Desmosterol accumulation in users of amiodarone.

BACKGROUND: Amiodarone is an effective and widely used antiarrhythmic drug with many possible adverse effects including hypercholesterolaemia and hepatotoxicity. OBJECTIVE: Our aim was to evaluate how long-term amiodarone treatment affects cholesterol metabolism. METHODS: The study population consisted of 56 cardiac patients, of whom 20 were on amiodarone (amiodarone + group) and 36 did not use the drug (amiodarone - group). We also studied a control group of 124 individuals selected randomly from the population. Cholesterol metabolism was evaluated by analysis of serum noncholesterol sterols by gas-liquid chromatography and gas chromatography-mass spectrometry. RESULTS: Comparisons of serum lipids and noncholesterol sterols across the three groups showed increased serum triglyceride in users of amiodarone but no statistically significant group differences in total, LDL or HDL cholesterol or serum proprotein convertase subtilisin/kexin type 9 concentrations. Nor did the groups differ in the ratios of cholestanol or plant sterols to cholesterol in serum, suggesting that cholesterol absorption was unaltered. However, all users of amiodarone had very markedly elevated serum desmosterol concentrations: the desmosterol-to-cholesterol ratio (102 × µmol mmol-1 ) averaged 1030.7 ± 115.7 (mean ± SE) in the amiodarone + group versus 82.7 ± 3.4 and 75.9 ± 1.4 in the amiodarone - and the population control groups (P < 0.001), respectively. CONCLUSION: Use of amiodarone was associated with on average 12-fold serum desmosterol concentrations compared with the control groups. This observation is fully novel and suggests that amiodarone interferes with the conversion of desmosterol to cholesterol in the cholesterol synthesis pathway. Whether accumulation of desmosterol plays a role in amiodarone-induced hepatotoxicity deserves to be studied in the future.

Diagnosing isolated cardiac sarcoidosis.

OBJECTIVES: Cardiac sarcoidosis (CS) without clinically apparent extracardiac disease may escape detection because of the poor sensitivity of endomyocardial biopsy (EMB). We set out to analyse our experience of repeated and imaging-guided biopsies in clinically isolated CS. METHODS: We retrospectively reviewed the medical records, laboratory test results, imaging studies and pathological analyses of 74 patients with either histologically proven or clinically probable CS at our institution between January 2000 and December 2010. RESULTS: Fifty-two patients had histologically proven CS, of whom 33 (26 women) had disease that was clinically isolated to the heart. Sarcoidosis was detected in the first EMB in 10 of the 31 patients who underwent biopsy. CS was found by repeated EMBs, targeted by cardiac imaging, in seven additional patients, and 11 patients were diagnosed by sampling 18-F-fluorodeoxyglucose position emission tomography-positive mediastinal lymph nodes at mediastinoscopy. Together, the first biopsy (cardiac or mediastinal lymph node) provided the diagnosis in 34%, the second biopsy in 31% and the third in 22% of biopsied patients with isolated CS. Four (13%) of the remaining diagnosis were made after cardiac transplantation and one in a patient who did not undergo biopsy) at autopsy after sudden cardiac death. CONCLUSIONS: Cardiac sarcoidosis may present without clinically apparent disease in other organs. At least two-thirds of patients remain undiagnosed after a single EMB session. The detection rate can be improved by repeated and imaging-guided cardiac or mediastinal lymph-node biopsies. Nevertheless, false-negative biopsy results remain a problem in CS patients with no apparent extracardiac disease.

Duration of the haemodynamic action of a 24-h infusion of levosimendan in patients with congestive heart failure.

