Hopelessness and cognitive impairment are risk markers for mortality in systolic heart failure patients.

OBJECTIVE: Depression exacerbates the burden of heart failure and independently predicts mortality. The aim of this study was to investigate which specific symptoms of depression predict all-cause mortality in systolic heart failure patients. METHODS: Consecutive outpatients with heart failure and impaired left ventricular ejection fraction (LVEF), attending an Australian metropolitan heart function clinic between 2001 and 2011, were enrolled. The Cardiac Depression Scale (CDS) was completed as a component of usual care. Baseline clinical characteristics were drawn from hospital databases. The primary end-point was all-cause mortality, obtained from the Australian National Death Index. RESULTS: A total of 324 patients (68.5% male) were included (mean age at enrolment = 66.8 ±â€¯14.36 years), with a median follow-up time of 6.7 years (95% CI 5.97-7.39) and a mortality rate of 50% by the census date. Mean LVEF = 31.0 ±â€¯11.31%, with 25% having NYHA functional class of III or IV. Factor analysis of the CDS extracted six symptom dimensions: Hopelessness, Cognitive Impairment, Anhedonia/Mood, Irritability, Worry, and Sleep Disturbance. Cox regression analyses identified Hopelessness (HR 1.024, 95% CI 1.004-1.045, p = .018) and Cognitive Impairment (HR 1.048, 95% CI 1.005-1.093, p = .028) as independent risk markers of all-cause mortality, following adjustment of known prognostic clinical factors. CONCLUSION: Hopelessness and cognitive impairment are stronger risk markers for all-cause mortality than other symptoms of depression in systolic heart failure. These data will allow more specific risk assessment and potentially new targets for more effective treatment and management of depression in this population.

A nurse-led up-titration clinic improves chronic heart failure optimization of beta-adrenergic receptor blocking therapy--a randomized controlled trial.

BACKGROUND: Beta-adrenergic blockade has been shown to improve left ventricular function, reduce hospital admissions and improve survival in chronic heart failure with reduced ejection fraction (HFrEF), with mortality reduction starting early after beta-adrenergic receptor blocker initiation and being dose-related. The aim of this pilot study was to determine the effectiveness of a nurse-led titration clinic in improving the time required for patients to reach optimal doses of the beta-adrenergic receptor blocking agents. METHOD: We conducted a prospective pilot randomized controlled trial. Twenty eight patients with CHF were randomized to optimisation of beta-adrenergic receptor blocker therapy over six months by either a nurse-led titration (NLT) clinic, led by a nurse specialist with the support of a cardiologist in a CHF clinic, or by their primary care physician (usual care (UC)). The primary endpoint was time to maximal beta-adrenergic receptor blocker dose. The secondary end-point was the proportion of patients reaching the target dose of beta-adrenergic receptor blocker by six months. RESULTS: The patients were predominantly men (72%), age 67 ± 16 years; New York Heart Association (NYHA) functional class I (32%), II (44%) and III (20%); baseline left ventricular ejection fraction 33 ± 10%, and a low mean Charlson co-morbidity score of 2.5 ± 1.4. The time to maximum dose was shorter in the NLT group compared to the UC group (90 ± 14 vs 166 ± 8 days, p < 0.0005). At six months, in the NLT group there were nine patients (82%) on high dose and one patient (9%) on low dose beta-adrenergic receptor blocker compared to the UC group with five (42%) patients reaching maximum dose and five (42%) patients on low dose (p = 0.04). The patients allocated to the NLT group also had significantly less worsening of depression between baseline and six months (p = 0.006). CONCLUSION: A NLT clinic improves optimisation of beta-adrenergic receptor blocker therapy through increasing the proportion of patients reaching maximal dose and facilitating rapid up-titration of beta-adrenergic receptor blocker agents in patients with chronic HFrEF. TRIAL REGISTRATION: Australian Clinical Trials Registry (ACTRN012606000383561).

Effect of exercise training on left ventricular remodeling in diabetic patients with diastolic dysfunction: rationale and design.

