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Background: We aimed to investigate whether the assessment of functional capacity by the 6-minute walking test (6MWT) might improve the predictive ability of 2 validated clinical scores for risk stratification in heart failure (HF)., Methods and Results: The Cardiac and Comorbid Conditions HF (3C-HF) and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) scores were evaluated in 466 consecutive HF patients who completed a pre-discharge 6MWT. The 12-month event rate was 7.7%. Both the 2 scores and the 6MWT predicted all-cause mortality (all P<0.0001), with a hazard ratio of 2.650 [95%CI 1.879-3.737], 2.754 [95%CI 1.870-4.056] for each one SD increase in the 3C-HF and MAGGIC, respectively, and of 2.080 [95% CI 1.619-2.671] for each one SD decrease in the meters walked. The addition of a 6MWT to both the 3C-HF and MAGGIC scores significantly improved predictive discrimination (c-index 0.793 [95% CI 0.722-0.864] and 0.802 [95% CI 0.733-0.871], respectively) and risk classification (integrated discrimination improvement, IDI 0.052 [95% CI 0.024-0.101] and 0.046 [95% CI 0.020-0.102], respectively). In the intermediate and high risk strata identified on the basis of both the 3C-HF and MAGGIC scores, mortality rates significantly differed according to a distance walked < or ≥376 m., Conclusions: In HF patients, a pre-discharge evaluation combining the 6MWT to clinical scores improves prediction of 12-month mortality.

Objectives: Muscle release of the amino acid 3-methyl-histidine (3MH) is a sensitive index of myofibrillar protein overdegradation (MPO). We hypothesized that patients with chronic heart failure (CHF) could have increased muscle release of 3MH, which in turn reflects MPO, and that serum electrolyte sodium (Na(+)) and potassium (K(+)) levels may be associated with this 3MH muscle release., Methods: Thirty-one overweight outpatients (body mass index, 27 ± 4.4 kg/m(2); 22 men and 9 women; age, 56 ± 8.7 y) with clinically stable CHF were studied. After a 24-hour meat-free diet and overnight fasting, patients underwent blood sampling from a cannulated arm vein (V) and concomitantly from the arterial artery (A) to determine plasma 3MH levels and to calculate the A-V difference. Serum levels of Na(+) and K(+) in the venous blood were determined, and the Na(+)/K(+) ratio was calculated. Ten healthy subjects who were matched for gender, age, and body mass index served as controls and underwent the same protocol as the patients with CHF., Results: The patient group had higher arterial (P = 0.02) and venous (P = 0.005) 3MH levels but a similar A-V 3MH difference (P = 0.28) as compared with the controls. Within the CHF group, 67.7% of patients released 3MH, which resulted in a negative A-V value (P < 0.02 as compared with controls). In patients with CHF, the A-V 3MH difference correlated positively with the serum K(+) level (r = 0.62; P = 0.0002) and negatively with Na(+)/K(+) ratio (r = -0.55; P = 0.002). No association was found between the A-V 3MH difference and the Na(+) level., Conclusions: The study demonstrated the existence of MPO in resting overweight patients with CHF, thereby suggesting that low serum levels of K(+) may contribute to MPO., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Unlabelled: Treatment with long-chain n-3 polyunsaturated fatty acids (n-3 PUFAs) can improve clinical outcomes in patients with heart failure (HF). Circulating levels of n-3 PUFA, an objective estimation of exposure, have never been measured in a large cohort of patients with HF., Methods: We measured n-3 PUFA in plasma phospholipids at baseline and after 3 months in 1,203 patients with chronic HF enrolled in the GISSI-Heart Failure trial and randomized to n-3 PUFA 1 g/daily or placebo. N-3 PUFA levels were related to clinical characteristics, pharmacologic treatments, dietary habits, circulating biomarkers, and mortality., Results: Baseline n-3 PUFA (5.1 ± 1.8 mol%) was associated with dietary fish intake, with an average difference of 43% between patients with the lowest and highest consumptions (P < .0001). Baseline eicosapentaenoic acid (EPA) but not docosahexaenoic acid (DHA) was inversely related to C-reactive protein, pentraxin-3, adiponectin, natriuretic peptide, and troponin levels. Three-month treatment with n-3 PUFA raised their levels by 43%, independently of dietary fish consumption; increases in EPA levels were associated with decreased pentraxin-3. Low baseline levels of EPA but not DHA were no longer related to higher mortality after the addition of circulating biomarkers to multivariable models., Conclusion: Before supplementation, circulating n-3 PUFA levels in patients with chronic HF mainly depend on dietary fish consumption and are inversely related to inflammatory markers and disease severity. Three-month treatment with n-3 PUFA markedly enriched circulating EPA and DHA, independently of fish intake, and lowered pentraxin-3. Low EPA levels are inversely related to total mortality in patients with chronic HF., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background: We hypothesized that obese chronic heart failure (CHF) patients, who are known to have less cardiac dysfunction, could show preserved muscle protein balance. The aim of this study was to relate muscle protein balance and cardiac function to body mass index (BMI) in order to provide further insight to the obesity paradox in CHF patients., Methods: Thirty stable CHF patients were categorized by BMI (n=6, normal; n=14, overweight; n=10, obese) and underwent post-absorptive: (i) right heart catheterization to determine cardiac hemodynamics and (ii) arterial and venous blood sampling to measure arterial and venous levels of essential amino acids (EAAs) and to calculate arterovenous differences (positive = uptake; negative = release). Muscle protein over-degradation was assessed by muscle release of the EAA phenylalanine. Plasma N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) was also determined. Twenty healthy subjects, matched for age, served as controls and underwent radial artery and vein sampling only., Results: Obese CHF patients had normal muscle protein balance, muscle EAA release, and arterial EAA concentration. Among the non-obese patients, normally weighted ones had more pronounced muscle protein over-degradation and greater reduction of arterial EAAs (p<0.01 for both) and EAA release (p<0.06) than overweight ones. Arterial leucine levels correlated negatively with NT-pro-BNP (r=-0.75; p<0.0001) and positively with LVEF (r=+0.68; p<0.0001). Within EAAs, branched chain amino acids were positively associated with stroke volume index (r=+0.51; p=0.004)., Conclusions: Only obese patients with CHF have balanced muscle protein metabolism. This may contribute to explain the obesity paradox., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)

