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.

Pathophysiology of Advanced Heart Failure: What Knowledge Is Needed for Clinical Management?

Understanding of heart failure (HF) has evolved from a simple hemodynamic problem through a neurohormonally and proinflammatory-driven syndrome to a complex multiorgan dysfunction accompanied by inadequate energy handling. This article discusses the most important clinical aspects of advanced HF pathophysiology. It presents the concept of neurohormonal activation and its deleterious effect on cardiovascular system and reflex control. The current theories regarding the role of inflammation, cytokine activation, and myocardial remodeling in HF progression are presented. Advanced HF is a multiorgan syndrome with interplay between cardiovascular system and other organs. The role of iron deficiency is also discussed.

High soluble transferrin receptor in patients with heart failure: a measure of iron deficiency and a strong predictor of mortality.

AIMS: Iron deficiency (ID) is frequent in heart failure (HF), linked with exercise intolerance and poor prognosis. Intravenous iron repletion improves clinical status in HF patients with left ventricular ejection fraction (LVEF) ≤45%. However, uncertainty exists about the accuracy of serum biomarkers in diagnosing ID. The aims of this study were (i) to identify the iron biomarker with the greatest accuracy for the diagnosis of ID in bone marrow in patients with ischaemic HF, and (ii) to establish the prevalence of ID using this biomarker and its prognostic value in HF patients. METHODS AND RESULTS: Bone marrow was stained for iron in 30 patients with ischaemic HF with LVEF ≤45% and 10 healthy controls, and ID was diagnosed for 0-1 grades (Gale scale). A total of 791 patients with HF with LVEF ≤45% were prospectively followed up for 3 years. Serum ferritin, transferrin saturation, soluble transferrin receptor (sTfR) were assessed as iron biomarkers. Most patients with HF (n = 25, 83%) had ID in bone marrow, but none of the controls (P < 0.001). Serum sTfR had the best accuracy in predicting ID in bone marrow (area under the curve 0.920, 95% confidence interval 0.761-0.987, for cut-off 1.25 mg/L sensitivity 84%, specificity 100%). Serum sTfR was ≥1.25 mg/L in 47% of HF patients, in 56% and 46% of anaemics and non-anaemics, respectively (P < 0.05). The reclassification methods revealed that serum sTfR significantly added the prognostic value to the baseline prognostic model, and to the greater extent than plasma N-terminal pro B-type natriuretic peptide. Based on internal derivation and validation procedures, serum sTfR ≥1.41 mg/L was the optimal threshold for predicting 3-year mortality, independent of other established variables. CONCLUSIONS: High serum sTfR accurately reflects depleted iron stores in bone marrow in patients with HF, and identifies those with a high 3-year mortality.

Frailty and cognitive impairment are predictive of takotsubo syndrome following pacemaker implantation.

BACKGROUND: Pacemaker (PM) implantation may cause acute emotional distress leading to takotsubo syndrome (TTS). Frailty and cognitive impairment are known to influence outcomes after surgical procedures. It is unclear whether they may also predispose to TTS following PM implantation. METHODS: We identified nine cases (81 ± 6 years) of TTS following PM implantation that took place between 2013 and 2017 in one high volume implantation center. TTS was diagnosed based on typical echocardiographic appearance with resolution over time and (in cases where deemed necessary) normal coronary angiography. The TTS cases were compared with 30 consecutive cases of PM implantation (75 ± 9 years), which were not complicated by TTS (control group). Frailty was assessed using retrospective Risk Analysis Index (RAI-A). Pacing parameters were analyzed during PM implantation and after 1 month. RESULTS: Cognitive impairment was more prevalent (67% vs 10%, P = .0005), and RAI-A index was significantly higher in the TTS group compared to the control group (26 ± 13.7 vs 13.1 ± 9.8, P = .008). Perioperative right ventricular threshold was significantly higher in patients with TTS comparing to controls (0.99 ± 0.43 V vs 0.74 ± 0.20 V, P = .04). The magnitude of decrease in right ventricular threshold between implantation and 1 month follow-up was greater in TTS patients compared to controls (-0.41 ± 0.29 V vs -0.15 ± 0.38 V, P = .049). CONCLUSIONS: TTS is a rare complication of PM implantation. Patients with cognitive impairment and frailty are at risk of TTS. Right ventricular pacing threshold is acutely affected by TTS and improves over time.

Seat belts-related behaviors in car drivers with cardiac implantable electronic devices.