INTRODUCTION: This study will examine the effects of combined aerobic and resistance training on left ventricular remodeling in diabetic patients with diastolic dysfunction. This is the first randomized controlled trial to look for effects of combined strength training and aerobic exercise on myocardial function as well as other clinical, functional, or psychological parameters in diabetic patients with isolated diastolic dysfunction, and will provide important insights into the potential management strategies for heart failure with preserved ejection fraction. METHODS AND ANALYSIS: This is a prospective, randomized controlled investigator initiated single center trial. Diabetic patients with LV diastolic dysfunction suitable for exercise training intervention will be randomized to three months of a supervised combination of aerobic and strength training exercises, or supervised light stretching (control arm). Pre and post intervention assessment will include stress echocardiography, peak aerobic power with 12-lead ECG, dual-energy X-ray absorptiometry, muscle strength, the capacity to perform activities of daily living (ADLs), and questionnaires to assess self-perceived quality of life and symptoms of depression. The primary endpoint is to compare any change in tissue Doppler-derived LV systolic and early diastolic velocities. ETHICS AND DISSEMINATION: The current trial protocol has been approved by the Human Research Ethics Committee of Austin Health and the University of Melbourne, Melbourne. The study will be performed in accordance with the Declaration of Helsinki. The investigator, regardless of the outcome, will publish the results of the study. AUSTRALIAN NEW ZEALAND CLINICAL TRIALS REGISTRY: ACTRN12610000943044.

Cardiorenal anemia syndrome as a prognosticator for death in heart failure.

Anemia and chronic kidney disease are common in patients with heart failure (HF) and are associated with adverse outcomes. We analyzed the effect of cardiorenal anemia (CRA) syndrome, defined as anemia (hemoglobin <130 g/L for men, <120 g/L for women) and stage 3 or greater chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73 m(2)), in outpatients with HF. Consecutive patients with HF were prospectively enrolled from 2000 to 2005 (n = 748). The baseline clinical characteristics, pathology test results, and medication use were compared between those with and without CRA syndrome. The primary end point was all-cause mortality. The mean follow-up was 2.5 ± 1.6 years, with a left ventricular ejection fraction <45% present in 70% of patients. Angiotensin-converting enzyme inhibitors, ß blockers, and spironolactone were used in 87%, 67%, and 37%, respectively. CRA syndrome was present in 224 patients (30%). These patients had greater all-cause mortality (51% vs 26%, p <0.001), older age (mean 77 ± 8 vs 67 ± 14 years, p <0.001), and greater rates of diabetes mellitus (35% vs 23%, p <0.001) and ischemic heart disease (50% vs 35%, p <0.001). The independent predictors of mortality were CRA syndrome (hazard ratio 2.0, 95% confidence interval 1.4 to 2.8, p <0.001), left ventricular systolic dysfunction per grade (hazard ratio 1.5, 95% confidence interval 1.3 to 1.8, p <0.001), the absence of a ß blocker (hazard ratio 1.6, 95% confidence interval 1.1 to 2.2, p = 0.005), New York Heart Association class per class (hazard ratio 1.5, 95% confidence interval 1.2 to 1.9, p <0.01), and age per decade (hazard ratio 1.6, 95% confidence interval 1.4 to 2.0, p <0.001). In conclusion, CRA syndrome was common in patients with HF and was an independent predictor of all-cause mortality. Consideration should be given to identifying CRA syndrome and modifying reversible factors.

Differential response to resistance training in CHF according to ACE genotype.

BACKGROUND: The Angiotensin Converting Enzyme (ACE) gene may influence the risk of heart disease and the response to various forms of exercise training may be at least partly dependent on the ACE genotype. We aimed to determine the effect of ACE genotype on the response to moderate intensity circuit resistance training in chronic heart failure (CHF) patients. METHODS: The relationship between ACE genotype and the response to 11weeks of resistance exercise training was determined in 37 CHF patients (New York Heart Association Functional Class=2.3±0.5; left ventricular ejection fraction 28±7%; age 64±12years; 32:5 male:female) who were randomised to either resistance exercise (n=19) or inactive control group (n=18). Outcome measures included V˙O(2peak), peak power output and muscle strength and endurance. ACE genotype was determined using standard methods. RESULTS: At baseline, patients who were homozygous for the I allele had higher V˙O(2peak) (p=0.02) and peak power (p=0.003) compared to patients who were homozygous for the D allele. Patients with the D allele, who were randomised to resistance training, compared to non-exercising controls, had greater peak power increases (ID p<0.001; DD p<0.001) when compared with patients homozygous for the I allele, who did not improve. No significant genotype-dependent changes were observed in V˙O(2peak), muscle strength, muscle endurance or lactate threshold. CONCLUSION: ACE genotype may have a role in exercise tolerance in CHF and could also influence the effectiveness of resistance training in this condition.

