Exercise Training for Amyloid Cardiomyopathy

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Brigham and Women's Hospital

Must be taking: Tafamidis

Disqualifiers: Coronary artery disease, Aortic stenosis, Kidney disease, others

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

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

40 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, participants in aim 2 must be taking tafamidis, so you may need to continue that medication if you are already on it.

What data supports the effectiveness of this treatment for amyloid cardiomyopathy?

The research suggests that cardiopulmonary exercise testing (CPET) can help assess the functional capacity and predict outcomes in patients with cardiac amyloidosis, which may indirectly support the use of exercise training and rehabilitation in managing the condition. ^{1 2 3 4 5}

Is exercise training safe for people with heart conditions?

Exercise training, including resistance and aerobic exercises, is generally safe for people with heart conditions like chronic heart failure and hypertension. Studies show it can improve muscle strength, exercise capacity, and quality of life without harmful effects on heart function. ^{6 7 8 9 10}

How does exercise training differ from other treatments for amyloid cardiomyopathy?

Exercise training is unique because it focuses on improving heart function and overall health through physical activity, rather than using medications or surgery. It includes endurance, resistance, and respiratory exercises, which can enhance exercise capacity, quality of life, and reduce hospitalizations, making it a holistic approach compared to traditional treatments. ^{11 12 13 14 15}

What is the purpose of this trial?

Transthyretin cardiac amyloidosis causes debilitating heart failure in older adults. The proposed research will develop a personalized exercise training program to improve functional capacity in patients on optimal treatment for transthyretin cardiac amyloidosis. This is a vital next step to improve functional capacity and quality of life of people suffering from transthyretin cardiac amyloidosis.

Eligibility Criteria

This trial is for older adults with transthyretin cardiac amyloidosis who can walk and are independent in daily activities. They must be on stable medical treatment, not already doing regular intense exercise, and have heart failure symptoms with a specific biomarker level. People with certain other health conditions or devices like pacemakers that limit exercise aren't eligible.

Inclusion Criteria

I can walk 4 meters on my own and take care of myself.

Your ability to take in oxygen during exercise is less than 80% of what is expected for someone like you.

I have heart failure, need diuretics, and my BNP levels are high.

Exclusion Criteria

I do not have any conditions like a stroke that would stop me from joining the study.

You have more than 70% blockage in your coronary arteries.

I do not have dementia affecting my ability to exercise or follow study instructions.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo 12 weeks of supervised personalized exercise training to improve functional capacity

12 weeks

Weekly supervised exercise sessions

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Exercise Training

Trial Overview The study aims to create a personalized exercise program for patients with transthyretin cardiac amyloidosis to improve their ability to perform physical tasks and enhance life quality. Participants will follow this tailored exercise regimen while being monitored for its effects on their heart condition.

Participant Groups

Group I: Intervention arm Experimental Treatment 1 Intervention

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Findings from Research

In a study of 56 patients with wild-type transthyretin amyloidosis (ATTRwt), increased levels of the VE/VCO2 ratio, along with C-reactive protein, sodium, and creatinine, were identified as significant risk factors for mortality, indicating their potential role in assessing patient outcomes.

The study found that patients with a VE/VCO2 ratio greater than 40 had a significantly lower median survival of 38.54 months compared to 88.69 months for those with a ratio of 40 or less, suggesting that VE/VCO2 could be a useful measure for evaluating the severity of ATTRwt cardiomyopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of Ventilatory Efficiency Slope as a Marker for Increased Mortality in Wild-Type Transthyretin Cardiac Amyloidosis. Yunis, A., Doros, G., Luptak, I., et al.[2020]

In a study of 33 patients with wild-type transthyretin cardiac amyloidosis treated with tafamidis, low peak oxygen consumption (VO2) and peak circulatory power (CP) were found to be significant predictors of worse outcomes, including mortality and the need for heart transplant or palliative care.

Patients who had an exercise duration of less than 5.5 minutes during cardiopulmonary exercise testing also showed a higher risk of adverse outcomes, highlighting the importance of exercise capacity in assessing prognosis for these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic Role of Cardiopulmonary Exercise Testing in Wild-Type Transthyretin Amyloid Cardiomyopathy Patients Treated With Tafamidis. Dalia, T., Acharya, P., Chan, WC., et al.[2022]

In a study of 72 patients with Transthyretin amyloid cardiomyopathy, the CardioPulmonary Exercise Test (CPET) revealed that a significant number of patients (36%) had inadequate blood pressure responses during exercise, indicating potential cardiovascular issues.

