|Year : 2019 | Volume
| Issue : 4 | Page : 114-117
Study design: The effects of photobiomodulation therapy combined with exercise training on functional capacity and quality of life in patients with heart failure (double-blind randomized)
Homa Bahrami1, Hassan Matin Homaei1, Majid Maleki2, Nasim Naderi2
1 Islamic Azad University, Science and Research Branch, Tehran, Iran
2 Rajaie Cardiovascular Medical and Research Center, Tehran, Iran
|Date of Submission||16-Dec-2019|
|Date of Acceptance||27-Dec-2019|
|Date of Web Publication||30-Jan-2020|
Dr. Nasim Naderi
Rajaie Cardiovascular Medical and Research Center, Valiasr Ave, Hashemi Rafsanjani Blvd, Tehran
Source of Support: None, Conflict of Interest: None
Background: Photobiomodulation therapy (PBMT), used to be called low-level laser therapy (LLLT), is a novel therapeutic method in which the red or near-infrared light is used to stimulate healing, relieve pain, and inflammation and prevent tissue from dying. Although in experimental investigations PBMT demonstrated to have many favorable effects on patients with cardiovascular disease, few clinical studies have been conducted in patients with heart failure (HF). Material and Methods: The present study is a single-center, randomized, double-blind, parallel-group controlled trial with placebo which will evaluate the effect of PBMT on functional capacity, quality of life (QOL), echocardiographic parameters, and serum biomarkers of patients with HF-reduced ejection fraction (HFREF) (left ventricular ejection fraction ≤ 40%) who will be referred to cardiac rehabilitation programs. The primary endpoint of the present study is to show the beneficial effect of PBMT on New York Heart Association functional class and the maximum distance walked during 6 min compared to control group. Our secondary endpoint is to show the effects of PBMT on serum pro-brain natriuretic peptide level and QOL. Conclusion: In the present clinical trial, for the 1st time, we will evaluate the effect of LLLT in patients with HFREF. The result of the present trial might introduce a new method for the rehabilitation of these patients.
Keywords: Heart failure, low-level laser therapy, photobiomodulation
|How to cite this article:|
Bahrami H, Homaei HM, Maleki M, Naderi N. Study design: The effects of photobiomodulation therapy combined with exercise training on functional capacity and quality of life in patients with heart failure (double-blind randomized). Res Cardiovasc Med 2019;8:114-7
|How to cite this URL:|
Bahrami H, Homaei HM, Maleki M, Naderi N. Study design: The effects of photobiomodulation therapy combined with exercise training on functional capacity and quality of life in patients with heart failure (double-blind randomized). Res Cardiovasc Med [serial online] 2019 [cited 2020 Feb 24];8:114-7. Available from: http://www.rcvmonline.com/text.asp?2019/8/4/114/277275
| Introduction|| |
Heart failure (HF) is a debilitating syndrome which should be considered as a global health priority. This syndrome is progressive with a high morbidity and mortality. Although the treatment of HF has been optimized by advances in pharmacological and nonpharmacological therapies, the number of end-stage HF patients who have severe symptoms and are frequently admitted in hospital is increasing. Thus, there is a need for new approaches to decrease the symptoms and enhance the quality of life (QOL) of these patients.,
Photobiomodulation therapy (PBMT), used to be called low-level laser therapy (LLLT), is a novel therapeutic method in which the red or near-infrared light is used to stimulate healing, relieve pain, and inflammation and prevent tissue from dying.,
PBMT can activate heat-independent tissue repair processes by direct effect on intracellular mechanisms without causing any tissue damage. It has also been shown that PBMT increases mitochondrial respiration and adenosine triphosphate (ATP) and nitric oxide (NO) availability. It can also accelerate wound healing and skeletal muscle regeneration after injury by decreasing inflammatory response after injury, increasing neovascularization in the injured area, and direct effect on wound-healing cells such as fibroblasts.,,,
The favorable effects of PBMT in cardiovascular diseases have also been shown in many experimental and clinical studies.,,,,,,,,,,
For example, many studies on rat and mouse myocardial infarction models have been shown that PBMT using transthoracic and/or leg muscle LLLT can reduce myocardial inflammation and infarct size and improve cardiac remodeling and mortality., The histological and molecular analyses in these studies have revealed improvements in cardiomyocyte arrangement and a positive effect on mitochondrial respiration pathways, including reduction in mitochondrial damage and a sustained ATP production which, it was suggested, may account for an increase in the availability of ATP and NO.
In addition, in an experimental rat model of HF, PBMT intervention was shown to be effective in improving functional capacity and inflammatory profile and modulate oxidative stress positively.
