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Background: Physical activity is an effective management strategy for heart failure with reduced ejection fraction, but patients' compliance is challenging. Walking is a suitable form of physical activity due to its convenience and sustainability, and it can potentially improve functional capacity in heart failure patients. Objectives: The WATCHFUL trial aims to determine whether a pedometer-based walking intervention combined with face-to-face sessions and regular telephone contact improves functional capacity in heart failure patients. Methods: The WATCHFUL trial is a 6-month multicenter, parallel-group, randomized, controlled, superiority trial with a 6-month follow-up. A total of 202 patients were recruited for the trial. The primary analysis will evaluate the change in distance walked during the 6-min walk test from baseline to 6 months based on the intention-to-treat population; the analysis will be performed using a linear mixed-effect model adjusted for baseline values. Missing data will be imputed using multiple imputations, and the impact of missing data will be assessed using a sensitivity analysis. Adverse events are monitored and recorded throughout the trial period. Discussion: The trial has been designed as a pragmatic trial with a scalable intervention that could be easily translated into routine clinical care. The trial has been affected by the COVID-19 pandemic, which slowed patients' recruitment and impacted their physical activity patterns. Conclusions: The present publication provides details of the planned statistical analyses for the WATCHFUL trial to reduce the risks of reporting bias and erroneous data-driven results. Trial registration: ClinicalTrials.gov (identifier: NCT03041610, registered: 3/2/2017). [ABSTRACT FROM AUTHOR]

Aims: Diabetes mellitus is associated with worse outcomes and lower attainment of disease‐modifying therapies in patients with heart failure with reduced ejection fraction (HFrEF). This post hoc analysis of TRANSITION compared the patterns of tolerability and uptitration of sacubitril/valsartan in patients with HFrEF stabilized after hospital admission due to acute decompensated HF depending on the presence or absence of diabetes as a co‐morbidity. Methods: TRANSITION, a randomized, open‐label study compared sacubitril/valsartan initiation pre‐discharge vs. post‐discharge (up to14 days) in 991 patients hospitalized for acutely decompensated HFrEF. The impact of diabetes status on tolerability and safety was studied at 10‐week and 26‐week post‐randomization. Results: Among the 991 patients analysed at baseline, 460 (46.4%) had diabetes and exhibited a higher risk profile. At 10 weeks, sacubitril/valsartan target dose (97/103 mg bid) was achieved in a similar proportion of patients in each subgroup, when initiated pre‐discharge or post‐discharge respectively [diabetes subgroup: 47% (n = 105/226) vs. 50% (n = 115/228); relative risk ratio (RRR), 0.923; P = 0.412; non‐diabetes subgroup: 45% (n = 119/267) vs. 51% (n = 133/261); RRR, 0.878; P = 0.155]. The proportions of patients achieving and maintaining either 49/51 mg or 97/103 mg bid [diabetes subgroup: 61.1% (n = 138/226) vs. 67.5% (n = 154/228); RRR, 0.909; P = 0.175; non‐diabetes subgroup: 62.9% [n = 168/267] vs 69.3% [n = 181/261]; RRR, 0.906; P = 0.118] or any dose for ≥2 weeks leading to Week 10 [diabetes subgroup: 85% (n = 192/226) vs. 88.2% (n = 201/228); RRR, 0.966; P = 0.356; non‐diabetes subgroup: 86.9% (n = 232/267) vs. 90.8% (n = 237/261); RRR, 0.963; P = 0.215] were also similar in each subgroup, when initiated pre‐discharge or post‐discharge, respectively. At 10 weeks, hypotension and renal dysfunction rates were similar, although hyperkalaemia was higher among patients with diabetes (15.9% vs. 9.5%). The rate of permanent discontinuation due to adverse events was similar in the diabetes and non‐diabetes subgroups at 10 weeks, respectively: pre‐discharge (7.5% vs. 7.1%) or post‐discharge (5.7% vs. 4.2%). Similar patterns of uptitration and tolerability were observed at 26 weeks. Cardiac biomarkers including NT‐proBNP (P < 0.005) and hs‐TnT (P < 0.005) reduced significantly from baseline levels in both subgroups at Weeks 4 and 10; however, the response was greater among patients without diabetes. Mortality (diabetes vs. non‐diabetes subgroups: 3.3% vs 4.0%; P = 0.438) and HF rehospitalization (diabetes vs. non‐diabetes subgroups: 36.3% vs. 33.0%; P = 0.295) did not differ between the groups at 26 weeks. Conclusions: Despite a higher risk profile among patients with diabetes, sacubitril/valsartan initiation either before or shortly after discharge in hospitalized patients with HFrEF resulted in comparable rates of dose up‐titration and tolerability as in those without diabetes. [ABSTRACT FROM AUTHOR]

