Impact of zolpidem and lemborexant on sleep and morning symptoms when used as a single dose for polysomnography.

This study evaluated the effect of zolpidem and lemborexant on sleep and morning symptoms in patients undergoing type-1 polysomnography for suspected sleep-disordered breathing based on questionnaires and polysomnography results. We enrolled 127 patients (lemborexant: N = 57, zolpidem: N = 25, without hypnotics: N = 45). Rapid eye movement sleep in patients on lemborexant was higher than that in patients without hypnotics (P = 0.02). Frequency of unsteadiness in the morning was higher in patients on zolpidem than that in patients without hypnotics (P = 0.04), which remained after adjustment for potential confounders (P = 0.03). Low-dose lemborexant might be suitable when administered as a single dose during polysomnography.

Difference in the Dynamics of Antibody Titers between COVID-19 Vaccination and SARS-CoV-2 Infection in Healthcare Workers - A Case Study Based on Long-Term and Densely Repeated Measurements of Antibody Titers.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is prevalent worldwide, and effective and safe vaccines against this virus have been developed. Although trends in antibody titers after vaccination and/or SARS-CoV-2 infection have been reported, long-term studies with high frequency of measurements are limited. This report describes the long-term and detailed trends in the antibodies against SARS-CoV-2 S protein receptor-binding domain (S-RBD) measured repeatedly after vaccination and/or infection in 3 healthcare workers. All healthcare workers were administered 30 µg of the messenger RNA vaccine, BNT162b2, during all vaccinations. The peak value of the SARS-CoV-2 S-RBD titer was reached at 1-2 weeks after vaccination and then decreased by half within 8 weeks after vaccination; the peak values of the antibody titer increased with repeated vaccinations. In contrast, after SARS-CoV-2 infection, the peak value of the antibody titer was reached at 4-8 weeks after infection, and the antibody titer remained elevated up to 16-40 weeks after the peak. This report describes the long-term and detailed trends in the anti-SARS-CoV-2 S-RBD titers, showing different patterns after vaccination and/or SARS-CoV-2 infection.

Analysis of the effect of CPAP on hemodynamics using clinical data and a theoretical model: CPAP therapy decreases cardiac output mechanically but increases it via afterload reduction.

BACKGROUND: Noninvasive positive pressure ventilation (NIPPV) has been established as an effective treatment for heart failure. Positive airway pressure such as continuous positive airway pressure (CPAP) increases cardiac output (CO) in some patients but decreases it in others. However, the mechanism behind such unpredictable responses remains undetermined. METHODS AND RESULTS: We measured hemodynamic parameters of 38 cases using Swan-Ganz catheter before and after CPAP in chronic heart failure status. In those whose CO increased by CPAP, pulmonary vascular resistance (PVR) was significantly decreased and SpO2 significantly increased, but the other parameters were not changed. On the other hand, PVR was not changed, but systemic vascular resistance (SVR) was increased in those whose CO decreased by CPAP. To explain this phenomenon, we simulated the cardiovascular system using a cardiac model of time-varying elastance. In this model, it was indicated that CPAP decreases CO irrespective of cardiac function or filling status under constant PVR condition. However, when reduction of PVR by CPAP was taken into account, an increase in CO was expected especially in the hypervolemic and low right ventricle (RV) systolic function cases. CONCLUSIONS: CPAP would increase CO only where PVR can be reduced by CPAP therapy, especially in the case with hypervolemia and/or low RV systolic function. Understanding the underlying mechanism should help identify the patients for whom NIPPV would be effective.

Successful Total Management of Multi-Causative Sleep-Disordered Breathing Complicated with Patient with Adult Congenital Heart Disease.

Sleep-disordered breathing is one of the complications commonly seen in patients with adult congenital heart disease (ACHD) due to multiple causes including complex underlying cardiac defects, cardiomegaly, previous thoracotomies, obesity, scoliosis, and paralysis of the diaphragm. It is often hard to determine its main cause and predict the efficacy of each treatment in its management. We herein report a 30-year-old woman after biventricular repair of pulmonary atresia with intact ventricular septum diagnosed as sleep-related hypoventilation disorder. Simultaneous treatment targeting obesity, paralysis of the diaphragm, and cardiomegaly followed by respiratory muscle reinforcement through non-invasive ventilation resolved her sleep-related hypoventilation disorder. Such management for each factor responsible for the hypoventilation is expected to provide synergetic therapeutic efficacy and increase daily activity in a patient with ACHD.

