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Archives of cardiovascular diseases
Volume 111, n° 10
pages 573-581 (octobre 2018)
Doi : 10.1016/j.acvd.2018.03.005
Received : 24 May 2017 ;  accepted : 3 Mars 2018
Clinical research

Is ventilatory therapy combined with exercise training effective in patients with heart failure and sleep-disordered breathing? Results of a randomized trial during a cardiac rehabilitation programme (SATELIT-HF)
La ventilation nocturne associée à l’entraînement physique est-elle efficace chez les patients insuffisants cardiaques ? Résultats d’une étude randomisée durant un programme de réadaptation cardiaque (SATELIT HF)
 

Marie-Christine Iliou a, , 1 , Sonia Corone b, 1, Barnabas Gellen c, d, Thierry Denolle e, Frederic Roche f, Anaïs Charles Nelson g, h, Christian Darné i
a Cardiac Rehabilitation Department, hôpital Corentin-Celton, AP–HP, 4, parvis Corentin-Celton, 92130 Issy-Les-Moulineaux, France 
b Cardiac Rehabilitation, centre hospitalier Bligny, 91640 Briis-sous-Forge, France 
c GHU Henri-Mondor/hôpital Albert-Chenevier, Assistance publique–Hôpitaux de Paris, 94010 Créteil, France 
d Faculté de médecine et de pharmacie, université de Poitiers, 86073 Poitiers, France 
e Cardiac Rehabilitation, hôpital Arthur-Gardiner, 35800 Dinard, France 
f Cardiac Rehabilitation Service, hôpital Nord, CHU de Saint-Étienne, 42270 Saint-Priest en Jarez, France 
g Unité d’épidémiologie et de recherche clinique, hôpital européen Georges-Pompidou, AP–HP, 75015 Paris, France 
h Centre de recherche des Cordeliers, UMRS 1138, université Paris–Descartes, Sorbonne Paris Cité, 75006 Paris, France 
i Pneumology Department, centre hospitalier Bligny, 91640 Briis-sous-Forge, France 

Corresponding author.
Summary
Background

Sleep-related disordered breathing is common in patients with chronic heart failure.

Aim

To assess the efficacy of short-term nocturnal ventilatory therapy combined with exercise training (V+ET) compared with exercise training alone (ET) in patients with chronic heart failure with sleep-disordered breathing.

Methods

Patients in New York Heart Association functional class II–IIIb, with an apnoea-hypopnoea index (AHI)>15/h, and enrolled in a cardiac rehabilitation programme, were centrally randomized to V+ET or ET. Subjects were classified as having obstructive sleep apnoea (OSA) (n =49) or central sleep apnoea (CSA)/mixed (n =69). The primary outcome was the change in the 10-second average oxygen consumption at maximum exercise (VO2peak ) at the end of the cardiac rehabilitation programme.

Results

Fifty-eight patients were randomized to V+ET and 60 patients to ET. The median increase in VO2peak was 15% [interquartile range 6–36%] in the V+ET group and 16% [0–31%] in the ET group (P =0.34). AHI decreased in both groups, but significantly more in the V+ET group (P =0.006). The decrease in the ventilatory efficiency (VE/VCO2 ) slope was not statistically different between the two-randomization groups (P =0.10). In subjects with CSA, the VE/VCO2 slope decreased significantly more in the V+ET group (P =0.03), while there was no difference between the two-randomization groups in subjects with OSA (P =0.75). Six cardiovascular events occurred in patients with OSA (all randomized to the ET group); in subjects with CSA, two events occurred in the V+ET group and three in the ET group.

Conclusions

Short-term nocturnal ventilation combined with exercise training does not increase the exercise capacity of patients with chronic heart failure.

The full text of this article is available in PDF format.
Résumé
Introduction

Les troubles respiratoires du sommeil sont fréquents chez les patients insuffisants cardiaques chroniques (IC). Le but de cette étude est d’évaluer l’efficacité d’une ventilation nocturne associée à un entraînement physique (V+EP) comparé à l’entraînement physique seul (EP) chez des patients IC avec des troubles respiratoires du sommeil.

Méthodes

Les patients IC en classe NYHA II à IIIb, avec un index d’apnée-hypopnée>15/h, inclus dans un programme de réadaptation cardiaque, ont été randomisés en deux groupes V+EP ou EP. Les patients ont été classés selon leur type d’apnée : obstructives (n =49) ou centrales/mixtes (n =69). Le critère principal de l’étude est le gain du pic de VO2  à la fin du programme de réadaptation cardiaque.

