Sacubitril/valsartan for the treatment of non-obstructive hypertrophic cardiomyopathy: An open label randomized controlled trial (SILICOFCM).

AIM: Sacubitril/valsartan treatment reduces mortality and hospitalizations in heart failure with reduced ejection fraction but has limited application in hypertrophic cardiomyopathy (HCM). The aim of this study was to evaluate the effect of sacubitril/valsartan on peak oxygen consumption (VO2) in patients with non-obstructive HCM. METHODS AND RESULTS: This is a phase II, randomized, open-label multicentre study that enrolled adult patients with symptomatic non-obstructive HCM (New York Heart Association class I-III) who were randomly assigned (2:1) to receive sacubitril/valsartan (target dose 97/103 mg) or control for 16 weeks. The primary endpoint was a change in peak VO2. Secondary endpoints included echocardiographic measures of cardiac structure and function, natriuretic peptides and other cardiac biomarkers, and Minnesota Living with Heart Failure quality of life. Between May 2018 and October 2021, 354 patients were screened for eligibility, 115 patients (mean age 58 years, 37% female) met the study inclusion criteria and were randomly assigned to sacubitril/valsartan (n = 79) or control (n = 36). At 16 weeks, there was no significant change in peak VO2 from baseline in the sacubitril/valsartan (15.3 [4.3] vs. 15.9 [4.3] ml/kg/min, p = 0.13) or control group (p = 0.47). No clinically significant changes were found in blood pressure, cardiac structure and function, plasma biomarkers, or quality of life. CONCLUSION: In patients with HCM, a 16-week treatment with sacubitril/valsartan was well tolerated but had no effect on exercise capacity, cardiac structure, or function.

Physical Activity, Inactivity and Sleep in Individuals with Hypertrophic Cardiomyopathy.

Physical activity presents an important cornerstone in the management and care of individuals with hypertrophic cardiomyopathy (HCM). Twenty-one individuals with HCM (age: 52±15 years old, body mass index (BMI): 30±7 kg/m2) completed 7-day monitoring using wrist-worn triaxial accelerometers (GENEActiv, ActivInsights Ltd, UK) and were compared to age and sex-matched healthy controls (age: 51±14 years old, BMI: 25±4 kg/m2). For individuals with HCM, clinical parameters (left atrial diameter and volume, peak oxygen consumption, NTproBNP and Minnesota Living with Heart Failure (MLHF)) were correlated with accelerometry. After adjusting for BMI, individuals with HCM spent less time in moderate-vigorous physical activity (MVPA) (86 (55-138) vs. 140 (121-149) minutes/day, p<0.05) compared to healthy controls. Individuals with HCM engaged in fewer MVPA-5 min (6 (2-15) vs. 27 (23-37) minutes/day, p<0.01) and MVPA-10 min bouts (9 (0-19) vs. 35 (17-54) minutes/day, p<0.01) versus healthy controls. For HCM only, peak oxygen consumption was correlated with MVPA (r=0.60, p<0.01) and MVPA-5 min bouts (r=0.47, p<0.05). MLHF score was correlated with sleep duration (r=0.45, p<0.05). Individuals with HCM should be encouraged to engage in moderate-intensity physical activity bouts and reduce prolonged periods of inactivity in order to potentially improve exercise tolerance and reduce disease burden.

Application of non-invasive bioreactance to assess hemodynamic function in patients with hypertrophic cardiomyopathy.

