Steeve Jouini

Contexte : Le syndrome de Marfan (SDM) est une maladie génétique autosomique dominante rare provoquée par la mutation du gène FBN1 codant pour la protéine fibrilline-1. La fibrilline-1 est le principal composant des microfibrilles, éléments présents dans l’ensemble des tissus de l’organisme. Ce syndrome se caractérise par la multitude d’atteintes cliniques dues à l’altération de cette protéine.Les patients SDM peuvent développer des anévrismes au niveau de la racine aortique (i.e., sinus de Valsalva) conduisant à la dissection aortique. Ceci est l’un des principaux facteurs de morbidité́ chez ces patients. Actuellement, la prévention passe principalement par la chirurgie aortique. Cependant, les répercussions sont globales et peuvent altérer le fonctionnement d’autres tissus tels que le tissu musculaire squelettique, le tissu osseux, le tissu pulmonaire et le tissu oculaire. L’association des atteintes squelettiques (e.g. scoliose, hyperlaxité), musculaires et oculaires engendrent une diminution de la qualité́ de vie des patients. Ces atteintes sont associées à des douleurs et des handicaps qui retentissent sur l’activité professionnelle, les loisirs et la vie de famille. Dans ce contexte, l’activité physique pourrait représenter une alternative pertinente pour la prise en charge de des patients SDM. Une étude animale récente suggère que l’entrainement modéré serait bénéfique.Hypothèses : 1/ L’entrainement physique améliore la qualité de vie des patients SDM. 2/ La combinaison d’un entraînement en résistance avec un entraînement en aerobie est efficace pour améliorer la puissance musculaire, la force musculaire et la qualité de vie des patients SDM.Objectif principal : Démontrer que l’entrainement physique réalisé à domicile améliore la qualité de vie des patients SDM. Objectifs secondaires : 1/ Déterminer les effets bénéfiques de l’entrainement personnalisé à domicile sur la capacité physique des patients. 2/ Démontrer le caractère sécuritaire de la prise en charge des patients SDM par l’entraînement physique personnalisé.Méthodologie : au moins 117 patients atteints du SDM et 35 sujets sains ont été inclus dans cette étude. Les patients ont été randomisés en 3 groupes : Groupe 1 : sujets sains (pas d’entrainement) ; groupe 2 : patients SDM (entraînement personnalisé de 3 mois) et ; groupe 3 : patients SDM contrôle (pas d’entrainement).Le protocole d’entrainement a duré 3 mois et a été réalisé au domicile des patients SDM. Il consistait en 2 séances d'entraînement par semaine réalisées par un spécialiste de l'activité physique adaptée (AP). Des évaluations pré et post-entrainement ont été effectuées au centre de référence national Marfan de l'hôpital Bichat-Paris. Elles consistaient à évaluer la psychométrie sur la base de questionnaires auto-administrés (e.g. IPAQ, MOS SF-36) et des paramètres physiologiques tels que la consommation maximale d'oxygène, le diamètre de l'aorte, la fonction du ventricule gauche, l’analyse de l’onde de pouls et la puissance musculaire squelettique au repos et pendant l'exercice. Nos résultats ont montré une amélioration significative de la qualité de vie, de la capacité cardiorespiratoire, de la force musculaire squelettique et une baisse de la pression artérielle chez les patients ayant terminé le programme d'entraînement. Nos résultats ont également montré une non-aggravation du sinus de Valsalva et aucune dissection aortique. Enfin, nos résultats ont montré une amélioration des pressions sanguines au cours de l’effort chez les patients SDM entraînés. Conclusion : Cette approche expérimentale randomisée et contrôlée pourrait représenter une nouvelle alternative thérapeutique non médicamenteuse et personnalisée des patients atteints du SDM.

