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Aims: The aim of this study was to clarify whether worsening of independence in activities of daily living (ADL) and also difficulties in ADL are triggered by hospitalization in older patients with heart failure (HF) and whether difficulties in ADL can predict readmission for HF regardless of independence in ADL in these patients., Methods and Results: We enrolled 241 HF patients in the present multi-institutional, prospective, observational study. The patients were divided according to age into the non-older patient group (<75 years, n = 137) and the older patient group (≥75 years, n = 104). The Katz index and the Performance Measure for Activities of Daily Living-8 (PMADL-8) were used to evaluate independence and difficulties in ADL, respectively. The endpoint of this study was rehospitalization for HF. Independence as indicated by the Katz index at discharge was significantly lower than that before admission only in the older patient group, and the value of the PMADL-8 at discharge was significantly higher than that before admission (P < 0.001). In all patients, after adjusting for the Katz index and other variables, PMADL-8 score was a significant predictor of rehospitalization for HF (hazard ratio 1.50; 95% confidence interval 1.07-2.13; P = 0.021)., Conclusions: Worsening of both independence and difficulties in ADL was triggered by hospitalization in older HF patients, and difficulties in ADL were relevant factors for risk of rehospitalization regardless of independence in ADL. These findings indicate the importance of preventing not only decreased independence but also increased difficulties in ADL during and after hospitalization., Competing Interests: Conflict of interest: The authors certify that there are no conflicts of interest with any financial organizations regarding the material discussed in this manuscript., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Lower leg strength at hospital discharge is strongly associated with poor prognosis in older patients with acute decompensated heart failure (ADHF). Improving leg strength is important in acute-phase cardiac rehabilitation (CR)., Aims: This study aimed to clarify whether a change in leg strength occurs during hospitalization of older ADHF patients receiving CR and whether it affects leg strength at discharge., Methods and Results: We enrolled 247 ADHF patients who underwent CR during hospitalization. They were divided into the non-older patient group (&lt;75 years; n = 142) and older patient group (≥75 years; n = 105). Quadriceps isometric strength (QIS), body mass-corrected QIS (%BM QIS), and change in QIS during hospitalization (QIS ratio) were evaluated in all patients. Physical function in the stable phase was measured by the Performance Measure for Activities of Daily Living-8 (PMADL-8). The QIS value increased during hospitalization in the non-older patient group (30.0 ± 11.1 vs. 31.6 ± 10.9 kgf, P &lt; 0.001) but did not increase in the older patient group (19.1 ± 6.3 vs. 19.5 ± 6.1 kgf, P = 0.275). Multiple regression analysis revealed that PMADL-8 significantly predicted %BM QIS at discharge in the non-older patient group (β = -0.254, P = 0.004), whereas in the older patient group, QIS ratio and PMADL-8 significantly predicted %BM QIS at discharge (β = 0.264, P = 0.008 for QIS ratio and β = -0.307, P = 0.003 for PMADL-8)., Conclusions: Leg strength was not improved in older ADHF patients during hospitalization even if they received CR, and this affected leg strength at discharge, suggesting that careful skeletal muscle intervention should be provided during hospitalization, and patients need to continue exercise after discharge., Competing Interests: Conflicts of interest: The authors declare that there is no conflict of interest., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

This study aimed to determine the relation between the regression slope relating minute ventilation to carbon dioxide output (VE/VCO2 slope) and maximum phonation time (MPT), and the MPT required to attain a threshold value for VE/VCO2 slope of ≤ 34 in chronic heart failure (CHF) patients. This cross-sectional study enrolled 115 CHF patients (mean age, 54.5 years; men, 84.9%). VE/VCO2 slope was assessed during cardiopulmonary exercise testing (CPX). Thereafter, patients were divided into 2 groups according to exercise capacity: VE/VCO2 slope ≤ 34 (VE/VCO2 ≤ 34 group, n = 81) and VE/VCO2 slope > 34 (VE/VCO2 > 34 group, n = 34). For MPT measurements, all patients produced a sustained vowel/a:/ for as long as possible during respiratory effort from the seated position. All subjects showed significant negative correlation between VE/VCO2 slope and MPT (r = -0.51, P < 0.001). After adjustment for clinical characteristics, MPT was significantly higher in the VE/VCO2 ≤ 34 group vs VE/VCO2 > 34 group (21.4 ± 6.4 vs 17.4 ± 4.3 s, F = 7.4, P = 0.007). The appropriate MPT cut-off value for identifying a VE/VCO2 slope ≤ 34 was 18.12 seconds. An MPT value of 18.12 seconds may be a useful target value for identifying CHF patients with a VE/VCO2 slope ≤ 34 and for risk management in these patients.

