Search PubMed⌕ Search

Biomedical subjects

S D Anker

Publications and source records attributed to S D Anker.

At least 91 records · Page 5Linked to original sources
PubMed1997

Augmented peripheral chemosensitivity as a potential input to baroreflex impairment and autonomic imbalance in chronic heart failure.

BACKGROUND: The precise mechanisms responsible for the sympathetic overactivity and blunted baroreflex control in chronic heart failure (CHF) remain obscure. Augmented peripheral chemosensitivity has recently been demonstrated in CHF. We evaluated the relation between peripheral chemoreflex sensitivity and autonomic activity in patients with CHF. METHODS AND RESULTS: We studied in 26 stable patients with CHF the peripheral chemosensitivity (ventilatory response to hypoxia using transient inhalations of pure nitrogen), autonomic balance (spectral analysis of heart rate variability [HRV]), and baroreflex sensitivity (bolus phenylephrine method and alpha index). To determine whether transient inactivation of peripheral chemoreceptors might influence autonomic balance, 12 patients underwent a second study during which they breathed 100% O2. Peripheral chemosensitivity correlated inversely with HRV power within the low-frequency band (0.04 to 0.15 Hz) (r=-.52, P=.006) and inversely with baroreflex sensitivity (r=-.60, P=.005). When the patients were divided into two groups according to the chemosensitivity of age-matched normal controls (above and below mean+2 SDs of chemosensitivity of control subjects), those above the normal range revealed more impaired autonomic balance, ie, lower baroreflex sensitivity (1.4 +/- 1.3 versus 5.0 +/- 1.5 ms/mm Hg, P<.0001) and depressed values of low-frequency power (2.5 +/- 1.8 versus 4.1 +/- 0.8 ln ms2, P<.005) compared with those with normal chemosensitivity. Transient hyperoxia did not alter heart rate or systolic pressure but resulted in an increase in HRV and an improvement in baroreflex sensitivity. CONCLUSIONS: A link between increased peripheral chemosensitivity and impaired autonomic control, including baroreflex inhibition, is demonstrated. The clinical importance of this phenomenon warrants further investigation.

Aged↗
PubMed1997

Hormonal changes and catabolic/anabolic imbalance in chronic heart failure and their importance for cardiac cachexia.

BACKGROUND: The role of hormonal and cytokine abnormalities in the development of cardiac cachexia remains obscure. METHODS AND RESULTS: Healthy control subjects (n=16) and patients with chronic heart failure (CHF), classified clinically as cachectic (8% to 35% weight loss over > or = 6 months before study, n=16) or noncachectic (n=37), were assessed for markers of disease severity (maximal oxygen consumption, left ventricular ejection fraction, NYHA functional class). These markers were compared with plasma concentrations of potentially important anabolic and catabolic factors. The degree of neurohormonal activation and catabolic/anabolic imbalance was closely related to wasting but not to conventional measures of the severity of heart failure. Compared with control subjects and noncachectic patients, cachectic patients had reduced plasma sodium and increased norepinephrine, epinephrine (all P<.0001), cortisol, tumor necrosis factor (TNF)-alpha (both P<.002), and human growth hormone (P<.05). Insulin-like growth factor-1, testosterone, and estrogen were similar in all groups. Insulin was increased only in the noncachectic patients (P<.005 versus control subjects). Dehydroepiandrosterone was reduced in the cachectic patients (P<.02 versus control subjects). Insulin, cortisol, TNF-alpha, and norepinephrine correlated independently with wasting in CHF (P<.05; multiple regression of these four factors versus percent ideal weight, R2=.50, P<.0001). CONCLUSIONS: Cachexia is more closely associated with hormonal changes in CHF than conventional measures of the severity of CHF. This study suggests that the syndrome of heart failure progresses to cardiac cachexia if the normal metabolic balance between catabolism and anabolism is altered.

