Heart Failure Subjects Research Articles

The resistive and elastic work of breathing during exercise in patients with chronic heart failure

Patients with heart failure (HF) display numerous derangements in ventilatory function, which together serve to increase the work of breathing (W(b)) during exercise. However, the extent to which the resistive and elastic properties of the respiratory system contribute to the higher W(b) in these patients is unknown. We quantified the resistive and elastic W(b) in patients with stable HF (n = 9; New York Heart Association functional class I-II) and healthy control subjects (n = 9) at standardised levels of minute ventilation (V'(E)) during graded exercise. Dynamic lung compliance was systematically lower for a given level of V'(E) in HF patients than controls (p<0.05). HF patients displayed slightly higher levels of inspiratory elastic W(b) with greater amounts of ventilatory constraint and resistive W(b) than control subjects during exercise (p<0.05). Our data indicates that the higher W(b) in HF patients is primarily due to a greater resistive, rather than elastic, load to breathing. The greater resistive W(b) in these patients probably reflects an increased hysteresivity of the airways and lung tissues. The marginally higher inspiratory elastic W(b) observed in HF patients appears related to a combined decrease in the compliances of the lungs and chest wall. The clinical and physiological implications of our findings are discussed.

A new approach to detect congestive heart failure using Teager energy nonlinear scatter plot of R–R interval series

A novel approach to distinguish congestive heart failure (CHF) subjects from healthy subjects is proposed. Heart rate variability (HRV) is impaired in CHF subjects. In this work hypothesizing that capturing moment to moment nonlinear dynamics of HRV will reveal cardiac patterning, we construct the nonlinear scatter plot for Teager energy of R–R interval series. The key feature of Teager energy is that it models the energy of the source that generated the signal rather than the energy of the signal itself. Hence, any deviations in the genesis of HRV, by complex interactions of hemodynamic, electrophysiological, and humoral variables, as well as by the autonomic and central nervous regulations, get manifested in the Teager energy function. Comparison of the Teager energy scatter plot with the second-order difference plot (SODP) for normal and CHF subjects reveals significant differences qualitatively and quantitatively. We introduce the concept of curvilinearity for central tendency measures of the plots and define a radial distance index that reveals the efficacy of the Teager energy scatter plot over SODP in separating CHF subjects from healthy subjects. The k-nearest neighbor classifier with RDI as feature showed almost 100% classification rate.

Changes in Galectin-3 Levels over Time Predict Mortality and Morbidity in Chronic HF

Background: Elevated circulating levels of galectin-3, a protein implicated in myocardial fibrosis and remodeling, are associated with significantly increased risk of morbidity and mortality among chronic heart failure (HF) subjects. The clinical utility of serial measurements of galectin-3, however, has not been reported. Methods: Galectin-3 was measured at baseline and at 3 months in a study comprising 1,329 subjects of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA), and at baseline and 6 months in 324 subjects of the Coordinating Study Evaluating Outcomes of Advising and Counseling in Heart Failure (COACH). An assay recently cleared by the U.S. Food and Drug Administration was used to measure galectin-3, and the indicated threshold value of 17.8 ng/mL was adopted to categorize subjects into 4 categories: subjects whose galectin-3 values remained either below or above 17.8 ng/mL, and subjects whose galectin-3 levels either increased or decreased between baseline and the second sampling time point. Results: Categorical changes in galectin-3 were observed in 17.3% of subjects from CORONA over 3 months, and 23.5% of subjects from COACH over 6 months. For the composite endpoint of total mortality and HF hospitalization, the outcome of subjects with a low baseline galectin-3 level that increased over time was significantly worse than that of subjects that maintained a low level (Cox hazard ratio (HR) in CORONA, 1.60 (95% CI: 1.152.22), p50.005; HR in COACH, 2.46 (95% CI: 1.05-5.73, p50.037)). Similarly, subjects with a high baseline level that decreased over time exhibited significantly fewer endpoints than subjects that remained high over time (HR in CORONA, 0.68 (95% CI: 0.49-0.94), p50.020; HR in COACH, 0.48 (95% CI: 0.27-0.87), p50.015). Analyses of multiple secondary endpoints yielded comparable results. Conclusions: In two large cohorts of chronic HF subjects, serial measurements of galectin-3 concentration are shown to provide important and significant prognostic value for morbidity and mortality risk assessment. 295