Background: The goal of the present study was to determine knee extensor muscle strength (KEMS) and degree of renal dysfunction associated with an exercise capacity of ≥5 metabolic equivalents (METs) in male chronic heart failure (CHF) patients with chronic kidney disease (CKD)., Methods: In this cross-sectional study of 75 male CHF patients with CKD (65.3 ± 11.6 years), we measured clinical characteristics, peak [Formula: see text], estimated glomerular filtration rate (eGFR), and KEMS. Patients were divided into two groups by exercise capacity: ≥5 METs group (n = 41) and <5 METs group (n = 34). Cutoff values for KEMS and eGFR resulting in an exercise capacity of ≥5 METs were selected with ROC curves. Patients were divided into four groups according to cutoff values, and numbers of patients attaining an exercise capacity of ≥5 METs were compared between groups., Results: Age was significantly higher although eGFR, Hb, and KEMS were lower in the <5 METs versus ≥5 METs group (P < 0.001). Multiple logistic regression analysis revealed a positive significant relation between KEMS and eGFR and exercise capacity of ≥5 METs. Exercise capacity of ≥5 METs was associated with KEMS of approximately 1.69 Nm/kg and an eGFR of 45.7 mL/min/1.73 m(2). The number of patients attaining an exercise capacity of ≥5 METs in the patients who did not reach both cutoff values was significantly lower than that in any other patients (P < 0.001)., Conclusion: KEMS and eGFR may be useful indices for predicting attainment of exercise capacity of ≥5 METs in male CHF patients with CKD.

Purpose: Poor mental health (MH) is common in chronic heart failure (CHF) patients. No studies have reported a relation between MH status and objectively measured physical activity (PA) in CHF patients. The study aim was to determine self-reported MH-related differences associated with PA and target values of PA for improved MH in CHF outpatients., Methods: We divided 243 CHF outpatients (mean age 57.1 years) into two groups according to MH assessed by Short Form-36 score: high-MH (≥68 points) group (n = 148) and poor-MH (<68 points) group (n = 95). Average step count (steps) and energy expenditure on PA (EE) (kcal) per day for 1 week of PA were assessed by an accelerometer and compared between groups. PA resulting in high MH was determined by the receiver-operating characteristic (ROC) analysis., Results: PA correlated positively with MH in all patients (steps: r = 0.46, p < 0.001; EE: r = 0.43, p < 0.001). After adjusting for patient characteristics, steps and EE were significantly lower in the poor-MH versus high-MH group (5020.1 ± 280.7 versus 7174.1 ± 221.5 steps, p < 0.001; 133.9 ± 10.8 versus 215.9 ± 8.4 kcal, p < 0.001). Cut-off values of 5590.8 steps and 141.1 kcal were determined as PA target values associated with improved MH., Conclusions: Poor MH status may reduce PA. Attaining PA target values may improve MH status of CHF outpatients.