BACKGROUND: Seat belt use is the single most effective means of reducing fatal injuries in road traffic accidents. The presence of a cardiac implantable electronic device (CIED) might influence seat belt-related behaviors due to the physical proximity of the seat belt and left subclavian area in which the device is usually implanted. Understanding the underlying mechanisms of improper seat belt use may improve safety of these patients. METHODS: We performed a prospective study using a structured questionnaire with 120 CIED recipients (age, 63.9 ± 10.9 years) attending a pacing outpatient clinic. All study participants were active drivers and predominantly male. The majority of patients (79%) had undergone high-energy device implantation. RESULTS: We found that 18% of study participants do not fasten seat belts on a regular basis or use the seat belt in an atypical fashion (such as under the armpit). Moderate or high level of discomfort from the interaction between seat belt and CIED was present in 27%, while more than half (51%) were afraid of seat belt-induced CIED damage. In multifactorial analysis, we found the following independent predictors of improper seat belt use: (1) at least moderate level of discomfort at the CIED site (P = 0.02); (2) fear of CIED damage (P = 0.009); and (3) irregular seat belt use prior to CIED implantation (P = 0.037). CONCLUSIONS: Improper seat belt-related behaviors are common in CIED recipients. They arise from previous habits and from CIED-related physical and psychological factors. Patients' education regarding the importance and safety of proper seat belt use is a priority.

Structural and functional abnormalities in iron-depleted heart.

Iron deficiency (ID) is a common and ominous comorbidity in heart failure (HF) and predicts worse outcomes, independently of the presence of anaemia. Accumulated data from animal models of systemic ID suggest that ID is associated with several functional and structural abnormalities of the heart. However, the exact role of myocardial iron deficiency irrespective of systemic ID and/or anaemia has been elusive. Recently, several transgenic models of cardiac-specific ID have been developed to investigate the influence of ID on cardiac tissue. In this review, we discuss structural and functional cardiac consequences of ID in these models and summarize data from clinical studies. Moreover, the beneficial effects of intravenous iron supplementation are specified.

Do we differ in terms of indications and demographics in cardiac resynchronisation recipients in Poland? Insights from the European CRT Survey II Registry.

BACKGROUND: Multiple randomised clinical trials have proven that cardiac resynchronisation therapy (CRT) reduces morbidity and mortality in appropriately selected patients with congestive heart failure and is recommended for such patients as per the European Society of Cardiology guidelines. AIM: In this paper we compare the indications and demographics in cardiac resynchronisation recipients in Poland and other European countries. METHODS: In 2015 and 2016, physicians from 42 European countries participated in the second edition of the European Cardiac Resynchronisation Therapy Survey. For 14 months, 288 implanting centres gathered data regarding demography, indications, implanting methods, and guidance compatibility from 11,088 patients receiving CRT. RESULTS: The survey revealed that a vast group of patients were eligible for CRT implantation (although some of them with rela-tively weak guidance recommendations) and showed essential variety in clinical practice when national data were benchmarked. CONCLUSIONS: The population of CRT recipients in Poland and other European countries did not differ in terms of demographic and clinical characteristics. In most cases, indications for CRT were in accordance with the guidelines; however some devices were implanted in patients beyond the guideline recommendations. For these procedures, the decision regarding CRT im-plantation relies mainly on the physicians' experience.

Iron Depletion Affects Genes Encoding Mitochondrial Electron Transport Chain and Genes of Non-Oxidative Metabolism, Pyruvate Kinase and Lactate Dehydrogenase, in Primary Human Cardiac Myocytes Cultured upon Mechanical Stretch.

(1) Background: Oxidative energy metabolism is presumed to rely on the optimal iron supply. Primary human cardiac myocytes (HCM) exposed to different iron availability conditions during mechanical stretch are anticipated to demonstrate expression changes of genes involved in aerobic and anaerobic metabolic pathways. (2) Methods: HCM were cultured for 48 h either in static conditions and upon mechanical stretch at the optimal versus reduced versus increased iron concentrations. We analyzed the expression of pyruvate kinase (PKM2), lactate dehydrogenase A (LDHA), and mitochondrial complexes I⁻V at the mRNA and protein levels. The concentration of l-lactate was assessed by means of lactate oxidase method-based kit. (3) Results: Reduced iron concentrations during mechanical work caused a decreased expression of complexes I⁻V (all p < 0.05). The expression of PKM2 and LDHA, as well as the medium concentration of l-lactate, was increased in these conditions (both p < 0.05). HCM exposed to the increased iron concentration during mechanical effort demonstrated a decreased expression of mitochondrial complexes (all p < 0.01); however, a decrement was smaller than in case of iron chelation (p < 0.05). The iron-enriched medium caused a decrease in expression of LDHA and did not influence the concentration of l-lactate. (4) Conclusions: During mechanical effort, the reduced iron availability enhances anaerobic glycolysis and extracellular lactate production, whilst decreasing mitochondrial aerobic pathway in HCM. Iron enrichment during mechanical effort may be protective in the context of intracellular protein machinery of non-oxidative metabolism with no effect on the extracellular lactate concentration.

Iron deficiency as energetic insult to skeletal muscle in chronic diseases.