Hierarchical entropy analysis for biological signals

We develop a hierarchical entropy (HE) method to quantify the complexity of a time series based on hierarchical decomposition and entropy analysis. The proposed method is applied to the Gaussian white noise and the 1 / f noise. We prove that the difference frequency components of the Gaussian white noise with the same scale factor have the same value of entropies, and the values decline as the scale factor increases. We also apply the HE method to the 1 / f noise, and prove mathematically that a lower frequency component of a 1 / f noise is also a 1 / f noise and verify numerically that a higher frequency component of a 1 / f random vector is approximately equal to a Gaussian random vector. The theoretical results are confirmed by numerical results. Moreover, we show that the HE method is an efficient method to analyze heartbeat signals by applying it to the cardiac interbeat interval time series of healthy young and elderly subjects, congestive heart failure (CHF) subjects and atrial fibrillation (AF) subjects.

Global and regional putamen volume loss in patients with heart failure

Heart failure (HF) is accompanied by diminished cognitive, motor, learning, emotional, and planning deficits, which are associated with increased morbidity and mortality. A basal ganglia structure, the putamen, serves many functions that are affected in HF, but its global or localized structural integrity is unknown. Our aim was to evaluate global and regional putamen volume differences in HF over control subjects. We collected two high-resolution T1-weighted scans from 16 HF patients (age, 54.1 ± 8.3 years; 12 males; left ventricular ejection fraction, 27.8 ± 6.8%) and 32 control subjects (52.4 ± 7.3 years; 24 males) using a 3.0 T magnetic resonance imaging scanner. After realigning, averaging, and reorienting the T1-weighted volumes into a common space, the structures were manually outlined, tracings were normalized for head size, volumes calculated, and surface models generated. Demographic data were compared between groups with χ(2) and independent samples t-tests, global putamen volumes were evaluated using independent samples t-tests, and regional differences were examined with surface morphometry. No significant differences in age or sex appeared between groups, but body mass index differed significantly (P = 0.008). Heart failure patients showed significantly lower left (controls vs. HF; 4842.1 ± 740.0 vs. 4224.1 ± 894.4 mm(3), P = 0.014) and right (4769.3 ± 651.9 vs. 4193.7 ± 876.2 mm(3), P = 0.014) global putamen volumes than controls, with localized reductions in bilateral rostral, mid-dorsal, and medial-caudal regions (left, P < 0.003; right, P < 0.0002). Putamen structures showed global and localized volume reductions in HF over controls. The localized volume losses suggest deficits in motor and neuropsychological functions, which are evident in HF subjects, and may be due to hypoxic and ischaemic processes targeting these areas.

Platelet nitric oxide signalling in heart failure: role of oxidative stress

Heart failure is associated with deficient endothelial nitric oxide (NO) production as well as increased oxidative stress and accelerated NO degradation. The aim of this study was to evaluate platelet NO biosynthesis and superoxide anion (O(2)(-)) production in patients with heart failure. In platelets from patients with heart failure due to idiopathic dilated cardiomyopathy (n= 16) and healthy control subjects (n= 23), NO synthase (NOS) activity was evaluated by L-[(3)H]-arginine to l-[(3)H]-citrulline conversion, cGMP was determined by radioimmunoassay, vasodilator-stimulated phosphoprotein (VASP: total and serine-239-phosphorylated) was assessed by western blotting, and O(2)(-) production and O(2)(-) scavenging capacity were measured by pholasin-enhanced chemiluminescence. In platelets from patients with heart failure, basal NOS activity was higher than in those from controls; furthermore, whereas platelet NOS activity increased as expected in response to albuterol or collagen in controls, no increase occurred in platelets from heart failure subjects. Despite this, basal intraplatelet NO-attributable cGMP was lower in heart failure than in control subjects, as was serine-239 phosphorylation of VASP, suggesting a decrease in bioactive NO. Platelets from heart failure subjects exhibited higher basal and collagen-stimulated O(2)(-) production and impaired O(2)(-) scavenging capacity, resulting in higher oxidative stress, consistent with the observed decrease in bioactive NO. In heart failure, despite activation of NOS, platelets produce less bioactive NO, probably as a result of NO scavenging due to increased O(2)(-) production. This functional defect in the platelet l-arginine/NO/guanylyl cyclase pathway could contribute to the platelet activation observed in heart failure.

