The Female Athlete’s Heart: Overview and Management of Cardiovascular Diseases

The number of female athletes taking part in elite and amateur sport is ever increasing. In contrast with male athletes, few studies have focused on cardiovascular adaptations to exercise in women, the effects of lifelong exercise on heart muscle and electrical tissue, the risk of exercise-related sudden cardiac death and the management of cardiovascular disease. Women have a lower prevalence of large QRS complexes, repolarisation changes including inferior and lateral T-wave inversion, and cardiac dimensions exceeding predicted limits compared with men. The risk of exercise-related sudden cardiac death is significantly lower in women than men. Also, women who have engaged in lifelong exercise do not have a higher prevalence of AF, coronary artery calcification or myocardial fibrosis than their sedentary counterparts. Apart from providing an overview of the existing literature relating to cardiac adaptations, this review explores possible reasons for the sex differences and focuses on the management of cardiovascular disorders that affect female athletes

Hypertrophic cardiomyopathy: insights from extracellular volume mapping

Hypertrophic cardiomyopathy (HCM) is a genetic cardiac disease characterized by myocardial hypertrophy and fibrosis. The phenotypic expression ranges from asymptomatic patients to heart failure and sudden death.1 Disease progression and relationship between hypertrophy and fibrosis are not well understood. Extracellular volume fraction (ECV) mapping on cardiovascular magnetic resonance (CMR) can demonstrate pixel-by-pixel ECV elevation (focal or diffuse fibrosis) or reduction (cellular hypertrophy).2 Furthermore, it has been shown that physical training induces remodelling of both heart and vasculature.3,4 In particular, it has been shown that hypertrophied myocardium in athletes has lower ECV, suggesting that cardiac athletic adaptation is an adaptive one caused predominantly by cellular rather than interstitial expansion.4 Hypothesizing that ECV mapping can reveal both differential responses of left ventricular hypertrophy (LVH), we explored the distribution of ECV in HCM

Generation of the human induced pluripotent stem cell (hiPSC) line PSMi003-A from a patient affected by an autosomal recessive form of Long QT Syndrome type 1

Abstract We generated human induced pluripotent stem cells (hiPSCs) from dermal fibroblasts of a 51 years old female patient homozygous for the mutation c.535 G>A p.G179S on the KCNQ1 gene, causing a severe form of autosomal recessive Long QT Syndrome type 1 (AR-LQT1), not associated with deafness. The hiPSCs, generated using four retroviruses each encoding for a reprogramming factor OCT4, SOX2, KLF4, cMYC, are pluripotent and can differentiate into spontaneously beating cardiomyocytes (hiPSC-CMs)

Systolic anterior motion of the anterior mitral valve leaflet begins in subclinical hypertrophic cardiomyopathy

AIMS: Anterior mitral valve leaflet (AMVL) elongation is detectable in overt and subclinical hypertrophic cardiomyopathy (HCM). We sought to investigate the dynamic motion of the aorto-mitral apparatus to understand the behaviour of the AMVL, and mechanisms of left ventricular outflow tract obstruction (LVOTO) predisposition in HCM. METHODS & RESULTS: Cardiovascular magnetic resonance imaging (CMR) using 1.5 Tesla scanner was performed on 36 HCM sarcomere gene mutation carriers without left ventricular hypertrophy (G + LVH-), 31 HCM patients with preserved ejection fraction carrying a pathogenic sarcomere gene mutation (G + LVH+), and 53 age, sex and BSA-matched healthy volunteers.Dynamic excursion of the aorto-mitral apparatus was assessed semi-automatically on breath-held 3-chamber cine steady-state free precession images. Four pre-defined regions of interest (ROI) were tracked: ROIPMVL: hinge point of the posterior MVL; ROITRIG: intertrigonal mitral annulus; ROIAMVL: AMVL tip; ROIAAO: anterior aortic annulus. Compared to controls, normalized two-dimensional displacement-versus-time plots in G + LVH- revealed subtle but significant systolic anterior motion (SAM) of the AMVL (P < 0.0001) and reduced longitudinal excursion of ROIAAO (P = 0.014) and ROIPMVL (P = 0.048). In overt and subclinical HCM, excursion of the ROITRIG/AMVL/PMVL was positively associated with burden of LV fibrosis (p < 0.028). As expected, SAM was observed in G + LVH + together with reduced longitudinal excursion of ROITRIG (P = 0.049) and ROIAAO (P = 0.008). CONCLUSION: Dyskinesia of the aorto-mitral apparatus, including SAM of the elongated AMVL, is detectable in subclinical HCM, before the development of LVH or LA enlargement. These data have the potential to improve our understanding of early phenotype development and LVOTO-predisposition in HCM

Abnormal septal convexity into the left ventricle occurs in subclinical hypertrophic cardiomyopathy.

BACKGROUND: Sarcomeric gene mutations cause hypertrophic cardiomyopathy (HCM). In gene mutation carriers without left ventricular (LV) hypertrophy (G + LVH-), subclinical imaging biomarkers are recognized as predictors of overt HCM, consisting of anterior mitral valve leaflet elongation, myocardial crypts, hyperdynamic LV ejection fraction, and abnormal apical trabeculation. Reverse curvature of the interventricular septum (into the LV) is characteristic of overt HCM. We aimed to assess LV septal convexity in subclinical HCM. METHODS: Cardiovascular magnetic resonance was performed on 36 G + LVH- individuals (31 ± 14 years, 33 % males) with a pathogenic sarcomere mutation, and 36 sex and age-matched healthy controls (33 ± 12 years, 33 % males). Septal convexity (SCx) was measured in the apical four chamber view perpendicular to a reference line connecting the mid-septal wall at tricuspid valve insertion level and the apical right ventricular insertion point. RESULTS: Septal convexity was increased in G + LVH- compared to controls (maximal distance of endocardium to reference line: 5.0 ± 2.5 mm vs. 1.6 ± 2.4 mm, p ≤ 0.0001). Expected findings occurred in G + LVH- individuals: longer anterior mitral valve leaflet (23.5 ± 3.0 mm vs. 19.9 ± 3.1 mm, p ≤ 0.0001), higher relative wall thickness (0.31 ± 0.05 vs. 0.29 ± 0.04, p ≤ 0.05), higher LV ejection fraction (70.8 ± 4.3 % vs. 68.3 ± 4.4 %, p ≤ 0.05), and smaller LV end-systolic volume index (21.4 ± 4.4 ml/m(2) vs. 23.7 ± 5.8 ml/m(2), p ≤ 0.05). Other morphologic measurements (LV angles, sphericity index, and eccentricity index) were not different between G + LVH- and controls. CONCLUSIONS: Septal convexity is an additional previously undescribed feature of subclinical HCM

Genome-wide association analyses identify new Brugada syndrome risk loci and highlight a new mechanism of sodium channel regulation in disease susceptibility

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel NaV1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on NaV1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings