Exercise Training for Heart Failure

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Stanford University

Must not be taking: Insulin, Antidepressants, Antipsychotics, others

Disqualifiers: Diabetes, COPD, Cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to discover how exercise improves heart failure symptoms by examining changes in blood proteins. Participants with heart failure will either undergo a 12-week cardiac rehabilitation program (exercise therapy) or delay starting it to observe exercise's molecular impact. The ultimate goal is to identify proteins that future medications can target to mimic exercise benefits. The trial seeks individuals with heart failure who can exercise on a treadmill and have not participated in cardiac rehabilitation in the past year. As an unphased trial, participants can contribute to groundbreaking research that may lead to new heart failure treatments.

Will I have to stop taking my current medications?

The trial requires participants to stop taking certain medications, including steroids, insulin, and some psychiatric drugs. If you're on any of these, you may need to stop or adjust them before joining the study.

What prior data suggests that cardiac rehabilitation is safe for heart failure patients?

Research shows that cardiac rehabilitation is generally safe and well-tolerated for people with heart failure. Studies have demonstrated that it can help lower the risk of future heart problems because cardiac rehab includes exercise, education, and counseling, which together support heart health.

One study found that patients who participated in cardiac rehab had fewer overall health issues and specific heart failure problems. The REHAB-HF trial confirmed that cardiac rehab is safe, even for older patients with heart failure.

While cardiac rehab involves physical activity, which might seem challenging, it is designed to be safe and beneficial for the heart. Always consult a healthcare provider if there are any concerns about starting a new exercise routine. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about this trial because it explores how exercise training, specifically through cardiac rehabilitation, can help people with heart failure beyond the usual medication and device-based treatments. The trial is unique in that it looks at both the immediate and long-term effects of exercise on heart health, which could lead to a better understanding of how regular physical activity impacts heart failure. By comparing the outcomes of patients who undergo exercise training with those who do not, researchers hope to uncover the potential of exercise as a powerful tool in managing heart failure, possibly offering a natural and effective complement to existing treatments.

What evidence suggests that cardiac rehabilitation is effective for heart failure?

This trial will compare the effects of cardiac rehabilitation with and without an initial acute exercise session. Studies have shown that cardiac rehabilitation can greatly benefit people with heart failure. Research indicates that this exercise program can lower the risk of death from any cause, including heart failure. For patients, this means improved daily life and overall health. Additionally, one study found that cardiac rehab can enhance heart function and quality of life. Experts agree that cardiac rehabilitation effectively reduces symptoms and improves outcomes in heart failure patients. ^{2 3 5 6 7}

Who Is on the Research Team?

Daniel H Katz, MD

Principal Investigator

Stanford University

Are You a Good Fit for This Trial?

This trial is for adults aged 18-89 with heart failure where the heart's pumping power is reduced (ejection fraction <40%). Participants must be willing to undergo cardiac rehabilitation and not be pregnant, planning pregnancy, or have given birth in the last year. They should not be on certain medications that could affect the study results or have had recent psychiatric hospitalizations.

Inclusion Criteria

I am willing to join a heart health program.

Not be pregnant or lactating in the last 12 months, or planning to become pregnant for the next 4 months. A pregnancy test will be performed on the day of DXA scan in women of child-bearing potential. Not be post-partum during the last 12 months.

Be willing to provide informed consent for all study procedures

Exclusion Criteria

I am taking medication for diabetes or to lower my blood sugar.

I am not taking any drugs to specifically increase muscle size.

My kidneys are not working well (GFR <60).

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Acute Exercise and Blood Sampling

Participants undergo a 40-minute bout of moderate intensity exercise with blood samples collected before and after at 10, 30, and 210 minutes.

1 day

1 visit (in-person)

Cardiac Rehabilitation

Participants engage in a 12-week exercise program called cardiac rehabilitation.

12 weeks

Regular visits (in-person)

Follow-up

Participants are monitored for changes in proteomic profiles and cardiopulmonary fitness after the intervention.

12 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Cardiac rehabilitation

Trial Overview

The study aims to understand how a 12-week cardiac rehabilitation exercise program affects protein levels in blood samples of heart failure patients. By comparing these changes to those whose rehab is delayed, researchers hope to identify potential targets for 'exercise-in-a-pill' treatments.

How Is the Trial Designed?