Non-invasive technologies have become popular for the clinical evaluation of cardiac function. The present study evaluated hemodynamic response to cardiopulmonary exercise stress testing using bioreactance technology in patients with hypertrophic cardiomyopathy. The study included 29 patients with HCM (age 55 ± 15 years; 28% female) and 12 age (55 ± 14 years), and gender matched (25% female) healthy controls. All participants underwent maximal graded cardiopulmonary exercise stress testing with simultaneous non-invasive hemodynamic bioreactance and gas exchange. At rest, patients with HCM demonstrated significantly lower cardiac output (4.1 ± 1.3 vs. 6.1 ± 1.2 L/min; p < 0.001), stroke volume (61.5 ± 20.8 vs. 89.5 ± 19.8 mL/beat; p < 0.001), and cardiac power output (0.97 ± 0.3 vs. 1.4 ± 0.3watt; p < 0.001), compared to controls. At peak exercise, the following hemodynamic and metabolic variables were lower in HCM patients that is, heart rate (118 ± 29 vs. 156 ± 20 beats/min; p < 0.001), cardiac output (15.5 ± 5.8 vs. 20.5 ± 4.7 L/min; p = 0.017), cardiac power output (4.3 ± 1.6 vs. 5.9 ± 1.8 watts; p = 0.017), mean arterial blood pressure (126 ± 11 vs. 134 ± 10 mmHg; p = 0.039), and oxygen consumption (18.3 ± 6.0 vs. 30.5 ± 8.3 mL/kg/min; p < 0.001), respectively. Peak arteriovenous oxygen difference and stroke volume were not significantly different between HCM patients and healthy controls (11.2 ± 6.4 vs. 11.9 ± 3.1 mL/100 mL, p = 0.37 and 131 ± 50.6 vs. 132 ± 41.9 mL/beat, p = 0.76). There was a moderate positive relationship between peak oxygen consumption and peak heart rate (r = 0.67, p < 0.001), and arteriovenous oxygen difference (r = 0.59, p = 0.001). Functional capacity is significantly reduced in patients with HCM primarily due to diminished central (cardiac) rather than peripheral factors. Application of non-invasive hemodynamic assessment may improve understanding of the pathophysiology and explain mechanisms of exercise intolerance in hypertrophic cardiomyopathy.

Physical activity, inactivity and sleep in older patients with coronary artery disease following percutaneous coronary intervention: a longitudinal, observational study.

OBJECTIVES: Physical activity presents an important cornerstone in the management and care of coronary artery disease (CAD) patients following percutaneous coronary intervention (PCI) and research in older patients continues to be overlooked. This study evaluated differences in physical activity, inactivity and sleep of CAD patients following PCI for acute coronary syndrome consisting of ST-segment elevation myocardial infarction (STEMI) and non-STEMI (NSTEMI) and elective admission of stable angina patients over 12 months. METHODS: This was an observational, longitudinal study. Fifty-eight patients were recruited (STEMI, n  = 20, NSTEMI, n  = 18 and stable angina, n  = 20) and completed 7-day monitoring (physical activity, inactivity and sleep) using wrist-worn tri-axial accelerometers (GENEActiv, ActivInsights Ltd, Kimbolton, Cambridgeshire, UK) upon discharge from a tertiary centre and repeated measurements at 3 months ( n  = 43), 6 months ( n  = 40) and 12 months ( n  = 33). RESULTS: Following PCI, CAD patients showed a general trend of increasing light and moderate-vigorous physical activity over the 12-month follow-up. Time in inactivity remained high but decreased over time. Sleep duration and sleep efficiency remained consistent. NSTEMI patients spent less time asleep, more time inactive and less time in light and moderate-vigorous physical activity in comparison to STEMI and stable angina patients. Differences between the groups over time were minimal. CONCLUSION: These findings suggest that older patients with CAD spend long periods in inactivity but the increasing trend of both light and moderate-vigorous physical activity over time presents a positive change in behaviour in the year following PCI.

Heart rate variability and haemodynamic function in individuals with hypertrophic cardiomyopathy.

OBJECTIVES: Heart rate variability (HRV) is a measure of cardiac autonomic function. This study: (1) evaluated the differences in HRV and haemodynamic function between individuals with hypertrophic cardiomyopathy (HCM) and healthy controls, and (2) determined the relationship between HRV and haemodynamic variables in individuals with HCM. METHODS: Twenty-eight individuals with HCM (n = 7, females; age 54 ± 15 years; body mass index: 29 ± 5 kg/m2 ) and 28 matched healthy individuals (n = 7 females; age 54 ± 16 years; body mass index: 29 ± 5 kg/m2 ) completed 5-min HRV and haemodynamic measurements under resting (supine) conditions using bioimpedance technology. Frequency domain HRV measures (absolute and normalized low-frequency power (LF), high-frequency power (HF) and LF/HF ratio) and RR interval were recorded. RESULTS: Individuals with HCM demonstrated higher vagal activity (i.e., absolute unit of HF power (7.40 ± 2.50 vs. 6.03 ± 1.35 ms2 , p = 0.01) but lower RR interval (914 ± 178 vs. 1014 ± 168 ms, p = 0.03) compared to controls. Stroke volume (SV) index and cardiac index were lower in HCM compared with healthy individuals (SV, 33 ± 9 vs. 43 ± 7 ml /beat /m², p < 0.01; cardiac index,2.33 ± 0.42 vs. 3.57 ± 0.82 L/min/m2 , p < 0.01), but total peripheral resistance (TPR) was higher in HCM (3468 ± 1027 vs. 2953 ± 1050 dyn·s·m2 cm-5 , p = 0.03). HF power was significantly related to SV (r = -0.46, p < 0.01) and TPR (r = 0.28, p < 0.05) in HCM. CONCLUSIONS: Short-term frequency domain indices of HRV provide a feasible approach to assess autonomic function in individuals with HCM. Vagal activity, represented by HF power, is increased, and associated with peripheral resistance in individuals with HCM.

