Showing papers in "European Heart Journal in 1998"

Eisenmenger syndrome. Factors relating to deterioration and death

Abstract: Aims To assess the natural history, risk factors for death and deterioration of patients with Eisenmenger Syndrome. Methods The clinical course of 188 patients from three different cardiac centres specialized in adult congenital heart defects, followed for a median period of 31 years, was retrospectively analysed. According to the diagnosis, 64 males and 124 females, mean age at last follow-up 33·02±12·8 years, were divided into two groups: simple (128) and complex (60) congenital heart disease. Events analysed were: time variation of Ability Index, pulmonary and cerebral complications, non-cardiac surgery, urate metabolism and renal function, arrhythmias, pregnancy and contraception, medical therapy and transplantation, death from all causes and sudden death. Results Eighty-four percent of the overall population showed a satisfactory Ability Index (1 and 2) at the first attendance (median age 25 years). Patients with complex heart disease and Eisenmenger reaction had earlier clinical deterioration (18·6±11·3 vs 26·7±12·2) and shorter survival (25·8±7·9 vs 32·5±14·6 years). Thirty-eight (20·2%) patients had at least one episode of haemoptysis between 20 and 40 years of age but it did not modify overall survival; 25 (13·2%) had pulmonary thromboembolism at a mean age of 35·2±13·4 years. Fifteen (7·9%) had a stroke and 7 (3·7%) a cerebral abscess at a mean age of 31·4±15·7 and 24·1±4·9 years, respectively. Cerebral complications influenced the quality of life but did not modify survival. Patients who had venesection showed a 2·04 times greater hazard ratio for haemoptysis. Venesection did not reduce cerebral complications and in 20% caused anaemia and iron deficiency. Other non-cardiac surgery with general anaesthesia carried risks (23·5% of deaths). Significant maternal mortality (27%) in relation to pregnancy occurred with constant deterioration in physical status, high incidence of spontaneous abortions (35·8%) and cardiac abnormalities in offspring (20%). Sixty-one patients died during follow-up, mainly by sudden death (29·5%), heart failure (22·9%) and from haemoptysis (11·4%). Eight patients had heart and lung transplantation and five died 1 week to 4 years after transplant. Deterioration in Ability Index (worsening symptoms), age, complex defects, blood creatinine level, right ventricular dysfunction and non-cardiac surgery were variables which affected the prognosis adversely with uni- and multivariate analysis. Conclusions patients with Eisenmenger syndrome can survive to the seventh decade with informed medical care and protection from special risks

Intravascular ultrasound-guided optimized stent deployment Immediate and 6 months clinical and angiographic results from the Multicenter Ultrasound Stenting in Coronaries Study (MUSIC Study)

Abstract: Objectives A study was set up to validate the safety and feasibility of intravascular ultrasound-guided stenting without subsequent anticoagulation, and its impact on the 6 months restenosis rate. Methods The study was designed to be multicentred, prospective, and observational. Results One hundred and sixty-one patients with stable angina and a de novo coronary artery lesion were enrolled. In four patients, the implantation of a Palmaz–Schatz (with spiral bridge) stent had failed. One of these four patients died 3 days following bypass surgery. In two other patients, intravascular ultrasound assessment was not performed. One hundred and twenty-five of the remaining 155 patients (81%) were treated with aspirin (100mg.day−1), because all three criteria for optimized stent expansion were met. Twenty-two of the remaining 38 patients (25%), in whom at least one criterion was not met were treated with aspirin and acenocoumarol (3 months, INR 2·5–3·5), while 16 patients only received aspirin. Stent thrombosis was documented in two patients (1·3%) for which repeat angioplasty was performed. During the hospital stay, there were no deaths or Q-wave myocardial infarctions. Five patients (3·2%) sustained a non-Q-wave myocardial infarction. During the follow-up period (198±38 days, complete for all patients, except one), one patient (0·6%) sustained a Q-wave myocardial infarction, one (0·6%) underwent bypass surgery, and repeat angioplasty was performed in nine patients (5·7%). In two of the nine patients, repeat angioplasty involved another lesion. Therefore, the target lesion revascularization rate during follow-up was 4·5% (seven patients).At quantitative coronary angiography, the minimal lumen diameter (mean±SD) increased from 1·12± 0·34mm before to 2·89±0·35mm after stenting. Repeat angiography at 6 months was performed in 144 patients (92%). The minimal lumen diameter at follow-up was 2·12±0·67mm. Restenosis (diameter stenosis of 50% or more) was documented in 12 patients or 8·3%. When the two patients with documented stent thrombosis are included, the restenosis rate amounts to 9·7%. Conclusions These data confirm that, in selected patients, stents can safely be implanted without the use of systemic anticoagulation, provided optimal stent expansion is achieved. The exact role of intravascular ultrasound in the achievement of these results needs to be established by appropriately designed studies. In the meantime, intra-vascular ultrasound coupled with the Palmaz–Schatz stent incorporating a spiral bridge, may have contributed considerably to the immediate angiographic outcome, which in turn may explain the favourable clinical and angiographic outcome at 6 months.

The Münster Heart Study (PROCAM). Results of follow-up at 8 years.

