1·87 (95% CI 0·91, 3·85) to 1·70 (95% CI 0·72, 3·99) in moderate smokers. Similar adjustment also had little effect on the risk of coronary artery disease associated with smoking. Conclusion The combined effect of smoking on the cardiovascular risk factors studied may explain part of its influence on peripheral and coronary arterial disease, but the majority of the effect appears to be due to other mechanisms.

Cytokines and neurohormones relating to body composition alterations in the wasting syndrome of chronic heart failure.

Abstract: Background Chronic heart failure is one of a number of disorders associated with the development of a wasting syndrome. The precise mechanisms of this remain unknown, but previous studies have suggested a role for immune and neurohormonal factors. Methods We aimed to investigate in detail the differences in body composition (dual X-ray absorptiometry) and the relationship to candidate biochemical factors of the immune, neurohormonal and metabolic systems in 15 healthy controls, 36 stable non-cachectic and 18 cachectic patients with chronic heart failure. Results Non-cachectic patients showed reduced leg lean tissue (−9·1%, P <0·01) compared to controls. Cachectic patients had significantly reduced lean (−21·0% vs controls, −19·9% vs non-cachectics), fat (−33·0% vs controls, −37·0% vs non-cachectics) and bone tissue (−17·5% vs controls, −15·9% vs non-cachectics) (all P <0·0001). Cachectic patients showed a significantly increased cortisol/dehydroepiandrosterone ratio (+203% vs controls, P <0·0001; +89% vs non-cachectics, P =0·0011) and increased cytokine levels (TNF-α, soluble TNF-receptor 1, interleukin-6). The levels of catabolic hormones and cytokines correlated significantly with reduced muscle and fat tissue content and reduced bone mass. Conclusion Peripheral loss of muscle tissue is a general finding in chronic heart failure. The wasting in cardiac cachexia affects all tissue compartments and is significantly related to neurohormonal and immunological abnormalities.

Treatment with the antibiotic roxithromycin in patients with acute non-Q-wave coronary syndromes. The final report of the ROXIS study

Abstract: Aims Mounting evidence suggests infection, specifically Chlamydia pneumoniae, plays a role in atherosclerosis. We tested whether antibiotic treatment with the macrolide roxithromycin improves clinical outcome in patients with acute non-Q-wave coronary syndromes. Preliminary reports revealed a reduction in events in the roxithromycin group at 30 days. We now report the long-term follow-up results. Methods and Results Sixty-four per cent of the initial 202 patients with unstable angina who were randomly assigned to receive either roxithromycin or placebo for 30 days completed the active treatment period. At day 30, the primary triple and double end-point rates were 9% and 4% in the placebo group compared to 2% and 0% in the roxithromycin group (unadjusted P =0·032 and 0·058, respectively). The secondary triple and double end-point rates were again higher in the placebo group at day 90 (12·5% and 6·25% vs 4·37% and 0%, unadjusted P =0·065 and 0·029, respectively), and at day 180 (14·6% and 7·29% vs 8·69% and 2·17%, unadjusted P =0·259 and 0·17, respectively). Anti- C. pneumoniae IgG titres were unchanged in both groups while C-reactive protein levels decreased in both strategies, with a more significant decrease in the roxithromycin arm ( P =0·03). Elevated C-reactive protein levels predicted the need for revascularization. Conclusions In this pilot trial, roxithromycin appears to extend the clinical benefit of preventing death and re-infarction for at least 6 months after initial treatment.

The circadian pattern of the development of ventricular fibrillation in patients with Brugada syndrome

Abstract: Aims Brugada syndrome is considered to be a distinctive subgroup of idiopathic ventricular fibrillation. Identification of the circadian pattern of ventricular fibrillation would contribute to the elucidation of its underlying pathophysiology, but this pattern remains unknown in patients with Brugada syndrome. Methods and Results A total of 12 consecutive Brugada syndrome patients (46±14 years, all male) who underwent implantation of an implantable cardioverter–defibrillator were studied. The distribution of the time of ventricular fibrillation detection was examined and classified into four 6-hour time periods of the day. The mean follow-up period following implantation was 777±535 days. In six out of the 12 patients, ventricular fibrillation occurred during follow-up. The data logs revealed that ventricular fibrillation was detected 30 times (range, 3–9). Ventricular fibrillation was observed more frequently at night (1800h to 0600h) than in the day (0600h to 1800h) (93·3% [28/30] vs 6·7% [2/30], P <0·001), and during sleep than while awake (86·7% [26/30] vs 13·3% [4/30], P <0·001). Ventricular fibrillation occurred most frequently between midnight and 0600h in patients with ventricular fibrillation episodes during sleep (76·9% [20/26] vs 23·1% [6/26], P <0·01). Conclusion These results suggest that increased nocturnal vagal activity and withdrawal sympathetic activity may play an important role in the arrhythmogenesis of the Brugada syndrome.

Prolonged QT interval predicts cardiac and all-cause mortality in the elderly. The Rotterdam Study.

