Showing papers in "European Heart Journal in 1997"

The fetal origins of coronary heart disease

Abstract: Animal studies have shown that undernutrition before birth programmes persisting changes in a range of metabolic, physiological and structural parameters. Studies in humans have shown that men and women whose birthweights were at the lower end of the normal range, who were thin or short at birth or small in relation to placental size have increased rates of coronary heart disease. We are beginning to understand something of the mechanisms underlying these associations.

The burden of cardiovascular diseases mortality in Europe. Task Force of the European Society of Cardiology on Cardiovascular Mortality and Morbidity Statistics in Europe

Abstract: Cardiovascular diseases are the major cause of death in adults and the elderly in the majority of the developed countries and in many developing countries. Cardiovascular diseases result in substantial disability and loss of productivity and contribute in large part, to the escalating costs of health care, especially in the presence of an ageing population. Papers published by the World Health Organization of the United Nations (WHO) and others have previously reported trends in cardiovascular mortality over time. These reports showed large international between-country differences both in the levels and in the trends in mortality from cardiovascular diseases, especially from ischaemic heart disease. More recent analysis of mortality data points to a substantial increase in cardiovascular diseases in countries of Central and Eastern Europe concomitant with recent nutritional, economical and political changes. Although most European countries perform analysis of mortality at the sub-national (regional) level, international analysis using sub-national data have been made only for selected diseases, for example cancer mortality by the International Agency for Research on Cancer, Lyon. The advantage of this type of analysis is that spatial variability in mortality patterns can be shown across borders. This may help in identifying factors responsible for this variation. The importance of population control of cardiovascular diseases was highlighted by the European Union in article 129 of the Treaty on European Union, which contains specific provisions on public health and focuses on the ‘prevention of disease, in particular the major health scourges’. The Council Resolution recognized the need for monitoring and surveillance of cardiovascular diseases within the general framework of health monitoring. Accordingly, the Board of the European Society of Cardiology upon recommendation from the Committee for Scientific and Clinical Initiatives, set up a Task Force to study the latest available data on cardiovascular mortality and morbidity in order to assess the burden of these diseases in Europe. This report reviews total cardiovascular, ischaemic heart disease, cerebrovascular and all causes mortality in European countries for the years 1990–1992. Regional mortality rates are presented for the years 1990–1991. Finally, the country mortality trends for the period 1970 to 1992 are analysed.

Accuracy and reproducibility of biplane two-dimensional echocardiographic measurements of left ventricular dimensions and function

Abstract: Objectives To investigate sources of variability in serial echocardiographic recordings in a core laboratory we assessed the impact of repeated echo recordings, repeated video measurements and measurements made by different investigators. Patients, methods Two investigators each recorded and analysed two-dimensional echos in 12 individuals (n=24 in total) three times at one week intervals. Left ventricular end-diastolic and end-systolic volumes were measured using the biplane modified Simpson's rule. Ejection fraction was derived from these volumes and left ventricular mass estimated using the area-length method. The left ventricular spherity index was expressed as the ratio of the short axis area and the long axis area at end-diastole. A video recording from each examination was reexamined twice by both investigators. Results Deviations between repeated echo recordings and repeated video measurements ranged from −5 to +5% between investigators. A three-way repeated analysis of variance indicated a small, but systematic difference between investigators. Reproducibility, measured by coefficients of variation, ranged from 3–9% for different investigators, 3–6% for repeated video measurements and 7–19% for repeated echo recordings across the different variables. The total variability of all three factors should be considered when the smallest detectable significant change in a variable is assessed. These ranged from 16–28% across the five variables studied, when a 10% error of classification was accepted for a one-sided change in a variable. Conclusion Repeated echo recordings were the dominant component of variation. Two-dimensional echo measurements are reproducible and accurate, but the same investigator should follow the same patients.

Serum uric acid as an index of impaired oxidative metabolism in chronic heart failure

Abstract: Background Elevated serum uric acid concentrations have been observed in clinical conditions associated with hypoxia. Since chronic heart failure is a state of impaired oxidative metabolism, we sought to determine whether serum uric acid concentrations correlate with measures of functional capacity and disease severity. Methods Fifty nine patients with a diagnosis of chronic heart failure due to coronary heart disease (n=34) or idiopathic dilated cardiomyopathy (n=25) and 20 healthy controls underwent assessment of functional capacity. Maximal oxygen uptake (MVO2) and regression slope relating to minute ventilation to carbon dioxide output (VE-VCO2) were measured during a maximal treadmill exercise test. Metabolic assessment consisted of measuring serum uric acid and fasting lipids, and insulin sensitivity, obtained by minimal modelling analysis of glucose and insulin responses during an intravenous glucose tolerance test. Clustering of indices of functional disease capacity and metabolic factors was explored using factor analysis and multivariate regression analysis. Results Compared to 20 healthy controls, patients with chronic heart failure had a 52% lower MVO2 ( P <0·001), 56·8% higher serum uric acid concentrations ( P <0·001) as well as a 60·5% lower insulin sensitivity ( P <0·001). Salient univariate correlations in the chronic heart failure group included serum uric acid concentrations with exercise time during the exercise test (r= − 0·53), MVO2 (r= − 0·50) (both P <0·001), VE-VCO2 slope (r=0·45), and NYHA functional class (r=0·36) (both P <0·01). In factor analysis of the chronic heart failure group, serum uric acid formed part of a principal cluster of metabolic variables which included MVO2 and VE-VCO2, slope. In multivariate regression analysis, serum uric acid concentrations emerged as a significant predictor of MVO2, exercise time (both P <0·001,) VE-VCO2 slope and NYHA functional class (both P <0·02), independent of diuretic dose, age, body mass index, serum creatinine, alcohol intake, plasma insulin levels, and insulin sensitivity index. Conclusions There is an inverse relationship between serum uric acid concentrations and measures of functional capacity in patients with cardiac failure. The strong correlation between serum uric acid and MVO2 suggests that in chronic heart failure, serum uric acid concentrations reflect an impairment of oxidative metabolism.