Group I: Active arm: Acute exercise + 12 weeks Cardiac Rehabilitation Experimental Treatment 2 Interventions

This arm includes two-thirds of enrollees and focuses on both acute and chronic effects of exercise. Qualifying participants with heart failure randomized to this arm will undergo a 40 minute bout of moderate intensity exercise on a date prior to beginning in cardiac rehabilitation. Blood samples will be collected before and after the acute bout at 10, 30, and 210 minutes after exercise. Participants will then go to cardiac rehabilitation for a 12 week period. A single blood sample will be obtained at 6 weeks. The participants will return after the 12 weeks of cardiac rehabilitation for a second bout of acute exercise and blood sampling identical to the first. Finally, 12 weeks after completion of cardiac rehab, patients will return for another single blood sample.

Group II: Control arm: No exercise Active Control 1 Intervention

This arm includes one-third of enrollees and serves as control. Qualifying participants with heart failure randomized to this arm will begine with a 40 minute period of rest on a date prior to beginning in cardiac rehabilitation. Blood samples will be collected before and after the the 40 minute period at 10, 30, and 210 minutes after exercise. Participants will then defer cardiac rehabilitation for a 12 week period. A single blood sample will be obtained at 6 weeks of this control intervention period. The participants will return after the 12 weeks of control intervention for an actual bout of acute exercise and blood sampling identical to those completed by the active arm. They will then enter cardiac rehabilitation as per standard of care. Finally, 12 weeks after completion of cardiac rehab, patients will return for another single blood sample.

Cardiac rehabilitation is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Cardiac rehabilitation for:

• Heart failure
• Coronary artery disease
• Post-myocardial infarction

Approved in United States as Cardiac rehabilitation for:

• Heart failure
• Coronary artery disease
• Post-myocardial infarction
• Chronic obstructive pulmonary disease

Approved in Canada as Cardiac rehabilitation for:

• Heart failure
• Coronary artery disease
• Post-myocardial infarction

Approved in Japan as Cardiac rehabilitation for:

• Heart failure
• Coronary artery disease

Who Is Running the Clinical Trial?

Stanford University

Lead Sponsor

Trials

2,527

Recruited

17,430,000+

American Heart Association

Collaborator

Trials

352

Recruited

6,196,000+

National Heart, Lung, and Blood Institute (NHLBI)

Collaborator

Trials

3,987

Recruited

47,860,000+

Published Research Related to This Trial

Cardiac rehabilitation significantly benefits heart failure patients by enhancing their physical capacity and quality of life, while also reducing comorbidities and hospitalizations.

Physiotherapy plays a crucial role in cardiac rehabilitation, providing structured and multidisciplinary care that can be delivered both on an outpatient basis and during hospital stays.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cardiac rehabilitation for heart failure patients]. Agard, O., Cristobal, L., Caffray, M.[2013]

Exercise training is safe and beneficial for patients with heart failure, improving functional capacity, quality of life, and even survival rates, as shown in various studies.

Supervised exercise programs, particularly in cardiac rehabilitation settings, yield the best outcomes due to personalized exercise prescriptions and comprehensive management of patients' health needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac rehabilitation: a comprehensive program for the management of heart failure. Boudreau, M., Genovese, J.[2019]

In a study involving 25,420 patients undergoing cardiac rehabilitation, the rate of severe cardiovascular events during exercise training was very low, with only 20 serious events reported, indicating a high level of safety for patients participating in these programs.

The study found that the event rate was 1 per 49,565 patient-hours of exercise training, and there were no fatal complications or emergency defibrillations, suggesting that supervised exercise training is a safe practice for cardiac rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of exercise training for cardiac patients: results of the French registry of complications during cardiac rehabilitation. Pavy, B., Iliou, MC., Meurin, P., et al.[2022]

Physical exercise is a crucial therapy for chronic heart failure, significantly improving exercise capacity, quality of life, and reducing hospitalizations, yet it is underutilized in clinical practice despite strong evidence from meta-analyses.

Both moderate continuous endurance training and interval training are safe and effective for chronic heart failure patients, and combining endurance with resistance training can enhance benefits, emphasizing the importance of tailored exercise regimens and monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Exercise training as a key component of heart failure therapy]. Dörr, M., Halle, M.[2018]

Exercise training in chronic heart failure patients has shown significant improvements in exercise capacity, comparable to the best pharmacological treatments, without deteriorating cardiac function.

