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.

Effects of a 10-Week Integrated Curriculum Intervention on Physical Activity, Resting Blood Pressure, Motor Skills, and Well-Being in 6- to 7-Year-Olds.

BACKGROUND: Integrated curriculum interventions have been suggested as an effective means to increase physical activity (PA) and health. The feasibility of such approaches in children living in deprivation is unknown. This study sought to pilot an integrated curriculum pedometer intervention in children living in deprivation on school-based PA, body fatness, resting blood pressure, motor skills, and well-being. METHODS: Using a pilot cluster randomized intervention design, children (6-7 y old, n = 64) from 2 schools in central England undertook: (1) 10-week integrated curriculum intervention or (2) control (regular school-based activity). School-based PA, body fatness, resting blood pressure, motor skills, and well-being were assessed preintervention and postintervention. RESULTS: For the intervention group, PA was higher on school days when children had physical education lessons or there were physically active integrated curriculum activities. Body fatness significantly decreased, and well-being and perceived physical competence increased, pre-post for the intervention group compared with the control group. Accelerometer-derived PA, motor skills, and resting blood pressure were not significantly different pre-post for intervention or control groups. CONCLUSIONS: A 10-week integrated curriculum PA intervention is feasible to conduct and can positively impact aspects of health in 6- to 7-year-old children in England.

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.

The Role of Cardiopulmonary Exercise Testing in Hypertrophic Cardiomyopathy.

This review emphasizes the importance of cardiopulmonary exercise testing (CPET) in patients diagnosed with hypertrophic cardiomyopathy (HCM). In contrast to standard exercise testing and stress echoes, which are limited due to the ECG changes and wall motion abnormalities that characterize this condition, CPET allows for the assessment of the complex pathophysiology and severity of the disease, its mechanisms of functional limitation, and its risk stratification. It is useful tool to evaluate the risk for sudden cardiac death and select patients for cardiac resynchronization therapy (CRT), cardiac transplantation, or mechanical circulatory support, especially when symptomatology and functional status are uncertain. It may help in differentiating HCM from other forms of cardiac hypertrophy, such as athletes' heart. Finally, it is used to guide and monitor therapy as well as for exercise prescription. It may be considered every 2 years in clinically stable patients or every year in patients with worsening symptoms. Although performed only in specialized centers, CPET combined with echocardiography (i.e., CPET imaging) and invasive CPET are more informative and provide a better assessment of cardiac functional status, left ventricular outflow tract obstruction, and diastolic dysfunction during exercise in patients with HCM.

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.

Cardiovascular implications and physical activity in middle-aged and older adults with a history of COVID-19 (CV COVID): a protocol for a randomised controlled trial.

BACKGROUND: The clinical manifestation of COVID-19 is associated with infection and inflammation of the lungs, but there is evidence to suggest that COVID-19 may also affect the structure and function of the cardiovascular system. At present, it is not fully understood to what extent COVID-19 impacts cardiovascular function in the short- and long-term following infection. The aim of the present study is twofold: (i) to define the effect of COVID-19 on cardiovascular function (i.e. arterial stiffness, cardiac systolic and diastolic function) in otherwise healthy individuals and (ii) to evaluate the effect of a home-based physical activity intervention on cardiovascular function in people with a history of COVID-19. METHODS: This prospective, single-centre, observational study will recruit 120 COVID-19-vaccinated adult participants aged between 50 and 85 years, i.e. 80 with a history of COVID-19 and 40 healthy controls without a history of COVID-19. All participants will undergo baseline assessments including 12-lead electrocardiography, heart rate variability, arterial stiffness, rest and stress echocardiography with speckle tracking imaging, spirometry, maximal cardiopulmonary exercise testing, 7-day physical activity and sleep measures and quality of life questionnaires. Blood samples will be collected to assess the microRNA expression profiles, cardiac and inflammatory biomarkers, i.e. cardiac troponin T; N-terminal pro B-type natriuretic peptide; tumour necrosis factor alpha; interleukins 1, 6 and 10; C-reactive protein; D-dimer; and vascular endothelial growth factors. Following baseline assessments, COVID-19 participants will be randomised 1:1 into a 12-week home-based physical activity intervention aiming to increase their daily number of steps by 2000 from baseline. The primary outcome is change in left ventricular global longitudinal strain. Secondary outcomes are arterial stiffness, systolic and diastolic function of the heart, functional capacity, lung function, sleep measures, quality of life and well-being (depression, anxiety, stress and sleep efficiency). DISCUSSION: The study will provide insights into the cardiovascular implications of COVID-19 and their malleability with a home-based physical activity intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT05492552. Registered on 7 April 2022.