Although in experimental investigations PBMT demonstrated to have many favorable effects on patients with cardiovascular disease, few clinical studies in this field have been conducted and the results of these studies are conflicting.
Most of these studies have been conducted in the setting of ischemic heart disease,, and, to the best of our knowledge, there is only a pilot study in acute HF patients in which no benefit was observed in the functional capacity of these group of patients.
In light of the previous studies in this field, we aim to evaluate the effects of PBMT (LLLT) on functional capacity, QOL, echocardiographic parameters, and serum biomarkers of patients with HF-reduced ejection fraction (HFREF) who were referred for cardiac rehabilitation programs. To date, no randomized clinical trial (RCT) has evaluated the effects of PBMT in patients with chronic HF.
The primary endpoint of the present study is to show the beneficial effect of PBMT on New York Heart Association (NYHA) class and the maximum distance walked during 6 min (6MWT) compared to control group.
The secondary endpoint is to show the effects of PBMT on serum probrain natriuretic peptide (pro BNP) level, QOL, and some echocardiographic variables such as left ventricular ejection fraction (LVEF), left ventricular end diastolic and systolic diameters, and its global longitudinal strain (GLS) compared to control group.
This study has been designed in the science and research branch of Islamic Azad University, Tehran/Iran, and will be conducted in the Cardiac Rehabilitation Department of Rajaie Cardiovascular, Medical, and Research Center. The study protocol was approved by the Ethics Committee of Islamic Azad University (ethics code: IR.IAU.SRB.REC.1397.041) and has also been registered and approved by the Iranian Registry of Clinical Trial (IRCT) with a code number of IRCT20191207045638N1.
For all patients, the purpose and procedures of the study will be explained and a written informed consent will be provided before entering the study.
We will enroll patients who have diagnosed as HFREF (an LVEF ≤40%) according to the ESC guideline.
The randomization will be performed through block randomization, and allocation secrecy will be kept by numbered, opaque, sealed envelopes. Both patients and the investigators who evaluate the primary and secondary outcomes will be blinded to the randomization groups.
- Expressed readiness to comply with all the study procedures and availability for the duration of the study
- Provision of dated and signed informed consent form
- Age 18–65 years
- A diagnosis of HFREF (LVEF ≤40%)
- NYHA function Class II–III
- Optimal guideline-directed medical therapies including angiotensin-converting enzyme inhibitors, β-blockers, aldosterone antagonists, and diuretics for at least 3 months.
- History of hospitalization for any cause including acute HF in the preceding month
- Presence of chronic renal failure or dialysis
- Presence of chronic hepatic failure
- Patients who have pacemaker, intracardiac defibrillator, or cardiac resynchronization therapy<
- Presence of neuromuscular disorders<
- Psychiatric conditions
- Presence of chronic pulmonary disease
- Inability to perform 6MWT and/or exercise training by stationary bike.
The sample volume was calculated after a pilot trial on five HF patients. The measured outcome in the pilot study was 6MWT distance which was increased from a mean (standard deviation [SD]) of 300 (48) m to 470 (60) m after submaximal exercise training accompanied with LLLT for 8 weeks.
The calculated sample volume considering two mean (SD), alpha = 1%, and power 97% using the following formula was about 12 patients, and finally 15 patients were chosen for each study group.
Training protocol and active or placebo low-level laser therapy intervention
The study population will be randomly assigned to an interventional (n = 15) and a placebo group (n = 15).
Both interventional and placebo groups will perform exercise training, three sessions per week for 8 weeks.
The exercise training program
The exercise training program will include 5 min of warm-up, 20 min of submaximal training with stationary bike, and 5 min of cooling down.
The warm-up phase will include dynamic exercises with simple rhythmic movements to increase heart rate gradually, to prepare for submaximal training phase, and to prevent injuries of higher intensity exercises. The training phase will include two 10-min training at approximately 55%–75% of peak heart rate with a 5-min rest between the two training phases. The cooling-down phase will include low-intensity and stretching exercises, to reduce the muscle tone and prevent shortening of muscle fibers as well as maintaining venous blood flow in the transition from high to low intensity.
The LASER employed will be gallium aluminum arsenide (GaA1As), W. medical GmbH, D-37697 by a LASER probe ƛ=650nm,50 mW which will be put in contact to the skin at six acupuncture points on forearm (PC6-PC7-HR4-HR5-HR6 and ulnar artery acupuncture point) and irradiate for 20 min by a physical therapist who is expert in acupuncture and LLLT.
Intervention group or active LASER group (n = 15)
The intervention group will receive LLLT before each session of submaximal exercise program. The LASER therapy will be applied with a power of 150 J/cm2 per point.
