Efficacy of High Intensity Interval Training vs Moderate Intensity and Continuous Training on Autonomic Nervous System Modulations in Chronic Heart Failure
Phase: NA
Conditions: Chronic Heart Failure
Sponsor: Cardiovascular and Pulmonary Rehabilitation Center of Saint Orens

    
       
 
 
 
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Efficacy of High Intensity Interval Training vs Moderate Intensity and 
Continuous Training on Autonomic Nervous System modulations in 
Chronic Heart Failure. 
 
HRVFIT 2 - Study 
 
 
 
Ethics committee / Regulatory Provisions 
Number 
French National Agency for Medicines and Health Products Safety (ANSM) 
2015-A00166-43 
National Information Commissioner's Office / French Data Protection Authority (CNIL) 
1835544 
Ethical Research Committee (CPP) 
2-15-12 
 
 
 
 
 
 
 
Instigator:  
Clinique de Saint-Orens 
Cardiovascular and Pulmonary Rehabilitation Center 
12, av de Revel, 31650, St-Orens de Gameville, France 
Tél. 05.61.39.33.33 
Fax. 05.61.39.34.65 
 
Dr Thibaut Guiraud 
Clinique de Saint-Orens 
Cardiovascular and Pulmonary Rehabilitation Center 
12, av de Revel, 31650, St-Orens de Gameville, France 
thibaut.guiraud@gmail.com 
Tél. 05.61.39.33.33 
Fax. 05.61.39.34.65 
 
 
 
 
 
 
 
 
 
 
 

    
       
 
 
 
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UPDATE OF THE PROTOCOL 
 
VERSION 
DATE 
DESCRIPTION 
V 1.0 
25.02.2015 
Version 1.0 
V 1.1 
17.03.2016 
-addition of two investigators 
-changes to inclusion / non-inclusion criteria 
 
 
 
 
 
 

    
       
 
 
 
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Protocol Signature 
Instigator 
 
 
 
 
 
 
Thibaut Guiraud 
Clinique de Saint-Orens 
Cardiovascular and pulmonary rehabilitation center 
12, av de Revel, 31650, St-Orens de Gameville, France 
t.guiraud@clinique-saint-orens.fr 
thibaut.guiraud@gmail.com 
Tél. 05.61.39.33.33 
Fax. 05.61.39.34.65 
 
    
  
Main Investigator 
 
 
 
 
 
 
 
Dr. Lisa Richard 
Clinique Saint Orens 
Cardiovascular and pulmonary rehabilitation center 
12, av de Revel, 31650, St-Orens de Gameville, France 
l.richard@clinique-saint-orens.fr 
Tél. 05.61.39.33.33 
Fax. 05.61.39.34.65 
 
 
 
 
 
 
 
 
 
 

 
 
 
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Clinical Routine Care Study 
 
Efficacy of High Intensity Interval Training vs Moderate Intensity and 
Continuous Training on Autonomic Nervous System modulations in Chronic 
Heart Failure. 
 
HRVFIT2 Study 
 
Instigator  
Clinique de Saint Orens 
Cardiovascular and pulmonary rehabilitation Center 
12 Avenue de Revel 
31650 Saint-Orens-de-Gameville, France 
Tél. 05.61.39.33.33 
Fax. 05.61.39.34.65  
Represented by Dr Thibaut Guiraud (PhD)  
t.guiraud@clinique-saint-orens.fr 
thibaut.guiraud@gmail.com 
 
 
Investigator 
Dr Lisa Richard, Cardiologist 
Clinique Saint Orens 
12 Avenue de Revel 
31650 Saint-Orens-de-Gameville, France 
Tél. 05.61.39.33.33 
Fax. 05.61.39.34.65 
l.richard@clinique-saint-orens.fr 
 
Dr Marc Bousquet  
Cardiologist 
Clinique Saint Orens 
Mail : m.bousquet@clinique-saint-orens.fr 
 
Dr Laurent Soukarié 
Cardiologist 
Clinique Saint Orens 
Mail : l.soukarie@clinique-saint-orens.fr 
 