Obstructive sleep apnea and its management in patients with atrial fibrillation: An International Collaboration of Sleep Apnea Cardiovascular Trialists (INCOSACT) global survey of practicing cardiologists.

Background: Among international cardiologists it is unclear whether equipoise exists regarding the benefit of diagnosing and managing obstructive sleep apnea (OSA) to improve atrial fibrillation (AF) outcomes and whether clinical practice and equipoise are linked. Methods: Between January 2019 and June 2020 we distributed a web-based 12-question survey regarding OSA and AF management to practicing cardiologists in 16 countries. Results: The United States, Japan, Sweden, and Turkey accounted for two-thirds of responses. 863 cardiologists responded; half were general cardiologists, a quarter electrophysiologists. Responses regarding treating OSA with CPAP to improve AF endpoints were mixed. 33% of respondents referred AF patients for OSA screening. OSA was diagnosed in 48% of referred patients and continuous positive airway pressure (CPAP) was prescribed for 59% of them. Nearly 70% of respondents believed randomized controlled trials (RCTs) of OSA treatment in AF patients were necessary and indicated willingness to contribute to such trials. Conclusions: There was no clinical equipoise among surveyed cardiologists; a majority expressed certainty that combined OSA and AF treatment is superior to AF treatment alone for improving AF outcomes. However, a minority of surveyed cardiologists referred AF patients for OSA testing, and while half of screened AF patients had OSA, CPAP was prescribed in little more than half of them, reflecting the view that better clinical trial evidence is needed to support this practice. Our results underscore the need for larger, multi-national prospective studies of OSA treatment and AF outcomes to inform more uniform society guideline recommendations.

Characteristics of sleep-disordered breathing in children with down syndrome - A comparison with typically developing children.

Background: Compared with typically developing control children (CC), children with Down syndrome (DS) frequently exhibit sleep-disordered breathing (SDB) and unusual sleep postures (USPs). No studies have directly compared SDB-related signs and symptoms, SDB-related parameters, and USPs between children with DS and CC. This study aimed to evaluate the prevalences of SDB and USPs in children with DS and CC. Methods: We analyzed SDB-related parameters measured via overnight pulse oximetry and questionnaires administered to parents on SDB-related signs and symptoms, including sleeping postures. Estimated SDB was defined as a 3% oxygen desaturation index (ODI) ≥5 dips/h. Results: Fifty-one children with DS (4-5 years: N = 12, 6-10 years: N = 23, 11-15 years: N = 16) and sixty-three CC (4-5 years: N = 18, 6-10 years: N = 27, 11-15 years: N = 18) were included. The prevalence of estimated SDB and observed USPs was higher in children with DS than in CC (p < 0.0001). Among children aged 11-15 years old, but not those aged 4-5 and 6-10 years old, frequency of arousal and apnea (p = 0.045 and p = 0.01, respectively) were higher in children with DS than in CC. Multivariate analyses showed that DS was associated with SDB-related signs and symptoms, estimated SDB, 3% ODI, average oxygen saturation (SpO2), and nadir SpO2, while USPs were associated only with higher values of SpO2 <90%. Conclusions: Estimated SDB tended to increase in children with DS but decreased in CC with growth. USPs were more frequent in children with DS than in CC, especially in older children. USPs might indicate severe hypoxemia due to SDB in DS.

Pulse transit time-estimated blood pressure: a comparison of beat-to-beat and intermittent measurement.