Objective: The proteins in the lungs are in constant flux, undergoing degradation and resynthesis. We investigated pulmonary protein and amino acid metabolism, the biochemical basis of the remodeling process, in individuals with chronic heart failure receiving or not receiving β-blocker therapy with bisoprolol (BIS)., Methods: Clinically stable rehabilitative patients with chronic heart failure, without metabolic diseases or liver/renal failure, and with a stable weight over the preceding 3 mo underwent right heart catheterization, and radial artery cannulation. Mixed central venous and arterial blood samples were drawn simultaneously to calculate the venous-arterial difference of amino acids (pulmonary uptake and release)., Results: Twenty-two patients on BIS therapy and eight not receiving BIS were analyzed. The two groups showed a net pulmonary protein synthesis (i.e., a positive value of phenylalanine [venous-arterial difference] × cardiac index product) and amino acid extraction, the rates of which were significantly lower in patients on BIS therapy. The two groups had pulmonary hypertension (mean pulmonary artery pressure >19 mmHg). Pulmonary vascular resistance was 57% higher in patients not receiving BIS than in those on BIS therapy (6.65 ± 2.90 versus 4.23 ± 1.49 mmHg/L · min⁻¹ · m⁻², P < 0.05). Pulmonary vascular resistance correlated positively with the pulmonary extraction of total essential amino acids (r = +0.4576, P = 0.01) and leucine (r = +0.5083, P = 0.004), the most important amino acid for protein synthesis., Conclusion: Patients with chronic heart failure have increased rates of amino acid extraction and pulmonary protein synthesis, suggesting, at least in part, an increased rate of lung remodeling. Therapy with BIS attenuates lung metabolic abnormalities., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Unlabelled: INTRODUCTION. Psychological research on Chronic Heart Failure has mainly focused on the patient's emotional status, particularly on anxiety and depression., Aim: To describe the psychological characteristics of a sample of hospitalized CHF inpatients and to assess their illness perception and their dispositional optimism and pessimism, and the mutual relations among these variables., Method: 77 CHF inpatients of a Department of Cardiovascular Rehabilitation (aged 57.4 +/- 10.0) were consecutively enrolled. The following psychological constructs were assessed: anxiety (HADS-A), depression (BDI-II: total score, Cognitive and Affective Factors), illness perception (Brief IPQ) and dispositional optimism and pessimism (LOT-R). Correlations between Brief IPQ and LOT-R data were calculated and subsequently ANOVAs were performed on Brief IPQ and LOT-R data divided by sex, anxiety and depression. RESULTS. As to anxiety, 57 (74.0%) patients resulted not anxious, whereas 10 (13.0%) reported light anxious symptomatology, 8 (10.4%) moderate and 2 (2.6%) severe. Thirty nine patients (50.7%) resulted not depressed, whereas 19 (24.7%) resulted severely depressed. Significant correlations emerged among dispositional pessimism (LOT-R) and the following Brief IPQ variables: Treatment Control (r = - 0.40 p < 0.0001) and Coherence (r = -0.35 p = 0.002). Anxiety and depression differentiated the sample considering illness perception but not dispositional optimism and pessimism. CONCLUSIONS. As to anxiety and depression our data enlighten the presence of emotional disorders in CHF patients. Moreover illness perception differentiates the sample when analysed considering the emotional status. Interesting are the relationships among illness representations and dispositional pessimism, which deserve further studies. In our sample pessimism seems not to be opposed, in a bipolar construct, to optimism and results not related to depression; besides pessimism might have a predictive role in patient's disease management in a not yet explored direction. Finally our data confirm what usually qualitatively observed in clinical practice during the psychological intervention in rehabilitation cardiology. They also provide scientific information on the utility of an accurate psychological screening and a consequent specific intervention aimed at both providing psychological support and cognitive restructuring.