AIMS: To determine the duration of haemodynamic and neurohormonal action of a 24-h infusion of levosimendan in heart failure. METHODS AND RESULTS: This was a double-blind, parallel group study in patients with New York Heart Association class II to IV heart failure. Twenty-two patients, with left ventricular ejection fraction <35% and pulmonary capillary wedge pressure (PCWP) above 12 mmHg, were randomised to receive either levosimendan (12 microg/kg followed by a continuous infusion of 0.1-0.2 microg/min) or placebo. Invasively measured cardiac output (CO) increased from 4.3 l/min to 5.4 l/min in the levosimendan group at 6 h. PCWP decreased from 20 mmHg to 15 mmHg in response to levosimendan. Echocardiographically measured maximal effect on PCWP occurred after 6 h, whereas CO reached its highest value at 24 h. The estimated duration of the decrease in PCWP was 7-9 days, and in CO was 12-13 days. Plasma NT-proANP and NT-proBNP levels reached their lowest values at days 3 and 2, and the treatment effect was estimated to last 16 and 12 days, respectively. The long-acting haemodynamic responses reflect levels of the active metabolites OR-1896 and OR-1855, maximal metabolite levels occurred at day 3. CONCLUSIONS: Levosimendan infusion achieved a rapid improvement in haemodynamic parameters in patients with congestive heart failure with maximal effects occurring 1-3 days after starting the infusion, effects were sustained for up to at least a week.

Joint effects of an aldosterone synthase (CYP11B2) gene polymorphism and classic risk factors on risk of myocardial infarction.

BACKGROUND: The -344C allele of a 2-allele (C or T) polymorphism in the promoter of the gene encoding aldosterone synthase (CYP11B2) is associated with increased left ventricular size and mass and with decreased baroreflex sensitivity, known risk factors for morbidity and mortality associated with myocardial infarction (MI). We hypothesized that this polymorphism was a risk factor for MI. METHODS AND RESULTS: We used a nested case-control design to investigate the relationships between this polymorphism and the risk of nonfatal MI in 141 cases and 270 matched controls from the Helsinki Heart Study, a coronary primary prevention trial in dyslipidemic, middle-aged men. There was a nonsignificant trend of increasing risk of MI with number of copies of the -344C allele. However, this allele was associated in a gene dosage-dependent manner with markedly increased MI risk conferred by classic risk factors. Whereas smoking conferred a relative risk of MI of 2.50 (P=0.0001) compared with nonsmokers in the entire study population, the relative risk increased to 4.67 in -344CC homozygous smokers (relative to nonsmokers with the same genotype, P=0.003) and decreased to 1.09 in -344TT homozygotes relative to nonsmokers with this genotype. Similar joint effects were noted with genotype and decreased HDL cholesterol level as combined risk factors. CONCLUSIONS: Smoking and dyslipidemia are more potent risk factors for nonfatal MI in males who have the -344C allele of CYP11B2.

Prevalence of aortic valve abnormalities in the elderly: an echocardiographic study of a random population sample.

OBJECTIVES: This study was undertaken to elucidate the prevalence of aortic valve abnormalities in the elderly. BACKGROUND: The age of persons treated actively for valve disorders is increasing. More information is needed about the prevalence of aortic valve disease in old age. METHODS: Randomly selected men and women in the age groups 75 to 76, 80 to 81 and 85 to 86 years (n = 501) participating in the Helsinki Ageing Study were studied with imaging and Doppler echocardiography. Additionally, 76 persons 55 to 71 years of age were included. The systolic aortic valve area was calculated by the continuity equation. The velocity ratio (peak velocity in the left ventricular outflow tract/peak velocity across the aortic valve) was a supplementary criterion for aortic stenosis. Valve regurgitation and cusp calcification were assessed visually. RESULTS: Evaluation of the aortic valve was possible in 552 persons (96%). Mild calcification was found in 222 (40%) and severe calcification in 72 (13%). Two persons (0.4%) had an aortic valve prosthesis. Critical native valve stenosis (calculated aortic valve area < or = 0.8 cm2 and velocity ratio < or = 0.35) was found in 12 persons (2.2%). Six of these were symptomatic and potentially eligible for valvular surgery. All persons with aortic valve stenosis were in the three oldest age groups. The prevalence of critical aortic valve stenosis was 2.9% (95% confidence interval 1.4% to 5.1%) in the group 75 to 86 years of age. Aortic regurgitation, mostly mild, was found in 29% of the entire study cohort. CONCLUSIONS: Calcific aortic valve stenosis constitutes a significant health problem in the elderly. Only a minority of those with potentially operable aortic valve stenosis undergo surgery.

Blood ketone bodies in congestive heart failure.