Dr Hélène Kerroz 
Cardiologist 
Clinique Saint Orens 
Mail : h.keroz@clinique-saint-orens.fr 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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Table of contents 
 
 
Abreviations List ................................................................................................................................... 7 
Scientifical Background ........................................................................................................................ 8 
Chronic Heart Failure : definition and epidemiology ....................................................................... 8 
Chronic Heart Failure and the autonomic nervous system ............................................................. 8 
Effects of exercise training on the autonomic nervous system in CHF.......................................... 10 
Hypothesis .......................................................................................................................................... 10 
Objectives........................................................................................................................................... 11 
Routine medical examination ............................................................................................................ 12 
Cardiopulmonary Exercise Test...................................................................................................... 12 
24-h Holter ECG recording ............................................................................................................. 12 
Echocardiography .......................................................................................................................... 12 
Endothelial Function ...................................................................................................................... 13 
Blood Sample Analysis ................................................................................................................... 13 
Rehabilitation Program: MICE and HIIT training mode...................................................................... 13 
Primary and secondary endpoints ..................................................................................................... 14 
Primary endpoint ........................................................................................................................... 14 
Secondary Endpoint ....................................................................................................................... 14 
Design of the study ............................................................................................................................ 15 
Randomization ................................................................................................................................... 15 
Eligibility criteria (inclusion / exclusion) ............................................................................................ 15 
Recruitment ....................................................................................................................................... 15 
Expected fallout ................................................................................................................................. 16 
Statistics ............................................................................................................................................. 17 
Sample Size .................................................................................................................................... 17 
Statistical analyses ......................................................................................................................... 17 
Research Calendar ............................................................................................................................. 18 
Specific terms of monitoring .............................................................................................................. 19 
Rules for stopping research ........................................................................................................... 19 
The final stop rules ......................................................................................................................... 19 
Research Monitoring Committee................................................................................................... 20 
Ethical and regulatory compliance..................................................................................................... 21 
References ......................................................................................................................................... 22 
 

 
 
 
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Abreviations List 
 
 
ANS : autonomic nervous system 
CHF : chronic heart failure 
HIIT : high intensity interval exercise training 
HR : heart rate 
HRR : heart rate recovery 
HRV : heart rate variability 
MAP : maximal aerobic power 
MICE : moderate intensity and continous exercise training 
RMSSD : root mean square successive difference of heart rate 
SDNN : Standard Deviation of Normal-Normal interbeat interval 
VO2 max : maximal oxygen consumption 

 
 
 
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Scientifical Background 
 
Chronic Heart Failure : definition and epidemiology 
 
Chronic Heart Failure (CHF) is defined as a structural or functional abnormalities of the heart leading to 
insufficient oxygen supply to the tissues. The prevalence is estimated between 2 and 3% in Europe by the 
European Society of Cardiology and increases sharply with age from 75 years [1]. Despite a significant 
reduction in mortality between 2000 and 2010, CHF remains a common cause of death, especially among 
the elderly [2]. In France, the mortality rate is 60% in the five years following diagnosis [2] and up to 40% 
of CHF patients die within one year of their first hospitalization [3]. 
It is estimated that nearly half of the deaths related to the pathology are due to rhythm disorders leading to 
sudden cardiac death. The role of the autonomic nervous system (ANS) and in particular the imbalance of 
the sympatho-vagal balance is recognized as a main factor in the occurrence of a number of rhythm 
disorders that can lead to sudden cardiac death [4]. 
 