Résultats

L’analyse a porté sur 118 patients : 58 dans le groupe V+EP et 60 patients dans le groupe EP. L’augmentation du pic VO2  est de 15 % (6 % ; 36 %) dans le groupe V+EP et de 16 % (0 % ; 31 %) dans le groupe EP (p =0,34). L’index d’apnée-hypopnée diminue dans les deux groupes, mais de façon significativement plus importante dans le groupe V+EP (p =0,006). La diminution de la pente VE/VCO2  n’est pas statistiquement différente entre les deux groupes (p =0,10). Toutefois, chez les patients avec des apnées centrales, la diminution de la pente VE/VCO2  est significativement plus prononcée dans le groupe V+EP (p =0,03) alors qu’aucune différence entre les deux groupes n’apparaît chez les patients avec des apnées obstructives (p =0,75). Durant l’étude, 11 patients ont eu des événements cardiovasculaires : 6 patients avec des apnées obstructives (tous dans le groupe EP) et 5 chez les patients avec des apnées centrales : 2 dans le groupe V+EP et 3 dans le groupe EP.

Conclusions

La ventilation nocturne associée à l’entraînement physique n’apporte pas d’augmentation significative, à court terme, des capacités d’effort chez les patients en insuffisance cardiaque.

The full text of this article is available in PDF format.

Keywords : Exercise training, Sleep apnea, Heart failure, Cardiopulmonary exercise test, Ventilation

Mots clés : Entraînement physique, Apnées du sommeil, Insuffisance cardiaque, Épreuve d’effort cardio-pulmonaire, Ventilation

Abbreviations : AHI, CHF, CPAP, CSA, NYHA, OSA, VCO2 , VE, VE/VCO2 , VO2 , VO2peak


Background

Sleep-related disordered breathing is common in patients with chronic congestive heart failure (CHF), with a reported prevalence of 30–75% [1, 2]. The frequency of obstructive sleep apnoea (OSA) and central sleep apnoea (CSA) depends on the severity of the CHF [2]. The presence of CSA is independently associated with an increased risk of death in patients with CHF [3, 4]. Patients with CHF and OSA are also at higher risk of death [5].

Exercise training is standard care for patients with CHF [6, 7]. In a non-randomized study, 6 months of aerobic exercise training increased exercise capacity and reduced the apnoea-hypopnoea index (AHI) in patients with CHF and CSA [8]. Moreover, a recent meta-analysis of five studies, with a total of 129 patients, showed that exercise reduced the severity of sleep apnoea in patients with OSA, independent of changes in body weight [9]. Furthermore, in patients with CHF, treatment of coexisting OSA by continuous positive airway pressure (CPAP) improved left ventricular function and was associated with improved long-term outcomes [10]. The effect of CPAP or adaptive ventilation on co-existing CSA is more controversial [11, 12, 13, 14].

The aim of the present study was therefore to assess the efficacy of ventilatory therapy combined with exercise training compared with exercise training alone in patients with CHF with sleep-disordered breathing. We hypothesized that short-term nocturnal ventilatory therapy combined with exercise training would enhance the exercise capacity of patients with CHF and sleep-disordered breathing. The study was designed before the publication of the SERVE-HF trial; therefore, we hypothesized that nocturnal ventilatory therapy would be beneficial in both OSA and CSA [15].

Methods
Study design

The sleep apnoea treatment during cardiac rehabilitation of patients with CHF (SATELIT-HF) trial was a multicentre prospective two-parallel-group active-controlled trial conducted in 13 cardiac rehabilitation centres in France. Subjects were enrolled in a cardiac rehabilitation programme and were randomized to nocturnal ventilation on top of exercise training (V+ET group) or to exercise training alone (ET group). Randomization was generated by computer (RandoWeb), centralized and stratified by centre in a 1:1 ratio.

The institutional review board “CPP Île-de-France VI, Pitié-Salpêtrière” approved the trial (number 2010-A00079-30). All participants gave informed consent. The trial was conducted in accordance with the amended Declaration of Helsinki and was registered on ClinicalTrials.gov (NCT identifier number NCT01120548).

Subject selection

The eligibility criteria for inclusion were: age 18–85 years; New York Heart Association (NYHA) functional class II–IIIb; left ventricular ejection fraction40% assessed by echocardiography; AHI>15/h determined by nocturnal polygraphy and entering a cardiac rehabilitation programme.

