Improved simulated ventilation with a novel tidal volume and peak inspiratory pressure controlling bag valve mask: A pilot study.

Introduction: The dangers of hyperventilation during resuscitation are well known. Traditional bag valve mask (BVM) devices rely on end users to control tidal volume (Vt), rate, and peak inspiratory pressures (PIP) of ventilation. The Butterfly BVM (BBVM) is a novel device intending to give greater control over these parameters. The objective of this pilot study was to compare the BBVM against a traditional device in simulated resuscitations. Methods: Senior emergency medicine residents and fellows participated in a three-phase simulation study. First, participants used the Ambu Spur II BVM in adult and pediatric resuscitations. Vt, PIP, and rate were recorded. Second, participants repeated the resuscitations after a brief introduction to the BBVM. Third, participants were given a longer introduction to the BBVM and were tested on their ability to adjust its various settings. Results: Nineteen participants were included in the adult arm of the study, and 16 in the pediatric arm. The BBVM restricted Vt delivered to a range of 4-8 ml/kg vs 9 ml/kg and 13 ml/kg (Ambu adult and Ambu pediatric respectively). The BBVM never exceeded target minute ventilations while the Ambu BVMs exceeded target minute ventilation in 2 of 4 tests. The BBVM failed to reliably reach higher PIP targets in one test, while the pediatric Ambu device had 76 failures of excessive PIP compared to 2 failures by the BBVM. Conclusion: The BBVM exceeded the Ambu Spur II in delivering appropriate Vts and in keeping PIPs below target maximums to simulated adult and pediatric patients in this pilot study.

Addition of Supervised Exercise Training to a Post-Hospital Disease Management Program for Patients Recently Hospitalized With Acute Heart Failure: The EJECTION-HF Randomized Phase 4 Trial.

OBJECTIVES: This study sought to measure the impact on all-cause death or readmission of adding center-based exercise training (ET) to disease management programs for patients with a recent acute heart failure (HF) hospitalization. BACKGROUND: ET is recommended for patients with HF, but evidence is based mainly on ET as a single intervention in stable outpatients. METHODS: A randomized, controlled trial with blinded outcome assessor, enrolling adult participants with HF discharged from 5 hospitals in Queensland, Australia. All participants received HF-disease management program plus supported home exercise program; intervention participants were offered 24 weeks of supervised center-based ET. Primary outcome was all-cause 12-month death or readmission. Pre-planned subgroups included age (<70 years vs. older), sex, left ventricular ejection fraction (≤40% vs. >40%), and exercise adherence. RESULTS: Between May 2008 and July 2013, 278 participants (140 intervention, 138 control) were enrolled: 98 (35.3%) age ≥70 years, 71 (25.5%) females, and 62 (23.3%) with a left ventricular ejection fraction of >40%. There were no adverse events associated with ET. There was no difference in primary outcome between groups (84 of 140 [60.0%] intervention vs. 90 of 138 [65.2%] control; p = 0.37), but a trend toward greater benefit in participants age <70 years (OR: 0.56 [95% CI: 0.30 to 1.02] vs. OR: 1.56 [95% CI: 0.67 to 3.64]; p for interaction = 0.05). Participants who exercised to guidelines (72 of 101 control and 92 of 117 intervention at 3 months) had a significantly lower rate of death and readmission (91 of 164 [55.5%] vs. 41 of 54 [75.9%]; p = 0.008). CONCLUSIONS: Supervised center-based ET was a safe, feasible addition to disease management programs with supported home exercise in patients recently hospitalized with acute HF, but did not reduce combined end-point of death or readmission. (A supervised exercise programme following hospitalisation for heart failure: does it add to disease management?; ACTRN12608000263392).

Limited utility of exercise stress testing in the evaluation of suspected acute coronary syndrome in patients aged less than 40 years with intermediate risk features.