Pulse transit time (PTT), which refers to the travel time between two arterial sites within the same cardiac cycle, has been developed as a novel cuffless form of continuous blood pressure (BP) monitoring. The aim of this study was to investigate differences in BP parameters, including BP variability, between those assessed by beat-to-beat PTT-estimated BP (eBPBTB) and those assessed by intermittent PTT-estimated BP at fixed time intervals (eBPINT) in patients suspected of having sleep disordered breathing (SDB). In 330 patients with SDB (average age, 66.8 ± 11.9 years; 3% oxygen desaturation index [ODI], 21.0 ± 15.0/h) from 8 institutes, PTT-estimated BP was continuously recorded during the nighttime. The average systolic eBPBTB, maximum systolic and diastolic eBPBTB, standard deviation (SD) of systolic and diastolic eBPBTB, and coefficient variation (CV) of systolic and diastolic eBPBTB were higher than the respective values of eBPINT (all P < 0.05). Bland-Altman analysis showed a close agreement between eBPBTB and eBPINT in average systolic BP and SD and CV of systolic BP, while there were disagreements in both minimum and maximum values of eBPBTB and eBPINT in patients with high systolic BP (P < 0.05). Although systolic BP variability incrementally increased according to the tertiles of 3%ODI in both eBPBTB and eBPINT (all P < 0.05), there was no difference in this tendency between eBPBTB and eBPINT. In patients with suspected SDB, the difference between eBPBTB and eBPINT was minimal, and there were disagreements regarding both the minimum and maximum BP. However, there were agreements in regard to the index of BP variability between eBPBTB and eBPINT.

Relationship between Restless legs syndrome associated symptoms and presence of depression during pregnancy.

Restless legs syndrome (RLS) is associated with depression in the general population. Although depression can lead to adverse events during the perinatal period, the association between RLS and depression remains under debate. Thus, we examined the association between depression and RLS, including RLS-associated symptoms, in pregnant women. We evaluated the presence of RLS and RLS-associated symptoms in 135 pregnant women using questionnaires on RLS symptoms based on Allen's symptoms and the International Restless Legs Syndrome Rating Scale (IRLS), respectively. We defined RLS as 4/4 on Allen's symptoms. Depressive status was evaluated using the Edinburgh Postnatal Depression Scale. The mean±SD of age was 31.8 ± 4.3 years, and none of the participants had a family history of RLS. Ten percent of women had depression during their pregnancy and demonstrated higher IRLS scores than those without depression (6.1 ± 10.5 vs. 0.7 ± 3.8 points, P = 0.001). A significant association between IRLS score, including its subscales, and depression was observed, even after adjusting for confounders. It was concluded that RLS-associated symptoms may be indicators of depression during pregnancy. Comprehensive sleep evaluations and examinations of RLS-associated symptoms are needed to improve psychiatric health during pregnancy.

Acute Lymphocyte Myocarditis Associated with Influenza Vaccination.

An elderly patient was admitted to our hospital for acute heart failure soon after receiving influenza vaccination. On admission, chest radiography revealed pulmonary edema. An electrocardiogram showed poor R progression, and echocardiography showed diffuse hypokinesis and myocardial edema. The serum troponin level was elevated. A histopathological evaluation indicated active myocarditis with lymphocyte-predominant infiltrates. A drug-induced lymphocyte stimulation test (DLST) was positive. The patient rapidly recovered from heart failure after treatment with conventional heart failure drugs, such as intravenous diuretics and vasodilators. These experimental data and the clinical course suggest that influenza vaccination was responsible for heart failure due to acute lymphocyte myocarditis.

Sex differences in the effectiveness and affecting factors to adherence of continuous positive airway pressure therapy.

Although sex differences in clinical backgrounds of patients with obstructive sleep apnea (OSA) are well known, studies of sex differences about the influencing factors on adherence to continuous positive airway pressure (CPAP) are very sparse. Our aim was to investigate the effects of CPAP use affecting therapeutic adherence in sex differences. We retrospectively assessed demographic data, clinical characteristics, OSA-related symptoms, and effects and adherence of CPAP use in 348 patients (264 males, median age 58 years) who continued CPAP for at least 1 year. Poor adherence was defined as CPAP dropout within 1 year after starting CPAP or the average cumulative CPAP use less than four hours/night. We also studied the predictors or influencing factors of CPAP adherence by multivariate logistic regression analyses. Age was higher and the severity of OSA was lower in female patients. Although the adherence level itself was not significantly different between both sexes, influencing factors were different. OSA severity, such as apnea-hypopnea index and sleepiness, and many effects from CPAP use (respiratory difficulty, difficult adaptation to CPAP use, improved awakening, reduced nocturia, and easy adaptation to CPAP) influenced adherence only in men. Common factors of poor adherence in both sexes were lower age, insomnia by CPAP use, and improved daytime sleepiness. No other specific factors predicted poor adherence in women. We found that there were sex differences in influencing factors on CPAP adherence not only in clinical characteristics of OSA, but also in effectiveness and side effects of CPAP use.