Abstract: Aims To examine the association between heart-rate corrected QT prolongation and cardiac and all-cause mortality in the population-based Rotterdam Study among men and women aged 55 years or older and to compare the prognostic value of the QT interval, using diVerent formulas to correct for heart rate. Methods and Results After exclusion of participants with arrhythmias or bundle branch block on the ECG, the study population consisted of 2083 men and 3158 women. The QT interval was computed by the Modular ECG Analysis System (MEANS). Data were analysed using Cox’ proportional hazards model. Participants in the highest quartile of the heart-rate corrected QT interval had about a 70% age- and sex-adjusted increased risk for both all-cause mortality (hazard ratio (HR) 1·8; 95%CI:1·3‐2·4) and cardiac mortality (HR 1·7; 95%CI:1·0‐2·7) compared to those in the lowest quartile. In women, the increased risk associated with prolonged QT for cardiac death was more pronounced than in men. These risk estimates did not change after adjustment for potential confounders, including history of myocardial infarction, hypertension and diabetes mellitus. Conclusion A prolonged heart-rate corrected QT interval is an independent predictor for cardiac and all-cause mortality in older men and women. The risk associated with prolonged QT is hardly aVected by the heart-rate correction formula used. (Eur Heart J 1999; 20: 278‐284)

A randomized placebo-controlled trial of fluvastatin for prevention of restenosis after successful coronary balloon angioplasty; final results of the fluvastatin angiographic restenosis (FLARE) trial.

Abstract: Background The 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase inhibitors competitively inhibit biosynthesis of mevalonate, a precursor of non-sterol compounds involved in cell proliferation. Experimental evidence suggests that fluvastatin may, independent of any lipid lowering action, exert a greater direct inhibitory effect on proliferating vascular myocytes than other statins. The FLARE (Fluvastatin Angioplasty Restenosis) Trial was conceived to evaluate the ability of fluvastatin 40mg twice daily to reduce restenosis after successful coronary balloon angioplasty (PTCA). Methods Patients were randomized to either placebo or fluvastatin 40mg twice daily beginning 2–4 weeks prior to planned PTCA and continuing after a successful PTCA (without the use of a stent), to follow-up angiography at 26±2 weeks. Clinical follow-up was completed at 40 weeks. The primary end-point was angiographic restenosis, measured by quantitative coronary angiography at a core laboratory, as the loss in minimal luminal diameter during follow-up. Clinical end-points were death, myocardial infarction, coronary artery bypass graft surgery or re-intervetion, up to 40 weeks after PTCA. Results Of 1054 patients randomized, 526 were allocated to fluvastatin and 528 to placebo. Among these, 409 in the fluvastatin group and 427 in the placebo group were included in the intention-to-treat analysis, having undergone a successful PTCA after a minimum of 2 weeks of pre-treatment. At the time of PTCA, fluvastatin had reduced LDL cholesterol by 37% and this was maintained at 33% at 26 weeks. There was no difference in the primary end-point between the treatment groups (fluvastatin 0·23±0·49mm vs placebo 0·23±0·52mm, P =0·95) or in the angiographic restenosis rate (fluvastatin 28%, placebo 31%, chi-square P =0·42), or in the incidence of the composite clinical end-point at 40 weeks (22·4% vs 23·3%; logrank P =0·74). However, a significantly lower incidence of total death and myocardial infarction was observed in six patients (1·4%) in the fluvastatin group and 17 (4·0%) in the placebo group (log rank P =0·025). Conclusion Treatment with fluvastatin 80mg daily did not affect the process of restenosis and is therefore not indicated for this purpose. However, the observed reduction in mortality and myocardial infarction 40 weeks after PTCA in the fluvastatin treated group has not been previously reported with statin therapy. Accordingly, a priori investigation of this finding is indicated and a new clinical trial with this intention is already underway.

New signs characteristic of myocardial bridging demonstrated by intracoronary ultrasound and Doppler.

Abstract: Background Large discrepancies exist concerning the incidence of myocardial bridging. This has been reported to be 0·5%–2·5% following coronary angiography but 15%–85% following autopsy. The purpose of the study was to use intravascular ultrasound and intracoronary Doppler to study the morphology and flow characteristics of myocardial bridging in order to find feasible parameters of this syndrome. Methods and Results Intravascular ultrasound was performed in 62/69 patients in whom typical angiographic ‘milking effects’ were present. In 48 patients, intracoronary Doppler was performed. A specific, echolucent ‘half moon’ phenomenon surrounding the myocardial bridge was found in all the patients. The thickness of the half moon area was 0·47±0·19mm in diastole and 0·52±0·23mm in systole. There was systolic compression of the myocardial bridge with a lumen reduction during systole of 36·4±8·8%. Using intracoronary Doppler, a characteristic early diastolic ‘finger tip’ phenomenon was observed in 42 (87%) of the patients. All patients showed no or reduced antegrade systolic flow. Coronary flow velocity reserve was 2·03±0·54. After intracoronary nitroglycerin injection, retrograde systolic flow occurred in 37 (77%) of the 48 patients, with a velocity of −22·2±13·2cm.s−1. Intravascular ultrasound revealed atherosclerotic involvement of the proximal segment in 61 (88%) of the 69 patients, with an area stenosis of 42±13%. No plaques were found in the bridge or distal segments in the 62 patients in whom it was possible to introduce the ultrasound catheter throughout the bridging segment. Conclusion Myocardial bridging is characterized by the following morphological and functional signs: a specific, echolucent half moon phenomenon over the bridge segment, which exists throughout the cardiac cycle; systolic compression of the bridge segment of the coronary artery; accelerated flow velocity at early diastole (finger-tip phenomenon); no or reduced systolic antegrade flow; decreased diastolic/systolic velocity ratio; retrograde flow in the proximal segment, which is provoked and enhanced by nitroglycerin injection.

Risk factors for coronary heart disease and acute-phase proteins. A population-based study.