HRT (heart rate turbulence), describing the heart rate changes following a premature ventricular contraction, has been regarded as an indirect index of baroreflex function. However, limited data are available on its relationship with invasive assessment by phenylephrine injection (Phe-slope). In the present study, we therefore compared these methodologies in a series of patients with HF (heart failure) in which both measures together with clinical and haemodynamic data were available. HRT parameters [TO (turbulence onset) and TS (turbulence slope)] were measured from 24-h Holter recordings obtained within 1 week of baroreflex sensitivity assessment and right heart haemodynamic evaluation (Swan-Ganz catheter). HRT was computable in 135 out of 157 (86%) patients who had both a phenylephrine test and haemodynamic evaluation. TO and TS significantly correlated with Phe-slope (r=-0.39, P<0.0001 and r=0.66, P<0.0001 respectively). Age, baseline heart rate, LVEF (left ventricular ejection fraction), PCP (pulmonary capillary pressure), CI (cardiac index) and sodium were significant and independent predictors of Phe-slope, accounting for 51% of its variability. Similarly, age, baseline heart rate and PCP, and NYHA (New York Heart Association) classes III-IV were independent predictors for TS and explained 48% of its variability, whereas only CI and LVEF were found to be significantly related to TO and explained a very limited proportion (20%) of the variability. In conclusion, these results suggest that HRT may be regarded as a surrogate measure of baroreflex sensitivity in clinical and prognostic evaluation in patients with HF.

Objectives: No studies have compared the prognostic values of invasive (phenylephrine, Phe) and noninvasive (transfer function) assessments of baroreflex sensitivity (BRS)., Methods: Three hundred and one heart failure patients [age: 53 ± 8 years, New York Heart Association class II-III: 88%, left-ventricular ejection fraction (LVEF): 28 ± 8%] underwent an 8 min ECG and arterial pressure recording, followed by Phe administration., Results: Phe-BRS and transfer function BRS (TF-BRS) could be measured in 89 and 72% of cases, respectively. The correlation and the 5-95th percentiles of the difference between the two methods were 0.61 (P < 0.0001), and -7.6, +7.5 ms/mmHg, respectively. During a median of 36 months, 23% of the patients experienced a cardiac event. In the common dataset of 202 patients, both BRS measurements (<3 ms/mmHg) were significantly associated with the outcome (both P < 0.001), but Phe-BRS had a better discriminatory power (area under the curve (AUC): 0.74 vs. 0.66, P  = 0.03). Patients with a missing BRS (due to high grade ectopic activity) had a higher event rate (Phe-BRS: 38 vs. 24%, P  = 0.23; TF-BRS: 37 vs. 19%, P  = 0.002). Using this information, a prognostic index was derived for each BRS method, increasing measurability to 94 and 98%, respectively. Both indexes significantly predicted the outcome after adjustment for clinical covariates [hazard ratio (95% CI): 1.9 (1.1-3.3), P  = 0.03 for Phe index and 2.0 (1.1-3.7), P  = 0.02 for transfer function index]., Conclusion: Although the measurability of TF-BRS in heart failure patients is impaired, prognostic information can be extended to almost all patients, with a predictive power similar to that of Phe-BRS. The two measurements, however, convey a certain amount of independent prognostic information. Hence, TF-BRS can be integrated with but not replace Phe-BRS.

