Peripheral Microvascular Dysfunction in Children and Adults with Congenital Heart Disease: A Literature Review.

Although there is a continually growing number of patients with congenital heart disease (CHD) due to medical and surgical advances, these patients still have a poorer prognosis compared to healthy individuals of similar age. In patients with heart failure, microvascular dysfunction (MVD) has recently emerged as a crucial modulator of disease initiation and progression. Because of the substantial pathophysiological overlap between CHD and heart failure induced by other etiologies, MVD could be important in the pathophysiology of CHD as well. MVD is believed to be a systemic disease and may be manifested in several vascular beds. This review will focus on what is currently known about MVD in the peripheral vasculature in CHD. Therefore, a search on the direct assessment of the vasodilatory capacity of the peripheral microcirculation in patients with CHD was conducted in the PubMed database. Since there is little data available and the reported studies are also very heterogeneous, peripheral MVD in CHD is not sufficiently understood to date. Its exact extent and pathophysiological relevance remain to be elucidated in further research.

Elevated oxidative stress in patients with congenital heart disease and the effect of cyanosis: a meta-analysis.

Oxidative stress is an important pathophysiological mechanism in the development of numerous cardiovascular disorders. To improve therapy and preventive strategies, clinicians need a better understanding of the underlying pathophysiological mechanisms of congenital heart diseases (CHD). The objective of this meta-analysis was to determine whether oxidative stress is elevated in patients with CHD compared to healthy controls, and to evaluate whether a difference in oxidative stress parameters can be observed between patients with cyanotic (cCHD) and acyanotic CHD (aCHD). Therefore, 21 studies investigating oxidative stress in peripheral blood of both children and adults with CHD were reviewed. Different methods to assess the oxidant status were compared and divided into three categories: pro-oxidative or anti-oxidative stress markers and the ratio of pro-to-anti oxidative stress markers. This meta-analysis showed elevated oxidative stress levels in patients with CHD, and more specifically in patients with cCHD. Moreover, this indicates that there could be potential in oxidative stress measurements as a new biomarker of disease severity. Further research will be needed to clarify the exact role of oxidative stress and its contributors in CHD in order to get a better and more in-depth understanding of the underlying pathophysiology of CHD, especially the higher susceptibility of the right ventricle (RV) to progress to heart failure (HF). This could facilitate the development of antioxidant treatments and RV-specific HF therapies, which are necessary to improve survival in these patients and could be of particular importance in cCHD.

Circulating Reactive Oxygen Species in Adults with Congenital Heart Disease.

Oxidative stress is an important pathophysiological mechanism in the development of numerous cardiovascular disorders, but few studies have examined the levels of oxidative stress in adults with congenital heart disease (CHD). The objective of this study was to investigate oxidative stress levels in adults with CHD and the association with inflammation, exercise capacity and endothelial function. To this end, 36 adults with different types of CHD and 36 age- and gender-matched healthy controls were enrolled. Blood cell counts, hs-CRP, NT-proBNP, fasting glucose, cholesterol levels, iron saturation and folic acid concentrations were determined in venous blood samples. Levels of superoxide anion radical in whole blood were determined using electron paramagnetic resonance spectroscopy in combination with the spin probe CMH. Physical activity was assessed with the IPAQ-SF questionnaire. Vascular function assessment (EndoPAT) and cardiopulmonary exercise testing were performed in the patient group. Superoxide anion radical levels were not statistically significantly different between adults with CHD and the matched controls. Moreover, oxidative stress did not correlate with inflammation, or with endothelial function or cardiorespiratory fitness in CHD; however, a significant negative correlation with iron saturation was observed. Overall, whole blood superoxide anion radical levels in adults with CHD were not elevated, but iron levels seem to play a more important role in oxidative stress mechanisms in CHD than in healthy controls. More research will be needed to improve our understanding of the underlying pathophysiology of CHD.

Plasma-Derived microRNAs Are Influenced by Acute and Chronic Exercise in Patients With Heart Failure With Reduced Ejection Fraction.