Abstract: AIMS: Circulating levels of C-reactive protein and serum amyloid A protein increase markedly, and albumin levels fall, during the acute-phase response to tissue injury, infection and inflammation. Some acute-phase proteins have been associated with increased risks of coronary heart disease in long-term prospective studies. The aim of the present study was to determine whether circulating concentrations of C-reactive protein, albumin and serum amyloid A protein are correlated with one another, standard vascular risk factors, markers of persistent infection, or indicators of socio-economic status. METHODS AND RESULTS: We report a cross-sectional study of 704 individuals without a history of coronary heart disease from five general practices in Bedfordshire, U.K. Plasma levels of C-reactive protein and serum amyloid A protein were strongly associated with each other (2 P<0.00001) and inversely related to levels of serum albumin (2 P<0.00001). There were highly significant associations of plasma C-reactive protein concentrations with cigarette smoking and obesity (2 P<0.00001 for each). Serum albumin levels were strongly associated with blood pressure (2 P<0.0001) and plasma lipids (2 P<0.001), and concentrations of serum amyloid A protein were strongly correlated with obesity (2 P<0.0001). CONCLUSION: Previously reported long-term prospective studies have found an increased risk of coronary heart disease of about 50% in people with raised baseline levels of plasma C-reactive protein or low albumin. The strong cross-sectional associations we have found between levels of these proteins with each other and with concentrations of serum amyloid A protein suggest that some underlying process related to inflammation is likely to be of relevance to the causation of disease. Further studies are needed to determine if the strong associations of plasma levels of C-reactive protein with cigarette smoking and obesity indicate that this particular protein can mediate some of the effects of those risk factors on coronary heart disease.

Plasma brain natriuretic peptide level as a biochemical marker of morbidity and mortality in patients with asymptomatic or minimally symptomatic left ventricular dysfunction. Comparison with plasma angiotensin II and endothelin-1

Abstract: Aims To evaluate the level of plasma brain natriuretic peptide as a predictor of morbidity and mortality in patients with asymptomatic or minimally symptomatic left ventricular dysfunction. Methods We measured plasma levels of atrial natriuretic peptide, brain natriuretic peptide, norepinephrine, angiotensin II, and endothelin-1 and monitored haemodynamic parameters in 290 consecutive patients with asymptomatic or minimally and newly symptomatic left ventricular dysfunction (functional classes I–II, mean left ventricular ejection fraction=37%). All patients were followed up for a median period of 812 days. The Cox proportional hazards model was used to assess the association of variables with mortality and morbidity. Results At the end of the follow-up, 24 patients had suffered cardiac death and 25 had been hospitalized for worsening heart failure during the follow-up period. Among 21 variables such as clinical characteristics, treatment, haemodynamics, and neurohumoral factors, high levels of plasma brain natriuretic peptide ( P <0·0001), norepinephrine ( P =0·042), left ventricular end-diastolic volume index ( P =0·0035), and left ventricular end-diastolic pressure ( P =0·033) were shown to be independent predictors of mortality and morbidity by stepwise multivariate analysis. Moreover, only a high level of plasma brain natriuretic peptide ( P <0·0001) was shown to be an independent predictor of mortality in these patients. Conclusions These results indicate that a high plasma brain natriuretic peptide level provides information about mortality and morbidity in patients with asymptomatic or minimally symptomatic left ventricular dysfunction.

Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non-Q wave myocardial infarction: FRAX.I.S. (FRAxiparine in Ischaemic Syndrome)

Abstract: AIM To assess the benefit of short-term low molecular weight heparin nadroparin compared with unfractionated heparin in unstable angina or non-Q wave myocardial infarction patients and to determine whether a longer, 2-week low molecular weight heparin regimen would offer additional clinical benefit. PATIENTS, METHODS AND RESULTS This was a multicentre, prospective, randomized, double-blind study in three parallel groups, involving 3468 patients. Patients received one of three treatment regimens: the unfractionated heparin group received an intravenous bolus of unfractionated heparin 5000 IU, followed by an activated partial thromboplastin time adjusted infusion of unfractionated heparin for 6+/-2 days; the nadroparin 6 group received an intravenous bolus of nadroparin 86 anti-Xa IU. kg(-1), followed by twice daily subcutaneous injections of nadroparin 86 anti-Xa IU. kg(-1)for 6+/-2 days, and the nadroparin 14 group received an intravenous bolus of nadroparin 86 anti-Xa IU. kg(-1), followed by twice daily subcutaneous injections of nadroparin 86 anti-Xa IU. kg(-1)for 14 days. No statistically significant differences were observed between the three treatment regimens with respect to the primary outcome (cardiac death, myocardial infarction, refractory angina, or recurrence of unstable angina at day 14). The absolute differences between the groups in the incidence of the primary outcome were: -0.3% (P=0.85) for the nadroparin 6 group vs the unfractionated heparin group and +1.9% (P=0.24) for the nadroparin 14 group vs the unfractionated heparin group. Furthermore, there were no significant intergroup differences regarding any of the secondary efficacy outcomes. However, there was an increased risk of major haemorrhages in the nadroparin 14 group compared with unfractionated heparin (3.5% vs 1.6%;P=0.0035). CONCLUSIONS Treatment with nadroparin for 6+/-2 days provides similar efficacy and safety to treatment with unfractionated heparin, for the same period, in the therapeutic management of acute unstable angina or non-Q wave myocardial infarction, and may be easier to administer. A prolonged regimen of nadroparin (14 days) does not provide any additional clinical benefit.

