The impact of dissection membrane motility on mid-term aortic remodelling after thoracic endovascular repair.

OBJECTIVES: The aim of this study was to assess preoperative dissection flap motility and to evaluate its impact on the aortic remodelling and the development of distal stent-induced new entry after thoracic endovascular aneurysm repair (TEVAR)/frozen elephant trunk (FET). METHODS: Patients with primary or residual type B dissections were included in a retrospective study with transoesophageal echocardiography analysis of the preoperative dissection flap motility assessed by the true lumen (TL) strain. Three-dimensional computing tomography centreline reconstructions before TEVAR/FET and during the follow-up were conducted to measure aortic remodelling: false lumen thrombosis, TL expansion and aortic diameters at 10 and 20 cm downstream the left subclavian artery, at the coeliac trunk and in the infrarenal aorta. All continuous variables are reported as median with first and third quartiles. RESULTS: Fifty-six consecutive patients were treated with TEVAR (n = 45) or FET (n = 11) in the acute (n = 16), subacute (n = 16) and chronic (n = 24) dissection phase. At a median follow-up of 6 (3-12) months, they showed a favourable TL expansion in the descending aorta, significantly higher in the acute [+9 mm (5-12); P < 0.001] and subacute groups [+5 mm (3-8); P = 0.039] than in the chronic group [+2 mm (0-5)]. The dissection flap motility parameter TL strain was superior in the acute (P = 0.006) and subacute (P = 0.035) groups in comparison to the chronic group. The motile flap [TL strain >22.5% (median)] was associated with a higher TL expansion rate in the thoracic aorta (P = 0.009) and a comparable distal stent-induced new entry incidence (overall: 16%) in comparison to the immobile flap (P = 0.89). CONCLUSIONS: The intraoperative assessment and the inclusion of the dissection flap motility parameters in the decision-making during TEVAR/FET may refine the distal endograft sizing for an improved remodelling of the TL.

Serum and glucocorticoid inducible kinases in the regulation of the cardiac sodium channel SCN5A.

The serum and glucocorticoid inducible kinase SGK1 and its isoform SGK3 are both expressed in cardiac tissue. One of the functions of SGK1 is the phosphorylation and inactivation of the ubiquitin ligase Nedd4-2, which in turn could be shown to downregulate the voltage-gated Na+ channel SCN5A (hH1). The present study has been performed to test for a role of SGK1 and SGK3 in the regulation of SCN5A. To this end cRNA encoding the human Na+ channel SCN5A was injected into Xenopus laevis oocytes with or without cRNA encoding the wild-type kinases SGK1, the constitutively active kinase (S422D)SGK1, the inactive form K127NSGK1 or the wild-type SGK3. SCN5A currents were activated by coexpression of either wild-type SGK1 or SGK3 or the constitutively active S422DSGK1. In contrast, the inactive mutant K127NSGK1 significantly decreased the currents. Moreover, coexpression of SGK3 significantly altered SCN5A gating, i.e. it hyperpolarized the activation threshold and depolarized the prepotential required for 50% availability of the channel. Opposite shifts of gating properties were elicited by mutation of serine to alanine (S483ASCN5A and S663ASCN5A) in the SGK consensus sequences of SCN5A. The present observations disclose a role of the kinases SGK1 and SGK3 in the regulation of cardiac Na+ channels. As SGK1 is upregulated by glucocorticoids, mineralocorticoids and a variety of inflammatory mediators and both kinases are activated by insulin and IGF1, the kinases could mediate effects of those hormones and mediators on cardiac function.