• cardiovascular diseases
• epinephrine
• hypertension
• muscle, skeletal
• sarcopenia

• Humans
• Aging/metabolism
• Aging/physiology
• Muscle, Skeletal/metabolism
• Muscle, Skeletal/physiology
• Obesity/metabolism
• Obesity/physiopathology
• Obesity/therapy
• Exercise/physiology
• Animals
• Signal Transduction
• Energy Metabolism

• R01 DK133859 NIDDK NIH HHS
• T32 HL166132 NHLBI NIH HHS

• Body mass index
• Infective endocarditis
• Korean
• Underweight

• Humans
• Heart Failure/physiopathology
• Heart Failure/complications
• Heart Failure/psychology
• Male
• Cross-Sectional Studies
• Quality of Life
• Middle Aged
• Female
• Respiratory Muscles/physiopathology
• Muscle Strength
• Aged
• Surveys and Questionnaires
• Stroke Volume

• Exercise training
• Palliative care
• Physical function
• Quality of life
• Sports

• Humans
• Quality of Life
• Palliative Care
• Feasibility Studies
• Exercise
• Exercise Therapy

• Universitätsklinikum RWTH Aachen (8915)

• Humans
• Female
• Cardiac Rehabilitation
• Quality of Life
• Outpatients
• Retrospective Studies
• Heart-Assist Devices
• Cardiomyopathies
• Heart Failure

• blood pressure
• exercise
• hypertension
• rehabilitation

• Humans
• Blood Pressure/physiology
• High-Intensity Interval Training
• Exercise Tolerance
• Hypertension/therapy
• Exercise/physiology

• COVID-19
• aftercare
• cardiac telerehabilitation
• cardiology
• health care costs
• quality of life

Impaired exercise capacity is the key symptom of heart failure (HF) and is associated with reduced quality of life and higher mortality rates. Unfortunately, current therapies, although generally lifesaving, have only small or marginal effects on exercise capacity. Specific strategies to alleviate exercise intolerance may improve quality of life, while possibly improving prognosis as well. There is overwhelming evidence that physical exercise improves performance in cardiac and skeletal muscles in health and disease. Unravelling the mechanistic underpinnings of exercise‐induced improvements in muscle function could provide targets that will allow us to boost exercise performance in HF. With the current review we discuss: (i) recently discovered signalling pathways that govern physiological muscle growth as well as mitochondrial quality control mechanisms that underlie metabolic adaptations to exercise; (ii) the mechanistic underpinnings of exercise intolerance in HF and the benefits of exercise in HF patients on molecular, functional and prognostic levels; and (iii) potential molecular therapeutics to improve exercise performance in HF. We propose that novel molecular therapies to boost adaptive muscle growth and mitochondrial quality control in HF should always be combined with some form of exercise training.

• Cardiac and skeletal muscle
• Exercise intolerance
• Exercise training
• Heart failure
• Mitochondrial adaptation
• Physiological muscle hypertrophy

• Guidelines
• adult congenital heart disease
• aortopathies
• arrhythmias
• cancer
• cardiomyopathy
• cardiovascular risk factors
• chronic coronary syndromes
• exercise
• heart failure
• peripheral vascular disease
• pregnancy
• recommendations
• risk stratification
• sport – special environments
• valvular heart disease

• Cardiology
• Cardiovascular Diseases/prevention & control
• Exercise
• Humans
• Sports

• IK6 RX002477 RRD VA

• Diabetes Mellitus, Type 2/complications
• Diabetes Mellitus, Type 2/drug therapy
• Glucose
• Heart Failure/drug therapy
• Humans
• Myocardium
• Sodium
• Sodium-Glucose Transporter 2 Inhibitors
• Symporters

• Buddhist
• Exercise capacity
• Heart failure
• Quality of life
• Walking meditation

To explore the beneficial effects and underlying mechanisms of aerobic exercise on chronic heart failure (CHF).

A CHF rat model was induced via left anterior descending coronary artery ligation. Four weeks post-surgery, CHF rats received aerobic exercise training over an 8-week period and cardiac function indexes including xxx were analyzed. To investigate the mechanisms involved in the aerobic exercise-induced benefits on CHF, overexpression of the long non-coding RNA MALAT1 was examined both in vivo and in vitro. Furthermore, the interaction between MALAT1 and the microRNA miR-150-5p and the downstream PI3K/Akt signaling pathway was investigated.

