Exercise Training for Amyloid Cardiomyopathy
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: Brigham and Women's Hospital
Must be taking: Tafamidis
Disqualifiers: Coronary artery disease, Aortic stenosis, Kidney disease, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
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.
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.
12345Is 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.
678910How 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.
1112131415Eligibility 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.
+4 more
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.
+14 more
Trial 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
Participant Groups
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.
1Treatment groups
Experimental Treatment
Group I: Intervention armExperimental Treatment1 Intervention
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Brigham and Women's HospitalBoston, MA
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Who Is Running the Clinical Trial?
Brigham and Women's HospitalLead Sponsor
References
Use of Ventilatory Efficiency Slope as a Marker for Increased Mortality in Wild-Type Transthyretin Cardiac Amyloidosis. [2020]Wild-type transthyretin amyloidosis (ATTRwt) results in an infiltrative cardiomyopathy often culminating in symptomatic heart failure. The use of cardiopulmonary exercise testing (CPET) in determining outcomes in ATTRwt cardiac amyloidosis is unknown. Given the emergence of novel therapies to treat transthyretin amyloidosis, we sought to investigate the utility of CPET on outcomes in patients with ATTRwt cardiomyopathy. Fifty-six patients, with biopsy and immunohistochemically proved ATTRwt, were enrolled between 2005 and 2015, as part of an NIH ATTRwt substudy at the Boston University Amyloidosis Center. Patients were prospectively studied, which included laboratory tests, electrocardiogram, echocardiography, in addition to CPET. In this cohort of ATTRwt patients who performed CPET were elderly, all were male, and predominantly white (69.9%). The overall median survival was 59.01 months (95% confidence interval [CI] 49.29 to 88.69). By multivariate analysis, C-reactive protein (CRP; hazard ratio [HR] 1.10 [1.03 to 1.18]), decreased sodium (HR 0.75 [0.58 to 0.97]), creatinine (HR 7.48 [2.44 to 22.98]) and VE/VCO2 (HR 1.10 [1.05 to 1.16]) were significant risk factors for mortality (p <0.05). Peak VO2 was insignificant by both univariate and multivariate analyses. ATTRwt patients with VE/VCO2 >40 had a worse median survival of 38.54 months (95% CI 32.63 to 51.47) versus 88.69 months (95% CI 56.26 to 89.49) than patients with VE/VCO2 slope ≤40. Receiver-operating characteristic curve showed that the combination of VE/VCO2, CRP, sodium, and creatinine (Area under the ROC Curve [AUC], 0.89) predicted 1-year mortality in ATTRwt cardiac amyloidosis. In conclusion, increased VE/VCO2, in combination with CRP, sodium, and creatinine, may identify patients at increased risk of death in ATTRwt cardiomyopathy. VE/VCO2 might have a role in objectively assessing therapeutic response in ATTRwt cardiac amyloidosis.
Prognostic Role of Cardiopulmonary Exercise Testing in Wild-Type Transthyretin Amyloid Cardiomyopathy Patients Treated With Tafamidis. [2022]The prognostic value of cardiopulmonary exercise testing (CPET) in patients with wild-type transthyretin cardiac amyloidosis treated with tafamidis is unknown.
Poor right ventricular function is associated with impaired exercise capacity and ventilatory efficiency in transthyretin cardiac amyloid patients. [2021]CardioPulmonary Exercise Test (CPET) is the gold standard to evaluate functional capacity in patients at high risk of heart failure (HF). Few studies with a limited number of subjects and conflicting results, analyzed the role of CPET in patients with systemic amyloidosis. Aims of our study were the assessment of the response to exercise in patients with Transthyretin amyloid (ATTR) cardiomyopathy (CA), and the correlation of clinical, biohumoral and echocardiographic parameters with CPET parameters, such as VO2 peak and VE/VCO2 slope. From February 2018 to March 2019, 72 cardiac ATTR patients were prospectively enrolled and underwent a complete clinical, biohumoral, echocardiographic and CPET assessment. All patients completed the exercise stress test protocol, without any adverse event. At CPET, they achieved a mean VO2 peak of 14 mL/Kg/min and a mean VE/VCO2 slope of 31. The blood pressure response to exercise was inadequate in 26 (36%) patients (flat in 25 and hypotensive in 1), while 49/72 patients (69%) showed an inadequate heart rate recovery. In multivariate analysis, s' tricuspidalic was the only independent predictor of VO2 peak, while in the two test models performed to avoid collinearity, both TAPSE and s' tricuspidalic were the strongest independent predictors of VE/VCO2 slope. Our data demonstrate the role of right ventricular function as an independent predictor of exercise capacity and ventilatory efficiency in ATTR. In CPET evaluation, a significant proportion of patients presented an abnormal arterial pressure response and heart rate variation to exercise.