The purpose of this study was to determine both an association between mortality and physical activity (PA) objectively measured by accelerometer and cutoff values for PA in Japanese outpatients with heart failure (HF). This prospective observational study comprised 170 HF outpatients (mean age, 65.2 years; 77% men). Peak oxygen uptake (VO2) and the relation between ventilation and carbon dioxide production (VE/VCO2 slope) as indices of exercise capacity were measured during cardiopulmonary exercise testing with a cycle ergometer. PA was assessed by accelerometer-measured average step count (steps) per day for 1 week. Study endpoint was cardiovascular-related death. Over an average follow-up of 1,377.1 (median, 1,335) days, 31 cardiovascular-related deaths occurred. Patients were then divided into survivor (n = 139) and nonsurvivor (n = 31) groups. Brain natriuretic peptide level was significantly different between groups. Peak VO2 and steps were also significantly lower and VE/VCO2 slope higher in the nonsurvivors versus survivors. Univariate Cox proportional hazards analysis showed brain natriuretic peptide, peak VO2, VE/VCO2 slope, and steps to be significant prognostic indicators of survival. Multivariate analysis showed PA of ≤4,889.4 steps/day to be a strong and independent predictor of prognosis (hazard ratio: 2.28, 95% confidence interval: 1.31-6.30; p = 0.008). Kaplan-Meier curves after log-rank test showed significant prognostic difference between PA of ≤4,889.4 and >4,889.4 steps/day in the 2 groups (log-rank: 12.19; p = 0.0005). In conclusion, step count as objectively measured by accelerometer may be a prognostic indicator of mortality in Japanese outpatients with HF., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Background: This study aimed to investigate and compare prevalence of sleep disordered breathing (SDB) in Japanese patients with heart failure with reduced ejection fraction (HFrEF) versus those with HF with preserved EF (HFpEF)., Methods: This study consecutively included 101 Japanese patients (77 males) with de novo CHF. Echocardiography was performed twice, on admission and at discharge. All patients underwent portable overnight polygraphy within one week before discharge. The patients were stratified into two groups based on LVEF on admission, HFrEF (R group; LVEF<50%, n=82) or HFpEF (P group; LVEF≧50%, n=19); the prevalence of SDB and sleep study data were assessed., Results: When patients with the apnea hypopnea index ≥15 were defined as having SDB, 50% of the study patients had SDB (OSA, 10%; CSA, 39%; MSA, 1%). No significant differences in the prevalence of SDB or sleep data as well as RVSP, E/e' or plasma brain natriuretic peptide (BNP) were found between the two groups., Conclusions: SDB was identified in 50% of de novo Japanese HF patients. When E/e', RVSP and plasma BNP did not significantly differ between the two groups, the prevalence of SDB was similar regardless of LVEF., (Copyright © 2012 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Background: Patients with chronic heart failure (CHF) commonly fatigue easily due to low peak oxygen uptake (peak VO(2)), an important index of exercise capacity. Maximum phonation time (MPT) is widely used to evaluate maximum vocal capabilities because it is non-invasive, quick, and inexpensive., Aim: The aim of this study was to determine the relation between MPT and exercise capacity, and MPT required to attain an exercise capacity of ≥5 metabolic equivalents (METs) in CHF outpatients., Design: Cross-sectional study., Setting: Outpatient cardiac rehabilitation unit., Population: We enrolled 111 CHF outpatients (mean age 54.2±10.1 years)., Methods: Peak VO(2) was assessed during cardiopulmonary exercise testing (CPX) as the index of exercise capacity. After CPX, we divided the patients into two groups according to exercise capacity: ≥5 METs group (N.=68) and <5 METs group (N.=43). Measurements of MPT were taken in the seated position. All patients were asked to produce a sustained vowel /a:/ for as long as possible and were verbally encouraged during respiratory effort., Results: After adjustment for patient clinical characteristics, MPT in the CHF patients was found to be significantly higher in the ≥5 METs group than in the <5 METs group (22.1±8.4 vs. 17.0±11.6 s, F=13.5, P<0.001). Receiver-operating characteristic curve analysis of exercise capacity of ≥5 METs extracted a cutoff value for MPT of 18.27 s, with a sensitivity of 0.76, 1-specificity of 0.33, and AUC value of 0.81 (95% CI: 0.70-0.87, P<0.001)., Conclusion: There were differences in MPT in relation to an exercise capacity threshold of ≥5 METs in CHF outpatients. A MPT of 18.27 sec may be the best cutoff value to identify people with or without exercise capacity of ≥5 METs., Clinical Rehabilitation Impact: Measurement of MPT may be a useful method for estimating exercise capacity in CHF outpatients.

BACKGROUND AND PURPOSE Chronic heart failure (CHF) is associated with action potential prolongation and Ca(2+) overload, increasing risk of ventricular tachyarrhythmias (VT). We therefore investigated whether I(Ca) blockade was anti-arrhythmic in an intact perfused heart model of CHF. EXPERIMENTAL APPROACH CHF was induced in rabbits after 4 weeks of rapid ventricular pacing. Hearts from CHF and sham-operated rabbits were isolated and perfused (Langendorff preparation), with ablation of the AV node. VT was induced by erythromycin and low [K(+) ] (1.5mM). Electrophysiology of cardiac myocytes, with block of cation currents, was simulated by a mathematical model. KEY RESULTS Repolarization was prolonged in CHF hearts compared with sham-operated hearts. Action potential duration (APD) and overall dispersion of repolarization were further increased by erythromycin (300 µM) to block I(Kr) in CHF hearts. After lowering [K(+) ] to 1.5mM, CHF and sham hearts showed spontaneous episodes of polymorphic non-sustained VT. Additional infusion of verapamil (0.75 µM) suppressed early afterdepolarizations (EAD) and VT in 75% of sham and CHF hearts. Verapamil shortened APD and dispersion of repolarization, mainly by reducing transmural dispersion of repolarization via shortening of endocardial action potentials. Mathematical simulations showed that EADs were more effectively reduced by verapamil assuming a state-dependent block than a simple block of I(Ca) . CONCLUSIONS AND IMPLICATIONS Blockade of I(Ca) was highly effective in suppressing VT via reduction of transmural dispersion of repolarization and suppression of EAD. Such blockade might represent a novel therapeutic option to reduce risk of VT in structurally normal hearts and also in heart failure. LINKED ARTICLE This article is commented on by Stams et al., pp. 554-556 of this issue. To view this commentary visit http://dx.doi.org/10.1111/j.1476-5381.2011.01818.x., (© 2011 The Authors. British Journal of Pharmacology © 2011 The British Pharmacological Society.)