Control group or placebo low-level LASER therapy group (n = 15)
In the placebo group, the LASER system will remain off state.
New York Heart Association functional class
The NYHA function class will be assessed considering the severity of the limitations in physical activities, where Class I indicates no HF symptom (dyspnea), Class II indicates presence of HF symptoms in ordinary activities, Class III indicates HF symptoms at less than ordinary activities, and finally Class IV indicates HF symptoms at rest.
Six-min walk test
The 6MWT will be performed at baseline and after completion of the trial according to the protocol of Guyatt et al. by an investigator who is blinded to the randomization groups.
All echocardiography examinations will be done by an echocardiographer who is blinded to the randomization groups.
All study population will undergo transthoracic echocardiography using a commercially available Cardiovascular Ultrasound System (Philips EPIQ 7). Measurement of left ventricular end diastolic and systolic dimensions will be performed at the parasternal long-axis view by M-mode echocardiography. LVEF is measured by modified Simpson's method. Two-dimensional peak systolic left ventricular GLS is measured by Tom Tec software.
Assessment of quality of life
Patients will be asked to complete the Iranian questionnaire to assess QOL in patients with HF (IHF-QOL) at baseline and after completion of the trial. IHF-QOL has been developed and validated by Naderi et al. in 2012 and is the first Iranian questionnaire for assessing QOL in HF patients. It comprises of five different domains of QOL including 15 questions. The domains evaluated are symptoms and their severity, physical limitations, social interference, psychological condition, self-efficacy, and knowledge. A score equal to 32–47 is considered as moderate satisfaction.
The serum level of N-terminal pro BNP will be measured at our laboratory at baseline and after completion of the trial.
IBM SPSS statistics 19 for Windows (IBM Corp., Armonk, NY, USA) will be used for all statistical analyses. The normality of distribution for all variables will be verified by the one-sample Kolmogorov–Smirnov test. Categorical variables will be reported as number (percentage), and quantitative variables will be expressed as mean (SD) or median (interquartile range) as appropriate. Student's t-test, Chi-square, and Mann–Whitney tests will be used for comparisons and associations, as appropriate. For intragroup analysis, the paired Student's t-test will be used and ANOVA test for repeated measures when necessary. P< 0.05 will be considered statistically significant.
| Discussion|| |
Despite many studies regarding the application of PBMT in cardiovascular diseases,,,,,,,,,,, few data are available about its influence in exercise capacity of patients with HF. In addition, there are gaps in literature regarding PBMT use accompanied with cardiac rehabilitation in patients with chronic HF. Considering the suggested benefits of PBMT and presence of gaps in literature, we decided to conduct this study. For as far as we have researched and investigated, there is no published data regarding the effects of PBMT on functional capacity and QOL of patients with chronic HF who have entered cardiac rehabilitation programs.
We could find only one registered clinical trial in the clinicaltrial.gov web site, with an ID of NCT02508792 and a title of “Acute Effects of Low Level Laser Therapy in Muscle Function of Patients with Heart Failure” which has been submitted in 2015, and there is nothing available regarding the recruiting status and the results (https://www.clinicaltrials.gov/ct2/show/study/NCT02508792).
In 2016, Bublitz et al. published a study, in which the acute effects of LLLT in functional capacity of hospitalized patients with acute HF have been investigated. The findings of their study indicated that the acute effects of LLLT did not improve functional performance in patients with acutely decompensated HF. However, they suggested that acute LLLT reduced perception of muscle fatigue as well as improved blood lactate removal rate.
It is well known that beginning of anaerobic metabolism and accumulation of lactate during exercise occur earlier and removal of lactic acid is significantly slower in patients with HF compared to normal individuals.
The investigators suggest that the laser irradiation would be a modulator of lactate metabolism and its application in a successive series of sessions can decrease accumulation and improve the elimination of blood lactate which could have favorably influenced functional performance in patients with HF.
HF places great stresses on patients, their caregivers, and health-care systems. Demands on health-care services, in particular, are predicted to increase dramatically over the next decade as patient numbers rise owing to aging populations, detrimental lifestyle changes, and improved survival of those who go on to develop HF as the final stage of another cardiovascular disease. It is time to find new and safe therapeutic methods for managing different aspects of this progressive and debilitating syndrome.
| Conclusion|| |
In the present clinical trial, for the first time, we will evaluate the effect of LLLT along with cardiac rehabilitation programs on symptoms, physical performance, and QOL of patients with HFREF. The result of the present trial might introduce a new method for rehabilitation of these patients.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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