Abstract: The Munster Heart Study (PROCAM) was initiated in 1979 in order to examine cardiovascular risk factors, cardiovascular events including myocardial infarction and stroke, and mortality in people at work. Examination at entry comprised a standardized case history, measurement of blood pressure and anthropometric data, a resting electrocardiogram, and measurement of more than 20 laboratory parameters in a fasting blood sample. The prevalence data in this report are based upon a single examination of 17,437 men aged 40.4 +/- 11.3 years (mean +/- SD) and 8065 women aged 35.7 +/- 12.1 years, which took place between 1979 and 1991. Severe hypercholesterolaemia (> 300 mg.dl-1) was seen in 5% of men and 8% of women aged 45 to 64 years. In men, the prevalence of hypertriglyceridaemia (> 200 mg.dl-1) rose from 5% at age 20 to 20% at age 45 and remained constant thereafter; in women the prevalence of hypertriglyceridaemia increased linearly from 2% at age 20 to 7% at age 60. The LDL/HDL ratio was higher in men than in women at all age groups; in the age group 45 to 64 years, LDL/HDL ratios > 5 were approximately twice as common in men. Lipoprotein(a) levels were distributed in a highly skewed fashion. In men, a slight rise in the geometric mean lipoprotein(a) concentration occurred with age, whereas in women a dramatic increase was seen after age 40. Using multivariate analysis by the multiple logistic function method, total cholesterol, HDL cholesterol, LDL cholesterol and log-transformed triglycerides showed a significant (P < 0.001) age-adjusted correlation with the presence of major coronary events. A risk algorithm has been developed for men aged 40 to 65 years which takes into account the independent risk factors of HDL cholesterol, LDL cholesterol, triglycerides, fibrinogen, age, systolic blood pressure, cigarette smoking, presence of diabetes mellitus and family history of myocardial infarction and angina pectoris. This algorithm can be used in clinical practice to calculate the 8-year risk of an individual suffering a myocardial infarction.

Clinical epidemiology of heart failure: public and private health burden.

Abstract: Clinically overt heart failure is common, costly, disabling, and deadly; it remains so despite the tremendous benefit of angiotensin-converting enzyme inhibitors. Better treatments for and earlier detection of heart failure are needed if the situation to improve. However, even this may not be enough. The dramatic deterioration in quality of life and prognosis when a patient progresses from asymptomatic left ventricular dysfunction to overt heart failure suggests that only a programme of screening and prevention will effectively reduce the public health burden of heart failure. Moreover, the economic consequences of developing overt heart failure suggest that such an approach is likely to be cost-effective.

Oxidative stress during myocardial ischaemia and heart failure

Abstract: Oxidative stress is a condition in which oxidant metabolites exert toxic effects because of their increased production or an altered cellular mechanism of protection. The heart needs oxygen but it is also susceptible to oxidative stress, which occurs during post-ischaemic reperfusion, for example. Ischaemia causes alterations in the defence mechanisms against oxygen free radicals. At the same time, production of oxygen free radicals increases. In man, there is evidence of oxidative stress during surgical reperfusion of the whole heart, or after thrombolysis, and it is related to transient left ventricular dysfunction or stunning. At present, there are few data on oxidative stress in the failing heart. It is not clear whether the defence mechanisms of the myocyte are altered or whether the production of oxygen free radicals is increased, or both. Recent data have shown a close link between oxidative stress and apoptosis. Importantly, tumour necrosis factor causes a rapid rise in intracellular reactive oxygen intermediates and apoptosis. This series of events is not confined to the myocytes, but also occurs at the level of endothelium, where tumour necrosis factor causes expression of inducible nitric oxide synthase, production of the reactive radical nitric oxide, oxidative stress and apoptosis. The immunological response to heart failure may result in endothelial and myocyte dysfunction through oxidative stress-mediated apoptosis. A better understanding of these mechanisms may lead to novel therapeutic strategies.

Heart rate variability and heart rate in healthy volunteers. Is the female autonomic nervous system cardioprotective

Abstract: Aims Heart rate variability has been proposed as an indicator of cardiovascular health. Since women have a lower cardiovascular risk, we hypothesized that there are gender diVerences in autonomic modulation. Methods and Results In 276 healthy subjects (135 women, 141 men) between 18 and 71 years of age, 24 h heart rate and heart rate variability were determined. All heart rate variability parameters, except for pNN50 and high frequency power, were higher in men. After adjustment for heart rate, we obtained gender diVerences for: the standard deviation (P=0·049), the standard deviation of the 5 min average (P=0·047), low frequency power (absolute values, P=0·002; normalized units, P<0·001) and ratio low frequency/high frequency (P<0·001). There were no significant gender diVerences in heart rate variability parameters denoting vagal modulation. Gender diVerences were confined to age categories of less than 40 years of age. The majority of heart rate variability parameters decreased with age. Only in men, was a higher body mass index associated with a higher heart rate and with lower heart rate variability parameters (P<0·001). Conclusion Cardiac autonomic modulation as determined by heart rate variability, is significantly lower in healthy women compared to healthy men. We hypothesize that this apparently paradoxical finding may be explained by lower sympathetic activity (low frequency power) in women. This may provide protection against arrhythmias and against the development of coronary heart disease. (Eur Heart J 1998; 19: 1334‐1341)

Atrial fibrillation: current knowledge and recommendations for management

Abstract: Atrial fibrillation, a commonly encountered arrhythmia, has in recent years, been the subject of increased interest and intensive clinical research. There is also increasing awareness that atrial fibrillation is a major cause of embolic events which in 75% of cases are complicated by cerebrovascular accidents[1,2]. Atrial fibrillation is often associated with heart disease but a significant proportion of patients (about 30%) have no detectable heart disease[3]. Symptoms, occasionally disabling, haemo-dynamic impairment and a decrease in life expectancy are among the untoward effects of atrial fibrillation, resulting in an important morbidity, mortality and an increased cost for the health care provider[4]. The Working Group of Arrhythmias of the European Society of Cardiology created a Study Group on Atrial Fibrillation in order to establish recommen-dations for the better management of this arrhythmia and to promote multicentre studies. The purpose of this paper is to briefly outline the state of our knowledge on the clinical presentation, the causes, the mechanisms and therapeutic approaches currently available and to propose recommendations for management. Although atrial flutter can coexist with atrial fibrillation, it is considered a different arrhythmia and will not be covered in the present paper.