OBJECTIVE: National guidelines for management of intermediate risk patients with suspected acute coronary syndrome, in whom AMI has been excluded, advocate provocative testing to final risk stratify these patients into low risk (negative testing) or high risk (positive testing suggestive of unstable angina). Adults less than 40 years have a low pretest probability of acute coronary syndrome. The utility of exercise stress testing in young adults with chest pain suspected of acute coronary syndrome who have National Heart Foundation intermediate risk features was evaluated. METHODS: A retrospective analysis of exercise stress testing performed on patients less than 40 years was evaluated. Patients were enrolled on a chest pain pathway and had negative serial ECGs and cardiac biomarkers before exercise stress testing to rule-out acute coronary syndrome. Chart review was completed on patients with positive stress tests. RESULTS: The 3987 patients with suspected intermediate risk acute coronary syndrome underwent exercise stress testing. One thousand and twenty-seven (25.8%) were aged less than 40 years (age 33.3 ± 4.8 years). Four of these 1027 patients had a positive exercise stress test (0.4% incidence of positive exercise stress testing). Of those, three patients had subsequent non-invasive functional testing that yielded a negative result. One patient declined further investigations. Assuming this was a true positive exercise stress test, the incidence of true positive exercise stress testing would have been 0.097% (95% confidence interval: 0.079-0.115%) (one of 1027 patients). CONCLUSIONS: Routine exercise stress testing has limited value in the risk stratification of adults less than 40 years with suspected intermediate risk of acute coronary syndrome.

Implementation of a chest pain management service improves patient care and reduces length of stay.

OBJECTIVE: Chest pain is one of the most common complaints in patients presenting to an emergency department. Delays in management due to a lack of readily available objective tests to risk stratify patients with possible acute coronary syndromes can lead to an unnecessarily lengthy admission placing pressure on hospital beds or inappropriate discharge. The need for a co-ordinated system of clinical management based on enhanced communication between departments, timely and appropriate triage, clinical investigation, diagnosis, and treatment was identified. METHODS: An evidence-based Chest Pain Management Service and clinical pathway were developed and implemented, including the introduction of after-hours exercise stress testing. RESULTS: Between November 2005 and March 2013, 5662 patients were managed according to a Chest Pain Management pathway resulting in a reduction of 5181 admission nights by more timely identification of patients at low risk who could then be discharged. In addition, 1360 days were avoided in high-risk patients who received earlier diagnosis and treatment. CONCLUSIONS: The creation of a Chest Pain Management pathway and the extended exercise stress testing service resulted in earlier discharge for low-risk patients; and timely treatment for patients with positive and equivocal exercise stress test results. This service demonstrated a significant saving in overnight admissions.

Non-physician-led exercise stress testing is a safe and effective practice.

Exercise stress testing is a non-invasive procedure that provides diagnostic and prognostic information for the evaluation of several pathologies, including arrhythmia provocation, assessment of exercise capacity, and coronary heart disease. Historically, exercise tests were directly supervised by physicians; however, cost-containment issues and time constraints on physicians have encouraged the use of health professionals with specific training and experience to supervise selected exercise stress tests. Evidence suggests that non-physician-led exercise stress testing is a safe and effective practice with similar morbidity and mortality rates as those performed or supervised by a physician.

Exercise training in recently hospitalized heart failure patients enrolled in a disease management programme: design of the EJECTION-HF randomized controlled trial.

AIMS: The Exercise Joins Education: Combined Therapy to Improve Outcomes in Newly-discharged Heart Failure (EJECTION-HF) study will evaluate the impact of a supervised exercise training programme (ETP) on clinical outcomes in recently hospitalized heart failure patients attending a disease management programme (DMP). Methods This multisite, pragmatic randomized controlled trial enrols patients discharged from participating hospitals with clinical evidence of heart failure who are willing and able to participate in a DMP and considered clinically safe to exercise. Enrolment includes participants with impaired and preserved left ventricular systolic function. Baseline assessment and programme commencement occur within 6 weeks of hospital discharge. The control group DMP includes individualized education and follow-up from a multidisciplinary heart failure team; a weekly education programme for 12 weeks; self-management advice; and medical follow-up. Home exercise is recommended for all participants. In addition, intervention participants are offered 36 supervised, structured gym-based 1 h exercise sessions over 24 weeks. Sessions are tailored to exercise capacity and include aerobic, resistance, and balance exercises. Enrolment target is 350 participants. Primary outcome is 12-month mortality and readmissions. Secondary outcomes include blinded evaluation of depressive symptoms, sleep quality, cognition, and functional status (activities of daily living, 6 min walk distance, grip strength) at 3 and 6 months. A cost-utility analysis will be conducted. CONCLUSION: This study will enrol a representative group of hospitalized heart failure patients and measure a range of patient and health service outcomes to inform the design of post-hospital DMPs for heart failure. Enrolment will be completed in 2013. ACTRN12608000263392.