The occurrence and prognostic significance of atrial fibrillation/-flutter following acute myocardial infarction

Abstract: Aims To investigate the occurrence and prognostic significance of atrial fibrillation/-flutter following acute myocardial infarction Methods and Results The occurrence and prognostic significance of atrial fibrillation/-flutter were studied in 6676 consecutive patients with acute myocardial infarction screened in 27 centres in Denmark for inclusion into the TRAndolapril Cardiac Evaluation (TRACE) study. Information about occurrence of atrial fibrillation/-flutter during hospitalization was prospectively collected for the following three periods: day 1–2, day 3–4 and from day 5 until discharge. A total of 1395 patients (21%) suffered from atrial fibrillation/-flutter in one or more of the specified periods during hospitalization. Patients with atrial fibrillation/-flutter were significantly older, a significantly greater proportion were women, left ventricular systolic dysfunction was more extensive, thrombolytic therapy was received less frequently, and anterior Q wave myocardial infarction was experienced more frequently than patients without atrial fibrillation/-flutter. History of acute myocardial infarction and/or angina pectoris was similar in patients with and without atrial fibrillation/-flutter, whereas significantly more patients with atrial fibrillation/-flutter had a history of hypertension, congestive heart failure, diabetes mellitus, pulmonary disease and stroke. The unadjusted in-hospital mortality rate was significantly higher in patients with atrial fibrillation/-flutter in one or more of the specified periods during hospitalization (18%) than in patients without atrial fibrillation/-flutter (9%), P <0·001. After adjustment for baseline characteristics, the presence of atrial fibrillation/-flutter was still associated with increased in-hospital mortality; odds ratio=1·5 (95% Cl: 1·2–1·8), P <0·001. In patients surviving hospitalization, the unadjusted 5-year mortality rate was also significantly higher in patients suffering from atrial fibrillation/-flutter (56%) than in patients without atrial fibrillation/-flutter (34%), P <0·001. After adjustment for important prognostic baseline characteristics, the presence of atrial fibrillation/-flutter was still associated with an increased mortality, relative risk=1·3 (95% Cl: 1·2–1·4). Subgroup analysis revealed that sustained atrial fibrillation/-flutter during hospitalization was associated with the highest risk of dying, relative risk=1·4 (95% Cl: 1·2–1·7). Conclusion Atrial fibrillation/-flutter often occurs after acute myocardial infarction and our analysis demonstrated that it was an independent predictor of an increased short and long-term mortality.

Body weight and weight gain during adult life in men in relation to coronary heart disease and mortality. A prospective population study.

Abstract: Aims To assess the risk of death from coronary disease, and all causes associated with body mass index and weight gain from age 20 to middle age. Methods and Results In this study, 6874 men aged 47 to 55 years at baseline and free of a history of myocardial infarction were followed with respect to mortality from coronary disease and from all causes over an average follow-up of 19·7 years, and with respect to non-fatal myocardial infarction for 11·8 years. High body mass index predicted death from coronary disease, but only at levels above 27·5m.kg−2. Men with stable weight (defined as ±4% change from age 20) had the lowest death rate from coronary disease and the lowest risk of non-fatal myo-cardial infarction. Relative risk of coronary death increased with increasing weight gain, from 1·57 (1·14–2·15) (after adjustment for age, physical activity, and smoking) in the group who gained 4 to 10%, to 2·76 (1·97–3·85) in men with a weight gain of more than 35% ( P for trend 0·0001), compared to men who remained stable. After further adjustment for serum cholesterol, systolic blood pressure, and diabetes, relative risks were reduced but still significantly elevated in all weight gain groups ( P for trend 0·004). Data concerning non-fatal myocardial infarction were available for the first 11·8 years and showed a relative risk of 3·35 (2·05–5·47) after adjustment for age, physical activity, and smoking in men with a weight gain of more than 35%. Conclusion Weight gain from age 20, even a very moderate increase, is strongly associated with an increased risk of coronary death and non-fatal myocardial infarction.

Sulfonylureas and ischaemic preconditioning; a double-blind, placebo-controlled evaluation of glimepiride and glibenclamide.

Abstract: Aims Glimepiride is a new sulfonylurea for diabetes treatment which is supposed to impact less on extra-pancreatic ATP-dependent K+channels than the conventional drug glibenclamide. This study was performed to evaluate whether this results in a better maintenance of ATP-dependent K+channel mediated ischaemic myocardial preconditioning. Methods and Results In a double-blind placebo-controlled study the period of total coronary occlusion during balloon angioplasty of high grade coronary artery stenoses was used as a model to compare the effects of both drugs. Quantification of myocardial ischaemia was achieved by recording the intracoronary ECG and the time to the occurrence of angina during vessel occlusion. All patients underwent three dilatations. The first dilatation (dilatation 1) served to determine the severity of ischaemia during vessel occlusion. During dilatation 2, baseline values were recorded. Thereafter, glimepiride (15 patients: 1·162mg), glibenclamide (15 patients: 2·54mg) or placebo (15 patients) were intravenously administered over 12min. Dilatation 3 started 10min after the beginning of the drug administration. Mean ST segment shifts in the placebo group decreased by 35% (dilatation 2: 0·23; dilatation 3: 0·15mV; CI −0·55 to 0·00mV; P =0·049). A similar reduction also occurred in the glimepiride group, in which repetitive balloon occlusion led to a 34% reduction (dilatation 2: 0·35; dilatation 3: 0·23mV; CI −0·21 to −0·02mV; P =0·01). There was little influence however, on mean ST segment shifts in the glibenclamide group (dilatation 2 and dilatation 3: 0·24mV; CI −0·10 to 0·25mV; P =0·34). Accordingly, time to angina during balloon occlusion slightly increased (by 30%) in the placebo group (dilatation 2: 37s; dilatation 3: 48s; CI 0·0 to 15·0s; P =0·16); increased by 13% in the glimepiride group (dilatation 2: 40s; dilatation 3: 45s; CI 0·0 to 14·0s; P =0·023); and remained unchanged in the glibenclamide group (dilatation 2 and dilatation 3: 30s; CI −7·5 to 7·5s; P =0·67). Conclusion These results show that glimepiride maintains myocardial preconditioning, while glibenclamide might be able to prevent it.