The prognostic value of the QT interval and QT interval dispersion in all-cause and cardiac mortality and morbidity in a population of Danish citizens

Abstract: Aims. To evaluate the prognostic value of the QT interval and QT interval dispersion in total and in cardiovascular mortality, as well as in cardiac morbidity, in a general population. Methods and results. The QT interval was measured in all leads from a standard 12-lead ECG in a random sample of 1658 women and 1797 men aged 30–60 years. QT interval dispersion was calculated from the maximal difference between QT intervals in any two leads. All cause mortality over 13 years, and cardiovascular mortality as well as cardiac morbidity over 11 years, were the main outcome parameters. Subjects with a prolonged QT interval (430ms or more) or prolonged QT interval dispersion (80ms or more) were at higher risk of cardiovascular death and cardiac morbidity than subjects whose QT interval was less than 360ms, or whose QT interval dispersion was less than 30ms. Cardiovascular death relative risk ratios, adjusted for age, gender, myocardial infarct, angina pectoris, diabetes mellitus, arterial hypertension, smoking habits, serum cholesterol level, and heart rate were 2·9 for the QT interval (95% confidence interval 1·1–7·8) and 4·4 for QT interval dispersion (95% confidence interval 1·0–19·1). Fatal and non-fatal cardiac morbidity relative risk ratios were similar, at 2·7 (95% confidence interval 1·4–5·5) for the QT interval and 2·2 (95% confidence interval 1·1–4·0) for QT interval dispersion. Conclusion. Prolongation of the QT interval and QT interval dispersion independently affected the prognosis of cardiovascular mortality and cardiac fatal and non-fatal morbidity in a general population over 11 years.

The emergence of triglycerides as a significant independent risk factor in coronary artery disease

Abstract: The Prospective Cardiovascular Munster (PROCAM) study involved 4849 middle-aged men who were followed up for 8 years to record the incidence of coronary heart disease (CHD) events according to the risk factors present at study entry. The study showed that fasting levels of triglycerides were an independent risk factor for CHD events, irrespective of serum levels of high density lipoprotein cholesterol (HDL-C) or low density lipoprotein cholesterol (LDL-C). Other independent predictors of CHD included serum levels of LDL-C and HDL-C, age, systolic blood pressure, cigarette smoking, diabetes mellitus, a family history of myocardial infarction and angina pectoris, but did not include total serum cholesterol levels. Individuals with an LDL-C/HDL-C ratio > 5 had a 19.2% chance of experiencing a CHD event in the next 8 years. Furthermore, if an LDL-C/HDL-C ratio > 5 was combined with hypertriglyceridaemia (> or = 2.3 mmol. l-1), the risk of CHD increased to 26.9%. The association between hypertriglyceridaemia and CHD events may be related to the presence of atherogenic, triglyceride-rich particles in plasma, such as LDL and very low density lipoproteins. High triglyceride levels may also predispose to thrombosis. Individuals with potentially atherogenic lipid profiles should be managed initially through the introduction of lifestyle changes. However, if these fail to achieve recommended target values, lipid-lowering therapy should be considered.

Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting.

Abstract: Aims The aim of the study was to evaluate the effects on systemic and coronary haemodynamics and myocar-dial substrate utilization of a new calcium sensitizer, levosimendan, after coronary artery bypass grafting. Methods and Results Twenty-three low-risk patients were included in this randomized and double-blind study. They received placebo (n=8), 8 (n=8) or 24 (n=7) μg.kg−1of levosimendan after coronary artery bypass operation. Systemic and coronary sinus haemodynamics with thermodilution and myocardial substrate utilization were measured. The heart rate increased 11 beats.min−1after the higher dose (P<0·05). Cardiac output increased by 0·7 and 1·6l.min−1(P<0·05 for both) after 8 and 24μg.kg−1of levosimendan, respectively. Systemic and pulmonary vascular resistance decreased significantly after both doses. Coronary sinus blood flow increased by 28 and 42ml/(P=0·054 for the combined effect) after the lower and higher dose, respectively. Myocardial oxygen consumption or substrate extractions did not change statistically significantly. Conclusion Despite improved cardiac performance, levosimendan did not increase myocardial oxygen con-sumption or change myocardial substrate utilization. Thus levosimendan has the potential to treat low cardiac output states after cardiopulmonary bypass surgery.