Additional predictive value of both left and right ventricular ejection fractions on long-term survival in idiopathic dilated cardiomyopathy

Abstract: Background In idiopathic dilated cardiomyopathy, long-term outcome is poor and left ventricular ejection fraction is a major powerful predictor of survival. However, right ventricular function might also play an important role in the long-term prognosis of this disease. Aim The aim of this study was to determine the role of right ventricular parameters, mainly right ventricular ejection fraction, on survival in idiopathic cardiomyopathy. Methods We prospectively assessed long-term follow-up and predictors of survival in 62 consecutive patients referred from 1990 to 1992 for evaluation of idiopathic dilated cardiomyopathy, including haemodynamic evaluation, thermodilution right ventricular ejection fraction and volume measurements. Results At the time of catheterization, dyspnoea class III or IV was present in 60% of the patients, atrial fibrillation in 19% and complete left bundle branch block in 35%. Left ventricular ejection fraction was 30±10% and right ventricular ejection fraction was 30±l6%. During follow-up (2·2±1·3 years), 15 patients (24%) had heart transplantation and nine (14%) died before cardiac transplantation. Cumulative survival rate without heart transplantation was 74% and 56% at 1 and 4 years, respectively. In univariate analysis, survival was related to: dyspnoea class I or II ( P <0·04), absence of complete left bundle branch block ( P <0·05), administration of lower doses of furosemide ( P <0·01), high left ventricular ejection fraction ( P <0·0001), low pulmonary artery pressure ( P 0·002), high right ventricular ejection fraction ( P <0·0001), high cardiac index ( P <0·006), and low right ventricular volumes ( P <0·001). Multivariate analysis showed only two independent predictors of survival: left ventricular ejection fraction ( P <0·001) and right ventricular ejection fraction ( P <0·004). Conclusion In addition to left ventricular ejection fraction, right ventricular ejection fraction appears to be a complementary predictor of survival in idiopathic dilated cardiomyopathy, suggesting the importance of assessing right ventricular function in this disease.

Pacing in hypertrophic obstructive cardiomyopathy

Abstract: Background Uncontrolled studies have shown that short atrioventricular delay dual chamber pacing reduces outflow tract obstruction in hypertrophic obstructive cardiomyopathy. Although the exact mechanism of this beneficial effect is unclear, this seems a promising potential new treatment for hypertrophic obstructive cardiomyopathy. Method In order to evaluate the impact of pacing therapy, we performed a randomized multicentre double-blind crossover (pacemaker activated vs non activated) study to investigate modification of echocardiography, exercise tolerance, angina, dyspnoea and quality of life in 83 patients with a mean age of 53 (range 22–87) years with symptoms refractory or intolerant to classical drug treatment. Results After 12 weeks of activated or inactivated pacing, independent of which phase was first, the pressure gradient fell from 59±36 mmHg to 30±25 mmHg ( P <0·001) with active pacing. Exercise tolerance improved by 21% in those patients who at baseline tolerated less than 10 min of Bruce protocol; symptoms of dyspnoea and angina also improved significantly from NYHA class 2·4 to 1·4 and 1·0 to 0·4, respectively ( P <0·007). Quality of life assessment with a validated questionnaire objectivated the subjective improvement. Conclusion Pacemaker therapy is of clinical and haemodynamic benefit for patients with hypertrophic obstructive cardiomyopathy, left ventricular outflow gradient at rest over 30 mmHg who are symptomatic despite drug treatment.

Upregulation of cell adhesion molecules and the presence of low grade inflammation in human chronic heart failure.

Abstract: Background In the present study, the hypothesis was tested that cell adhesion molecules are expressed in failing human hearts and that a chronic inflammatory process contributes to chronic degeneration known to occur in cardiac incompetence. The cell adhesion molecules: ICAM-1, VCAM-1, PECAM-1, and E-selectin were studied, in addition to cellular markers of inflammation. Methods and results Tissue was obtained at transplantation from patients with either myocarditis, chronic ischaemic heart disease, or dilated cardiomyopathy. Controls were taken from patients with normal ventricles. Cell adhesion molecules were qualitatively evaluated and counted using specific antibodies and confocal microscopy. Additionally, semiquantitative evaluation of the presence of the CD3 antigen (T-lymphocytes), CD68 (macrophages), CD 11 a/CD 18 (ICAM-1 receptor) and human tumour necrosis factor-a were used as indicators of chronic inflammation. PECAM-1 stained all endothelial cells but ICAM-1 was only present in 80% of all capillaries in control tissue. The ratio ICAM-l/PECAM-1 was significantly enhanced in all groups of diseased hearts. Myocytes in myocarditic hearts expressed ICAM-ICAM. CD3 positive lymphocytes, CD68 positive macrophages and CDlla/CD18 positive cells were more abundantly present than in control. Macrophages expressing tumour necrosis factor-a were found in failing myocardium but not in control tissue. Conclusion Independent of the cause of heart failure, chronic low grade inflammation is present in failing human myocardium. This may significantly contribute to the structural deterioration that is the basis of reduced cardiac function in congestive heart failure. (Eur Heart J 1997; 18: 47