The study found that right ventricular function, specifically measured by tricuspidal s' wave, was a strong independent predictor of exercise capacity and ventilatory efficiency, highlighting its importance in assessing patients with ATTR cardiomyopathy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Poor right ventricular function is associated with impaired exercise capacity and ventilatory efficiency in transthyretin cardiac amyloid patients. Bartolini, S., Baldasseroni, S., Fattirolli, F., et al.[2021]

In a study of 150 patients with cardiac amyloidosis, the cardiopulmonary exercise test (CPET) was found to be effective in assessing functional capacity and predicting prognosis, with key metrics like peak oxygen consumption (VO2) and circulatory power being significant indicators of risk.

Patients with a peak VO2 of 13 mL/kg/min or lower, along with elevated NT-proBNP levels, were identified as a very high-risk group for death or heart failure hospitalization, highlighting the importance of CPET in risk stratification for cardiac amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic value of cardiopulmonary exercise testing in cardiac amyloidosis. Nicol, M., Deney, A., Lairez, O., et al.[2022]

In a study of 27 patients with cardiac amyloidosis, reduced peak oxygen uptake (peak V'O2) during cardiopulmonary exercise testing (CPET) was identified as an independent predictor of mortality, with 70% of patients dying within a median follow-up of 38 months.

Patients with lower peak V'O2 also exhibited more severe heart failure symptoms, higher cardiac biomarkers, and impaired heart function, indicating that CPET can effectively assess disease severity in cardiac amyloidosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peak V'O2 is an independent predictor of survival in patients with cardiac amyloidosis. Hein, S., Aus Dem Siepen, F., Bauer, R., et al.[2019]

Exercise training, both aerobic and resistance, significantly improves physical capacity and quality of life in patients with chronic heart failure (CHF), with benefits primarily arising from enhanced peripheral circulation and skeletal muscle function rather than direct effects on the heart.

A study involving 19 CHF patients showed that after 4 months of resistance training and dietary supplementation, participants were able to return to normal activities without complaints, highlighting the safety and efficacy of this rehabilitation approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive rehabilitation in chronic heart failure. Gąsiorowski, A., Dutkiewicz, J.[2013]

Isometric resistance training (IRT) has been shown to significantly lower blood pressure by an average of 7.4/3.3 mmHg, which is comparable to the effects of antihypertensive medications, and can reduce the risk of major cardiovascular events by 13% to 22%.

IRT is safe for a variety of patient populations and is particularly beneficial for individuals who cannot engage in aerobic exercise or have resistant hypertension, requiring only about 17 minutes of training per week.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evidence-based guide to the efficacy and safety of isometric resistance training in hypertension and clinical implications. Baffour-Awuah, B., Pearson, MJ., Dieberg, G., et al.[2023]

Regular exercise significantly benefits patients with heart disease by improving exercise tolerance, controlling risk factors, and potentially influencing the progression of coronary artery disease.

Patients should follow physician-guided exercise plans that include dynamic endurance activities and moderate-intensity circuit weight training, with a recommended duration of 2 to 3 hours per week, while high-risk patients should exercise at lower intensities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Heart patient and sports]. Niederhauser, HU.[2008]

Dynamic resistance training is a safe and effective exercise method for patients with chronic heart failure (CHF), helping to improve muscle strength and function without putting excessive stress on the heart.

Research shows that resistance exercise can lead to significant improvements in exercise tolerance, muscle mass, and overall quality of life for CHF patients, making it a valuable addition to traditional aerobic exercise programs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Resistance exercise training in patients with heart failure. Volaklis, KA., Tokmakidis, SP.[2018]

Resistance training is safe and effective for patients in cardiac rehabilitation, showing fewer signs of myocardial ischemia compared to aerobic training, which may be due to lower heart rates and improved coronary artery filling.