Uric acid in chronic heart failure: a marker of chronic inflammation

Abstract: Background Chronic heart failure is associated with hyperuricaemia and elevations in circulating markers of inflammation. Activation of xanthine oxidase, through free radical release, causes leukocyte and endothelial cell activation. Associations could therefore be expected between serum uric acid level, as a marker of increased xanthine oxidase activity, and markers of inflammation. We have explored these associations in patients with chronic heart failure, taking into account the hyperuricaemic effects of diuretic therapy and insulin resistance. Methods and Results Circulating uric acid and markers of inflammation were measured in 39 male patients with chronic heart failure and 16 healthy controls. All patients underwent a metabolic assessment, which provided a measure of insulin sensitivity (intravenous glucose tolerance tests and minimal modelling analysis). Compared to controls, patients with chronic heart failure had significantly higher levels of circulating uric acid, interleukin-6, soluble tumour necrosis factor receptor (sTNFR)-1, soluble intercellular adhesion molecule-1 (ICAM-1, all P <0·001), E-selectin and sTNFR2 (both P <0·05). In patients with chronic heart failure, serum uric acid concentrations correlated with circulating levels of sTNFR1 (r=0·74), interleukin-6 (r=0·66), sTNFR2 (r=0·63), TNFα (r=0·60) (all P <0·001), and ICAM-1 (r=0·41, P<0·01). In stepwise regression analyses, serum uric acid emerged as the strongest predictor of ICAM-1, interleukin-6, TNF, sTNFR1 and sTNFR2, independent of diuretic dose, age, body mass index, alcohol intake, serum creatinine, plasma insulin and glucose, and insulin sensitivity. Conclusions Serum uric acid is strongly related to circulating markers of inflammation in patients with chronic heart failure. This is consistent with a role for increased xanthine oxidase activity in the inflammatory response in patients with chronic heart failure.

Changes in platelet size and count in unstable angina compared to stable angina or non-cardiac chest pain

Abstract: Aims An increase in platelet aggregability is associated with unstable angina and myocardial infarction. Platelet size and activity correlate and mean platelet volume was found to be increased before acute myocardial infarction. We measured the mean platelet volume and platelet count in patients with stable angina, unstable angina and non-cardiac chest pain. Methods and results We studied 981 patients (734 men; 247 women) defined clinically as stable angina (n=688), unstable angina (n=108) and unstable angina requiring immediate angioplasty (n=52). After coronary angiography the patients were subdivided into single (n=269), double (n=304) and triple-vessel disease (n=311) and the control group of non-cardiac chest pain (n=97). There was no significant difference in platelet count between the control group and patients with 1, 2, or 3-vessel disease. However, the platelet size in patients with coronary artery disease was significantly larger (single: 8·7±1·19fl; double: 8·7±1·12fl; triple-vessel disease: 8·8±1·18fl) than the control group (8·2±0·95fl) ( P <0·01). Patients with stable angina similarly had no significant difference in platelet count compared to the control group but did have a significantly increased mean platelet volume (8·7±1·13; P <0·01). In contrast, patients with unstable angina had a decreased platelet count (245±56×10/l) compared to either stable angina (262±62×10/l; P <0·05) or the control group (261±58×10/l; P <0·05); furthermore, the mean platelet volume (9·4±1·23fl) was significantly greater than for stable angina ( P <0·01). Patients with unstable angina requiring immediate PTCA had an even lower platelet count (231±55×10/l) and higher mean platelet volume (10·4±1·03fl) ( P <0·01) than the rest of the population with unstable angina. Conclusions In stable angina the platelet count is unchanged compared to patients with normal coronary arteries but the platelet size is increased. However, in unstable angina there is a decrease in platelet count and an even larger increase in platelet size. We interpret this as meaning that unstable angina might be associated or preceded by an increase in platelet destruction rate that is not completely compensated for by an increase in platelet production rate. The large, more reactive platelets might be causally related to an ongoing coronary artery obstruction in unstable angina.

An overview of reverse cholesterol transport.

Abstract: Reverse cholesterol transport is a multi-step process resulting in the net movement of cholesterol from peripheral tissues back to the liver via the plasma compartment. Cellular cholesterol efflux is mediated by HDL, acting in conjunction with the cholesterol esterifying enzyme, lecithin: cholesterol acyltransferase. Cholesteryl ester accumulating in HDL can then follow a number of different fates: uptake in the liver in HDL containing apolipoprotein (particle uptake) by LDL receptors, selective uptake of HDL cholesteryl ester in liver or other tissues involving scavenger receptor B1, or transfer to triglyceride-rich lipoproteins as a result of the activity of cholesteryl ester transfer protein, with subsequent uptake of triglyceride-rich lipoprotein remnants in the liver. Recently, we and others have taken a molecular approach to analysing the different components of reverse cholesterol transport, by over- or under-expression of individual molecules in induced mutant mouse models, or by the study of human mutations involving molecules of reverse cholesterol transport. Such studies reveal that over-expression of the major HDL apoprotein, apolipoprotein A-I, is clearly anti-atherogenic. However, over- or under-expression of molecules such as cholesteryl ester transfer protein, which have opposite effects on HDL levels and reverse cholesterol transport, suggest that both HDL levels as well as the dynamics of cholesterol movement through HDL are involved in the anti-atherogenic actions of HDL.

Risk stratification in chronic heart failure.

Abstract: Despite advances in medical and surgical management, the prognosis of chronic heart failure remains poor. Few patients with chronic heart failure can be considered to have a good prognosis, but different trials have indicated a 6 month mortality between 5% and 60% depending on the severity of heart failure; identifying patients at truly low risk is difficult. A host of factors have been identified that predict outcome, at least in univariate analyses. Cohn wrote an article entitled ‘Poverty Amidst a Wealth of Variables’ some years ago, describing the difficulties in choosing which prognostic variables to use for clinical purposes in heart failure. This article reviews in a systematic fashion those peer-reviewed papers that have assessed the utility of prognostic variables in heart failure. This summary of existing knowledge should determine those prognostic factors that have proved most reliable so far, indicate which of the many new potential factors are most promising for further research and suggests ways in which the interpretation and reporting of such information might be improved.

