Chronic Heart Failure Clinical Trial
Official title:
Effectiveness of Combined Aerobic and Strength Training in Acute and Chronic Adaptations in Patients With Heart Failure
Patients with chronic heart failure (CHF) underwent to a hospital-based cardiac
rehabilitation (CR) program in the Lisbon district Hospitals will be recruited. The
participants will be randomized into one of the following exercise groups: A) combined
exercise training with more aerobic training and less strength training (CAT); B) combined
exercise training with more strength training and less aerobic training (CST). The
investigators will test two proportions in combined training, CAT and CST. There hasn't been
any data on the so called combined regimes, which include both aerobic exercise with HIIT and
ST and the investigators will evaluate the effects of acute and chronic response.
The research project will contribute to a better understanding in several aspects that are
unexplained by scientific research.
Literature Review:CHF is the major public health problem in the world[1], highly prevalent in
older individuals and a major cause of disability, hospitalizations, morbidity and
mortality[2]. Generally, CHF patients have reduced exercise capacity, with main symptoms of
effort intolerance, early fatigue and breathlessness[3], also exhibiting increased peripheral
and central chemosensitivity, and impaired sympathovagal balance with sympathetic
activation(SA) predominance[4].
Understanding the oxidative metabolism and intracellular energy transfer in both skeletal and
cardiac muscle, mechanisms of endothelial dysfunction, and the role of SA and inflammatory
cytokines provide possible mechanistic explanations of the pathophysiologic factors involved
in the development of exercise intolerance[5,6]. It has been shown in CHF patients that
increased arterial stiffness is associated with cardiovascular morbidity and mortality[7].
There are evidences that increased arterial stiffness predicts exercise intolerance in CHF
patients[8].
Increased carotid IMT is associated with subclinical left ventricular(LV) myocardial
dysfunction, suggesting a possible role of carotid IMT in HF risk determination [9]. CHF is
associated too with endothelial dysfunction including impaired endothelium-mediated,
flow-dependent dilation(FMD). Since endothelial function is thought to play an important role
in coordinating tissue perfusion and modulating arterial compliance, interventions to improve
endothelial dysfunction are imperative.
Systemic vasoconstriction and impaired peripheral perfusion are hallmarks in advanced CHF.
While a number of factors, including increased sympathetic tone and an activated
renin-angiotensin system, have been proposed to be involved in the reduced arterial
vasodilatory capacity in HF, the pivotal role of the endothelium in coordinating tissue
perfusion has now been recognized.
Several clinical studies have documented endothelial dysfunction of large conduit and small
resistance vessels in patients with CHF. Endothelial dysfunction may affect the
cardiovascular system in two ways: first, endothelial dysfunction of resistance vessels may
impair peripheral perfusion, and, second, endothelial dysfunction of large conduit vessels
may limit the increase in blood flow provided by the supplying large vessels and may increase
impedance of the failing LV and consequently impair LV ejection fraction(LVEF). An important
functional consequence of endothelial dysfunction is the inability to release nitric
oxide(NO) in response to physiological stimuli such as increases in flow, reflecting impaired
FMD[10]. Conversely, chronically increased blood flow enhances the release of NO in
experimental models, by upregulation of NO synthase, the enzyme that uses L-arginine to
generate NO. The intermittent increases of blood flow by physical training may increase the
capability of the endothelium to release NO and therefore may restore endothelial function in
patients with CHF who are usually subjected to a limited degree of physical activity[5]. The
dysfunctional endothelium contributes to increased vascular stiffness and impaired arterial
distensibility, augmenting myocardial damage[10].
The direct relationship between exercise and vascular health is certain, but the complex set
of metabolic pathways, haemodynamic effects of exercise on cardiovascular cells/tissues, and
the regulation of genetic expression activated by exercise is still largely undefined[11].
The effects of aerobic and resistance exercise on clinical blood pressure might be different,
because they have different mechanical characteristics. Aerobic training(AT) is characterized
by the execution of cyclic exercises, carried out with large muscle groups contracting at
mild to moderate intensities for a long period of time. On the other hand, strength
training(ST) is characterized by the execution of exercises in which muscles from a specific
body segment are contracted against a force that opposes the movement[12].
Aerobic capacity is directly related to arterial function, including endothelial function,
arterial stiffness and wave reflection. In addition, coupling of arterial and cardiac
function is a major determinant of aerobic capacity. Thus, poor resting arterial function
likely limits aerobic capacity, but it is also possible that changes in arterial function
during acute exercise may play a role. Arterial function is not only associated with aerobic
capacity, but is also an independent predictor of mortality[5].
