Sex differences in congenital heart defects and genetically induced arrhythmias

Mercuro, Giuseppe; Bassareo, Pier Paolo; Mariucci, Elisabetta; Deidda, Martino; Zedda, Angela Maria; Bonvicini, Marco

doi:10.2459/jcm.0b013e32835ec828

Cited by 20 publications

(10 citation statements)

References 92 publications

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“…Our results reiterate the importance of sex in congenital heart defects [ 15 ]. RV growth and function in this population seem to be different among genders, with males being more prone to develop RV dilation and, consequently, to undergo PVR earlier than females [ 1 , 16 , 17 ], in addition to having a lower RVEF.…”

Section: Discussionsupporting

confidence: 85%

Risk Factors of Right Ventricular Dysfunction and Adverse Cardiac Events in Patients with Repaired Tetralogy of Fallot

Leonardi

Calvieri

Perrone

et al. 2021

IJERPH

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Aim: This study evaluates the risk factors associated with right ventricular (RV) dilation and dysfunction leading to pulmonary valve replacement (PVR) or adverse cardiac events in repaired Tetralogy of Fallot (rToF) patients. Methods: Data from all rToF patients who underwent magnetic resonance imaging (MRI) evaluation at our hospital between February 2007 and September 2020 were collected. Results: Three hundred and forty-two patients (60% males, 42% older than 18 years), with a median age of 16 years (IQR 13–24) at the time of MRI, were included. All patients underwent complete repair at a median age of 8 months (IQR 5–16), while palliation was performed in 56 patients (16%). One hundred and forty-four patients (42%) subsequently received pulmonary valve replacement (PVR). At the multivariate analysis, male gender was an independent predictor for significant RV dilation, RV and left ventricular (LV) dysfunction. Transventricular ventricular septal defect (VSD) closure and previous palliation significantly affected LV function and RV size, respectively. Male gender and the transventricular VSD closure were independent predictors for PVR. Conclusions: Male gender and surgical history (palliation, VSD closure approach) significantly affected the long-term outcomes in rToF patients and should be taken into consideration in the follow-up management and in PVR timing in this patient population.

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Section: Discussionsupporting

confidence: 85%

Risk Factors of Right Ventricular Dysfunction and Adverse Cardiac Events in Patients with Repaired Tetralogy of Fallot

Leonardi

Calvieri

Perrone

et al. 2021

IJERPH

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“…Within the field of cardiology, the issue of gender differences has received attention because it is recognized that risk factors for cardiovascular defects are unevenly distributed by sex [ 36 ]. Possibly, genetic, morphological, and neuro-hormonal factors all contribute towards determining sex-dependent differences in such prevalence [ 37 ].…”

Section: Discussionmentioning

confidence: 99%

Risk Factors for Ventricular Septal Defects in Murmansk County, Russia: A Registry-Based Study

Kovalenko

Anda

Odland

et al. 2018

IJERPH

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Cardiovascular malformations are one of the most common birth defects among newborns and constitute a leading cause of perinatal and infant mortality. Although some risk factors are recognized, the causes of cardiovascular malformations (CVMs) remain largely unknown. In this study, we aim to identify risk factors for ventricular septal defects (VSDs) in Northwest Russia. The study population included singleton births registered in the Murmansk County Birth Registry (MCBR) between 1 January 2006 and 31 December 2011. Infants with a diagnosis of VSD in the MCBR and/or in the Murmansk Regional Congenital Defects Registry (up to two years post-delivery) constituted the study sample. Among the 52,253 infants born during the study period there were 744 cases of septal heart defects (SHDs), which corresponds to a prevalence of 14.2 [95% confidence interval (CI) of 13.2–15.3] per 1000 infants. Logistic regression analyses were carried out to identify VSD risk factors. Increased risk of VSDs was observed among infants born to mothers who abused alcohol [OR = 4.83; 95% CI 1.88–12.41], or smoked during pregnancy [OR = 1.35; 95% CI 1.02–1.80]. Maternal diabetes mellitus was also a significant risk factor [OR = 8.72; 95% CI 3.16–24.07], while maternal age, body mass index, folic acid and multivitamin intake were not associated with increased risk. Overall risks of VSDs for male babies were lower [OR = 0.67; 95% CI 0.52–0.88].

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“…Since many diseases with developmental origins display sex biases (90,91), it is important to study the role of sexbiased gene expression-and any underlying mechanismsduring embryogenesis. More specifically, many congenital heart defects exhibit unexplained sex biases in presentation, mortality and morbidity (92)(93)(94)(95). The fact that 45% of Turner Syndrome patients (X chromosome monosomy) suffer from congenital heart defects underscores the role of the sex chromosomes in embryogenesis (96).…”

Section: The Embryonic Origins Of Sexual Dimorphismmentioning

confidence: 99%

Sexual Dimorphism of the Heart: Genetics, Epigenetics, and Development

Deegan

Nigam

Engel

2021

Front. Cardiovasc. Med.

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The democratization of genomic technologies has revealed profound sex biases in expression patterns in every adult tissue, even in organs with no conspicuous differences, such as the heart. With the increasing awareness of the disparities in cardiac pathophysiology between males and females, there are exciting opportunities to explore how sex differences in the heart are established developmentally. Although sexual dimorphism is traditionally attributed to hormonal influence, expression and epigenetic sex biases observed in early cardiac development can only be accounted for by the difference in sex chromosome composition, i.e., XX in females and XY in males. In fact, genes linked to the X and Y chromosomes, many of which encode regulatory factors, are expressed in cardiac progenitor cells and at every subsequent developmental stage. The effect of the sex chromosome composition may explain why many congenital heart defects originating before gonad formation exhibit sex biases in presentation, mortality, and morbidity. Some transcriptional and epigenetic sex biases established soon after fertilization persist in cardiac lineages, suggesting that early epigenetic events are perpetuated beyond early embryogenesis. Importantly, when sex hormones begin to circulate, they encounter a cardiac genome that is already functionally distinct between the sexes. Although there is a wealth of knowledge on the effects of sex hormones on cardiac function, we propose that sex chromosome-linked genes and their downstream targets also contribute to the differences between male and female hearts. Moreover, identifying how hormones influence sex chromosome effects, whether antagonistically or synergistically, will enhance our understanding of how sex disparities are established. We also explore the possibility that sexual dimorphism of the developing heart predicts sex-specific responses to environmental signals and foreshadows sex-biased health-related outcomes after birth.

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Sex differences in congenital heart defects and genetically induced arrhythmias

Cited by 20 publications

References 92 publications

Risk Factors of Right Ventricular Dysfunction and Adverse Cardiac Events in Patients with Repaired Tetralogy of Fallot

Risk Factors of Right Ventricular Dysfunction and Adverse Cardiac Events in Patients with Repaired Tetralogy of Fallot

Risk Factors for Ventricular Septal Defects in Murmansk County, Russia: A Registry-Based Study

Sexual Dimorphism of the Heart: Genetics, Epigenetics, and Development

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