Increased cholesterol absorption is associated with In-stent-restenosis after stent implantation for stable coronary artery disease.

BACKGROUND AND AIMS: Blood cholesterol levels are regulated by competing mechanisms of cholesterol synthesis, absorption and excretion. Plant sterols are natural constituents of plants, are not synthesized in humans, and serve as markers for cholesterol absorption. Ezetimibe lowers the intestinal absorption of cholesterol and plant sterols. We analyzed the associations of differences in cholesterol metabolism, in particular increased cholesterol absorption, and the occurrence of in-stent restenosis (ISR) in patients with stable coronary artery disease. METHODS: Elective stent implantation of de novo stenosis was conducted in 59 patients (74.6 % males, 67.2 ± 9.6 years). Cholesterol and non-cholesterol sterols were quantified in serum samples by gas chromatography or mass spectrometry. ISR was assessed by optical coherence tomography (OCT) and quantitative angiography (QCA) after six months. RESULTS: Markers for cholesterol absorption (e.g. campesterol-to-cholesterol) were positively associated with ISR measured by QCA (%diameter stenosis, late lumen loss) and OCT (proliferation volume, %area stenosis), whereas markers for cholesterol synthesis (e.g. lathosterol-to-cholesterol) were negatively associated with ISR (%area stenosis: r = -0.271, p = 0.043). There was no association between ISR and total cholesterol, LDL, HDL, triglycerides. Markers for cholesterol absorption (e.g. campesterol-to-cholesterol) were significantly lower in ezetimibe-treated patients compared to patients on a statin only (1.29 ± 0.69 vs. 2.22 ± 1.23; p = 0.007). Combined lipid-lowering with ezetimibe plus statin reduced ISR compared to statin only (13.7 ± 10.4 vs. 22.5 ± 12.1 %diameter stenosis, p = 0.015). CONCLUSIONS: Differences in cholesterol metabolism, more specifically increased cholesterol absorption, are associated with ISR.

Aortic annulus measurement with computed tomography angiography reduces aortic regurgitation after transfemoral aortic valve replacement compared to 3-D echocardiography: a single-centre experience.

BACKGROUND: Accurate assessment of the aortic annulus is crucial for successful transcatheter aortic valve replacement (TAVR), in particular to prevent paravalvular regurgitation (PVR). We compared aortic annular sizing using multidetector computed tomography (MDCT) and three-dimensional transoesophageal echocardiography (3-D TEE) to determine the predictive value of MDCT. METHODS AND RESULTS: All patients admitted for transfemoral TAVR [n = 227; 48.9% balloon expandable (Edwards Sapien 3); 51.1% self-expandable (Core Valve, Evolut R)] at our institution from January 2015 until December 2016 were analysed retrospectively. Aortic annular parameters were obtained either by MDCT or 3-D TEE. Additionally, we included a cohort of patients (n = 27) assessed by both MDCT and 3D TEE between October 2017 and April 2018 to enable intra-individual comparison of the two methods. Indications for TAVR were severe degenerative aortic stenosis (AS; 94.7%) or re-stenosis after surgical AVR (5.3%). 74.4% were classified as high-gradient AS. The mean age was 80 (37-94) years and 75.8% presented with NYHA III/IV. STS risk of mortality was intermediate (3.5 ± 2.3). MDCT and 3-D TEE were performed in 116 and 111 patients for aortic annulus sizing, respectively. Significantly larger implants were chosen in the CT group irrespective of prosthesis type or post-dilatation. Follow-up (median at 79 days) revealed significantly less PVR in the MDCT compared to 3-D TEE group (absence of PVR in 59.3% and 40.7%, p = 0.016), without differences in mortality. Patients without PVR or mild PVR had a better clinical performance according to NYHA class (p = 0.016). CONCLUSION: MDCT is superior to 3-D TEE in terms of sizing accuracy and clinical outcomes. Reduction of PVR after TAVR with MDCT is likely due to valve annulus undersizing by TEE.

Detection of coronary microembolization by Doppler ultrasound in patients with stable angina pectoris during percutaneous coronary interventions under an adjunctive antithrombotic therapy with abciximab: design and rationale of the High Intensity Transient Signals ReoPro (HITS-RP) study.

BACKGROUND: Embolization of atherosclerotic debris from the rupture of a vulnerable atherosclerotic plaque occurs iatrogenically during percutaneous coronary interventions (PCI) and can induce myocardial necrosis. These microembolizations are detected as high intensity transient signals (HITS) using intracoronary Doppler technology. PRESENTATION OF THE HYPOTHESIS: In the presented study we will test if abciximab (ReoPro®) infusion reduces high intensity transient signals in patients with stable angina pectoris undergoing PCI in comparison to standard therapy alone. TESTING THE HYPOTHESIS: The High Intensity Transient Signals ReoPro® (HITS-RP) study will enroll 60 patients. It is a prospective, single center, randomized, double-blinded, controlled trial. The study is designed to compare the efficacy of intravenous abciximab administration for reduction of microembolization during elective PCI. Patients will be randomized in a 1:1 fashion to abciximab or placebo infusion. The primary end point of the HITS-RP-Study is the number of HITS during PCI measured by intracoronary Doppler wire. Secondary endpoints are bleeding complications, elevation of cardiac biomarkers or ECG changes after percutaneous coronary interventions, changes in coronary flow velocity reserve, hs-CRP elevation, any major adverse cardio-vascular event during one month follow-up. IMPLICATIONS OF THE HYPOTHESIS: The HITS-RP-Study addresses important questions regarding the efficacy of intravenous abciximab administration in reducing microembolization and periprocedural complications in stable angina pectoris patients undergoing PCI. TRIAL REGISTRATION: The trial is registered under http://www.drks-neu.uniklinik-freiburg.de/drks_web/:DRKS00000603.