Marie-Christine Picot

Key Points: Children with CKD exhibit markedly lower cardiopulmonary fitness with an absolute maximal oxygen uptake deficit of 10 ml/kg per minute compared with reference values. More than half of the patients show impaired fitness as early as CKD stage 3, highlighting early functional vulnerability. Maximal oxygen uptake is independently associated with modifiable parameters commonly targeted by rehabilitation, supporting tailored intervention strategies. Background: Children with CKD are at high cardiovascular risk, yet cardiopulmonary fitness is rarely assessed in routine care. Maximal oxygen uptake (VO ₂ max) is a powerful prognostic marker, and Z -score–based evaluations may improve early risk stratification. Methods: In this prospective multicenter study, children aged 6–17 years with CKD stages 2–5 (Kidney Disease Improving Global Outcome) underwent standardized cardiopulmonary exercise testing (CPET). VO ₂ max was expressed as Z -scores using contemporary pediatric reference values. Impaired fitness was defined as VO ₂ max Z -score <–1.64. Multivariable linear regression was used to identify independent determinants of VO ₂ max. Results: Among 88 enrolled patients (mean age 12±4 years, 67% male), 77 completed a valid CPET. Mean VO ₂ max Z -score was −1.8±2.1, corresponding to 33.5±9.2 ml/kg per minute, that is, an absolute lowering of approximately 10 ml/kg per minute compared with age-matched and sex-matched reference values. Overall, 57% had impaired fitness. VO ₂ max was progressively lower across higher CKD stages ( P < 0.001 ). In multivariable analysis, higher VO ₂ max was independently associated with higher hemoglobin concentration, better pulmonary function (forced expiratory volume in 1 s), better ventilatory efficiency (VE/VCO ₂ slope), and higher ventilatory anaerobic threshold, explaining 77% of VO ₂ max variability. Conclusions: Cardiopulmonary fitness is markedly lower in children with CKD, with a clear stage-dependent decline that is already evident at early disease stages. The magnitude of VO ₂ max impairment is substantial and related to potentially modifiable clinical and functional factors, supporting early CPET-based screening and the development of targeted, multidisciplinary rehabilitation in pediatric CKD. Clinical Trial registry name and registration number: Clinicaltrials.gov identifier NCT04897672 and Montpellier University Hospital Institutional Review Board (IRB 202100852).

Background: The QUALIREHAB (Cardiac Rehabilitation in Youth With Congenital Heart Disease) trial demonstrated the efficacy of a hybrid cardiac rehabilitation model in adolescents and young adults with congenital heart disease. This post hoc mixed‐methods study aimed to identify baseline predictors of clinical improvement and to characterize key components supporting implementation and scalability. Methods: Seventy participants aged 13 to 25 years from the intervention arm were analyzed. Clinical improvement was defined as a clinically meaningful increase in cardiopulmonary fitness (increase in peak oxygen uptake ≥3.5 mL/kg per min) or health‐related quality of life (Pediatric Quality of Life Inventory increase ≥4.3 points). Multivariable logistic regression models identified predictors of clinical improvement. Semistructured interviews with patients and health care professionals explored experiences, barriers, and implementation mechanisms. Results: The absence of prior cardiac surgery or interventional catheterization was independently associated with short‐term improvement in peak oxygen uptake. At 1 year, male sex and lower baseline ventilatory anaerobic threshold were associated with greater peak oxygen uptake improvement. Lower baseline ventilatory anaerobic threshold was also the only predictor of clinically meaningful health‐related quality of life improvement. Qualitative findings highlighted the accessibility and acceptability of the hybrid model but underscored the need for higher‐intensity and more varied exercise modalities, integrated digital tools, continuous psychological support, family involvement, and structured postrehabilitation follow‐up to sustain long‐term benefits. Conclusions: Among treated participants, male sex, absence of prior cardiac surgery, and marked baseline deconditioning were associated with greater clinical improvement, supporting a shift from standardized toward tailored cardiac rehabilitation in congenital heart disease. By addressing key logistical and psychosocial barriers, this scalable framework offers a pragmatic model for routine care implementation and may be transferable to other pediatric chronic conditions. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03690518.

