Physical Fitness Is Directly Related to Exercise Capacity and Ventilatory Response to Exercise in Men with HFrEF.

Background: Heart failure (HF) patients experience reduced functional fitness level (determining the performance of routine, daily activities) and diminished exercise capacity (linked to more effortful activities). Aim: The aim of the study is to assess this relationship using functional fitness tests compared to peak VO2 and VE/VCO2 slope in the context of exercise capacity and ventilatory response to exercise. Methods: A total of 382 men with stable HFrEF (age: 61 ± 10, NYHA class I/II/III/IV: 16/50/32/2%, LVEF: 30.5 ± 8.3%) underwent cardiopulmonary exercise testing (CPX) and a Senior Fitness Test (SFT). Afterwards, the patients were divided according to the 2capacity with peak VO2 ≥ 18 mL/kg/min, those with higher or lower ventilatory responses (VE/VCO2 slope ≥ 35 vs. <35) to the exercise were compared. Results: Patients who covered shorter distances in the 6 min walking test showed worse results in the functional tests ('stand up and go', 'chair stand' and 'arm curl') and CPX (lower peak VO2, shorter exercise time and higher VE/VCO2 slope). Subjects classified into Class D demonstrated the worst results in all elements of SFT; those in Class A demonstrated the best results. Significant differences that were analogous occurred also between classes B and C. Among the participants who reached peak VO2 ≥ 18 mL/kg/min (n = 170), those with VE/VCO2 slope ≥ 35 were characterized by worse physical fitness as compared to those with VE/VCO2 < 35. Conclusion: Reduced exercise tolerance led to worsening physical function in patients with HFrEF. Moreover, limitations in physical fitness seem to be distinctive for those patients showing excessive ventilatory response to exercise slope VE/VCO2 (≥35). The Senior Fitness Test may be considered as a useful tool for assessing comprehensive functional and clinical status and risk stratification in patients with HFrEF, especially those with extremely low exercise capacity.

Intravenous iron supplementation improves energy metabolism of exercising skeletal muscles without effect on either oxidative stress or inflammation in male patients with heart failure with reduced ejection fraction.

BACKGROUND: Skeletal muscle dysfunction is a feature of heart failure (HF). Iron deficiency (ID) is prevalent in patients with HF associated with exercise intolerance and poor quality of life. Intravenous iron in iron deficient patients with HF has attenuated HF symptoms, however the pathomechanisms remain unclear. The aim of study was to assess whether intravenous iron supplementation as compared to placebo improves energy metabolism of skeletal muscles in patients with HF. METHODS: Men with heart failure with reduced ejection fraction (HFrEF) and ID were randomised in 1:1 ratio to either intravenous ferric carboxymaltose (IV FCM) or placebo. In vivo reduction of lactates by exercising skeletal muscles of forearm was analyzed. A change in lactate production between week 0 and 24 was considered as a primary endpoint of the study. RESULTS: There were two study arms: the placebo and the IV FCM (12 and 11 male patients with HFrEF). At baseline, there were no differences between these two study arms. IV FCM therapy as compared to placebo reduced the exertional production of lactates in exercising skeletal muscles. These effects were accompanied by a significant increase in both serum ferritin and transferrin saturation in the IV FCM arm which was not demonstrated in the placebo arm. CONCLUSIONS: Intravenous iron supplementation in iron deficient men with HFrEF improves the functioning of skeletal muscles via an improvement in energy metabolism in exercising skeletal muscles, limiting the contribution of anaerobic reactions generating ATP as reflected by a lower in vivo lactate production in exercising muscles in patients with repleted iron stores.

Impact of assisted exercises on skeletal muscle oxygenation levels in men with acutely decompensated heart failure.