Sacubitril/valsartan reverses cardiac structure and function in experimental model of hypertension-induced hypertrophic cardiomyopathy.

This study evaluated the effect of sacubtril/valsartan on cardiac remodeling, molecular and cellular adaptations in experimental (rat) model of hypertension-induced hypertrophic cardiomyopathy. Thirty Wistar Kyoto rats, 10 healthy (control) and 20 rats with confirmed hypertension-induced hypertrophic cardiomyopathy (HpCM), were used for this study. The HpCM group was further subdivided into untreated and sacubitril/valsartan-treated groups. Myocardial structure and function were assessed using echocardiography, Langendorff's isolated heart experiment, blood sampling and qualitative polymerase chain reaction. Echocardiographic examinations revealed protective effects of sacubitril/valsartan by improving left ventricular internal diameter in systole and diastole and fractional shortening. Additionally, sacubitril/valsartan treatment decreased systolic and diastolic blood pressures in comparison with untreated hypertensive rats. Moreover, sacubitril/valsartan treatment reduced oxidative stress and apoptosis (reduced expression of Bax and Cas9 genes) compared to untreated rats. There was a regular histomorphology of cardiomyocytes, interstitium, and blood vessels in treated rats compared to untreated HpCM rats which expressed hypertrophic cardiomyocytes, with polymorphic nuclei, prominent nucleoli and moderately dilated interstitium. In experimental model of hypertension-induced hypertrophic cardiomyopathy, sacubitril/valsartan treatment led to improved cardiac structure, haemodynamic performance, and reduced oxidative stress and apoptosis. Sacubitril/valsartan thus presents as a potential therapeutic strategy resulted in hypertension-induced hypertrophic cardiomyopathy.

Validity and reliability of short-term heart-rate variability from disposable electrocardiography leads.

Background and Aims: Single-use electrocardiography (ECG) leads have been developed to reduce healthcare-associated infection. This study compared the validity and reliability of short-term heart rate variability (HRV) obtained from single-use disposable ECG leads. Methods: Thirty healthy subjects (33 ± 10 years; 9 females) underwent 5-min resting HRV assessments using disposable (single use) ECG cable and wire system (Kendall DL™ Cardinal Health) and a standard, reusable ECG leads (CardioExpress, Spacelabs Healthcare). Results: Intraclass correlation coefficient (ICC) with 95% confidence interval (CI) between disposable and reusable ECG leads was for the time domain [R-R interval (ms); 0.99 (0.91, 1.00)], the root mean square of successive normal R-R interval differences (RMSSD) (ms); 0.91 (0.76, 0.96), the SD of normal-to-normal R-R intervals (SDNN) (ms); 0.91 (0.68, 0.97) and frequency domain [low-frequency (LF) normalized units (nu); 0.90 (0.79, 0.95), high frequency (HF) nu; 0.91 (0.80, 0.96), LF power (ms2); 0.89 (0.62, 0.96), HF power (ms2); 0.90 (0.72, 0.96)] variables. The mean difference and upper and lower limits of agreement between disposable and reusable leads for time- and frequency-domain variables were acceptable. Analysis of repeated measures using disposable leads demonstrated excellent reproducibility (ICC 95% CI) for R-R interval (ms); 0.93 (0.85, 0.97), RMSSD (ms); 0.93 (0.85, 0.97), SDNN (ms); 0.88 (0.75, 0.95), LF power (ms2); 0.87 (0.72, 0.94), and HF power (ms2); 0.88 (0.73, 0.94) with coefficient of variation ranging from 2.2% to 5% (p > 0.37 for all variables). Conclusion: Single-use Kendall DL™ ECG leads demonstrate a valid and reproducible tool for the assessment of HRV.