Background: Marfan syndrome (MFS) carries a high risk of aortic dilation and dissection, yet the cardiovascular impact of specific exercise modalities remains uncertain. Methods and Results: Forty-five adults with MFS were randomised to 12 weeks of endurance (END), resistance (RES) or combined endurance–resistance (COMB) training (15 per group). Primary outcomes were resting and exercise systolic blood pressure (SBP), augmentation index normalised to 75 beats·min ^-1 (AIx@75), pulse-wave velocity (PWV), aortic root diameter, left-ventricular ejection fraction (LVEF) and global longitudinal strain (GLS). Compared with END, RES reduced resting SBP by –11 mm Hg versus –5 mm Hg and lowered AIx@75 by –29 % versus –9 % (interaction P < 0.05). PWV declined by –1.71 m·s ^-1 (RES) and –1.24 m·s ^-1 (COMB) versus –0.37 m·s ^-1 (END; P < 0.001). LVEF rose by +4.4 % (RES) and +3.2 % (COMB) compared with +1.6 % (END), paralleled by similar GLS improvements. Muscle strength increased in RES (+21 %) and COMB (+18 %) but not END (+3 %). No group showed a significant change in aortic root diameter, and no adverse events occurred. Conclusions: In adults with MFS, a 3-month programme incorporating resistance exercise— alone or combined with endurance—confers larger reductions in blood pressure and arterial stiffness and enhances ventricular function without short-term aortic enlargement. These findings support the safe inclusion of resistance training in exercise prescriptions for MFS, with continued surveillance to confirm long-term safety. Clinical Trial Registration: URL: https://clinicaltrials.gov ; Unique identifier: NCT04553094 . Clinical perspective: What’s new ?: Safe integration of resistance training : Patients with Marfan syndrome who followed a resistance or combined (endurance + resistance) program showed greater improvements in vascular and cardiac parameters than those assigned to purely endurance training. Significant reduction in blood pressure and improvement in Augmentation Index normalized to a heart rate of 75 beats per minute (bpm) AIx@75 : The Resistance and Combined groups experienced a drop in resting blood pressure (≈ 8 to 10% corresponding to –11 to –13 mmHg) and a much more pronounced decrease in AIx@75 (–25 to –30 mmHg) compared to the Endurance group (–9 mmHg),). Improved myocardial function : Myocardial strain and left ventricular ejection fraction (LVEF) tended to increase more in the groups performing resistance-type training (approximately +8% for strain and +7% for LVEF), without negatively impacting the diameter of the Valsalva sinuses. What are the clinical implications?: Improved cardiovascular health : The significant reduction in blood pressure during exercise and the improvement in AIx@75 reflect a decrease in hemodynamic stress at the aortic root, which could help reduce the risk of aortic complications such as aneurysm or dissection. Expansion of exercise-based therapeutic options : These results suggest that a supervised training program incorporating resistance exercises is more beneficial for improving vascular and cardiac function in Marfan patients than endurance training and can be safely provided. Need for rigorous echocardiographic follow-up : Despite the absence of any worsening in Valsalva sinus diameter, regular echocardiography remains essential to monitor the evolution of cardiovascular parameters and to determine optimal exercise loads in these high-risk patients.

Background: Marfan syndrome (MFS) is a genetic disorder affecting the vascular and musculoskeletal systems. Limited knowledge exists regarding the exercise benefits for this population. This study aimed to explore the impact of a structured exercise program on the quality of life (QoL) and physical capabilities of patients with MFS. Methods and Results: This was a randomized, controlled, parallel‐group trial. Patients with MFS were randomized in a 1:1 ratio to either a training group or a control group. The trial included a 3‐month online supervised training program. Seventy patients with MFS were compared with healthy subjects. They were randomized into a training group (MFS‐T) and a control group (MFS‐C). The training consisted of 2 supervised online sessions weekly for 3 months. The primary outcome was QoL, assessed using the Medical Outcomes Study Short‐Form 36 questionnaire. Baseline QoL in all dimensions was lower in patients with MFS. Their peak oxygen uptake was 25% lower, and muscle elasticity was diminished compared with healthy subjects. Postintervention, significant improvements were observed in the MFS‐T group relative to the MFS‐C group: QoL (+20.2±14.3 versus +0.7±0.5), peak oxygen uptake (+34% versus +14%), muscle elasticity index (11.5±8.2 versus +1.2±1.7), reduced blood pressures during isometric squats (systolic −19±30 versus 0±6; diastolic −27±39 versus +2±15), and reduced pulse wave velocity at rest (−1.20±1.89 versus −0.40±1.61) and postexercise (−0.42±0.45 versus +0.08±0.48). The aortic diameter remained stable in both groups (MFS‐T−0.19±1.1 versus MFS‐C+0.11±0.78). After training, QoL remained lower in MFS‐T than in healthy subjects, but peak oxygen uptake, pulse wave velocity at rest, and postexercise were similar to those of healthy subjects. Conclusions: The 3‐month online training program significantly enhanced QoL and cardiovascular/muscular metrics in patients with MFS without affecting aortic root diameter, suggesting its potential as part of a management strategy for MFS. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04553094.