Prognostic value of cardiopulmonary exercise testing in cardiac amyloidosis. [2022]In amyloid patients, cardiac involvement dramatically worsens functional capacity and prognosis. We sought to study how the cardiopulmonary exercise test (CPET) could help in functional assessment and risk stratification of patients with cardiac amyloidosis (CA).
Peak V'O2 is an independent predictor of survival in patients with cardiac amyloidosis. [2019]Cardiopulmonary exercise testing (CPET) has repeatedly been reported to reliably predict adverse outcomes in different forms of heart failure. However, it has not been elucidated in detail in cardiac amyloidosis (CA). Therefore, we evaluated the predictive value of CPET parameters in patients with CA regarding disease severity and prediction of mortality.
Comprehensive rehabilitation in chronic heart failure. [2013]Chronic heart failure (CHF) is a complex disease process connected with cardiovascular system as well as other organs and skeletal muscles. In connection with the above, cardiac rehabilitation, consisting of exercise training and diet supplementation, aims at recovery of physical, social and psychic function and removing risk factors influencing the occurrence of circulatory system diseases. Evidence has shown that exercise training in CHF patients, both aerobic and resistance, can increase peak oxygen consumption and exercise capacity, improve NYHA (New York Heart Association) functional class, reduce mortality and improve the quality of life. Evidence suggests that most improvement is due to the effects of training on the peripheral circulation and skeletal muscle, rather than on the heart itself. Exercise training can improve skeletal muscle metabolism, increase blood flow within the active skeletal muscles, increase capillary density, promote the synthesis and release of nitric oxide, improve angiogenesis, and decrease oxidative stress. Physical effort reduces sympathetic arousal and increases parasympathetic arousal, thus reducing cardiac dysrythmia and ischemia. Mitochondria start working harder, as the demand for energy is higher and electron flow provides energy in the form of ATP. Studies have consistently demonstrated that exercise training is safe and has no deleterious effect on central haemodynamics, left ventricular remodeling, systolic or diastolic function, or myocardial metabolism. Taking several supplements that have documented roles in medical therapy, including vitamins B, C and E, coenzyme Q10, alpha-lipoic acid, chromium, omega-3 polyunsaturated fatty acids, L-carnitine, and quercetin, has beneficiary effect on many diseases, including CHF. In our experience, 19 patients with CHF who undertook resistance (weight) training and food supplementation, returned to their normal activities after 4 months, without any complaints.
An evidence-based guide to the efficacy and safety of isometric resistance training in hypertension and clinical implications. [2023]More than 30 randomized controlled trials, supported by individual patient-level and group-level meta-analyses and a Delphi analysis of expert opinion, unequivocally show isometric resistance training (IRT) elicits antihypertensive benefits in healthy people and those with chronic illness. We aim to provide efficacy and safety evidence, and a guide for IRT prescription and delivery. Recommendations are made for the use of IRT in specific patient populations and appropriate methods for IRT delivery. Published data suggest IRT consistently elicits mean blood pressure reductions of 7.4/3.3 mmHg systolic blood pressure/diastolic blood pressure, equivalent to antihypertensive medication monotherapy. Blood pressure reductions of this size are associated with an approximate 13% to 22% reduction in major cardiovascular events. Moreover, IRT is safe in a range of patient populations. We suggest that IRT has the greatest potential benefit when used as an antihypertensive therapy in individuals unwilling and/or unable to complete aerobic exercise, or who have had limited adherence or success with it; individuals with resistant or uncontrolled hypertension, already taking at least two pharmacological antihypertensive agents; and healthy or clinical populations, as an adjunct to aerobic exercise and dietary intervention in those who have not yet attained control of their hypertension. IRT is efficacious and produces clinically meaningful blood pressure reductions (systolic blood pressure, 7 mmHg; diastolic blood pressure, 3 mmHg). IRT is safe and typical program delivery requires only about 17 min weekly. IRT should be used as an adjunct to other exercise modalities, in people unable to complete other types of exercise, or in resistant hypertension.
