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

Trial Summary

What is the purpose of this trial?

The heart failure syndrome that occurs when the heart is too sick to properly do its job. One of the main symptoms is difficulty with exercise. One way to improve symptoms is to start patients in a 12 week exercise program called cardiac rehabilitation. Cardiac rehabilitation been shown to improve symptoms for heart failure patients. However, the investigators do not know exactly what exercise does to the molecules that make up the human body. If the investigators could answer this question, the investigators might find a whole new way to treat the symptoms of heart failure. Therefore the investigators want to know what molecules might be responsible for the benefits of exercise. The plan for this study is to measure the levels of thousands of proteins in blood samples which come from people with heart failure and see how those levels change after 12 weeks of cardiac rehabilitation, compared to the protein levels in patients whose cardiac rehabilitation is delayed until after the study period. If the investigators know the proteins that change with exercise, the investigators can then look to see if targeting these proteins with medicines can mimic the benefits of exercise. The long term goal of our work is to identify "exercise-in-a-pill" medicines that will help people with heart failure.

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 data supports the effectiveness of the treatment for heart failure?

Research shows that cardiac rehabilitation, which includes exercise training, can improve exercise tolerance, reduce symptoms, and enhance quality of life for heart failure patients. It also helps reduce hospitalizations and improve heart function, making it a beneficial part of heart failure management. ^{1 2 3 4 5}

Is exercise training safe for heart failure patients?

Exercise training, including cardiac rehabilitation, is generally considered safe for heart failure patients and can improve quality of life and functional capacity. Supervised settings are particularly effective in ensuring safety and maximizing benefits. ^{1 6 7 8 9}

How does cardiac rehabilitation differ from other treatments for heart failure?

Cardiac rehabilitation is unique because it combines exercise training with lifestyle changes and psychological support, improving heart function and quality of life without medication. Unlike drug treatments, it focuses on physical activity tailored to each patient's tolerance, aiming to enhance overall health and reduce heart-related complications. ^{2 5 10 11 12}

Research Team

Daniel H Katz, MD

Principal Investigator

Stanford University

Eligibility Criteria

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 between 18 and 89 years old.

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.

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

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)

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. Poland pubmed.ncbi.nlm.nih.gov

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

2. France pubmed.ncbi.nlm.nih.gov

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

3. France pubmed.ncbi.nlm.nih.gov

[Cardiac rehabilitation for heart failure patients]. [2013]

4. France pubmed.ncbi.nlm.nih.gov

[Physical rehabilitation of patients suffering from chronic heart failure]. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

Exercise training in heart failure. [2019]

6. United States pubmed.ncbi.nlm.nih.gov

Cardiac Rehabilitation for Patients With Heart Failure: JACC Expert Panel. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Safety of exercise training for cardiac patients: results of the French registry of complications during cardiac rehabilitation. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Cardiac rehabilitation: a comprehensive program for the management of heart failure. [2019]

9. England 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) [2007]

10. Switzerland pubmed.ncbi.nlm.nih.gov

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

11. Germany pubmed.ncbi.nlm.nih.gov

[Exercise training as a key component of heart failure therapy]. [2018]

12. Germany pubmed.ncbi.nlm.nih.gov

[Physical activity and training in heart failure]. [2019]