Chronic Heart Failure and the autonomic nervous system 
 
The activation of the orthosympathetic nervous system is constantly found in CHF [5]. The Holter-ECG-
24h and heart rate variability (HRV) allows non-invasive analysis of ANS activity and abnormalities. With 
CHF, the HRV index as SDNN, rMSSD, HFnu%, are decreased and indicate alteration of the ANS [6]. 
Several studies have shown that in cardiovascular diseases, the HRV parameters were prognostic markers of 
mortality [7]. In both healthy subjects and CHF, studies show that regular exercise improves HRV by 
increasing vagal tone and decreasing sympathetic nervous system activity [6, 8, 9]. In CHF, exercise 
training is a non-pharmacological treatment and improves symptoms, quality of life, physical fitness and 
has a favorable impact on morbi-mortality [10]. The ESC/AHA recommend moderate-intensity and 
continuous-exercise training sessions (MICE) [11, 12]. However, recent data suggest that high intensity 
interval training (HIIT) is superior to MICE to improve quality of life, maximal oxygen uptake (VO2max) 
and cardiac remodeling of CHF patients [13]. Our team has also study high-intensity exercises on different 
parameters in these patients with interesting results [14-18]. The two exercise training mode is illustrated by 
the figure 1. 
 
 
 
 
 
 
 
 
 

 
 
 
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Figure 1 : exercise training mode of MICE or HIIT  
 
 
 
 
 
The following table illustrated this new mode of training and is from the latest ESC guideline [12]. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
 
 
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Effects of exercise training on the autonomic nervous system in CHF 
 
Several studies have shown a reduction of the sympathetic activity measured by microneurography 
(MSNA) after an exercise training program in heart failure [19, 20]. This is also found on other ANS 
parameters such as the Heart Rate Variability that is improving [6, 9]. Catecholamines also tends to 
decrease with aerobic activity [21]. This improvement in vegetative balance is associated with an 
improvement in the different vegetative reflexes involved in the regulation of cardiovascular ANS. Thus, 
the abnormalities noted on the baroreflex, the chemoreflex, the ergoreflex and the central control are all 
potentially improved by repeated aerobic exercise [22, 23]. Thus the sympathetic stimulation induced 
during the exercise is followed by a period of increase in vagal tone, explaining the benefit on the rhythmic 
profil . To our knowledge there is no study comparing the effects on the ANS of MICE training versus HIIT 
training in CHF. 
 
Hypothesis 
 
Our team recently used an intermittent exercise protocol that has been optimized in CHF patients [24] in 
order to induce a strong cardiovascular and muscular stimulus while ensuring safety and comfort of the 
patient (30 seconds at 100% of peak power alternate with 30 sec of passive recovery). In 18 CHF patients, 
we showed that a single intermittent exercise session increases parasympathetic tone (high frequency index 
in normalized units HFnu%) and significantly decreases premature ventricular contraction within the 24h of 
the exercise, compared to a single session of MICE [16]. These results appear promising and suggest that 
stimuli associated with intense intermittent exercise and passive recovery, as opposed to continuous-type 
exercise of moderate intensity, would be more effective to increase sympatho-vagal balance and arrytmias. 
Nevertheless, the effects of a several weeks of an HIIT program on explanatory parameters of sudden death 
(SNA activity, arrhythmias, cardiac function) have never been studied in CHF patients. We therefore 
hypothetize that HIIT is superior to MICE for 1/ increasing parasympathetic activity measured by HRV, 2 / 
the cardiorespiratory fitness. In addition, we also hypothesize that there is a link between improved physical 
capacity and vagal tone and decreased arrhythmias. 

 
 
 
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Objectives 
 
Main objective: 
To compare, in patients with chronic heart failure, the efficacy of 4-weeks exercise training programs 
(MICE vs HIIT) on the evolution of the spectral high frequency (HF) component of HRV. 
 
Secondary Objectives: 
To compare, in patients with heart failure, the effectiveness of 4-weeks exercise training programs (MICE 
vs HIIT) on: 
- The temporal and spectral component of HRV 
- The number and nature of arrhythmias 
- Diastolic and systolic functions measured by echocardiography 
- The maximum oxygen consumption (VO2max) 
- Arterial vasomotricity 
-biomarkers measurements (BNP, catecholamines) 
 
 

 
 
 
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Routine medical examination 
 
All the evaluations of this research are part of the patient follow-up classically performed in a 
cardiovascular rehabilitation center. Thus, for this study, the current care evaluated will include: an ECG-
24h holter, a maximal cardiopulmonary exercise test, an echocardiography, a blood sample test, an 
endothelial function analysis (Endopath system). The exams will be done at the inclusion (J0), after 4 weeks 
of rehabilitation (S4). 
 