Objectives: This study investigated the clinical correlates and prognostic value of depressed baroreceptor-heart rate reflex sensitivity (BRS) among patients with heart failure (HF), with and without beta-blockade., Background: Abnormalities in autonomic reflexes play an important role in the development and progression of HF. Few studies have assessed the effects of beta-blockers on BRS in HF., Methods: The study population consisted of 103 stable HF patients, age (median [interquartile range]) 54 years (48 to 57 years), with New York Heart Association (NYHA) functional class > or =III in 22, and with a left ventricular ejection fraction (LVEF) of 30% (24% to 36%), treated with beta-blockers; and 144 untreated patients, age 55 years (48 to 60 years), with NYHA functional class > or =III in 47%, and an LVEF of 26% (21% to 30%). They underwent BRS testing (phenylephrine technique)., Results: In both treated and untreated patients, a lower BRS was associated with a higher (> or =III) NYHA functional class (p = 0.0002 and p < 0.0001, respectively); a more severe (> or =2) mitral regurgitation (p = 0.007 and p = 0.0002), respectively; a lower LVEF (p = 0.0004 and p = 0.001, respectively), baseline RR interval (p = 0.0004 and p = 0.0002, respectively), and SDNN (p < 0.0001, p = 0.002, respectively); and a higher blood urea nitrogen (p = 0.004, p < 0.0001, respectively). Clinical variables explained only 43% of BRS variability among treated and 36% among untreated patients. During a median follow-up of 29 months, 17 of 103 patients and 55 of 144 patients, respectively, experienced a cardiac event. A depressed BRS (<3.0 ms/mm Hg) was significantly associated with the outcome, independently of known risk predictors and beta-blocker treatment (adjusted hazard ratio: 3.0 [95% confidence interval: 1.5 to 5.9], p = 0.001)., Conclusions: Baroreceptor-heart rate reflex sensitivity does not simply mirror the pathophysiological substrate of HF. A depressed BRS conveys independent prognostic information that is not affected by the modification of autonomic dysfunction brought about by beta-blockade.

Background: Periodic Breathing (PB, waxing and waning of tidal volume in which hyperventilation alternates with periods of apnoea or hypopnoea), is common during sleep and wakefulness in patients with Heart Failure (HF) and may increase mortality., Aim: To assess the effect of short-term, day-time PB on prognosis, in HF patients., Methods: We prospectively studied 380 consecutive HF referrals who had a 10 min, supine day-time respiratory recording. We related PB (adjusted for known predictors) to total cardiac mortality, during a median follow-up of 41 months., Results: Day-time PB occurred in 145/380 patients who had more severe HF and more compromised left ventricular function (p<0.005). Survival curves began to separate after 10 months and diverged steadily over the next 4 years with a cumulative risk of 41% (PB) vs 26% (No-PB), p=0.002. PB was independently predictive of increased cardiac mortality when entered into a clinical prognostic model (including NYHA Class, LVEF, LVEDD, Systolic Arterial Pressure, beta-blocker treatment, peak VO2 and blood urea) with a RR: 1.8, 95% CI 1.20-2.81., Conclusion: In advanced HF the presence of PB during a short day-time recording adds to known predictors of cardiac mortality. This may have practical implications for trials of HF therapy.

Aims: Anaemia is often observed in patients with chronic heart failure (CHF), and it may be associated with a worse prognosis. Aim of this study was to identify the individual mechanisms of anaemia in CHF patients., Methods and Results: One hundred and forty-eight consecutive patients with haemoglobin concentration <13 g/dL (if males) or <12 g/dL (if females) were enrolled. Factors responsible for anaemia were investigated by evaluating endogenous erythropoietin (Epo) production, serum cytokines levels, body iron status, and iron supply for erythropoiesis. Most patients (57%) presented anaemia of chronic disease and among them, 92% showed evidence of a defective endogenous Epo production. This was indicated by an observed/predicted log(serum Epo) ratio less than 0.8 and/or a defective iron supply for erythropoiesis diagnosed by low transferrin saturation and/or increased value of soluble transferrin receptor. According to regression analysis sex, renal failure, and serum Epo were correlated with anaemia., Conclusion: According to our study, about half of anaemic CHF patients showed anaemia of chronic disease with blunted endogenous Epo production and/or a defective iron supply for erythropoiesis. Determination of the individual mechanisms of anaemia in CHF could justify a rational therapeutic approach to anaemia.

Objectives: We sought to assess applicability, clinical correlates, and prognostic value of the transfer function method for measuring baroreflex sensitivity (TF-BRS)., Background: Abnormalities in autonomic reflexes play an important role in the development and progression of chronic heart failure (CHF). Simple and non-invasive techniques for clinical measurement of such reflexes are desirable., Methods: In 317 stable CHF patients in sinus rhythm (median age [interquartile range]: 54 years [48 to 59 years], New York Heart Association [NYHA] functional class II to III: 88%, left ventricular ejection fraction [LVEF]: 27% [22% to 33%]) we recorded electrocardiograms and non-invasive arterial pressure during paced breathing to measure TF-BRS., Results: Owing to a high number of ectopic beats, TF-BRS could be computed in 72% of the patients; TF-BRS was lower in NYHA functional class III to IV and mitral regurgitation 2 to 3 (p < 0.0005 for both). Correlation with LVEF and standard deviation of all normal-to-normal intervals was 0.18 and 0.31 (p < 0.001 for both). During a mean follow-up of 26 months, 23% of the patients experienced a cardiac event. A depressed TF-BRS (< or =3.1 ms/mm Hg) was significantly associated with the outcome (hazard ratio 3.2, 95% confidence interval [CI] 1.7 to 6.0, p = 0.0003). Patients with a missing TF-BRS had a high event rate (36%). Combining this information with available TF-BRS measurements, a new prognostic index could be computed in 97% of the patients that significantly predicted the outcome after adjustment for clinical and functional variables (hazard ratio 2.5, 95% CI 1.3 to 4.6 p = 0.004)., Conclusions: In CHF patients in sinus rhythm, TF-BRS conveys relevant clinical and prognostic information, but its measurability is markedly affected by ectopic activity. Nevertheless, a TF-BRS-based risk index carrying significant and independent prognostic information can be computed in almost all patients.