Objectives: The VACIMRA trial demonstrated that delaying MTX initiation in RA by 1 month after the 13-valent pneumococcal conjugate vaccine (PCV13) improves humoral responses at 1 and 12 months. Whether this delay impacts disease activity and radiographic progression over 1 year remains uncertain. Methods: This ancillary study compared changes in disease activity (DAS28-ESR) from inclusion (M0) to months 1, 2, 3, 6 and 12 between patients with early RA who started MTX immediately vs 1 month after PCV13. Structural progression was assessed using the van der Heijde–modified Sharp score (mSHS) on X-rays at inclusion, 6 and 12 months. The primary outcome was the proportion of patients in remission (DAS28-ESR < 2.6) or low disease activity (LDA) (DAS28-ESR ≤ 3.2) at 1 year. Results: Among 276 VACIMRA participants, 100 were enrolled at the Montpellier centre (96 analysable at M0, 83 at M12). Both groups had similar baseline characteristics: mean age 58 ± 14 years, DAS28-ESR 4.88 ± 0.94, total mSHS 1.53 ± 3.62. Treatments during follow-up were comparable except for MTX cumulative dose at 1, 3, 6 months. At 12 months, remission (53.7% vs 46.3%, P = 0.51) and LDA rate (75.6% vs 61.0%, P = 0.15) were similar. DAS28-ESR was similar at 1 and 3 months but favoured the DELAY group at 6 (2.66 ± 1.07 vs 3.28 ± 1.34, P = 0.02) and 12 months (2.23 ± 1.03 vs 3.00 ± 1.16, P < 0.01). mSHS progression was comparable at 6 and 12 months. Conclusion: Deferring MTX for 1 month after PCV13 to enhance immunity did not worsen RA disease control, radiographic progression or treatment escalation after 1 year of follow-up.

Despite significant medical advances in recent decades, cardiopulmonary fitness decreases faster in youth with congenital heart disease (CHD) than in healthy peers, resulting in impaired health-related quality of life (HRQoL) and increased cardiovascular risk. Apart from cardiac rehabilitation, non-pharmacological preventive interventions have been scarcely evaluated in this population. Sophrology, a mind-body method involving dynamic relaxation in full awareness, breathing exercises, and imagination, has demonstrated benefits for mental health and well-being. This multicenter randomized controlled trial evaluated the impact of a remote sophrology program on cardiopulmonary fitness and HRQoL in youth with CHD. A total of 200 13-to-25-year-old CHD patients were randomly assigned to either the intervention (i.e., eight remote individual sophrology sessions), or the standard of care. The primary outcome was the change in maximum oxygen uptake (VO_2max) measured by cardiopulmonary exercise testing from baseline to 12 months. Secondary outcomes included HRQoL and mental health assessments. No significant VO_2max group difference was observed (mean difference -0.11; 95% CI -2.02, 1.79; p=0.91). The HRQoL “Mental Component Summary”, “Mental Health” and “Vitality” SF-36 scores increased in the young adult intervention subgroup (18-25 years) by 8.98 (95% CI 2.73; 15.23, p, effect size 0.84), 14.49 (95% CI 3.17; 25.81, p=0.01, effect size 0.74), and 15.75 (95% CI 3.97; 27.53, p, effect size 0.78) points, respectively The remote sophrology program did not improve cardiopulmonary fitness, but significantly enhanced HRQoL in young adults with CHD. Integrating mind-body practices into preventive cardiology programs should be further evaluated. Registration: Clinicaltrials.gov (NCT03999320).