Habitual physical activity levels of adults with heart failure: systematic review and meta-analysis.

OBJECTIVE: To conduct a systematic review and meta-analysis to quantify habitual physical activity (PA) levels of patients with heart failure (HF) and assess the quality of reporting of device-assessed PA. METHODS: Eight electronic databases were searched up to 17 November 2021. Data on the study and population characteristics, method of PA measurement and PA metrics were extracted. A random-effects meta-analysis (restricted maximum likelihood with Knapp-Hartung SE adjustment) was conducted. RESULTS: Seventy-five studies were included in the review (n=7775 patients with HF). Meta-analysis was restricted to mean steps per day, encompassing 27 studies (n=1720 patients with HF). Pooled mean steps per day were 5040 (95% CI: 4272 to 5807). The 95% prediction interval for mean steps per day in a future study was 1262 to 8817. Meta-regression at the study level revealed that a 10-year increment in the mean age of patients was associated with 1121 fewer steps per day (95% CI: 258 to 1984). CONCLUSIONS: Patients with HF are a low-active population. These findings have implications for the way in which PA is targeted in patients with HF, and interventions should focus on addressing the age-related decline observed as well as increasing PA to improve HF symptoms and quality of life. PROSPERO REGISTRATION NUMBER: CRD42020167786.

Physical activity, inactivity and sleep during the Diabetes Remission Clinical Trial (DiRECT).

AIMS: As sustained weight loss is vital for achieving remission of type 2 diabetes, we explored whether randomisation to weight loss plus maintenance in the DiRECT trial was associated with physical activity, inactivity or sleep. METHODS: Participants were randomised to either a dietary weight management programme or best-practice care. The weight management group were encouraged to increase daily physical activity to their sustainable maximum. Objective measurement was achieved using a wrist-worn GENEActiv accelerometer for 7 days at baseline, 12 and 24 months in both groups. RESULTS: Despite average weight loss of 10 kg at 12 months in the intervention (n = 66) group, there were no differences in total physical activity or inactivity compared with the control (n = 104) at any time point. However, in our exploratory analysis, those who lost more than 10% of their baseline body weight performed on average 11 mins/day more light activity than the <10% group at 24 months (p = 0.033) and had significantly lower bouts of Inactivity30min (interaction, p = 0.005) across 12 and 24 months. At 24 months, the ≥10% group had higher daily acceleration (38.5 ± 12.1 vs. 33.2 ± 11.1 mg, p = 0.020), and higher accelerations in the most active 5-hour period (59.4 ± 21.8 vs. 50.6 ± 18.3 mg, p = 0.023). Wakefulness after sleep onset decreased in the intervention group compared with the control group and also in the ≥10% weight loss group at 12 and 24 months. CONCLUSIONS: Randomisation to a successful intensive weight loss intervention, including regular physical activity encouragement, was not associated with increased physical activity although sleep parameters improved. Physical activity was greater, and night-time waking reduced in those who maintained >10% weight loss at 12 and 24 months. TRIAL REGISTRATION ISRCTN03267836.

Exploring factors influencing uptake and adherence to a home-based prehabilitation physical activity and exercise intervention for patients undergoing chemotherapy before major surgery (ChemoFit): a qualitative study.