Compared to the control group, the CHF rats showed evidence of left ventricular dysfunction including aggravated cardiac function indexes and lung to body weight ratio. The Masson staining demonstrated a significant degree of blue-stained fibrotic myocardial tissue in CHF rats compared to control rats. Furthermore, the levels of collagen I and collagen II were also markedly increased in CHF rats. Aerobic exercise improved cardiac function and left ventricular remodeling in rats with CHF. There was a significant reduction in the levels of the reactive oxygen species (ROS), inflammatory cytokines including TNF-α, IL-6, and IL-1β, and inflammatory mediums containing the matrix metalloproteinases (MMPs) MMP-2 and MMP-9. Moreover, CHF rats receiving aerobic exercise showed decreased myocardial apoptosis and increased expression of autophagy-related proteins including beclin-1 and LC3B-II. Overexpression of the lncRNA MALAT1 eliminated all the beneficial effects related to aerobic exercise in CHF rats. Subsequent investigations demonstrated that miR-150-5p expression was up-regulated in CHF-Tr rats and down-regulated in CHF-Tr-MALAT1 rats. Furthermore, the downstream PI3K/Akt signaling pathway was re-activated in CHF-Tr-MALAT1 rats. In vitro experiments revealed that overexpression of MALAT1 reduced the miR-150-5p levels, resulting in increased cellular apoptosis and less autophagy. In addition, overexpression of MALAT1 suppressed the downstream PI3K/Akt signaling pathway. Restoring miR-150-5p level with a miR-150-5p mimic decreased the cellular apoptosis and increased autophagy, and the downstream PI3K/Akt signaling pathway was re-activated.

Aerobic exercise improved cardiac function through inhibition of the lncRNA MALAT1 in CHF, and the potential mechanisms may be mediated via the miR-150-5p/PI3K/Akt signaling pathway.

• Aerobic exercise
• chronic heart failure (CHF)
• metastasis-associated lung adenocarcinoma transcript 1

Heart failure is a chronic disease affecting patient morbidity and mortality. Current guidelines for heart failure patient treatment are focused on improving their clinical status, functional capacity, and quality of life. However, these guidelines implement numerous instructions including medical treatment adherence, physical activity, and self-care management. The complexity of the therapeutic instructions makes them difficult to follow especially by older adults.

The challenge of this project is to (1) measure real-life adherence to a regular physical exercise program and (2) attempt to influence older adult patients with heart failure toward embracing a more physically active self-care lifestyle.

This research consists of two studies, including a lab experiment and a pragmatic evaluation of technology at patients’ homes. The lab experiment aims at exploring in an objective way (measuring neurophysiological responses to stimuli) patient engagement with different characteristics of virtual agents, while the home study is a 3-phase prospective study where the developed technology platform is tested by heart failure patients in their own home environments. Patients undergo evaluation of their physical activity and cognitive status using standard evaluation methods (6-minute walk test, questionnaires) and receive wearable devices to accurately measure everyday life activity levels (home study phases 1-3). During home study phases 2 and 3, exergames (serious games for physical exercise) to provide a physical exercise plan as a joyful activity are delivered to patients’ private households and e-coaching techniques are implemented in the final phase (home study phase 3) of the protocol, to influence patient attitudes toward a more healthy and recommended lifestyle.

The trial is still ongoing. Recruitment is ongoing, and the project has progressed for some participants through phase 2 of the home study. The sample size for both studies is 28 participants; 10 have already been included in the study, and both baseline clinical and patient-reported outcome data are retrieved. Phases 2 and 3 of the home pilot study are expected to be completed within 6 months.

The main challenge of the project is the change of attitude of older age heart failure patients through an e-coaching system. Given the adoption of a cocreation and living lab approach and the main objective for real-life evaluation, the project is ready to react to any collected feedback, even during the implementation of the research plan. Clinical assessment and objective evaluation are expected to provide all required information for reliable findings.