Effects of beta-blocker therapy on mortality in patients with heart failure : A systematic overview of randomized controlled trials

Abstract: Aims Several randomized trials have reported that beta-blocker therapy improves left ventricular function and reduces the rate of hospitalization in patients with congestive heart failure. However, most trials were individually too small to assess reliably the effects of treatment on mortality. In these circumstances a systematic overview of all trials of beta-blocker therapy in patients with congestive heart failure may provide the most reliable guide to treatment effects. Methods and results Details were sought from all completed randomized trials of oral beta-blocker therapy in patients with heart failure of any aetiology. In particular, data on mortality were sought from all randomized patients for the scheduled treatment period. The typical effect of treatment on mortality was estimated from an overview in which the results of all individual trials were combined using standard statistical methods. Twenty-four randomized trials, involving 3141 patients with stable congestive heart failure were identified. Complete data on mortality were obtained from all studies, and a total of 297 deaths were documented during an average of 13 months of follow-up. Overall, there was a 31% reduction in the odds of death among patients assigned a beta-blocker (95% confidence interval 11 to 46%, 2 P =0·0035), representing an absolute reduction in mean annual mortality from 9·7% to 7·5%. The effects on mortality of vasodilating beta-blockers (47% reduction SD 15), principally carvedilol, were nonsignificantly greater (2 P =0·09) than those of standard agents (18% reduction SD 15), principally metoprolol. Conclusion Beta-blocker therapy is likely to reduce mortality in patients with heart failure. However, large-scale, long-term randomized trials are still required to confirm and quantify more precisely the benefit suggested by this overview.

Endothelial dysfunction and atherosclerosis.

Abstract: The endothelium mediates a number of responses (relaxation or contraction) of arteries and veins from animals and humans. The endothelium-dependent relaxations are due to the release, by endothelial cells, of potent non-prostanoid vasodilator substances. Among these, the best characterized is endothelium-derived relaxing factor (EDRF), which is believed to be nitric oxide (NO). Nitric oxide is formed by the metabolism of L-arginine by the constitutive NO synthase of endothelial cells. In arterial smooth muscle, the relaxation evoked by EDRF is explained by the stimulation by NO of soluble guanylate cyclase that leads to the accumulation of cGMP. In a number of animal blood vessels and in human coronary arteries, the endothelial cells release a substance that causes hyperpolarization of the cell membrane (endothelium-derived hyperpolarizing factor, EDHF). The release of EDRF from the endothelium can be mediated by both pertussis toxin-sensitive (alpha 2-adrenoceptor activation, serotonin, aggregating platelets, leukotrienes) and insensitive (adenosine diphosphate (ADP), bradykinin) G proteins. In blood vessels from animals with regenerated and reperfused endothelium, and/or atherosclerosis, there is a selective loss of the pertussin toxin-sensitive mechanism of EDRF release, which favours the occurrence of vasospasm, thrombosis and cellular growth. The available information from isolated human blood vessels or obtained in situ concurs with the conclusions reached from studies with isolated animal tissues. In addition to relaxing factors, the endothelial cells can produce contracting factors (endothelium-derived contracting factors; EDCFs) which include superoxide anions, endoperoxides, thromboxane A2 and endothelin. From animal studies it can be concluded that the propensity to release EDCFs is maintained, or even augmented, in diseased blood vessels. The switch from a normally predominant release of EDRFs to that of EDCFs may play a crucial role in atherosclerosis.

Prognostic value of plasma endothelin-1 in patients with chronic heart failure.

Abstract: Aims Endothelin-1 is a potent vasoconstrictive and multifunctional peptide. Elevated concentrations have been reported in congestive heart failure. We hypothesized that the level of endothelin-1 in plasma is a prognostic marker in congestive heart failure. Methods and results Plasma levels of endothelin-1 were measured by radioimmunoassay in 120 congestive heart failure patients with ischaemic or non-ischaemic cardiomyopathy (mean ejection fraction 28±11%, in New York Heart Association (NYHA) functional class I: 21, class II: 35, class III: 61, class IV: 3). During a median follow-up of 361±338 days, 14 cardiac deaths occurred. In the univariate Cox model, endothelin-1 was the most powerful prognostic marker among the variables tested ( P =0 0001). A multivariate model, including plasma atrial natriuretic peptide and noradrenaline, NYHA class, age, and echocardiographic left ventricular end-diastolic diameter index was highly predictive of mortality ( P =0·00008), but only endothelin-1 remained significantly associated with outcome ( P =0·02). Patients with plasma endothelin-1≥5 pg . ml−1 had a higher mortality rate than those with endothelin-1<5 pg. ml−1 (21% vs 4%, P =0·001). Conclusion Our results suggest that elevated endothelin-1 plasma levels are associated with a poor prognosis and routine plasma endothelin-1 determination provides important prognostic information in mild to moderate heart failure.