Background: Molecular remodeling in heart failure includes slowing of repolarization, leading to proarrhythmia., Objective: To evaluate the effects of Na(+)/Ca(2+) exchanger (NCX) inhibition on repolarization as a novel antiarrhythmic concept in chronic heart failure (CHF)., Methods and Results: CHF was induced by rapid ventricular pacing in rabbits. Left ventricular function was assessed by echocardiography. Monophasic action potentials (MAPs) showed a prolongation of repolarization in CHF after atrioventricular block and stimulation at different cycle lengths. Sotalol (100 μM, n = 13) or veratridine (0.5 μM; n = 15) resulted in a further significant increase in the MAP duration. CHF was associated with an increased dispersion of repolarization, as compared with sotalol-treated (+22 ± 7 ms; P < .05) and veratridine-treated (+20 ± 6 ms; P < .05) sham hearts. In the presence of a low potassium concentration, sotalol and veratridine reproducibly induced early afterdepolarizations (EADs) and polymorphic ventricular tachyarrhythmias (VTs). SEA0400 (1 μM), a pharmacological inhibitor of NCX, significantly shortened the MAP duration (P < .01) and reduced dispersion (P < .05). It suppressed EAD in 6 of 13 sotalol-treated failing hearts and in 9 of 10 veratridine-treated failing hearts, leading to a reduction in VT (60% in sotalol-treated failing hearts and 83% in veratridine-treated failing hearts). Simulations using a mathematical model showed a reduction in the action potential duration and the number of EADs by the NCX block in all subgroups., Conclusions: In an experimental model of CHF, the acute inhibition of NCX (1) reduces the MAP duration, (2) decreases dispersion of repolarization, and (3) suppresses EAD and VT. Our observations indicate for the first time that pharmacological NCX inhibition increases repolarization reserve and protects against VTs in heart failure., (Copyright © 2012 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Purpose: Exercise capacity of fewer than 5 metabolic equivalents (METs) has been associated with high risk of death and poor physical functioning in male patients with heart failure (HF). Therefore, we aimed to determine upper and lower extremity muscle strength levels required to attain an exercise capacity of 5 or more METs in male outpatients with HF., Methods: We enrolled 148 male HF patients (age 60.1 ± 1.0 years). Peak oxygen uptake (peak (Equation is included in full-text article.)o2) was assessed by cardiopulmonary exercise testing (CPX). After CPX, we further divided the patients into groups according to exercise capacity: 5 or more METs (group A, n = 85) and fewer than 5 METs (group B, n = 63). Handgrip strength and knee extensor and flexor muscle strengths were assessed as indices of upper and lower extremity muscle strength, respectively. Receiver operating characteristic curves were used to select cutoff values for upper and lower extremity muscle strength resulting in an exercise capacity of 5 or more METs in these patients., Results: Exercise capacity of 5 or more METs in male HF patients was equivalent to approximately 35.2 kgf of handgrip strength and 1.70 Nm/kg of knee extensor and 0.90 Nm/kg of knee flexor muscle strengths., Conclusions: These upper and lower extremity muscle strength values may be useful target goals for improvement of exercise capacity, risk management, and activities of daily living in male HF patients.

Purpose: Patients with exercise capacity of <5 metabolic equivalents (METs) are considered to have a high risk of death. The aim of this study was to determine age-related differences in physical activity associated with an exercise capacity of ≥5 METs in chronic heart failure (CHF) outpatients., Methods: We enrolled 157 stable CHF patients (79.6% men, age 60.3 ± 11.5 years). Patients were divided into two age-based groups (middle-aged, <65 years, n = 97) and (older-aged, ≥65 years, n = 60). Peak oxygen uptake (peak (V)O(2)) was assessed by cardiopulmonary exercise testing. We further divided patients into groups according to exercise capacity: ≥5 METs and <5 METs. Physical activity was assessed by measuring the average number of steps/day for 1 week with an electronic pedometer., Results: Receiver-operating characteristic curves were used to select cutoff values for steps associated with an exercise capacity of ≥5 METs in the middle- and older-aged patients. Cutoff values of 6045 steps in the middle-aged and 6070 steps in the older-aged patients were determined., Conclusions: Both middle- and older-aged CHF patients with exercise capacity of ≥5 METs completed approximately 6000 steps/day. This could become a target amount for minimal physical activity that could contribute to increased exercise capacity in CHF patients., Implications for Rehabilitation: • Middle-aged and older-aged chronic heart failure (CHF) patients with a measured exercise capacity of ≥5 METs completed approximately 6000 steps/day as measured by electronic pedometer. • This amount of steps could become a target amount for minimal physical activity that could contribute to increased exercise capacity in CHF patients.