OBJECTIVES: The present study was designed to assess whether blood ketone bodies are elevated in congestive heart failure (CHF) and whether ketonemia is related to the hemodynamic and neurohumoral abnormalities of CHF. BACKGROUND: In CHF, consumption of the body's fat stores may become abnormally high, contributing to the development of cardiac cachexia. Increased mobilization of free fatty acids could, in theory, augment ketogenesis, but whether patients with CHF are prone to ketosis remains unknown. METHODS: Forty-five patients with chronic CHF (mean age [+/- SD] 57 +/- 13 years) and 14 control subjects free of CHF (mean age 53 +/- 13 years) underwent invasive and noninvasive cardiac studies and determination of blood ketone bodies (acetoacetate plus beta-hydroxybutyrate), circulating free fatty acids, glucose, lactate, insulin, glucagon, growth hormone, cortisol, norepinephrine, N-terminal proatrial natriuretic peptide, tumor necrosis factor-alpha and interleukin-6 after an overnight fast. RESULTS: Patients with CHF had elevated blood ketone bodies (median 267 mumol/liter, range 44 to 952) compared with control subjects (median 150 mumol/liter, range 31 to 299, p < 0.05). In the total study group, blood ketone bodies were related to pulmonary artery wedge pressure (r5 = 0.45, p < 0.001), left ventricular ejection fraction (r3 = -0.37, p < 0.01), right atrial pressure (r3 = 0.36, p < 0.01) and circulating concentrations of free fatty acids (r5 = 0.52, p < 0.001), glucose (r5 = -0.39, p < 0.001), norepinephrine (r3 = 0.45, p < 0.001), growth hormone (r5 = 0.30, p < 0.05) and interleukin-6 (r3 = 0.27, p < 0.05). In multivariate analysis, left ventricular ejection fraction, serum free fatty acids and serum glucose were independent predictors of ketonemia. CONCLUSIONS: Blood ketone bodies are elevated in CHF in proportion to the severity of cardiac dysfunction and neurohormonal activation. This may be at least partly attributable to increased free fatty acid mobilization in response to augmented neurohormonal stimulation. Additional studies are needed to identify the detailed mechanisms and clinical implications of CHF ketosis.

Baroreflex sensitivity and variants of the renin angiotensin system genes.

OBJECTIVES: Because the renin-angiotensin-aldosterone system (RAS) modifies cardiovascular autonomic regulation, we studied the possible associations between baroreflex sensitivity (BRS) and polymorphism in the RAS genes. BACKGROUND: Wide intersubject variability in BRS is not well explained by cardiovascular risk factors or life style, suggesting a genetic component responsible for the variation of BRS. METHODS: Baroreflex sensitivity as measured from the overshoot phase of the Valsalva maneuver and genetic polymorphisms were examined in a random sample of 161 women and 154 men aged 41 to 61 years and then in an independent random cohort of 29 men and 37 women aged 36 to 37 years. An insertion/deletion (I/D) polymorphism of angiotensin-converting enzyme (ACE), M235T variants of angiotensinogen (AGT) and two diallelic polymorphisms in the gene encoding aldosterone synthase (CYP11B2), one in the promoter (-344C/T) and the other in the second intron, were identified by polymerase chain reaction. RESULTS: In the older population, BRS differed significantly across CYP11B2 genotype groups in women (10.1 +/- 4.5, 8.7 +/- 3.8 and 7.1 +/- 3.2 ms x mm Hg(-1) in genotypes -344TT, CT and CC, respectively, p = 0.003 and 11.1 +/- 4.4, 8.9 +/- 4.1 and 7.5 +/- 3.4 ms x mm Hg(-1) in intron 2 genotypes 1/1, 1/2 and 2/2, respectively, p = 0.002), but not in men. No comparable associations were found for BRS with the I/D polymorphism of ACE or the M235T variant of AGT. In the younger population, BRS was even more strongly related to the CYP11B2 promoter genotype (p = 0.0003). The association was statistically significant both in men (p = 0.015) and in women (p = 0.03). CONCLUSIONS: Common genetic polymorphisms in the aldosterone synthase (CYP11B2) gene is associated with interindividual variation in BRS.