OBJECTIVES: Preoperative exercise training can improve cardiorespiratory fitness before major surgery. However, little is known about what influences participation and adherence in high-risk patient groups. We identified barriers and facilitators to uptake, engagement and adherence to a presurgical, home-based physical activity and exercise intervention called ChemoFit delivered during chemotherapy and before major oesophagogastric surgery. DESIGN: A qualitative study using focus group discussions and individual semi-structured interviews was conducted. All were audio-recorded, transcribed verbatim and data thematically analysed. SETTING: Northern Oesophagogastric Unit, Royal Victoria Infirmary, Newcastle upon Tyne NHS Hospitals Foundation Trust. PARTICIPANTS: Patients with oesophagogastric cancer who participated in the ChemoFit intervention recruited between March 2020 and January 2021. INTERVENTION: A home-based physical activity and exercise intervention involving cardiovasular and strength exercise using resistance bands and pedometers to monitor step count. Weekly telephone calls provided feedback, support and positive reinforcement. RESULTS: Twenty-two participants (18 men, 4 women; aged 67±8 years old) took part in a focus group discussion (n=17) or a semi-structured interview (n=5). Fifteen themes were identified from the data generated. Participants reported that the intervention was physically and mentally beneficial, and data highlighted features of the intervention that influenced uptake and adherence. An opportunity to increase the likelihood of surviving the pending operation was reported by participants as the most salient factor to engagement, and using the intervention as a distraction from illness and taking steps to positively influence the situation were the most salient factors to adherence. CONCLUSIONS: Uptake to the ChemoFit intervention was encouraged by provision of information that participation could reduce surgical risk and that participants could play an active role in risk reduction. Adherence was facilitated by the intervention being considered a positive distraction and participants being able to do something that could ultimately provide benefit. While participants reported difficulties and avoidance with some of the exercises recommended, understanding the importance of physical activity and exercise as part of their treatment regimen led to individual adaptations to intervention components to reach individual goals. TRIAL REGISTRATION NUMBER: NCT04194463.

A feasibility trial of prehabilitation before oesophagogastric cancer surgery using a multi-component home-based exercise programme: the ChemoFit study.

BACKGROUND: Treatment for locally advanced oesophagogastric adenocarcinoma involves neoadjuvant chemotherapy which has a negative impact on patient fitness. Using 'prehabilitation' to increase activity levels and fitness may affect physiology, postoperative outcomes and improve patient wellbeing and quality of life. The aims of the trial were to address the feasibility and acceptability of recruiting participants to a home-based prehabilitation programme and provide data to allow design of future studies. METHODS: We recruited patients to a single-arm feasibility trial of home-based exercise prehabilitation. Eligible patients were aged ≥18years, had operable oesophageal or gastric adenocarcinoma and were receiving neoadjuvant chemotherapy at our tertiary referral hospital. All participants commenced a home-based exercise programme utilising pedometers and step counting to target daily aerobic exercise sessions alongside daily strengthening exercises. A weekly telephone consultation directed the exercise programme and facilitated weekly data collection. The primary (feasibility) outcomes for the trial were (a) recruitment rate, (b) completion rate, (c) engagement with the programme (use of pedometers, recording step counts, telephone consultations) and (d) compliance with exercise sessions, exercise intensity and strengthening exercises. RESULTS: There were 42 patients recruited, and the recruitment rate was 72.4% (42/58). 92.3% (36/39) of patients completed the exercise programme. There was 98.7% (IQR 93.2-100.0%) compliance with wearing a pedometer and recording data, and 100.0% (IQR 93.1-100.0%) compliance with a weekly telephone consultation. Exercise sessions and strengthening exercises were completed 70.2% (IQR 53.1-88.9%) and 69.4% (IQR 52.1-84.3%) of the time, respectively. Appropriate exercise intensity was recorded 96% (IQR 85.4-99.4%) of the time. There were no adverse events. Participants were enrolled in the exercise programme for a median of 91 days (IQR 84 to 105 days). CONCLUSIONS: The results of this trial support the feasibility and acceptability of recruiting participants to an appropriately powered randomised controlled trial of prehabilitation. TRIAL REGISTRATION: Clinicaltrials.gov NCT04194463 . Registered on 11th December 2019-retrospectively registered.

Movement as Medicine for Cardiovascular Disease Prevention: Pilot Feasibility Study of a Physical Activity Promotion Intervention for At-Risk Patients in Primary Care.