Putative contribution of prostaglandin and bradykinin to muscle reflex hyperactivity in patients on Ace-inhibitor therapy for chronic heart failure.

AIMS: In patients with chronic heart failure (CHF), an overactive muscle ergoreceptor reflex (chemo-afferents sensitive to the products of muscle work) is thought to play an important role in the origin of dyspnoea. We sought to investigate whether raised intra-muscular prostaglandins (PG) and bradykinin, as estimated by levels within the venous effluent from exercising skeletal muscle may be involved in symptom generation through the stimulation of the ergoreflex. METHODS AND RESULTS: In 19 stable CHF patients and 12 normal controls, cardiopulmonary exercise capacity (peak O2 consumption [peak VO2]) and the ergoreflex contribution to ventilation (post-handgrip regional circulatory occlusion method) were measured. Venous resting and exercise plasma PGE2, PGF1alpha and bradykinin concentrations were assessed. Eleven patients on angiotensin converting enzyme inhibitors and 10 controls were challenged with ketoprofen infusion (to inhibit PG synthesis and bradykinin activity). Patients vs. controls presented lower exercise tolerance (peak VO2 15.9+/-0.7 vs. 33.0+/-1.3 mL/kg/min), an increased ventilatory response to exercise (VE/VCO2 slope 43+/-2 vs. 27+/-0.9) (p<0.0001 for all comparisons). The overactive ergoreflex of CHF (5.1+/-1.3 vs. 0.1+/-0.3 L/min) was significantly related to the increase in PGF1alpha (adjusted R2=0.34, p<0.005) but not PGE2 (adjusted R2=0.16, p>0.05). The increased PG and bradykinin productions both at rest and during exercise in CHF were attenuated after ketoprofen infusion, associated with ergoreflex reduction (-5.1+/-2.2 L/min, p<0.05 vs. saline). CONCLUSION: In CHF, overactive muscle ergoreflex is associated with elevated blood concentration of PG and bradykinin. Modulation of these metabolite concentrations acutely reduces the muscle ergoreflex activity, which suggests a causative role in triggering and/or mediating the ergoreflex response.

Differential contribution of dead space ventilation and low arterial pCO2 to exercise hyperpnea in patients with chronic heart failure secondary to ischemic or idiopathic dilated cardiomyopathy.

In chronic heart failure (CHF), the abnormally large ventilatory response to exercise (VE/VCO(2) slope) has 2 conceptual elements: the requirement of restraining arterial partial pressure of carbon dioxide (pCO(2)) from increasing (because of an increased ratio between increased physiologic dead space and tidal volume [VD/VT]) and the depression of arterial pCO(2) by further increased ventilation, which necessarily implies an important non-carbon dioxide stimulus to ventilation. We aimed to assess the contribution of these 2 factors in determining the elevated VE/VCO(2) slope in CHF. Thirty patients with CHF underwent cardiopulmonary exercise testing (age 65 +/- 11 years, left ventricular ejection fraction 34 +/- 15%, peak oxygen uptake 15.2 +/- 4 ml/kg/min, VE/VCO(2) slope 36.4). At rest and during exercise, arterial pCO(2) was measured and VD was calculated and separated into serial and alveolar components. VD/VT decreased from 0.57 at rest to 0.44 at peak exercise (p <0.01). VE/VCO(2) slope was correlated with peak exercise VD/VT (r = 0.67), the serial VD/VT ratio (r = 0.64), and alveolar VD/VT ratio (r = 0.51) at peak exercise (all p <0.01). VE/VCO(2) slope was also correlated with arterial pCO(2) (r = -0.75, p <0.001). Despite this, arterial pCO(2) was not related to peak oxygen uptake (r = 0.2) or to arterial lactate (r = -0.25) and only weakly to New York Heart Association functional class (F = 3.7). First, the increased VE/VCO(2) slope was caused by both the high VD/VT ratio and by other mechanisms, as shown by low arterial pCO(2) during exercise. Second, this latter component (depression of arterial pCO(2)) was not related to conventional measures of heart failure severity.

Reproducibility of the measurement of the muscle ergoreflex activity in chronic heart failure.