Reproducibility of the systolic time intervals: effect of the temporal range of measurements.

The aim of this study was to evaluate the reproducibility of conventionally measured systolic time intervals. To that end, three to eight serial measurements were performed on four different groups of healthy subjects (total number, 49) within dissimilar time periods: 1) within 3 h; 2) within 24 h; 3) within 1 to 2 weeks; and 4) within 14 to 18 months. Judged as the mean coefficients of variation, the variability of the systolic time intervals tended to be smallest in the 3 h measurements and largest in the 24 h measurements. The pooled variances of the serial measurements made within 24 h were in general significantly larger than the respective variances in the measurements made within 3 h. This was due to statistically significant diurnal decreases in left ventricular ejection time and total electromechanic systole in the 24 h study. Otherwise the reproducibility of the method was high. For instance, the mean coefficients of variation for ejection time and total electromechanic systole corrected for heart rate were only 1% and 1.2%, respectively, in serial measurements made at identical diurnal time points within 14 to 18 months. The pooled variances of the measurements made within the shortest and longest temporal ranges were not statistically different. It is concluded that measurement of the systolic time intervals is very applicable to intervention and follow-up studies provided the normal circadian rhythmicity of the phases of systole is adequately taken into account in the design of the study.

Aortic valve closure and cardiac vibrations in the genesis of the second heart sound.

Simultaneous M-mode echocardiograms and external phonocardiograms were recorded in 15 healthy subjects to evaluate the genesis of the second heart sound. The onset of the second sound was found synchronous with the coaptation of the aortic valve cusps and a sharp vibration on the aortic wall. The closed valve was oscillating for 30 to 45 ms after the coaptation of the cusps. Magnified echocardiographic studies of the interventricular septum revealed a consistent, momentary quiver across the septal myocardium a mean of 4 ms after the onset of the second sound. In most subjects, a transient myocardial vibration was observed in temporal association with the first heart sound as well. The present observations suggest that the aortic valve closure initiates the production of the second heart sound, the main audible component resulting, however, from vibrations in the cardiac structures after the valve closure.

Systolic flow velocity profile in the left ventricular outflow tract in persons free of heart disease.

It is a common but unsubstantiated belief that blood flows through the left ventricular outflow tract (LVOT) with a spatially uniform velocity. Doppler echocardiography was performed to study in an apically obtained view of the LVOT the profile of subaortic velocities in 79 subjects free of clinical heart disease. The systolic velocities and time intervals were determined in the medial and lateral margins and the center of the LVOT. Peak systolic velocity measured 98 +/- 16 cm/s (mean +/- SD) in the medial margin of the LVOT close to the subaortic ventricular septum, 89 +/- 14 cm/s in the midline of the LVOT, and 79 +/- 14 cm/s in the lateral margin of the LVOT close to the base of the mitral valve (p < 0.001). The respective means of the velocity-time integrals were 19 +/- 3, 17 +/- 3 and 14 +/- 3 cm (p < 0.001). Systolic time intervals determined from the flow signals differed also statistically significantly across the recording sites in the LVOT. The velocity measurements obtained in the center of the LVOT were nearly identical with the values averaged over all measurements across the LVOT. It is concluded that the systolic flow velocity profile in the LVOT is not flat, as has been assumed, but skewed toward faster flow along the subaortic ventricular septum. Measurements made in the center of the LVOT can be used as surrogate for the spatial average velocities.

Time of onset of supraventricular tachyarrhythmia in relation to alcohol consumption.

