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Biomedical subjects

A J Coats

Publications and source records attributed to A J Coats.

At least 19 recordsLinked to original sources
PubMed1999

Central and peripheral components of chronic heart failure: determinants of exercise tolerance.

This study sought to determine the relationship between myocardial dysfunction and peripheral haemodynamic disorders to exercise intolerance in patients with chronic heart failure (CHF). Seventeen patients with mild to moderate CHF (peak oxygen consumption (VO2) >16 ml/min/kg) and 13 with severe CHF (peak VO2 <16 ml/min/kg) underwent invasive (Swan-Ganz) cardiopulmonary exercise testing and forearm venous occlusion plethysmography at rest and during maximal dilatation in reactive hyperaemia. There was a shift from central to peripheral haemodynamic factors limiting exercise, suggesting an increasing importance of peripheral factors in parallel to the progression of CHF. In mild to moderate CHF peak VO2 was closely related to central haemodynamics (r = 0.57 for cardiac index at rest; r = 0.76 for cardiac index at maximal workload; r = -0.54 for right arterial pressure at maximal workload; all p<0.05) and poorly correlated with peripheral haemodynamics (blood flow, vascular resistance and venous tone). In contrast, in severe CHF peak VO2 was closely related to peripheral haemodynamic factors (r = 0.79 for forearm blood flow; r = -0.82 for vascular resistance; r = -0.77 for venous tone; all p<0.05) and less to central ones. Thus, exercise tolerance of patients with mild to moderate CHF is predominantly determined by central haemodynamic factors, notably by the cardiac index. In severe CHF peripheral factors assume ever greater importance in the determining of exercise capacity.

Adult↗
PubMed1999

Endotoxin and immune activation in chronic heart failure: a prospective cohort study.

BACKGROUND: Immune activation in patients with chronic heart failure may be secondary to endotoxin (lipopolysaccharide) action. We investigated the hypothesis that altered gut permeability with bacterial translocation and endotoxaemia would be increased in patients with oedema secondary to congestive heart failure. METHODS: We compared 20 patients who had chronic heart failure with recent-onset peripheral oedema (mean age 64 years [SD 10], New York Heart Association [NYHA] class 3.3 [0.7]), 20 stable non-oedematous patients with chronic heart failure (mean age 63 years [19], NYHA class 2.6 [0.7]), and 14 healthy volunteers (mean age 55 years [16]). Biochemical markers of endotoxaemia, inflammation, and immune activation were measured. Ten patients were studied within 1 week of complete resolution of oedema. Five patients survived longer than 6 months and were restudied again after remaining free of oedema for more than 3 months. FINDINGS: Mean endotoxin concentrations were higher in oedematous patients with chronic heart failure than in stable patients with chronic heart failure (0.74 [SD 0.45] vs 0.37 EU/mL [0.23], p=0.0009) and controls (0.46 EU/mL [0.21], p=0.02). Oedematous patients had the highest concentrations of several cytokines. After short-term diuretic treatment, endotoxin concentrations decreased from 0.84 EU/mL [0.49] to 0.45 EU/mL [0.21], p<0.05) but cytokines remained raised. After freedom of oedema for more than 3 months after oedema resolved, endotoxin concentrations remained unchanged from the previous visit (0.49 EU/mL [0.06], p=0.45). INTERPRETATION: Raised concentrations of endotoxin and cytokines are found in patients with chronic heart failure during acute oedematous exacerbation. Intensified diuretic treatment can normalise endotoxin concentrations. Our preliminary findings suggest that endotoxin may trigger immune activation in patients with chronic heart failure during oedematous episodes.

Acute-Phase Proteins↗
PubMed1999

Left ventricular remodelling: common process in patients with different primary myocardial disorders.

Currently the problem of left ventricular remodelling in the early and late stages after myocardial infarction are under intense study. Studies of the role of remodelling of the left ventricle in patients with long-term arterial hypertension have been recently initiated. The purpose of this investigation was to study whether left ventricular remodelling is common for different primary myocardial disorders. The study population consisted of 212 patients with primary myocardial lesions (121 with dilated cardiomyopathy, 45 with chronic myocarditis and 46 with prolonged damage of the myocardium with alcohol; 196 male and 16 female, mean age 42.6+/-11.3 years) and 32 age matched normal subjects (24 male and eight female). Cardiac catheterization for ventriculography and coronary angiography was performed in all subjects for detection of left ventricular haemodynamics, including chamber volume and shape at end-systole and end-diastole. Worsening of heart failure was associated with a progressive enlargement of the left ventricle, with increases in end-systolic left ventricular wall stress, that lead to increases in left ventricular muscle mass, alteration of left ventricular geometry from a more ellipsoid to a more spherical shape and a progressive decrease of relative wall thickness index that reflects inadequate enlargement of the ventricular chamber in comparison with the increase in muscle mass. This process of left ventricular remodelling was common to all the primary myocardial disorders studied. Thus, regardless of the different etiological nature, most primary myocardial disorders show a similar left ventricular remodelling process suggesting common mechanisms for the development of chronic heart failure.