Background: Correct classification of chronic heart failure (CHF) patients by dual evidence of congestion and adequate perfusion is the primary clinical focus for management., Objectives: To evaluate the accuracy of echo-Doppler compared with clinical evaluation in determining the hemodynamic profile of patients with CHF; and to compare therapeutic changes based on hemodynamic or echo-Doppler findings., Methods: Three hundred and sixty-six consecutive CHF patients (ejection fraction 25+/-7%) in sinus rhythm, undergoing evaluation for cardiac transplantation, underwent physical examination prior to right heart catheterization and echo-Doppler studies. Subsequently, patients were randomized to therapeutic optimization using either right heart catheterization or echo-Doppler data. The end-points were: identification of low cardiac output (cardiac index <2.2 l/min/m(2)); high pulmonary wedge pressure (PWP >18 mm Hg); high right atrial pressure (RAP >5 mm Hg) and analysis of therapeutic changes made in response to the right heart catheterization and echo-Doppler studies., Results: Echo-Doppler showed better accuracy in estimating abnormal hemodynamic indices than clinical variables (cardiac index <2.2 l/min/m(2): echo positive predictive accuracy (PPA) 98% vs. clinical PPA 52% p<0.00001; PWP >18 mm Hg: echo PPA 85% vs. clinical PPA 76% p=0.0011; RAP >5 mm Hg: echo PPA 82% vs. clinical PPA 57% p<0.00001). When applied to individual patients, the echo-Doppler assessment was more accurate than clinical evaluation in defining the different hemodynamic profiles: wet/cold (89% vs. 13%, p<0.0001); wet/warm (73% vs. 30%, p<0.0001); dry/cold (68% vs. 12%, p<0.0001); dry/warm (88% vs. 51%, p<0.0001). Therapeutic decision-making based on echo-Doppler findings was similar to that based on hemodynamics., Conclusion: Echo-Doppler hemodynamic monitoring proved accurate in estimating hemodynamic profiles and influenced therapeutic management.

Background: The prognosis of chronic heart failure (CHF) remains poor despite advances in medical management. Several different variables determine prognosis. Recently anemia has emerged as an independent prognostic variable in the evaluation of CHF. It is therefore important to analyze the role of anemia in patients with mild to severe CHF already well characterized by hemodynamic, echo-Doppler, and cardiopulmonary exercise testing., Objective: We performed this study to evaluate, in a large general cohort of CHF patients, the frequency of anemia and its correlation with their clinical profile. We assessed the prognostic value of anemia in relation to other known prognostic variables., Methods: Two-dimensional echocardiography, right heart catheterization, cardiopulmonary tests and laboratory examinations were performed in a population of 980 consecutive patients with CHF (53 +/- 9.4 years, 85% male, LVEF 25 +/- 8%; 45% with NYHA class III-IV). A hemoglobin (Hb) concentration less than 12 g/dl was used to define anemic patients. The primary end point was cardiac death or urgent heart transplantation., Results: Nineteen percent of patients were anemic. These patients had a lower body mass index (24 +/- 3 vs. 25 +/- 4 Kg/m2 p < 0.0004), a worse functional class (64% were in NYHA class III-IV vs 41% in the non-anemic group, p < 0.0001), poorer exercise capacity (12.4 vs. 14.8 ml/kg/min peak VO2, p < 0.0001) and increased right (7 +/- 5 vs. 5 +/- 4 mmHg, p < .0004) and left (21 +/- 9 vs. 19 +/- 10 p < 0.007) ventricular filling pressures. During a 3-year follow-up cardiac deaths occurred in 236 (24%) and 52 (5%) of patients received an urgent heart transplant. On univariate regression analysis anemia was significantly correlated with these "hard" cardiac events (39% of anemic patients vs 27% of non-anemic patients). By multivariate logistic regression analysis different prognostic models were identified using non-invasive, with or without peak VO2, or invasive parameters. The prognostic model including anemia (AUC(ROC): 0.720) showed similar accuracy in predicting cardiac events to other prognostic models with peak VO2 (AUC(ROC): 0.719) or invasive variables (AUC(ROC): 0.719)., Conclusions: The present study demonstrates that anemia in CHF patients is associated with prognosis, worse NYHA functional class, exercise capacity and hemodynamic profiles. The relationship between anemia and mortality is independent of other simple non-invasive prognostic factors. Prognostic models with more complex or invasive independent predictors did not increase the accuracy to predict cardiac mortality or the need for urgent transplantation.