It is widely believed but has never been proved that idiopathic supraventricular tachyarrhythmias beginning during or after weekends or winter holidays are frequently alcohol-related ("holiday heart" syndrome). The time of arrhythmia onset was therefore studied in relation to self-reported ethanol consumption and results of a screening test for alcoholism (CAGE questionnaire) in 289 patients aged less than 65 years admitted for supraventricular tachyarrhythmias. There were 102 patients having an etiologically idiopathic arrhythmia with a known time of onset. Among them, but not among those with disease-related arrhythmias, patients with arrhythmic episodes beginning on Saturdays or on Sundays were more often chronic alcohol abusers (9 of 19, 47%) than either patients with episodes beginning from Mondays through Fridays (18 of 83, 22%; p = 0.040) or control subjects from the out-of-hospital population (8 of 66, 12%; p = 0.002). In multivariate analysis, the time of arrhythmia onset was related to the CAGE response (G2 = 6.0, p = 0.014) but not to the most recent ethanol use. However, the increased frequency of problem drinkers among patients with weekend-onset idiopathic arrhythmias was only relative, and resulted from a decreased number of abstainers and non-problem drinkers. No conspicuous clustering of alcohol-related arrhythmias was seen after New Year's or May Day. Thus, although the present study confirms an association between heavy drinking and idiopathic arrhythmias beginning during weekends, it shows that the question may be of a relative rather than an absolute overrepresentation. The term holiday heart may also be somewhat misleading since no postholiday accumulation of alcohol-related arrhythmias was found.

Relation of left ventricular function to habitual alcohol consumption.

Left ventricular (LV) dysfunction is a frequent finding in chronic alcoholic subjects. LV function's relation to alcohol use in the general population, where low and moderate consumption predominate, was studied in this work. A random sample of 120 people born in 1954 was invited to participate in the study, and 93 (42 men and 51 women) enrolled. Ethanol use was studied by 2-month daily recording of all alcoholic drinks; smoking and physical activity were quantified likewise, and salt intake by 7-day food records. Subsequently, subjects underwent an LV examination by M-mode echocardiography, and a transmitral flow velocity study by pulsed Doppler ultrasound. The relations of LV measurements to alcohol use were studied by multiple linear regression adjusting for sex, body size, blood pressure, heart rate, smoking, physical activity and dietary salt intake. No subject had clinical heart disease. The average daily ethanol consumption ranged from 0 to 1.2 g/kg of body weight (median 0.2). Statistically significant associations with square-root daily ethanol use were found for LV end-systolic diameter (regression coefficient [b] +/- SE 4.0 +/- 1.5 mm/square root of g/kg; p < 0.01), fractional shortening (b = -3.9 +/- 1.8%/square root of g/kg; p < 0.05), peak early transmitral velocity (b = -8.9 +/- 3.5 cm/s/square root of g/kg; p < 0.05), and peak atrial transmitral velocity (b = -4.9 +/- 1.9 cm/s/square root of g/kg; p < 0.05). No interactions with sex were observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Comparison of the cardiotoxicity of ethanol in women versus men.

Subclinical left ventricular (LV) dysfunction is a common occurrence in alcoholic men but has been claimed to be absent or very rare in alcoholic women. M-mode echocardiography was performed to study LV size, mass and systolic function, and Doppler ultrasound to study LV filling in 14 chronic female alcoholics aged 24 to 48 years and in 2 age-matched control groups consisting of 17 healthy women and 22 alcoholic men. Compared with healthy women, female alcoholics had no differences in heart rate or blood pressure but a shorter LV end-diastolic diameter (mean +/- standard deviation, 46 +/- 4 vs 48 +/- 3 mm, p less than 0.05), lower fractional shortening (31 +/- 6 vs 34 +/- 3%, p less than 0.05), increased wall thickness to radius ratio (0.43 +/- 0.08 vs 0.37 +/- 0.05, p less than 0.05), reduced peak early diastolic transmitral velocity (45 +/- 11 vs 68 +/- 7 cm/s, p less than 0.001), reduced deceleration of the early diastolic velocity (-274 +/- 69 vs -572 +/- 107 cm/s2, p less than 0.001), and an increased atrial filling fraction (35 +/- 12 vs 27 +/- 5%, p less than 0.05). Although alcoholic men had a longer duration of heavy drinking than alcoholic women (median 19 vs 5 years, p less than 0.001), and a higher systolic blood pressure (140 +/- 17 vs 120 +/- 17 mm Hg, p less than 0.001), there were no statistically significant differences between the sexes either in LV diameters, wall thickness or mass normalized to body area, or in indexes of systolic or diastolic LV function.(ABSTRACT TRUNCATED AT 250 WORDS)

Role of alcohol in recurrences of atrial fibrillation in persons less than 65 years of age.