Cardiopulmonary Exercise Test 
 
CPET will be performed according to current guidelines for CHF patients [12]. A continuous progressive 
exercise protocol will be performed on a cycle ergometer (Ergoline 800S, Ergoline, Bitz, Germany). A 2-
min warm-up at 20 W ; and the power will be increased by 10 W/min until exhaustion [12]. Peak power 
output (PPO) is define as the power output reached at the last fully completed stage. All subjects will be 
encouraged to provide a maximal effort. Oxygen (V̇ O2) and carbon dioxide (CO2) were registered by a 
breath by breath analysis (PowerCube, Ganshorn Electronic Medizin, Germany). Heart rate, blood pressure, 
and rating of perceived exertion (RPE) using the Borg scale (level 6 to 20) will be recorded before the test 
and at 2-min intervals during exercise and recovery. Electrocardiographic activity will be continuously 
monitored using a 12-lead ECG (GE Healthcare Marquette) and will be recorded throughout the test and 
during the 6-min passive recovery after the test.  
 
24-h Holter ECG recording 
24-h ECG monitoring will be performed at baseline and at the end of the stay using a two-lead 24-h Holter 
ECG system (Spiderview, ELA medical, France). Patients will be requested to avoid any exercise, 
caffeinated beverages, and smoking during the 24 h of recording. An experienced technician blinded to 
randomization will analyse the recordings (Synescope, ELA medical, France). 
 
Echocardiography  
 
Echocardiography will be performed using a phased-array transducer (Vivid T8, GE Healthcare). Three 
cine loops from the three standard apical planes (four-chamber, two-chamber and long-axis) as well as 
short-axis (basal, mid-papillary and apical) will be recorded in gray scale harmonic mode and tissue 
Doppler mode. B-mode recordings will be done with an average of 53 frames/s and tissue Doppler with 154 
frames/s. Measurements will be done in accordance with recommended procedures of the European 
Association of Cardiovascular Imaging. LV volumes and ejection fraction (EF) will be calculated from 
apical recordings by modified biplane Simpson’s method. Left ventricle inflow velocity was measured by 
pulsed Doppler with the sample volume at the tips level of mitral valves. Measurements will included early 
diastolic filling (E) and late diastolic filling (A). Stroke volume (SV) and cardiac output (CO) were 
calculated by Doppler flow measurement in the LV outflow tract (LVOT). Tissue Doppler recordings of the 

 
 
 
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mitral annulus will be obtained from the septal and lateral points in four-chamber and in the anterior and 
inferior points in two chamber views. Peak annulus velocity in systole (S’), early diastole (e’) and late 
diastole (A’) will be measured as average of the four points. 
 
Endothelial Function 
 
Reactive hyperemia index (RHI), a surrogate of endothelial function, will be assessed using the EndoPAT 
2000 device (Itamar Medical, Israel) and an automated algorithm provided with the accompanying software 
(v3.1.2) according to the manufacturer's instructions. Briefly, patients will be in a supine position for a 
minimum of 20 min before measurement in a quiet, temperature-controlled (21–24 °C) room with dimmed 
lights. Each recording will consist of 5 min baseline measurement, 5 min occlusion measurement, and 5 min 
post-occlusion measurement (hyperemic period). Occlusion of the brachial artery involved the non-
dominant upper arm. The natural logarithmic scaled RHI (LnRHI) will be calculated from the ratio between 
the digital pulse volume during RH and at baseline [25]. 
 
Blood Sample Analysis 
Measurements will include: NT-pro-BNP (electrochemiluminescence immunoassay) and both epinephrine 
and norepinephrine plasma levels (HPLC). 
 