G-CSF (granulocyte colony-stimulating factor) treatment has been shown to cause beneficial effects including a reduction of inducible arrhythmias in rodent models of ischemic cardiomyopathy. The aim of the present study was to test whether these effects do also apply to pacing-induced non-ischemic heart failure. In 24 female rabbits, heart failure was induced by rapid ventricular pacing. 24 rabbits were sham operated. The paced rabbits developed a significant decrease of ejection fraction. 11 heart failure rabbits (CHF) and 11 sham-operated (S) rabbits served as controls, whereas 13 sham (S-G-CSF) and 13 heart failure rabbits (CHF-G-CSF) were treated with 10 μg/kg G-CSF s.c. over 17 ± 4 days. G-CSF treatment caused a ~25% increased arterial and capillary density and a ~60% increased connexin 43 expression in failing hearts. In isolated, Langendorff-perfused rabbit hearts eight monophasic action potential recordings showed prolongation of repolarization in CHF as compared with controls in the presence of the QT prolonging agent erythromycin (+33 ± 12 ms; p < 0.01). Moreover, a significant increase in dispersion of repolarization contributed to a significantly higher rate of ventricular tachyarrhythmias in CHF. G-CSF-pre-treated hearts showed a further increase in prolongation of repolarization as compared with S and CHF. The further increase in dispersion of repolarization [S-G-CSF: +23 ± 9 ms (spatial), +13 ± 7 ms (temporal); CHF-G-CSF: +38 ± 14 ms (spatial), +10 ± 4 ms (temporal); p < 0.05 as compared with S and CHF], increased the incidence of ventricular tachyarrhythmias. In summary, chronic G-CSF treatment has moderate beneficial effects on parameters potentially related to hemodynamic function in the non-ischemic rabbit CHF model. However, a significant reduction of repolarization reserve might seriously challenge its suitability as a therapeutic agent for chronic CHF therapy.

Aims: Life-threatening arrhythmias are a major problem in chronic heart failure (CHF). The aim of the present study was to investigate the mechanism underlying the low proarrhythmic potential of amiodarone in a model of pacing-induced heart failure., Methods and Results: Heart failure was induced in 35 female rabbits by rapid ventricular pacing, resulting in a significant decrease of ejection fraction. Thirty-four rabbits were sham-operated. In 17 of 35 CHF-rabbits and 20 of 34 'sham'-rabbits, amiodarone (50 mg/kg/day) was fed for 6 weeks. Eight monophasic action potentials and a simultaneously recorded 12-lead electrocardiogram showed prolongation of QT-interval and action potential duration (APD(90)) in all failing hearts (P< 0.05). Amiodarone pre-treatment led to a prolongation of APD(90) (+19 ms) as compared with sham-controlled hearts but showed only a marginal effect on APD(90) in failing hearts. Infusion of sotalol (50-100 µM) led to a significant prolongation of APD(90) in sham and a further prolongation of APD(90) in failing hearts [+55 ms (50 µM); +70 ms (100 µM); P< 0.01 as compared with sham hearts]. Sotalol led to a triangular action potential configuration in sham and failing hearts, whereas amiodarone did not cause triangularization but caused a rapid phase-III repolarization. Moreover, amiodarone did not increase dispersion of repolarization either in sham or in failing hearts. Infusion of sotalol led to a significant increase in dispersion of repolarization in sham (+29 ms) and a further increase in failing hearts (+67 ms; P< 0.05)., Conclusion: Chronic amiodarone results in a rapid phase-III-repolarization and does not increase dispersion of repolarization. These electrophysiological findings are present in healthy hearts and are preserved in heart failure. This contributes to the low proarrhythmic potential of amiodarone in heart failure.

To determine self-reported sleep quality-related differences in physical activity (PA) and health-related quality of life (HRQOL) and target values of PA for high-quality sleep in chronic heart failure (CHF) outpatients, 149 CHF outpatients (mean age 58 years) were divided into two groups by sleep-quality level determined via self-reported questionnaire: shallow sleep (SS) group (n = 77) and deep sleep (DS) group (n = 72). Steps were assessed by electronic pedometer, HRQOL was assessed with the Short Form 36 (SF-36) survey, and data were compared between groups. PA resulting in high-quality sleep was determined by receiver-operating characteristics curves. All SF-36 subscale scores except that of bodily pain were significantly decreased in the SS versus DS group. A cutoff value of 5723.6 steps/day and 156.4 Kcal/day for 1 week were determined as target values for PA. Sleep quality may affect PA and HRQOL, and attaining target values of PA may improve sleep quality and HRQOL of CHF outpatients. Patents relevant to heart failure are also discussed in this article.

Background: Whether upper-extremity and lower-extremity muscle strength can predict a prognosis of congestive heart failure (CHF) patients is unclear. This study evaluated the impact of muscle strength on long-term mortality in patients with CHF., Design: Prospective observational study of male Japanese CHF patients., Methods: Clinical characteristics (age, body mass index, left ventricular ejection fraction, heart failure etiology, and medications) were obtained from hospital records of 148 male outpatients with stable CHF. Brain natriuretic peptide was determined as an index of disease severity. Peak oxygen uptake ((Equation is included in full-text article.)), handgrip, and knee extensor muscle strength were also determined., Results: After 1331.9+/-700.3 days of follow-up, 13 cardiovascular-related deaths occurred, and the patients were divided into two groups: survival (n=135) and nonsurvival (n=13). No significant differences were found between the groups in clinical characteristics, brain natriuretic peptide levels, and knee extensor muscle strength. Peak(Equation is included in full-text article.)(P=0.011) and handgrip strength (P=0.008) were significantly lower in the nonsurvival versus survival group. Left ventricular ejection fraction, peak(Equation is included in full-text article.), and handgrip strength were found by univariate Cox proportional hazards analysis to be significant prognostic indexes of survival. Multivariate analysis, however, revealed handgrip strength to be an independent predictor of prognosis. A handgrip strength cutoff value of 32.2 kgf was determined by the analysis of receiver-operating characteristics and was assessed. Kaplan-Meier survival curves after log-rank test showed significant prognostic difference between the two groups (P=0.008)., Conclusion: Handgrip strength may be useful for forecasting prognosis in patients with CHF.