The role of alcohol in recurrences of atrial fibrillation (AF) was assessed in a consecutive series of 98 patients (75 men) aged less than 65 years. In addition to etiologic assessment using clinical and laboratory methods and echocardiography, the patients' drinking habits were evaluated by recording the amount of alcohol used during the week preceding AF, by responses to the CAGE (Cut, Annoying, Guilt, Eye; see below) questionnaire (a screening test for alcohol abuse) and by selected laboratory tests. Two groups of control subjects were studied: 98 sex- and age-matched patients admitted to the emergency ward for acute illnesses, and 50 subjects selected randomly from the local out-of-hospital population. The mean alcohol consumption among men during the study week was 186 g (median 45 g; range 0 to 2,100 g) among patients, whereas among male hospital and population control subjects it was 86 g (30 g; 0 to 1,050 g) and 94 g (35 g; 0 to 630 g), respectively. When the weekly alcohol consumption was analyzed in 3 categories (0; 1 to 210 g; greater than 210 g), there was a significant difference between AF cases and hospital control patients (p = 0.03), but not between AF cases and population control subjects. Multivariate analysis of data of AF cases and population control subjects showed that alcohol intake and a positive response to 1 or more of the CAGE questions were independently related to AF in men. Other independent risk factors were the presence of heart disease, low serum potassium and lack of sleep or experience of excess psychologic stress, or both.(ABSTRACT TRUNCATED AT 250 WORDS)

Left ventricular size, mass and function in relation to the duration and quantity of heavy drinking in alcoholics.

Left ventricular (LV) hypertrophy and mild dysfunction are frequently observed in alcoholics but little is known about how they relate to the duration and severity of alcohol abuse. LV size, mass and function were studied using echocardiography and systolic time intervals in 78 middle-aged male alcoholics who also gave detailed accounts of the duration of heavy drinking, the quantity of recent ethanol consumption and the duration of abstinence. Compared with 34 healthy nonalcoholics, alcoholics had a higher LV mass index (85 +/- 2 [mean +/- standard error] vs 77 +/- 2 g/m2, p = 0.001), a thicker posterior wall (11 +/- 0.2 vs 10 +/- 0.2 mm, p = 0.02), a longer end-systolic diameter index (18 +/- 0.3 vs 17 +/- 0.3 mm/m2, p = 0.02), and a higher preejection period/ejection time ratio (0.36 +/- 0.01 vs 0.33 +/- 0.01, p = 0.002). In multivariate linear regression models, these abnormalities proved independent of the drinking history, except that posterior wall thickness was weakly related to the duration of heavy drinking (standardized correlation coefficient 0.36, p = 0.01). Univariate analyses suggested that the LV mass index and systolic time interval ratio had, if anything, a curvilinear relation to the total duration of heavy alcohol consumption. It is concluded that the LV hypertrophy and dysfunction found in alcoholics are poorly related to the duration and severity of self-reported alcohol abuse. Together with other data, this suggests that there is no simple linear dose-injury relation in the long-term cardiotoxicity of ethanol. Factors modifying the myocardial effects of ethanol need to be studies more in the future.

Echocardiographic evidence of left ventricular hypertrophy in a general aged population.

The purpose of this study was to measure the frequency of left ventricular (LV) hypertrophy in old age. Random subjects born in 1904, 1909, and 1914 (n = 501), and 76 born in 1920 to 1935 were studied. All subjects underwent clinical and echocardiographic investigation. An electrocardiogram was obtained in 449 subjects. Complete data for calculation of LV mass corrected for body size were available in 422 of the studied subjects (73%). LV hypertrophy was defined as calculated LV mass exceeding either an internal standard of the Helsinki Aging Study, earlier published limits from the Framingham Heart Study, or criteria from Devereux et al. LV wall thickness and mass were positively related to age. Hypertrophy was present in both sexes, the rate even exceeding 70% in the oldest cohort aged 85 to 86 years using the Framingham and Devereux limits. LV hypertrophy (LV mass exceeding defined limits after correction for body height) was significantly and independently related to age, systolic blood pressure, body mass index, and mitral regurgitation. A sustained apex beat, third heart sound, and electrocardiographic changes were significantly more frequent in the group with echocardiographic hypertrophy, although with considerable overlapping. The fourth heart sound was unrelated to hypertrophy. Use of age-independent criteria result in an extremely high prevalence of LV hypertrophy in old age. This is partly due to age-related diseases increasing LV mass, but also partly to an independent effect of age. The usefulness of clinical signs for detecting LV hypertrophy is limited in old age.

