Sex differences in metabolic adaptation in infants with cyanotic congenital heart disease.

BACKGROUND: Female infants with congenital heart disease (CHD) face significantly higher postoperative mortality rates after adjusting for cardiac complexity. Sex differences in metabolic adaptation to cardiac stressors may be an early contributor to cardiac dysfunction. In adult diseases, hypoxic/ischemic cardiomyocytes undergo a cardioprotective metabolic shift from oxidative phosphorylation to glycolysis which appears to be regulated in a sexually dimorphic manner. We hypothesize sex differences in cardiac metabolism are present in cyanotic CHD and detectable as early as the infant period. METHODS: RNA sequencing was performed on blood samples (cyanotic CHD cases, n = 11; controls, n = 11) and analyzed using gene set enrichment analysis (GSEA). Global plasma metabolite profiling (UPLC-MS/MS) was performed using a larger representative cohort (cyanotic CHD, n = 27; non-cyanotic CHD, n = 11; unaffected controls, n = 12). RESULTS: Hallmark gene sets in glycolysis, fatty acid metabolism, and oxidative phosphorylation were significantly enriched in cyanotic CHD females compared to male counterparts, which was consistent with metabolomic differences between sexes. Minimal sex differences in metabolic pathways were observed in normoxic patients (both controls and non-cyanotic CHD cases). CONCLUSION: These observations suggest underlying differences in metabolic adaptation to chronic hypoxia between males and females with cyanotic CHD. IMPACT: Children with cyanotic CHD exhibit sex differences in utilization of glycolysis vs. fatty acid oxidation pathways to meet the high-energy demands of the heart in the neonatal period. Transcriptomic and metabolomic results suggest that under hypoxic conditions, males and females undergo metabolic shifts that are sexually dimorphic. These sex differences were not observed in neonates in normoxic conditions (i.e., non-cyanotic CHD and unaffected controls). The involved metabolic pathways are similar to those observed in advanced heart failure, suggesting metabolic adaptations beginning in the neonatal period may contribute to sex differences in infant survival.

Gender differences in congenital heart defects: a narrative review.

Background and Objective: Congenital heart defects (CHD) represent the most frequent human birth defects, occurring in almost 1% of all live newborns. Understanding the effects of gender in the prevalence of CHD has a key role in defining personalized prevention, disease identification, prognosis definition and individualized therapeutic strategies. Recently, the attempt to achieve a holistic approach to patients with CHD cannot be separated from accounting for existing gender differences. The main aim of this narrative review is to provide an overview of gender differences in the epidemiology of CHD. Methods: A standardized research through three electronic databases (PubMed/Scopus/Embase) was performed using a combination of keywords and Medical Subject Headings (MeSH) terms to include congenital heart diseases, gender difference(s), prevalence. Observational, prospective, population based and retrospective studies reporting gender differences in the prevalence of CHD were included. Conference abstracts were excluded as well as studies not written in English language and non-human studies. Further relevant papers were selected by hand-searching of the references list of selected articles. Key Content and Findings: Search results returned 1,904 papers. Screening articles by title and abstracts resulted in 17 articles for full text review. Of these, 10 were included for analysis and additional 11 articles were included after hand searching review of reference lists. A total of 21 articles were included. Conclusions: Our narrative review confirms that there is a significant gender variation in specific CHD subgroups. In particular, we summarized the evidence that there is a significantly greater risk for males to be born with severe CHD and for females with milder CHD subtypes. The etiology of the different distribution of CHD among genders is still under investigation and a deeper understanding of how gender influences the risk for CHD is warranted. In the future, a gender-based management of CHD should become an established medical approach.

An Image-Based Computational Fluid Dynamics Study of Mitral Regurgitation in Presence of Prolapse.

PURPOSE: In this work we performed an imaged-based computational study of the systolic fluid dynamics in presence of mitral valve regurgitation (MVR). In particular, we compared healthy and different regurgitant scenarios with the aim of quantifying different hemodynamic quantities. METHODS: We performed computational fluid dynamic (CFD) simulations in the left ventricle, left atrium and aortic root, with a resistive immersed method, a turbulence model, and with imposed systolic wall motion reconstructed from Cine-MRI images, which allowed us to segment also the mitral valve. For the regurgitant scenarios we considered an increase of the heart rate and a dilation of the left ventricle. RESULTS: Our results highlighted that MVR gave rise to regurgitant jets through the mitral orifice impinging against the atrial walls and scratching against the mitral valve leading to high values of wall shear stresses (WSSs) with respect to the healthy case. CONCLUSION: CFD with prescribed wall motion and immersed mitral valve revealed to be an effective tool to quantitatively describe hemodynamics in case of MVR and to compare different regurgitant scenarios. Our findings highlighted in particular the presence of transition to turbulence in the atrium and allowed us to quantify some important cardiac indices such as cardiac output and WSS.

Helical structure of the ventricular myocardium. A narrative review of cardiac mechanics.