Regional diastolic function in ischaemic heart disease using pulsed wave Doppler tissue imaging.

Abstract: Aims The aim of this study was to determine the utility of pulsed wave Doppler tissue imaging in the evaluation of regional left ventricular diastolic function in patients with ischaemic heart disease. Methods and Results In 30 normal subjects and 43 patients with ischaemic heart disease, Doppler tissue imaging was performed in each of the 16 segments of the myocardium. The following diastolic pulsed wave Doppler tissue imaging parameters were obtained for each segment: (1) regional early diastolic peak velocity (regional e wave cm.s−1); (2) regional late diastolic peak velocity (regional a wave cm.s−1); (3) regional diastolic e/a velocity ratio; and (4) the regional isovolumic relaxation time, defined as the time interval from the second heart sound to the onset of the diastolic E wave. In patients with ischaemic heart disease, each of these parameters was evaluated and compared in ischaemic and normally perfused segments, based on the presence or absence of obstructive lesions of the supplying coronary artery. In patients with coronary artery disease, several differences were observed between diseased and normal wall segments: the mean segmental peak early diastolic velocity (e wave) was reduced (mean±SD: 6·4±2·1cm.s−1vs 8·5±2·8cm.s−1; P <0·01); the e/a diastolic velocity ratio was decreased (0·95±0·3 vs 1·5±0·6, respectively; P <0·01) and the regional isovolumic relaxation time was prolonged (104±36·7ms vs 69·6±30ms; P <0·01. No differences were observed in any of these parameters between the normally perfused segments of ischaemic patients and normal subjects. Patients with a normal transmitral diastolic Doppler inflow pattern had a mean of 3·7±2·7 myocardial segments with a local e/a pulsed wave Doppler tissue imaging velocity ratio <1, fewer than those with an inverted diastolic transmitral Doppler inflow pattern (10·3±3 segments; P <0·001). Overall sensitivity and specificity for an inverted local e/a ratio and a local isovolumetric relaxation time ≥85ms were of 62% and 72% and 69% and 80%, respectively. Conclusion Regional diastolic wall motion is impaired at baseline in ischaemic myocardial segments, even when systolic contraction is preserved. Pulsed wave Doppler tissue imaging is a useful non-invasive technique which allows the assessment of regional diastolic performance and dynamics of the left ventricular myocardium. Further studies are required to define this role in the evaluation of coronary heart disease.

Acute and long-term results after transcoronary ablation of septal hypertrophy (TASH). Catheter interventional treatment for hypertrophic obstructive cardiomyopathy.

Abstract: Aims To evaluate acute and long-term symptomatic, haemodynamic (at rest and during exercise) and electrophysiological results of transcoronary ablation of septal hypertrophy (TASH), a catheter interventional treatment for hypertrophic obstructive cardiomyopathy. Methods and Results Sixty-two transcoronary ablations of septal hypertrophy were performed by injection of 4·6±2·6ml 96% ethanol into septal branches in 50 patients with hypertrophic obstructive cardiomyopathy and severe symptoms. Serial left and right heart catheterization, transoesophageal echocardiography and electrophysiological investigations were repeated 2 weeks and 7±1 months (n=37) after intervention. Transcoronary ablation of septal hypertrophy led to a reduction in septal thickness, sustained elimination of the outflow obstruction (51±41 vs 6±10mmHg at rest, P <0·001; 134±48 vs 28±32mmHg, P <0·001, post-extrasystolic), a decrease in left ventricular filling pressures at rest and during exercise and a pronounced clinical improvement. There was no evidence for the creation of an arrhythmogenic substrate as assessed by serial programmed electrical stimulation in 39 patients. However, permanent high-grade atrioventricular block occurred in 17% of the patients. There were two early, but no late deaths during a mean follow-up time of 10·6±5·6 months. Conclusion Transcoronary ablation of septal hypertrophy is a promising new treatment for hypertrophic obstructive cardiomyopathy in patients with severe symptoms. It should now be compared with alternative treatment strategies in prospective randomized studies.

Long-term survival in severe heart failure in patients treated with enalapril. Ten year follow-up of CONSENSUS I.