Effects of Sitting Callisthenic Balance and Resistance Exercise Programs on Cognitive Function in Older Participants.

BACKGROUND: Exercise training programs have the potential to improve cognitive function in older subjects. However, the majority of training programs are based on aerobic modality. In the current study, the influence of 3 months programs of sitting callisthenic balance (SCB) and resistance training (RT) on cognitive functioning and the mediating role that a change in the level of neurotrophic factors and strength in older, healthy participants plays were examined. MATERIAL AND METHODS: Global cognitive function was examined using MoCA, short-term memory using Digit Span and Delayed Matching to Sample, set shifting using Trial Making Test Part B, speed of processing simple visual stimuli using Simple Reaction Time, decision making using Choice Reaction Time, visual attention with Visual Attention Test (VAT), tests. Strength of lower and upper limbs, neurotrophin level (irisin, brain-derived neurotrophic factor (BDNF), neurotrophin 3 (NT-3), neurotrophin 4/5 (NT 4/5) were examined. RESULTS: Improved scores in RT vs. SCB were noted in MoCA (p = 0.02), reaction time in SRT (p = 0.02), TMT B (p = 0.03), errors committed in CRT (p = 0.04) and VAT (p = 0.02) were observed. No significant changes in the level of neurotrophic factors were observed. Changes in upper limb strength were related to changes in the number of errors committed in the SRT (p = 0.03). Lower limb strength changes explained the dynamics of the number of correct answers (p = 0.002) and errors committed (p = 0.006) in VAT. CONCLUSIONS: Both SCB and RT influenced multiple cognitive domains. The RT program improved global cognitive functioning, while no improvement was noticed in the SCB group. Decision making, visual attention and global cognitive function were improved after the RT program. Set-shifting, short-term visual memory processing speed of simple visual stimuli were improved after the SCB program, while a decrease in the processing speed of simple visual stimuli was noted in the RT group. Changes in irisin were related to set-shifting and short-term memory, while in BDNF to an improvement in the processing speed of simple visual stimuli. Resistance exercise training programs could be applied to prevent age related declines of cognitive function in healthy older subjects.

Haemodynamic determinants of quality of life in chronic heart failure.

BACKGROUND: Heart failure patients demonstrate reduced functional capacity, hemodynamic function, and quality of life (QOL) which are associated with high mortality and morbidity rate. The aim of the present study was to assess the relationship between functional capacity, hemodynamic response to exercise and QOL in chronic heart failure. METHODS: A single-centre prospective study recruited 42 chronic heart failure patients (11 females, mean age 60 ± 10 years) with reduced left ventricular ejection fraction (LVEF = 23 ± 7%). All participants completed a maximal graded cardiopulmonary exercise test with non-invasive hemodynamic (bioreactance) monitoring. QOL was assessed using Minnesota Living with Heart Failure Questionnaire. RESULTS: The average value of QOL score was 40 ± 23. There was a significant negative relationship between the QOL and peak O2 consumption (r = - 0.50, p ≤ 0.01). No significant relationship between the QOL and selected exercise hemodynamic measures was found, including peak exercise cardiac power output (r = 0.15, p = 0.34), cardiac output (r = 0.22, p = 0.15), and mean arterial blood pressure (r = - 0.08, p = 0.60). CONCLUSION: Peak O2 consumption, but not hemodynamic response to exercise, is a significant determinant of QOL in chronic heart failure patients.