The main exclusion criteria were:

valvular heart disease with surgical indication; decompensated CHF or coronary angioplasty<10 days;
myocardial infarction<2 weeks;
cardiac surgery<3 weeks;
current use of nocturnal ventilation therapy;
severe chronic respiratory failure or hypercapnia>46mmHg;
subject unable to perform a 6-minute walk test or an exercise test or with contraindication to cardiac rehabilitation according to French guidelines [16];
resting systolic blood pressure<80mmHg or >180mmHg;
haemoglobin concentration<9g/dL.

Interventions
Procedures and cardiopulmonary exercise test

Before the first and after the last exercise training session, subjects underwent a clinical examination, had a blood sample taken (natremia, serum creatinine, protein, haemoglobin and B-type natriuretic peptide) and underwent a cardiac examination, including a 12-lead electrocardiogram, echocardiography, a cardiopulmonary exercise test, a 6-minute walk test and nocturnal polygraphy. Clinical characteristics included age, sex, NYHA class, body mass index, resting respiratory rate, heart rate, resting blood pressure and medications.

The cardiopulmonary exercise tests were performed in the cardiac rehabilitation centres under the supervision of a cardiologist, either on a treadmill using the modified Naughton protocol or on a cycle ergometer with an increased 10W workload every minute until exhaustion. Exercise ventilation and expired gases were measured; breath-by-breath expired gas analysis included oxygen consumption (VO2 ), carbon dioxide output (VCO2 ) and minute ventilation (VE). Data are reported as measured values at maximum exercise and at the first ventilatory threshold [17]. Derived variables included the respiratory exchange ratio and ventilatory equivalents per expired CO2 (ventilatory efficiency; VE/VCO2 ). The 10-second average VO2 at maximum exercise was recorded as the VO2peak . VE was plotted against VCO2 over the exercise period, to give the VE/VCO2 slope. Maximum workload and total duration of exercise were also reported.

All drug treatments were left at the discretion of the investigator. Adverse events, including cardiovascular events (acute heart failure, arrhythmias, stroke, death) were recorded throughout the trial. The patients were followed in the trial up to the second exercise test or second polygraph, whichever occurred last.

Exercise training programme

The exercise-training programme could differ between centres, but included at least 180minutes per week of supervised exercise training. The training programme included 20–30minute bouts of bicycle or treadmill endurance and another dynamic physical activity (calisthenics, resistance training, water-based exercise, walking, etc.). The intensity of endurance exercise training was individualized according to the ventilatory threshold and/or was set at 12–14 on the Borg scale. When possible, the duration of training sessions was increased progressively, up to a maximum of 300minutes of endurance exercise per week. Training sessions were performed 3–5 days a week over a period of 4–9 weeks. A total of 1200–1440minutes of exercise was the goal to be achieved for each patient.

Polygraphy

Full diagnostic polygraphy was performed in the cardiac rehabilitation centres, with possible support from the local polysomnography reference centre. All polygraphs were recorded digitally and reviewed by one author. The central review was blinded to the randomization group. Subjects were classified into three groups based on polygraphy findings: CSA, for an AHI>15/h with >50% of the apnoea-hypopnoea events occurring without any respiratory effort and with at least 10 central events per hour; OSA, for an AHI>15/h with 80% or more obstructive events; or mixed OSA/CSA, if the AHI was >15/h, with none of the above [17]. Patients with Cheyne-Stokes respiration could be classified as having CSA or mixed OSA/CSA.

Nocturnal ventilation

In agreement with the published results of the CANPAP study, ventilatory therapy was adapted to the type of sleep-disordered breathing (OSA, CSA or mixed) [12]. Nasal or full-face masks were adapted individually. The use of a humidifier was recommended, but not mandatory.

Nocturnal ventilation for the CSA group was adaptive servoventilation (AutoSet CS™ 2 or S9 AutoSet CS™; ResMed, San Diego, CA, USA) set at default settings before first use: expiratory positive airway pressure range, 4–10cm of water; minimum pressure support at 3cm of water; maximum pressure support at 10cm of water. The OSA group was treated with CPAP with a range of pressures between 4 and 12cm of water (AutoSet S8 Spirit™; ResMed). For mixed OSA/CSA, the choice of treatment was determined with the expert doing the central review of the polygraphs.

In the V+ET group, blood pressure was measured automatically at first use, before the start of ventilation, then at 5minutes, 20minutes and 60minutes. Systolic blood pressure<85mmHg or poor tolerance led to the withdrawal of nocturnal ventilation and exclusion.