Abstract: Background The CONSENSUS trial was the first study to show prognostic improvement by an ACE inhibitor. Patients in NYHA class IV heart failure were treated with enalapril or placebo. After study completion (average 183 days) all patients were offered open-label enalapril therapy. This paper reports on the survival at the 10-year follow up of the patients randomized in the CONSENSUS trial. Methods All 35 participating centres in CONSENSUS I were asked to complete a questionnaire on the survival status at 1 November 1996 of patients randomized in CONSENSUS. Results At 10-year follow up, one patient was lost to follow-up. Five patients, all in the enalapril group, were long-term survivors ( P =0·004). Averaged over the duration of the trial (double-blind plus open-label extension) the risk reduction was 30% ( P =0·008), with a 95% confidence interval of 11% to 46%. At the end of the double-blind study period, mortality was considerably higher among patients who did not receive open ACE inhibitor therapy compared to those who did. Conclusion After a treatment period of, on average, 6 months, enalapril was shown to be effective. The effect was sustained for at least 4 years i.e. for another 3·5 years. The present follow-up is the first heart failure trial where the full life-cycle has been followed from randomization. In severe heart failure, mortality is significantly reduced by enalapril. On average, the beneficial effect is maintained for several years and overall survival time is prolonged by 50% (from 521 to 781 days).

Perivalvular abscesses associated with endocarditis: clinical features and prognostic factors of overall survival in a series of 233 cases

Abstract: Aims The purposes of this study were to determine the clinical features and to identify prognostic factors of abscesses associated with infective endocarditis. Methods and Results During a 5-year period from January 1989, 233 patients with perivalvular abscesses associated with infective endocarditis were enrolled in a retrospective multicentre study. Of the patients, 213 received medical–surgical therapy and 20 medical therapy alone. No causative microorganism could be identified in 31% of cases. Sensitivity for the detection of abscesses was 36 and 80%, respectively using transthoracic and transoesophageal echocardiography. Surgical treatment consisted of primary suture of the abscess (38%), insertion of a felt aortic or mitral ring using Teflon or pericardium (42%), or debridment of the abscess cavity (20%). The 1 month operative mortality was 16%. Actuarial rates for overall survival at 3 and 27 months in operated patients were 75±10% and 59±11%, respectively. Increasing patient age, staphylococcal infection, and fistulization of the abscess were found to be independent risk factors in both 1 month and overall operative mortality. Renal failure was a risk factor predictive of operative mortality at 1 month, whereas uncontrolled infection and circumferential abscess were regarded as risk factors predictive of overall operative mortality. Conclusion The data determined prognostic factors of abscesses associated with infective endocarditis.

Myocardial ischaemia in children with isolated ventricular non-compaction

Abstract: Aims Isolated ventricular non-compaction is a rare congenital cardiomyopathy with a high morbidity and mortality due to malignant arrhythmias and pump failure. Areas affected by non-compaction are characterized by increased trabecularization and deep inter-trabecular spaces. We hypothesized perfusion defects in these areas and performed positron emission tomography to evaluate the myocardial perfusion in non-compacted areas. Methods and Results Five children (age 10–14 years) with isolated ventricular non-compaction underwent positron emission tomography using N-13-ammonia as flow marker and intravenous dipyridamole for stress testing. Myocardial blood flow was quantified using the positron emission tomography time–activity curves in non-compacted areas and normal myocardium, which were diagnosed by echocardiography, magnetic resonance imaging, and angiography. Coronary angiography, performed in two children with extensive forms of left ventricular non-compaction, demonstrated normal coronary arteries. Myocardial blood flow measurements at rest and after dipyridamole application demonstrated 16–33% and 32–57% perfusion impairment, respectively, in non-compacted areas compared to normal myocardium. Areas of restricted myocardial perfusion corresponded well to the non-compacted areas, defined echographically and by magnetic resonance imaging. Conclusion Positron emission tomography demonstrates restricted myocardial perfusion and decreased flow reserve in areas of ventricular non-compaction in children. The myocardial perfusion defects in non-compacted areas may be the cause of myocardial damage and possibly form the basis of arrhythmias and pump failure.

Diabetes mellitus and congestive heart failure. Further knowledge needed.

Abstract: Diabetes mellitus, and in particular the type 2, has progressively become more common. Factors increasing the prevalence include an ageing population, an increasing body mass and decreased demands of physical activity. In type 2 diabetes manifestations of atherosclerosis are frequently present at the time of diagnosis. Approximately 20% of patients admitted to Swedish coronary care units for myocardial infarction have diabetes. In a recent health survey, 22% of diabetic patients reported that they needed to see a cardiologist during the previous 12 months and up to 50% had cardiovascular disease. As type 2 diabetes, including the pre-diabetic period, is an important risk factor for atherosclerosis the increasing prevalence suggests that there will be a considerable increase in diabetes-related cardiovascular disease in the near future. Ischaemic heart disease is still the leading cause of congestive heart failure despite advances in its prevention and treatment. Heart failure has increased in prevalence while there has been a decrease in the age-adjusted morbidity and mortality of coronary artery disease. An ageing population and increased survival of patients with myocardial infarction are likely explanations. Thus, diabetes mellitus is closely linked to congestive heart failure. Proper treatment, including meticulous metabolic control of the diabetes, may considerably improve the prognosis for diabetic patients with myocardial infarction and also possibly prevent its occurrence. Nevertheless, even with the best preventive strategies and expert treatment of established cardiovascular disease, a considerable proportion of heart failure patients will have diabetes. Further research is needed for the proper handling of these subjects. This may contribute not only to patient relief but also to a decrease of future demands on health care resources.

Economics of myocardial perfusion imaging in Europe--the EMPIRE Study.