Controlled clinical trials have shown that in HF patients ExT programs improve peripheral and
cardiac adaptations and also the aerobic capacity, delay the onset of anaerobic metabolism,
and improve the autonomic balance[1,13]. Apart from adaptation in maximal cardiac output,
heart contractility, and stroke volume, aerobic ExT is also able to promote amelioration in
the peripheral microvascular background by reducing resistance to flow, increasing the
compliance of the arteries and endothelial function [13]. Abnormalities in endothelium and
FMD are a key phenomenon in the blunted vasodilatory response in CHF patients. ExT enables
the improvement of both basal endothelial NO formation and agonist-mediated FMD of the
skeletal muscle(SM) vasculature in CHF patients. The correction of endothelial dysfunction is
associated with a significant improvement in exercise capacity evidenced by a 26% increase in
peak oxygen uptake(VO2peak)[14].
Previous studies in HF have been showing that 16.4% of 171 patients had cachexia, and the
mortality at 18 months of follow up was as high as 50% in the subset of patients with
cachexia compared with 17% in those without cachexia. Cardiac cachexia is defined as an
advanced stage of HF associated with involuntary loss of at least 5% of non-oedematous body
weight. And muscle wasting, also known as sarcopenia, is the loss of muscle mass(MM) and
strength, whereas cachexia describes loss of weight. Distinction of the two clinical
conditions might also be challenging, because cachexia and muscle wasting can co-exist in the
same patient. Indeed, cachexia might lead to muscle wasting and vice versa, although muscle
wasting can occur earlier in the course of the disease[15].
SM strength, in upper and lower limbs, are parameters that independently predict
survival[16,17,18]. This alternative treatment should focus on increasing MM, strength and
power in the limbs to improve functionality and performance[19]. SM dysfunction includes
reduced cardiac contractile performance that contributes to changes in SM physiology, muscle
atrophy, weakness and reduced oxidative capacity [20]. Muscle function is also enhanced in
response to ST in CHF patients, including myofilament function and whole muscle[21] as well
as SM oxidative capacity[21].
It's crucial that the ExT in such patients should be train the peripheral muscles effectively
without producing great cardiovascular stress. An alternative treatment approach should focus
on the application of specific resistance exercise program to improve body composition[22],
increase the cross-sectional area, muscle fiber[23], all of which counteract muscle wasting
and may be cornerstone in the prevention of sarcopenia and cardiac cachexia in CHF
patients[24].
ExT is a major component of rehabilitation/secondary prevention interventions, inducing
significant beneficial changes in mechanisms of pathophysiology, exercise tolerance,
functional capacity and QoL, while a positive impact on hospitalization and mortality
reduction. There has been growing interest in the characteristics and modalities of exercise
training able to induce optimal benefits. High intensity and interval mode have been shown to
induce greater benefits than moderate intensity and continuous mode regimes. Considering the
current body of evidence of high-intensity interval training(HIIT) in CHF, HIIT demonstrated
to be more efficient, resulting in long-term adherence, which be an important practical
aspect to consider during the ExT and consequently optimized improvements in central and
peripheral adaptations[25]. More studies are needed to proof their safety and benefits on
this type of patients.
Additionally, there has been sound rationale for the inclusion of ST to the HIIT, which has
been also shown able to yield benefits in terms of exercise capacity and QoL. It is well
known that combined AT and ST is the preferred exercise intervention to reverse or attenuate
the loss of MM and improve exercise and functional capacity, muscle strength in this
individuals[19]. But there are underlying mechanisms from the ST in the CHF patient's
peripheral capacity that remains unidentified. And isn't known what is the benefits of
combine different proportions of AT and ST.
For that reason, the investigators will test two proportions in combined training, CAT and
CST. There hasn't been any data on the so called combined regimes, which include both aerobic
exercise with HIIT and ST and the investigators will evaluate the effects of acute and
chronic response.
Purpose:The research project will contribute to a better understanding in several aspects
that are unexplained by scientific research. The purpose of this research project are:
1. To determine the effectiveness of an ExT programme with different proportions of CAT and
CST in promoting cumulative effects in acute and chronic adaptations in CHF patients;
2. To identify the mechanisms of the potential improvement in effectiveness promoted by ST;
This research project is going to employ state of the art methods focusing peripheral
adaptations analysis in both groups namely in echocardiography variables,
cardiopulmonary exercise testing, arterial stiffness, functional physical fitness, QoL
and body composition in 2 distinguished moments: M1)baseline and M2)3 month.
Plan and Methods:This project will assess the acute and chronic effects in central and
peripheral adaptations of a combined training to patients with CHF would address a number of
important breaches in scientific knowledge with potential clinical benefits.
Study Design: A longitudinal randomized control trial (RCT) research design using two
distinct ExT prescriptions (CAT and CST) will be applied in CHF patients. All the same
assessments will be done in two moments: M0 - baseline and M1 - 3 months after starting the
ExT. The patients will be randomized into either one of the two ExT group.
