Lifestyle Walking Intervention for Patients With Heart Failure With Reduced Ejection Fraction: The WATCHFUL Trial.

BACKGROUND: Physical activity is pivotal in managing heart failure with reduced ejection fraction, and walking integrated into daily life is an especially suitable form of physical activity. This study aimed to determine whether a 6-month lifestyle walking intervention combining self-monitoring and regular telephone counseling improves functional capacity assessed by the 6-minute walk test (6MWT) in patients with stable heart failure with reduced ejection fraction compared with usual care. METHODS: The WATCHFUL trial (Pedometer-Based Walking Intervention in Patients With Chronic Heart Failure With Reduced Ejection Fraction) was a 6-month multicenter, parallel-group randomized controlled trial recruiting patients with heart failure with reduced ejection fraction from 6 cardiovascular centers in the Czech Republic. Eligible participants were ≥18 years of age, had left ventricular ejection fraction <40%, and had New York Heart Association class II or III symptoms on guidelines-recommended medication. Individuals exceeding 450 meters on the baseline 6MWT were excluded. Patients in the intervention group were equipped with a Garmin vívofit activity tracker and received monthly telephone counseling from research nurses who encouraged them to use behavior change techniques such as self-monitoring, goal-setting, and action planning to increase their daily step count. The patients in the control group continued usual care. The primary outcome was the between-group difference in the distance walked during the 6MWT at 6 months. Secondary outcomes included daily step count and minutes of moderate to vigorous physical activity as measured by the hip-worn Actigraph wGT3X-BT accelerometer, NT-proBNP (N-terminal pro-B-type natriuretic peptide) and high-sensitivity C-reactive protein biomarkers, ejection fraction, anthropometric measures, depression score, self-efficacy, quality of life, and survival risk score. The primary analysis was conducted by intention to treat. RESULTS: Of 218 screened patients, 202 were randomized (mean age, 65 years; 22.8% female; 90.6% New York Heart Association class II; median left ventricular ejection fraction, 32.5%; median 6MWT, 385 meters; average 5071 steps/day; average 10.9 minutes of moderate to vigorous physical activity per day). At 6 months, no between-group differences were detected in the 6MWT (mean 7.4 meters [95% CI, -8.0 to 22.7]; P=0.345, n=186). The intervention group increased their average daily step count by 1420 (95% CI, 749 to 2091) and daily minutes of moderate to vigorous physical activity by 8.2 (95% CI, 3.0 to 13.3) over the control group. No between-group differences were detected for any other secondary outcomes. CONCLUSIONS: Whereas the lifestyle intervention in patients with heart failure with reduced ejection fraction improved daily steps by about 25%, it failed to demonstrate a corresponding improvement in functional capacity. Further research is needed to understand the lack of association between increased physical activity and functional outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03041610.

Statistical analysis plan for a randomized controlled trial examining pedometer-based walking intervention in patients with heart failure with reduced ejection fraction: the WATCHFUL trial.

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).

Cardiac device-related infective endocarditis in the Czech Republic: Prospective data from the ESC EORP EURO-ENDO registry.

AIM: Understanding cardiac electronic device infective endocarditis epidemiology is essential for the management of this serious complication. Only monocentric and limited data have been published regarding patients in the Czech republic so far. The aim of this study was to describe the current profile, microbiology and clinical characteristics of this population. PATIENTS AND METHODS: National data from the prospective ESC-EORP EURO-ENDO registry were collected. 57 consecutive patients with a diagnosis of cardiac device-related infective endocarditis (CDRIE) from 11 Czech centres were included. RESULTS: Staphylococcus spp. was responsible for 43.9% of isolates, whereas Culture negative endocarditis was documented in 26.3% episodes. The most frequent complications under therapy were acute renal failure (17.5%), septic shock and heart failure (both 10.5%). Extraction of device was performed in 75.4% of all patients, and the 1-year mortality was 22.5%. CONCLUSIONS: The high proportion of culture-negative endocarditis is alarming and warrants further investigation. Cardiac device related infective endocarditis is a serious complication with a high 1-year mortality in a highly polymorbid spectrum of patients.

The detrimental effect of COVID-19 nationwide quarantine on accelerometer-assessed physical activity of heart failure patients.