Trends in hospitalization and mortality for heart failure in Spain, 1980–1993

Abstract: AIMS To describe, for the first time, trends in hospitalization and mortality rates for congestive heart failure in Spain during the period 1980-1993. METHODS AND RESULTS Data on primary diagnosis of congestive heart failure were taken from the National Hospital Morbidity Survey and the National Vital Statistics. The number of hospital admissions for congestive heart failure rose by 71% (from 42,965 in 1980 to 73,448 in 1993) and hospitalization rates for congestive heart failure increased by 47% (from 348 per 100,000 in 1980 to 511 per 100,000 in 1993). The rise in hospitalizations was limited to persons aged > or = 65 years, and proved greater among women. Congestive heart failure was the leading cause of hospitalization in persons aged > or = 65 years, accounting for 5% of all hospital admissions in this age group. Age-adjusted congestive heart failure mortality declined by 23%. The decline affected all age groups, with the sole exception of the > or = 80-year group in which mortality rose. Nevertheless, congestive heart failure remained the third leading cause of cardiovascular death. CONCLUSION Congestive heart failure represents a significant hospital and demographic burden for the Spanish population. The hospital burden increased substantially in the period 1980-1993, and will continue to do so in future with the growth of the elderly population.

The influence of muscle mass, strength, fatigability and blood flow on exercise capacity in cachectic and non-cachectic patients with chronic heart failure

Abstract: Background The influence of age, skeletal muscle function and peripheral blood flow on exercise capacity in chronic heart failure patients is controversial, possibly due to variations in skeletal muscle atrophy. Methods and results To assess predictors of exercise capacity in patients with clinical cardiac cachexia, we studied 16 cachectic and 39 non-cachectic male chronic heart failure patients of similar age and ejection fraction. All cachectic patients were wasted (% ideal body weight: 81 1·9 vs 105·2±2·1, P <0· mean±SEM) and had documented weight loss (5–30 kg). Peak oxygen consumption (14·9±1·4 vs 16·3±0·6 ml.kg−1, min −1, resting, and peak blood flow (plethysmography) and 20 min fatigability (% baseline strength) were all similar between the two groups. Quadriceps strength, muscle size (all P <0·0001), strength per unit muscle (right: P <0·05; left: P <0·0·01) and 5 min fatigability ( P <0·05) were all lower in cachectic patients. In non-cachectic patients, age (R=0·48 and quadriceps strength ( R =0·43, all P <0·01) predicted peak oxygen consumption. Only in cachectic patients did peak blood flow predict peak oxygen consumption significantly (R=0·72, P 0·005), whereas age and strength did not. Similar findings were confirmed using other previously published definitions of cardiac cachexia. Conclusion The predictors of exercise capacity change with the development of cardiac cachexia from age and strength to peak blood flow. This shift may be caused by additional endocrine or catabolic abnormalities active in end stage heart failure.

Out-of-hospital cardiac arrests of non-cardiac origin. Epidemiology and outcome.

Abstract: Aims The aim of the study was to determine the epidemiology of out-of-hospital cardiac arrests of non-cardiac origin and survival following resuscitation, using the Utstein method of data collection. Methods and results The study was of prospective cohort design and was conducted in a middle-sized urban city (population 525 000) served by a single emergency medical services system. Consecutive out-of-hospital cardiac arrests of non-cardiac origin occurring between 1 January 1994 and 31 December 1995 were included. Survival from cardiac arrest to hospital discharge, and factors associated with survival were considered as main outcome measures. Of the 809 patients, 276 (34·1%) had a cardiac arrest of non-cardiac origin. The mean (SD) age of the patients was 49·8 (20·9) years. Resuscitation was attempted in 204 cases, 82 of whom (40·2%) were hospitalized alive and 23 (11·3%) were discharged. Thirteen (56·5%) of the survivors were discharged neurologically intact or with mild disability (overall performance category I or II). The survivors, during the study period, who suffered an out-of-hospital cardiac arrest of non-cardiac origin comprised 19·2% of all out-of-hospital cardiac arrest survivors. Trauma (62), non-traumatic bleeding (36), intoxication (31), near drowning (22) and pulmonary embolism (18) were the most common aetiologies, comprising 61·2% of cases. The non-cardiac aetiology was suspected pre-hospital in 176 (63·8%) cases; in the remaining cases, the aetiology was revealed only after in-hospital investigations or autopsy. In a logistic regression model, time interval to first responding unit, collapse outside the home, and aetiologies of near-drowning, airway obstruction, intoxication and convulsions were associated with survival. Conclusions These results indicate that sudden out-of-hospital cardiac arrest more often has a non-cardiac cause than previously believed. Although survival is not as likely as from cardiac arrest of cardiac origin, since non-cardiac-cause survivors comprise one fifth of all out-of-hospital cardiac arrest survivors, resuscitation efforts are worthwhile.