Rehabilitation Program: MICE and HIIT training mode 
 
The rehabilitation program focus on controlling cardiovascular risk factors, diet monitoring, therapeutic 
education sessions and psychological support when needed. In our clinical center, the RP last 3 hours per 
day, 5 days per week during 3.5 weeks. The daily activity training include a cycling endurance training 
(HIIT or MICT), a 30-min of gymnastics or muscle strengthening (3 series of 15 repetitions at 50% of 1-
repetition maximum test in chest press, leg press, pull over, low row, leg extension) and 45-min outside 
walking sessions. Each session will be monitored by a physiotherapist and was supervised by a cardiologist.  
 
The HIIT consist of two sets of 8-min intervals at 100% of peak power output (PPO) [24, 26]. Each interval 
set is composed of repeated bouts of 30 s at 100% of PPO interspersed by 30 s of passive recovery in the 
seated position. Four minutes of passive recovery are allowed between the two sets. The MICT training 
consist of cycling 30 minutes at 60% of peak power output. Each mode of training start with 5 minutes of 
warm up and finish with 5 minutes of cool down at 30% of PPO. 
 
 

 
 
 
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Primary and secondary endpoints 
Primary endpoint 
Evolution between day 0 (D0) and Week 4 (W4), of the High Frequency component of HRV measured 
during the night time period and expressed in normalized units (%): HF nu%. 
 
Secondary Endpoint 
The analysis will also focus on the evolution of the following variables: 
Variables extracted from the analysis of the HRV (Holter-ECG 24h) 
Heart Rate rest (beats per minute - bpm) 
LF, HF (milliseconds ², standard units) 
VLF (milliseconds ²) 
Total Spectral Power (milliseconds ²) 
SDNN (milliseconds) 
rMSSD (milliseconds) 
LF / HF ratio 
Number and nature of arrhythmias 
Variables of echocardiography 
Size of the cardiac cavities (diameter (mm), surface (cm²), volume (ml.m²)) 
LV systolic function (Ejection fraction (%), parietal thickness (mm)) 
Filling LV (E / A, E / e ', Ap-Am (ms), E / Vp) 
Systolic function of RV (shortening fraction (%), S 'wave (cm.s), systolic excursion of tricuspid ring (mm)) 
Variables of the cardiopulmonary exercise test 
Maximum oxygen consumption (VO2pic (ml.min)) 
Maximum heart rate (bpm) 
Heart rate after 1 minute, 2 minutes and 3 minutes of passive recovery 
Oxygen pulse (ml.min.batt) 
Slope VE / VCO2 
Maximum aerobic power (watts) 
Variables of endothelial function 
Reactive Hyperemia Index (RHI) 
Variables of the blood test 
Blood glucose (mmol.L); HbA1c (%) 
Adrenaline, norepinephrine (ng.L) 
NT pro BNP (ng.L) 

 
 
 
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Design of the study 
Prospective / randomized study in 2 parallel groups (1:1): arm 1 (MICE) and arm 2 (HIIT). 
 
Randomization 
The randomization to assign each patient to one of the 2 groups will be done just after the verification of the 
eligibility criteria and the collection of the sign consent of participation of the patient. The numbers of the 2 
groups (arm 1: MICE / arm 2: HIIT) are balanced with a 1: 1 ratio 
 
Eligibility criteria (inclusion / exclusion) 
Inclusion 
Inclusion criteria will be stable CHF with NYHA functional class from I to III, stable left ventricular 
ejection fraction (LVEF) < 45% over at least 6 months, stable optimal medical therapy including a beta-
blocker and an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blockers (ARB) for 
at least 6 weeks and ability to perform a maximal CPET. 
 
Exclusion 
Exclusion criteria will be any relative or absolute contraindications to exercise training according to current 
recommendations [12], fixed-rate pacemaker with HR limits set lower than exercise training target HR, 
major cardiovascular event or procedure within the 3 months preceding enrolment, chronic atrial 
fibrillation, heart failure secondary to significant uncorrected primary valve disease (except for mitral 
regurgitation secondary to left ventricular dysfunction), and heart failure secondary to congenital heart 
disease or obstructive cardiomyopathy. 
 