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.

The Assessment of Serum Drug Levels to Diagnose Non-Adherence in Stable Chronic Heart Failure Patients.

BACKGROUND: The aim of our study was to evaluate the prevalence of drug non-adherence in stable chronic heart failure (CHF) patients using serum drug levels (SDL) assessment. METHODS: CHF patients were prospectively enrolled during scheduled outpatient visit. Except standard procedures an unanticipated blood sampling for the SDL assessment was obtained. Analysis was focused on the prescribed heart failure and antihypertensive medication and was performed by liquid chromatography coupled with mass spectrometry. The patient was labelled as non-adherent if at least one of drugs assessed was not found in the serum. In the first half of patients multiple SDL have been evaluated during the follow-up. RESULTS: Eighty one patients were enrolled. The non-adherence was proven in twenty of them (25%). In the subgroup of thirty eight patients with multiple SDL evaluation the non-adherence raised significantly with increasing number of visits assessed together (21% for single visit, 29% for two of three visits assessed together and 34% for all three visits evaluated together, all p < 0.001). CONCLUSION: The non-adherence was proven in significant part of stable CHF patients using SDL assessment. This method seems to be reliable and effective and should be a part of clinical assessment in selected patients with CHF.

Effect of a 6-month pedometer-based walking intervention on functional capacity in patients with chronic heart failure with reduced (HFrEF) and with preserved (HFpEF) ejection fraction: study protocol for two multicenter randomized controlled trials.

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).

Serum drug levels to diagnose non-adherence in acute decompensated heart failure.

BACKGROUND: The aim of this study was to analyze medication non-adherence by measuring serum drug levels (SDL) in patients presenting with acute decompensated heart failure (ADHF). METHODS: Included in the study were chronic heart failure patients presenting with signs of acute decompensation. Blood sampling for the measurement of SDL was performed shortly after presentation. SDL were measured using liquid chromatography coupled with mass spectrometry. The estimation of SDL was calculated from the recommended chronic cardiac medications with the exception of drugs administered as part of the acute treatment prior to blood sampling. The patients were labeled as non-adherent when any one of the evaluated medications was not found in the serum. RESULTS: Fifty patients with ADHF were prospectively enrolled. All of the evaluated drugs were detected in the sera of 28 (56%) patients. Non-adherence was diagnosed in the remaining 22 (44%) patients. None of the evaluated medications was detected in the sera of 5 (10%) patients. CONCLUSION: The estimation of SDL indicates that non-adherence to the recommended chronic therapy is a common problem among patients presenting with ADHF. This method should be an essential aspect of routine clinical evaluation in these patients.

Clinical manifestations of infective endocarditis in relation to infectious agents: An 8-year retrospective study.

AIM: To compare clinical complications and outcomes of infective endocarditis (IE) episodes caused by Staphylococcus aureus (S. aureus) and other most frequent aetiological agents (streptococci, enterococci, coagulase-negative staphylococci, and culture-negative IE). METHODS: A total of 117 IE episodes assessed by all internal medicine services of a major teaching institution in the Czech Republic over an eight-year period were identified. RESULTS: We found that S. aureus IE episodes (n = 36) were significantly more associated with systemic embolism (41.7% vs 18.5%, P = 0.01), severe sepsis/septic shock (33.3% vs 3.7%, P < 0.0001), and in-hospital mortality (33% vs 12.3%, P = 0.01). No differences in local, structural, and/or functional complications (cardiac abscess formation, impaired integrity of the valvular apparatus, conduction disturbances, or incidence of heart failure) were observed between studied groups. Long-term survival estimates were significantly improved in patients with IE caused by agents other than S. aureus (13.78 median years vs 5.48 median years, P=0.03). CONCLUSIONS: IE episodes caused by S. aureus are associated with both increased short-term and long-term mortality. Of all the studied parameters, only systemic embolism and severe sepsis/septic shock predicted in-hospital mortality.

Confirmatory testing in primary aldosteronism: extensive medication switching is not needed in all patients.

