BACKGROUND: This cross-sectional controlled study aims to assess health-related quality of life (HRQoL) of children and adolescents with a molecular diagnosis of Marfan syndrome (MFS) or related disorders and to evaluate the factors associated with HRQoL in this population. Sixty-three children with MFS and 124 age- and sex-matched healthy children were recruited. HRQoL was assessed using the Pediatric Quality of Life Inventory (PedsQL™) generic questionnaire. The correlation between HRQoL scores and the different continuous parameters (age, body mass index, disease severity, systemic score, aortic sinus diameter, and aerobic physical capacity) was evaluated using Pearson\'s or Spearman\'s coefficient. A multiple linear regression analysis was performed on the two health summary self-reported PedsQL™ scores (physical and psychosocial) to identify the factors associated with HRQoL in the MFS group.
RESULTS: Except for emotional functioning, all other domains of HRQoL (psychosocial and physical health, social and school functions) were significantly lower in children with MFS compared to matched healthy children. In the MFS group, the physical health summary score was significantly lower in female than in male patients (self-report: absolute difference [95%CI] = -8.7 [-17.0; -0.47], P = 0.04; proxy-report: absolute difference [95%CI] = -8.6 [-17.3; 0.02], P = 0.05) and also negatively correlated with the systemic score (self-report: R = -0.24, P = 0.06; proxy-report: R = -0.29, P = 0.03) and with the height Z-score (proxy-report: R = -0.29, P = 0.03). There was no significant difference in the physical health summary scores between the different genetic subgroups. In the subgroup of 27 patients who performed a cardiopulmonary exercise test, self- and proxy-reported physical health summary scores were highly correlated with their aerobic physical capacity assessed by peak oxygen consumption (VO2max) and ventilatory anaerobic threshold (VAT). In the multivariate analysis, the most important independent predictors of decreased physical health were increased height, decreased body mass index, decreased VAT and use of prophylactic therapy.
CONCLUSIONS: This study reports an impaired HRQoL in children and adolescents with MFS or related conditions, in comparison with matched healthy children. Educational and rehabilitation programs must be developed and evaluated to improve exercise capacity and HRQoL in these patients.
BACKGROUND: ClinicalTrials.gov, NCT03236571 . Registered 28 July 2017.

OBJECTIVE: This study aims to develop a regression model to estimate peak oxygen consumption (VO2peak) in individuals with spinal cord injury (SCI) by employing different variables.
METHODS: In this study, 34 participants were divided into two groups: 19 with cervical injury (CI) and 15 with thoracic injury (TI). Key measurements included VO2peak and related factors such as age, height, weight, body mass index (BMI), fat-free mass, body fat percentage, limb and trunk circumferences, spinal cord independence (SCIM III), Korean activities of daily living (K-ADL), and respiratory functions (forced vital capacity (FVC), peak expiratory flow (PEF), and maximum voluntary ventilation (MVV)). Statistical analyses were conducted using forward selection regression to examine the relationships between these variables.
RESULTS: Height, calf circumference, SCIM III score, and PEF were key variables in all patients with SCI (TSCI). For patients with CI, the key variables were height, calf circumference, and MVV, whereas for patients with TI, the key variable was calf circumference. The average explanatory powers of the VO2peak regression model for TSCI were 70.3% (R2) and 66.2% (adjusted R2), with an average standard error of estimate (SEE) of 2.94 ml/kg/min. The average explanatory power for patients with CI was 71.7% (R2) and 66.1% (adjusted R2), with an average SEE of 1.88 ml/kg/min. The average explanatory power for patients with TI was 55.9% (R2) and 52.5% (adjusted R2), with an average SEE of 3.41 ml/kg/min. There was no significant difference between the VO2peak measured and predicted VO2peak for each type of injury.
CONCLUSIONS: The regression model for estimating VO2peak in SCI patients in this preliminary study is as follows: TSCI=39.684-0.144×(Height)-0.513×(Calf)+0.136×(SCIM III)+1.187×(PEF), CI=38.842-0 .158×(Height) - 0.371×(Calf)+0.093×(MVV), TI=42.325-0.813×(Calf).