This type of training enhances muscle strength, leading to better exercise performance and quality of life, including improvements in mood and emotional health, although its effects on blood pressure and lipid profiles remain unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of resistance training in heart disease. McCartney, N.[2019]

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]

A 12-week concurrent exercise training program combining aerobic and resistance exercises significantly improved functional capacity and muscular strength in 95 male patients with chronic heart failure, compared to traditional aerobic training alone.

Patients in the concurrent training group experienced greater improvements in quality of life and lower body strength, with no reported side effects leading to discontinuation of the training program.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Concurrent, Within-Session, Aerobic and Resistance Exercise Training on Functional Capacity and Muscle Performance in Elderly Male Patients with Chronic Heart Failure. Volterrani, M., Caminiti, G., Perrone, MA., et al.[2023]

Exercise training significantly improves cardiac symptoms, exercise capacity, and quality of life in patients with chronic heart failure, with benefits including increased ejection fraction and reduced rehospitalization rates.

The training helps counteract peripheral myopathy and may enhance myocardial perfusion, although the exact mechanisms remain unclear; it is recommended as a primary treatment alongside standard pharmacological therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cardiac rehabilitation in patients with heart failure--is there a treatment beyond pharmacotherapy, surgery and device implantation?]. Lefkovits, M.[2013]

Home exercise programs for patients who have had a myocardial infarction can significantly enhance their exercise capacity and overall quality of life.

While some studies indicated that exercise training might cause further damage to the heart in patients with reduced left ventricular function, recent analyses suggest that it can actually promote beneficial remodeling of the heart, especially when combined with ACE inhibition therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Rehabilitative intervention after a myocardial infarct]. Napoli, E.[2006]

In a study of 24 patients with nonischemic dilated cardiomyopathy, a 2-month exercise training program significantly improved peak oxygen uptake (VO2) and VO2 at the lactate threshold, indicating enhanced aerobic capacity.

Despite no changes in left ventricular volumes or systolic function, the exercise training improved diastolic function as evidenced by increased relaxation velocity, suggesting that exercise is safe and beneficial for patients with this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of exercise training on left ventricular volumes and function in patients with nonischemic cardiomyopathy: application of magnetic resonance myocardial tagging. Myers, J., Wagner, D., Schertler, T., et al.[2022]

References

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

Use of Ventilatory Efficiency Slope as a Marker for Increased Mortality in Wild-Type Transthyretin Cardiac Amyloidosis. [2020]

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

Prognostic Role of Cardiopulmonary Exercise Testing in Wild-Type Transthyretin Amyloid Cardiomyopathy Patients Treated With Tafamidis. [2022]

3. Italy pubmed.ncbi.nlm.nih.gov

Poor right ventricular function is associated with impaired exercise capacity and ventilatory efficiency in transthyretin cardiac amyloid patients. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Prognostic value of cardiopulmonary exercise testing in cardiac amyloidosis. [2022]

5. England pubmed.ncbi.nlm.nih.gov

Peak V'O2 is an independent predictor of survival in patients with cardiac amyloidosis. [2019]

6. Poland pubmed.ncbi.nlm.nih.gov

Comprehensive rehabilitation in chronic heart failure. [2013]

7. England pubmed.ncbi.nlm.nih.gov

An evidence-based guide to the efficacy and safety of isometric resistance training in hypertension and clinical implications. [2023]

8. Switzerland pubmed.ncbi.nlm.nih.gov

[Heart patient and sports]. [2008]

9. New Zealand pubmed.ncbi.nlm.nih.gov

Resistance exercise training in patients with heart failure. [2018]

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

Role of resistance training in heart disease. [2019]

11. Switzerland pubmed.ncbi.nlm.nih.gov

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

12. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Concurrent, Within-Session, Aerobic and Resistance Exercise Training on Functional Capacity and Muscle Performance in Elderly Male Patients with Chronic Heart Failure. [2023]

13. Switzerland pubmed.ncbi.nlm.nih.gov

[Cardiac rehabilitation in patients with heart failure--is there a treatment beyond pharmacotherapy, surgery and device implantation?]. [2013]

14. Italy pubmed.ncbi.nlm.nih.gov

[Rehabilitative intervention after a myocardial infarct]. [2006]

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

Effects of exercise training on left ventricular volumes and function in patients with nonischemic cardiomyopathy: application of magnetic resonance myocardial tagging. [2022]