Background: Exercise training improves VO2peak in heart failure with reduced ejection fraction (HFrEF), but the effect is highly variable as it is dependent on peripheral adaptations. We evaluated changes in plasma-derived miRNAs by acute and chronic exercise to investigate whether these can mechanistically be involved in the variability of exercise-induced adaptations. Methods: Twenty-five male HFrEF patients (left ventricular ejection fraction < 40%, New York Heart Association class ≥ II) participated in a 15-week combined strength and aerobic training program. The effect of training on plasma miRNA levels was compared to 21 male age-matched sedentary HFrEF controls. Additionally, the effect of a single acute exercise bout on plasma miRNA levels was assessed. Levels of 5 miRNAs involved in pathways relevant for exercise adaptation (miR-23a, miR-140, miR-146a, miR-191, and miR-210) were quantified using RT-qPCR and correlated with cardiopulmonary exercise test (CPET), echocardiographic, vascular function, and muscle strength variables. Results: Expression levels of miR-146a decreased with training compared to controls. Acute exercise resulted in a decrease in miR-191 before, but not after training. Baseline miR-23a predicted change in VO2peak independent of age and left ventricular ejection fraction (LVEF). Baseline miR-140 was independently correlated with change in load at the respiratory compensation point and change in body mass index, and baseline miR-146a with change in left ventricular mass index. Conclusion: Plasma-derived miRNAs may reflect the underlying mechanisms of exercise-induced adaptation. In HFrEF patients, baseline miR-23a predicted VO2peak response to training. Several miRNAs were influenced by acute or repeated exercise. These findings warrant exploration in larger patient populations and further mechanistic in vitro studies on their molecular involvement.

Unsupervised Exercise Training Was Not Found to Improve the Metabolic Health or Phenotype over a 6-Month Dietary Intervention: A Randomised Controlled Trial with an Embedded Economic Analysis.

Ectopic fat leads to metabolic health problems. This research aimed to assess the effectiveness of a hypocaloric diet intervention together with an unsupervised exercise training program in comparison with a hypocaloric diet alone to reduce ectopic fat deposition. Sixty-one premenopausal women with overweight or obesity participated in this controlled trial and were each randomised into either a usual care group (hypocaloric diet) or intervention group (hypocaloric diet + unsupervised exercise training). Ectopic fat deposition, metabolic parameters, incremental costs from a societal perspective and incremental quality-adjusted life years (QALYs) were assessed before, during and after the six-month intervention period. In the total sample, there was a significant decrease in visceral adipose tissue (VAT: -18.88 cm2, 95% CI -11.82 to -25.95), subcutaneous abdominal adipose tissue (SAT: -46.74 cm2, 95% CI -29.76 to -63.18), epicardial fat (ECF: -14.50 cm3, 95% CI -10.9 to -18.98) and intrahepatic lipid content (IHL: -3.53%, 95% CI -1.72 to -5.32). Consequently, an "adapted" economic analysis revealed a non-significant decrease in costs and an increase in QALYs after the intervention. No significant differences were found between groups. A multidisciplinary lifestyle approach seems successful in reducing ectopic fat deposition and improving the metabolic risk profile in women with overweight and obesity. The addition of unsupervised exercise training did not further improve the metabolic health or phenotype over the six months.

The Effect of Diet or Exercise on Visceral Adipose Tissue in Overweight Youth.

OBJECTIVE: Excess visceral adipose tissue (VAT) in children with obesity is associated with the development of cardiovascular and metabolic disease. This meta-analysis investigated if lifestyle interventions can reduce VAT in overweight and obese youth. METHODS: Pubmed, Cochrane, and PEDro were searched for clinical trials that objectively assessed VAT and included study arms with supervised diet, exercise, or a combination of both. If there was a no-therapy control group, the data of the control group and the intervention groups were used to meta-analyze the data. In all other cases, the preintervention and the postintervention data were used to meta-analyze. Effect sizes were calculated as standardized mean differences or changes of VAT and expressed as Hedges' g. RESULTS: The overall weighted mean effect size on VAT of all included interventions was -0.69 (95% confidence interval [CI] = -0.90 to -0.48) (P < 0.001). Subgroup analysis showed that the overall weighted mean effect size of diet-only interventions on VAT was 0.23 (95% CI = -0.22 to 0.68) (P = 0.311). Interventions that combined diet and exercise showed a pooled effect size on VAT of -0.55 (95% CI = -0.75 to -0.39) (P < 0.001). The pooled effect size of exercise-only interventions on VAT was -0.85 (95% CI = -1.20 to -0.57) (P < 0.001). CONCLUSIONS: Supervised exercise-only or combined diet and exercise interventions can reduce VAT in overweight and obese children and adolescents. The strongest effect was found in exercise-only groups. However, high-quality randomized controlled trials describing the effect of supervised dietary interventions on VAT in children are lacking.

The Effect of Lifestyle Interventions on Excess Ectopic Fat Deposition Measured by Noninvasive Techniques in Overweight and Obese Adults: A Systematic Review and Meta-Analysis.