Aged↗
PubMed1997

Depressed heart rate variability as an independent predictor of death in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

After acute myocardial infarction, depressed heart rate variability (HRV) has been proven to be a powerful independent predictor of a poor outcome. Although patients with chronic congestive heart failure (CHF) have also markedly impaired HRV, the prognostic value of HRV analysis in these patients remains unknown. The aim of this study was to investigate whether HRV parameters could predict survival in 102 consecutive patients with moderate to severe CHF (90 men, mean age 58 years, New York Heart Association [NYHA] class II to IV, CHF due to idiopathic dilated cardiomyopathy in 24 patients and ischemic heart disease in 78 patients, ejection fraction [EF], 26%; peak oxygen consumption, 16.9 ml/kg/min) after exclusion of patients in atrial fibrilation with diabetes or with chronic renal failure. In the prognostic analysis (Cox proportional-hazards model, Kaplan-Meier survival analysis), the following factors were investigated: age, CHF etiology, NYHA class, EF, peak oxygen consumption, presence of ventricular tachycardia on Holter monitoring, and HRV measures derived from 24-hour electrocardiography monitoring, calculated in the time (standard deviation of all normal RR intervals [SDNN], standard deviation of 5-minute RR intervals [SDANN], mean of all 5-minute standard deviations of RR intervals [SD], root-mean-square of difference of successive RR intervals [rMSSD], and percentage of adjacent RR intervals >50 ms different [pNN50]) and frequency domain (total power [TP], power within low-frequency band [LF], and power within high-frequency band [HF]). During follow-up of 584 +/- 405 days (365 days in all who survived), 19 patients (19%) died (mean time to death: 307 +/- 315 days, range 3 to 989). Cox's univariate analysis identified the following factors to be predictors of death: NYHA (p = 0.003), peak oxygen consumption (p = 0.01), EF (p = 0.02), ventricular tachycardia on Holter monitoring (p = 0.05), and among HRV measures: SDNN (p = 0.004), SDANN (p = 0.003), SD (p = 0.02), and LF (p = 0.003). In multivariate analysis, HRV parameters (SDNN, SDANN, LF) were found to predict survival independently of NYHA functional class, EF, peak oxygen consumption, and ventricular tachycardia on Holter monitoring. The Kaplan-Meier survival curves revealed SDNN < 100 ms to be a useful risk factor; 1-year survival in patients with SDNN < 100 ms was 78% when compared with 95% in those with SDNN > 100 ms (p = 0.008). The coexistence of SDNN < 100 ms and a peak oxygen consumption < 14 ml/kg/min allowed identification of a group of 18 patients with a particularly poor prognosis (1-year survival 63% vs 94% in the remaining patients, p <0.001). We conclude that depressed HRV on 24-hour ambulatory electrocardiography monitoring is an independent risk factor for a poor prognosis in patients with CHF. Whether analysis of HRV could be recommended in the risk stratification for better management of patients with CHF needs further investigation.

Aged↗
PubMed1997

Elevated soluble CD14 receptors and altered cytokines in chronic heart failure.

We hypothesized that in patients with chronic heart failure mesenteric venous congestion leads to increased bowel permeability, bacterial translocation, and thereby endotoxin release; the increased endotoxin challenge then causes immune activation with increased soluble CD14 levels and tumor necrosis factor (TNF)-alpha production. Patients with high soluble CD14 levels (indicative of endotoxin-cell interaction) have markedly increased plasma levels of TNF-alpha, soluble TNF receptors 1 and 2, and intracellular adhesion molecule-1, supporting this hypothesis.

Cardiac Output, Low↗
PubMed1997

Wasting as independent risk factor for mortality in chronic heart failure.