BACKGROUND: A causative role for symptom generation in heart failure has been attributed to overactive muscle afferents, metaboreflex and mechanoreflex. We examined the reproducibility of the methods commonly used to assess these reflexes. MATERIAL AND METHODS: Twelve stable heart failure patients (62.8+/-2.4 years) and 18 normals were studied. The metaboreflex was evaluated on both leg and arm exercises, by performing two runs of 5-min submaximal handgrip and leg exercises. On one run the subjects recovered normally (control recovery), while on the other a post-exercise regional circulatory occlusion (PE-RCO) was induced in the exercising limb, to isolate the stimulation of the metaboreceptor after exercise. The metaboreflex was quantified as the difference in ventilation between the PE-RCO and the control recovery periods with respect to rest. The existence of a mechanoreflex was sought by comparing the ventilatory increment per unit of active work (dV(E)/dVO(2) ratio) between leg passive movement and active low level exercise. The coefficients of variation (CV) were computed to express the reproducibility of these reflexes in heart failure. RESULTS: The metaboreflex was overactive in patients vs. normals during both arm (7.2+/-2.8 l/min vs. 0.06+/-0.3 l/min) and leg (5.6+/-1.2 l/min vs. 0.5+/-0.2 l/min) tests. The mechanoreflex was not different between patients and normals: dV(E)/dVO(2) during passive movement 48.9+/-18.3 and 22.4+/-26.5; active exercise 42.3+/-18.4 and 31.9+/-18.7 (P=NS). In patients, the CV for the metaboreflex was 23.4% in the arm and 35.3% in the leg, while for the mechanoreflex test CV was 38.1% during passive movement and 21.1% during active exercise. CONCLUSION: The described method of measuring the muscle reflex activity shows an adequate reproducibility in heart failure patients.

Aerobic exercise physiology in a professional rugby union team.

INTRODUCTION: In professional rugby, different positional roles may require different levels of aerobic fitness. Forward and backline players from a team of elite rugby players were tested to evaluate the differences between the two groups. METHODS: 28 male players, 15 backs and 13 forwards, underwent maximal treadmill cardiopulmonary exercise testing (CPX), lung spirometry, a 3 km timed run, and body fat measurement. RESULTS: Peak oxygen uptake was higher in backs than in forwards (peak VO(2) 48.3+/-2.1 vs. 41.2+/-2.7 ml kg(-1) min(-1), P<0.05) with no significant difference in peak respiratory exchange ratio (1.08+/-0.02 vs. 1.07+/-0.02, P=NS), exercise time (1306+/-39.7 vs. 1217+/-25.1 s, P=NS) or time for 3 km run (667.5+/-14.1 vs. 699.0+/-20.7 s, P=NS). However, the forwards were taller and heavier (height 190.2+/-2.2 vs. 179.5+/-1.3 cm, P<0.001, body mass 104+/-2.4 vs. 86.3+/-1.7 kg, P<0.0001) and had a higher fat content (body fat percentage 12.8+/-0.8 vs. 9.7+/-0.6%, P<0.01) and forced expiratory volume in 1 s (FEV1, 4.9+/-0.1 vs. 4.5+/-0.2 l, P<0.05). There was a significant negative correlation between peak VO(2), 3 km run time (r=-0.45, P<0.05) and weight (r=-0.54, P<0.003) for all subjects. CONCLUSION: Backline players have a higher peak oxygen uptake per kilogram than forwards, although the cardiopulmonary exercise test duration, degree of anaerobic metabolism and 3 km run time are not significantly different. These results could be due to the two groups' different body structure, being shorter, lighter and having a lower percentage body fat. These differences, which are likely to be a result of selection for specific roles in the game, should be taken into account when evaluating aerobic fitness within a rugby team.

Muscle metaboreflex-induced increases in stroke volume.