Lung-to-finger circulation time can be measured stably with high reproducibility by simple breath holding method in cardiac patients.

Lung to finger circulation time (LFCT) has been used to estimate cardiac function. We developed a new LFCT measurement device using a laser sensor at fingertip. We measured LFCT by measuring time from re-breathing after 20 s of breath hold to the nadir of the difference of transmitted red light and infrared light, which corresponds to percutaneous oxygen saturation. Fifty patients with heart failure were enrolled. The intrasubject stability of the measurement was assessed by the intraclass correlation coefficient (ICC). The ICC calculated from 44 cases was 0.85 (95% confidence interval: 0.77-0.91), which means to have "Excellent reliability." By measuring twice, at least one clear LFCT value was obtained in 89.1% of patients and the overall measurability was 95.7%. We conducted all LFCT measurements safely. High ICCs were obtained even after dividing patients according to age, cardiac index (CI); 0.85 and 0.84 (≥ 75 or < 75 years group, respectively), 0.81 and 0.84 (N = 26, ≥ or < 2.2 L/min/M2). These results show that our new method to measure LFCT is highly stable and feasible for any type of heart failure patients.

Idiopathic and secondary restless legs syndrome during pregnancy in Japan: Prevalence, clinical features and delivery-related outcomes.

OBJECTIVE: The aim of this study was to investigate prevalence of idiopathic and secondary restless legs syndrome (RLS) according to pregnancy trimester, and its effects on delivery-related outcomes among pregnant women in Japan. METHODS: This was a single-center, prospective observational study. One hundred eighty-two consecutive pregnant women participated in the study from June 2014 to March 2016. Participants were interviewed and examined in the second and third trimesters of pregnancy and 1 month after delivery. At each term, RLS was identified by a research assistant and then specialist in sleep medicine based on the diagnostic criteria of the International Restless Legs Syndrome Study Group. Delivery-related data was collected from medical charts. RLS was classified as idiopathic RLS, which originally existed before the index pregnancy, or secondary RLS, which newly appeared during the index pregnancy. RESULTS: The prevalence of RLS was 4.9% (idiopathic 3.3%, secondary 1.6%) in the second trimester, 5.0% (idiopathic 0.0%, secondary 5.0%) in the third trimester, and 0.6% (idiopathic 0.0%, secondary 0.6%) after delivery. Prolonged labor, emergency Cesarean section, and arrest of labor tended to be more frequent in idiopathic and/or second RLS (all p<0.05). CONCLUSIONS: The prevalence of RLS during pregnancy was 4-5% and decreases after delivery in current Japan. The presence of RLS was associated with an increase in some delivery-related outcomes. Early detection and treatment of RLS during pregnancy may be beneficial to safe delivery for pregnant women.

Changes in lung to finger circulation time measured via cardiopulmonary polygraphy in patients with varying types of heart disease.

Cardiopulmonary polygraphy (PG) demonstrates not only parameters for sleep disordered breathing (SDB) but also hemodynamics. We previously developed a software that detects lung to fingertip circulation time (LFCT) derived from PG dataset and reported that those LFCT reflected the cardiac output. The purpose of this study is to investigate how the LFCT changes during clinical course and whether reflects the impact of in-hospital treatment on cardiac function. Consecutive patients (N = 89) who admitted to the cardiovascular division, underwent PG at the early and late phase of admission. Parameters for SDB and LFCT were compared between an acute decompensated heart failure (ADHF) group (n = 51) and non-ADHF group (n = 38). ADHF group was further divided into subgroups: preserved ejection fraction (pEF) (EF > 40%) and reduced EF (rEF) (EF ≤ 40%). Using our original algorithm, we obtained LFCT values from all of the patients, though 29.4% of ADHF and 44.7% of non-ADHF had no or mild SDB. LFCT significantly shortened in the ADHF-rEF group, in contrast to ADHF-pEF group or non-ADHF group (ADHF-rEF group: 26.9 ± 7.6 to 24.2 ± 6.1 s, p = 0.01; ADHF-pEF group: 25.3 ± 7.3 to 25.3 ± 6.9 s, p = 0.98; non-ADHF group: 21.5 ± 5.5 to 21.9 ± 5.0 s, p = 0.65). The respiratory disorder index in the ADHF group improved after treatment, irrespective of EF (pEF: 26.9 ± 16.1 to 15.8 ± 11.9/h, p < 0.01; rEF: 27.0 ± 16.5 to 20.7 ± 13.6/h, p = 0.03). Automatic detection of LFCT was feasible in almost all cardiac patients. LFCT value changed according to the heart failure treatment in ADHF-rEF patients and reflected cardiac function. LFCT might be a useful indicator of effective cardiac disease treatment.