Abstract: Background Physicians use myocardial perfusion imaging to a variable extent in patients presenting with possible coronary artery disease. There are few clinical data on the most cost-effective strategy although computer models predict that routine use of myocardial perfusion imaging is cost-effective. Objectives To measure the cost-effectiveness of four diagnostic strategies in patients newly presenting with possible coronary artery disease, and to compare cost-effectiveness in centres that routinely use myocardial perfusion imaging with those that do not. Methods We have studied 396 patients presenting to eight hospitals for the diagnosis of coronary artery disease. The hospitals were regular users or non-users of myocardial perfusion imaging with one of each in four countries (France, Germany, Italy, United Kingdom). Information was gathered retrospectively on presentation, investigations, complications, and clinical management, and patients were followed-up for 2 years in order to assess outcome. Pre- and post-test probabilities of coronary artery disease were computed for diagnostic tests and each test was also assigned as diagnostic or part of management. Diagnostic strategies defined were: 1: Exercise electrocardiogram/coronary angiography, 2: exercise electrocardiogram/myocardial perfusion imaging/coronary angiography, 3: myocardial perfusion imaging/coronary angiography, 4: coronary angiography. Primary outcome measures were the cost and accuracy of diagnosis, the cost of subsequent management, and clinical outcome. Secondary measures included prognostic power, normal angiography rate, and rate of angiography not followed by revascularization. Results Mean diagnostic costs per patient were: strategy 1: £490, 2: £409, 3: £460, 4: £1253 ( P <0·0001). Myocardial perfusion imaging users: £529, non-users £667 ( P =0·006). Mean probability of the presence of coronary artery disease when the final clinical diagnosis was coronary artery disease present were, strategy 1: 0·85, 2: 0·82, 3: 0·97, 4: 1·0 ( P <0·0001), users 0·93, non-users 0·88 ( P =0·02), and when coronary artery disease was absent, 1: 0·26, 2: 0·22, 3: 0·16, 4: 0·0 ( P <0·0001), users 0·21, non-users 0·20 ( P =ns). Total 2-year costs (coronary artery disease present/absent) were: strategy 1: £4453/£710, 2: £3842/£478, 3: £3768/£574, 4: £5599/£1475 ( P <0·05/0·0001), users: £5563/£623, non-users: £5428/£916 ( P =ns/0·001). Prognostic power at diagnosis was higher ( P <0·0001) and normal coronary angiography rate lower ( P =0·07) in the scintigraphic centres and strategies. Numbers of soft and hard cardiac events over 2 years and final symptomatic status did not differ between strategy or centre. Conclusion Investigative strategies using myocardial perfusion imaging are cheaper and equally effective when compared with strategies that do not use myocardial perfusion imaging, both for cost of diagnosis and for overall 2 year management costs. Two year patient outcome is the same.

Genetic and molecular basis of cardiac arrhythmias; impact on clinical management. Study group on molecular basis of arrhythmias of the working group on arrhythmias of the european society of cardiology.

Abstract: Clinical cardiologists who manage arrhythmias are increasingly faced with new complexities in management decisions. The once obscure science and jargon of medical genetics is assuming a much more prominent position in the mainstream medical literature, with seemingly weekly reports of new mutations to explain what once seemed very obscure diseases. This rapidly expanding knowledge base places the clinician — who usually trained when the concepts were not a major component of the medical school or fellowship training curricula — at a disadvantage in making day-to-day decisions with respect to managing common symptoms, such as unexplained syncope or heart failure. Even entertaining a diagnosis such as the congenital long QT syndrome or hypertrophic cardiomyopathy used to be a medical curiosity. Now, with increased public and physician awareness of these and even more esoteric conditions, the questions on patient management have become more common, and more complex. They include not only broad questions like ‘How can I establish (or better yet, rule out) a diagnosis?’ but also more specific issues such as ‘Should this patient undergo genetic testing? Where? How? And how can I interpret the results?’ The first and second parts of this article attempt to answer these questions. They neither teach molecular genetics nor do they provide an exhaustive review of the current state-of-the-art of molecular and genetic cardi-

A randomized evaluation of early revascularization to treat shock complicating acute myocardial infarction. The (Swiss) Multicenter Trial of Angioplasty for Shock—(S)MASH

Abstract: Aim To test whether emergency revascularization improves survival in patients with acute myocardial infarction and shock. Methods and Results Patients with acute myocardial infarction and early shock were randomized either to undergo emergency angiography, followed immediately by revascularization when indicated, or to receive initial medical management. In five of the nine participating centres, patients with shock but not randomized were entered in a registry. Only 55 patients could be randomized. Of the 32 patients in the invasive group, 30 (94%) underwent early angiography, 27 (84%) PTCA, and one (4%) CABG. Twenty-two (69%) died within 30 days in the invasive group vs 18/23 (78%) in the medically managed group (ns, RR=0·88, 95% confidence interval 0·6–1·2). Among the registry patients, 24/51 were excluded from randomization solely because of patient or physician preference for the invasive approach: 23 (96%) of them underwent emergency angiography, 21 (88%) PTCA, and 12 (50%) died within 30 days. Among the remaining registry patients (n=27) only nine (33%) underwent early angiography, nine (33%) PTCA and 20 (74%) died. Conclusion We failed to demonstrate that emergency PTCA significantly improves survival in patients with acute myocardial infarction and early cardiogenic shock. Because the study was stopped prematurely, due to an insufficient patient inclusion rate, a clinically meaningful benefit of early reperfusion may have been missed.

Improved physical fitness and quality of life following training of elderly patients after acute coronary events. A 1 year follow-up randomized controlled study.