[Heart patient and sports]. [2008]Patients with heart disease may benefit from scheduled exercising in different ways. Exercise tolerance is increased, risk factors are controlled, and even progression and regression of coronary artery disease can be influenced by training and diet. Psychological effects include lessened depression and reduced anxiety. Overall, regular physical activity is important for maintenance of health and may lead to a better quality of life. In order to minimize the risk of training, the patients should be provided with guidelines for exercising by the physician. Activities should include dynamic endurance exercises and properly selected calisthenics (without a need for high technical skills). Circuit weight training of moderate intensity is helpful for promoting muscle strength. Training has to be followed not less than 2 to 3 hours per week in at least three sessions at an intensity corresponding to 60 to 85% of the maximum heart rate achieved in a symptom-limited maximum exercise-test. Cardiac patients at high risk (decreased left ventricular function, persisting ischaemia, low exercise capacity, severe symptoms, older age) should exercise at lower intensities.
Resistance exercise training in patients with heart failure. [2018]The utility, safety and physiological adaptations of resistance exercise training in patients with chronic heart failure (CHF) are reviewed and recommendations based on current research are presented. Patients with CHF have a poor clinical status and impaired exercise capacity due to both cardiac limitations and peripheral maladaptations of the skeletal musculature. Because muscle atrophy has been demonstrated to be a hallmark of CHF, the main principle of exercise programmes in such patients is to train the peripheral muscles effectively without producing great cardiovascular stress. For this reason, new modes of training as well as new training methods have been applied. Dynamic resistance training, based on the principles of interval training, has recently been established as a safe and effective mode of exercise in patients with CHF. Patients perform dynamic strength exercises slowly, on specific machines at an intensity usually in the range of 50-60% of one repetition maximum; work phases are of short duration (1 : 2). Patients with a low cardiac reserve can use small free weights (0.5, 1 or 3 kg), elastic bands with 8-10 repetitions, or they can perform resistance exercises in a segmental fashion. Based on recent scientific evidence, the application of specific resistance exercise programmes is safe and induces significant histochemical, metabolic and functional adaptations in skeletal muscles, contributing to the treatment of muscle weakness and specific myopathy occurring in the majority of CHF patients. Increased exercise tolerance and peak oxygen consumption (V-dotO(2peak)), changes in muscle composition, increases in muscle mass, alterations in skeletal muscle metabolism, improvement in muscular strength and endurance have also been reported in the literature after resistance exercise alone or in combination with aerobic exercise. According to new scientific evidence, appropriate dynamic resistance exercise should be recommended as a safe and effective alternative training mode (supplementary to conventional aerobic exercise) in order to counteract peripheral maladaptation and improve muscle strength, which is necessary for recreational and daily living activities, and thus quality of life, of patients with stable, CHF.
Role of resistance training in heart disease. [2019]Since the mid-1980s resistance training has become an accepted part of the exercise rehabilitation process for patients eligible for traditional cardiac rehabilitation programs. A growing number of studies have demonstrated the safety of resistance training in Phase III/IV programs (Phase III--community based, beginning 6-12 wk posthospital discharge; a typical patient would be clinically stable with a functional capacity of > or = 5 METs; Phase IV--long-term maintenance) and more recently in Phase II (beginning within 3 wk posthospital discharge and lasting up to 3 months). Evidence is consistent that this form of training provokes fewer signs and symptoms of myocardial ischemia than aerobic testing and training, perhaps because of a lower heart rate (HR) and higher diastolic pressure combining to produce improved coronary artery filling. The major role of resistance training in heart disease patients is to promote increased dynamic muscle strength. Increases in muscular strength have been associated with increased peak exercise performance, improved submaximal endurance, and reduced ratings of perceived leg effort. Two studies show that resistance training may result in improved self-efficacy for strength and exercise tasks and improved quality of life parameters such as total mood disturbance, depression/dejection, fatigue/inertia, and emotional health domain scores. The data on risk factor modification are somewhat equivocal. Studies on blood lipid profiles have mostly been contaminated by confounders, and the effects on blood pressure (BP) are inconsistent. There are encouraging reports that resistance training may increase glucose tolerance and insulin sensitivity, independent of changes in body fat or aerobic capacity. Future studies are needed in patients with congestive heart failure and orthotopic heart transplantation; muscle weakness is common in these groups and makes them excellent candidates to benefit from this form of exercise.