Patients eligible for the study must not have participated in biomedical research within 30 days of the start 
of this research and will not be able to participate in another research at the same time. 
 
Recruitment 
The recruitment of CHF patients will be done only at the Clinic of Saint-Orens, during the first day of 
consultation and only by investigators avowed by the Ethical Commitee. After verification of the eligibility 
criteria, the cardiologist will explain to the patient the research and propose to participate. He will then give 
him the information notice. The expected duration of the inclusion period is 1 year. 
 

 
 
 
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Expected fallout 
 
If HIIT is more interesting to improve ANS activity, arrhythmias, cardiac function and cardiorespiratory 
fitness (all are parameters of sudden cardiac death), then the optimization and the prescription of this type 
of exercise training would be important. That would demonstrate the great interest and the feasibility of an 
intense exercise training program specific to chronic heart failure patients. This prescription could later be 
transposable at home for a long term period of pratice. Thus this study will open the field to other research 
perspectives in particular in terms of longer-term impact on the mortality that remains to be evaluated. 

 
 
 
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Statistics 
 
Sample Size 
The primary outcome measure is the change of High Frequency power in normalized units (HFnu) measure 
at night as a surrogate of cardiac parasympathetic modulation. Based on our first study [16], we hypothesise 
that HIIT mode will induce a ~11% change in HFnu compare to MICT training mode. With a mean value of 
the main criteria (HFnu %) of 31.5%, a standard deviation of 3%, a statistical power (1-β) to 90% and a α 
risk set to 0.05 in bilateral hypothesis, 16 patient per group must be recruited. 
 
Statistical analyses 
Data will be summarized by mean ± standard deviation (SD) for continuous variables; percentages and 
frequencies for categorical ones. Shapiro-Wilk and Bartlett tests will be used to assess normality and 
equality of variance among variables analysed, respectively. Baseline inclusion characteristics will be 
compared between groups using one-way ANOVA or Mann-Whitney non-parametric test for quantitative 
variables.  Changes within groups (difference between post and pre training values) will be analysed using a 
paired t-test for normally distributed data or paired Wilcoxon signed-rank test for non-normally distributed 
data. To analyse the differences between HIIT and MICT groups, repeated ANOVA analysis will be carried 
out estimating time effect (post vs pre), group effect (HIIT vs MICT) and the interaction time x group. P 
value <0.05 will be considered as significant. Correlation between parameters will be analyzed using the 
Pearson Correlation Test or Spearman's Rank Correlation Test, depending on the nature of the conditional 
distribution and the shape of the relation. 
 

 
 
 
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Research Calendar 
Provisional schedule 
Beginning of inclusions: June 2015 
Duration of the inclusion period: 1 year 
Duration of participation of each patient: 7 months (4 weeks in rehabilitation centre) 
Total duration of the research: 3 years 
Summary table of patient follow-up 
 
 
Pre-inclusion 
D- 1 à D- 2 
Inclusion 
D 0 +/- 2 days 
Week 4 +/- 3 days 
eligibility criteria 
 
 
 
Patient information of the research 
 
 
 
Collection of sign informed consent 
 
 
 
Randomization 
 
 
 
Clinical Exam1 (Nurse) 
 
 
 
Holter ECG-24h (nurse) 
 
 
 
Endothelial function (nurse) 
 
 
 
Biological assessment 2 (nurse) 
 
 
 
Echocardiography (cardiologist) 
 
 
 
Cardiopulmonary exercsie  test 
(cardiologist) 
 
 
 
1Clinical examination: measurement of: height, weight, analysis of body composition by impedance, measurement of 
waist circumference and resting blood pressure. 
2Biological assessment: lipid balance, glycemic, adrenaline, norepinephrine, NT-pro-BNP, beta hCG for women(D0). 
 

 
 
 
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Specific terms of monitoring 
In addition to the usual medical care of the patient, a Supervisory Committee will ensure the proper conduct 
of research, the safety of proposed programs. , Any adverse effects caused by physical exercise training 
(muscle pain cramp, fatigue of the patient), change of drug treatment, compliance with the protocol will be 
noted in the medical file. In case of fatigue of a patient or for medical or paramedical reason, the exercise 
training intensity may be reduced or even removed. In this case, any changes to the exercise training 
program will be documented in the medical file. 
 