Gender and the relationship between ventricular repolarization and cardiac cycle length during 24-h Holter recordings

Abstract: Aims There are gender-related differences in the QT interval measured from standard ECG tracings. However, these observations are based on a limited number of beats recorded in resting conditions. Computerized Holter techniques enable ventricular repolarization and its relationship with cardiac cycle length to be analysed long term. Previous studies used only the initial portion of the QT interval to the T wave apex (QTa) to measure ventricular repolarization; however, QTa may underestimate the total QT duration (QTe). The aims of this study were to verify whether QTa and QTe had similar rate-dependence in normal subjects and whether gender-related QTc differences observed in the resting ECG were also present in the long-term QT interval-cycle length relationship. Methods and results Twenty-four hour Holter recordings were obtained in 40 healthy young subjects, 20 females and 20 males (mean age 28±9 and 26±5 years, respectively ns). Two-channel ECG digitized signals were processed using new automatic QT analysis software (Ela Medical), which converted the 24-h recordings into 2880 30-s templates. It also measured the QT apex (QTa) QT end (QTe) and the RR interval (ms) of each template, and computed the slopes of the linear regressions of QTe and QTa values plotted against the corresponding RR interval (QTe/RR and QTa/RR). Females had a shorter RR interval than males (803±129 vs 877±86 ms, p =0·037), with longer mean QTc (420±17 vs 400±200 ms, p =0·0005). In both genders, QTa/RR slopes were steeper than QTe/RR slopes ( p =0·0001). Both QTa7sol;RR and QTe/RR slopes were steeper in females than in males (QTa/RR 0·20±0·04 vs 0·16±0·03, p =0·001; QTe/RR 0·16±0·04 vs 0·13±0·03, p =0·027). Of note, QTa and QTe at fixed long cycle lengths (1000 ms) were longer in women than in men (QTa1000 330±20 vs 309±18 ms; p =0·002; QTe1000 410±17 vs 389±19 ms; p =0·002), while they did not differ at fixed short cycle lengths (600 ms). Conclusions This study demonstrates that both the initial portion of the QT interval (QTa) and the entire QT interval (QTe) are useful since QTa is more prolonged than QTe at increasing cycle lengths, and thus includes most of the heart rate dependency of ventricular repolarization. In normal subjects, both the QTc and the long-term relationship between ventricular repolarization and heart rate are affected by gender. The differences in QTa and QTe duration between males and females are more marked at long cycle lengths and disappear at short cycle lengths. Finally, this study also proves the clinical feasibility of assessing the long-term relationship between ventricular repolarization and heart rate by utilizing the automatic measurement of the QT interval from 24-h Holter recordings.

Effect of ramipril on morbidity and mode of death among survivors of acute myocardial infarction with clinical evidence of heart failure. A report from the AIRE Study Investigators.

Abstract: Background The importance of the effects of ACE inhibitors on sudden death, progressive heart failure and recurrent infarction to the reduction in overall mortality in heart failure and after myocardial infarction is disputed. Methods The AIRE study randomized 2006 patients with clinical or radiological evidence of heart failure within 2-9 days of a myocardial infarction to receive ramipiril 5 mg b.d. or matching placebo. Outcomes were assessed independently by members of an end-points committee blinded to treatment allocation. Results Fewer patients developed severe resistant heart failure as their first validated end-point on rampril, despite the greater number of at-risk survivors, compared to placebo (n = 143 vs 178; risk reduction 23%; CI 5 to 39%; P = 0.017). Ramipril did not alter the rate of reinfarction or stroke. Irrespective of treatment allocation 182 (46%) patients developed resistant heart failure prior to death. A validated acute or remote myocardial reinfarction occurred in 76 (19%) patients prior to death and chest pain occurred in 90 (23%) patients around the time of death suggesting an ischaemic element to these deaths Eighty deaths occurred on the index admission, 167 during re-admission and 145 out-of-hospital. Sudden death accounted for 54% of all deaths and 93% of out-of-hospital deaths. Ramipril reduced the risk of sudden death by 30% (95% CI: 8-47%; P = 0.011). However, overall, 45% of those patients who died suddenly had severe or worsening heart failure prior to their death. Only 39% of sudden deaths were considered to be due to arrhythmias. Ramipril reduced the risk of death from circulatory failure by 18%, but this did not reach statistical significance (95% CI; 41 to -14%; P = 0.237). The magnitude of the effects on sudden death and death due to circulatory failure were not significantly different. However, 38% of the reduction in overall mortality was from the subgroup with sudden death who had developed prior severe resistant heart failure (placebo n = 35, ramipril n = 15), again emphasizing the marked benefit in preventing failure. Ramipril did not selectively alter the proportion of in- to out-of-hospital deaths. Conclusion Ramipril reduces mortality and progression to resistant heart failure among patients with evidence of heart failure early after myocardial infarction. Retarding the progression of heart failure appears to be a major factor contributing to the reduction in mortality both by reducing circulatory failure and by reducing sudden death.