Peak atrio-ventricular mechanics predicts exercise tolerance in heart failure patients.

PURPOSE: Exercise intolerance is a cardinal symptom of patients with heart failure (HF). We hypothesized that patients with HF with preserved ejection fraction (HFpEF) in comparison with those with reduced ejection fraction (HFrEF) have disproportionate exercise-induced impairment of left atrial (LA) function that may explain the effort intolerance. METHODS: Total 40 HFpEF patients, 40 HFrEF patients, and 20 matched healthy controls underwent resting and exercise stress transthoracic echocardiography using modified Bruce protocol with speckle-tracking derived assessments of peak atrial longitudinal strain (PALS) and left ventricular global longitudinal strain (LVGLS). RESULTS: In comparison to controls, PALS and LVGLS were reduced in HFpEF and HFrEF patients (P < 0.01); however, the strain magnitudes were significantly lower in HFrEF than in HFpEF (P < 0.01). Both HFpEF and HFrEF showed a 28% and 30% reduction in exercise time in comparison with controls (HFpEF, 363 ± 152, HFrEF 352 ± 91, controls, 505 ± 42 s, P < 0.01) and exercise-related rise in E/E' in HFpEF patients. However, during exercise PALS reduced from resting values by 26% (resting 23.1 ± 4.7 and peak 18.5 ± 3.5, P < 0.01) in HFpEF but only 8% in HFrEF (resting 11.5 ± 1.4 and peak 10.5 ± 1.5, P < 0.01), and remained unchanged in controls (resting 34 ± 1.9 and peak 34.4 ± 1.2, P = 0.4). Regression analysis of the combined data from the HF patients and controls revealed that PALS was independently associated with exercise time such that a 1% reduction in PALS was associated with a 10 s reduction in exercise duration (p < 0.01). PALS at baseline and peak exercise differentiated normal from HF patients. LVGLS at baseline and peak exercise differentiated HFpEF from HFrEF and patients of HFpEF showed abnormality of both PALS and LVGLS. CONCLUSION: Although left ventricle and LA strain are lower in HFrEF than HFpEF at rest and exercise compared to healthy controls, patients with HFpEF show more profound deterioration of LA reservoir function with exercise which appears to contribute to exercise intolerance.

Gender Related Differences in the Clinical Presentation of Hypertrophic Cardiomyopathy-An Analysis from the SILICOFCM Database.

Background and Objectives: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease that affects approximately 1 in 500 people. Due to an incomplete disease penetrance associated with numerous factors, HCM is not manifested in all carriers of genetic mutation. Although about two-thirds of patients are male, it seems that female gender is associated with more severe disease phenotype and worse prognosis. The objective of this study was to evaluate the gender related differences in HCM presentation. Materials and Methods: This study was conducted as a part of the international multidisciplinary SILICOFCM project. Clinical information, laboratory analyses, electrocardiography, echocardiography, and genetic testing data were collected for 362 HCM patients from four clinical centers (Florence, Newcastle, Novi Sad, and Regensburg). There were 33% female patients, and 67% male patients. Results: Female patients were older than males (64.5 vs. 53.5 years, p < 0.0005). The male predominance was present across all age groups until the age of 70, when gender distribution became comparable. Females had higher number of symptomatic individuals then males (69% vs. 52%, p = 0.003), most frequently complaining of dyspnea (50% vs. 30%), followed by chest pain (30% vs. 17%), fatigue (26% vs. 13%), palpitations (22% vs. 13%), and syncope (13% vs. 8%). The most common rhythm disorder was atrial fibrillation which was present in a similar number of females and males (19% vs. 13%, p = 0.218). Levels of N-terminal pro-brain natriuretic peptide were comparable between the genders (571 vs. 794 ng/L, p = 0.244). Echocardiography showed similar thickness of interventricular septum (18 vs. 16 mm, p = 0.121) and posterolateral wall (13 vs. 12 mm, p = 0.656), however, females had a lower number of systolic anterior motion (8% vs. 16%, p = 0.020) and other mitral valve abnormalities. Conclusions: Female patients are underrepresented but seem to have a more pronounced clinical presentation of HCM. Therefore, establishing gender specific diagnostic criteria for HCM should be considered.