After the first night, the settings were adjusted according to the ventilation variables recorded by the device. Subjects were instructed to use the device for at least 4hours every night and were reminded regularly about the use of the nocturnal device.

After 1 week and at the end of the programme, the following ventilation variables were collected:

compliance;
mask leaks;
AHI;
ventilation mode;
used pressures.

Adherence was estimated based on the number of nights when the device was used and the mean duration of nightly use, using the reports extracted from the device.

Outcomes

The primary outcome was the change in the VO2peak at the end of the cardiac rehabilitation programme compared with baseline (at inclusion). The secondary outcomes were cardiopulmonary exercise testing measures:

maximal and sub-maximal workload;
test duration;
VE/VCO2 slope;
6-minute walk distance.

Statistical analysis

The sample size was determined for the hypothesis of 10% superiority for V+ET compared with ET, with a type I error of 5%. Fifty patients per group allowed for an 80% probability of detecting a significant difference (calculation done with MFCalc software). The statistical plan was prespecified.

The analysis was based on intention to treat. Randomized subjects with AHI<15/h or with consent withdrawal were excluded from the intention-to-treat set (Figure 1). Randomization groups were compared by covariance analysis, with the baseline value as covariate and the change from baseline as dependent variable. Differences in proportions were tested by the χ 2 test or Fisher's exact test. Data are summarized as means±standard deviations or medians [interquartile ranges]. All statistical tests were two-sided, and a P value<0.05 was considered statistically significant.



Figure 1


Figure 1. 

CONSORT diagram showing the flow of participants. All patients discontinued from intervention were included in the safety analysis. AHI: apnoea-hypopnoea index; CPET: cardiopulmonary exercise test.

Zoom

Following the publication of the results of the SERVE-HF trial, a post-hoc subgroup analysis on AHI, VE/VCO2 slope and safety was performed in each type of sleep-disordered breathing [17].

Statistical analysis was done using SAS software, version 9.2 (SAS Institute, Inc., Cary, NC, USA).

Results

A total of 159 subjects with CHF were enrolled. The first participant was enrolled in November 2010 and the last patient completed the study in July 2014. One hundred and twenty-six subjects were randomized and 118 (94%) were included in the intention-to-treat set. Fifty-eight of the 61 patients randomized to the ET group and 60 of the 65 patients randomized to the V+ET group were analyzed (Figure 1). The characteristics of the two-randomization groups at baseline are presented in Table 1. Overall, 49 (41.5%) subjects were diagnosed with OSA, 60 (50.8%) with CSA and nine (7.6%) with mixed CSA/OSA at baseline. The nine subjects with mixed OSA/CSA had mainly CSA and therefore were treated with adaptive servoventilation; these nine subjects were grouped with CSA thereafter.

The median trial duration was 34 [28–48] days. At the end of the study, body mass index was unchanged at 26.0±4.8kg/m2 and 26.4±3.6kg/m2 in the ET group and V+ET groups, respectively.

The duration of nocturnal ventilation was 24 [14–37] nights and 6.4±1.7hours/night in the V+ET group. Overall, the mean percentage of scheduled nights with nocturnal ventilation was 70.5% (64.7% and 79.0% in those with OSA and CSA, respectively). The percentages of scheduled nights with more than 4hours of nocturnal ventilation were 48% and 52% in those with OSA and CSA, respectively (P not significant).

The mean total number of training sessions was 18±6 in the ET group and 19±5 in the nocturnal V+ET group (P =0.40). It has to be noted that only one patient did the exercise testing and training on a treadmill.

Left ventricular ejection fraction measured by echocardiography increased from 34±7% to 38±9% during the follow-up, but without any statistical differences between the two groups.

Exercise capacity was increased in both groups at the end of the trial. The median increase in VO2peak was 16% [0–31%] in the ET group and 15% (6–36%) in the V+ET group. There was no statistically significant difference between the two groups in terms of VO2peak at the end of the cardiac rehabilitation programme (P =0.34) (Table 2).

There were no differences between the two groups in ventilatory threshold variables or duration of exercise test (P =0.43) (Table 2).

The VE/VCO2 slope decreased by 7±14% in the ET group and by 9±18% in the V+ET group, respectively (P =0.10). In subjects with CSA, the VE/VCO2 slope decreased significantly more in the V+ET group than in the ET group (P =0.03); in subjects with OSA, there was no difference between the two-randomization groups (P =0.75) (Figure 2).