The relationship between resting heart rate and all-cause, cardiovascular and cancer mortality

Abstract: Aims The association between resting heart rate and changes in heart rate with all-cause, cardiovascular and cancer mortality was studied among 1827 men and 2929 women, aged 40-80 years, followed for 12 years. Methods and results After adjustment for initial age, serum cholesterol, body mass index, systolic blood pressure, smoking and diabetes, the all-cause mortality hazard ratio was 1.7 (95% confidence interval 1.4-2.2) for heart rate increments of 20 beats.min-1 for men and 1.4 (confidence interval 1.1-1.8) for women. For cardiovascular mortality, the risk estimates were 1.7 (confidence interval 1.2-2.6) for men and 1.3 (confidence interval 0.9-2.0) for women. We observed no significant association between heart rate and cancer mortality. For women, stronger predictive information for all-cause mortality was provided if changes in heart rate were evident at the 2-year review. Conclusion The resting heart rate is a predictor of mortality, independent of major cardiovascular risk factors.

Prevalence of coronary artery disease and coronary risk factors in rural and urban populations of north India

Abstract: Objective This study was conducted to determine and compare the prevalence of coronary artery disease and coronary risk factors in both a rural and an urban population of Moradabad in north India. Design and setting A cross-sectional survey of two randomly selected villages from the Moradabad district and 20 randomly selected streets in the city of Moradabad. Subjects and methods The 3575 subjects were between 25 and 64 years old; 1769 (894 men and 875 women) lived in the countryside and 1806 (904 men and 902 women) lived in the city. The survey methods were questionnaires, physical examination and electrocardiography. Results The overall prevalence of coronary artery disease, based on a clinical diagnosis and an electrocardiogram, was 9·0% in the urban and 3·3% in the rural population. The prevalences were significantly ( P <0·001) higher in the men compared with the women in both urban (11·0 vs 6·9%) and rural (3·9 vs 2·6%) populations, respectively. The prevalence of symptomatic coronary artery disease (known coronary disease and Rose questionnaire-positive angina) was 23% in the men (n=19) and 1·5% in the women (n=13) in the rural subjects, and 8·5% in the men (n=77) and 3·4% in the women (n=31) in the urban population. When diagnosed on the basis of electrocardiographic changes alone, the prevalences were 1·5% (n=26) in the rural population and 3·0% (n=55) in the urban. Coronary risk factors were two- or three-fold more common among urban subjects compared to the rural population in both sexes. Central obesity was four times more common in the urban population compared to the rural in both sexes. Sedentary lifestyle and alcohol intake were significantly ( P <0·01) higher in the urban population compared to the rural subjects. There was a significant association between coronary disease and age, hypercholesterolaemia, hypertension and central obesity in both sexes. Smoking was a significant risk factor of coronary disease in men. Conclusions Coronary artery disease and coronary risk factors were two or three times higher among the urban compared with the rural subjects, which may be due to greater sedentary behaviour and alcohol intake among urbans. It is possible that some Indian populations can benefit by reducing serum cholesterol, blood pressure and central obesity and increasing physical activity.

Conversion of atrial fibrillation to sinus rhythm and rate control by digoxin in comparison to placebo

Abstract: Aims A randomized, double-blind study with a high dose of digoxin administered intravenously for conversion of atrial fibrillation (not due to haemodynamic alterations) to sinus rhythm, and for rate control in converters and nonconverters was set up. Outcome measures were conversion within 12 h; time to conversion; early rate control; and stable slowing within 12 h. Methods We studied 40 patients with recent onset (<1 week) atrial fibrillation; controls received saline intravenously, the other patients digoxin 1·25 mg. Results One patient converted before digoxin administration. Conversion occurred in 9/19 patients on digoxin and in 8/20 on placebo (ns). The mean time to conversion tended to be shorter only for digoxin. Two late conversions on placebo were observed within 24 h. Heart rate during atrial fibrillation decreased after 30 min for converters and non-converters ( P <0·05). For all patients on digoxin, heart rate after 30 min was lower compared to baseline ( P <0·002) and to placebo ( P <0·02). Persistent, stable slowing occurred only in 3/10 non-converters on digoxin ( P <0·05), and two patients developed bradyarrhythmias. QTc was shortened immediately after conversion in all patients. Converters had baseline characteristics similar to those of non-converters. Conclusions Intravenous digoxin offers no substantial advantages over placebo in recent onset atrial fibrillation with respect to conversion, and provides weak rate control.

Both endothelium-dependent and endothelium-independent function is impaired in patients with angina pectoris and normal coronary angiograms

Abstract: Background The aim of this study was to investigate both endothelium-dependent and endothelium-independent vasodilatation in syndrome X patients. Recently selective impairment of endothelium-dependent function has been reported in a small number of syndrome X patients. However, other investigators have reported impaired endothelium-independent function. Methods We infused the endothelium-independent vasodilators papaverine and glyceryl trinitrate, and endothelium-dependent vasodilator acetyicholine in the left coronary artery of 35 patients with syndrome X and in 17 control subjects (atypical chest pain, negative exercise test, and normal coronary angiograms). Coronary blood flow was measured with an intracoronary Doppler catheter positioned in the proximal left anterior descending coronary artery, and the artery diameter was assessed using quantitative coronary angiography. Result The mean increase in coronary blood flow in response to a 12 mg dose of papaverine was significantly less in the syndrome X group (185±74% vs 411 ± 59%, P 0·001). The increase in coronary blood flow in response to acetylcholine, at doses of 1, 3, 10, and 30 μg. min−1, was also significantly lower in the syndrome X group (12±13 ( P >0·05), 41 ± 33, 57 ± 68, and 124 ± 87% ( P >0·001)) as compared to the control group (76 ± 49, 214 ± 116, 355 ± 115, and 361 ± 74%). Conclusion These findings demonstrate that both endothelium-dependent and endothelium-independent dilatation of the coronary microvasculature is impaired in syndrome X.