BACKGROUND: Wasting in chronic heart failure (CHF) has long been known but is little investigated. We sought to find out whether the cachectic state in CHF provides additional prognostic information about all-cause mortality. METHODS: Between June, 1993, and May, 1995, we studied 171 consecutive patients with CHF (mean age 60 years [SD 11; range 27-86]; 17 female). We assessed exercise capacity (peak oxygen consumption; mean 17.5 mL kg-1 min-1 [6.7]), functional status (New York Heart Association [NYHA] class: 21 class I, 63 class II, 68 class III, 19 class IV), and left-ventricular ejection fraction (mean 30% [SD 15]; n = 115). The cachectic status was defined prospectively as a non-intentional documented weight loss of at least 7.5% of previous normal weight (28 patients; range 9-36% or 6-30 kg) during at least 6 months. The Cox proportional-hazards model was used to assess the association of variables with survival, and Kaplan-Meier cumulative survival plots were constructed to estimate the influence of risk factors. FINDINGS: At the end of follow-up in November, 1996, 49 patients had died (after a mean 324 days [SD 283]). The mean follow-up of the survivors was 834 days (SD 186; range 549-1269). The cachectic state was predictive of 18-month mortality independent of age, NYHA class, left-ventricular ejection fraction, and peak oxygen consumption. Mortality in the cachectic patients (n = 28) was 18% at 3 months, 29% at 6 months, 39% at 12 months, and 50% at 18 months. Patients who had a peak oxygen consumption below 14 mL kg-1 min-1 (n = 53) had mortality at 3, 6, 12, and 18 months of 19%, 30%, 40%, and 51%. 18-month survival was 23% (95% CI 0-46) for the 13 patients with both of these risk factors (cachexia and low peak oxygen consumption) compared with 93% (88-98) in those (n = 103) with neither risk factor (p < 0.0001). INTERPRETATION: The cachectic state is a strong independent risk factor for mortality in patients with CHF. Combined with a low peak oxygen consumption, it identifies a subset of patients at extremely high risk of death. Assessment of cachexia should be included in transplant programmes and studies that investigate the effect of interventions by survival analyses.

Adult↗
PubMed1997

Clinical correlates and prognostic significance of the ventilatory response to exercise in chronic heart failure.

OBJECTIVES: This study sought to investigate the clinical characteristics of patients with chronic heart failure and an increased ventilatory response to exercise and to examine the prognostic usefulness of this response. BACKGROUND: The ventilatory response to exercise is increased in many patients with chronic heart failure and may be characterized by the regression slope relating minute ventilation to carbon dioxide output (VE-VCO2 slope) during exercise. METHODS: One hundred seventy-three consecutive patients (155 men; mean [+/-SD] age 59.8 +/- 11.5 years; radionuclide left ventricular ejection fraction [LVEF] 28.4 +/- 14.6%) underwent cardiopulmonary exercise testing (peak oxygen consumption 18.5 +/- 7.3 ml/kg per min; VE-CO2 slope 34.8 +/- 10.6) over a 2-year period. Using 1.96 standard deviations above the mean VE-VCO2 slope of 68 healthy age-matched subjects (mean slope 26.3 +/- 4.1), we defined a high ventilatory response to exercise as a slope >34. RESULTS: Eighty-three patients (48%) had an increased VE-VCO2 slope (mean 43.1 +/- 8.9). There was a difference in age (62.2 vs. 57.3 years, p = 0.005), New York Heart Association functional class (2.9 vs. 2.1, p < 0.001), LVEF (24.7 vs. 31.9%, p = 0.0016), peak oxygen consumption (14.9 vs. 21.7 ml/kg per min, p < 0.0001) and radiographic cardiothoracic ratio (0.58 vs. 0.55, p = 0.002) between these patients and those with a normal slope. In the univariate Cox proportional hazards model, the E-VCO2 slope was an important prognostic factor (p < 0.0001). In the multivariate Cox analyses using several variables (age, peak oxygen consumption, VE-VCO2 slope and LVEF), the VE-VCO2 slope gave additional prognostic information (p = 0.018) beyond peak oxygen consumption (p = 0.022). Kaplan-Meier survival curves at 18 months demonstrated a survival rate of 95% in patients with a normal VE-VCO2 slope compared with 69% in those with a high slope (p < 0.0001). CONCLUSIONS: A high VE-VCO2 slope selects patients with more severe heart failure and is an independent prognostic marker. The VE-VCO2 slope may be used as a supplementary index in the assessment of patients with chronic heart failure.