Figure 2


Figure 2. 

Ventilatory efficiency (VE/VCO2 ) slope at baseline and end of study per type of sleep-disordered breathing in each randomization group. A. Patients with obstructive sleep apnoea. B. Patients with central or mixed sleep apnoea. Data are expressed as mean±standard deviation. P values are for within-group comparisons from baseline.

Zoom

AHI decreased in both groups, but significantly more in the V+ET group (P =0.006) (Table 3).

We did not find any correlation between the number of hours/night or the number of nights under ventilation and the gain in VO2peak (r =0.05; not significant).

Overall, 11 cardiovascular events were reported in 11 subjects:

nine cases of acute congestive heart failure, one ventricular tachycardia treated by an implantable cardioverter defibrillator and one transient ischaemic attack;
nine events were reported in the ET group;
two in the V+ET group (P =0.03).

Of these, six events occurred in patients with OSA (all randomized to the ET group), three events occurred in subjects with CSA in the ET group and two events occurred in subjects with CSA in the V+ET group. No deaths occurred.

Discussion

The SATELIT-HF trial showed that short-term nocturnal ventilatory therapy combined with a standard cardiac rehabilitation programme led to no additional gain in the exercise capacity of patients with CHF with sleep-disordered breathing [8]. Moreover, exercise training alone had a positive impact on AHI in both OSA and CSA, independent of weight loss.

The VE/VCO2 slope has been shown to be a major prognostic factor in patients with heart failure [18]. In the present study, the VE/VCO2 slope decreased in the two groups, with no statistical difference between the two groups. However, in the subgroup of patients with CSA, the decrease was significantly greater in the V+ET group, while no significant difference was observed in patients with OSA. In a previous crossover study, 8 weeks of regular exercise training reduced VE, the VE/VCO2 slope and the sensation of breathlessness in patients with CHF [19]. A recent meta-analysis showed that aerobic exercise may be effective in improving the VE/VCO2 slope in patients with systolic HF, but these effects were limited to a specific heart failure population meeting specific inclusion criteria in a limited number of studies [20].

It is common for patients with CHF and CSA to have exaggerated peripheral and central chemosensitivity to CO2 , and for the degree of CO2 hypersensitivity to correlate with the AHI [21, 22, 23, 24, 25]. We hypothesized that exercise induces a transient decrease in the sensitivity of the central CO2 receptor, and that ventilatory therapy allows a levelling of the oscillatory ventilation during the night. We also hypothesized that the combination of the two treatments would synergistically attenuate the alteration of the CO2 -dependent threshold of apnoea in patients with CSA.

In the present study, exercise training per se led to an improvement in exercise capacity and mitigated sleep-breathing disorders, which are two major prognostic variables in heart failure. The present study confirmed a beneficial effect of ventilatory therapy in patients with CHF and OSA [10]. In our study, all cardiovascular events in subjects with OSA were reported in the ET group, while the numbers of events were similar in the two-randomization groups in subjects with CSA. The relatively high rate of cardiovascular events reported in the ET group suggests that ventilatory therapy should be recommended in patients with OSA undergoing cardiac rehabilitation.

Contrary to the SERVE-HF study, which was conducted on many more subjects than the present study, no negative trend was shown in subjects with CSA. In fact, even if few cardiovascular events were reported, the lower number of cardiovascular events was reported in the V+ET group. In SERVE-HF and the present study, heart failure medication was optimal. Besides, SATELIT-HF was a short-term study with close follow-up of the patients, guaranteeing correct control of CHF. Subjects in SERVE-HF were slightly older (mean age 69–70 years) and more often in NYHA class III, while the number of AHI events per hour was similar at inclusion [15]. An ongoing trial (Effect of Adaptive Servo Ventilation on Survival and Hospital Admissions in Heart Failure [ADVENT-HF]) should help to determine the optimal ventilation treatment of patients with CSA, if any [26].

Study limitations

SATELIT-HF has some limitations. First, the sample size calculation was based on an assumption of an 18–20% increase in VO2peak , while a 16% increase was observed in the ET group; however, the very small difference between the two-randomization groups suggests that short-term ventilatory therapy on top of exercise training does not increase exercise capacity. Second, even if compliance with nocturnal ventilation was moderate and in homogenously distributed, our trial showed that AHI decreased dramatically in ventilated patients; we cannot exclude that more days on nocturnal ventilator therapy might be effective. Third, no data were recorded after cessation of cardiac rehabilitation and the evolution of AHI after the end of the cardiac rehabilitation programme is unknown.