Left ventricular systolic and diastolic function in aortic stenosis. Prognostic value after valve replacement and underlying mechanisms.

Abstract: tality, with 5-year crude survival of 92%, 77%, and 50%, respectively (P<00001). Systolic wall stress was without prognostic value. Further analyses indicated that impairment of left ventricular function occurred with increasing muscle mass over two phases: (1) diastolic dysfunction characterized by a pattern of severe relative concentric hypertrophy; (2) the addition of systolic dysfunction characterized by a more dilated, less concentric chamber geometry. Coronary artery disease seemed to provoke the latter development sooner. Conclusions Impaired systolic and diastolic left ventricular function, irrespective of afterload, were decisive independent pre-operative risk factors for early as well as late mortality after aortic valve replacement for aortic stenosis. The adverse influence of concentric hypertrophy was the main underlying mechanism. Operative intervention, before impairment of diastolic and systolic function, should be advocated. (Eur Heart J 1997; 18: 1977-1987)

Repolarization dispersion and sudden cardiac death in patients with impaired left ventricular function

Abstract: Aims Prolongation of repolarization dispersion measured from the 12-lead surface ECG has been associated with sudden cardiac death and ventricular tachyarrhythmia in a variety of heart disorders. This study tested the hypothesis that increased repolarization dispersion is of prognostic value in identifying chronic heart failure patients at high risk of sudden cardiac death and ventricular tachyarrhythmia. Results In 163 patients, ischaemic (n=126) and idiopathic dilated (n=37) cardiomyopathy with a left ventricular ejection fraction ≤40% were diagnosed by left ventricular angiography. During follow-up (26±15 months) 24 patients died suddenly, 10 experienced ventricular tachyarrhythmia, 19 died from pump failure, six died from acute myocardial infarction, and 97 survived. Bazett's formula rate-corrected JT-interval dispersion (JTc-d) was found to be 109±23 ms in sudden cardiac death/ventricular tachyarrhythmia patients, 57±20 ms in survivors, and 55+20 ms in patients who died from pump failure or acute myocardial infarction. Both univariate and multivariate analyses showed JTc-d to be the most important independent predictor of sudden cardiac death/ventricular tachyarrhythmia. A cut-off value of 85 ms for JTc-d had a 74% positive and a 98% negative predictive accuracy in identifying patients at risk for sudden cardiac death/ventricular tachyarrhythmia. Conclusion Analysis of repolarization dispersion from the 12-lead surface ECG seems to be a useful screening method for identifying chronic heart failure patients at high risk for sudden cardiac death/ventricular tachyarrhythmia.

Smoking, atherosclerosis and risk of abdominal aortic aneurysm.

Abstract: Aims The role of cardiovascular risk factors and atherosclerosis in the aetiology of abdominal aortic aneurysms is not well understood. The aim of this study was to determine the association between atherosclerosis and aortic aneurysm in the general population and the extent to which cardiovascular risk factors might increase the risk of aneurysm independently of an effect on atherosclerotic disease. Methods and Results In the Edinburgh Artery Study, 1592 men and women aged 55-74 years were followed prospectively over a period of 5 years. Forty subjects were identified as having an abdominal aortic aneurysm and, for each, five controls were randomly selected. Cases showed a higher prevalence of cardiovascular disease (f<0001) and had a lower ankle brachial pressure index (P<001). Current and recent ex-cigarette smokers had an increased risk of aortic aneurysm compared with long time ex-smokers and never smokers (odds ratio 308, 95% CI 1-53 to 6-21). Adjustment for concurrent atherosclerotic disease reduced the odds ratio to 2-63 (95% CI 1-26 to 5-45). The risk of aortic aneurysm was not related to elevation in diastolic blood pressure or in serum cholesterol. Conclusions These findings indicate that atherosclerotic disease is associated with risk of aortic aneurysm in the general population. In addition, cigarette smoking appears to have a direct effect on the risk of aortic aneurysm which is independent of atherosclerosis. (Eur Heart J 1997; 18: 671-676)

Effects of mental and physical stress on platelet function in patients with stable angina pectoris and healthy controls

Abstract: The effects of mental and physical stress on platelet function in patients with stable angina pectoris and healthy controls were investigated. Platelet function was studied at rest, and during mental stress (colour word test), or after exercise (bicycle ergometry), in 113 angina patients (21 on aspirin) and 50 matched controls. Platelet function was assessed by filtragometry ex vivo (reflecting platelet aggregability), by measuring platelet secretion (/?thromboglobulin and platelet factor 4 levels in plasma), and by Born aggregometry in vitro. At rest, platelet function did not differ between patients and controls. Exercise increased platelet aggregability and secretion similarly in both groups. Aspirin did not attenuate the platelet activating effect of exercise despite inhibition at rest. Mental stress increased heart rate, blood pressure and plasma catecholamines, but platelet responses were highly variable. However, mental stress tended to shorten filtragometry readings in patients but not in controls (P<005 between the groups); plasma /?-thromboglobulin showed a similar difference between patients and controls (P<0-05 between the groups; aspirin-treated patients included). Physical exercise activates platelets in patients with stable angina pectoris and healthy controls. Aspirin is not an effective inhibitor of exercise-induced platelet aggregation. Platelet responses to mental stress are variable, but more pronounced in angina patients. (Eur Heart J 1997; 18: 807-815)

Superiority of mitral valve repair in surgery for degenerative mitral regurgitation

Abstract: Objectives We aimed to assess the influence of type of operation on outcome in degenerative mitral regurgitation. Methods We compared outcomes in 278 consecutive patients who underwent mitral valve repair (167 patients), replacement with subvalvular preservation (22 patients) and without subvalvular preservation (89 patients) for degenerative mitral regurgitation. Results There was a trend towards lower mortality with repair and replacement with subvalvular preservation compared to replacement without subvalvular preservation. Thirty-day mortality was 1·2% vs 0·0% vs 4·7% (ns) respectively. Six-year survival was, respectively, 67·8±7·4% ( P =0·088) vs 80·8±11·0% ( P =0·25 vs 63·3±5·9% for all-cause death, 78·5±6·8% ( P =0·063) vs 95·5±4·4% ( P =0·092) vs 67·6±5·9% for all complication-related death and 80·5±6·9% ( P =0·076) vs 100·0±0·0% (P=0·045) vs 72· ± 5·8% for complication-related death due to myocardial failure. Multivariate analysis confirmed independent beneficial effects from repair compared to replacement without subvalvular preservation on complication-related death (hazard ratio 0·42, P =0·010) and death from myocardial failure (hazard ratio 0·40 P =0·014), and from repair compared to mechanical replacement on thromboembolism (hazard ratio 0·45, P =0·029) and anticoagulation-related haemorrhage (hazard ratio 0·19, P =0·026). Conclusions Mitral valve repair is superior to replacement. The greatest survival advantage is in reduced mortality from myocardial failure. Repair should be the operation of choice for degenerative mitral regurgitation.

The technique of impedance cardiography

Abstract: Other than fluctuations caused by respiration thoracic tissue impedance is constant. Blood-related impedance changes repeat themselves with every heart beat and are linked to cardiac activity.

Clinical characteristics of chronic heart failure patients with an augmented peripheral chemoreflex

Abstract: Aims The peripheral chemoreflex may be augmented in chronic heart failure and may play a role in its pathophysiology including the mediation of exercise hyperpnoea and sympathetic activation. The objective of this study was to characterize the patients with an augmented peripheral chemoreflex. Methods and results Peripheral chemoreflex sensitivity was assessed by measuring the ventilatory response to hypoxia using transient inhalations of pure nitrogen in 50 patients with chronic heart failure (age 58·±12·1 (SD) years; radionuclide left ventricular ejection fraction 26·5±13·0%). The peripheral chemoreflex of 12 healthy controls with similar demographic characteristics was 0·272±0·201 1.min−1. %Sao2−1 compared with 0·673±0·4101.min−1.%Sao2−1 ( P <0·0001) in the chronic heart failure patients. Using 2 standard deviations above the mean level of the controls' peripheral chemoreflex sensitivity as the upper limit of normal, we defined an augmented chemoreflex as greater than 0·6751.min−1.%Sao2−1 Twenty of the chronic heart failure patients (40%) demonstrated such an augmented peripheral chemoreflex. Compared with patients with peripheral chemoreflex sensitivity within the normal range, they had a reduced peak oxygen consumption during cardiopulmonary exercise (15·1±4·4 vs 18·5±5·8 ml.kg−1.min−1, P =0·02), reduced radionuclide left ventricular ejection fraction (21·8±11·8 vs 29·4±13·1%, P =0·046) and were in a worse New York Heart Association functional class (2·8 vs 2·4 P =0·05). The ventilatory response to exercise, as characterized by the regression slope relating minute ventilation to carbon dioxide output during exercise, was also higher (40·48±9·32 vs 34·54±7·19, P =0·02), consistent with the role of the peripheral chemoreflex in mediating exercise hyperpnoea. There was also an increased proportion of patients with non-sustained ventricular tachycardia in the group with an augmented peripheral chemoreflex (61% vs 21%, chisquared 7·08, P <0·01). No difference was seen in the age, height, weight and lung function measurements of these patients compared with the normal chemoreflex group. Conclusion An augmented peripheral chemoreflex is a common finding in chronic heart failure patients, one associated with increasing severity and with the exercise hyperpnoea seen in the condition. That there was an excess of patients with non-sustained ventricular tachycardia in the group with an augmented peripheral chemoreflex may be related to the chemoreflex-driven sympathetic stimulation. The peripheral chemoreflex may be important in the pathophysiology of chronic heart failure, both in terms of symptoms and exercise limitation.