Objectives: The goal of this study was to investigate the nutrition adequacy and energy availability for physical activity in free-living, clinically stable patients with chronic heart failure (CHF)., Background: Little information exists regarding the nutrition adequacy and alimentary habits of patients with clinically stable CHF. We hypothesized that CHF patients have an inadequate intake of calories and protein, leading to a negative calorie and nitrogen balance, an expression of increased tissue breakdown., Methods: In 57 non-obese patients with CHF (52 males and 5 females; 52 +/- 3 years; body mass index <25 kg/m(2)) and in 49 healthy subjects (39 males and 10 females) matched for age, body mass index, and sedentary life style we evaluated total energy expenditure (TEE), calorie intake (kcal(I)), and nitrogen intake (N(I)) from a seven-day food diary, total nitrogen excretion (TNE), and energy availability (EA = kcal(I) - resting energy expenditure). A zero calorie balance (CB) occurred when kcal(I) = TEE; a nitrogen balance (NB) in equilibrium was set at NB (= N(I) - TNE) 0 +/- 1 g/day., Results: In patients and controls kcal(I) and N(I) were similar. However, in CHF patients the kcal(I) was

Background: The predictive value of heart rate variability (HRV) in chronic heart failure (CHF) has never been tested in a comprehensive multivariate model using short-term laboratory recordings designed to avoid the confounding effects of respiration and behavioral factors., Methods and Results: A multivariate survival model for the identification of sudden (presumably arrhythmic) death was developed with data from 202 consecutive patients referred between 1991 and 1995 with moderate to severe CHF (age 52+/-9 years, left ventricular ejection fraction 24+/-7%, New York Heart Association class 2.3+/-0.7; the derivation sample). Time- and frequency-domain HRV parameters obtained from an 8' recording of ECG at baseline and during controlled breathing (12 to 15 breaths/min) were challenged against clinical and functional parameters. This model was then validated in 242 consecutive patients referred between 1996 and 2001 (validation sample). In the derivation sample, sudden death was independently predicted by a model that included low-frequency power (LFP) of HRV during controlled breathing < or =13 ms2 and left ventricular end-diastolic diameter > or =77 mm (relative risk [RR] 3.7, 95% CI 1.5 to 9.3, and RR 2.6, 95% CI 1.0 to 6.3, respectively). The derivation model was also a significant predictor in the validation sample (P=0.04). In the validation sample, LFP < or =11 ms2 during controlled breathing and > or =83 ventricular premature contractions per hour on Holter monitoring were both independent predictors of sudden death (RR 3.0, 95% CI 1.2 to 7.6, and RR 3.7, 95% CI 1.5 to 9.0, respectively)., Conclusions: Reduced short-term LFP during controlled breathing is a powerful predictor of sudden death in patients with CHF that is independent of many other variables. These results refine the identification of patients who may benefit from prophylactic implantation of a cardiac defibrillator.

Background: Physical training has proven to be a valid and effective therapeutic tool capable of counteracting muscle changes that occur in chronic heart failure (CHF) patients. Nevertheless, few studies have analyzed the frequency of use of this therapy and the reasons for any reduced compliance and adherence to the prescription. The aim of this study was to quantify the frequency of the participation of CHF patients in a program of domiciliary physical training and to analyze the factors that can influence adherence to the program., Methods: Three hundred and twenty-two consecutive CHF patients (ejection fraction 28 +/- 7%) in a stable condition with optimized medical therapy performed a cardiopulmonary test, including determination of peak oxygen consumption, at baseline and after 9 +/- 3 months. All the patients had participated in sessions of health education on the relationship between illness/physical activity. The prescription of physiotherapy was decided by the physician on the basis of each patient's clinical need assessed in the diagnostic-therapeutic management. The patient referred for physiotherapy entered a therapeutic strategy that included sessions of training on anaerobic threshold, self-management of the session, and formulation of a domiciliary physical training program. During the follow-up evaluation the patients were asked to complete a questionnaire, which investigated the relationship between several factors and the patient's adherence to the physical training program, which was objectively evaluated by the change in peak oxygen consumption recorded at the end of the training, taking into account the spontaneous variations found in the control group., Results: Two hundred and eighty-two of the patients (88%) satisfied the criteria for inclusion in the study. Only 61 (22%) of them were judged to have adhered to the recommended physical training. Type of employment (chi 2 = 7.08, p < 0.02), the state of retirement (chi 2 = 8.9, p < 0.01), ischemic etiology (chi 2 = 5.91, p < 0.01), compatibility with employment (chi 2 = 15.8, p < 0.0004), availability of suitable domestic conditions (chi 2 = 14.5, p < 0.0008), the structure of the training program (chi 2 = 22.33, p < 0.0001) and a learning phase in a gym (chi 2 = 71.33, p < 0.0001) were significantly correlated at univariate analysis with the performance of the physical training. Multivariate analysis identified the structure of the training program (odds ratio 9.6, 95% confidence interval 2.8-33) and a learning phase in a gym (odds ratio 49.6, 95% confidence interval 11-210.8) as independent factors (r2 = 0.48) determining adherence to the physical training program., Conclusions: Adherence to unmonitored, recommended domiciliary physical training appears to be modest even in patients who have been in-patients in a cardiac rehabilitation center. Various factors seem to influence the adherence of the patient to this therapy, but structural factors, such as the organization and learning of the program, more strongly influenced the patient's subsequent compliance.