Defining the importance of stress reduction in managing cardiovascular disease - the role of exercise.

Traditional risk factors for cardiovascular disease (CVD) have long been the focus of preventive strategies. The impact of family stress, depression, anxiety, hostility, pessimism, job strain, social isolation, lack of purpose in life and social support, are well recognized risks for CVD development, however they are under-appreciated in clinical practice guidelines. The purpose of this article is to review the impact of acute and chronic stress on CVD risk, elaborate repositioning in guidelines, with emphasis to approaches for stress reduction. Regular exercise, both aerobic and resistance, leads to better adaptiveness to other types of stress, however, it remains unknown whether the total amount of stress one can receive before negative health effects is unlimited. Evidently, marked reductions in stress related disorders are shown following formal cardiac rehabilitation programs. Attendance of cardiac rehabilitation is highly recommended for the stress-related mortality risk reduction. Innovative approaches to offset the broad challenges that CVD pose, augmented by sustained exposure to stress, are desperately needed, but hindered by a lack of successful population-level interventions that promote lasting change.

Disease Progression of Hypertrophic Cardiomyopathy: Modeling Using Machine Learning.

BACKGROUND: Cardiovascular disorders in general are responsible for 30% of deaths worldwide. Among them, hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease that is present in about 1 of 500 young adults and can cause sudden cardiac death (SCD). OBJECTIVE: Although the current state-of-the-art methods model the risk of SCD for patients, to the best of our knowledge, no methods are available for modeling the patient's clinical status up to 10 years ahead. In this paper, we propose a novel machine learning (ML)-based tool for predicting disease progression for patients diagnosed with HCM in terms of adverse remodeling of the heart during a 10-year period. METHODS: The method consisted of 6 predictive regression models that independently predict future values of 6 clinical characteristics: left atrial size, left atrial volume, left ventricular ejection fraction, New York Heart Association functional classification, left ventricular internal diastolic diameter, and left ventricular internal systolic diameter. We supplemented each prediction with the explanation that is generated using the Shapley additive explanation method. RESULTS: The final experiments showed that predictive error is lower on 5 of the 6 constructed models in comparison to experts (on average, by 0.34) or a consortium of experts (on average, by 0.22). The experiments revealed that semisupervised learning and the artificial data from virtual patients help improve predictive accuracies. The best-performing random forest model improved R2 from 0.3 to 0.6. CONCLUSIONS: By engaging medical experts to provide interpretation and validation of the results, we determined the models' favorable performance compared to the performance of experts for 5 of 6 targets.

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.

LVAD decommissioning for myocardial recovery: Long-term ventricular remodeling and adverse events.