UNASSIGNED: Heart failure (HF) is a debilitating and often fatal disease that affects millions of people worldwide. Diminished nitric oxide synthesis, signaling, and bioavailability are believed to contribute to poor skeletal muscle function and aerobic capacity. The aim of this clinical trial (iNIX-HF) is to determine the acute and longer-term effectiveness of inorganic nitrate supplementation on exercise performance in patients with HF with reduced ejection fraction (HFrEF).
UNASSIGNED: This clinical trial is a double-blind, placebo-controlled, randomized, parallel-arm design study in which patients with HFrEF (n = 75) are randomized to receive 10 mmol potassium nitrate (KNO3) or a placebo capsule daily for 6 wk. Primary outcome measures are muscle power determined by isokinetic dynamometry and peak aerobic capacity (VO2peak) determined during an incremental treadmill exercise test. Endpoints include the acute effects of a single dose of KNO3 and longer-term effects of 6 wk of KNO3. The study is adequately powered to detect expected increases in these outcomes at P < 0.05 with 1-β>0.80.
UNASSIGNED: The iNIX-HF phase II clinical trial will evaluate the effectiveness of inorganic nitrate supplements as a new treatment to ameliorate poor exercise capacity in HFrEF. This study also will provide critical preliminary data for a future \'pivotal\', phase III, multi-center trial of the effectiveness of nitrate supplements not only for improving exercise performance, but also for improving symptoms and decreasing other major cardiovascular endpoints. The potential public health impact of identifying a new, relatively inexpensive, safe, and effective treatment that improves overall exercise performance in patients with HFrEF is significant.

The klotho and fibroblast growth factor 23 (FGF-23) pathway is implicated in cardiovascular pathophysiology. This substudy aimed to assess the changes in klotho and FGF-23 levels 1-month after dapagliflozin in patients with stable heart failure and reduced ejection fraction (HFrEF). The study included 29 patients (32.2% of the total), with 14 assigned to the placebo group and 15 to the dapagliflozin, as part of the double-blind, randomized clinical trial [DAPA-VO2 (NCT04197635)]. Blood samples were collected at baseline and after 30 days, and Klotho and FGF-23 levels were measured using ELISA Kits. Between-treatment changes (raw data) were analyzed by using the Mann-Whitney test and expressed as median (p25%-p75%). Linear regression models were utilized to analyze changes in the logarithm (log) of klotho and FGF-23. The median age was 68.3 years (60.8-72.1), with 79.3% male and 81.5% classified as NYHA II. The baseline medians of left ventricular ejection fraction, glomerular filtration rate, NT-proBNP, klotho, and FGF-23 were 35.8% (30.5-37.8), 67.4 ml/min/1.73 m2 (50.7-82.8), 1,285 pg/ml (898-2,305), 623.4 pg/ml (533.5-736.6), and 72.6 RU/ml (62.6-96.1), respectively. The baseline mean peak oxygen uptake was 13.1 ± 4.0 ml/kg/min. Compared to placebo, patients on dapagliflozin showed a significant median increase of klotho [Δ+29.5, (12.9-37.2); p = 0.009] and a non-significant decrease of FGF-23 [Δ-4.6, (-1.7 to -5.4); p = 0.051]. A significant increase in log-klotho (p = 0.011) and a decrease in log-FGF-23 (p = 0.040) were found in the inferential analysis. In conclusion, in patients with stable HFrEF, dapagliflozin led to a short-term increase in klotho and a decrease in FGF-23.

UNASSIGNED: Cancer therapy-related cardiotoxicity is a major cause of cardiovascular morbidity in childhood cancer survivors. The aims of this study were to investigate systolic myocardial function and its association to cardiorespiratory fitness in pediatric childhood cancer survivors.
UNASSIGNED: In this sub-study of the international study \"Physical Activity and fitness in Childhood Cancer Survivors\" (PACCS), echocardiographic measures of left ventricular global longitudinal strain (LV-GLS) and right ventricular longitudinal strain (RV-LS) were measured in 128 childhood cancer survivors aged 9-18 years and in 23 age- and sex-matched controls. Cardiorespiratory fitness was measured as peak oxygen consumption achieved on treadmill and correlated to myocardial function.
UNASSIGNED: Mean LV-GLS was reduced in the childhood cancer survivors compared to the controls, -19.7% [95% confidence interval (CI) -20.1% to -19.3%] vs. -21.3% (95% CI: -22.2% to -20.3%) (p = 0.004), however, mainly within normal range. Only 13% of the childhood cancer survivors had reduced LV longitudinal strain z-score. Mean RV-LS was similar in the childhood cancer survivors and the controls, -23.2% (95% CI: -23.7% to -22.6%) vs. -23.3% (95% CI: -24.6% to -22.0%) (p = 0.8). In the childhood cancer survivors, lower myocardial function was associated with lower peak oxygen consumption [correlation coefficient (r) = -0.3 for LV-GLS]. Higher doses of anthracyclines (r = 0.5 for LV-GLS and 0.2 for RV-LS) and increasing time after treatment (r = 0.3 for LV-GLS and 0.2 for RV-LS) were associated with lower myocardial function.
UNASSIGNED: Left ventricular function, but not right ventricular function, was reduced in pediatric childhood cancer survivors compared to controls, and a lower left ventricular myocardial function was associated with lower peak oxygen consumption. Furthermore, higher anthracycline doses and increasing time after treatment were associated with lower myocardial function, implying that long-term follow-up is important in this population at risk.