Sleep-disordered breathing (SDB) is frequently observed in patients with congestive heart failure. Recent studies have shown that SDB negatively affects the onset of congestive heart failure; however, no studies have addressed the relationship between the level of SDB and the onset time of acute dyspnea. We hypothesized that SDB affects the acute onset time of dyspnea (AOT) and investigated the relationship between SDB and AOT. We examined 80 patients (mean age, 61.6 years) with congestive heart failure in a clinically stable condition. AOT was divided into 5 time periods (0:00 - 6:00, 6:00 - 12:00, 12:00 - 18:00, 18:00 - 24:00, and unknown). The apnea-hypopnea index (AHI) was obtained based on the results of polysomnography (PSG) to evaluate the severity of SDB. Acute dyspnea occurred in 59 (73.7%) of the 80 patients. When we divided the patients into an AHI < 5 group and an AHI >or= 5 group, there was no significant difference in the AOT; however, a significant difference was observed in those divided into AHI < 20 and AHI >or= 20 groups (P < 0.001). The patients with AHI >or= 20 had more acute dys-pnea between 18:00 - 24:00 and between 0:00 - 6:00 than those with AHI < 20 (32% and 19%, and 4.1% and 4.1%, respectively). Severe SDB patients tended to have acute dyspnea between midnight and dawn. The results suggest SDB might be one of the risk factors of heart failure.

Objective: Indices of exercise capacity such as peak oxygen uptake (VO2peak) and muscle strength are important in association with reduced mortality. The present study compared differences in VO2peak and muscle strength indices (grip strength and knee extensor and flexor muscle strength) with disease severity and investigated the relation of these variables in congestive heart failure (CHF) patients., Design: The study comprised 102 patients with stable CHF (93 men, age 61.4 +/- 10.2 yrs) with left ventricular ejection fraction (LVEF) <40% by echocardiography. We used New York Heart Association (NYHA) functional class to index disease severity. VO2peak, grip strength, knee extensor, and flexor muscle strength were determined. Patients were divided into three groups by NYHA class: class I (n = 39), class II (n = 49), and class III (n = 14)., Results: Age, sex, and LVEF did not differ according to NYHA class. VO2peak and all muscle strength indices decreased with increases in NYHA class (P < 0.05). VO2peak correlated positively with all muscle strengths (P < 0.05). Stepwise linear regression analysis revealed that grip and knee extensor strength were important in predicting VO2peak., Conclusions: Exercise capacity and disease severity in CHF patients may be influenced not only by lower-limb but also upper-limb muscle strength.

We investigated the correlations between exercise intolerance and the plasma levels of neurohormonal factors and proinflammatory cytokines in chronic heart failure (CHF) patients. Sixty-two CHF patients who underwent cardiopulmonary exercise testing (CPX) were enrolled in this study. Peak oxygen uptake (peak VO2) and the plasma concentrations of noradrenaline (NA), brain natriuretic peptide (BNP), and soluble tumor necrosis factor receptors I and II (TNFR-I and -II) were all measured during the CPX. The patients were divided into three groups according to their peak VO2; a severe exercise intolerance group (severe group; peak VO2 < 18 mL/min/kg), moderate exercise intolerance group (moderate group; 18 24). There were no significant differences in left ventricular ejection fraction (EF) among the three groups. NA and BNP both increased gradually in parallel with the worsening of exercise intolerance (NA, 211.5 +/- 75.7 pg/mL, 331.8 +/- 163.7, 441.9 +/- 202.9, respectively; BNP, 37.9 +/- 25.4 pg/mL, 148.9 +/- 117.1, 247.9 +/- 150.0, respectively). TNFR-I and II were significantly higher in the severe group than in the moderate group (1746.1 +/- 950.7 versus 1085.2 +/- 370.5 pg/mL and 2855.3 +/- 1550.9 versus 2047.7 +/- 648.7 pg/mL, respectively), while the values in the moderate group were not significantly different from those in the mild group. EF showed no significant correlations with NA, BNP, TNFR-I, or TNFR-II, whereas peak VO2 exhibited significant negative correlations with NA (r = -0.50, P < 0.0001), BNP (r = -0.53, P < 0.0001), TNFR-I (r = -0.50, P < 0.0001), and TNFR-II (r = -0.45, P < 0.0001). It is concluded that NA and BNP rise in parallel with the degree of exercise intolerance, while TNFR-I and -II rise only when exercise intolerance reaches severe levels.