Rules for stopping research 
The rules for temporary cessation of the participation of a person in research or part or all of the research: 
1) Anyone is free to temporarily stop participating in the research at any time. 
2) Anyone can ask to temporarily interrupt their participation due to side effects of physical activity (pain, 
muscle fatigue ...). 
3) Anyone may be temporarily unavailable for personal reasons. 
4) A person who has not missed more than 3 consecutive sessions on the 4 weeks of the rehabilitation 
program can maintain their participation in the research if they wish. 
5) The Supervisory Committee has the possibility to stop the search 
 
The final stop rules: 
1) Anyone is free to permanently stop his participation in research at any time without having to give 
reason. 
2) Anyone with an incapacitating health problem that prohibits the practice of a physical activity will be 
excluded from research by decision of the investigator who will inform the coordinator, the rehabilitation 
team and the research manager. 
 
There are no plans to replace people who permanently stop the search. The data will be excluded from the 
statistical analysis. A temporary or permanent stop of the research will be automatically documented in the 
medical file. 

 
 
 
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Research Monitoring Committee 
 
Research Monitoring Committee is composed of: 
 
SENARD Jean-Michel (PU-PH, scientific manager) 
RICHARD Lisa (Cardiologist, investigator) 
LABRUNEE Marc (PH, Scientific Officer) 
PATHAK Atul (Cardiologist, Scientific Officer) 
GUIRAUD Thibaut (PhD, Deputy Director of Clinique Saint Orens, project leader) 
BESNIER Florent (Teacher in Adapted Physical Activities, PhD student, coordinator of the project) 
 
The Research Monitoring Committee will meet 3 times: before the start of the research for the 
implementation visit, once 10 patients are included in the study, and at the end of the last end-of-study visit 
of the last patient. The Supervisory Committee ensures the smooth running of the research. 
 

 
 
 
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Ethical and regulatory compliance 
 
Exams and methods used in this research are part of the routine care as defined by Law No. 2004-806 of 9 
August 2004 (Article L1121-1, 2 ° paragraph and Article R1121-3 of the Public Health Code). This study is 
a  Clinical Routine Care Study 
The instigator, the coodinator, and the investigators who drive and  supervise the research undertake that 
this research is carried out in accordance with the law n ° 2004-806 of August 9th, 2004, as well as in line 
with Good Clinical Practice and the Declaration of Helsinki (Ethical Principles for Medical Research 
Involving Humans, Tokyo 2004). 
The research will be conducted in accordance with this protocol. Except in emergency situations requiring 
the implementation of specific therapeutic acts. 
This research received the favourable opinion of the Committee for the Protection of Persons (ethical 
committee) (CPP) Sud-Ouest and Outremer II on May 6, 2015. This research is covered by the liability 
insurance of La Clinique Saint Orens. 
The data recorded during this research are in accordance with the law n ° 78-17 of January 6, 1978 relating 
to data, files and freedoms modified by the law 2004-801 of August 6, 2004. The Saint Orens Clinic will 
send a request for an opinion to the Advisory Committee on the Treatment of Information in the Field of 
Health Research (CCTIRS) and a request of authorization to the National Information Commissioner's 
Office / French Data Protection Authority (CNIL). 
 