BACKGROUND: Reduction of ectopic fat accumulation plays an important role in the prevention of insulin resistance in people with overweight or obesity. This systematic review and meta-analysis summarizes the current evidence for the use of noninvasive weight loss interventions (exercise or diet) on ectopic fat. METHODS: A systematic literature search was performed according to the PRISMA statement. Clinical trials in PubMed, PEDro, and the Cochrane database were searched. RESULTS: All 33 included studies described the effect of lifestyle interventions on ectopic fat storage in internal organs (liver, heart, and pancreas) and intramyocellular lipids (IMCL), hereby including 1146, 157, 87, and 336 participants. Overall, a significant decrease of ectopic fat was found in liver (-0.53 Hedges' g, P < .001), heart (-0.72 Hedges' g, P < .001) and pancreas (-0.55 Hedges' g, P = .098) respectively. A trend toward decrease in IMCL was also observed. Meta-regression indicated a dose-response relationship between BMI reduction and decreased hepatic adiposity. Exercise alone decreased ectopic fat but the effect was greater when combined with diet. CONCLUSION: Lifestyle interventions can reduce ectopic fat accumulation in the internal organs of overweight and obese adults. The results on IMCL should be interpreted with care, keeping the 'athlete's paradox' in mind.

Prognostic respiratory parameters in heart failure patients with and without exercise oscillatory ventilation - a systematic review and descriptive meta-analysis.

The purpose of this review was to describe the occurrence of prognostic variables as derived from cardiopulmonary exercise testing (CPET) in patients with heart failure (HF), presenting exercise oscillatory ventilation (EOV) compared to patients without EOV. The effect of EOV on peak oxygen consumption (VO2), minute ventilation/carbon dioxide production (VE/VCO2) slope, oxygen uptake efficiency slope (OUES), rest and peak pulmonary end-tidal carbon dioxide pressure (PETCO2) was meta-analysed. A systematic search strategy was performed in five databases (Pubmed, Cochrane Library, PEDro, Science Direct and Web of Science) assessing 252 articles for eligibility. Nineteen citations met the inclusion criteria totalling 3032 patients with HF (EOV=1111; non-EOV=1921). The risk of bias was assessed by two researchers. Extracted data were pooled using random or fixed effects meta-analysis, if appropriate. The level of significance was set at p≤0.05. Overall, the presentation of EOV significantly indicated aggravated prognostic markers. Subgroup analysis revealed left ventricular ejection fraction (LVEF) and mode of CPET protocol as independent factors, whereas defining EOV significantly influenced the results. A meta-analysis of studies reporting hazard ratios for cardiovascular events demonstrated that HF patients with EOV run a fourfold risk for an adverse event compared to HF patients without EOV. In general, these findings suggest that the presence of EOV in patients with HF is associated with a deterioration of the prognostic CPET parameters. Furthermore, EOV can occur in HF patients with reduced as well as preserved ejection fraction. Further research on defining and assessing EOV in a more accurate and reproducible way is required.

The effect of exercise on visceral adipose tissue in overweight adults: a systematic review and meta-analysis.

Excessive visceral adipose tissue appears to trigger a cascade of metabolic disturbances that seem to coexist with ectopic fat storage in muscle, liver, heart and the ß-cell. Therefore, the reduction of visceral adipose tissue potentially plays a pivotal role in the treatment of the metabolic syndrome. The purpose of this systematic review and meta-analysis is to describe the overall effect of exercise on visceral adipose tissue and to provide an overview of the effect of different exercise regimes, without caloric restriction, on visceral adipose tissue in obese persons. A systematic literature search was performed according to the PRISMA statement for reporting systematic reviews and meta-analyses. The initial search resulted in 87 articles after removing duplicates. After screening on title, abstract and full-text 15 articles (totalling 852 subjects) fulfilled the a priori inclusion criteria. The quality of each eligible study was assessed in duplicate with "The Critical Review Form for Quantitative Studies". Using random-effects weights, the standardized mean difference (Hedge's g) of the change in visceral adipose tissue was -0.497 with a 95% confidence interval of -0.655 to -0.340. The Z-value was -6.183 and the p-value (two tailed) was <0.001. A subgroup analysis was performed based on gender, type of training and intensity. Aerobic training of moderate or high intensity has the highest potential to reduce visceral adipose tissue in overweight males and females. These results suggest that an aerobic exercise program, without hypocaloric diet, can show beneficial effects to reduce visceral adipose tissue with more than 30 cm(2) (on CT analysis) in women and more than 40 cm(2) in men, even after 12 weeks.