Lung fluid balance in patients with heart failure: effect of beta‐2 adrenergic‐receptor stimulation

Background β2-adrenergic receptor (β2AR) stimulation promotes lung fluid removal in animals and healthy humans. It is possible that lung fluid accumulation in heart failure (HF) patients is caused by impairment in lung fluid regulation via desensitization of the lung β2ARs. Purpose To determine the effect of an acute inhaled β2AR agonist on lung fluid in HF. Methods/Results 22 stable HF patients and 22 healthy age and gender matched subjects were studied. Lung fluid was estimated at baseline (BL) and up to 30 min after administration of nebulized albuterol by measuring lung diffusing capacity for CO (DLCO), alveolar-capillary conductance (Dm) and pulmonary capillary blood volume (Vc) using a rebreathe method. Pre-inhalation, DLCO was not different in HF vs. healthy subjects (16±5 vs. 19±4 ml/min/mmHg, P=0.06). By contrast, Dm/Vc was greater in HF vs. healthy subjects (0.42 ± 0.14 vs. 0.33 ± 0.15, P=0.04). In HF, group mean DLCO, Dm and Dm/Vc were not different pre- vs. post-albuterol. However, patients who had an increase in DLCO and Dm/Vc with albuterol administration had significantly lower BL values compared to patients who had no improvement (P<0.05). That is, β2AR stimulation improved DLCO and Dm/Vc only in subjects who had evidence for increased lung fluid at BL. Conclusion Stimulation of β2AR may stimulate fluid removal in stable HF patients who exhibit evidence for elevated lung water at rest. HL71478.

Assessment of systolic and diastolic function in heart failure using ambulatory monitoring with acoustic cardiography

Introduction. The circadian variation of heart function and heart sounds in patients with and without heart failure (HF) is poorly understood. We hypothesized HF patients would exhibit less circadian variation with worsened cardiac function and sleep apnea. Methods. We studied 67 HF patients (age 67.4 ± 8.2 years; 42% acute HF) and 63 asymptomatic control subjects with no history of HF (age 61.6 ± 7.7 years). Subjects wore a heart sound/ECG/respiratory monitor. The data were analyzed for sleep apnea, diastolic heart sounds, and systolic time intervals. Results. The HF group had significantly greater prevalence of the third heart sound and prolongation of electro-mechanical activation time, while the control group had an age-related increase in the prevalence of the fourth heart sound. The control group showed more circadian variation in cardiac function. The HF subjects had more sleep apnea and higher occurrence of heart rate non-dipping. Conclusions. The control subjects demonstrated an increasing incidence of diastolic dysfunction with age, while systolic function was mostly unchanged with aging. Parameters related to systolic function were significantly worse in the HF group with little diurnal variation, indicating a constant stimulation of sympathetic tone in HF and reduction of diurnal regulation.

Transcriptomic biomarkers of the response of hospitalized geriatric patients admitted with heart failure. Comparison to hospitalized geriatric patients with infectious diseases or hip fracture

The abundance of a preselection of transcripts involved in inflammation, immunosenescence and stress response was compared between PBMC of healthy aged donors and aged patients in acute phase of heart failure and at recovery. This study identified 22 transcripts differentially abundant in acute phase of heart failure versus healthy aged subjects. Transcripts involved in inflammation and oxidative stress were more abundant. Those associated with T-cell functions were less abundant. The results were compared to two other major acute geriatric issues: infectious diseases and hip fracture. In acute phase, compared to healthy aged subjects, the abundance of 15/22 transcripts was also altered in both geriatric infectious diseases and hip fracture. Many variations had not vanished at the recovery phase. The abundance of CD28, CD69, LCK, HMOX1, TNFRSF1A transcripts, known to be altered in healthy aged versus healthy young subjects, was further affected in acute phase of the three geriatric diseases considered. The transcript levels of BCL2, CASP8, CCL5, DDIT3, EGR3, IL10RB, IL1R2, SERPINB2 and TIMP1 were affected in all three pathological conditions compared to healthy aged, but not versus healthy young subjects. In conclusion, this work provides critical targets for therapeutic research on geriatric heart failure, infectious diseases and hip fracture.