Specific skeletal myopathy constitutes a common feature of heart failure, chronic obstructive pulmonary disease, and type 2 diabetes mellitus, where it can be characterized by the loss of skeletal muscle oxidative capacity. There is evidence from in vitro and animal studies that iron deficiency affects skeletal muscle functioning mainly in the context of its energetics by limiting oxidative metabolism in favour of glycolysis and by alterations in both carbohydrate and fat catabolic processing. In this review, we depict the possible molecular pathomechanisms of skeletal muscle energetic impairment and postulate iron deficiency as an important factor causally linked to loss of muscle oxidative capacity that contributes to skeletal myopathy seen in patients with heart failure, chronic obstructive pulmonary disease, and type 2 diabetes mellitus.

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.

[Patient with the intervention of an implantable cardioverter-defibrillator in a hospital emergency department].

OBJECTIVE: Introduction: Implantable cardioverter-defibrillators (ICD) improve prognosis in patients with malignant ventricular arrhythmias. Patients with ICD represent a significant proportion of all Emergency Department (ED) admissions. The number of these visits due to the high-energy therapy or antitachycardia pacing (ATP) delivered by the implanted cardioverter-defibrillator is constantly increasing. The aim: To present the prevalence and type of therapeutic interventions of an ICD in patients admitted to ED in 2014-2017 at two medical centers covering approx. 400 000 residents. PATIENTS AND METHODS: Materials and methods: The patients' documentation was analyzed to find patients admitted to emergency department because of the suspicion of the ventricular arrhythmias' therapy delivered by ICD. RESULTS: Results: In most cases adequate high-energy therapies due to life-threatening ventricular arrhythmias were the reason for hospitalization. We identified 126 patients aged 63.0±12.0 years, 108 (86&) of male and 18 (14&) of female. Among 171 ED admissions 6 were associated with ATP and 149 with high-energy therapy, 10 cases presented with VT without therapies, 5 with fantom shocks and in one case the patient had only a pacemaker but not ICD. The number of ICD shocks ranged from 1 to 108. Inadequate ICD discharges were found in 26 (17.4&) of high energy therapies. CONCLUSION: Conclusions:1. The number of patients with ICD admitted to Emergency Department due to the initiation of high-energy or anti-tachyarrhythmic therapy has been steadily increasing in recent years. 2. In most cases, the reason for the admissions are adequate high-energy therapies, i.e. ICD discharges that disrupt the potentially life threatening arrhythmia. 3. Accurate medical history, the possibility of assessing the heart rate stored in the ICD memory during its intervention form the basis for establishing a plan of action in patients with ICD.

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.

Could an analysis of mean corpuscular volume help to improve risk stratification in non-anemic patients with acute myocardial infarction?

BACKGROUND: Nowadays, when the majority of patients with acute myocardial infarction (AMI) are treated with primary percutaneous coronary intervention and modern pharmacotherapy, risk stratification becomes a challenge. Simple and easily accessible parameters that would help in a better determination of prognosis are needed. The aim of the study was to estimate the prevalence of high mean corpuscular volume (MCV, defined as MCV > 92 fL) and to establish its prognostic value in non-anemic patients with AMI. METHODS: We retrospectively analyzed the data of 248 consecutive non-anemic patients hospitalized due to AMI (median age: 65 [59-76] years, men: 63%, ST segment elevation myocardial infarction: 31%, and median left ventricular ejection fraction [LVEF]: 50%). RESULTS: The prevalence of high MCV was 39 ± 6% (± 95% confidence interval) in the entire AMI population. High MCV was more prevalent in males, patients with low body mass index, non-diabetics and cigarette smokers (all p < 0.05). During the 180-day follow-up, there were 38 (15%) events, defined as another AMI or death. In a multivariable Cox proportional hazard model, female gender (p < 0.01), low LVEF (p < 0.001), previous AMI (p < 0.05), arterial hypertension (p < 0.05), and high MCV (p < 0.001) were prognosticators of pre-defined events. CONCLUSIONS: In non-anemic patients with AMI, high MCV is an independent prognostic factor of poor outcome defined as another AMI or death.

Skeletal myopathy in patients with chronic heart failure: significance of anabolic-androgenic hormones.

In heart failure, impairment of cardiac muscle function leads to numerous neurohormonal and metabolic disorders, including an imbalance between anabolic and catabolic processes, in favour of the latter. These disorders cause loss of muscle mass with structural and functional changes within the skeletal muscles, known as skeletal myopathy. This phenomenon constitutes an important mechanism that participates in the pathogenesis of chronic heart failure. both its clinical symptoms and the progression of the disease. Attempts to reverse the above-mentioned pathologic processes by exploiting the anabolic action of androgenic hormones could provide a potentially attractive treatment option. The current concepts of anabolic androgen deficiency and resultant skeletal myopathy in patients with heart failure are reviewed, and the potential role of anabolic-androgenic hormones as an emerging therapeutic option for targeting heart failure is discussed.