Objectives: The relations between muscle strength, muscle endurance, and cardiopulmonary parameters were investigated in patients with chronic heart failure., Methods: The subjects comprised 33 outpatients with stable chronic heart failure (27 men, 6 women, mean age 60.3 +/- 12.7 years). A pedal-type isokinetic device was used throughout the study. The safety of the study protocol was examined first. Maximum muscle power (peak power), an index of muscle strength, was measured for 6 consecutive revolutions(3 revolutions of each leg). The strength decrement index (SDI) was measured for 20 consecutive maximal revolutions (10 revolutions in each leg). The SDI is an index of muscle endurance and compares the mean power for revolutions 9 and 10 with that for revolutions 2 and 3. Each subjects underwent symptom-limited cardiopulmonary exercise testing with a cycle ergometer on another day., Results: No subject experienced continuous abnormal heart rate or blood pressure response, chest pain, ischemic ST-T change, or severe arrhythmia. The peak power and the SDI were correlated with the anaerobic threshold (r = 0.42, 0.52, respectively), with peak oxygen uptake (r = 0.66, 0.61), and with the increase in oxygen uptake per unit increase in work rate (r = 0.43, 0.63). However, the slope of the ventilation equivalent to carbon dioxide output was correlated only with the SDI (r = -0.54) and the time constant for the oxygen uptake decrease was correlated only with the peak power (r = -0.46)., Conclusions: Peak functional capacity depends on both muscle strength and endurance, and subjective symptoms in daily activity, especially dyspnea on exertion, depend mainly on muscle endurance in patients with chronic heart failure.

Objectives: To develop a measure for disease-specific health-related quality of life in patients with heart failure and examine its reliability and validity., Methods: One hundred and four patients with stable chronic heart failure (74 males, 30 females, mean age 64.2 +/- 10.0 years) with left ventricular ejection fractions of less than 40% were enrolled in this study. Each patient responded to the Medical Outcomes Study Short Form 36 (SF-36) and a disease specific questionnaire comprising four categories (dyspnea, sleep, appetite and fatigue), each consisting of five to six questions. A stepwise exploratory factor analysis was applied to the disease-specific measure to consider categorical fitness. In 25 of the 104 patients, the data in the questionnaire were compared with peak oxygen uptake, anaerobic threshold, slope of the regression line relating the ventilatory equivalent to carbon dioxide output (VE/VCO2 slope) and peak work rate. Correlations between the questionnaire and eight components of SF-36 were evaluated., Results: The appetite category proved unreliable and was excluded from consideration, so 12 questions were adopted from the other three categories. Cronbach's a values ranged from 0.68 to 0.89 and the coefficients of test-retest were from 0.84 to 0.94, so both internal consistency and reproducibility of these questions were considered excellent. The scores of three categories well reflected the severity of heart failure based in New York Heart Association functional class. The anaerobic threshold (r = 0.53), peak oxygen uptake (r = 0.66), VE/VCO2 slope (r = -0.48) and peak work rate (r = 0.41) correlated with the total score of the 12 questions. The total scores were closely correlated with the eight components of SF-36., Conclusions: This study suggests that the disease-specific questionnaire is applicable to evaluation of the health-related quality of life in patients with heart failure.

The present study was undertaken to investigate the relationship between the extent of impaired chronotropic response and cardiac output during exercise, and exercise tolerance in patients with chronic heart failure. The subjects consisted of 24 patients (mean 60.1 +/- 14.0 years) who had mild chronotropic incompetence. Cardiopulmonary exercise testing was performed in all patients, and heart rate (HR), anaerobic threshold (AT), maximum oxygen uptake (peak VO2), slope of the regression line relating the ventilatory equivalent to carbon dioxide output (VE/VCO2 slope), and exercise time were measured. Cardiac output (CO) was measured by a thoracic bioimpedance method and cardiac index (CI) was calculated. Plasma norepinephrine (NE) was measured at rest and immediately after the exercise test. The changes in HR, NE, and CI from the resting state to immediately after exercise were calculated as deltaHR, deltaNE, and deltaCI, respectively. The deltaNE was converted to a logarithmic scale and deltaHR/log deltaNE was used as a parameter of HR response to sympathetic nerve stimulation. The results were as follows: HR and NE in the resting state had no correlation with AT and with peak VO2. DeltaHR/log deltaNE correlated positively with both AT and peak VO2, and negatively with the VE/CO2 slope. DeltaHR/log deltaNE correlated positively with peak CI, %deltaCI, and deltaCI/exercise time. The data suggest that one of the mechanisms of low exercise tolerance in chronic heart failure patients was due to an inadequate increase in CO response against exercise caused by an impaired HR response to increased NE.