BACKGROUND: The complex clinical status of modern day patients hospitalized due to acute heart failure (AHF) results from their advanced age, comorbidities, frailty, heart failure symptoms (including massive swelling of the lower limb), and dramatic reduction of exercise tolerance. Hence, there is a need to implement physiotherapeutic procedures as early as possible, aiming to both accelerate the restoration of clinical stabilization and prevent post-hospital disability. OBJECTIVES: We investigated whether assisted lower limb exercises have an impact on perfusion and oxygenation in skeletal muscle and if they are feasible in patients with AHF. MATERIAL AND METHODS: We examined 34 men (age: 66 ±11 years; left ventricular ejection fraction (LVEF): 34 ±11%; clinical presentation: 31 wet-warm and 3 wet-cold). The intervention (carried out on the 2nd day of hospitalization) included: 1) a 3-minute rest period; 2) an exercise phase (45 repetitions of assisted flexion and extension of the lower limb; and 3) a 10-minute relaxation period. We analyzed blood pressure (BP), heart rate (HR), respiratory rate (RR), tissue oxygenation (reflected by oxygen saturation measured with a pulse oximeter), and changes in peripheral tissue perfusion (reflected by the tissue oxygenation index (TOI) measured with near-infrared spectroscopy (NIRS)). RESULTS: The hemodynamic parameters (both ΔHR and Δsystolic BP) and oxygen saturation did not change (all p > 0.05), whereas the RR declined (p < 0.001). The exercises improved venous outflow (reflected by decreased oxygenated, deoxygenated and total hemoglobin, all p < 0.05) and increased peripheral tissue perfusion, as reflected by the TOI (p < 0.05). The patients reported relief and lack of dyspnea during and after the assisted exercises. CONCLUSIONS: The physiotherapeutic intervention improved both venous outflow and muscle oxygenation in men with AHF. The presented protocol was safe, feasible and well-tolerated, and resulted in relief for the patients. We believe that such procedures might be recommended for the initial period of rehabilitation in this challenging subgroup of patients.

Iron status, catabolic/anabolic balance, and skeletal muscle performance in men with heart failure with reduced ejection fraction.

BACKGROUND: Metabolic derangements related to tissue energetics constitute an important pathophysiological feature of heart failure. We investigated whether iron deficiency and catabolic/anabolic imbalance contribute to decreased skeletal muscle performance in men with heart failure with reduced ejection fraction (HFrEF), and whether these pathologies are related to each other. METHODS: We comprehensively examined 23 men with stable HFrEF (median age [interquartile range]: 63 [59-66] years; left ventricular ejection fraction: 28 [25-35]%; New York Heart Association class I/II/III: 17/43/39%). We analyzed clinical characteristics, iron status, hormones, strength and fatigability of forearm flexors and quadriceps (surface electromyography), and exercise capacity (6-minute walking test). RESULTS: None of the patients had anemia whereas 8 were iron-deficient. Flexor carpi radialis fatigability correlated with lower reticulocyte hemoglobin content (CHR, p < 0.05), and there was a trend towards greater fatigability in patients with higher body mass index and lower serum ferritin (both p < 0.1). Flexor carpi ulnaris fatigability correlated with lower serum iron and CHR (both p < 0.05). Vastus medialis fatigability was related to lower free and bioavailable testosterone (FT and BT, respectively, both p < 0.05), and 6-minute walking test distance was shorter in patients with higher cortisol/FT and cortisol/BT ratio (both p < 0.05). Lower ferritin and transferrin saturation correlated with lower percentage of FT and BT. Men with HFrEF and iron deficiency had higher total testosterone, but lower percentage of FT and BT. CONCLUSIONS: Iron deficiency correlates with lower bioactive testosterone in men with HFrEF. These two pathologies can both contribute to decreased skeletal muscle performance in such patients.

Evaluation of Skeletal Muscle Function and Effects of Early Rehabilitation during Acute Heart Failure: Rationale and Study Design.