Efficacy and Safety of Carvedilol in Treatment of Heart Failure with Chronic Kidney Disease

Background— The safety and efficacy of different types of β-blocker therapy in patients with non–dialysis-dependent chronic kidney disease (CKD) and systolic heart failure (HF) are not well described. We assessed whether treatment of systolic HF with carvedilol is efficacious and safe in adults with CKD. Methods and Results— We performed a post hoc analysis of pooled individual patient data (n=4217) from 2 multinational, double-blinded, placebo-controlled, randomized trials, CAPRICORN (Carvedilol Postinfarct Survival Control in Left Ventricular Dysfunction Study) and COPERNICUS (Carvedilol Prospective Randomized, Cumulative Survival study). Primary outcome was all-cause mortality. Secondary outcomes included cardiovascular mortality, HF mortality, first HF hospitalization, the composite of cardiovascular mortality or first HF hospitalization, and sudden cardiac death. Non–dialysis-dependent CKD was defined by estimated glomerular filtration rate ≤60 mL/min/1.73 m 2 , using the abbreviated Modification of Diet in Renal Disease equation. CKD was present in 2566 of 4217 (60.8%) of the cohort, 50.4% of whom were randomly assigned to carvedilol therapy. Within the CKD group, treatment with carvedilol decreased the risks of all-cause mortality (hazard ratio [HR], 0.76; 95% confidence interval [CI], 0.63 to 0.93; P =0.007), cardiovascular mortality (HR, 0.76; 95% CI, 0.62 to 0.94; P =0.011), HF mortality (HR, 0.68; 95% CI, 0.52 to 0.88; P =0.003), first hospitalization for HF (HR, 0.74; 95% CI, 0.61 to 0.88; P =0.0009), and the composite of cardiovascular mortality or HF hospitalization (HR, 0.75; 95% CI, 0.65 to 0.87; P &lt;0.001) but was without significant effect on sudden cardiac death (HR, 0.76; 95% CI, 0.56 to 1.05; P =0.098). There was no significant interaction between treatment arm and study type. Carvedilol was generally well tolerated by both groups of patients, with an increased relative incidence in transient increase in serum creatinine without need for dialysis and other electrolyte changes in the CKD patients. However, in a sensitivity analysis among HF subjects with estimated glomerular filtration rate &lt;45 mL/min/1.73 m 2 (CKD stage 3b), the efficacy of carvedilol was not significantly different from placebo. Conclusions— This analysis suggests that the benefits of carvedilol therapy in patients with systolic left ventricular dysfunction with or without symptoms of HF are consistent even in the presence of mild to moderate CKD. Whether carvedilol therapy is similarly efficacious in HF patients with more advanced kidney disease requires further study.

Diminished Antioxidant Activity of High-Density Lipoprotein–Associated Proteins in Systolic Heart Failure

Diminished serum arylesterase activity, catalyzed by the high-density lipoprotein-associated paraoxonase-1, is associated with heightened systemic oxidative stress and atherosclerosis risk. In the present study, we sought to determine the prognostic role of serum arylesterase activity in subjects with systolic heart failure, particularly in relation to established cardiac biomarkers. We measured serum arylesterase activity in 760 subjects with impaired left ventricular systolic function (left ventricular ejection fraction <50%), and prospectively followed major adverse cardiac events (including death, nonfatal myocardial infarction, and stroke) for 3 years. In our study cohort (mean age, 64±11 years; 74% men; median left ventricular ejection fraction, 35%; median creatinine clearance, 96 mg/dL), mean serum arylesterase activity (98±25 μmol/L/min/mL) was lower compared with that in healthy control subjects (mean, 115±26 μmol/L/min/mL, P<0.01) but higher compared with advanced decompensated heart failure subjects (mean, 69±22 μmol/L/min/mL, P<0.01). Within our cohort, there was modest correlation between serum arylesterase activity and high-density lipoprotein cholesterol (r=0.33, P<0.01) as well as B-type natriuretic peptide (r=-0.23, P<0.01). Lower serum arylesterase activity was a strong predictor of poorer outcomes (hazard ratio, 2.94; 95% confidence interval, 1.54, 5.62; P<0.001). After adjusting for traditional risk factors, medication use, B-type natriuretic peptide, and creatinine clearance, lower serum arylesterase still conferred an increased risk of major adverse cardiac events at 3 years (hazard ratio, 2.69; 95% confidence interval, 1.37 to 5.28; P=0.004). In patients with systolic heart failure, decreased serum arylesterase activity, a measure of diminished antioxidant properties of high-density lipoprotein, predicts higher risk of incident long-term adverse cardiac event independent of established clinical and biochemical risk factors.