 
 
 
 

 
 
 
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References 
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Dickstein K, Vardas PE, Auricchio A, Daubert JC, Linde C, McMurray J, et al. 2010 focused 
update of ESC Guidelines on device therapy in heart failure: an update of the 2008 ESC Guidelines for the 
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resynchronization therapy. Developed with the special contribution of the Heart Failure Association and the 
European Heart Rhythm Association. European journal of heart failure. 2010 Nov;12(11):1143-53. 
2. 
Gabet A, Chatignoux E, Ducimetiere P, Danchin N, Olie V. Differential trends in myocardial 
infarction mortality over 1975-2010 in France according to gender: An age-period-cohort analysis. 
International journal of cardiology. 2016 Nov 15;223:660-4. 
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Blackledge HM, Tomlinson J, Squire IB. Prognosis for patients newly admitted to hospital with 
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Coumel P. Cardiac arrhythmias and the autonomic nervous system. Journal of cardiovascular 
electrophysiology. 1993 Jun;4(3):338-55. 
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Floras JS. Clinical aspects of sympathetic activation and parasympathetic withdrawal in heart 
failure. Journal of the American College of Cardiology. 1993 Oct;22(4 Suppl A):72A-84A. 
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Routledge FS, Campbell TS, McFetridge-Durdle JA, Bacon SL. Improvements in heart rate 
variability with exercise therapy. The Canadian journal of cardiology. 2010 Jun-Jul;26(6):303-12. 
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Galinier M, Pathak A, Fourcade J, Androdias C, Curnier D, Varnous S, et al. Depressed low 
frequency power of heart rate variability as an independent predictor of sudden death in chronic heart 
failure. European heart journal. 2000 Mar;21(6):475-82. 
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INFORMED CONSENT FORM 
Efficacy of High Intensity Interval Training vs Moderate Intensity and Continuous Training on Autonomic 
Nervous System modulations in Chronic Heart Failure. 
HRVFIT 2 - Study 
 
 
I, the undersigned …………………………..…… (last name, first name), certify that I have read and understood The 
Informed Consent. 
I had the opportunity to ask all the questions that I wanted to the investigator who explained to me the nature, the 
objectives, the potential risks and the constraints related to my participation in this clinical care research. 
Before taking part in this research, I benefited from medical examinations whose results were communicated to me 
and allow me to participate. 
I know the opportunity to interrupt my participation in this research at any time without having to justify my decision 
and I will do my best to inform the doctor who follows me in the research. This will not naturally call into question the 
quality of subsequent care. 
I have been assured that the decisions that are required for my health will be made at all times, in accordance with the 
current state of medical knowledge. 
I have noted that this research is conducted in accordance with Articles L1121-1 and following of the Public Health 
Code, relating to the protection of persons who are suitable for biomedical research and in accordance with Good 
Clinical Practice. 
I became aware that this research received the favourable opinion of the Ethical Research Committee on May 6, 2015 
and the authorization of the French National Agency for Medicines and Health Products Safety (ANSM) on January 
29, 2015 and was the subject of a statement to the National Information Commissioner's Office / French Data 
Protection Authority (CNIL). 
The research is a current care research according to the Ethical Research Committee, which means that there is no 
additional risk related to the study, the insurance is that of the Clinic responsible for care (Article L. 1142 -2). 
I agree that only persons who collaborate in this research or who are mandated by the instigator, as well as Health 
Authorities, have access to information in the strictest respect of confidentiality. 
I have received, in accordance with the provisions of the law relating to data, files and freedoms, I have a right of 
access and rectification. I also have the right to oppose the transmission of data covered by professional secrecy that 
may be used in the context of this research and to be processed. These rights are exercised with my doctor in the 
context of this research and who knows my identity. 
My consent does not relieve the investigator and the research manager of their responsibilities to me. I retain all rights 
guaranteed by law. 
The overall results of the research are communicated to me directly, if I wish, in accordance with the law of 4 March 
2002 on the rights of the sick and the quality of the health system. 
Having had sufficient time for reflection before making my decision, I freely and voluntarily agree to participate in the 
HRVFIT2 research. 
I can at any time ask additional information to the doctor who offered me to participate in this research. 
 
 
Done at : ………………     date : |__|__|__|__|__|__|__|__|            Done at : ………………       date : |__|__|__|__|__|__|__|__| 
 
Patient’s signature:  
 
 
    
            Doctor’s signature: 
 
- 1st sheet (original): to be kept apart by the investigator for 30 years in a secure lockable place 
- 2nd sheet: to give to the patient after signatures 
- 3rd leaflet: to be stored in the patient's file