Background: Superpotent topical corticosteroids (STS) are highly effective in bullous pemphigoid (BP), but prolonged use is associated with practical limitations and a risk of relapse. Objectives: To evaluate whether combining short-term STS with methotrexate (MTX) could maintain efficacy, reduce relapses and preserve safety compared with prolonged STS alone. Methods: In this multicentre randomized open-label noninferiority trial, adults with BP were assigned to receive either STS (clobetasol propionate) for 1 month plus low-dose MTX as maintenance (MTX + STS arm), or prolonged STS alone (STS arm). The primary endpoint was 9-month overall survival (OS), with a predefined noninferiority margin of 15%. Secondary outcomes included relapse-free survival (RFS) and serious adverse events (SAEs). Results: Among 266 randomized patients (mean age 80.8 years), 9-month OS was 86.5% in the MTX + STS arm and 83.5% in the STS arm [P = 0.498; hazard ratio (HR) 0.80, 95% confidence interval (CI) 0.40–1.50]. The lower limit of the 90% CI for the difference in survival rates (−4.6%) remained within the predefined noninferiority margin, meeting the primary endpoint. Among the 87.4% of patients who achieved disease control within 28 days, relapse occurred in 31 patients in the MTX + STS arm and 52 in the STS arm, corresponding to a 9-month RFS of 68.4% (95% CI 59.3–78.8) vs. 47.4% (95% CI 37.7–59.5), respectively (P = 0.042). SAEs were more frequent in the MTX + STS arm than in the STS arm [mean number per patient per month 0.40 (95% CI 0.23–0.57) vs. 0.19 (95% CI 0.01–0.36), P = 0.005]. One limitation of this study was its open-label design. Moreover, it did not include a validated disease activity score and was conducted in a selected BP population managed under clinical trial conditions. Conclusions: Maintenance therapy with low-dose MTX is noninferior to prolonged STS in terms of survival and is associated with a reduced risk of relapse, at the cost of increased toxicity.

Aims: Coarctation of the aorta (CoA) is the most common undiagnosed congenital heart disease (CHD) during pre-natal screening and its overall prognosis relies on the quality of the surgical repair. This study aimed to identify the pre-natal and post-natal factors associated with the type of surgical technique repair in infant CoA. Methods and results: Multicentre, retrospective, observational study in 680 infants (68% males) aged <1 year who underwent CoA surgical repair in 4 CHD surgical centres in France over 11 years. The primary outcome was the surgical repair technique (simple end-to-end repair, extended end-to-end repair, or aortic arch repair). The aortic arch raw diameter, measured by echocardiography just beyond the brachiocephalic arterial trunk, was the most discriminating parameter for the type of surgical repair technique, outperforming the existing Z-score models. Cut-off value of aortic arch diameter ≤3.6 mm in children <1-year old was predictive of an aortic arch repair [area under the curve (95% CI) = 0.76 (0.67;0.86)]. In multivariable analysis, a pre-natal associated cardiac malformation [odd ratio (OR) (95% CI) = 4.39 (1.99; 9.69)] and aortic arch diameter ≤3.6 mm [OR (95% CI) = 3.78 [1.61; 8.62)] were predictive of an aortic arch repair. Conclusion: The aortic arch diameter is the most discriminating parameter for the type of surgical repair technique in infant CoA. An aortic arch threshold value of 3.6 mm in infant population is predictive of aortic arch repair and should be considered a practical indicator of the hypoplastic nature of the aortic arch.

Aims: The systemic right ventricle (SRV) represents one of the most complex congenital heart diseases (CHD), involving two main anatomical presentations: D-looped transposition of the great arteries and congenitally corrected transposition of the great arteries. Recent therapeutic advances have attempted to improve prognosis in adults with an SRV, but the impact on health-related quality of life (HRQoL) has not been clearly established. Methods and results: Adult patients aged >18 years with an SRV were prospectively enrolled in a multicentre cross-sectional study with recruitment across 13 CHD centres. Demographic, clinical, biological, and imaging data were analysed to assess HRQoL and its determinants. A total of 99 patients (mean age, 38.7 ± 9.2 years; 52% male) were included. Most were symptomatic (NYHA II: 52.2%; NYHA III: 33.7%) with reduced exercise capacity (mean VO₂max = 20 ± 6.1 mL/Kg/min, i.e. 62.4±16.8% of predicted values). HRQoL showed moderate impairment with a physical component score of 45.9 ± 8.7 and a mental component score of 46.2 ± 9.5. A lower physical component score was independently associated with a reduced VO₂max, a recent episode of decompensated heart failure, vitamin K antagonist medication, and being unemployed. The use of antiarrhythmic medications, the number of heart-failure related treatments, and being unemployed were independently associated to a lower mental component score, but having undergone interventional cardiac catheterization was associated with a better mental component score. Conclusion: HRQoL in adults with SRV shows moderate impairment compared to normative data. Cardiopulmonary fitness and clinical factors significantly influence physical and mental components of HRQoL, underscoring the importance of targeted interventions to optimize patient outcomes. Registration: ClinicalTrials.gov ID: NCT03379831