BACKGROUND: Acute heart failure (AHF) is associated with disturbances of the peripheral perfusion leading to the dysfunction of many organs. Consequently, an episode of AHF constitutes a "multiple organ failure" which may also affect the skeletal muscles. However, the abnormalities within skeletal muscles during AHF have not been investigated so far. The aim of this project is to comprehensively evaluate skeletal muscles (at a functional and tissue level) during AHF. METHODS: The study will include ≥63 consecutive AHF patients who will be randomized into 2 groups: ≥42 with cardiac rehabilitation group versus ≥21 with standard pharmacotherapy alone. The following tests will be conducted on the first and last day of hospitalization, at rest and after exercise, and 30 days following the discharge: clinical evaluation, medical interview, routine physical examination, echocardiography, and laboratory tests (including the assessment of NT-proBNP, inflammatory markers, and parameters reflecting the status of the kidneys and the liver); hemodynamic evaluation, noninvasive determination of cardiac output and systemic vascular resistance using the impedance cardiography; evaluation of biomarkers reflecting myocyte damage, immunochemical measurements of tissue-specific enzymatic isoforms; evaluation of skeletal muscle function, using surface electromyography (sEMG) (maximum tonus of the muscles will be determined along with the level of muscular fatigability); evaluation of muscle tissue perfusion, assessed on the basis of the oxygenation level, with noninvasive direct continuous recording of perfusion in peripheral tissues by local tissue oximetry, measured by near-infrared spectroscopy (NIRS). RESULTS AND CONCLUSIONS: Our findings will demonstrate that the muscle tissue is another area of the body which should be taken into consideration in the course of treatment of AHF, requiring a development of targeted therapeutic strategies, such as a properly conducted rehabilitation.

Depleted iron stores are associated with inspiratory muscle weakness independently of skeletal muscle mass in men with systolic chronic heart failure.

BACKGROUND: Skeletal and respiratory muscle dysfunction constitutes an important pathophysiological feature of heart failure (HF). We assessed the relationships between respiratory muscle function, skeletal muscle mass, and physical fitness in men with HF with reduced left ventricular ejection fraction (HFrEF), and investigated the hypothesis of whether iron deficiency (ID) contributes to respiratory muscle dysfunction in these patients. METHODS: We examined 53 male outpatients with stable HFrEF without asthma or chronic obstructive pulmonary disease (age: 64 ± 10 years; New York Heart Association [NYHA] class I/II/III: 36/51/13%; ischaemic aetiology: 83%; all with left ventricular ejection fraction ≤40%) and 10 middle-aged healthy men (control group). We analysed respiratory muscle function (maximal inspiratory and expiratory pressure at the mouth [MIP and MEP, respectively]), appendicular lean mass/body mass index (ALM/BMI; ALM was measured using dual-energy X-ray absorptiometry), physical fitness (components of Functional Fitness Test for Older Adults), and iron status. RESULTS: MIP, MEP, and ALM/BMI (but not MIP adjusted for ALM/BMI) were lower in men with HFrEF vs. healthy men. MIP, MEP, and MIP adjusted for ALM/BMI (but not ALM/BMI) were lower in men with HFrEF with vs. without ID. In a multivariable linear regression model lower serum ferritin (but not transferrin saturation) was associated with lower MIP independently of ALM/BMI, left ventricular ejection fraction, N-terminal pro-B-type natriuretic peptide (NT-proBNP), and haemoglobin concentration. In multivariable linear regression models, lower MIP was associated with worse results in Functional Fitness Test when adjusted for ALM/BMI or relevant clinical variables (NYHA class, estimated glomerular filtration rate, NT-proBNP, and haemoglobin concentration). CONCLUSIONS: In men with HFrEF, low ferritin reflecting depleted iron stores is associated with inspiratory muscle weakness independently of skeletal muscle mass. Inspiratory muscle dysfunction correlates with worse physical fitness independently of either skeletal muscle mass or disease severity.

Nordic Walking May Safely Increase the Intensity of Exercise Training in Healthy Subjects and in Patients with Chronic Heart Failure.