Aims: A reduction of habitual physical activity due to prolonged COVID‐19 quarantine can have serious consequences for patients with cardiovascular diseases, such as heart failure. This study aimed to explore the effect of COVID‐19 nationwide quarantine on accelerometer‐assessed physical activity of heart failure patients. Methods and results: We analysed the daily number of steps in 26 heart failure patients during a 6‐week period that included 3 weeks immediately preceding the onset of the quarantine and the first 3 weeks of the quarantine. The daily number of steps was assessed using a wrist‐worn accelerometer worn by the patients as part of an ongoing randomized controlled trial. Multilevel modelling was used to explore the effect of the quarantine on the daily step count adjusted for weather conditions. As compared with the 3 weeks before the onset of the quarantine, the step count was significantly lower during each of the first 3 weeks of the quarantine (P < 0.05). When the daily step count was averaged across the 3 weeks before and during the quarantine, the decrease amounted to 1134 (SE 189) steps per day (P < 0.001), which translated to a 16.2% decrease. Conclusions: The introduction of the nationwide quarantine due to COVID‐19 had a detrimental effect on the level of habitual physical activity in heart failure patients, leading to an abrupt decrease of daily step count that lasted for at least the 3‐week study period. Staying active and maintaining sufficient levels of physical activity during the COVID‐19 pandemic are essential despite the unfavourable circumstances of quarantine. [ABSTRACT FROM AUTHOR]

Aims: Sacubitril/valsartan has shown efficacy and tolerability in patients with heart failure (HF) and reduced ejection fraction (HFrEF) in the ambulatory setting (PARADIGM-HF), and following stabilisation of acutely decompensated HF (ADHF) (PIONEER-HF and TRANSITION). However, data are lacking for the initiation of sacubitril/valsartan in newly diagnosed (de novo) HFrEF. Here, we assess the tolerability of initiating sacubitril/valsartan following ADHF in TRANSITION subgroups of patients with a de novo vs. prior diagnosis of HFrEF.Methods and Results: TRANSITION randomised 1002 patients to pre- and post-discharge initiation of sacubitril/valsartan (analysis set n = 991, following exclusions for mis-randomisation). In this post-hoc analysis, tolerability to sacubitril/valsartan [proportion of patients achieving target dose (97/103 mg b.i.d.) at 10 weeks post-randomisation], adverse events (AEs) and serious AEs (SAEs) were compared in de novo (n = 286) and prior HFrEF (n = 705) subgroups. More de novo than prior HFrEF patients achieved target dose at Week 10 (56% vs. 45%; relative risk ratio 1.30, 95% confidence interval 1.12-1.52, P < 0.001), and fewer had SAEs and permanent treatment discontinuations. Initiation of sacubitril/valsartan did not prevent the concomitant initiation and up-titration of guideline-directed HF therapies. De novo patients showed faster and greater decreases in N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin-T, and lower rates of HF and all-cause rehospitalisation vs. prior HFrEF.Conclusions: After ADHF, first-line initiation of sacubitril/valsartan in de novo HFrEF, alongside the initiation of other guideline-directed therapies, is feasible and is associated with a better risk-benefit profile than in patients with prior HFrEF. Early intervention with sacubitril/valsartan may be considered to delay disease progression in patients with de novo HFrEF.Clinical Trial Registration: ClinicalTrials.gov, NCT02661217. [ABSTRACT FROM AUTHOR]