Free fatty acid kinetics and oxidation in congestive heart failure.

To characterize fuel utilization of patients with congestive heart failure (CHF), we measured serum free fatty acid (FFA), counterregulatory hormone concentrations, whole body substrate oxidation rates (indirect calorimetry), and the turnover and oxidation rates of FFA ([1-(14)C]-palmitate infusion) in 7 patients with CHF and in 7 cardiac patients without CHF after an overnight fast. Plasma glucose and serum insulin concentrations were comparable, whereas serum FFA, blood ketone body, and fasting blood lactate (p <0.05 for all) concentrations were significantly increased in patients with CHF compared to those without CHF. Fasting plasma norepinephrine (p <0.05), serum cortisol (p <0.01), and growth hormone (p <0.01) concentrations were also higher in patients with CHF than in those without CHF. Rates of energy expenditure at rest (62 +/- 2 vs 56 +/- 1 J x kg(-1) x min(-1), p <0.05), FFA turnover (6.5 +/- 0.5 vs 5.0 +/- 0.4 micromol x kg(-1) x min(-1), p <0.05), and oxidation (2.0 +/- 0.2 vs 1.5 +/- 0.1 micromol x kg(-1) x min(-1)], p <0.05) were significantly higher in patients with CHF than in control subjects. In univariate analysis, the left ventricular ejection fraction was inversely correlated and the plasma norepinephrine concentration positively correlated with both energy expenditure at rest, FFA turnover, and the FFA oxidation rate. In multivariate analysis, the plasma norepinephrine concentration was the most significant predictor of increased FFA oxidation rate. We conclude that release of FFAs to the circulation and their subsequent oxidation are increased in patients with severe CHF after an overnight fast. These changes might reflect stress hormone-induced lipolysis and accompanying stimulation of serum FFA oxidation via mass action.

Left ventricular filling impairment in asymptomatic chronic alcoholics.

Systolic left ventricular dysfunction is relatively common in even asymptomatic alcoholics, but whether diastolic function is also altered is much less well-studied. We used M-mode and Doppler echocardiography to study left ventricular size, mass, systolic function and diastolic filling in 32 alcoholics free of clinically detectable heart disease and in 15 healthy control subjects. Left ventricular mass index and posterior wall thickness were higher in alcoholics than in controls, but there was no statistically significant difference either in end-diastolic size or in systolic ventricular function. More abnormalities were found in the Doppler indexes of diastolic function, however. The alcoholics had a prolonged relaxation time (200 +/- 6 vs 184 +/- 5 ms [mean +/- standard error], p less than 0.05), a decreased peak early diastolic velocity (52 +/- 2 vs 60 +/- 3 cm/s, p less than 0.05), a slower acceleration of the early flow (410 +/- 18 vs 552 +/- 43 cm/s2, p less than 0.01), and a higher atrial-to-early peak velocity ratio (0.74 +/- 0.04 vs 0.60 +/- 0.05, p less than 0.05). This pattern of changes suggests a primary abnormality in the relaxation of the left ventricle. In multivariate analyses, the abnormalities in the Doppler indexes were independent of the duration of alcoholism, the quantity of the most recent ethanol exposure and the increased mass of the left ventricle. Impaired early filling of the left ventricle due to delayed relaxation is common in asymptomatic alcoholics and may in fact be the earliest functional sign of preclinical alcoholic cardiomyopathy.

Breath acetone in congestive heart failure.

To summarize, CHF predisposes to postabsorptive ketosis in relation to the severity of venous congestion. A simple and fully noninvasive measurement of breath acetone may add to the diagnostic assessment of patients with CHF.