Background: Marfan syndrome (MFS) is a rare genetic disorder affecting the vascular and musculoskeletal systems. Exercise is classically contraindicated and there are no data on the limitations associated with the syndrome and the benefits of training in this population. This study aimed to characterise the quality of life (QoL) and physical capacity of patients with MFS and to evaluate the benefits of a 3-month online personal training program. Methods: MFS patients were compared with healthy subjects (H-S) at baseline. They were then randomized 1:1 into a training group (MFS-T) and a control group (MFS-C). The training consisted of 2 supervised online training sessions per week at home for 3 months, and the session program was selected based on the initial assessment. The main outcome measure was QoL as assessed by the MOS SF-36. The evolution of parameters during training was compared between MFS-T and MFS-C. Results: At baseline, QoL in all dimensions was lower in MFS. Peak oxygen uptake (VDO ₂ peak) was also 25% lower, as was muscle elasticity. Training significantly improved 1) QoL (+20.2±14.3 MFS-T vs. 0.7±0.5 MFS-C), 2) VDO ₂ peak (+34% MFS-T vs. 14% MFS-C), 3) muscle elasticity index (11.5±8.2 MFS-T vs. +1.2±1. 7 MFS-C), reduced blood pressures during isometric squat (systolic −19±30 MFS-T vs. 0±6 MFS-C; diastolic −27±39 MFS-T vs. +2±15 MFS-C), reduced pulse wave velocity (PWV) at rest (-1.20±1.89 MFS-T vs. −0.40±1.61 MFS-C) and after peak exercise (-0.42±0.45 MFS-T vs. 0.08±0.48 MFS-C). Aorta diameter remained stable in both groups (MFS-T −0.19±1.1 vs. 0.11±0.78 MFS-C). After training, QoL remained lower in MFS-T than in H-S, but peak VDO ₂ , PWV at rest and after exercise were similar to those of H-S. Conclusions: A 3-month online training program had a beneficial effect on QoL, cardiovascular and muscular parameters in MFS without affecting aortic root diameter.

Aim: To provide a state-of-the-art review of the last 10 years focusing on cardiac fatigue following a marathon. Methods: The PubMed, Bookshelf and Medline databases were queried during a time span of 10 years to identify studies that met the inclusion criteria. Twenty-four studies focusing only on the impact of marathons on the cardiac function and factors involved in cardiac fatigue were included in this review. Results: Sixteen studies focused on the impact of marathons on several biomarkers (e.g., C-reactive protein, cardiac troponin T). Seven studies focused on the left (LV) or right (RV) ventricular function following a marathon and employed cardiac magnetic resonance, echocardiography, myocardial speckle tracking and heart rate variability to analyze global and regional LV or RV mechanics and the impact of the autonomic nervous system on cardiac function. One study focused on serum profiling and its association with cardiac changes after a marathon. Conclusions: This review reported a negligible impact of marathons on LV and RV systolic and contractile function but a negative impact on LV diastolic function in recreational runners. These impairments are often associated with acute damage to the myocardium. Thus, the advice of the present review to athletes is to adapt their training and have a regular medical monitoring to continue to run marathons while preserving their cardiac health.