Abstract: Aims Cardiac rehabilitation including exercise training is of proven value in ischaemic heart disease. However, elderly patients frequently are not encouraged to participate in such programmes. This study evaluates the physiological eVects and self-reported quality of life after an aerobic outpatient group-training programme in subjects above the age of 65 years. Methods and Results A consecutive series of 101 patients (males 80%) aged 65‐84 (mean 71) years recovering from an acute coronary event were randomized to either a supervised out patient group-training programme (n=50) or to a control group (n=51). The two groups were well balanced as regards clinical characteristics. The compliance in the training group was 87%. Exercise tolerance increased in the trained group from 104 to 122 and 111 W after 3 and 12 months respectively. The corresponding values were 102, 105 and 105 W among controls. Parameters, such as quality of life, self-estimated level of physical activity, fitness and well-being were graded higher by the trained patients than those who served as controls on the two occasions of follow-up. Conclusions Aerobic group-training of elderly patients recovering from an acute coronary event beneficially influences physical fitness and several parameters expressing quality of life. Great care has to be taken to preserve the initial eVects by continued training. (Eur Heart J 1999; 20: 1475‐1484)

Importance of left atrial appendage flow as a predictor of thromboembolic events in patients with atrial fibrillation

Abstract: Aim The purpose of this study was to investigate the role of transoesophageal echocardiography in predicting subsequent thromboembolic events in patients with atrial fibrillation. Methods and patients Transoesophageal echocardiography was performed in 88 patients with documented paroxysmal (n=53) or chronic atrial fibrillation (n=35) to assess morphological and functional predictors of thromboembolic events. Prospective selection was from patients with non-valvular atrial fibrillation who had undergone transoesophageal echocardiography because of previous thromboembolism (n=30); prior to electrical cardioversion (n=31); or for other reasons (n=27). All patients were followed up for 1 year. Results During the period of follow-up new thromboembolic events occurred in 18 of 88 patients (20%/year); 16 of these patients had a stroke and two a peripheral embolism. Univariate analysis revealed that previous thromboembolism (P<0·005; odds ratio 5·3 [CI 1·9, 12·1]), history of hypertension (P<0·01; odds ratio 4·0 [CI 1·4, 10·4), presence of left atrial spontaneous echo contrast (P<0·025; odds ratio 3·5 [CI 1·2, 10·0]), and presence of left atrial appendage peak velocity ƒ0·20 m . s "1 (P<0·01; odds ratio 4·1 [CI 1·4, 11·6]) were significantly related to subsequent thromboembolic events. Stepwise logistic regression showed that independent predictors of thromboembolic events were: history of thromboembolism (P<0·005), history of hypertension (P<0·05) and low left atrial appendage peak velocity ƒ0·20 m . s "1 (P<0·01). Conclusions In patients with atrial fibrillation, the presence of spontaneous echo contrast in the left atrium, and in particular a low left atrial appendage peak flow velocity, can be used to identify a subgroup of atrial fibrillation patients at either increased or decreased risk of subsequent thromboembolism, which might have important implications for anticoagulation therapy. (Eur Heart J 1999; 20: 979‐985)

Cardioprotection by opening of the K(ATP) channel in unstable angina. Is this a clinical manifestation of myocardial preconditioning? Results of a randomized study with nicorandil. CESAR 2 investigation. Clinical European studies in angina and revascularization.

Abstract: Aims To assess the anti-ischaemic and anti-arrhythmic effects and overall safety of nicorandil, an ATP sensitive potassium (K+) channel opener, with ‘cardioprotective’ effects, in patients with unstable angina. Methods In a multicentre, randomized, double-blind, parallel-group, placebo-controlled study, oral nicorandil 20mg twice daily or a matching placebo was administered for a minimum of 48h to patients admitted with unstable angina. Treatment was standardized to include, where tolerated, oral aspirin, a beta-blocker and diltiazem. Continuous Holter ECG monitoring was performed for 48h to assess the frequency and duration of transient myocardial ischaemia and any tachyarrhythmia, as the predefined end-points of the study. A pain chart recorded the inci-dence and severity of chest pain throughout the study period. Patients with myocardial infarction identified retrospectively from troponin-T analysis were excluded. Results Two hundred and forty-five patients were recruited into the study. Forty-three patients were excluded with an index diagnosis of myocardial infarction, two were not randomized and 12 had unsatisfactory tape data. In the remaining 188 patients, six out of 89 patients (6·7%) on nicorandil experienced an arrhythmia, compared with 17 out of 99 patients (17·2%) on placebo ( P =0·04). Three nicorandil patients experienced three runs of non-sustained ventricular tachycardia compared to 31 runs in 10 patients on placebo ( P =0·087 patients; P <0·0001 runs). Three nicorandil patients had four runs of supraventricular tachycardia, compared to 15 runs in nine patients on placebo ( P =0·14 patients; P =0·017 runs). Eleven (12·4%) patients on nicorandil had 37 episodes of transient myocardial ischaemia (mostly silent) compared with 74 episodes in 21 (21·2%) patients on placebo ( P =0·12 patients; P =0·0028 episodes). In the overall safety analysis, which included all patients who received at least one dose of study medication, there were no significant differences in the rates of myo-cardial infarction or death between the nicorandil or placebo-treated groups. Conclusions Nicorandil, added to aggressive anti-anginal treatment for unstable angina, reduces transient myocardial ischaemia, non-sustained ventricular, and supraventricular arrhythmia compared to placebo. The anti-arrhythmic activity with nicorandil is probably a secondary effect resulting from its anti-ischaemic action and we suggest that this may be related to its effect on the ATP sensitive potassium channel causing pharmacological preconditioning.