Aged↗
PubMed1997

Insulin resistance in chronic heart failure: relation to severity and etiology of heart failure.

OBJECTIVES: We attempted to assess insulin sensitivity in patients with chronic heart failure (CHF) and its relation to disease severity. BACKGROUND: Peripheral muscular changes influence the progression of heart failure. This effect may be due to chronic disturbances of insulin and glucose metabolism that affect the energy status of skeletal and myocardial muscle. METHODS: We investigated insulin sensitivity in 79 men-38 patients with CHF, 21 patients with angiographic evidence of coronary artery disease without CHF and 20 healthy control subjects-and assessed its relation to disease severity, etiology and hormonal status (all subjects had a similar age and body mass index). Insulin sensitivity was estimated by minimal modeling analysis of the glucose and insulin and profiles during a 0.5 g/kg body weight intravenous glucose tolerance test. RESULTS: Compared with control subjects, patients with CHF had similar mean fasting glucose but increased insulin levels (67 vs. 29 pmol/liter, p < 0.002) and a 58% reduced mean insulin sensitivity (2.01 vs. 4.84 min-1/pmol/ml x 10(5), p < 0.0001). Peak oxygen consumption (VO2) (r = 0.63), fasting triglycerides (r = -0.62) and age (r = -0.46, all p < 0.001) predicted insulin sensitivity independently. Rest norepinephrine and epinephrine levels, left ventricular ejection fraction and heart failure etiology were not related to insulin sensitivity. Patients with coronary artery disease but no CHF had an intermediate mean insulin sensitivity (3.30 min-1/pmol/ml x 10(5) [-32%, p = 0.042 vs. control subjects; +113%, p = 0.0023 vs. patients with CHF due to ischemic heart disease]). In multivariate analyses of all 79 subjects, age (p = 0.0006), triglycerides (p = 0.0023), fasting insulin (p = 0.0037) and the presence of CHF (p = 0.018) were independent predictors of impaired insulin sensitivity (adjusted joint R2 = 0.53, p < 0.0001). CONCLUSIONS: CHF is associated with marked insulin resistance, characterized by both fasting and stimulated hyperinsulinemia. Advanced heart failure (in terms of reduced peak VO2) is related to increased insulin resistance, but this is not directly mediated through ventricular dysfunction or increased catecholamine levels.

Blood Glucose↗
PubMed1997

Tumor necrosis factor and steroid metabolism in chronic heart failure: possible relation to muscle wasting.