Improvement in left ventricular ejection fraction and wall motion after successful recanalization of chronic coronary occlusions

Abstract: Aims This study assessed changes in left ventricular ejection fraction and regional radial shortening after successful angioplasty of chronic coronary occlusions. Methods We studied 95 patients with angina pectoris or exercise-induced ischaemia with a successfully recanalized chronic (median duration 4·3 months) coronary occlusion. Intracoronary stents were implanted in 71%. Left ventriculograms were obtained at baseline and after 6·7±1·4 months. Left ventricular ejection fraction and regional radial shortening were determined by a computer-assisted method. Results Left ventricular ejection fraction increased from 0·62±0·13 at baseline to 0·67±0·11 at follow-up (P<0·001). The change in left ventricular ejection fraction in patients with a patent artery and in patients with reocclusion (n=8) was 0·05±0·06 and 0·01±0·04, respectively (P=0·04). Regional radial shortening in the territory of the recanalized artery increased by 16% (from 0·28±0·11 to 0·32±0·11, P<0·001) in patients with a patent artery at follow-up, but was unchanged in patients with reocclusion. Conclusion Long-term patency after recanalization of old, chronic coronary occlusions in patients with angina pectoris is associated with improvement in global and regional left ventricular function. This may be a result of recovery of hibernating myocardium and supports the strategy of recanalizing chronic coronary occlusions.

Effect of oxygen on sleep quality, cognitive function and sympathetic activity in patients with chronic heart failure and Cheyne-Stokes respiration

Abstract: Background Cheyne-Stokes respiration disrupts sleep, leading to daytime somnolence and cognitive impairment. It is also an independent marker of increased mortality in heart failure. This study evaluated the effectiveness of oxygen therapy for Cheyne-Stokes respiration in heart failure. Methods Eleven patients with stable heart failure and Cheyne-Stokes breathing were studied. Oxygen and air were administered for 4 weeks in a double-blind, cross-over study. Sleep and disordered breathing was assessed by polysomnography. Symptoms were assessed using the Epworth Sleepiness Scale, visual analogue and quality of life scores. Cognitive function was assessed by neuropsychometric testing. Overnight urinary catecholamine excretion was used as a measure of sympathetic nerve activity. Results Ninety-seven percent of apnoeas were central in origin. Oxygen therapy reduced the central apnoea rate (18.4 ± 4.1 vs 3.8 ± 2.1 per hour; P =0.05) and periodic breathing time (33.6 ± 7.4 vs 10.7 ± 3.9% of actual sleep time; P =0.003). Oxygen did not improve sleep quality, patient symptoms or cognitive failure. Oxygen reduced urinary noradrenaline excretion (8.3 ± 1.5 vs 4.1 ± 0.6 nmol . mmol‒1 urinary creatinine; P =0.03). Conclusion Oxygen stabilized sleep disordered breathing and reduced sympathetic activity in patients with heart failure and Cheyne-Stokes respiration. We were unable to demonstrate an effect on either patient symptoms or cognitive function.

Experience from controlled trials of physical training in chronic heart failure. Protocol and patient factors in effectiveness in the improvement in exercise tolerance

Abstract: BACKGROUND Beneficial effects of physical training on exercise tolerance, autonomic and skeletal muscle function and limb blood flow have been demonstrated in chronic heart failure. Because this rehabilitation is expensive, may involve risk, and has unknown effects on prognosis, the possibility of predicting benefit on the basis of individual patient data is intriguing. The most suitable exercise training programme has not yet been established. METHODS AND RESULTS We reviewed the progress of 134 stable heart failure patients studied in randomized controlled trials of physical training. A significant training effect (+13% peak oxygen consumption, +17% exercise duration) was associated with improved autonomic indices (resting catecholamines and hormones, heart rate variability), without significant side-effects. No ventilatory, haemodynamic, autonomic or clinical factor at baseline was a predictor of outcome. Similar beneficial effects were observed in both male and female patients. The improvement in oxygen consumption after 16 weeks training was higher than after 6 weeks (+2.6 +/- 3.0 vs +0.3 +/- 3.1 ml.kg.min-1, P < 0.05). The combination of cycle ergometer with calisthenic exercises was more beneficial than cycle ergometer alone (+2.7 +/- 4.2 vs 1.2 +/- 2.0 ml.kg.min-1, P < 0.01). The presence of nonsustained ventricular tachycardia did not preclude a training effect. Patients older than 70 years were able to train, although less effectively than the younger ones. No difference in exercise gain was observed whether the patients trained in the hospital or at home. CONCLUSION The positive effects of physical rehabilitation in chronic stable heart failure patients are confirmed. No baseline patient factor was significantly correlated with outcome. A tailored, moderate, home-based, combined cycle ergometer, plus calisthenic exercise training seems safe and beneficial in a large cohort of heart failure patients, with similar benefits in a variety of conditions and different hospital settings.

Feasibility of a nurse-monitored, outpatient-care programme for elderly patients with moderate-to-severe, chronic heart failure.