Optimal Timing in Screening Patients with Congestive Heart Failure and Healthy Subjects During Circadian Observation

Congestive heart failure (CHF) is a major medical challenge in developed countries. In order to screen patients with CHF and healthy subjects during circadian observation, accurate judgment and fast response are imperative. In this study, optimal timing during circadian observation via the heart rate variability (HRV) was sought. We tested 29 CHF patients and 54 healthy subjects in the control group from the interbeat interval databases of PhysioBank. By invoking the α1 parameter in detrended fluctuation analysis of HRV, we found that it could be used as an indicator to screen the patients with CHF and subjects in normal sinus rhythm (NSR) under Kruskal-Wallis test. By invoking Fano factor, the optimal timing to screen CHF patients and healthy subjects was found to be from 7 PM to 9 PM during the circadian observation. In addition, this result is robust in a sense that the same result can be achieved by using different ECG recording lengths of 2, 5, 10, … , and 120min, respectively. Furthermore, a support vector machine was employed to classify CHF and NSR with α1 parameter of a moving half-hour ECG recordings via leave-one-out cross validation. The results showed that the superlative screening performance was obtained in the 7 pm-9 pm period during circadian observation. It is believed that this result of optimal timing will be helpful in the non-invasive monitoring and screening of CHF patients and healthy subjects in the clinical practice.

Preservation of long range temporal correlations under extreme random dilution

Many natural time series exhibit long range temporal correlations that may be characterized by power-law scaling exponents. However, in many cases, the time series have uneven time intervals due to, for example, missing data points, noisy data, and outliers. Here we study the effect of randomly missing data points on the power-law scaling exponents of time series that are long range temporally correlated. The Fourier transform and detrended fluctuation analysis (DFA) techniques are used for scaling exponent estimation. We find that even under extreme dilution of more than 50%, the value of the scaling exponent remains almost unaffected. Random dilution is also applied on heart interbeat interval time series. It is found that dilution of 70%–80% of the data points leads to a reduction of only 8% in the scaling exponent; it is also found that it is possible to discriminate between healthy and heart failure subjects even under extreme dilution of more than 90%.

Impact of diuretic treatment and sodium intake on plasma volume in patients with compensated systolic heart failure

In patients with heart failure (HF), the use of diuretics may be a double-edged sword that can alleviate symptoms of congestion, but also result in over-diuresis and intravascular volume depletion. The purpose of the present study was to examine plasma volume (PV) in HF patients receiving from 0 to 160 mg of furosemide and to investigate whether determination of plasma N-terminal fragment of pro-brain natriuretic peptide (NT-proBNP) concentrations can predict PV-status. Plasma volume, extracellular volume, glomerular filtration rate, NT-proBNP, and daily renal sodium excretion were measured in 18 patients with medically treated, compensated HF and in 27 healthy volunteers. Cardiac function was examined by non-invasive cardiac output determination and echocardiography. Exercise capacity was evaluated by 6 min walk test. There was a borderline significant difference in PV between patients with HF and control subjects (37.3 +/- 6.0 and 40.2 +/- 5.8 mL/kg, respectively, P = 0.092) with a significant tendency towards a contraction of PV with increasing use of diuretics (P = 0.031). There was no difference in extracellular volume between patients with HF and control subjects (P = 0.844). NT-proBNP plasma concentrations had no correlation to either sodium excretion (P = 0.193) or PV (P = 0.471) in patients with HF. Plasma volume in patients with HF was within normal limits, but patients treated with high doses of loop-diuretics tended to have subnormal PV. Single measurement of NT-proBNP plasma concentration could not be used to estimate intravascular volume status in patients with HF.