[Exercise Training and Physical Activity in Patients with Heart Failure]. [2018]Exercise Training and Physical Activity in Patients with Heart Failure Abstract. Heart failure is a clinical syndrome with different etiologies and phenotypes. For all forms, supervised exercise training and individual physical activity are class IA recommendations in current guidelines. Exercise training can start in the hospital, immediately after stabilization of acute heart failure (phase I). After discharge, it can continue in a stationary or ambulatory prevention and rehabilitation program (phase II). Typical components are endurance, resistance and respiratory training. Health insurances cover costs for three to six months. Patients with implantable cardioverter defibrillators or left ventricular assist devices may train in experienced centers. Besides muscular reconditioning, a major goal of phase II is to increase health literacy to improve long-term adherence to physical activity. In phase III, heart groups offer support.
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]The best format of exercise training (ET) in the setting of cardiac rehabilitation in patients with chronic heart failure (CHF) is still to be defined. Current guidelines recommend aerobic exercises, such as running and cycling, including some sessions per week of resistance exercise.
[Cardiac rehabilitation in patients with heart failure--is there a treatment beyond pharmacotherapy, surgery and device implantation?]. [2013]The reduced exercise capacity of patients with chronic heart failure cannot be explained solely on the basis of cardiac dysfunction. It seems to be the case that within the frame of the disease progression the importance of peripheral factors steadily increases. Chronic diminished perfusion of skeletal muscles, inactivity as well as harmful neuro-humoral activation leads to myopathy with loss of mitochondria and capillaries and to increased fibrosis. A systematic, controlled and properly dosed training improves in heart failure patients their cardiac symptoms like dyspnoe and exercise capacity. In addition an improved quality of life, augmented ejection fraction, diminished enddiastolic dimensions, improved respiratory efficiency will be achieved and the incidence of rehospitalization decreased. In the European guidelines there is a "class I recommendation" that is of the same class as the recommendation for a pharmacological standard therapy. The exact mechanism of the training of patients with heart failure is not known. In patients with ischemic heart failure training improves the myocardial perfusion due to a reduction of the endothelial dysfunction, and furthermore the training promotes collateralisation due to intermittend ischemic stimuli. The training is counteracting peripheral myopathy and it diminishes or even reverses the development of cardiac cachexia. In comparison of the prevalence of heart failure as well as the importance of training the referral pattern of some 500 patients per year encompasing all Swiss rehabilitation centers is considerably less than one would wish for. Heart failure exercise training should be started in a properly equipped center and evidenced with the advantage that it could be continued at home as a life long procedure.
[Rehabilitative intervention after a myocardial infarct]. [2006]The purpose of the present review was to determine whether exercise training improves cardiac function in patients with prior myocardial infarction. Home exercise programs for patients with myocardial infarction effectively improve their ability to exercise as well as quality of life. A computer-based, automated, telemetry system comprising central and peripheral computers and telephone line was developed. Myocardial infarction patients were evaluated for peak oxygen uptake and anaerobic threshold. Some studies have in fact suggested that using echocardiography, exercise training in patients with reduced left ventricular function after a myocardial infarction leads to further myocardial damage, including wall thinning, infarct and expansion. A more recent analysis by these investigators suggested that training actually has a beneficial effect on the remodeling process. Many factors appear to influence the extent of the remodeling process, including attenuation by Ace inhibition therapy, extent and site of the infarction, hypertension and continued ischemia. Some results suggest early physical training may be safe and improve the autonomic nerve balance and exercise tolerance in patients with acute myocardial infarction.
Effects of exercise training on left ventricular volumes and function in patients with nonischemic cardiomyopathy: application of magnetic resonance myocardial tagging. [2022]Exercise training is now an accepted component of the therapeutic regimen in patients with heart failure and underlying ischemia, but few data are available on the effects of training in patients with nonischemic dilated cardiomyopathy.