The reliability of the 1RM strength test for untrained middle-aged individuals.

The one-repetition maximum (1RM) test is considered the gold standard for assessing muscle strength in non-laboratory situations. Since most previous 1RM reliability studies have been conducted with experienced young participants, it is unclear if acceptable test-retest reliability exists for untrained middle-aged individuals. This study examined the reliability of the 1RM strength test of untrained middle-aged individuals. Fifty-three untrained males (n=25) and females (n=28) aged 51.2+/-0.9 years participated in the study. Participants undertook the first 1RM test (T1) 4-8 days after a familiarisation session with the same exercises. 1RM was assessed for seven different exercises. Four to eight days after T1, participants underwent another identical 1RM test (T2). Ten weeks later, 27 participants underwent a third test (T3). Intraclass correlation coefficients (ICC), typical error as a coefficient of variation (TEcv), retest correlation, repeated measures ANOVA, Bland-Altman plots, and estimation of 95% confidence limits were used to assess reliability. A high ICC (ICC>0.99) and high correlation (r>0.9) were found for all exercises. TEcv ranged from 2.2 to 10.1%. No significant change was found for six of the seven exercises between T1 and T2. Leg press was slightly higher at T2 compared to T1 (1.6+/-0.6%, p=0.02). No significant change was found between T2 and T3 for any exercise. 1RM is a reliable method of evaluating the maximal strength in untrained middle-aged individuals. It appears that 1RM-testing protocols that include one familiarisation session and one testing session are sufficient for assessing maximal strength in this population.

Circuit resistance training in chronic heart failure improves skeletal muscle mitochondrial ATP production rate--a randomized controlled trial.

BACKGROUND: We aimed to determine the role of skeletal muscle mitochondrial ATP production rate (MAPR) in relation to exercise tolerance after resistance training (RT) in chronic heart failure (CHF). METHODS AND RESULTS: Thirteen CHF patients (New York Heart Association functional class 2.3 +/- 0.5; Left ventricular ejection fraction 26 +/- 8%; age 70 +/- 8 years) underwent testing for peak total body oxygen consumption (VO(2peak)), and resting vastus lateralis muscle biopsy. Patients were then randomly allocated to 11 weeks of RT (n = 7), or continuance of usual care (C; n = 6), after which testing was repeated. Muscle samples were analyzed for MAPR, metabolic enzyme activity, and capillary density. VO(2peak) and MAPR in the presence of the pyruvate and malate (P+M) substrate combination, representing carbohydrate metabolism, increased in RT (P < .05) and decreased in C (P < .05), with a significant difference between groups (VO(2peak), P = .005; MAPR, P = .03). There was a strong correlation between the change in MAPR and the change in peak total body oxygen consumption (VO(2peak)) over the study (r = 0.875; P < .0001), the change in MAPR accounting for 70% of the change in VO(2peak). CONCLUSIONS: These findings suggest that mitochondrial ATP production is a major determinant of aerobic capacity in CHF patients and can be favorably altered by muscle strengthening exercise.

Reduced exercise tolerance in CHF may be related to factors other than impaired skeletal muscle oxidative capacity.

BACKGROUND: We sought to determine whether skeletal muscle oxidative capacity, fiber type proportions, and fiber size, capillary density or muscle mass might explain the impaired exercise tolerance in chronic heart failure (CHF). Previous studies are equivocal regarding the maladaptations that occur in the skeletal muscle of patients with CHF and their role in the observed exercise intolerance. Methods and results Total body O(2) uptake (VO(2peak)) was determined in 14 CHF patients and 8 healthy sedentary similar-age controls. Muscle samples were analyzed for mitochondrial adenosine triphosphate (ATP) production rate (MAPR), oxidative and glycolytic enzyme activity, fiber size and type, and capillary density. CHF patients demonstrated a lower VO(2peak) (15.1+/-1.1 versus 28.1+/-2.3 mL.kg(-1).min(-1), P<.001) and capillary to fiber ratio (1.09+/-0.05 versus 1.40+/-0.04; P<.001) when compared with controls. However, there was no difference in capillary density (capillaries per square millimeter) across any of the fiber types. Measurements of MAPR and oxidative enzyme activity suggested no difference in muscle oxidative capacity between the groups. CONCLUSIONS: Neither reductions in muscle oxidative capacity nor capillary density appear to be the cause of exercise limitation in this cohort of patients. Therefore, we hypothesize that the low VO(2peak) observed in CHF patients may be the result of fiber atrophy and possibly impaired activation of oxidative phosphorylation.