BACKGROUND: Left ventricular assist devices (LVADs) mechanically unload the heart and coupled with neurohormonal therapy can promote reverse cardiac remodeling and myocardial recovery. Minimally invasive LVAD decommissioning with the device left in place has been reported to be safe over short-term follow-up. Whether device retention reduces long-term safety, or sustainability of recovery is unknown. METHODS: This is a dual-center retrospective analysis of patients who had achieved responder status (left ventricular ejection fraction, LVEF ≥40% and left ventricular internal diastolic diameter, LVIDd ≤6.0 cm) and underwent elective LVAD decommissioning for myocardial recovery from May 2010 to January 2020. All patients had outflow graft closure and driveline resection with the LVAD left in place. Emergent LVAD decommissioning for an infection or device thrombosis was excluded. Patients were followed with serial echocardiography for up to 3-years. The primary clinical outcome was survival free of heart failure hospitalization, LVAD reimplantation, or transplant. RESULTS: During the study period 515 patients received an LVAD and 29 (5.6%) achieved myocardial recovery, 12 patients underwent total device explantation or urgent device decommissioning, 17 patients underwent elective LVAD decommissioning, and were included in the analysis. Median age of patients at LVAD implantation was 42 years (interquartile range, IQR: 25-54 years), all had a nonischemic cardiomyopathy, and 5 (29%) were female. At LVAD implantation, median LVEF was 10% (IQR: 5%-15%), and LVIDd 6.6 cm (IQR: 5.8-7.1 cm). There were 11 hydrodynamically levitated centrifugal-flow (65%), and 6 axial-flow LVADs (35%). The median duration of LVAD support before decommissioning was 28.7 months (range 13.5-36.2 months). As compared to the turndown study parameters, 1-month post-decommissioning, median LVEF decreased from 55% to 48% (p = 0.03), and LVIDd increased from 4.8 cm to 5.2 cm (p = 0.10). There was gradual remodeling until 6 months, after which there was no statistical difference on follow-up through 3-years (LVEF 42%, LVIDd 5.6 cm). Recurrent infections affected 41% of patients leading to 3 deaths and 1 complete device explant. Recurrent HF occurred in 1 patient who required a transplant. Probability of survival free of HF, LVAD, or transplant was 94% at 1-year, and 78% at 3-years. CONCLUSIONS: LVAD decommissioning for myocardial recovery was associated with excellent long-term survival free from recurrent heart failure and preservation of ventricular size and function up to 3-years. Reducing the risk of recurrent infections, remains an important therapeutic goal for this management strategy.

Prognostic Value of Peak Oxygen Uptake in Patients Supported With Left Ventricular Assist Devices (PRO-VAD).

OBJECTIVES: The purpose of this study was to examine whether peak oxygen uptake (pVO2) and other cardiopulmonary exercise test (CPET)-derived variables could predict intermediate-term mortality in stable continuous flow LVAD recipients. BACKGROUND: pVO2 is a cornerstone in the selection of patients for heart transplantation, but the prognostic power of pVO2 obtained in patients treated with a left ventricular assist device (LVAD) is unknown. METHODS: We collected data for pVO2 and outcomes in adult LVAD recipients in a retrospective, multicenter study and evaluated cutoff values for pVO2 including: 1) values above or below medians; 2) grouping patients in tertiles; and 3) pVO2 ≤14 ml/kg/min if the patient was not treated with beta-blockers (BB) or pVO2 ≤12 ml/kg/min if the patient was taking BB therapy. RESULTS: Nine centers contributed data from 450 patients. Patients were 53 ± 13 years of age; 78% were male; body mass index was 25 ± 5 kg/m2 with few comorbidities (stroke: 11%; diabetes: 18%; and peripheral artery disease: 4%). The cause of heart failure (HF) was most often nonischemic (66%). Devices included were the HeartMate II and 3 (Abbott); and Heartware ventricular assist devices Jarvik and Duraheart (Medtronic). The index CPET was performed at a median of 189 days (154-225 days) after LVAD implantation, and mean pVO2 was 14.1 ± 5 ml/kg/min (47% ± 14% of predicted value). Lower pVO2 values were strongly associated with poorer survival regardless of whether patients were analyzed for absolute pVO2 in ml/kg/min, pVO2 ≤12 BB/14 ml/kg/min, or as a percentage of predicted pVO2 values (P ≤ 0.001 for all). For patients with pVO2 >12 BB/14 and ventilation/carbon dioxide relationship (VE/VCO2) slope <35, the 1-year survival was 100%. CONCLUSIONS: Even after LVAD implantation, pVO2 has prognostic value, similar to HF patients not supported by mechanical circulatory support devices. (PROgnostic Value of Exercise Capacity Measured as Peak Oxygen Uptake [pVO2] in Recipients of Left Ventricular Assist Devices [PRO-VAD]; NCT04423562).