Abstract: Methods and Results Patients with chronic heart failure hospitalized in the medical wards were screened to find those eligible for a randomized study to compare the eVect of a nurse-monitored, outpatient-care programme aiming at symptom management, with conventional care. The inclusion criteria were patients classified in New York Heart Association classes III‐IV, age 65 years, and eligibility for an outpatient follow-up programme. The total in-hospital population of patients discharged with a heartfailure diagnosis was surveyed. Eighty-nine per cent of all the hospitalized patients (n=1541) were 65 years old. Of these, 69% (n=1058) were treated in the medical wards which were screened. The study criteria were met by 158 patients (15%). No visits to the nurse occurred in 23 cases among the 79 patients randomized to the structured-care group (29%), mainly on account of death or fatigue. The numbers of hospitalizations and hospital days did not diVer between the structured-care and the usual-care groups. Conclusions Given the selection criteria and the outline of the interventions, the outpatient, nurse-monitored, symptom-management programme was not feasible for the majority of these elderly patients with moderate-to-severe, chronic heart failure, mainly because of the small proportion of eligible patients and the high drop-out rate. Management of these patients would have to be more adjusted to their home situation. (Eur Heart J 1998; 19: 1254‐1260)

A placebo-controlled study of growth hormone in patients with congestive heart failure

Abstract: Aim Experimental data in heart failure models and an open trial of seven patients with idiopathic dilated cardiomyo-pathy have suggested beneficial effects of growth hormone on cardiac function. The aim of the present study was to evaluate growth hormone effects on cardiac function in a placebo-controlled study. Methods Twenty two patients with congestive heart failure of different aetiologies in NYHA II and III and an echocardiographic ejection fraction <0·45 were studied in a 3 month double-blind placebo-controlled study with growth hormone added to optimal heart failure therapy. Patients received either placebo (n=11) or recombinant human growth hormone (n=11) in an initial dose of 0·1IU.kg−1week−1for 1 week, and thereafter 0·25IU.kg−1week−1for the rest of the treatment period. Cardiac function was assessed by equilibrium radionuclide angiography and Doppler echocardiography. Functional capacity was evaluated by computerized bicycle exercise electrocardiography. Results Recombinant human growth hormone had no significant effect on systolic or diastolic cardiac function, exercise capacity or neuroendocrine activation. In addition, there was no overall improvement in functional class or dyspnoea grade. Insulin-like growth factor-I significantly increased demonstrating that the growth hormone had an endocrine effect. Conclusion This is the first double-blind and placebo-controlled study of the administration, over 3 months, of recombinant human growth hormone in patients with congestive heart failure of different aetiologies. The treatment was safe and without serious side effects. However, no beneficial effects on cardiac function or structure could be detected. The European Society of Cardiology

Inverse relationship between aldosterone and large artery compliance in chronically treated heart failure patients

Abstract: Aims The purpose of this study was to examine, in chronically treated heart failure patients vs control subjects, the influence of neurohumoral activation and aldosterone escape on arterial elastic behaviour, assessed by noninvasive mathematical lumped-parameter modelling of the compliance of the arterial system. Methods and Results Radial arterial pulse waves were recorded non-invasively for 30 s with an arterial tonometer sensor array in 13 chronic heart failure patients (mean age, 59 +/- 2.5 years) in New York Heart Association class II. The patients had been taking digoxin, furosemide, captopril and aspirin for more than 3 months. Thirteen healthy subjects (mean age, 50 +/- 4.0 years) acted as controls. Compliance of the proximal (aorta and major branches, C1) and distal parts (C2) of the circulation were derived from a third order four-element modified Windkessel model which can reproduce arterial pressure waveforms, including both exponential and oscillatory sections. Active renin, angiotensin II and aldosterone levels were determined on venous blood samples in the supine position and after 30 min active standing. There was decreased proximal (C1, 1.51 +/- 0.11 ml . mmHg(-1), P<0.01) and distal (C2, 0050+/-0.011 ml . mmHg(-1)) arterial compliance in the chronic heart failure patients vs controls (C1, 1.71 +/- 0.16 ml. mmHg(-1); C2, 0.054 +/- 0.006 ml . mmHg(-1)). The chronic heart failure patients were characterized by an aldosterone escape phenomenon which was inversely correlated with the proximal arterial compliance in both supine (r= -0.795, P=0.002) and standing (r= -0.628, P=0.029) positions. Conclusions In chronically treated heart failure patients with full angiotensin-converting enzyme-inhibition and diuretics, there is decreased compliance of the aorta and its major branches, which is inversely correlated with the aldosterone escape phenomenon.

Atherogenic, dense low-density lipoproteins. Pathophysiology and new therapeutic approaches.