OBJECTIVE: Confirmatory testing of suspected primary aldosteronism (PA) requires an extensive medication switch that can be difficult for patients with severe complicated hypertension and/or refractory hypokalemia. For this reason, we investigated the effect of chronic antihypertensive medication on confirmatory testing results. To allow the results to be interpreted, the reproducibility of confirmatory testing was also evaluated. DESIGN AND METHODS: The study enrolled 114 individuals with suspected PA who underwent two confirmatory tests. The patients were divided into two groups. In Group A, both tests were performed on the guidelines-recommended therapy, i.e. not interfering with the renin-angiotensin-aldosterone system. In Group B, the first test was performed on chronic therapy with the exclusion of thiazides, loop diuretics, and aldosterone antagonists; and the second test was performed on guidelines-recommended therapy. Saline infusion, preceded by oral sodium loading, was used to suppress aldosterone secretion. RESULTS: Agreement in the interpretation of the two confirmatory tests was observed in 84 and 66% of patients in Groups A and B respectively. For all 20 individuals in Group A who ever had end-test serum aldosterone levels ≥240 pmol/l, aldosterone was concordantly nonsuppressible during the other test. Similarly, for all 16 individuals in Group B who had end-test serum aldosterone levels ≥240 pmol/l on modified chronic therapy, aldosterone remained nonsuppressible with guidelines-recommended therapy. CONCLUSION: Confirmatory testing performed while the patient is on chronic therapy without diuretics and aldosterone antagonists can confirm the diagnosis of PA, provided serum aldosterone remains markedly elevated at the end of saline infusion.

Difficult-to-control arterial hypertension or uncooperative patients? The assessment of serum antihypertensive drug levels to differentiate non-responsiveness from non-adherence to recommended therapy.

Difficult-to-control arterial hypertension is a common medical problem that may result from severe hypertensive disease or from poor adherence to the recommended medical treatment. The identification of non-adherent patients is challenging, especially when non-adherence is intentional. The current report describes the use of serum levels of prescribed antihypertensive drugs to evaluate the adherence in individuals with difficult-to-control arterial hypertension. Serum drug levels (SDLs) were evaluated by liquid chromatography with mass spectrometry. The chromatographic separation was performed on a reversed-phase column with a gradient flow of the mobile phase. The detection of analyzed substances was accomplished on a linear ion-trap mass spectrometer. The subjects were labeled as non-adherent when the serum level of at least one of the evaluated drugs was below the limit of quantification. The study used data from 84 patients with arterial hypertension who underwent SDL assessment to verify compliance with the recommended treatment. Patients who presented with uncontrolled blood pressure despite the recommended combination of at least three antihypertensives were enrolled in the analysis. Based on the evaluation of the SDLs, all of the evaluated drugs were found in the sera of 29 (34.5%) of the study patients. In the remaining 55 (65.5%) patients, non-adherence was diagnosed. None of the prescribed antihypertensive drugs was detected in the sera of the 29 (34.5%) patients. Our data suggest that an assessment of SDLs might be helpful before an extensive evaluation is initiated for difficult-to-control hypertension.

Infective endocarditis in the Czech Republic: eight years of experience at one of the country's largest medical centers.

BACKGROUND AND AIM OF THE STUDY: Limited data have been reported that characterize infective endocarditis (IE) in the Czech Republic. Hence, some local cases of IE were examined to provide a current profile of the disease in Central Europe. METHODS: A descriptive case series of IE patients seen on all internal medicine services of a major teaching institution in the Czech Republic over an eight-year period was developed. RESULTS: Prosthetic valves and rheumatic carditis were the underlying predisposing conditions in 18% and 17%, respectively, of all IE episodes. Staphylococcal species were the most common pathogens identified, and were present in 45% of IE episodes. In contrast, streptococcal species were recovered in only 14% of episodes. The proportion of culture-negative endocarditis cases was sizable (18%). The aortic valve was most commonly involved in IE episodes (47%), followed by the mitral valve (33%). The in-hospital mortality rate was 21%. CONCLUSION: Younger patients, the occurrence of underlying rheumatic carditis, a lack of injection drug use, and an increased frequency of culture-negative infections are unique IE characteristics among Czech patients, as compared to those seen in patients from Western Europe and the United States. The heralded microbiological shift from viridans group streptococci to Staphylococcus aureus may apply to the current study.