To date, the ventricular myocardial band is the anatomical-functional model that best explains cardiac mechanics during systolic-diastolic phenomena in the cardiac cycle. The implications of the model fundamentally affect the anatomical interpretation of the ventricular myocardium, giving meaning to the direction that muscle fibers take, turning them into an object of study with potential clinical, imaging, and surgical applications. Re-interpreting the anatomy of the ventricular muscle justifies changes in the physiological interpretation, from its functional focus as a fiber unraveling the mechanical phenomena carried out during systole and diastole. We identify the functioning of the heart from the electrical and hemodynamic point of view, but it is necessary to delve into the mechanics that originate the hemodynamic changes observed flowmetrically, and that manifested during the pathology. In this review, the mechanical phenomena that the myocardium performs in each phase of the cardiac cycle are broken down in detail, emphasizing the physical displacements that each of the muscle segments presents, as well as a vision of their alteration and in which pathologies they are mainly identified. Visually, an anatomical correlation to the echocardiogram is provided, pointing out the direction of the segmental myocardial displacement by the strain velocity vector technique.

Normothermia for pediatric and congenital heart surgery: an expanded horizon.

Cardiopulmonary bypass (CPB) in pediatric cardiac surgery is generally performed with hypothermia, flow reduction and hemodilution. From October 2013 to December 2014, 55 patients, median age 6 years (range 2 months to 52 years), median weight 18.5 kg (range 3.2-57 kg), underwent surgery with normothermic high flow CPB in a new unit. There were no early or late deaths. Fifty patients (90.9%) were extubated within 3 h, 3 (5.5%) within 24 h, and 2 (3.6%) within 48 h. Twenty-four patients (43.6%) did not require inotropic support, 31 (56.4%) received dopamine or dobutamine: 21 ≤5 mcg/kg/min, 8 5-10 mcg/kg/min, and 2 >10 mcg/kg/min. Two patients (6.5%) required noradrenaline 0.05-0.1 mcg/kg/min. On arrival to ICU and after 3 and 6 h and 8:00 a.m. the next morning, mean lactate levels were 1.9 ± 09, 2.0 ± 1.2, 1.6 ± 0.8, and 1.4 ± 0.7 mmol/L (0.6-5.2 mmol/L), respectively. From arrival to ICU to 8:00 a.m. the next morning mean urine output was 3.8 ± 1.5 mL/kg/h (0.7-7.6 mL/kg/h), and mean chest drainage was 0.6 ± 0.5 mL/kg/h (0.1-2.3 mL/kg/h). Mean ICU and hospital stay were 2.7 ± 1.4 days (2-8 days) and 7.2 ± 2.2 days (4-15 days), respectively. In conclusion, normothermic high flow CPB allows pediatric and congenital heart surgery with favorable outcomes even in a new unit. The immediate post-operative period is characterized by low requirement for inotropic and respiratory support, low lactate production, adequate urine output, minimal drainage from the chest drains, short ICU, and hospital stay.

"Functionally" univentricular hearts: impact of pre-natal diagnosis.

Within the last few decades the pre-natal echocardiographic diagnosis of congenital heart defects has made substantial progresses, particularly for the identification of complex malformation. "Functionally" univentricular hearts categorize a huge variety of heart malformations. Since no one of the patients with these congenital heart defects can ever undergo a bi-ventricular type of repair, early recognition and decision-making from the neonatal period are required in order to allow for appropriate multiple-step diagnostic and treatment procedures, either of interventional cardiology and/or surgery, on the pathway of "univentricular" heart. In the literature strong disagreements exist about the potential impact of the pre-natal diagnosis on the early and late outcomes of complex congenital heart defects. This review of the recent reports has been undertaken to better understand the impact of pre-natal diagnosis in "functionally" univentricular hearts taking into consideration the following topics: pre-natal screening, outcomes and survival, general morbidity, neurologic and developmental consequences, pregnancy management and delivery planning, resources utilization and costs/benefits issues, ethical implications, parents counseling, and interruption of pregnancy versus treatment.

Congestive heart failure: experimental model.

INTRODUCTION: Surgically induced, combined volume and pressure overload has been used in rabbits to create a simplified and reproducible model of acute left ventricular (LV) failure. MATERIALS AND METHODS: New Zealand white male rabbits (n = 24, mean weight 3.1 ± 0.2 kg) were randomly assigned to either the Control group (n = 10) or to the Heart Failure group (HF, n = 14). Animals in the Control group underwent "sham" procedures. Animals in the HF group underwent procedures to induce LV volume overload by inducing severe aortic valve regurgitation with aortic cusp disruption and pressure overload using an occlusive silver clip positioned around the pre-renal abdominal aorta. RESULTS: Following Procedure-1 (volume overload) echocardiography confirmed severe aortic regurgitation in all animals in the HF group, with increased mean pulse pressure difference from 18 ± 3 to 38 ± 3 mmHg (P < 0.0001). After Procedure-2 (pressure overload) all animals in the HF group showed clinical and echocardiographic signs of constriction of the abdominal aorta and echocardiography confirmed progressively declining LV function. At the end of the protocol there was a significant increase of the heart/body weight ratio in the HF group vs. Control group (4.6 ± 0.2 vs. 2.9 ± 0.1 g/kg, P < 0.05), and echocardiography showed in HF group significant increase of the LV end-diastolic diameter (2.15 ± 0.09 vs. 1.49 ± 0.03 cm, P < 0.001) and reduction of the LV shortening fraction (26.3 ± 3.8 vs. 41.3 ± 1.6%, P < 0.001). CONCLUSION: This experimental model: (a) consistently produces LV hypertrophy/dilatation and subsequent congestive heart failure, (b) provides new data on the time course of LV dilatation, hypertrophy and failure, (c) allows study of the progress and evolution of LV systolic and diastolic dysfunction in the presence of induced LV failure, (d) is suitable to study intervention or pharmacological administration to reduce the negative effects of acute LV failure.