BACKGROUND: Physical activity (PA) can reduce cardiovascular disease (CVD) risk factors, and although primary care settings offer a large reach to promote PA and reduce CVD risk, primary health care professionals may lack self-efficacy and tools to effectively promote PA in practice. Movement as Medicine for CVD Prevention is a suite of 2 theory-based, web-based behavioral interventions-one for health care professionals and one for patients-which may offer a pathway for promoting PA and reducing CVD risk in primary care. OBJECTIVE: This study aims to examine the feasibility and possible effects of Movement as Medicine for CVD Prevention. METHODS: This nonrandomized pilot study recruited participants from primary care organizations in the Northeast of England. Enrolled health care professionals followed a theory-based, web-based course on PA counseling and motivational interviewing techniques. After the course, health care professionals delivered behavior change consultations based on motivational interviewing to inactive individuals with >20% risk of developing CVD within 10 years. Patients were then given access to a website based on self-determination and self-regulation theories, which targeted increased levels of PA. Outcomes were assessed at baseline and after 3 months, and patient data were analyzed on an intention-to-treat basis in a multiple imputation data set. RESULTS: Recruitment rates of primary care organizations fell below expectations. A total of 11 health care professionals from 3 enrolled primary care organizations completed the web-based course and reported increases in important theoretical determinants of PA promotion in practice (eg, self-efficacy, Cohen d=1.24, 95% CI 0.67-1.80; and planning, Cohen d=0.85, 95% CI -0.01 to 1.69). A total of 83 patients were enrolled in the study, and 58 (70%) completed both the baseline and 3-month assessments. Compared with baseline, patients had higher levels of objective (Cohen d=0.77, 95% CI 0.13-1.41) but not subjective (Cohen d=0.40, 95% CI -0.03 to 0.83) moderate to vigorous PA at 3 months. Patients also reported higher levels of the PA determinants of intention, self-efficacy, intrinsic motivation, and action planning and action control at 3 months (effect sizes ranged from Cohen d=0.39 to 0.60). CONCLUSIONS: The Movement as Medicine for CVD Prevention intervention seems to have the potential to improve patient PA behaviors and important determinants of health care professionals' PA promotion practices. However, the recruitment rates of primary care organizations in this study were low and would need to be increased to examine the efficacy of the program. This study offers several insights into improving the feasibility of this primary care PA promotion pathway. TRIAL REGISTRATION: ISRCTN Registry ISRCTN14582348; http://www.isrctn.com/ISRCTN14582348.

Taking the strain? Police well-being in the COVID-19 era.

Drawing on survey and interview data collected in one police force area, this article considers the varied impacts on police well-being arising during the COVID-19 pandemic. Approximately one-third of police officers surveyed reported feeling less safe in their role during the pandemic, and nearly half suffered increased anxiety. The toll on well-being appears to be most acute for frontline officers and those with caring responsibilities, and is strongly associated with increases in workload. The task of 'repairing' well-being will require detailed and sensitive consideration involving genuine efforts to hear the voices of those who have endured this prolonged tour of duty.

Feasibility of the cardiac output response to stress test in suspected heart failure patients.

BACKGROUND: Diagnostic tools available to support general practitioners diagnose heart failure (HF) are limited. OBJECTIVES: (i) Determine the feasibility of the novel cardiac output response to stress (CORS) test in suspected HF patients, and (ii) Identify differences in the CORS results between (a) confirmed HF patients from non-HF patients, and (b) HF reduced (HFrEF) vs HF preserved (HFpEF) ejection fraction. METHODS: Single centre, prospective, observational, feasibility study. Consecutive patients with suspected HF (N = 105; mean age: 72 ± 10 years) were recruited from specialized HF diagnostic clinics in secondary care. The consultant cardiologist confirmed or refuted a HF diagnosis. The patient completed the CORS but the researcher administering the test was blinded from the diagnosis. The CORS assessed cardiac function (stroke volume index, SVI) noninvasively using the bioreactance technology at rest-supine, challenge-standing, and stress-step exercise phases. RESULTS: A total of 38 patients were newly diagnosed with HF (HFrEF, n = 21) with 79% being able to complete all phases of the CORS (91% of non-HF patients). A 17% lower SVI was found in HF compared with non-HF patients at rest-supine (43 ± 15 vs 51 ± 16 mL/beat/m2, P = 0.02) and stress-step exercise phase (49 ± 16 vs 58 ± 17 mL/beat/m2, P = 0.02). HFrEF patients demonstrated a lower SVI at rest (39 ± 15 vs 48 ± 13 mL/beat/m2, P = 0.02) and challenge-standing phase (34 ± 9 vs 42 ± 12 mL/beat/m2, P = 0.03) than HFpEF patients. CONCLUSION: The CORS is feasible and patients with HF responded differently to non-HF, and HFrEF from HFpEF. These findings provide further evidence for the potential use of the CORS to improve HF diagnostic and referral accuracy in primary care.

