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Preprocedural manual multi-slice-CT-segmentation tools (MSCT-ST) define the gold standard for planning transcatheter aortic valve replacement (TAVR). They are able to predict the perpendicular line of the aortic annulus (PPL) and to indicate the corresponding C-arm angulation (CAA). Fully automated planning-tools and their clinical relevance have not been systematically evaluated in a real world setting so far.
Transcatheter aortic valve implantation (TAVI) in bicuspid aortic valve (BAV) stenosis has become more frequent in the last years. This may pose challenges for long-time valve durability. Therefore, we aimed to evaluate the prevalence of bioprosthetic valve dysfunction (BVD) with the newest-generation devices in BAV stenosis up to one-year follow-up (FU).
Red blood cells (RBC) are the major carriers of sphingosine-1-phosphate (S1P) in blood. Here we show that variations in RBC S1P content achieved by altering S1P synthesis and transport by genetic and pharmacological means regulate glucose uptake and metabolic flux. This is due to S1P-mediated activation of the catalytic protein phosphatase 2 (PP2A) subunit leading to reduction of cell-surface glucose transporters (GLUTs). The mechanism dynamically responds to metabolic cues from the environment by increasing S1P synthesis, enhancing PP2A activity, reducing GLUT phosphorylation and localization, and diminishing glucose uptake in RBC from diabetic mice and humans. Functionally, it protects RBC against lipid peroxidation in hyperglycemia and diabetes by activating the pentose phosphate pathway. Proof of concept is provided by the resistance of mice lacking the S1P exporter MFSD2B to diabetes-induced HbA1c elevation and thiobarbituric acid reactive substances (TBARS) generation in diabetic RBC. This mechanism responds to pharmacological S1P analogues such as fingolimod and may be functional in other insulin-independent tissues making it a promising therapeutic target.
Therapeutic options targeting post-ischaemic cardiac remodelling are sparse. The bioactive sphingolipid sphingosine-1-phosphate (S1P) reduces ischaemia/reperfusion injury. However, its impact on post-ischaemic remodelling independently of its infarct size (IS)-reducing effect is yet unknown and was addressed in this study.
Antiplatelet medication is standard of care in acute myocardial infarction (AMI). However, it may have obscured beneficial properties of the activated platelet secretome. We identify platelets as major source of a sphingosine-1-phosphate (S1P) burst during AMI, and find its magnitude to favorably associate with cardiovascular mortality and infarct size in STEMI patients over 12 months. Experimentally, administration of supernatant from activated platelets reduces infarct size in murine AMI, which is blunted in platelets deficient for S1P export (Mfsd2b) or production (Sphk1) and in mice deficient for cardiomyocyte S1P receptor 1 (S1P1). Our study reveals an exploitable therapeutic window in antiplatelet therapy in AMI as the GPIIb/IIIa antagonist tirofiban preserves S1P release and cardioprotection, whereas the P2Y12 antagonist cangrelor does not. Here, we report that platelet-mediated intrinsic cardioprotection is an exciting therapeutic paradigm reaching beyond AMI, the benefits of which may need to be considered in all antiplatelet therapies.
We aimed to identify predictors of mitral regurgitation recurrence (MR) after percutaneous mitral valve repair (PMVR) in patients with functional mitral regurgitation (FMR). Patients with FMR were enrolled who underwent PMVR using the MitraClip® device. Procedural success was defined as reduction of MR of at least one grade to MR grade ≤ 2 + assessed at discharge. Recurrence of MR was defined as MR grade 3 + or worse at one year after initially successful PMVR. A total of 306 patients with FMR underwent PMVR procedure. In 279 out of 306 patients (91.2%), PMVR was successfully performed with MR grade ≤ 2 + at discharge. In 11.4% of these patients, MR recurrence of initial successful PMVR after 1 year was observed. Recurrence of MR was associated with a higher rate of heart failure rehospitalization during the 12 months follow-up (52.0% vs. 30.3%; p = 0.029), and less improvement in New York Heart Association (NYHA) functional class [68% vs. 19% of the patients presenting with NYHA functional class III or IV one year after PMVR when compared to patients without recurrence (p = 0.001)]. Patients with MR recurrence were characterized by a higher left ventricular sphericity index {0.69 [Interquartile range (IQR) 0.64, 0.74] vs. 0.65 (IQR 0.58, 0.70), p = 0.003}, a larger left atrium volume [118 (IQR 96, 143) ml vs. 102 (IQR 84, 123) ml, p = 0.019], a larger tenting height 10 (IQR 9, 13) mm vs. 8 (IQR 7, 11) mm (p = 0.047), and a larger mitral valve annulus [41 (IQR 38, 43) mm vs. 39 (IQR 36, 40) mm, p = 0.015] when compared to patients with durable optimal long-term results. In a multivariate regression model, the left ventricular sphericity index [Odds Ratio (OR) 1.120, 95% Confidence Interval (CI) 1.039-1.413, p = 0.003)], tenting height (OR 1.207, 95% CI 1.031-1.413, p = 0.019), and left atrium enlargement (OR 1.018, 95% CI 1.000-1.038, p = 0.047) were predictors for MR recurrence after 1 year. In patients with FMR, baseline parameters of advanced heart failure such as spherical ventricle, tenting height and a large left atrium might indicate risk of recurrent MR one year after PMVR.
Data on non-vitamin K antagonist oral anticoagulants (NOACs) in transcatheter aortic valve replacement (TAVR) patients are controversial. In patients without atrial fibrillation (AF), rivaroxaban showed enhanced ischemia and bleeding as compared to standard of care. ENVISAGE showed enhanced bleeding in AF patients as compared to vitamin K antagonist (VKA). Only apixaban was non-inferior but failed superiority regarding bleeding in AF patients after TAVR. One could hypothesize that this might be due to pharmacokinetics of NOACs. Therefore, we compared outcome in rivaroxaban/edoxaban (once-daily) and apixaban (twice-daily) treated patients. 568 patients with indication for permanent oral anticoagulation due to AF undergoing TAVR were analyzed via inverse probability of treatment weighting. Valve academic research consortium complications during 30-day follow-up were assessed. Bleeding complications were similar in once-daily and twice-daily NOACs (major: 22 (7.5%) vs. 14 (5.3%), p = 0.285; minor: 66 (22.4%) vs. 46 (17.4%), p = 0.133). Complications did not change when splitting the cohort in the different agents apixaban, rivaroxaban and edoxaban. These findings remained robust after multivariate analysis. In summary, twice-daily and once-daily NOACs did not differ regarding bleeding complications in a hypothesis generating real-world cohort of TAVR patients with AF.
ST-segment elevation myocardial infarction (STEMI) still causes significant mortality and morbidity despite best-practice revascularization and adjunct medical strategies. Within the STEMI population, there is a spectrum of higher and lower risk patients with respect to major adverse cardiovascular and cerebral events (MACCE) or re-hospitalization due to heart failure. Myocardial and systemic metabolic disorders modulate patient risk in STEMI. Systematic cardiocirculatory and metabolic phenotyping to assess the bidirectional interaction of cardiac and systemic metabolism in myocardial ischemia is lacking.
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