Introduction: Although numerous activity trackers have been validated in healthy populations, validation is lacking in chronic heart failure patients who normally walk at a slower pace, making it difficult for researchers and clinicians to implement activity monitors during physical activity interventions. Methods: Six consumer-level activity monitors were validated in a 3-day field study in patients with chronic heart failure and healthy individuals under free living conditions. Furthermore, the same devices were evaluated in a lab-based study during treadmill walking at speeds of 2.4, 3.0, 3.6, and 4.2 km·h-1. Concordance correlation coefficients (CCC) were used to evaluate the agreement between the activity monitors and the criterion, and mean absolute percentage errors (MAPE) were calculated to assess differences between each device and the criterion (MAPE <10% was considered as a threshold for validity). Results: In the field study of healthy individuals, all but one of the activity monitors showed a substantial correlation (CCC ≥0.95) with the criterion device and MAPE <10%. In patients with heart failure, the correlation of only two activity monitors (Garmin vívofit 3 and Withings Go) was classified as at least moderate (CCC ≥0.90) and none of the devices had MAPE <10%. In the lab-based study at speeds 4.2 and 3.6 km·h-1, all activity monitors showed substantial to almost perfect correlations (CCC ≥0.95) with the criterion and MAPE in the range 1%-3%. However, at slower speeds of 3.0 and 2.4 km·h-1, the accuracy of all devices substantially deteriorated: their correlation with the criterion decreased below 90% and their MAPE increased to 4–8% and 10–45%, respectively. Conclusions: Even though none of the tested activity monitors fall within arbitrary thresholds for validity, most of them perform reasonably well enough to be useful tools that clinicians can use to simply motivate chronic heart failure patients to walk more. [ABSTRACT FROM AUTHOR]

Aims: To assess tolerability and optimal time point for initiation of sacubitril/valsartan in patients stabilised after acute heart failure (AHF).Methods and Results: TRANSITION was a randomised, multicentre, open-label study comparing two treatment initiation modalities of sacubitril/valsartan. Patients aged ≥ 18 years, hospitalised for AHF were stratified according to pre-admission use of renin-angiotensin-aldosterone system inhibitors and randomised (n = 1002) after stabilisation to initiate sacubitril/valsartan either ≥ 12-h pre-discharge or between Days 1-14 post-discharge. Starting dose (as per label) was 24/26 mg or 49/51 mg bid with up- or down-titration based on tolerability. The primary endpoint was the proportion of patients attaining 97/103 mg bid target dose after 10 weeks. Median time of first dose of sacubitril/valsartan from the day of discharge was Day -1 and Day +1 in the pre-discharge group and the post-discharge group, respectively. Comparable proportions of patients in the pre- and post-discharge initiation groups met the primary endpoint [45.4% vs. 50.7%; risk ratio (RR) 0.90; 95% confidence interval (CI) 0.79-1.02]. The proportion of patients who achieved and maintained for ≥ 2 weeks leading to Week 10, either 49/51 or 97/103 mg bid was 62.1% vs. 68.5% (RR 0.91; 95% CI 0.83-0.99); or any dose was 86.0% vs. 89.6% (RR 0.96; 95% CI 0.92-1.01). Discontinuation due to adverse events occurred in 7.3% vs. 4.9% of patients (RR 1.49; 95% CI 0.90-2.46).Conclusions: Initiation of sacubitril/valsartan in a wide range of heart failure with reduced ejection fraction patients stabilised after an AHF event, either in hospital or shortly after discharge, is feasible with about half of the patients achieving target dose within 10 weeks.Clinical Trial Registration: ClinicalTrials.gov ID: NCT02661217. [ABSTRACT FROM AUTHOR]

Extracorporeal membrane oxygenation (ECMO) has been used increasingly for both respiratory and cardiac failure in adult patients. Indications for ECMO use in cardiac failure include severe refractory cardiogenic shock, refractory ventricular arrhythmia, active cardiopulmonary resuscitation for cardiac arrest, and acute or decompensated right heart failure. Evidence is emerging to guide the use of this therapy for some of these indications, but there remains a need for additional evidence to guide best practices. As a result, the use of ECMO may vary widely across centers. The purpose of this document is to highlight key aspects of care delivery, with the goal of codifying the current use of this rapidly growing technology. A major challenge in this field is the need to emergently deploy ECMO for cardiac failure, often with limited time to assess the appropriateness of patients for the intervention. For this reason, we advocate for a multidisciplinary team of experts to guide institutional use of this therapy and the care of patients receiving it. Rigorous patient selection and careful attention to potential complications are key factors in optimizing patient outcomes. Seamless patient transport and clearly defined pathways for transition of care to centers capable of providing heart replacement therapies (e.g., durable ventricular assist device or heart transplantation) are essential to providing the highest level of care for those patients stabilized by ECMO but unable to be weaned from the device. Ultimately, concentration of the most complex care at high-volume centers with advanced cardiac capabilities may be a way to significantly improve the care of this patient population. [ABSTRACT FROM AUTHOR]