A New Signal From B-Type Natriuretic Peptide in ST-Elevation Myocardial Infarction

A New Signal From B-Type Natriuretic Peptide in ST-Elevation Myocardial Infarction

Central Nervous System Changes in Pediatric Heart Failure: A Volumetric Study

Autonomic dysfunction, mood disturbances, and memory deficits appear in pediatric and adult heart failure (HF). Brain areas controlling these functions show injury in adult HF patients, many of whom have comorbid cerebrovascular disease. We examined whether similar brain pathology develops in pediatric subjects without such comorbidities. In this study, high-resolution T1 brain magnetic resonance images were collected from seven severe HF subjects age (age 8–18 years [mean 13]; left ventricular shortening 9 to 19% [median 14%]) and seven age-matched healthy controls (age 8–18 years [mean 13]). After segmentation into gray matter (GM), white matter, and cerebrospinal fluid (CSF), regional volume loss between groups was determined by voxel-based morphometry. GM volume loss appeared on all HF scans, but ischemic changes and infarcts were absent. HF subjects showed greater CSF volume than controls (mean ± SD 0.30 ± 0.04 vs. 0.25 ± 0.04 l, P = 0.03), but total intracranial volume was identical (1.39 ± 0.11 vs. 1.39 ± 0.09 l, P = NS). Regional GM volume reduction appeared in the right and left posterior hippocampus, bilateral mid-insulae, and the superior medial frontal gyrus and mid-cingulate cortex of HF subjects (threshold P < 0.001). No volume-loss sites appeared in control brains. We conclude that pediatric HF patients show brain GM loss in areas similar to those of adult HF subjects. Substantial changes emerged in sites that regulate autonomic function as well as mood, personality and short-term memory. In the absence of thromboembolic disease and many comorbid conditions found in adult HF patients, pediatric HF patients show significant, focal GM volume loss, which may coincide with the multiple neurologic and psychological changes observed in patients with HF.

The Prognostic Value of N-Terminal Pro–B-Type Natriuretic Peptide for Death and Cardiovascular Events in Healthy Normal and Stage A/B Heart Failure Subjects

Our objective was to determine the prognostic value of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) for death and cardiovascular events among subjects without risk factors for heart failure (HF), which we term healthy normal. Previous studies report that plasma NT-proBNP has prognostic value for cardiovascular events in the general population even in the absence of HF. It is unclear if NT-proBNP retains predictive value in healthy normal subjects. We identified a community-based cohort of 2,042 subjects in Olmsted County, Minnesota. Subjects with symptomatic (stage C/D) HF were excluded. The remaining 1,991 subjects underwent echocardiography and NT-proBNP measurement. We further defined healthy normal (n = 703) and stage A/B HF (n = 1,288) subgroups. Healthy normal was defined as the absence of traditional clinical cardiovascular risk factors and echocardiographic structural cardiac abnormalities. Subjects were followed for death, HF, cerebrovascular accident, and myocardial infarction with median follow-up of 9.1, 8.7, 8.8, and 8.9 years, respectively. NT-proBNP was not predictive of death or cardiovascular events in the healthy normal subgroup. Similar to previous reports, in stage A/B HF, plasma NT-proBNP values greater than age-/sex-specific 80th percentiles were associated with increased risk of death, HF, cerebrovascular accident, and myocardial infarction (p < 0.001 for all) even after adjustment for clinical risk factors and structural cardiac abnormalities. These findings do not support the use of NT-proBNP as a cardiovascular biomarker in healthy normal subjects and have important implications for NT-proBNP-based strategies for early detection and primary prevention of cardiovascular disease.

Anti-heart and anti-intercalated disk autoantibodies: evidence for autoimmunity in idiopathic recurrent acute pericarditis

BackgroundIdiopathic recurrent acute pericarditis (IRAP) is a rare disease of suspected, yet unproved, immune-mediated origin. The finding of serum heart-specific autoantibodies in IRAP would strengthen the autoimmune hypothesis and provide...