Adult↗
PubMed1999

Loss of bone mineral in patients with cachexia due to chronic heart failure.

We studied body composition and cytokine levels in 58 patients with heart failure and 16 control patients using dual-energy x-ray absorptiometry. Bone mineral content and density, and lean and fat tissue content, were reduced in cachectic compared with noncachectic patients and control subjects, with negative relations between indexes of bone composition and tumor necrosis factor and tumor necrosis factor receptor 1.

Absorptiometry, Photon↗
PubMed1999

Effects of amiodarone on the P-wave triggered signal-averaged electrocardiogram in patients with paroxysmal atrial fibrillation and coronary artery disease.

The effects of a 6-week treatment with amiodarone on the P-wave triggered signal-averaged electrocardiogram in patients with paroxysmal atrial fibrillation and coronary artery disease have been studied. Amiodarone favorably influences P-wave triggered signal-averaged electrocardiographic parameters, predominantly in patients in whom amiodarone is effective in preventing paroxysmal atrial fibrillation.

Aged↗
PubMed1999

A neural link to explain the "muscle hypothesis" of exercise intolerance in chronic heart failure.

BACKGROUND: In chronic heart failure the cause of exercise limitation is still unclear: ergoreceptors, muscle afferents sensitive to exercise metabolites, are proposed as a neural link between muscular abnormalities and the limited exercise responses in this syndrome. METHODS: In 92 stable patients with heart failure (34 in New York Heart Association class I, 27 in class II, and 31 in class III) and 28 age-matched normal controls, we assessed exercise tolerance (maximal upright bicycle) and ergoreflex activity (2 dynamic hand grips: one control and one followed by 3 minutes of local circulatory occlusion to isolate the ergoreflex component by metabolite trapping). RESULTS: Patients, with respect to the controls, showed reduced exercise tolerance (peak VO2: 20 vs 33 mL/kg/min), increased ergoreflex effects on ventilation (9 vs 4 L/min), systolic pressure (37 vs 13 mm Hg), and leg vascular resistance (45 vs 22 units) (all P <.005); with the progression of the symptoms, a progressive increase in ergoreflex contribution to the ventilatory response to exercise was observed. The indexes of exercise limitation during arm and leg exercise (ie, peak VO 2, V/VCO2 slope) correlated highly with the ergoreflex contribution to ventilatory response during handgrip test ( r </= 0.7, P <.0001) but weakly with left ventricular ejection fraction (r </= 0.5). CONCLUSION: In chronic heart failure, the overactivity of the ergoreflex is related to a degree of functional limitation and appears, through direct ventilatory and cardiovascular responses, to contribute to the abnormal responses to exercise, explaining the "muscle hypothesis."

Aged↗
PubMed1999

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

AIMS: To determine the incidence and aetiology of heart failure in the general population. METHODS AND RESULTS: New cases of heart failure were identified from a population of 151 000 served by 82 general practitioners in Hillingdon, West London through surveillance of acute hospital admissions and through a rapid access clinic to which general practitioners referred all new cases of suspected heart failure. On the basis of clinical assessment, electrocardiography, chest radiography and transthoracic echocardiography, a panel of three cardiologists decided that 220 patients met the case definition of new heart failure over a 20 month period (crude incidence rate of 1.3 cases per 1000 population per year for those aged 25 years or over). The incidence rate increased from 0.02 cases per 1000 population per year in those aged 25-34 years to 11.6 in those aged 85 years and over. The incidence was higher in males than females (age-adjusted incidence ratio 1.75 [95% confidence interval 1.34-2.29, P<0.0001]). The median age at presentation was 76 years. The primary aetiologies were coronary heart disease (36%), unknown (34%), hypertension (14%), valve disease (7%), atrial fibrillation alone (5%), and other (5%). CONCLUSIONS: Within the general population, new cases of heart failure largely occur in the elderly, and the incidence is higher in men than women. The single most common aetiology is coronary heart disease, but in a third of cases the aetiology cannot be determined on the basis of non-invasive investigation alone. To be relevant to clinical practice, future clinical trials in heart failure should not exclude the elderly.