OBJECTIVES: We sought to assess the possible relations between clinical severity of chronic heart failure and catabolic factors, specifically tumor necrosis factor (TNF), soluble TNF receptors 1 and 2 (sTNFR-1 and sTNFR-2), cortisol, testosterone and dehydroepiandrosterone (DHEA). BACKGROUND: Chronic heart failure is associated with loss of muscle bulk that may be related to alteration of the balance between catabolism and anabolism. METHODS: Sixty-three patients (average age +/- SD 60.4 +/- 11.3 years) with stable chronic heart failure and 20 control subjects aged 52.8 +/- 11.4 years were studied. We measured body mass index (BMI) and obtained maximal incremental exercise testing with metabolic gas exchange measurements and measurements of venous levels of TNF, sTNFR-1 and sTNFR-2, cortisol and DHEA. RESULTS: There was no difference in total TNF-alpha levels between patients and control subjects (9.76 +/- 8.59 vs. 6.84 +/- 2.7 pg/ml). sTNFR-1 (128.9 +/- 84.5 vs. 63.6 +/- 23.3 pg/ml, p < 0.003) and sTNFR-2 (250.1 +/- 109.5 vs. 187.9 +/- 92.2 pg/ml, p = 0.03) were higher in patients. DHEA was lower in patients (9.88 +/- 6.94 vs. 15.64 +/- 8.33 nmol/liter, p = 0.004). The ratio of log cortisol to log DHEA correlated with log TNF level (r = 0.50, p < 0.001 for the patients alone; r = 0.48, p < 0.001 for the group as a whole). Peak oxygen consumption correlated with both sTNFR-1 and sTNFR-2 (r = -0.51, p < 0.001 and r = -0.39, p < 0.001, respectively). There was a negative correlation between BMI and TNF levels (r = -0.43, p < 0.001 for the patients) and the cortisol/DHEA ratio (r = -0.32, p = 0.01 for the patients). CONCLUSIONS: There is an increase in TNF and its soluble receptors in chronic heart failure. This increase is associated with a rise in the cortisol/DHEA (catabolic/anabolic) ratio. These changes correlate with BMI and clinical severity of heart failure, suggesting a possible etiologic link.

Aged↗
PubMed1997

Skeletal muscle function and its relation to exercise tolerance in chronic heart failure.

OBJECTIVES: This study sought to define the relation between muscle function and bulk in chronic heart failure (HF) and to explore the association between muscle function and bulk and exercise capacity. BACKGROUND: Skeletal muscle abnormalities have been postulated as determinants of exercise capacity in chronic HF. Previously, muscle function in chronic HF has been evaluated in relatively small numbers of patients and with variable results, with little account being taken of the effects of muscle wasting. METHODS: One hundred male patients with chronic HF and 31 healthy male control subjects were studied. They were matched for age (59.0 +/- 1.0 vs. 58.7 +/- 1.7 years [mean +/- SEM]) and body mass index (26.6 +/- 0.4 vs. 26.3 +/- 0.7 kg/m2). We assessed maximal treadmill oxygen consumption (VO2), quadriceps maximal isometric strength, fatigue (20-min protocol, expressed in baseline maximal strength) and computed tomographic cross-sectional area (CSA) at midthigh. RESULTS: Peak VO2 was lower in patients (18.0 +/- 0.6 vs. 33.3 +/- 1.4 ml/min per kg, p < 0.0001), although both groups achieved a similar respiratory exchange ratio at peak exercise (1.15 +/- 0.01 vs. 1.19 +/- 0.03, p = 0.13). Quadriceps (582 vs. 652 cm2, p < 0.05) and total leg muscle CSA (1,153 vs. 1,304 cm2, p < 0.005) were lower in patients with chronic HF. Patients were weaker than control subjects (357 +/- 12 vs. 434 +/- 18 N, p < 0.005) and also exhibited greater fatigue at 20 min (79.1% vs. 92.1% of baseline value, p < 0.0001). After correcting strength for quadriceps CSA, significant differences persisted (5.9 +/- 0.2 vs. 7.0 +/- 0.3 N/cm2, p < 0.005), indicating reduced strength per unit muscle. In patients, but not control subjects, muscle CSA significantly correlated with peak absolute VO2 (R = 0.66, p < 0.0001) and is an independent predictor of peak absolute VO2. CONCLUSIONS: Patients with chronic HF have reduced quadriceps maximal isometric strength. This weakness occurs as a result of both quantitative and qualitative abnormalities of the muscle. With increasing exercise limitation there is increasing muscle weakness. This progressive weakness occurs predominantly as a result of loss of quadriceps bulk. In patients, this muscular atrophy becomes a major determinant of exercise capacity.

Case-Control Studies↗
PubMed1997

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

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: 81.2 +/- 1.9 vs 105.2 +/- 2.1, P < 0.0001, 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 < 0.001) 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. CONCLUSIONS: 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.