Objective: This study compared the effectiveness and cost/utility ratio between a heart failure (HF) management program delivered by day-hospital (DH) and usual care in chronic heart failure (CHF) outpatients., Background: Previous studies showed that about 50% of readmissions for CHF can be prevented by a multidisciplinary approach. However, the performance, effectiveness, and cost/utility ratio of a process of HF outpatient management related to evidence-based medicine have not been considered., Methods: A total of 234 prospective patients discharged by a HF Unit were randomized to two management strategies: 122 patients to usual community care and 112 patients to a HF management program delivered by the DH. Management (rate of readmissions, therapeutic interventions), functional parameters (New York Heart Association [NYHA] functional class, left ventricular diameters, and ejection fraction, deceleration time of early diastolic mitral flow, peak oxygen uptake, and mitral regurgitation) and hard outcomes (cardiac death and urgent cardiac transplantation) were evaluated. The cost/utility ratios of the two strategies were compared., Results: After 12 +/- 3 months of follow-up, the individual rate access in DH was 5.5 +/- 3.8 days. The DH subjects were readmitted to the hospital less frequently than were the usual-care group patients (13 vs. 78, p < 0.00001). Patients allocated to usual-care management showed heterogeneous changes in NYHA functional class (13% improved and 16% worsened p = NS); In contrast, the DH group showed significant changes in NYHA functional class (23% improved and 11% worsened, p < 0.009). Hard cardiac events in the one-year follow-up occurred in 25/234 (10.6%) patients; cardiac death occurred in 21/122 (17.2%) of the community group and in 3/112 (2.7%) in the DH group (p < 0.0007). One DH patient underwent urgent transplantation. Comparison of the two managerial models by Cox regression analysis showed that DH management significantly protected against the appearance of hard events (relative risk [RR] 0.17; confidence interval [CI] 0.06 to 0.66). The cost/utility ratio of the two management strategies was similar (usual care $2,409 vs. DH $2,244). The incremental analysis revealed a cost savings of $1,068 for each quality-adjusted life year gained. The cost/utility ratio for the integration of DH management of CHF was $19,462 (CI $13,904 to $34,048)., Conclusions: A heart failure outpatient management program delivered by a DH can reduce mortality and morbidity of CHF patients. This management strategy is cost-effective and has an equitable value from a societal point of view.

Background: in patients with severe heart failure additional therapeutic support with intravenous inotropic or vasodilator drugs is frequently employed in an attempt to obtain hemodynamic and clinical control. No data comparing the use and efficacy of chronic intravenous inotropic and vasodilator therapy in patients with advanced heart failure are available.Aims: we evaluated, in a group of patients with advanced heart failure undergoing chronic infusion with dobutamine or nitroprusside, in addition to optimized oral therapy, (1) the safety of chronic infusion, (2) the efficacy of both drugs in managing unloading therapy and (3) clinical outcome of the two therapeutic strategies.Methods: one hundred and thirteen patients receiving optimized oral therapy, in functional class III/IV with symptoms and signs of refractory heart failure and requiring additional pharmacological support with either intravenous dobutamine or nitroprusside were evaluated. Clinical and therapeutic management and clinical outcome of the two groups were considered.Results: dobutamine was administered for 12 h/day for 20+/-23 days at a dosage of 7+/-3 microg/kg/min to 43 patients. The mean dose of nitroprusside was 0.76+/-0.99 microg/kg/min. The mean duration of use of this drug, administered as a 12-h/day infusion was 22+/-38 days. Nitroprusside infusion allowed greater doses of short-term ACE-inhibitors to be used compared to pre-infusion (ACE-inhibitor dose: 55+/-30 mg/day vs. 127+/-30 mg/day P<0.0001) and during dobutamine infusion (ACE-inhibitor dose: 85+/-47 mg/day vs. 127+/-30 mg/day P<0.002). Nitroprusside unlike dobutamine significantly improved the NYHA functional class. Of the 113 patients, 109 (97%) had a cardiac event during a mean follow-up of 337+/-264 days. Forty-four patients required hospitalization for worsening congestive heart failure, 45/113 (39%) patients died during the follow-up and 27/113 (24%) patients had a heart transplant in status one. Hospitalization, because of worsening heart failure was less frequent in the nitroprusside than in the dobutamine subgroup [29/51 (57%) vs. 19/22 (86%) P<0.02]. The overall mortality was 28% (20/70) in the nitroprusside group and 58% (25/43) in the dobutamine group (odds ratio 0.33 CI 0.16 to 0.73 P<0.006). In the group treated with nitroprusside, heart transplantation in status one was performed in 16/33 patients (48%), while in the dobutamine group this was done in 11/14 patients (78%) (odds ratio 0.25 CI 0.06-1.02 P<0.06). There was a significant reduction in the combined end-point of mortality/heart transplantation in status one in patients treated with nitroprusside compared to those treated with dobutamine (36/70 (51%) vs. 36/43 (84%) - (odds ratio 0.34 CI 0.14-0.80 P<0.01). The incidence of adverse events in the patients treated with nitroprusside was similar to that in those treated with dobutamine (20% vs. 17% P=ns).Conclusions: for patients awaiting heart transplantation chronic intermittent nitroprusside infusions are more effective and safer than dobutamine in relieving symptoms, facilitating unloading therapy management and improving survival. Whether chronic intermittent infusion of nitroprusside could represent a feasible medical strategy in out-patients with severe heart failure remains to be investigated. [ABSTRACT FROM AUTHOR]