Abstract: It is well established that elevated circulating concentrations of cholesterol-rich, low-density lipoproteins (LDL) represent a major risk factor for the premature development of coronary artery disease. Only recently, however, has attention been drawn to the relationship between the qualitative features of plasma LDL particles and cardiovascular risk, particularly in view of the frequent occurrence of increased levels of dense, small LDL in coronary artery disease patients. Combined hyperlipidaemia, a frequent form of dyslipidaemia which is associated with premature atherosclerosis, is characterized by elevated plasma concentrations of both triglyceride-rich, very-low-density lipoproteins (VLDL) and LDL. In combined hyperlipidaemia patients, small, dense LDL (d 1.04-1.06 g.ml-1) predominate over the light (d 1.02-1.03 g.ml-1) and intermediate (d 1.03-1.04 g.ml-1) LDL subpopulations. Dense LDL are highly atherogenic as a result of their low binding affinity for the LDL receptor, their prolonged plasma half-life and low resistance to oxidative stress. Biological modification of dense LDL is potentiated as a result of retention in the arterial intima upon binding to extracellular matrix components and exposure to oxidative stress, leading to uptake by macrophages with subsequent foam cell formation. Such cholesterol-loaded, macrophage foam cells are active secretory cells, and exert multiple proinflammatory, proatherogenic and prothrombogenic effects during the initiation and progression of atherosclerotic plaques. Indeed, the secretory products of foam cells play a key role in the fragilization of lipid-rich plaques, leading ultimately to plaque rupture and the associated thrombotic complications. As the pharmacological modulation of dense LDL levels is of special interest, representing a new therapeutic approach in the treatment of atherogenic dyslipidaemia, we probed the biological mechanisms which underlie formation of dense LDL particles in combined hyperlipidaemia patients with a fibrate derivate, fenofibrate. Drug treatment (micronized fenofibrate, 200 mg.day-1 for 8 weeks) induced significant reductions in the plasma concentrations of VLDL (-37%; P < 0.005), and of dense LDL (-21.5%; P < 0.05), with simultaneous increase in HDL-cholesterol (+19%; P < 0.0001). An endogenous assay of cholesteryl ester transfer from cardioprotective HDL to atherogenic, apolipoprotein B-containing lipoproteins (VLDL and LDL) revealed marked reduction (-38%) in cholesterol ester transfer from HDL to VLDL upon fenofibrate treatment, whereas no modification in the low rate of cholesteryl ester transfer between HDL and LDL was detected. Simultaneously, however, the LDL profile in combined hyperlipidaemia patients, which is characterized by a predominance of small, dense LDL, was shifted towards the LDL subpopulation of intermediate density and larger size. Particles of the intermediate LDL subclass are avidly bound and degraded by the cellular LDL receptor which represents the major, non-atherogenic pathway for catabolism of LDL-cholesterol. Our findings indicate that the overall mechanism of the fenofibrate-induced modulation of the atherogenic dense LDL profile in combined hyperlipidaemia involves reduction in cholesteryl ester transfer from HDL to VLDL, together with normalization of the intravascular transformation of hepatic VLDL to receptor-active LDL of intermediate density.

Classical risk factors and their impact on incident non-fatal and fatal myocardial infarction and all-cause mortality in southern Germany. Results from the MONICA Augsburg cohort study 1984-1992. Monitoring Trends and Determinants in Cardiovascular Diseases.

Abstract: Background The MONICA (Monitoring Trends and Determinants in Cardiovascular Diseases) project in Augsburg provides the first population-based cohort study in Germany to quantify the associations of the risk factors hypertension, hypercholesterolaemia and smoking with incident non-fatal and fatal myocardial infarction and all-cause mortality, and to assess their impact at the population level. Methods The cohort comprises 1074 men and 1013 women aged 45-64 years; they were followed over 8 years from 1984-1992. In the men, there were 61 non-fatal and fatal myocardial infarctions and 92 all-cause mortality events over this period; in the women the number of deaths from all causes was 45. Incidence rates, hazard rate ratios, population attributable fractions and rate advancement periods were calculated. Results Adjusting for confounders, the myocardial infarction hazard rate ratios for men with hypertension, or a total cholesterol/HDL-cholesterol ratio > or =5.5, or smoking > or =20 cigarettes/day, were 2.0 (95% CI 1.2-3.5), 2.9 (95%, CI 1.7-5.0), and 2.7 (95% confidence interval (CI) 1 4-5.0), respectively. The risk factor combination total cholesterol/HDL cholesterol ratio > or = 5.5 and cigarette smoking was particularly hazardous. The three risk factors contributed 65% of the burden of myocardial infarction in the population. The rate advancement period for myocardial infarction associated with hypertension, total cholesterol/HDL cholesterol ratio > or =5.5 or smoking > or =20 cigarettes/day was 8.3, 12.4 and 11.5 years, respectively. In women, these risk factors were similarly predictive of all-cause mortality. Comparing the cohort data from Augsburg with those of two occupational cohorts from Germany reveals higher absolute myocardial infarction risks in the Augsburg population; however, the relative risk estimates in the Augsburg and the two occupational cohorts were very similar. Conclusion Our results confirm the important contribution of the classical risk factors to the risk of myocardial infarction and all-cause mortality in Germany. The results pertaining to the concept of rate advancement periods particularly demonstrate the great potential for prevention.

Treatment of calcified coronary lesions with Palmaz-Schatz stents An intravascular ultrasound study

Abstract: Aims To evaluate the result of coronary stenting in calcified lesions and to find morphological and procedural factors influencing the final result. Methods and results Three hundred and twenty three native coronary artery lesions in 303 patients (197 men, mean age 63·9±11·5 years) treated with Palmaz–Schatz stents were differentiated into four groups depending on their degree of circumferential calcification as defined by intravascular ultrasound [0–90° (n=120), 91–180° (n=58, 181–270$ (n=71) and 271–360° (n=74)]. In 117 lesions rotational atherectomy was used prior to stent placement. Intravascular ultrasound and quantitative angiography were performed prior to treatment and after stent placement to measure minimal and maximal lumen diameter and lumen cross-sectional area at the lesion site and the reference segments. Acute lumen gain and eccentricity index were calculated. Although higher balloon pressures were used than in the minimally calcified lesions, the final angiographic minimal lumen diameter decreased with increasing arc of calcification (3·01±0·47, 3·04±0·43, 2·85±0·53, 2·83±0·40mm, respectively, P =0·0320) resulting in a decrease in acute diameter gain with increasing arc of calcification (2·06±0·51, 1·91±0·46, 1·81±0·56, 1·78±0·51mm, respectively, P =0·0067). Adjunctive rotational atherectomy prior to stent placement resulted in a greater acute diameter and a greater lumen cross-sectional area gain, coupled with less final residual stenosis than pre-treatment with balloon angioplasty. Conclusion Implantation of stents in calcified lesions results in less optimal stent expansion, especially in lesions with thick, eccentric calcific plaque layers. Use of adjunctive rotational atherectomy before stent placement may improve the procedural result.