Local temperature control improves the accuracy of cardiac output estimation using lung-to-finger circulation time after breath holding.

As timely measurement of the cardiac index (CI) is one of the key elements in heart failure management, a noninvasive, simple, and inexpensive method of estimating CI is keenly needed. We attempted to develop a new device that can estimate CI from the data of lung-to-finger circulation time (LFCT) obtained after a brief breath hold in the awake state. First, we attempted to estimate CI from the LFCT value by utilizing the correlation between 1/LFCT and CI estimated with MRI. Although we could obtain LFCT from 45 of 53 patients with cardiovascular diseases, we could not find the anticipated relation between 1/LFCT and CI. However, we realized that when we adopted only LFCT from patients with a finger temperature of ≥31°C, we could obtain a consistent and clear correlation with CI (correlation coefficient, r = .81). Thus, we next measured LFCT before and after warming the forearm. We found that LFCT decreased after the local temperature increased (from 27.5 ± 13.6 to 18.4 ± 5.3 s, p < 0.01). The correlation between the inverse of LFCT and CI improved after warming (1/LFCT vs. CI, from r = .69 to r = .82). The final Bland-Altman analysis between the measured and estimated CI values revealed that the bias and precision were -0.05 and 0.37 L min-1  m-2 , respectively, and the percentage error was 34.3%. This study clarified that estimating CI using a simple measurement of LFCT is feasible in most patients and a low fingertip temperature strongly affects the CI-1/LFCT relationship, causing an error that can be corrected by proper local warming.

A Cross-Sectional Comparison of the Prevalence of Obstructive Sleep Apnea Symptoms in Adults With Down Syndrome in Scotland and Japan.

Small studies in Western populations report a high prevalence of obstructive sleep apnea (OSA) in adults with Down syndrome. To date, ethnic differences have not been explored. A questionnaire sent to 2,752 adults with Down syndrome aged ≥16 years in Scotland and Japan (789 valid responses) estimated OSA prevalence based on reported symptoms. Symptoms were common in both countries, with snoring (p = 0.001) and arousals (p = 0.04) more prevalent in Japan. Estimated OSA prevalence in adults with Down syndrome was similar in the two countries, and raised in comparison with the general adult population (19.6% in Scotland and 14.3% in Japan; p = 0.08), though BMI was a confounder. Identification and treatment of OSA is recommended in adults with Down syndrome, regardless of ethnicity.

Recent advances in the management of secondary hypertension-obstructive sleep apnea.

Since obstructive sleep apnea (OSA) is known as a common cause of secondary hypertension, it is necessary to consider OSA a differential diagnosis in treating patients with hypertension. Apnea during sleep causes temporary and repeated hypoxia and subsequent sympathetic nerve activation. Furthermore, dysfunction of endothelial cells due to hypoxia is considered another mechanism leading to enhanced stiffness of the elastic artery and eventually, elevation of blood pressure (BP). As a result, OSA induces a nighttime or morning surge in BP, and long-standing severe OSA also causes daytime hypertension. Therefore, treatment of OSA may be important for BP control, especially in severe OSA cases. For the treatment of OSA, continuous positive airway pressure (CPAP) is a major treatment option, though alternative devices may be useful in CPAP-intolerant cases.

Accumulated nocturnal hypoxemia predict arterial endothelial function in patients with sleep-disordered breathing with or without chronic heart failure.