Background: Heart failure patients' management in non-intensive care units might be improved by telemetry monitoring. However, telemetry adds the cost and evidence of this effectiveness is not available.Aim: To evaluate the utility of the ECG monitoring in chronic heart failure patients admitted to a non-intensive care unit.Methods: A prospective analysis of the utility of telemetry in 711 patients admitted to a Heart Failure Unit from March 1996 to September 1997.Results: One hundred and ninety-nine patients underwent telemetry; 108 telemetry findings were recorded, in 35% of NYHA class II, in 46% in NYHA class III-IV and 43% in unstable patients. Reasons for telemetry were: known arrhythmia (n=82), electrolytes disturbances (n=20), atrial fibrillation (n=12), symptoms (n=48), i.v. dobutamine (n=13), drugs control (n=16), devices control (n=8). Crossing reasons for telemetry and detected events we had, respectively, 63, 11, 2, 17, 5, 6, and 0 telemetry findings. Treatment was guided by telemetry results in only 33 cases (respectively in 18, 0, 4, 5, 5, 1, and 0 cases). Physicians perceived telemetry as unhelpful in 30% of cases; as helpful in 70%. The percentage of inutility, usefulness with and without related medical intervention were similar between stable and unstable patients (30, 18, 51% and 31, 15, 54%, respectively).Conclusion: In a heart failure unit ECG monitoring is mostly used in severe and unstable patients. However, medical decisions are rarely guided by the telemetry findings. The usefulness of telemetry might be underestimated because one of the uncounted results might be the avoidance of inappropriate intervention. [ABSTRACT FROM AUTHOR]

A letter to the editor indicating underestimated association between Cushing's disease and severe heart failure is presented.

Objectives: The aim of this study was to analyze the long-term follow-up of dilated cardiolaminopathies. Background: Lamin A/C (LMNA) gene mutations cause a variety of phenotypes. In the cardiology setting, patients diagnosed with idiopathic dilated cardiomyopathy (DCM) plus atrioventricular block (AVB) constitute the majority of reported cases. Methods: Longitudinal retrospective observational studies were conducted with 27 consecutive families in which LMNA gene defects were identified in the probands, all sharing the DCM phenotype. Results: Of the 164 family members, 94 had LMNA gene mutations. Sixty of 94 (64%) were phenotypically affected whereas 34 were only genotypically affected, including 5 with pre-clinical signs. Of the 60 patients, 40 had DCM with AVB, 12 had DCM with ventricular tachycardia/fibrillation, 6 had DCM with AVB and Emery-Dreifuss muscular dystrophy type 2 (EDMD2), and 2 had AVB plus EDMD2. During a median of 57 months (interquartile range 36 to 107 months), we observed 49 events in 43 DCM patients (6 had a later event, excluded from the analysis). The events were related to heart failure (15 heart transplants, 1 death from end-stage heart failure) and ventricular arrhythmias (15 sudden cardiac deaths and 12 appropriate implantable cardioverter-defibrillator interventions). By multivariable analysis, New York Heart Association functional class III to IV and highly dynamic competitive sports for ≥10 years were independent predictors of total events. By a bivariable Cox model, splice site mutations and competitive sport predicted sudden cardiac death. Conclusions: Dilated cardiomyopathies caused by LMNA gene defects are highly penetrant, adult onset, malignant diseases characterized by a high rate of heart failure and life-threatening arrhythmias, predicted by New York Heart Association functional class, competitive sport activity, and type of mutation. [Copyright &y& Elsevier]