Relevance of heart rate as a prognostic factor in patients with acute myocardial infarction: insights from the GISSI-2 study

Abstract: Aims It is as yet undefined whether simple indexes of autonomic balance such as heart rate (HR) may play a role in risk stratification in patients with acute myocardial infarction (MI). The aim of this study was to quantify the prognostic significance of HR from the surface ECG obtained both at entry and at discharge, in a large population of patients all treated with fibrinolysis during the acute phase and having confirmed acute MI. Methods and Results Surface ECGs obtained at entry and at discharge in patients with confirmed MI enrolled in the GISSI-2 study, a large multicentre trial of different thrombolytic agents, were retrieved. Heart rhythm was evaluated and HR was measured: these data were then added to the main database of GISSI-2 allowing a complete evaluation of the prognostic significance of HR. Patients not in sinus rhythm or with grade 2-3 atrio-ventricular block were excluded. The prognostic significance of HR (cut-offs predefined at 60, 80, 100 beats. min - ') at entry for in-hospital mortality and at discharge for 6-month mortality was evaluated in the general population and in predefined subgroups. Multivariate analyses were used to assess the independent prognostic value of HR. A total of 8915 patients (more than 70% of the original population) were suitable for the analysis. There was a progressive increase in mortality with increasing HR in the general population (from 7.1% for HR 100 beats. min - ') and in the predefined subgroups. Multivariate analysis showed that HR exerted an independent prognostic significance. Data for analysis of HR at discharge were available for 7831 patients. Consistent with the data observed at entry, a progressive increase of 6-month mortality with increasing HR was present in the general population (from 0.8% for HR 100 beats. min -1 ) and for the different predefined subgroups. Multivariate analysis confirmed the independent prognostic significance of HR. There was no relation between HR and the incidence of fatal and non-fatal reinfarction. Conclusion The present study indicates that HR values from a standard 12-lead ECG independently predict mortality in patients with acute MI during the in-hospital phase and after discharge. This simple index appears very useful for risk stratification in clinical practice.

Infective endocarditis in the grown-up congenital heart (GUCH) population

Abstract: Aims Infective endocarditis accounts for 4% of admissions to a specialized unit for grown-up congenital heart patients. This study defines lesions susceptible to infection, antecedent events, organisms, outcome and surgical treatment in a group of such patients. Methods and results The grown-up congenital heart disease database was searched for all patients aged 13 years and above with adequate documentation of infective endocarditis retrospectively between 1983–1993 and thereafter between 1993–1996. There were 185 patients (214 episodes) divided into Group I: 128 patients unoperated or palliated and Group II: 57 patients after definitive repair and/or valve repair/replacement. In Group I, the commonest affected sites were ventricular septal defect in 31 (24%), left ventricular outflow tract in 22 (17%) and mitral valve in 17 (13%) and in Group II, left ventricular outflow tract in 20 (35%), repaired Fallot in 11 (19%), and atrioventricular defects in eight (14%). Infective endocarditis was not seen in secundum atrial septal defects before or after closure; in closed ventricular septal defects and ducts without left-sided valve abnormality; in isolated pulmonary stenosis; in unrepaired Ebstein; or after Fontan-type or Mustard operations. Surgery was performed in 39 patients: as an emergency in 17, and for failed medical therapy in 22. Only 87 (41%) of patients had a predisposing event: dental procedure or sepsis were the commonest events in Group I (33%) and cardiac surgery in Group II (50%). Streptococci species were found in 54% of Group I patients and in 45% of Group II. Staphylococci aureus was commoner in Group II (25%) compared to Group I (14%). Mean time from the onset of symptoms to diagnosis was 60 and 29 days in Groups I and II, respectively. Eight (4%) patients died as a result of septicaemia related to emergency or repeated surgery and Staphylococcus aureus infection. Recurrent attacks occurred in 21 (11%) patients. Conclusion Reparative surgery does not prevent endo-carditis except for closure of a ventricular septal defect and duct. Delay in diagnosis is serious since it contributes to mortality, although the overall mortality % is not high. Specific lesions are not affected so prophylaxis is probably unnecessary in those anomalies.

Exercise training in heart failure improves quality of life and exercise capacity.

Abstract: Aims Benefit from exercise training in heart failure has mainly been shown in men with ischaemic disease. We aimed to examine the effects of exercise training in heart failure patients ≤75 years old of both sexes and with various aetiology. Methods and Results Fifty-four patients with stable mild-to-moderate heart failure were randomized to exercise or control. and 49 completed the study (49% ≥65 years; 29% women; 24% non-ischaemic aetiology; training, n=22; controls. n=27). The exercise programme consisted of bicycle training at 80% of maximal intensity over a period of 4 months. Improvements vs controls were found regarding maximal exercise capacity 16 ± 12 vs - 4 ± 12%, [mean ± SD], P<0.01) and global quality-of-life (2 [1] vs 0 [1] units [median (inter-quartile range)], P<0.01), but not regarding maximal oxygen consumption or the dyspnoea-fatigue index. All of these four variables significantly improved in men with ischaemic aetiology compared with controls (n=11). However, none of these variables improved in women with ischaemic aetiology (n =5), or in patients with non-ischaemic aetiology (n=6). The training response was independent of age. left ventricular systolic function, and maximal oxygen consumption. No training-related adverse effects were reported. Conclusion Supervised exercise training was safe and beneficial in heart failure patients <75 years, especially in men with ischaemic aetiology. The effects of exercise training in women and patients with non-ischaemic aetiology should be further examined.