Adult↗
PubMed1999

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

BACKGROUND: Chronic heart failure is one of a number of disorders associated with the development of a wasting syndrome. The precise mechanisms of this remain unknown, but previous studies have suggested a role for immune and neurohormonal factors. METHODS: We aimed to investigate in detail the differences in body composition (dual X-ray absorptiometry) and the relationship to candidate biochemical factors of the immune, neurohormonal and metabolic systems in 15 healthy controls, 36 stable non-cachectic and 18 cachectic patients with chronic heart failure. RESULTS: Non-cachectic patients showed reduced leg lean tissue (-9.1%, P<0.01) compared to controls. Cachectic patients had significantly reduced lean (-21.0% vs controls, -19.9% vs non-cachectics), fat (-33.0% vs controls, -37. 0% vs non-cachectics) and bone tissue (-17.5% vs controls, -15.9% vs non-cachectics) (all P<0.0001). Cachectic patients showed a significantly increased cortisol/dehydroepiandrosterone ratio (+203% vs controls, P<0.0001; +89% vs non-cachectics, P=0.0011) and increased cytokine levels (TNF-alpha, soluble TNF-receptor 1, interleukin-6). The levels of catabolic hormones and cytokines correlated significantly with reduced muscle and fat tissue content and reduced bone mass. CONCLUSION: Peripheral loss of muscle tissue is a general finding in chronic heart failure. The wasting in cardiac cachexia affects all tissue compartments and is significantly related to neurohormonal and immunological abnormalities.

Adult↗
PubMed1999

Cardiac cachexia: a syndrome with impaired survival and immune and neuroendocrine activation.

Chronic heart failure (CHF) is a complex syndrome affecting many body systems. Body wasting (ie, cardiac cachexia) is a serious complication of CHF long known but little investigated. Although no specific diagnostic criteria have been established, we have suggested that cardiac cachexia be defined on the basis of the presence of documented nonintentional and nonedematous weight loss > 7.5% of the premorbid normal weight, occurring over a time period of > 6 months. Using this definition, 16% of an unselected CHF outpatient population was found to be cachectic. The cachectic state is predictive of impaired prognosis independently of age, functional disease classification, left ventricular ejection fraction, and peak oxygen consumption. The mortality in the cachectic cohort is 50% at 18 months. Analyzing body composition in detail, it has been found that patients with cardiac cachexia suffer from a general loss of fat tissue (ie, energy reserves), lean tissue (ie, skeletal muscle), and bone tissue (ie, osteoporosis). Cachectic CHF patients are weaker and fatigue earlier, which is due to both reduced skeletal muscle mass and impaired muscle quality. The pathophysiologic alterations leading to cardiac cachexia remain unclear, but initial cross-sectional studies have suggested that humoral neuroendocrine and immunologic abnormalities are linked, independently of established heart failure severity markers, to the presence of body wasting. Comparing the features of cachectic and noncachectic CHF patients with those of healthy control subjects, it is mainly the cachectic CHF patients who show raised plasma levels of epinephrine, norepinephrine, and cortisol; the highest plasma renin activity and aldosterone plasma concentrations; and the lowest plasma sodium level. Several studies have shown that cardiac cachexia is linked to raised plasma levels of tumor necrosis factor-ac. The degree of body wasting is strongly correlated with neurohormonal and immune abnormalities. The available evidence suggests that cardiac cachexia is a multifactorial neuroendocrine and metabolic disorder with a poor prognosis. A complex imbalance of different body systems may cause the development of body wasting.

Body Composition↗
PubMed1999

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Angiotensin-Converting Enzyme Inhibitors↗
PubMed1998

Is heart rate variability a reliable method to assess autonomic modulation in left ventricular dysfunction and heart failure? Assessment of autonomic modulation with heart rate variability.