Objectives: The 3-year survival rates of 500 patients with congestive heart failure (CHF) referred for heart transplantation were assessed to evaluate the clinical and exercise variables most useful for estimating prognostic risk., Background: Detailed prognostic risk stratification of patients with a peak exercise oxygen consumption (VO2) < or = 14 ml/min per kg to identify lower risk patient subsets has been limited in earlier series by relatively small sample size., Methods: Cardiopulmonary exercise testing was performed in 500 patients with CHF referred for heart transplantation; 154 (31%) had a peak exercise VO2 < or = 14 ml/min per kg. Univariate and multivariate analyses were performed to identify the 3-year prognostic risk., Results: The 55% 3-year survival rate of the 77 patients with a peak exercise VO2 < or = 14 ml/min per kg unable to reach a peak exercise systolic blood pressure (SBP) of 120 mm Hg was significantly lower than the 83% survival rate in the 74 patients able to reach this exercise blood pressure (p = 0.004). Multivariate analysis revealed that peak exercise SBP (p = 0.0005) and percent predicted peak VO2 < or = 50% (p = 0.04) were the two most important predictors for the combined end point of death or listing as Status 1., Conclusions: Peak exercise SBP and percent predicted peak exercise VO2 are two inexpensive and easily measured noninvasive variables that can be used to further prognostically risk stratify ambulatory patients with CHF referred for heart transplantation with a peak exercise VO2 < or = 14 ml/min per kg.

Cardiac index is widely used as a parameter of cardiac function for cardiovascular patients, but its value is limited when measured in the resting supine position, because it never demonstrates the maximal cardiac index performance. The incremental increase in cardiac index (delta CI) was evaluated during incremental exercise (delta work rate: delta WR), delta CI/delta WR, in patients with chronic congestive heart failure, and compared to brain natriuretic peptide (BNP), which is known to be increased in patients with chronic left ventricular dysfunction. The subjects were 18 heart failure patients (16 males and 2 females, mean age [+/-SD] 63.8 +/- 8.9 years). Symptom-limited cardiopulmonary exercise test using cycle ergometer was performed. Cardiac index was calculated with the Benchmark Exercise Test device using oxygen uptake, carbon dioxide output and respired flow. Blood samples were taken in the resting state before the exercise test. A positive correlation was obtained between delta CI/delta WR and peak oxygen uptake (peak VO2) (r = 0.71, p < 0.01), and delta CI/delta WR and peak oxygen pulse (r = 0.66, p < 0.01). A negative correlation was obtained between delta CI/delta WR and BNP (r = 0.45) in the resting state. Peak VO2 (20.9 +/- 7.5 vs 13.9 +/- 2.7 ml/min/kg, p < 0.05), peak cardiac index (7.2 +/- 1.7 vs 5.5 +/- 0.9 l/min/m2, p < 0.05), and delta CI/delta WR (20.1 +/- 8.1 vs 12.4 +/- 2.5 ml/m2/W, p < 0.05) were significantly higher in the group with normal BNP (mean [+/-SD] 11.0 +/- 3.2 pg/ml) than in the group with high BNP (40.7 +/- 22.7 pg/ml). Delta CI/delta WR reflects the grade of exercise tolerance and may be useful for evaluating exercise capacity in patients with congestive heart failure.

BACKGROUND AND PURPOSE Chronic heart failure (CHF) is associated with action potential prolongation and Ca2+ overload, increasing risk of ventricular tachyarrhythmias (VT). We therefore investigated whether ICa blockade was anti-arrhythmic in an intact perfused heart model of CHF. EXPERIMENTAL APPROACH CHF was induced in rabbits after 4 weeks of rapid ventricular pacing. Hearts from CHF and sham-operated rabbits were isolated and perfused (Langendorff preparation), with ablation of the AV node. VT was induced by erythromycin and low [K+] (1.5mM). Electrophysiology of cardiac myocytes, with block of cation currents, was simulated by a mathematical model. KEY RESULTS Repolarization was prolonged in CHF hearts compared with sham-operated hearts. Action potential duration (APD) and overall dispersion of repolarization were further increased by erythromycin (300 µM) to block IKr in CHF hearts. After lowering [K+] to 1.5mM, CHF and sham hearts showed spontaneous episodes of polymorphic non-sustained VT. Additional infusion of verapamil (0.75 µM) suppressed early afterdepolarizations (EAD) and VT in 75% of sham and CHF hearts. Verapamil shortened APD and dispersion of repolarization, mainly by reducing transmural dispersion of repolarization via shortening of endocardial action potentials. Mathematical simulations showed that EADs were more effectively reduced by verapamil assuming a state-dependent block than a simple block of ICa. CONCLUSIONS AND IMPLICATIONS Blockade of ICa was highly effective in suppressing VT via reduction of transmural dispersion of repolarization and suppression of EAD. Such blockade might represent a novel therapeutic option to reduce risk of VT in structurally normal hearts and also in heart failure. LINKED ARTICLE This article is commented on by Stams et al., pp. 554-556 of this issue. To view this commentary visit [ABSTRACT FROM AUTHOR]