Background: Regular physical activity is recommended for patients with chronic heart failure to improve their functional capacity, and walking is a popular, effective, and safe form of physical activity. Pedometers have shown potential to increase the amount of walking across a range of chronic diseases, but it is unknown whether a pedometer-based intervention improves functional capacity and neurohumoral modulation in heart failure patients.Methods: Two multicenter randomized controlled trials will be conducted in parallel: one in patients with chronic heart failure with reduced ejection fraction (HFrEF), the other in patients with chronic heart failure with preserved ejection fraction (HFpEF). Each trial will consist of a 6-month intervention with an assessment at baseline, at 3 months, at the end of the intervention, and 6 months after completing the intervention. Each trial will aim to include a total of 200 physically inactive participants with chronic heart failure who will be randomly assigned to intervention or control arms. The 6-month intervention will consist of an individualized pedometer-based walking program with weekly step goals, behavioral face-to-face sessions with a physician, and regular telephone calls with a research nurse. The intervention will be based on effective behavioral principles (goal setting, self-monitoring, personalized feedback). The primary outcome is the change in 6-min walk distance at the end of the 6-month intervention. Secondary outcomes include changes in serum biomarkers levels, pulmonary congestion assessed by ultrasound, average daily step count measured by accelerometry, anthropometric measures, symptoms of depression, health-related quality of life, self-efficacy, and MAGGIC risk score.Discussion: To our knowledge, these are the first studies to evaluate a pedometer-based walking intervention in patients with chronic heart failure with either reduced or preserved ejection fraction. The studies will contribute to a better understanding of physical activity promotion in heart failure patients to inform future physical activity recommendations and heart failure guidelines. Trial registration The trials are registered in ClinicalTrials.gov, identifiers: NCT03041610, registered 29 January 2017 (HFrEF), NCT03041376, registered 1 February 2017 (HFpEF). [ABSTRACT FROM AUTHOR]

Background: Obesity is clearly associated with increased morbidity and mortality rates. However, in patients with acute heart failure (AHF), an increased BMI could represent a protective marker. Studies evaluating the “obesity paradox” on a large cohort with long-term follow-up are lacking. Methods: Using the AHEAD database (a Czech multi-centre database of patients hospitalised due to AHF), 5057 patients were evaluated; patients with a BMI <18.5 kg/m2 were excluded. All-cause mortality was compared between groups with a BMI of 18.5–25 kg/m2 and with BMI >25 kg/m2. Data were adjusted by a propensity score for 11 parameters. Results: In the balanced groups, the difference in 30-day mortality was not significant. The long-term mortality of patients with normal weight was higher than for those who were overweight/obese (HR, 1.36; 95% CI, 1.26–1.48; p<0.001)). In the balanced dataset, the pattern was similar (1.22; 1.09–1.39; p<0.001). A similar result was found in the balanced dataset of a subgroup of patients with de novo AHF (1.30; 1.11–1.52; p = 0.001), but only a trend in a balanced dataset of patients with acute decompensated heart failure. Conclusion: These data suggest significantly lower long-term mortality in overweight/obese patients with AHF. The results suggest that at present there is no evidence for weight reduction in overweight/obese patients with heart failure, and emphasize the importance of prevention of cardiac cachexia. [ABSTRACT FROM AUTHOR]