BACKGROUND: Physical activity in patients with chronic heart failure (HF) improves the exercise capacity and quality of life, and may also reduce mortality and hospitalizations. The greatest benefits are achieved through high-intensity aerobic exercises resulting in a stronger cardiorespiratory response. Nordic walking (NW), a walking technique using two poles and mimicking the movements performed while cross-country skiing, is associated with the involvement of more muscle groups than in the case of classic walking, and should therefore make it possible to increase exercise intensity, resulting in more effective training for patients with HF. OBJECTIVES: The aim of the study was to assess the feasibility and safety of the NW technique, and to compare the effort intensity while walking with and without the NW technique in both healthy subjects and in patients with chronic HF. MATERIAL AND METHODS: The study involved 12 healthy individuals (aged 30 ± 10 years, 5 men) and 12 men with stable chronic systolic HF (aged 63 ± 11 years, all categorized in New York Heart Association class II, median LVEF 30%, median peak VO(2) 18.25 mL/kg/min). All the participants completed two randomly assigned submaximal walking tests (one with NW poles and one without) conducted on a level treadmill for 6 min at a constant speed of 5 km/h. RESULTS: Walking with the NW technique was feasible, safe and well tolerated in all subjects. In both the control group and the chronic HF group, walking with the NW technique increased peak VO(2), RER, VE, PET CO(2), HR and SBP over walking without the poles; and the fatigue grade according to the abridged Borg scale was higher. Dyspnea did not increase significantly with the NW technique. CONCLUSIONS: The NW technique can increase the intensity of aerobic training in a safe and well-tolerated way in both healthy individuals and in patients with chronic HF.

Could the two-minute step test be an alternative to the six-minute walk test for patients with systolic heart failure?

BACKGROUND: The consequence of exercise intolerance for patients with heart failure is the difficulty climbing stairs. The two-minute step test is a test that reflects the activity of climbing stairs. DESIGN: The aim of the study design is to evaluate the applicability of the two-minute step test in an assessment of exercise tolerance in patients with heart failure and the association between the six-minute walk test and the two-minute step test. METHODS: Participants in this study were 168 men with systolic heart failure (New York Heart Association (NYHA) class I-IV). In the study we used the two-minute step test, the six-minute walk test, the cardiopulmonary exercise test and isometric dynamometer armchair. RESULTS: Patients who performed more steps during the two-minute step test covered a longer distance during the six-minute walk test (r = 0.45). The quadriceps strength was correlated with the two-minute step test and the six-minute walk test (r = 0.61 and r = 0.48). The greater number of steps performed during the two-minute step test was associated with higher values of peak oxygen consumption (r = 0.33), ventilatory response to exercise slope (r = -0.17) and longer time of exercise during the cardiopulmonary exercise test (r = 0.34). Fatigue and leg fatigue were greater after the two-minute step test than the six-minute walk test whereas dyspnoea and blood pressure responses were similar. CONCLUSION: The two-minute step test is well tolerated by patients with heart failure and may thus be considered as an alternative for the six-minute walk test.

Late-onset hypogonadism in men with systolic heart failure: prevalence, clinical associates, and impact on long-term survival.

BACKGROUND: Male ageing is characterized by diminished circulating androgens with several adverse psychosomatic consequences and can be aggravated by concomitant chronic diseases. According to the European Male Aging Study (EMAS) Group, late-onset hypogonadism (LOH) refers to testosterone deficiency accompanied by sexual complaints. AIM: We investigated the prevalence of LOH in men with systolic heart failure (HF), and its clinical determinants and prognostic consequences. METHODS: Among 201 men with systolic HF (age: 60 ± 11 years), serum total testosterone (TT) was assessed using an immunoassay, and estimated free testosterone (eFT) was calculated using Vermeulen's formula. LOH was diagnosed when TT < 3.2 ng/mL and eFT < 64 pg/mL were accompanied by three sexual symptoms (decrease in the number of morning erections, reduced potency, and low libido) of at least moderate severity assessed using the Aging Males' Symptoms Scale. RESULTS: Decreased frequency of morning erections, reduced potency, and low libido were experienced by 56%, 62%, and 55% of men with HF, respectively; whereas 67%, 61%, and 44% of subjects complained of at least one, two, and three symptoms, respectively. Hypogonadal TT and eFT were observed in 34% and 47% of patients, respectively; and in 33% subjects, both TT and eFT were reduced. Finally, 30 men with HF (15%) were diagnosed with LOH as compared with 2% in a European male population (EMAS). In a multivariable model, older age and higher serum uric acid were independently associated with greater LOH prevalence (both P < 0.05). Among men aged ≤60 years (but not in those aged >60 years), LOH increased 5-year all-cause mortality in the univariable model; however, when adjusted for HF severity, the association lost its statistical significance. CONCLUSIONS: Men with systolic HF commonly report sexual complaints. LOH-the combination of sexual dysfunction and testosterone deficiency-occurs more frequently than in a general male population. LOH does not affect long-term mortality, when adjusted for HF severity.