OBJECTIVE: Improving cardiopulmonary reserve, or peak oxygen consumption( V ˙ O2peak ), may reduce postoperative complications; however, this may be difficult to achieve between diagnosis and surgery. Our primary aim was to assess the efficacy of an approximate 14-session, preoperative high-intensity interval training(HIIT) program to increase V ˙ O2peak by a clinically relevant 2 ml·kg-1 ·min-1 . Our secondary aim was to document clinical outcomes.
METHODS: In this prospective study, participants aged 45-85 undergoing major abdominal surgery were randomized to standard care or 14 sessions of HIIT over 4 weeks. HIIT sessions involved approximately 30 min of stationary cycling. Interval training alternated 1 min of high (with the goal of reaching 90% max heart rate at least once during the session) and low/moderate-intensity cycling. Cardiopulmonary exercise testing(CPET) measured the change in V ˙ O2peak from baseline to surgery. Clinical outcomes included postoperative complications, length of stay(LOS), and Short Form 36 quality of life questionnaire(SF-36).
RESULTS: Of 63 participants, 46 completed both CPETs and 50 completed clinical follow-up. There was a significant improvement in the HIIT group\'s mean ± SD V ˙ O2peak (HIIT 2.87 ± 1.94 ml·kg1 ·min-1 vs standard care 0.15 ± 1.93, with an overall difference of 2.73 ml·kg1 ·min-1 95%CI [1.53, 3.93] p < 0.001). There were no statistically significant differences between groups for clinical outcomes, although the observed differences consistently favored the exercise group. This was most notable for total number of complications (0.64 v 1.16 per patient, p = 0.07), SF-36 physical component score (p = 0.06), and LOS (mean 5.5 v 7.4 days, p = 0.07).
CONCLUSIONS: There was a significant improvement in V ˙ O2peak with a four-week preoperative HIIT program. Further appropriately powered work is required to explore the impact of preoperative HIIT on postoperative clinical outcomes.

Heart transplant recipients have reduced exercise capacity despite preserved graft function. The IronIC trial was designed to test the hypothesis that intravenous iron therapy would improve peak oxygen consumption in these patients.
This randomized, placebo-controlled, double-blind trial was performed at our national center for heart transplantation. One hundred and 2 heart transplant recipients with a serum ferritin <100 µg/liter or 100 to 300 µg/liter, in combination with transferrin saturation of <20%, and hemoglobin level >100 g/liter were enrolled ≥1 year after transplantation. A cardiopulmonary exercise test was performed before administration of the study drug and at 6 months follow-up. The primary endpoint was peak oxygen consumption. Key secondary outcomes included iron status, handgrip strength, quality of life, and safety. Fifty-two patients were randomized to receive ferric derisomaltose 20 mg/kg, and 50 to placebo. The between-group difference in baseline-adjusted peak oxygen consumption was 0.3 ml/kg/min (95% confidence interval -0.9 to 1.4, p = 0.66). In patients with a baseline ferritin <30 µg/liter, peak oxygen consumption was significantly higher in the ferric derisomaltose arm. At 6 months, iron stores were restored in 86% of the patients receiving ferric derisomaltose vs 20% in patients receiving placebo (p < 0.001). Quality of life was significantly better in patients receiving ferric derisomaltose. Twenty-seven adverse events occurred in the intravenous iron group vs 30 in the placebo group (p = 0.39).
Intravenous iron treatment did not improve peak oxygen consumption in heart transplant recipients with ferritin <100 µg/liter or 100 to 300 µg/liter in combination with transferrin saturation <20%.
http//www.clinicaltrials.gov identifier NCT03662789.