Adult↗
PubMed1997

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

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 58.7 +/- 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 +/- 0.201l.min-1.%Sao(2)-1 compared with 0.673 +/- 0.410l. min-1.%Sao(2)-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.%Sao(2)-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%, chi-squared 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.

Case-Control Studies↗
PubMed1997

Relation between serum uric acid and lower limb blood flow in patients with chronic heart failure.

OBJECTIVE: To determine whether lower limb blood flow is related to serum uric acid concentrations in patients with chronic heart failure, taking into account the hyperuricaemic effects of diuretic treatment and insulin resistance. DESIGN: Lower limb blood flow was measured at rest and after maximum exercise followed by a five minute period of ischaemia (maximum blood flow) using strain gauge venous occlusion plethysmography. All patients underwent a metabolic assessment, which included an intravenous glucose tolerance test (IVGTT)-to obtain an index of insulin sensitivity- and measurement of serum uric acid. SETTING: University and hospital departments specialising in cardiology and metabolic medicine. SUBJECTS: 22 patients with chronic heart failure. RESULTS: Mean (SEM) resting and maximum blood flow values were 2.87 (0.23) and 24.00 (1.83) ml/100 ml/min, respectively. Patients in the upper tertile of serum uric acid had lower maximum blood flow than those in the lowest tertile (15.6 (2.2) v 31.0 (2.1) ml/100 ml/min, P = 0.003). Serum uric acid correlated with maximum blood flow (r = -0.86, P < 0.001), but not with resting blood flow. In stepwise regression analysis, uric acid emerged as the only predictor of maximum blood flow (standardised coefficient = -0.83 (P < 0.001), R2 = 0.68 (P < 0.001)), independently of diuretic dose, age, body mass index, plasma creatinine, fasting and IVGTT glucose and insulin, insulin sensitivity, maximum oxygen uptake and exercise time during the treadmill exercise test, and alcohol intake. CONCLUSIONS: There is a strong inverse relation between serum uric acid concentrations and maximum leg blood flow in patients with chronic heart failure. Further studies are needed to determine whether serum uric acid can be used as an index of vascular function in cardiovascular diseases.

Biomarkers↗
PubMed1996

Heart rhythms, ventricular arrhythmias, and death in chronic heart failure.

BACKGROUND: The aim of this study was to evaluate whether abnormalities in heart rate variability (HRV) could act as markers of ventricular tachycardia and prognosis in patients with advanced, chronic heart failure. Fifty patients with chronic heart failure (45 men; mean age, 59 +/- 9 years; New York Heart Association [NYHA] class II-III; left ventricular ejection fraction [LVEF], 19 +/- 9% and peak oxygen consumption, 16.6 +/- 5.4 mL/kg/min) caused by idiopathic dilated cardiomyopathy (n = 12) and ischemic heart disease (n = 38) were included in the study. Heart rate variability measures derived from 24-hour electrocardiographic (ECG) monitoring (Marquette 8500 recorder, Marquette Electronics, Milwaukee, WI) were calculated in the time domain and frequency domain. METHODS AND RESULTS: Twenty-five patients (50%) revealed episodes of ventricular tachycardia on 24-hour ECG monitoring (1-143 episodes). The presence of ventricular tachycardia was associated with lower LVEF but there was no difference in NYHA class and peak oxygen consumption between patients with and without ventricular tachycardia (LVEF, 16 vs 22%, P = .01; NYHA class, 2.6 vs 2.4; peak oxygen consumption, 16.5 vs 16.8 mL/kg/min, not significant). Patients with ventricular tachycardia exhibited markedly lower HRV measures. Multiple regression analysis was used to test HRV parameters as potential predictors of ventricular tachycardia. Among them, high-frequency power was the only independent predictor of the presence of ventricular tachycardia, and this predictive correlation was independent of LVEF and mean R-R interval duration. During a follow-up period of 24 +/- 18 months, 12 patients (24%) died. No difference was found in age, etiology, NYHA class, peak oxygen consumption, or occurrence of ventricular tachycardia, but a lower LVEF (15 +/- 6 vs 21 +/- 9%, P = .046) was observed in those who died compared with those who survived. Certain estimates of HRV were in contrast, lower in those who subsequently died: standard deviation of all normal R-R intervals (61 +/- 30 vs 101 +/- 33 ms), standard deviation of 5-minute mean R-R intervals (55 +/- 27 vs 92 +/- 31 ms), mean of all 5-minute standard deviations of R-R intervals (22 +/- 12 vs 37 +/- 11 ms), and the low-frequency (3.2 +/- 1.8 vs 4.8 +/- 0.9 ln ms2) and high-frequency (3.0 +/- 1.1 vs 3.8 +/- 0.8 ln ms2) components of the HRV spectrum (all differences, P < .01). In univariate Cox analysis, all of these HRV measures were independent predictors of death. Kaplan-Meier survival analysis revealed that the standard deviations of all normal R-R intervals and of 5-minute mean R-R intervals dichotomized at median values (99 and 90.5 ms, respectively) were the best predictors of mortality. CONCLUSIONS: In patients with moderate to severe chronic heart failure, depressed indices of HRV on 24-hour ambulatory ECG monitoring could be related to higher risk of ventricular tachycardia and death, suggesting that analysis of HRV could be usefully applied to risk stratification in chronic heart failure patients.