Distance covered during a six-minute walk test predicts long-term cardiovascular mortality and hospitalisation rates in men with systolic heart failure: an observational study.

QUESTION: Does the distance covered during a 6-minute walk test predict risk of death or hospitalisation for cardiovascular reasons in men with stable heart failure over three years of follow-up? DESIGN: Prospective observational study. PARTICIPANTS: 243 men with stable systolic heart failure, with a mean age of 60 yr (SD 11) and left ventricular ejection fraction of 29% (SD 8). According to the New York Heart Association (NYHA) classification, 15% of the participants were in Class I, 44% in Class II, 37% in Class III, and 4% in class IV. OUTCOME MEASURES: The exercise capacity of participants was measured using the 6-minute walk test. The participants were followed up for at least three years in the case of survivors. The primary end-points of the survival analyses included cardiovascular death or urgent cardiovascular hospitalisation. RESULTS: During the 3-year follow-up, 44% of the participants died, and 69% died or required hospitalisation for cardiovascular reasons. A multivariate analysis showed that the shorter the distance covered in the 6-minute walk test, the greater the 1-year and 3-year mortality risk. Participants with a 6-minute walk test ≤ 468 m had a mortality hazard ratio of 3.22 (95% CI 1.17 to 8.86) at one year and 2.18 (95% CI 1.18 to 4.03) at three years. Multivariate analysis also showed that higher risk mortality or hospitalisation for cardiovascular reasons was predicted by a 6-minute walk distance ≤ 468m, with a hazard ratio of 2.77 (95% CI 1.30 to 5.88) at one year and 1.71 (95% CI 1.08 to 2.72) at three years. CONCLUSION: The 6-minute walk test distance constitutes an independent predictor of mortality and mortality or hospitalisation for cardiovascular reasons in men with stable systolic heart failure.

Determinants of physical fitness in males with systolic heart failure.

BACKGROUND: Heart failure (HF) is a systemic disease which affects mainly older adults. The main symptom of HF is exercise intolerance which in the course of disease can cause limitations in independent functioning. So far no study on the impact of HF on physical fitness in men, regardless of disease severity, has been reported. AIM: To evaluate physical fitness in men with HF independently of age, HF severity, concomitant diseases and pharmacological treatment. METHODS: The study group consisted of 228 men with stable systolic dysfunction (age 60+/-11, left ventricular ejection fraction--LVEF 29+/-9%, NYHA class I/II/III/IV--17/44/35/4%). In order to assess physical fitness the Functional Fitness Test by Rikli and Jones for older adults was used. RESULTS: The level of physical fitness decreased with age. Patients with greater severity of HF had worse aerobic endurance, agility and muscular endurance in comparison with men in NYHA classes I-II. A lower level of agility and dynamic balance was found in patients with higher concentration of NT-proBNP and lower levels of haemoglobin and eGFR. Coexisting atrial fibrillation and diabetes mellitus were associated with decreased physical fitness. No relationship between flexibility and clinical parameters or concomitant diseases was found in the study group. CONCLUSIONS: The most important determinants of physical fitness in men with HF were age and NYHA class. Additional factors which decreased physical fitness were atrial fibrillation and diabetes mellitus. Higher level of NT-proBNP and lower levels of haemoglobin were associated with a reduction of upper body strength and aerobic endurance.