• HR appears to be an prognostic parameter in AHF patients in sinus rythm • There are different prognostic cut-off points for HR depending on ejection fraction • HFpEF patients are more sensitive to HR than HFrEF patients • Optimal prognostic cut-offs of HR were identified for HFpEF at 80 bpm Heart rate (HR) at admission in patients with acute heart failure (AHF) has been shown to be an important risk marker of in-hospital mortality. However, its relation with mid and long-term prognosis as well as the impact of Ejection Fraction (EF) is unknown. Our objective was to study the relationship between long-term survival and HR at admission depending on EF in a cohort of patients hospitalized for AHF. We analyzed the data of 2335 patients in sinus rhythm hospitalized for AHF from AHEAD registry. Patients with cardiogenic shock and AHF from surgical or non-cardiac etiology were excluded. Survival rates at 6 and 12 months were 84.8% and 78% respectively. Increased age, decreased diastolic BP, lack of PCI during hospitalization, increased creatinine level and increased HR (with different cut-offs according to EF categories) were found as predictors whatever the EF at 6 and 12 months. Optimal prognostic cut-offs of heart rate were identified for Heart Failure with reduced EF at 100 bpm, for Heart Failure with mid-range EF at 90 bpm and for Heart Failure with preserved EF at 80 bpm for both 6 and 12 months. Our study suggests that HR at admission appears to be an independent prognostic parameter in AHF patients in sinus rhythm irrespective of EF and can be used to classify patients according to the severity of the disease. [ABSTRACT FROM AUTHOR]

Introduction: The benefit of sacubitril/valsartan (S/V) in patients with chronic heart failure and reduced ejection fraction (HFrEF) is associated with a reduction of biomarkers of myocardial stretch and necrosis. S/V initiation after an acute decompensation of HFrEF (ADHF) has not been studied and the impact of a pre-discharge (d/c) vs. post-d/c strategy on cardiac biomarkers is unknown Hypothesis: S/V initiation in the hospital after stabilization from ADHF is safe and well tolerated and results in early biomarker response. Methods: TRANSITION (NCT02661217) is a randomized, open-label study comparing S/V start pre- vs. 1-14 days post-d/c in HFrEF patients admitted for ADHF after hemodynamic stabilization. Patients were stratified by pre-admission treatment: on ACE-I, ARB, or ACE-I/ARB-naïve. Randomization occurred after hemodynamic stabilization 1:1 per stratum for initiation of S/V pre-d/c or post-d/c. NT-proBNP and cardiac troponin T were measured at randomization, discharge, 4 weeks (w) and 10w post-randomization. Results: 983 patients were included in the safety analysis (24% ACE-I/ARB naïve, 29% de novo HFrEF). Median NT-proBNP at randomization was 1902 pg/mL (Q1-Q3 [IQR]: 945-3883) in the pre-d/c arm (n=478) and 1669 pg/mL (IQR: 706-3577) in the post-d/c arm (n=473). At discharge, patients in the pre-d/c arm exhibited a significant reduction of NT-proBNP levels (change from randomization: 0.719, 95%CI: 0.677-0.762) which was greater than in the post-d/c arm (0.966, 95%CI: 0.905-1.031) (p<0.001 for comparison). After 10w the reduction was significant and comparable in both arms: pre-d/c (0.619, 95%CI 0.564-0.679) vs. post-d/c 0.663 (95CI%: 0.603-0.728) (p=0.239 for comparison). At randomization, median hsTnT was 29 pg/mL (IQR: 19-45) in the pre-d/c arm vs. 28 pg/mL (IQR: 17-43) in the post-d/c arm. At discharge, only patients in the pre-d/c arm showed a significant reduction in hsTnT (0.946, 95%CI 0.906-0.989), albeit not significantly greater than the reduction observed in the post-d/c arm (0.961, 95%CI 0.916-1.007) (p=0.440). After 10w, both strategies showed a significant reduction in hsTnT concentrations (pre-d/c: 0.743, 95%CI: 0.699-0.790; vs. post-d/c: 0.715, 95%CI 0.673-0.759; p=0.276). Conclusions: In hospitalized patients with ADHF, initiation of S/V after hemodynamic stabilization and before discharge is feasible and associated with a rapid reduction of NT-proBNP. After discharge, both S/V initiation strategies were associated with comparable reductions in cardiac biomarkers levels after 10w. [ABSTRACT FROM AUTHOR]