ClinicalTrials.gov NCT03877328; https://clinicaltrials.gov/ct2/show/NCT03877328

DERR1-10.2196/17714

• adherence
• chronic heart failure
• e-coaching
• electroencephalogram
• exergames
• treatment adherence
• wearable monitoring

• Heart failure
• exercise
• functional capacity
• rehabilitation nurse
• safety

Although low levels of reactive oxygen species (ROS) are beneficial for the organism ensuring normal cell and vascular function, the overproduction of ROS and increased oxidative stress levels play a significant role in the onset and progression of cardiovascular diseases (CVDs). This paper aims at providing a thorough review of the available literature investigating the effects of acute and chronic exercise training and detraining on redox regulation, in the context of CVDs. An acute bout of either cardiovascular or resistance exercise training induces a transient oxidative stress and inflammatory response accompanied by reduced antioxidant capacity and enhanced oxidative damage. There is evidence showing that these responses to exercise are proportional to exercise intensity and inversely related to an individual’s physical conditioning status. However, when chronically performed, both types of exercise amplify the antioxidant defense mechanism, reduce oxidative stress and preserve redox status. On the other hand, detraining results in maladaptations within a time-frame that depends on the exercise training intensity and mode, as high-intensity training is superior to low-intensity and resistance training is superior to cardiovascular training in preserving exercise-induced adaptations during detraining periods. Collectively, these findings suggest that exercise training, either cardiovascular or resistance or even a combination of them, is a promising, safe and efficient tool in the prevention and treatment of CVDs.

• combined exercise
• inactivity
• oxidative stress
• redox status
• resistance exercise

• Small molecule drug discovery
• adult human primary cardiomyocytes
• atrial fibrillation
• cardiotoxicity
• heart failure
• human heart
• translational sciences

• cardiovascular
• exercise
• myokines
• obesity—complications
• type 2 diabetes

• K01 DK116916 NIDDK NIH HHS
• R01 HL138738 NHLBI NIH HHS

• Cardiac repair
• Heart failure
• Leukocytes
• Myocardial infarction
• Resolution of inflammation
• Specialized pro-resolving mediators

• Patient adherence
• cardiac care
• cardiac rehabilitation
• cardiovascular disease
• daily physical activity
• lifestyle

Heart failure (HF), the leading cause of morbidity and mortality in the US, affects 6.6 million adults with an estimated additional 3 million people by 2030. More than 50% of HF patients have heart failure with preserved left ventricular ejection fraction (HFpEF). These patients have impaired cardiac muscle relaxation and diastolic filling, which investigators have associated with cellular energetic impairment. Patients with HFpEF experience symptoms of: (1) fatigue; (2) shortness of breath; and (3) swelling (edema) of the lower extremities. However, current HF guidelines offer no effective treatment to address these underlying pathophysiologic mechanisms. Thus, we propose a biobehavioral symptom science study using ubiquinol and D-ribose (therapeutic interventions) to target mitochondrial bioenergetics to reduce the complex symptoms experienced by patients with HFpEF.

Using a randomized, double-blind, placebo-controlled design, the overall objective is to determine if administering ubiquinol and/or D-ribose to HFpEF patients for 12 weeks would decrease the severity of their complex symptoms and improve their cardiac function. The measures used to assess patients’ perceptions of their health status and level of vigor (energy) will be the Kansas City Cardiomyopathy Questionnaire (KCCQ) and Vigor subscale of the Profile of Mood States. The 6-min walk test will be used to test exercise tolerance. Left ventricular diastolic function will be assessed using innovative advanced echocardiography software called speckle tracking. We will measure B-type natriuretic peptides (secreted from ventricles in HF) and lactate/ATP ratio (measure of cellular energetics).

Ubiquinol (active form of Coenzyme Q10) and D-ribose are two potential treatments that can positively affect cellular energetic impairment, the major underlying mechanism of HFpEF. Ubiquinol, the reduced form of CoQ10, is more effective in adults over the age of 50. In patients with HFpEF, mitochondrial deficiency of ubiquinol results in decreased adenosine triphosphate (ATP) synthesis and reduced scavenging of reactive oxygen species. D-ribose is a substrate required for ATP synthesis and when administered has been shown to improve impaired myocardial bioenergetics. Therefore, if the biological underpinning of deficient mitochondrial ATP in HFpEF is not addressed, patients will suffer major symptoms including lack of energy, fatigue, exertional dyspnea, and exercise intolerance.

ClinicalTrials.gov Identifier: NCT03133793; Data of Registration: April 28, 2017.

• Bioenergetics
• D-ribose
• Heart failure with preserved ejection fraction (HFpEF); ubiquinol