ABTSRACT: Sleep-disordered breathing (SDB) is often accompanied with the chronic heart failure (CHF). Hypoxemia due to pulmonary congestion from CHF and concurrent SDB might synergistically impair endothelial function and worsen the prognosis. However, the main factors affecting deterioration of endothelial function are unknown and whether the influence of hypoxemia differs in SDB patients with and without CHF remains unclear. Fifty-three patients (CHF group, n = 23; non-CHF group, n = 30) underwent polysomnography to evaluate their SDB and flow-mediated vasodilation (FMD) measurements to assess arterial endothelial function. We examined the relationships between FMD and SDB-related parameters, including our original index of accumulated hypoxemia by SDB throughout one-night sleep: the time desaturation summation index (TDS), calculated as follows: (100% - averaged arterial oxygen saturation during sleep) × total sleep time. The mean age in the CHF and non-CHF groups was 59.0 ± 13.5 and 57.7 ± 11.4 years, respectively. Although the FMD in the 2 groups were not significantly different, well-known adverse factors for FMD such as serum lipid profiles, blood pressure levels, and conventional indices of SDB were worse in the non-CHF group. Only the TDS was not significantly different between 2 groups and associated with FMD as shown by the univariate analysis (CHF: p < 0.05, non-CHF: p < 0.01) and multivariate analysis (CHF: p < 0.05, non-CHF: p < 0.01). Accumulated hypoxemia (TDS) rather than the frequency of hypoxemia might more influence on the endothelial function irrespective of the cardiac state. Removal of accumulation of nocturnal hypoxemia might be a target for treatment equally in the patients with and without CHF.

Comparison of the Apnea-Hypopnea Index Determined by a Peripheral Arterial Tonometry-Based Device With That Determined by Polysomnography　- Results From a Multicenter Study.

Background: Sleep disordered breathing (SDB) is prevalent and associated with increased mortality in patients both with and without cardiovascular disease (CVD). Many portable monitoring devices, including peripheral arterial tonometry (PAT)-based devices, have been developed. Although previous studies have demonstrated that the apnea-hypopnea index (AHI) determined by PAT devices (pAHI) is strongly correlated with AHI determined by polysomnography (AHI-PSG), no data have been reported from a Japanese patient population or patients with CVD. In this study we compared the parameters determined by PAT-based devices with those determined by polysomnography in Japanese patients with CVD. Methods and Results: We enrolled 120 patients undergoing overnight polysomnography at 6 Japanese centers. A PAT-based device was used simultaneously with polysomnography. Polysomnography recordings were scored centrally by a technician in a blinded manner. PAT-based device recordings were scored using an automatic algorithm. There was a strong correlation between pAHI and AHI-PSG (r=0.896; P<0.001) with acceptable agreement. The strong correlation between pAHI and AHI-PSG was observed in patients with CVD (n=55; P=0.849; P<0.001) and without CVD (n=65; r=0.927; P<0.001). The presence or absence of CVD did not affect the relationship between pAHI and AHI-PSG (P=0.225). Conclusions: A PAT-based device provides a reliable AHI in a Japanese patient population, even in patients with CVD. These findings may help reduce the number of patients with undiagnosed SDB and CVD.

Factors limiting habitual exercise in patients with chronic heart failure: a multicenter prospective cohort study.

Physical activity (PA) in the daily life is strongly related to prognosis in patients with or at high risk of heart failure (HF). However, factors limiting habitual exercise and their prognostic impacts remain unknown in HF patients. We sent questionnaires asking factors limiting habitual exercise in the daily life to 8370 patients with Stage A/B/C/D HF in our nationwide registry and received valid responses from 4935 patients (mean age 71.8 years, 71.0% male). Among the 5 components consisting of "busyness", "weak will", "dislike, "socioeconomic reasons" and "diseases" in the questionnaires, "busyness" (34.5%) and "diseases" (34.7%) were the most frequently reported factors limiting habitual exercise, while "socioeconomic reasons" were the least (15.3%). Multiple Cox proportional hazard models indicated that "busyness"and "diseases" were associated with better (hazard ratio (HR) 0.53, 95% confidence interval (CI) 0.39-0.72, P < 0.001) and worse prognosis (HR 1.57, 95% CI 1.21-1.98, P < 0.001), respectively, while other components were not. Furthermore, it was noted that, while prognostic relevance of "busyness" limiting exercise did not differ by age or sex, negative impact of "diseases" was particularly evident in patients with age < 75 years (P for interaction < 0.01). Factors limiting habitual exercise were associated with "busyness" and "diseases", but not with "weak will", "dislike, or "socioeconomic reasons". While "busyness" was associated with better prognosis regardless of age and sex, "diseases" was associated with worse prognosis in younger populations. Thus, physicians may pay more attentions to the reasons that limit exercise in the daily lives of HF patients rather than the low amount of exercise itself.