PURPOSE: Accumulation of by-products of metabolism within skeletal muscle may stimulate sensory nerves, thus evoking a pressor response named muscle metaboreflex. The aim of this study was to evaluate changes in central hemodynamics occurring during the metaboreflex activation. METHODS: In seven healthy subjects, the metaboreflex was studied by postexercise regional circulatory occlusion at the start of the recovery from a mild rhythmic forearm exercise. Central hemodynamics was evaluated by means of impedance cardiography. RESULTS: The main findings of this study were that, with respect to rest, the metaboreflex: 1) raised mean blood pressure (+13%; P < 0.01); 2) enhanced myocardial contractility (-12% in preejection period/left ventricular ejection time ratio; P < 0.01); 3) prolonged diastolic time (+11%; P < 0.01); 4) increased stroke volume (+ 10%; P < 0.05); and 5) increased cardiac output (+6%; P < 0.05). These responses were present neither during recovery without circulatory occlusion nor during circulatory occlusion without prior exercise. Moreover, the metaboreflex did not affect systemic vascular resistance and induced bradycardia with respect to recovery without circulatory occlusion. CONCLUSION: These results suggest that the blood pressure response during metaboreflex activation after mild rhythmic exercise is strongly dependent on the capacity to increase cardiac output rather than due to increased vascular resistance.

Skeletal muscle reflex in heart failure patients: role of hydrogen.

BACKGROUND: An important role of the increased stimulation of skeletal muscle ergoreceptors (intramuscular afferents sensitive to products of muscle work) in the genesis of symptoms of exertion intolerance in chronic heart failure (CHF) has been proposed. With the use of selective infusions and dietary manipulation methods, we sought to identify the role of H+, K+, lactate, and peripheral hemodynamics on ergoreflex overactivation. METHODS AND RESULTS: Ten stable CHF patients (aged 67.9+/-2.5 years, peak oxygen uptake 16.3+/-1.2 mL x kg(-1) x min(-1)) and 10 age-matched and sex-matched healthy subjects were studied. The ergoreflex contribution to ventilation was assessed by post-handgrip regional circulatory occlusion (PH-RCO) and computed as the difference in ventilation between PH-RCO and a control run without PH-RCO. This test was performed on 6 separate occasions. On each occasion a different chemical was infused (insulin, sodium nitroprusside, sodium bicarbonate, dopamine, or saline) or a 36-hour glucose-free diet was undertaken before the test. During all stages of the protocol, the local muscular blood effluent concentrations of H+, K+, glucose, and lactate were assessed. An ergoreflex effect on the ventilatory response was seen in patients (versus control subjects) during the saline infusions (6.7+/-2.3 L/min versus -0.1+/-0.5 L/min, P<0.01). The only intervention to significantly lower the ergoreflex was sodium bicarbonate (0.4+/-0.3 L/min versus -0.2+/-0.4 L/min in control subjects, P=NS; versus saline P<0.05), which also reduced H(+) concentration during exercise (47.4+/-1.3 versus 50.0+/-1.4 nmol/L on saline, P<0.05). CONCLUSION: A reduction of the H+ concentration by infusion of sodium bicarbonate abolishes the increased ergoreceptor activity in CHF, suggesting a role of H+ in ergoreflex activation, either directly or indirectly.

Abnormal temporal dynamics of blood pressure and RR interval regulation in patients with chronic heart failure: relationship to baroreflex sensitivity.

It is not known whether the temporal relationship between blood pressure (BP) and RR interval is modulated by the same mechanisms in normal controls and patients with chronic heart failure (CHF). We investigated this under conditions of controlled slow breathing. Fifty patients with CHF and 17 age-matched normals underwent recordings of BP and RR interval during 0.1 Hz controlled breathing. Fourier analysis was used to determine the phase relationships between the oscillations in respiration, BP and RR interval. There was no significant difference between patients and normals in the distribution of phase angle between respiration and BP (P=0.06) or between respiration and RR interval (P=0.21). There was, however, a significant difference in the phase relationship between BP and RR interval (P=0.03): in normals, BP led RR interval by a mean phase angle of 48.4 degrees (S.D. 16.8 degrees ). In patients with CHF, the distribution of phase difference was much wider [34.4 degrees (S.D. 62.8 degrees )]. The source of this wide distribution was patients with attenuated baroreflex sensitivity (BRS), with those with preserved BRS showing a relationship between BP and RR interval similar to the normal group. During controlled respiration, normal subjects exhibit a stereotyped relationship between oscillations in BP and RR interval, which is mediated by the baroreflex. This relationship is maintained in those patients with CHF who have a preserved BRS. In contrast, patients with an attenuated BRS show a wide distribution in the relationship between BP and RR interval ranging from completely in phase, to anti-phase. This may have important implications for the measurement and interpretation of BRS in patient groups where BRS is weak.

Chemical mediators of the muscle ergoreflex in chronic heart failure: a putative role for prostaglandins in reflex ventilatory control.