Physical activity (PA) programs are recommended for breast cancer care. However, their modalities remain to be discussed. This study determined the best time to begin a personalized or adapted program based on cardiopulmonary exercise test function. This randomized controlled trial evaluated the effect of home-based adapted PA (APA) performed during or after treatment on cardiorespiratory fitness (CRF) at 12 months.
The primary endpoint was the peak oxygen consumption (VO2peak) at 12 months (group A vs C and B vs C). Secondary endpoints included the 6-minute walking test, assessment of muscle strength, fatigue, quality of life, anxiety, and depression, and a questionnaire on PA levels. All tests were evaluated at baseline and at 6 and 12 months. A total of 94 patients with breast cancer were randomized to 3 different groups: group A, performing 6 months of APA during adjuvant care; group B, 6 months of APA after adjuvant care; and group C, 12 months of APA during and after specific care. The program combined 1 resistance session and 2 aerobic sessions per week. Analysis of variance was used for repeated measures, Student\'s t-test or the Mann-Whitney U-test for continuous variables, and χ2 test for binary or categorical variables.
The study assessed 81 participants at 6 months and 73 at 12 months. The majority of patients completed more than 85% of the exercise sessions. The baseline for VO2peak and secondary outcomes did not differ among the groups. VO2peak increased during the exercise period and decreased during the chemotherapy period without APA, but at 12 months no significant difference was observed. The same variation was observed in the 6-minute walking test, with significance at 6 months between A+C versus B (P = .04), but no difference among the groups at 12 months. In the 3 groups, no decreases in other studied parameters were noted, except at 6 months in group B without APA.
Home-based APA in breast cancer patients has a positive effect on CRF and physical functions, with no differences based on the timing of this program based on specific cancer treatment.
ClinicalTrials.gouv.fr (NCT01795612). Registered 20 February 2013.

High-intensity interval training (HIIT) has similar or better effects than moderate-intensity continuous training (MICT) in increasing peak oxygen consumption (VO2max), however, it has not been studied when HIIT is applied in a circuit (HIICT). The aim of this study was to compare the effects of a HIICT versus MICT on VO2max estimated (VO2max-ES), heart rate (HR) and blood pressure (BP) of middle-aged and older women. A quasi-experimental randomized controlled trial was used. Fifty-four women (67.8 ± 6.2 years) were randomized to either HIICT (n = 18), MICT (n = 18) or non-exercise control group (CG; n = 18) for 18 weeks. Participants in HIICT and MICT trained two days/week (one hour/session). Forty-one participants were assessed (HIICT; n = 17, MICT; n = 12, CG; n = 12). Five adverse events were reported. Cardiorespiratory fitness, HR and BP were measured. The tests were performed before and after the exercise intervention programs. VO2max-ES showed significant training x group interaction, in which HIICT and MICT were statistically superior to CG. Moreover, HIICT and MICT were statistically better than CG in the diastolic blood pressure after exercise (DBPex) interaction. For the systolic blood pressure after exercise (SBPex), HIICT was statistically better than CG. In conclusion, both HIICT and MICT generated adaptations in VO2max-ES and DBPex. Furthermore, only HIICT generated positive effects on the SBPex. Therefore, both training methods can be considered for use in exercise programs involving middle-aged and older women.

Sedentary behaviour (SB) and low physical activity (PA) are independently associated with non-alcoholic fatty liver disease (NAFLD). Compared to PA, high cardiorespiratory fitness (CRF) has been associated with a higher protection against all-cause mortality and a number of specific diseases. However, this relationship has not been investigated in NAFLD. This study examined the roles of SB and CRF on: i) the likelihood of having NAFLD in the general population, and ii) the risk of mortality over 9 years within individuals having NAFLD.
A cross-sectional analysis of 15,781 adults (52% female; age range 19-95 years) was conducted. Self-reported SB was divided into tertiles. CRF was estimated using validated non-exercise models, and the presence of NAFLD from the Fatty Liver Index. Adjusted Odds Ratios and 95% Confidence Intervals for NAFLD were estimated using logistic regression analyses. Hazard Ratios for all-cause mortality were estimated using Cox proportional hazard regression in individuals with NAFLD.
For each additional 1 h/d of SB, the likelihood of having NAFLD was significantly increased by 4% (CI, 3-6%). In combined analyses, compared with the reference group [high CRF and low (≤4 h/d) SB], individuals with low CRF had a markedly higher likelihood of having NAFLD (OR, 16.9; CI 12.9-22.3), even if they had SB ≤ 4 h/d. High CRF attenuated the negative role of SB up to 7 h/d on NAFLD. Over 9.4 ± 1.3 years of follow-up, individuals with NAFLD and low CRF had the risk of mortality increased by 52% (CI, 10-106%) compared to those with high CRF, regardless of SB or meeting PA guidelines.
Low CRF increases the risk of premature death in individuals with NAFLD, and is strongly associated with higher likelihood of having NAFLD, outweighing the influence of SB.