Moderate-intensity resistance exercise training in patients with chronic heart failure improves strength, endurance, heart rate variability, and forearm blood flow.

BACKGROUND: Resistance exercise training was applied to patients with chronic heart failure (CHF) on the basis that it may partly reverse deficiencies in skeletal muscle strength and endurance, aerobic power (VO(2peak)), heart rate variability (HRV), and forearm blood flow (FBF) that are all putative factors in the syndrome. METHODS AND RESULTS: Thirty-nine CHF patients (New York Heart Association Functional Class=2.3+/-0.5; left ventricular ejection fraction 28%+/-7%; age 65+/-11 years; 33:6 male:female) underwent 2 identical series of tests, 1 week apart, for strength and endurance of the knee and elbow extensors and flexors, VO(2peak), HRV, FBF at rest, and FBF activated by forearm exercise or limb ischemia. Patients were then randomized to 3 months of resistance training (EX, n=19), consisting of mainly isokinetic (hydraulic) ergometry, interspersed with rest intervals, or continuance with usual care (CON, n=20), after which they underwent repeat endpoint testing. Combining all 4 movement patterns, strength increased for EX by 21+/-30% (mean+/-SD, P<.01) after training, whereas endurance improved 21+/-21% (P<.01). Corresponding data for CON remained almost unchanged (strength P<.005, endurance P<.003 EX versus CON). VO(2peak) improved in EX by 11+/-15% (P<.01), whereas it decreased by 10+/-18% (P<.05) in CON (P<.001 EX versus CON). The ratio of low-frequency to high-frequency spectral power fell after resistance training in EX by 44+/-53% (P<.01), but was unchanged in CON (P<.05 EX versus CON). FBF increased at rest by 20+/-32% (P<.01), and when stimulated by submaximal exercise (24+/-32%, P<.01) or limb ischemia (26+/-45%, P<.01) in EX, but not in CON (P<.01 EX versus CON). CONCLUSIONS: Moderate-intensity resistance exercise training in CHF patients produced favorable changes to skeletal muscle strength and endurance, VO(2peak), FBF, and HRV.

Reliability of isokinetic strength and aerobic power testing for patients with chronic heart failure.

PURPOSE: The objective of this study was to assess the reliability of testing skeletal muscle strength and peak aerobic power in a clinical population of patients with chronic heart failure (CHF). METHODS: Thirty-three patients with CHF (New York Heart Association (NYHA) Functional Class 2.3 +/- 0.5; left ventricular ejection fraction 27% +/- 7%; age 65 +/- 9 years; 28:5 male-female ratio) underwent two identical series of tests (T1 and T2), 1 week apart, for strength and endurance of the muscle groups responsible for knee extension/flexion and elbow extension/flexion. The patients also underwent two graded exercise tests on a bicycle ergometer to measure peak oxygen consumption (VO(2peak)). Three months later, 18 of the patients underwent a third test (T3) for each of the measures. Means were compared using MANOVA with repeated measures for strength and endurance, and ANOVA with repeated measures for VO(2peak). RESULTS: Combining data for all four movement patterns, the expression of strength increased from T1 to T2 by 12% +/- 25% (P <.001; intraclass correlation coefficient [ICC] = 0.89). Correspondingly, endurance increased by 13% +/- 23% (P =.004; ICC = 0.87). Peak oxygen consumption was not significantly different (16.2 +/- 0.8 and 16.1 +/- 0.8 mL.kg(-1).min(-1) for T1 and T2, respectively; P =.686; ICC = 0.91). There were no significant differences between T2 and T3 for strength (2% +/- 17%; P =.736; ICC = 0.92) or muscle endurance (-1% +/- 15%; P =.812; ICC = 0.96), but VO(2peak) decreased from 16.7 +/- 1.2 to 14.9 +/- 0.9 mL.kg(-1).min(-1) (-10% +/- 18%; P =.021; ICC = 0.89). CONCLUSIONS: These data suggest that in a population of patients with CHF, a familiarization trial for skeletal muscle strength testing is necessary. Although familiarization is not required for assessing oxygen consumption as a single measurement, VO(2peak) declined markedly in the 3-month period for which these patients were followed. Internal consistency within patients was high for the second and third strength trials and the first and second tests of VO(2peak).