Heart failure (HF) is a global pandemic affecting 26 million people worldwide with an estimated 1 million people in the United Kingdom. Accurate early diagnosis of HF and the initiation of evidence-based treatment is essential to reduce morbidity and mortality and the associated burden on healthcare. As there are no state-of-the-art approaches, early diagnosis is challenging and often inaccurate, as initial signs and symptoms are nonspecific. We have developed an innovative test, named CORS (cardiac output response to stress test), to help general practitioners identify HF, which uses a method similar to an electrocardiogram and measures heart function at rest and during short step exercise. We recruited suspected HF patients from specialist HF diagnostic clinics in secondary care to complete the CORS test. We successfully demonstrated that 79% of patients with newly diagnosed HF (n = 38) and 91% of non-HF patients (n = 67) were able to complete all phases of the CORS test. Our findings demonstrate that newly diagnosed HF patients are able to complete this test, which provides further evidence for the potential use of the CORS test to improve HF diagnostic and referral accuracy in primary care.

Insights into heart failure hospitalizations, management, and services during and beyond COVID-19.

Coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus-2. The clinical presentation of this virus mainly manifests in the respiratory system but may also lead to severe complications in the cardiovascular system. The global burden of COVID-19 has led to an unprecedented need to gain further insight into patient outcomes, management, and clinical practice. This review aims to provide an overview of the current literature on heart failure (HF) hospitalizations, management, and care pathways for supporting patients during and beyond this pandemic. A literature review of five areas of interest was conducted and included: (i) HF hospitalization; (ii) recognizing the needs and supporting HF patients during COVID-19; (iii) supporting rehabilitation services; (iv) transitioning to a telehealth framework; and (v) the need for evidence. Patients with new-onset or existing HF are particularly vulnerable, but a significant reduction in HF hospital admissions has been reported. During these periods of uncertainty, the current care pathways for acute and elective cardiac patients have had to change with the relocation of HF services to protect the vulnerable and reduce transmission of COVID-19. Optimizing community HF services has the potential to reduce the pressures on secondary care during the recovery from this pandemic. Telemedicine and virtual health care are emerging technologies and overcome the risk of in-person exposure. Successful remote delivery of cardiac rehabilitation services has been reported during the pandemic. Delivery of a robust telehealth framework for HF patients will improve communication between clinician and patient. The reduction in HF admissions is a concern for the future and may result in unintended mortality. New-onset and current HF patients must understand their diagnosis and future prognosis and seek help and support using the appropriate platform when needed. Realigning HF services and the use of telemedicine and virtual health care has great potential but needs to be carefully understood to ensure engagement and approval in this population to overcome barriers and challenges.

Overcoming barriers to engagement and adherence to a home-based physical activity intervention for patients with heart failure: a qualitative focus group study.

OBJECTIVES: Clinical guidelines recommend regular physical activity for patients with heart failure to improve functional capacity and symptoms and to reduce hospitalisation. Cardiac rehabilitation programmes have demonstrated success in this regard; however, uptake and adherence are suboptimal. Home-based physical activity programmes have gained popularity to address these issues, although it is acknowledged that their ability to provide personalised support will impact on their effectiveness. This study aimed to identify barriers and facilitators to engagement and adherence to a home-based physical activity programme, and to identify ways in which it could be integrated into the care pathway for patients with heart failure. DESIGN: A qualitative focus group study was conducted. Data were analysed using thematic analysis. PARTICIPANTS: A purposive sample of 16 patients, 82% male, aged 68±7 years, with heart failure duration of 10±9 years were recruited. INTERVENTION: A 12-week behavioural intervention targeting physical activity was delivered once per week by telephone. RESULTS: Ten main themes were generated that provided a comprehensive overview of the active ingredients of the intervention in terms of engagement and adherence. Fear of undertaking physical activity was reported to be a significant barrier to engagement. Influences of family members were both barriers and facilitators to engagement and adherence. Facilitators included endorsement of the intervention by clinicians knowledgeable about physical activity in the context of heart failure; ongoing support and personalised feedback from team members, including tailoring to meet individual needs, overcome barriers and increase confidence. CONCLUSIONS: Endorsement of interventions by clinicians to reduce patients' fear of undertaking physical activity and individual tailoring to overcome barriers are necessary for long-term adherence. Encouraging family members to attend consultations to address misconceptions and fear about the contraindications of physical activity in the context of heart failure should be considered for adherence, and peer-support for long-term maintenance. TRIAL REGISTRATION NUMBER: NCT03677271.