Arrhythmias, Cardiac↗
PubMed1995

Inspiratory muscle strength is a determinant of maximum oxygen consumption in chronic heart failure.

OBJECTIVE: To investigate the significance of respiratory muscle weakness in chronic heart failure and its relation both to maximum oxygen consumption during cardiopulmonary exercise testing and to skeletal muscle (quadriceps) strength. SUBJECTS: Seven healthy men aged 54.9 (SEM 4.3) years and 20 men with chronic heart failure aged 61.4 (1.6) years (P = 0.20) with radionuclide left ventricular ejection fraction of 25.4 (3.0)%. METHODS: Mouth pressures during maximum static inspiratory effort (PImax) at functional residual capacity (FRC) and residual volume (RV) were measured in all subjects and taken as indices of inspiratory muscle strength. Similarly, mouth pressures during maximum static expiratory effort (PEmax) at FRC and total lung capacity (TLC) were taken as indices of expiratory muscle strength. Cardiopulmonary exercise testing was performed in all subjects. All controls and 15 heart failure patients also had their right quadriceps muscle strength measured. RESULTS: There was respiratory muscle weakness in heart failure patients, with reduction of PImax at FRC (59.7) (6.3) v 85.6 (9.6) cm H2O, P = 0.045), PEmax at FRC (94.8 (6.2) v 134.6 (9.1) cm H2O, P = 0.004), and PEmax at TLC (121.7 (8.5) v 160.7 (13) cm H2O, P = 0.028). PImax at RV was also reduced but this did not reach statistical significance (77.3 (6.6) v 89.3 (13) cm H2O, P = 0.44). There was also significant weakness of the right quadriceps muscle (308.5 (22) v 446.2 (28) N, P = 0.001). PImax at both FRC and RV correlated with maximum oxygen consumption (r = 0.59, P = 0.006, and r = 0.45, P = 0.048 respectively) but not PEmax. There was, however, no significant correlation between PImax and right quadriceps strength. CONCLUSIONS: Respiratory muscle weakness is seen in chronic heart failure. The results suggest that inspiratory muscles are important in determining maximum oxygen consumption and exercise tolerance in these patients. The lack of correlation between respiratory and right quadriceps muscle strength further suggests that the magnitude and time course of respiratory and locomotor muscle weakness may differ in individual patients. Treatment aimed at improving the function of the involved muscle groups may alleviate symptoms.

Adult↗