Glucagon-like peptide-1 based therapies as a novel approach for chronic heart failure

Glucagon-like peptide-1 (GLP-1) is an endogenous peptide hormone whose metabolic effects have been exploited for glycaemic control in diabetes, but which also exerts important cardiovascular actions. We have recently reported that the GLP-1 mimetic, exendin-4, exerts clear benefits post-myocardial infarction via specific effects on extracellular matrix remodelling which is dysregulated in the diabetic heart (Robinson E et al, Basic Res Cardiol 2015; 110: 20), and have now shown similar cardioprotective actions in experimental diabetes, which are mediated via direct effects on infiltrating macrophages (Tate M et al, Basic Res Cardiol 2015; in press). Taken together with the apparent complexity of GLP-1 signalling and disappointing results of recent cardiovascular trials, our work strongly suggests that selective targeting of GLP-1 may be required in order to realise therapeutic benefit for both diabetic and non-diabetic heart failure patients. This is particularly important given the epidemic increase in the incidence of diabetes which is associated with a markedly enhanced susceptibility to cardiovascular stress.

Glucagon-like peptide-1 based therapies as a novel approach for chronic heart failure

Glucagon-like peptide-1 (GLP-1) is an endogenous peptide hormone whose metabolic effects have been exploited for glycaemic control in diabetes, but which also exerts important cardiovascular actions. We have recently reported that the GLP-1 mimetic, exendin-4, exerts clear benefits post-myocardial infarction via specific effects on extracellular matrix remodelling which is dysregulated in the diabetic heart (Robinson E et al, Basic Res Cardiol 2015; 110: 20), and have now shown similar cardioprotective actions in experimental diabetes, which are mediated via direct effects on infiltrating macrophages (Tate M et al, Basic Res Cardiol 2016; 111: 1). Taken together with the apparent complexity of GLP-1 signalling and disappointing results of recent cardiovascular trials, our work strongly suggests that selective targeting of GLP-1 may be required in order to realise therapeutic benefit for both diabetic and non-diabetic heart failure patients. This is particularly important given the epidemic increase in the incidence of diabetes which is associated with a markedly enhanced susceptibility to cardiovascular stress.

Chronic heart failure programs : does more equal less? (BENCH study)

The national multi-centre study (49 programs, 1158 patients) developed a quality score (HF-IS) and the national benchmarks for heart programs. The higher a program scored on the HF-IS the greater the reduction in hospital admissions and mortality. This score has the potential to change national nursing practice and improve health outcomes of patients.

Comparing methods for prescribing exercise for individuals with chronic heart failure

This study examined the accuracy of current recommended guidelines for prescribing exercise intensity using the methods of percentage of heart rate reserve (%HRR), percentage of VO₂ peak (%VO₂peak) and percentage of VO₂ reserve (%VO₂R) in a clinical population of chronic heart failure (CHF) patients. The precision of prescription of exercise intensity for 45 patients with stable CHF (39:6 M:F, 65±9 yrs (mean±SD)) was investigated. VO₂peak testing is relatively common among patients with cardiac disease, but the assessment of VO₂rest is not common practice and the accepted standard value of 3.5 mL/kg/min is assumed in the application of %VO2R (%VO₂R_3.5). In this study, VO₂rest was recorded for 3 min prior to the start of a symptom-limited exercise test on a cycle ergometer. Target exercise intensities were calculated using the VO₂ corresponding to 50 or 80 %HRR, VO₂peak and VO₂R. The VO₂ values were then converted into prescribed speeds on a treadmill in km/hr at 1 %grade using ACSM’s metabolic equation for walking. Target intensities and prescribed treadmill speeds were also calculated with the %VO₂R method using the mean VO₂rest value of participants (3.9 mL/kg/min) (%VO₂R_3.9). This was then compared to the exercise intensities and prescribed treadmill speeds using patient’s measured VO₂rest. Error in prescription correlates the difference between %VO₂R_3.5 and %VO₂R_3.9 compared to %VO₂R with measured VO₂rest. Prescription of exercise intensity through the %HRR method is imprecise for patients on medications that blunt the HR response to exercise. %VO₂R method offers a significant improvement in exercise prescription compared to %VO₂peak. However, a disparity of 10 % still exists in the %VO₂R method using the standard 3.5 mL/kg/min for VO₂rest in the %VO₂R equation. The mean measured VO₂rest in the 45 CHF patients was 11 % higher (3.9±0.8 mL/kg/min) than the standard value provided by ACSM. Applying the mean measured VO₂rest value of 3.9 mL/kg/min rather than the standard assumed value of 3.5 mL/kg/min proved to be closer to the prescribed intensity determined by the actual measured resting VO₂. These results suggest that the %HRR method should not be used to prescribe exercise intensity for CHF patients. Instead, VO₂ should be used to prescribe exercise intensity and be expressed as %VO₂R with measured variables (VO₂rest and VO₂peak).

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.

Exercise and Sports Science Australia position statement on exercise training and chronic heart failure

Chronic heart failure (CHF) is a complex syndrome characterised by progressive decline in left ventricular function, low exercise tolerance and raised mortality and morbidity. Regular exercise participation has been shown to be a safe and effective treatment modality in the majority of CHF patients, partially reversing some of the maladaptations evident in myocardial and skeletal muscle function, and resulting in improvements in physical fitness and quality of life, and perhaps reduced mortality. The volume and intensity of exercise that is recommended depends on the syndrome severity, however in most patients it should consist of a combination of low-to-moderate intensity aerobic (endurance) exercise on most days of the week and individually prescribed low-to-moderate intensity resistance (strength) training at least twice per week. Additionally, all patients should be closely monitored prior to and during exercise for contraindications by an appropriately trained health professional. The purpose of this statement is to inform and guide exercise practitioners and health professionals in the safe and effective prescription and supervision of exercise for patients with CHF.

Respiratory muscle dysfunction and training in chronic heart failure

A characteristic feature of chronic heart failure (CHF) is reduced exercise tolerance. Several factors contributing to this have been identified, including alterations in central haemodynamics, skeletal muscle oxygen utilisation and respiratory muscle dysfunction. This review focuses on abnormalities identified in respiratory muscle structure and function in CHF and recent evidence for the benefit of selective inspiratory muscle training in CHF. Included in this review are findings from original investigations, with a specific focus on recent published data.