Recruitment and screening will last 9 months(October 2017 to June 2018) and the patient
assessment will last until August 2018. It is expected to finish the project with peer-review
redaction submitted and/or accepted in December 2018.
The following assessments on the 4 moments will be performed at the host Hospital, FMH-UL:
Echocardiogram(Echo); cardiopulmonary exercise test(CPET); arterial stiffness - Complior
Analyse; Intima-media thickness - ultrasound; body composition - dual-energy radiographic
absorptiometry; functional physical fitness - Fullerton Functional Fitness Test; isometric
strength - portable hand dynamometer JAMAR plus digital; maximal strength - 1RM and QoL
questionnaire.
All assessment moments will be done in 4 days:
Day 1-The CPET, Echo will be performed at the host Hospital; Day 2 and 3-during one day and
time of the ExT session at the host hospital, the patient will perform the functional
physical fitness tests; maximal strength; isometric strength and QoL questionnaire. In
another day the investigators will perform the arterial stiffness and the IMT before the
session in rest and after the ExT; Day 4-In FMH, and dual-energy radiographic
absorptiometry(DXA) exam. Individual reports will be sent by email or delivered on paper.
During the 1-year project the multidisciplinary team will have bimonthly meetings to update
the study information and discuss the patient's progress.
;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT03597646 -
The Effect of Kinesio Taping on Pulmonary Function and Functional Capacity in Patients With Chronic Heart Failure
|
N/A | |
Terminated |
NCT04065997 -
Apogee International
|
||
Withdrawn |
NCT03675113 -
Effect of Upper Extremity Aerobic Exercise Training on Exercise Capacity Patients With Chronic Heart Failure
|
N/A | |
Completed |
NCT02916160 -
Sacubitril-valsartan and Heart Failure Patients : the ENTRESTO-SAS Study
|
Phase 4 | |
Completed |
NCT03126656 -
Effects of Testosterone on Myocardial Repolarization
|
Phase 4 | |
Completed |
NCT02268500 -
VAccination to Improve Clinical outComes in Heart Failure Trial: a Feasibility Study (VACC-HeFT)
|
Phase 4 | |
Completed |
NCT02247245 -
The Influence of Heart Rate Limitation on Exercise Tolerance in Pacemaker Patients.
|
N/A | |
Completed |
NCT01919918 -
Muscle Afferent Feedback Effects in Patients With Heart Failure
|
Phase 1 | |
Terminated |
NCT01906957 -
Cognition and Exercise Training
|
N/A | |
Not yet recruiting |
NCT01669395 -
Severe Heart Failure and Homebased Rehabilitation - An Intersectoral Randomized Controlled Trial
|
N/A | |
Completed |
NCT00984529 -
Evaluation of Clinical Signs and Symptoms of Chronic Heart Failure in Patients Treated With Candesartan Cilexetil in Croatia
|
N/A | |
Recruiting |
NCT00863421 -
Sleep Disordered Breathing in Patients With Chronic Heart Failure
|
N/A | |
Completed |
NCT02840565 -
Tolerability, Pharmacokinetics and Pharmacodynamics of Six Multiple Rising Dose Regimens of BIA 5-453
|
Phase 1 | |
Completed |
NCT02441218 -
Effects of Ivabradine on Cardiovascular Events in Patients With Moderate to Severe Chronic Heart Failure and Left Ventricular Systolic Dysfunction. A Three-year International Multicentre Study
|
Phase 3 | |
Completed |
NCT00149409 -
Omega-3-Polyunsaturated Fatty-Acids (N3-Pufa) In Patients With Severe Chronic Heart Failure
|
Phase 2/Phase 3 | |
Terminated |
NCT05532046 -
A Study to Learn How Safe Study Drug BAY2413555 is, How it Affects the Body, and How it Moves Into, Through, and Out of the Body Over 4 Weeks of Use in Participants With Heart Failure and Implanted Cardiac Defibrillator or Cardiac Resynchronization Devices (ICD/CRT)
|
Phase 1 | |
Recruiting |
NCT04984928 -
Readmission Risk of Patients With Heart Failure.
|
||
Completed |
NCT02814097 -
A Study to Evaluate the Effects of 4 Weeks Treatment With Subcutaneous Elamipretide on Left Ventricular Function in Subjects With Stable Heart Failure With Preserved Ejection Fraction
|
Phase 2 | |
Active, not recruiting |
NCT05560737 -
ODYSSEE-vCHAT Mental Health Program for Heart Failure and Kidney Disease Patients
|
||
Recruiting |
NCT03286127 -
Palliative Outcome Evaluation Muenster I
|