What are the Physiological Benefits of Increased Daily Number of Steps in Middle-Aged Women?

BACKGROUND: Physical activity plays an important role in the prevention of cardio-metabolic diseases. The present study evaluated the effect of habitual physical activity on body composition, peak oxygen consumption, cardiac and metabolic function. METHODS: This was a retrospective study. Data was collected between February 2014 and November 2015. Thirty-six healthy women (age 50±16 years) were stratified according to daily number of steps into low- (<7500 steps/day, n=17) or high-active group (>12500 steps/day, n=19). All participants underwent body composition assessment, oral glucose tolerance test and non-invasive gas-exchange and haemodynamic (bioreactance) measurements at rest and in response to maximal graded cardiopulmonary exercise test. RESULTS: The high active group averaged 16280±3205 steps/day and the low active group averaged 6285±943 steps/day (difference p=0.00). High-active women (vs. low active) demonstrated significantly lower body weight (62.1±12.3 vs. 71.2±9.1 kg, p=0.02), body fat (27.2±9.1 vs 37.7±6.4 %, p=0.00), but increased lean body mass (72.8±9.1 vs. 62.3±6.4 %, p=0.00). Peak oxygen consumption was significantly higher in high- versus low active women (2.0±0.5 vs. 1.5±0.2 l/min, p=0.00). There were no significant differences between the groups in fasting- and 2-hour glucose levels (4.9±0.6 vs. 4.8±0.5, p=0.45 and 4.8±1.3 vs. 5.5±1.4 mmol/L, p=0.16) haemodynamic measures of cardiac function including cardiac power output, cardiac output, stroke volume and arterial blood pressure at rest and in response to exercise stress test (p>0.05). CONCLUSIONS: Increased levels of habitual physical activity improve body composition and peak oxygen consumption but appears to have limited effect cardio-metabolic function in middle-aged women.

Metabolic effects of bezafibrate in mitochondrial disease.

Mitochondrial disorders affect 1/5,000 and have no cure. Inducing mitochondrial biogenesis with bezafibrate improves mitochondrial function in animal models, but there are no comparable human studies. We performed an open-label observational experimental medicine study of six patients with mitochondrial myopathy caused by the m.3243A>G MTTL1 mutation. Our primary aim was to determine the effects of bezafibrate on mitochondrial metabolism, whilst providing preliminary evidence of safety and efficacy using biomarkers. The participants received 600-1,200 mg bezafibrate daily for 12 weeks. There were no clinically significant adverse events, and liver function was not affected. We detected a reduction in the number of complex IV-immunodeficient muscle fibres and improved cardiac function. However, this was accompanied by an increase in serum biomarkers of mitochondrial disease, including fibroblast growth factor 21 (FGF-21), growth and differentiation factor 15 (GDF-15), plus dysregulation of fatty acid and amino acid metabolism. Thus, although potentially beneficial in short term, inducing mitochondrial biogenesis with bezafibrate altered the metabolomic signature of mitochondrial disease, raising concerns about long-term sequelae.

Acceptability, Feasibility and Preliminary Evaluation of a Novel, Personalised, Home-Based Physical Activity Intervention for Chronic Heart Failure (Active-at-Home-HF): a Pilot Study.