Advanced heart failure and nocturnal hypoxaemia due to central sleep apnoea are associated with increased serum erythropoietin

Central sleep apnoea (CSA) and increased serum erythropoietin (EPO) concentration have each been associated with adverse prognosis in heart failure (HF) patients. The aim of this study was to examine the relationship between nocturnal hypoxaemia due to CSA and the serum EPO concentration in patients with HF. Heart failure subjects (n = 33) and healthy controls (n = 18) underwent polysomnography (PSG) for diagnosis of CSA and identification and quantification of hypoxaemia. Blood collection for measurement of EPO was performed immediately post-PSG. For the analysis, HF subjects were dichotomized into subgroups defined by the presence or absence of CSA and by HF severity. Multivariate analyses were performed to evaluate the relationships of hypoxaemia and advanced HF to EPO concentration. Mean EPO concentration was 62% higher for HF subjects with CSA than for healthy controls (P = 0.004). The magnitude of nocturnal hypoxaemia was significantly and positively related to EPO concentration (r = 0.45, P = 0.02). Advanced HF was also significantly and positively related to EPO concentration (r = 0.43, P = 0.02). On multivariate analysis, the presence of combined nocturnal hypoxaemia and advanced HF yielded greater correlation to EPO concentration than either factor alone (r = 0.57, P = 0.04 and P = 0.05, respectively). Linear regression demonstrated that the combination of New York Heart Association Class and CSA was strongly associated with EPO concentration (P < 0.0001). In non-anaemic HF patients, advanced HF and hypoxaemia due to CSA may each be independently associated with increased serum EPO concentration.

Myocardial Iodine-123 Meta-Iodobenzylguanidine Imaging and Cardiac Events in Heart Failure: Results of the Prospective ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) Study

The ADMIRE-HF (AdreView Myocardial Imaging for Risk Evaluation in Heart Failure) study prospectively evaluated iodine-123 meta-iodobenzylguanidine ((123)I-mIBG) imaging for identifying symptomatic heart failure (HF) patients most likely to experience cardiac events. Single-center studies have demonstrated the poorer prognosis of HF patients with reduced (123)I-mIBG myocardial uptake, but these observations have not been validated in large multicenter trials. A total of 961 subjects with New York Heart Association (NYHA) functional class II/III HF and left ventricular ejection fraction (LVEF) < or =35% were studied. Subjects underwent (123)I-mIBG myocardial imaging (sympathetic neuronal integrity quantified as the heart/mediastinum uptake ratio [H/M] on 4-h delayed planar images) and myocardial perfusion imaging and were then followed up for up to 2 years. Time to first occurrence of NYHA functional class progression, potentially life-threatening arrhythmic event, or cardiac death was compared with H/M (either in relation to estimated lower limit of normal [1.60] or as a continuous variable) using Cox proportional hazards regression. Multivariable analyses using clinical, laboratory, and imaging data were also performed. A total of 237 subjects (25%) experienced events (median follow-up 17 months). The hazard ratio for H/M > or =1.60 was 0.40 (p < 0.001); the hazard ratio for continuous H/M was 0.22 (p < 0.001). Two-year event rate was 15% for H/M > or =1.60 and 37% for H/M <1.60; hazard ratios for individual event categories were as follows: HF progression, 0.49 (p = 0.002); arrhythmic events, 0.37 (p = 0.02); and cardiac death, 0.14 (p = 0.006). Significant contributors to the multivariable model were H/M, LVEF, B-type natriuretic peptide, and NYHA functional class. (123)I-mIBG imaging also provided additional discrimination in analyses of interactions between B-type natriuretic peptide, LVEF, and H/M. ADMIRE-HF provides prospective validation of the independent prognostic value of (123)I-mIBG scintigraphy in assessment of patients with HF. (Meta-Iodobenzylguanidine Scintigraphy Imaging in Patients With Heart Failure and Control Subjects Without Cardiovascular Disease, NCT00126425; Meta-Iodobenzylguanidine [123I-mIBG] Scintigraphy Imaging in Patients With Heart Failure and Control Subjects Without Cardiovascular Disease, NCT00126438).