Gonadal and adrenal androgen deficiencies as independent predictors of increased cardiovascular mortality in men with type II diabetes mellitus and stable coronary artery disease.

BACKGROUND: Age-related decline in circulating androgens in men is associated with poor cardiovascular (CV) outcome. Men with type II diabetes mellitus (DM) are prone to develop androgen deficiency. OBJECTIVES: We studied the prevalence and prognostic consequences of deficiencies in circulating total and free testosterone (TT, FT) and dehydroepiandrosterone sulphate (DHEAS) in type II DM men with coronary artery disease (CAD). METHODS: We examined 153 diabetic men with stable CAD (age: 65±9 years). Serum levels of FT were estimated (eFT) from TT and sex hormone binding globulin levels. RESULTS: TT, eFT and DHEAS deficiencies (serum levels≤the 10th percentile of healthy peers) were found in 22%, 33% and 77% of DM men with CAD, being more frequent than in healthy peers (all p<0.001). During follow-up (median: 19 months), there were 43 (28%) CV deaths. We identified 4 independent predictors of CV mortality: testosterone (TT, eFT) and DHEAS deficiencies, high plasma N-terminal pro-B-type natriuretic peptide (≥2661 pg/mL, upper quartile), high serum high sensitivity C-reactive protein (≥6.58 mg/L, upper quartile) (all p<0.01). There was a graded relation between the number of risk factors and increased CV mortality: hazard risk (95% confidence interval) for 1, 2, 3-4 vs. no risk factors, respectively: 5.9 (0.8-45.6), p=0.09, 9.2 (1.2-69.2), 63.0 (8.0-498.7), p<0.0001 (χ(2)=42.23, p<0.0001). CONCLUSIONS: In diabetic men with stable CAD, testosterone and DHEAS deficiencies are common and related to high CV mortality. Whether an androgen substitution would improve prognosis in androgen deficient men with type II diabetes and stable CAD, requires further studies.

Abnormal indices of autonomic function are no longer predictors of poor outcome in diabetic patients without neuropathy but with coexisting coronary artery disease who receive optimal pharmacological therapy.

BACKGROUND: Cardiovascular autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) and has been regarded as a parameter associated with a poor outcome. AIM: We investigated whether indices of cardiovascular autonomic function have prognostic value in the current era of pharmacological therapy recommended for DM patients with coexisting coronary artery disease (CAD), which consists of drugs that affect autonomic balance, i.e. angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), beta-blockers, and statins. METHODS: We studied 127 consecutive patients with type 2 DM and angiographically documented stable CAD (age: 64 years, women: 28%, treatment: ACEI/ARBs: 100%, statins: 98%, beta-blockers: 88%, insulin therapy: 46%). The assessment of autonomic balance within the cardiovascular system included heart rate variability (HRV) (time and spectral-domain analyses) and non-invasive evaluation of baroreflex sensitivity (sequence and controlled breathing methods). Primary end-points were cardiovascular mortality and urgent hospital admissions due to cardiovascular symptoms. RESULTS: During the mean follow-up of 502 +/- 161 days, 28 patients (22%) experienced a cardiovascular event: 7 died and 21 were admitted to hospital. We found the following predictors of an increased risk of the combined end point (cardiovascular death and hospitalisation): elevated level of N-terminal BNP (for log NT-proBNP - HR = 2.6, p = 0.004), severe CAD (3-vessel disease - HR = 2.4, p = 0.02), renal insufficiency (eGFR < 60 ml/min/1.73 m2 - HR = 2.7, p = 0.008), and female gender (HR = 3.2, p = 0.002). None of the indices of autonomic balance had prognostic value (p > 0.2 for all). CONCLUSION: In the population of diabetic patients with stable CAD who receive optimal pharmacological therapy, indices of impaired autonomic function are no longer predictors of poor outcome.