PURPOSE: Less than 10% of heart failure patients in the UK participate in cardiac rehabilitation programmes. The present pilot study evaluated feasibility, acceptability and physiological effects of a novel, personalised, home-based physical activity intervention in chronic heart failure. METHODS: Twenty patients (68 ± 7 years old, 20% females) with stable chronic heart failure due to reduced left ventricular ejection fraction (31 ± 8 %) participated in a single-group, pilot study assessing the feasibility and acceptability of a 12-week personalised home-based physical activity intervention aiming to increase daily number of steps by 2000 from baseline (Active-at-Home-HF). Patients completed cardiopulmonary exercise testing with non-invasive gas exchange and haemodynamic measurements and quality of life questionnaire pre- and post-intervention. Patients were supported weekly via telephone and average weekly step count data collected using pedometers. RESULTS: Forty-three patients were screened and 20 recruited into the study. Seventeen patients (85%) completed the intervention, and 15 (75%) achieved the target step count. Average step count per day increased significantly from baseline to 3 weeks by 2546 (5108 ± 3064 to 7654 ± 3849, P = 0.03, n = 17) and was maintained until week 12 (9022 ± 3942). Following completion of the intervention, no adverse events were recorded and quality of life improved by 4 points (26 ± 18 vs. 22 ± 19). Peak exercise stroke volume increased by 19% (127 ± 34 vs. 151 ± 34 m/beat, P = 0.05), while cardiac index increased by 12% (6.8 ± 1.5 vs. 7.6 ± 2.0 L/min/m2, P = 0.19). Workload and oxygen consumption at anaerobic threshold also increased by 16% (49 ± 16 vs. 59 ± 14 watts, P = 0.01) and 10% (11.5 ± 2.9 vs. 12.8 ± 2.2 ml/kg/min, P = 0.39). CONCLUSION: The Active-at-Home-HF intervention is feasible, acceptable and effective for increasing physical activity in CHF. It may lead to improvements in quality of life, exercise tolerance and haemodynamic function. TRIAL REGISTRATION: www.clinicaltrials.gov NCT0367727. Retrospectively registered on 17 September 2018.

Opportunities and challenges of a novel cardiac output response to stress (CORS) test to enhance diagnosis of heart failure in primary care: qualitative study.

OBJECTIVE: To explore the role of the novel cardiac output response to stress (CORS), test in the current diagnostic pathway for heart failure and the opportunities and challenges to potential implementation in primary care. DESIGN: Qualitative study using semistructured in-depth interviews which were audio recorded and transcribed verbatim. Data from the interviews were analysed thematically using an inductive approach. SETTING: Newcastle upon Tyne, UK. PARTICIPANTS: Fourteen healthcare professionals (six males, eight females) from primary (general practitioners (GPs), nurses, healthcare assistant, practice managers) and secondary care (consultant cardiologists). RESULTS: Four themes relating to opportunities and challenges surrounding the implementation of the new diagnostic technology were identified. These reflected that the adoption of CORS test would be an advantage to primary care but the test had barriers to implementation which include: establishment of clinical utility, suitability for immobile patients and cost implication to GP practices. CONCLUSION: The development of a simple non-invasive clinical test to accelerate the diagnosis of heart failure in primary care maybe helpful to reduce unnecessary referrals to secondary care. The CORS test has the potential to serve this purpose; however, factors such as cost effectiveness, diagnostic accuracy and seamless implementation in primary care have to be fully explored.

Analyzing walking speeds with ankle and wrist worn accelerometers in a cohort with myotonic dystrophy.

Background: Accelerometers are accurate tools to assess movement and physical activity. However, interpreting standardly used outputs is not straightforward for populations with impaired mobility.Methods: The applicability of GENEActiv was explored in a group of 30 participants with myotonic dystrophy and compared to a group of 14 healthy-controls. All participants performed a set of tests while wearing four different accelerometers (wrists and ankles): [1] standing still; [2] ten-meters walk test; [3] six-minutes walking test; and, [4] ten-meters walk/run test.Results: Relevant findings were: [1] high intra-accelerometer reliability (i.e. 0.97 to 0.99; p < 0.001); [2] each test acceleration values differ significantly between each other; [3] no inter-accelerometer reliability between wrist-worn devices and ankle-worn; and [4] a significant difference between the myotonic dystrophy group and the healthy-controls detectable at each test (i.e. Left-ankle values at six-minutes walking test: 48±17 for the myotonic dystrophy group, vs, 74±16 for the healthy-controls; p < 0.001).Conclusions: GENEActiv demonstrated to be valid and reliable, capable of detecting walking periods and discriminating different speeds. However, inter-accelerometer reliability only applied when comparing opposite sides of the same limb. Specific movement characteristics of the myotonic dystrophy group were identified and muscle strength showed not to be a full determinant of limb acceleration.Implications for rehabilitationRehabilitation professionals in the field of neuromuscular disorders should be aware of the potential use of objective monitoring tools such as accelerometers whilst acknowledging the implications of assessing populations with altered movement patterns.Researchers should be cautious when translating accelerometry outputs previously validated in healthy populations to functionally impaired cohorts like myotonic dystrophy.Accelerometers can objectively expose movement disturbances allowing further investigations for the source of these disturbances.