Cardiovascular manifestations of hypermobile Ehlers–Danlos syndrome and hypermobility spectrum disorders

Introduction: Mitral valve prolapse and aortic root dilatation are reported in association with hypermobile Ehlers–Danlos syndrome (hEDS), but the full phenotypic spectrum of cardiovascular complications in this condition has not been studied in the aftermath of updated nosology and diagnostic criteria. Methods: We performed a retrospective review of 258 patients (> 94% adults) referred to a multidisciplinary clinic for evaluation of joint hypermobility between January 2017 and December 2020 and diagnosed with hEDS or a hypermobility spectrum disorder (HSD) to determine the incidence and spectrum of cardiovascular involvement. Results: Mitral valve prolapse was present in 7.5% and thoracic aortic dilatation in 15.2%. Aortic dilatation was more frequent in individuals with hEDS (20.7%) than with HSD (7.7%) and similarly prevalent between males and females, although was mild in > 90% of females and moderate-to-severe in 50% of males. Five individuals (1.9%) with hEDS/HSD had extra-aortic arterial involvement, including cervical artery dissection (CeAD, n = 2), spontaneous coronary artery dissection (SCAD, n = 2), and SCAD plus celiac artery pseudoaneurysm ( n = 1). This is the first series to report the prevalence of CeAD and SCAD in hEDS/HSD. Conclusions: Cardiovascular manifestations in adults with hEDS/HSD, especially females, are typically mild and readily assessed by echocardiography. Since the risk of progression has not yet been defined, adults with hEDS/HSD who are found to have aortic dilatation at baseline should continue ongoing surveillance to monitor for progressive dilatation. Cardiovascular medicine specialists, neurologists, and neurosurgeons should consider hEDS/HSD on the differential for patients with CeAD or SCAD who also have joint hypermobility.

Identifying Mitral Valve Prolapse at Risk for Ventricular Arrhythmias and Myocardial Fibrosis from 12-lead Electrocardiograms using Deep Learning

Background: Mitral valve prolapse (MVP) is a common valvulopathy, with a subset of MVP patients developing sudden cardiac death or cardiac arrest. Complex ventricular ectopy (ComVE) represents a marker of arrhythmic risk that is associated with myocardial fibrosis and increased mortality in MVP. We hypothesize that an ECG-based machine-learning model can identify MVP with ComVE and/or myocardial fibrosis on cardiac magnetic resonance (CMR) imaging. Methods: A deep convolutional neural network (CNN) was trained to detect ComVE using 6,916 12-lead ECGs from 569 MVP patients evaluated at the University of California San Francisco (UCSF) between 2012 and 2020. A separate CNN was also trained to detect late gadolinium enhancement (LGE) using 87 ECGs from MVP patients with contrast CMR. Results: The prevalence of ComVE was 160/569 or 28% (20 patients or 3% had cardiac arrest or sudden cardiac death). The area under the curve (AUC) of the CNN to detect ComVE was 0.81 (95% CI, 0.78-0.84). AUC remained high even after excluding patients with moderate-severe mitral regurgitation (MR) [0.80 (95% CI, 0.77-0.83)], or with bileaflet MVP [0.81 (95% CI, 0.76-0.85)]. The top ECG segments able to discriminate ComVE vs no ComVE were related to ventricular depolarization and repolarization (early-mid ST and QRS fromV1, V3, and III). LGE in the papillary muscles or basal inferolateral wall was present in 21 (24%) of 87 patients with available CMR. The AUC for detection of LGE was 0.75 (95% CI, 0.68-0.82). Conclusions: Standard 12-lead ECGs analyzed with machine learning can detect MVP at risk for ventricular arrhythmias and fibrosis and can identify novel ECG correlates of arrhythmic risk regardless of leaflet involvement or mitral regurgitation severity. ECG-based CNNs may help select those MVP patients requiring closer follow-up and/or a CMR.

The state of response of autonomic nervous system in children with mitral valve prolapse

The article presents summarized materials on connective tissue dysplasia of the heart, primary mitral valve prolapse, dysfunction of the autonomic system. Aim of research: to estimate the condition of autonomic nervous system in children with primary mitral valve prolapse. We examined 106 children with mitral valve prolapse aged from 13 to 17 years old on the clinical base of city hospital “Center of mother and child” in Vinnitsya. Research included time and frequency domain (evaluation with cardiointervalography. Final results were compared with the control group records. The results showed no statistical significance among time domain parameters in the main group of children. All these indices displayed tendency to sympathetic and parasympathetic autonomic nervous system tonus increase in boys. However, sympathicotonia tendency was noted in girls only. Frequency domain parameters showed similar results, compared with the previous. Nevertheless, very low frequency parameters had statistically significant difference in both subgroups of patience with mitral valve prolapse, including males (3205.8±190.9 against 1717±154, р<0.05) and females (3280±220.1 against 1433±811, р<0.05). There were no statistically significant difference among other frequency domain parameters. Conclusions: we estimated that children with mitral valve prolapse have imbalanced autonomic homeostasis manifested by tone disturbances of both autonomic vegetative system branches with sympathetic predominance. Patients with primary mitral valve prolapse generally have increased sympathetic tone - both boys and girls - according to spectral analysis of heart rate variability indices, heart rate oscillation power of a very low frequency in particular (p<0.05). In children with mitral valve prolapse, the tone of parasympathetic nervous system is generally normal; there is a tendency to its increase in boys and decrease in girls. These children should be under close medical supervision by pediatricians and cardiologists.