Autonomic dysfunction seems to be involved in the progression and prognosis of congestive heart failure. Measurement of heart rate variability (HRV) provides a noninvasive method to obtain reliable and reproducible information on autonomic modulation of heart rate, but there is a difficulty in using HRV as a quantitative estimate of autonomic dysfunction in heart failure. This study was aimed at testing the hypothesis that abnormal modulation of heart rate assessed by power spectrum analysis may be present also in asymptomatic patients with left ventricular dysfunction and progress in patients with overt symptoms of congestive heart failure. HRV was measured in three groups of subjects: Group 1: 30 patients with chronic heart failure; Group 2: 21 patients with asymptomatic left ventricular dysfunction; and Group 3: 25 healthy volunteers as control group. HRV was evaluated by autoregressive spectral analysis with 600-beat ECG samples, while subjects were quietly recumbent (BSI), in conditions of controlled breathing (15 acts/min) (RSC) and passive orthostatism after tilting (80 degrees) (TLT). Patients in group 1 showed a reduction in the standard deviation of the R-R intervals (SDRR) (p<0.0003) and in the low frequency component (LF) (p<0.0001) compared to normal subjects. Low frequency component was not detectable in 11 patients of group I (p<0.0008). On RSC and TLT, group 1 failed to show any modification in the low frequency and high frequency components (HF) under any stimulation. Group 2 showed no modification at baseline evaluation, no increase in the high frequency component on RSC and in LF during TLT compared to controls (p<0.01 and p<0.0001 respectively). At baseline, group 1 had a lower SDRR (p<0.03) and LF (p<0.0001) vs. group 2, whereas during stimulation the two groups exhibited the same behaviour. In conclusion, reduced heart rate variability is specific for both asymptomatic and symptomatic post-ischemic left ventricular dysfunction. Our results suggest that frequency domain analysis of heart rate variability during a stimulation test allows a more accurate definition of the degree of autonomic control of heart rate.

Autonomic Nervous System↗
PubMed1998

Impaired baroreflex sensitivity and sympathovagal balance in syndrome X.

Alterations of autonomic nervous control of cardiac function have been described in syndrome X. The characteristics, however, of the autonomic control of the cardiovascular system in patients with syndrome X have not been adequately studied; thus, the aim of the present study was to investigate the role of baroreceptor sensitivity and sympathovagal balance in syndrome X. The study group included 12 patients with syndrome X, 12 age- and sex-matched control patients with coronary artery disease, and 12 age- and sex-matched controls with no evidence of heart disease. Baroreceptor sensitivity was evaluated by calculating the regression line relating phenylephrine-induced increases in systolic blood pressure to the attendant changes in the RR interval. Sympathovagal balance was assessed by using heart rate variability in the time and frequency domain and measuring plasma norepinephrine at rest and during incremental bicycle exercise. Baroreceptor sensitivity was significantly reduced in syndrome X compared with that in control normal subjects (7.4 +/- 1.2 vs 16.8 +/- 2.3 ms/mm Hg; p < 0.02). This was associated with a significantly lower percentage of adjacent normal RR intervals that differ by >50 ms, lower root-mean-square of the difference of adjacent RR intervals, and lower logarithmic value of the high-frequency component in patients with syndrome X compared with normal subjects. A nonsignificant trend toward lower baroreceptor sensitivity was found in patients with syndrome X compared with control ischemic patients (7.4 +/- 2 vs 12.2 +/- 1.3 ms/mm Hg). A nonsignificant trend toward a higher value of the low- to high-frequency ratio was also observed in patients with syndrome X than in both control groups. No difference was detected in norepinephrine levels either at rest or during exercise or in the exercise-induced norepinephrine increase between the 3 groups. No difference was also observed between ischemic patients and normal subjects in either baroreceptor sensitivity or heart rate variability measurements. A significant correlation (r = 0.80, p < 0.01) was found between baroreceptor sensitivity and the high-frequency component in normal controls but not for other measurements of autonomic function in the 3 groups. In conclusion, patients with syndrome X have an altered autonomic control of the cardiovascular system characterized by impaired baroreceptor sensitivity and reduced heart rate variability. Abnormal autonomic regulation of the cardiovascular system may be of pathophysiologic importance in syndrome X.

Baroreflex↗
PubMed1998

Overview and meta-analysis of randomised trials of amiodarone in chronic heart failure.

Unlike other antiarrhythmic class I drugs, amiodarone showed in preliminary studies, benefits also in patients with left ventricular dysfunction. These positive results have induced the development of large randomised controlled studies: their results are reviewed and the controversial points are discussed. In a meta-analysis of randomised controlled trials the use of amiodarone in heart failure was associated with an approximate 20 to 25% reduction in deaths. However, amiodarone was also associated with a 120 to 124% increase in side effects.

Amiodarone↗