BACKGROUND: The overactivity of ergoreceptors (intramuscular afferents sensitive to products of skeletal muscle work) may be responsible for the abnormal responses to exercise and symptoms of exercise intolerance in chronic heart failure (CHF); however, little is known of the chemical nature of the stimuli involved. We investigated biochemical factors (H+, VCO2, VO2, HCO3, K+, phosphate, lactate, PGE2, PGF(1alpha), and bradykinin) potentially involved in ergoreceptor activation. METHODS AND RESULTS: Sixteen stable patients with CHF (64.9+/-2.7 years, peak VO2 15.8+/-0.7 mL/kg per min) and 10 age-matched controls were studied. The ergoreceptor test involved two 5-minute handgrip exercises. On one occasion, the subjects recovered normally (control recovery), whereas on the other a posthandgrip regional circulatory occlusion was induced in the exercising arm, isolating the stimulation of the ergoreceptor after exercise. The ergoreflex was quantified as the difference in ventilation between the posthandgrip regional circulatory occlusion and the control recovery periods. During the protocol, the local muscular blood effluent concentrations of metabolic mediators were assessed. Patients had an ergoreflex effect on ventilation greater than controls (4.8+/-1.4 versus 0.4+/-0.1 L/min, P<0.01). During the ergoreflex test in patients, the following metabolites were elevated with respect to resting values in comparison with controls: PGE2 (3.7+/-0.7 versus 1.1+/-0.2 pg/mL), PGF(1alpha) (16.2+/-2.8 versus 7.2+/-1.2 pg/mL), and bradykinin (2.1+/-0.3 versus 1.0+/-0.1 pg/mL), P<0.05 for all comparisons. Only the increases in prostaglandins were predictors of the ergoreflex response (r>0.41, P<0.01). CONCLUSIONS: Although multiple metabolites are concentrated in exercising muscle in CHF, only prostaglandins correlated with ergoreflex activity, suggesting these factors as potential triggers to the exaggerated ergoreflex, which is characteristic of CHF. This may have important implications for novel therapies to improve exercise tolerance.

Relationship of skeletal muscle metaboreceptors in the upper and lower limbs with the respiratory control in patients with heart failure.

Increased activity of muscle metaboreceptors (afferents sensitive to muscle contraction that are responsible for the ventilatory responses to exercise) has been proposed in patients with chronic heart failure (CHF) to constitute a missing link between muscle metabolic abnormalities and exercise overventilation. We looked at this reflex overactivation to determine if it is systemic or limited to a single muscle region in the same human subject. This was done by comparing the metaboreflex response of ventilatory control in the lower and upper limbs in CHF patients and healthy controls. Groups of 15 stable CHF patients (63.7+/-2.7 years) and eight control subjects (69.8+/-1.8 years) performed both leg and arm metaboreflex tests. These metaboreflex tests involved two 5 min episodes of bicycle or handgrip exercise: on one occasion after the exercise the subjects recovered normally, while on the other occasion tourniquet cuffs were inflated around the exercising limb to supra-systolic pressure at the onset of recovery to obtain a regional circulatory occlusion, which isolates and maintains the stimulation of the metaboreflex after exercise. The contribution of the metaboreflex to exercise ventilation was computed as the absolute increment of peak ventilation that was maintained by regional circulatory occlusion. The metaboreceptor contribution to the ventilatory response to both leg exercise (patients, 5.3+/-1.6 litres/min; controls, 0.2+/-0.7 litres/min) and arm exercise (patients, 3.7+/-1.0 litres/min; controls, 0.02+/-0.4 litres/min) was significantly higher in CHF patients (P<0.05). A significant correlation was present between metaboreflex responses to arm and leg exercises (r=0.4, P<0.05). Metaboreflex responses during both types of exercise were inversely correlated with peak oxygen uptake (leg, r=-0.43, P<0.05; arm, r=-0.633, P=0.0009), but only the reflex during arm exercise was correlated with the .V(E) (ventilation)/.V(CO)(2) (CO(2) production) slope (r=0.576, P<0.005). Thus the metaboreflex system is systemically overactive and may potentially contribute to exercise intolerance during both lower- and upper-limb efforts in CHF. This suggests a unique mechanism responsible for overactivation of this system in the skeletal muscle of heart failure patients.