Conclusions

Short-term nocturnal ventilation in addition to exercise training does not increase the exercise capacity of patients with CHF.

Sources of funding

The funding sources for this study were: the Exercise, Rehabilitation and Sports Working Group (groupe de travail exercice réadaptation et sports [GERS]) of the French Society of Cardiology, which was a grant recipient from the ResMed foundation and the Association d’Entraide des Polios et Handicapés (ADEP) Assistance, 92800 Puteaux, France.

Author contributions

M.-C.I. and S.C. are the guarantors of the manuscript and take responsibility for its content, including the data collection and analysis, and the review and writing of the manuscript. C.D. contributed to the study design, the central review of polygraphies and data collection, and the review of the manuscript. B.G., T.D., F.R., and A.C.N. contributed substantially to the data collection or analysis and the review and writing of the manuscript. All authors provided approval of the version to be published.

Disclosure of interest

The authors declare that they have no competing interest.


Acknowledgments

The authors thank Dr Bernadette Darné for writing assistance.


Appendix

Scientific committee

Dr Christian Darné and Dr François Viau, Centre Hospitalier Bligny, Briis-sous-Forge; Pr Marie Pia d’Ortho, Hôpital Bichat, Paris; Dr Carole Philippe, Hôpital Pitié-Salpêtrière, Paris; Dr Sylvie Rouault, ADEP Assistance, Paris, France.

Institutions where the work was performed

Cardiac Rehabilitation Department, Hôpital Corentin Celton, AP-HP, Issy-les-Moulineaux, France.

Cardiac Rehabilitation Department, Centre Hospitalier Bligny, Briis-sous-Forge, France.

Cardiac Rehabilitation Department, Hôpital Albert Chenevier, AP-HP, Créteil, France.

Cardiac Rehabilitation Centre, Hôpital Arthur Gardiner, Dinard, France.

Cardiac Rehabilitation Department, Hôpital Nord - CHU de Saint Etienne, Saint-Priest en Jarez, France.

Cardiac Rehabilitation Centre, Clinique de Chatillon, Chatillon, France.

Cardiac Rehabilitation Centre, Centre Cardiovasculaire de Valmante, Marseille, France.

Cardiac Rehabilitation Department, Hôpital Intercommunal Sud Léman Valserine, Saint-Julien-en-Genevois, France.

Cardiac Rehabilitation Centre, Clinique La Maison du Mineur, Vence, France.

Cardiac Rehabilitation Centre, Clinique Cardiocéan, Puilboreau, France.

Cardiac Rehabilitation Centre, Clinique de la Mitterie, Lille, France.

Cardiac Rehabilitation Centre, Centre de Réadaptation Cardio-Respiratoire Dieulefit Santé, Dieulefit, France.

Cardiac Rehabilitation Centre, Fondation Leopold Bellan, Tracy-le-Mont, France.

Investigators

Clinique de Chatillon, Chatillon: Jean Louis Bussiere, Dalila Bennegadi, Sophie Durand.

Centre Hospitalier Bligny, Briis-sous-Forge: Sonia Corone, Claudie Burgot.

Hôpital Corentin Celton, AP-HP, Issy-les-Moulineaux: Marie-Christine Iliou, Pascal Cristofini, François Ledru.

GHU Henri Mondor/Hôpital Albert Chenevier, AP-HP, Paris: Barnabas Gellen.

Hôpital Arthur Gardiner, Dinard: Thierry Denolle, Sophie Nicolas, Armelle Richard.

Hôpital Intercommunal Sud Leman Valserine, Saint-Julien-en-Genevois: Sophie Durand.

Clinique La Maison du Mineur, Vence: Anne Bellemain-Appaix, Hélène Lescaut.

Clinique Cardiocéan, Puilboreau: Muriel Bigot, Carole Dossetto.

Clinique de la Mitterie, Lille: Marie Emilie Lopes, Georges Deleporte.

Centre Cardiovasculaire de Valmante, Marseille: Jean-Etienne Touze, Anne Marie Gardiner.

Fondation Leopold Bellan, Tracy-le-Mont: Mohamed Ghannem.

Centre de Réadaptation Cardio-Respiratoire Dieulefit Santé, Dieulefit: Richard Brion, Frédéric Herengt.

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1  Marie-Christine Iliou and Sonia Corone are co-authors.


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