Next-generation self-expandable transcatheter heart valves preserve superiority in terms of post-interventional haemodynamics without presenting former drawbacks: rate of postoperative permanent pacemaker implantation and severity of residual paravalvular leakage were similar to balloon-expandable transcatheter heart valves.
Background: Intraoperative hypotension is a common problem and direct or indirect sympathomimetic drugs are frequently needed to stabilize blood pressure. AkrinorTM consists of the direct and the indirect sympathomimetic noradrenaline and norephedrine. Both substances are covalently bound to the phosphodiesterase (PDE) inhibitor theophylline, yielding theodrenaline and cafedrine, respectively. We investigated pharmacodynamic effects of AkrinorTM and its constituents on contractile force and tension in human atrial trabeculae and internal A. mammaria rings.Methods: Isometric contractions were measured in human atrial trabeculae at 1 Hz and 37°C. CGP 20712A and ICI 118,551 were used to elaborate β1- and β2-adrenoceptor (AR) subtypes involved and phenoxybenzamine to estimate indirect sympathomimetic action. PDE-inhibition was measured as a potentiation of force increase upon direct activation of adenylyl cyclase by forskolin. Human A. mammaria preparations were used to estimate intrinsic vasoconstriction and impact on the noradrenaline-induced vasoconstriction.Results: Clinically relevant concentrations of AkrinorTM (4.2–420 mg/l) robustly increased force in human atrial trabeculae (EC50 41 ± 3 mg/l). This direct sympathomimetic action was mediated via β1-AR and the effect size was as large as with high concentrations of calcium. Only the highest and clinically irrelevant concentration of AkrinorTM increased the potency of forskolin to a minor extent. Norephedrine has lost its indirect sympathomimetic effect when bound to theophylline. Increasing concentrations of AkrinorTM (4.2–168 mg/l) alone did not affect the tension of human A. mammaria interna rings, but shifted the noradrenaline curve rightward from -logEC50 6.18 ± 0.08 to 5.23 ± 0.05 M.Conclusion: AkrinorTM increased cardiac contractile force by direct sympathomimetic actions and PDE inhibition, did not constrict A. mammaria preparations, but shifted the concentration-response curve to the right, compatible with an α-AR antagonistic effect or PDE inhibition. The pharmacodynamic profile and potency of AkrinorTM differs from noradrenaline and norephedrine in vitro. We anticipate metabolism of theodrenaline and cafedrine resulting in a different pharmacodynamic profile of AkrinorTM
in vivo.
OBJECTIVES
The aim of the study was to determine the differences in outcomes of surgical aortic valve replacement (SAVR) and transcatheter aortic valve implantation (TAVI) in low-risk patients.
METHODS
All patients with a logistic EuroSCORE II <4% who underwent transfemoral TAVI between 2008 and 2016 (n = 955) or SAVR between 2009 and 2014 (n = 886) at our centre were included. One hundred and nine patients per group were available for propensity score matching.
RESULTS
Mortality during the 30-day follow-up showed no differences (SAVR vs TAVI: 1.1% vs 1.8%, P = 1.0) but the rates of permanent pacemaker implantation (0.0 vs 14.8%, P < 0.001) and paravalvular leakage ≥ moderate (0.0 vs 7.0%, P = 0.017) were higher in TAVI patients. No difference was found regarding postoperative effective orifice area and transvalvular pressure gradients. Although, the 1-year survival was similar between both groups; 3- and 5-year survival was significantly inferior in the TAVI patient cohort.
CONCLUSIONS
TAVI yielded similar short-term outcomes compared with SAVR despite higher rates of permanent pacemaker implantation and paravalvular leakage ≥ moderate, but inferior long-term survival. Poorer long-term outcomes of the TAVI patient cohort were attributable to a more comorbid TAVI population. This emphasizes the need for long-term results from randomized controlled trials before TAVI can be broadly expanded to younger low-risk patients.
MICS for ASD II is a safe and reproducible procedure with 0% mortality in our cohort. More complete closure of ASD, decreased rates of new onset AF and decreased need for oral anticoagulation are the advantages of the MICS procedure. Compared with the current standard of care, the MICS approach is feasible regardless of ASD morphology.
Preliminary experience suggests implantation of this type of THV in aortic annuli up to 32 mm to be feasible and safe, in particular calcification patterns. It does not result in a relevant incidence of PVL ≥ grade II, or increased rate of VARC-2 adjudicated clinical endpoints. Also, functional outcomes regarding transvalvular gradients or EOA demonstrate applicability of this THV in such patients.
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