Despite the lack of definitive evidence on improved survival rates, exercise training is recommended for selected heart failure patients, as it enhances muscle function, reduces ventilation during exercise, and improves overall quality of life when supervised properly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Physical activity and training in heart failure]. Weber, T., Kirchgatterer, A., Auer, J., et al.[2019]

Regular exercise training is highly recommended for heart failure patients, supported by strong evidence, yet many patients remain inactive due to various barriers.

Home telerehabilitation is proposed as an effective solution to encourage physical activity among heart failure patients, addressing the limitations of traditional outpatient rehabilitation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

How to do: telerehabilitation in heart failure patients. Piotrowicz, E.[2019]

Cardiac rehabilitation, which includes exercise training and various therapeutic adaptations, is crucial for patients with chronic heart failure and has been shown to improve functional capacity and reduce symptoms.

The program not only enhances physical health but also lowers cardiac morbidity and mortality by improving muscle function, endothelial health, and reducing sympathetic tone, which can help prevent arrhythmias.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Role of rehabilitation in the treatment of chronic heart insufficiency]. Iliou, MC.[2019]

Rehabilitation for heart failure has been shown to effectively improve peripheral vascular and muscular abnormalities, demonstrating both efficacy and excellent tolerance in patients.

Exercise rehabilitation can enhance functional outcomes and quality of life, proving to be as effective as medical treatments for patients with left ventricular systolic dysfunction who have not fully responded to medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Physical rehabilitation of patients suffering from chronic heart failure]. Cohen Solal, A., Beauvais, F., Tabet, JY.[2019]

Recent studies indicate that regular exercise training is safe and effective for patients with stable Class II and III heart failure, improving exercise tolerance and quality of life.

Moderate physical activity, such as 30 to 60 minutes of walking or cycling 3 to 5 days a week, can help reverse some muscle abnormalities and reduce stress on the heart, but more research is needed to fully understand its impact on long-term health outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exercise training in heart failure. Afzal, A., Brawner, CA., Keteyian, SJ.[2019]

A study involving 80 patients with chronic heart failure showed that a structured endurance training program was safe, with no reported adverse events, and led to significant improvements in exercise time and quality of life.

The training increased the anaerobic threshold and decreased the ventilatory equivalent for carbon dioxide during submaximal exercise, indicating enhanced exercise capacity, although it did not significantly improve peak oxygen consumption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and effects of physical training in chronic heart failure. Results of the Chronic Heart Failure and Graded Exercise study (CHANGE) Wielenga, RP., Huisveld, IA., Bol, E., et al.[2007]

Supervised exercise training and individual physical activity are strongly recommended for all patients with heart failure, starting in the hospital after stabilization and continuing in rehabilitation programs post-discharge.

These exercise programs, which include endurance, resistance, and respiratory training, not only help improve physical fitness but also aim to enhance health literacy for better long-term adherence to physical activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Exercise Training and Physical Activity in Patients with Heart Failure]. Wilhelm, M.[2018]

Cardiac rehabilitation (CR) is a safe and effective multidisciplinary program that significantly improves quality of life, functional capacity, and reduces hospitalizations related to heart failure in patients.

Despite its proven benefits and strong recommendations, CR is underutilized, highlighting the need for healthcare providers and payers to prioritize its integration into standard care for heart failure patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac Rehabilitation for Patients With Heart Failure: JACC Expert Panel. Bozkurt, B., Fonarow, GC., Goldberg, LR., et al.[2021]

Citations

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Core Components of Cardiac Rehabilitation Programs

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Abstract. Background: This study aimed to clarify the effects of exercise-based cardiac rehabilitation (CR) on patients with heart failure.

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jamanetwork.com/journals/jamanetworkopen/fullarticle/2836926

Early Cardiac Rehabilitation and Heart Failure Recovery

The landmark REHAB-HF (Rehabilitation Therapy in Older Acute Heart Failure Patients) randomized clinical trial (RCT) filled this knowledge gap.

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nature.com/articles/s41598-024-82608-z

Effects of exercise based cardiac rehabilitation delivery ...

Chronic heart failure (CHF) represents one of the most severe and advanced stages of cardiovascular disease. Despite the critical importance ...

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Eligible participants include those with heart failure, congenital heart disease, a recent myocardial infarction, and a history of cardiac ...

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jacc.org

jacc.org/doi/10.1016/j.jacc.2021.01.030

Cardiac Rehabilitation for Patients With Heart Failure

Race, exercise training, and outcomes in chronic heart failure: findings from Heart Failure—A Controlled Trial Investigating Outcomes in Exercise Training ...