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Background Treatment with monoclonal antibodies targeting circulating proprotein convertase subtilisin-kexin type 9 (PCSK9) was found to reduce all-cause mortality in addition to cardiovascular events, suggesting pleiotropic effects. Eicosanoids are bioactive metabolites involved in cardiovascular disease and have not yet been studied in the course of PCSK9 inhibition. Methods In this prospective translational single-center study, plasma samples were collected from 64 patients before and after initiation of PCSK9 inhibitor treatment. Metabolomic analyses were performed using liquid chromatography coupled to high-resolution mass spectrometry. Results A total of 62 bioactive eicosanoids were detected. Among the metabolites, four were significantly decreased by PCSK9 inhibition after one month and remained stable after 6 months (figure): arachidonic acid (p=0.003), 12,13-DiHOME (p Conclusion PCSK9 inhibition leads to significant changes in the eicosanoid profile already after one month, in particular to a downregulation of arachidonic acid. This discovery complements the presumed pleiotropic effects of PCSK9 inhibition and may provide additional benefit in the treatment of atherosclerotic disease. Funding Acknowledgement Type of funding sources: None.

Background Patients with acute myocardial infarction (AMI) frequently experience recurrent atherothrombotic events, largely attributable to non-culprit lesions with high-risk characteristics. Statins can halt the progression of coronary atherosclerosis, and addition of protein convertase subtilisin/kexin type 9-inhibitors (PCSK9i) results in incremental low-density lipoprotein cholesterol (LDL-C) lowering and atheroma regression. Purpose We sought to examine the interrelation between baseline imaging characteristics, on-treatment LDL-C levels, and changes in coronary atherosclerosis as assessed by serial, multi-modality intracoronary imaging in patients with AMI. Methods This is a post hoc analysis from the PACMAN-AMI randomized trial. Patients were randomly allocated to biweekly alirocumab 150 mg vs. placebo on top of high-intensity statin initiated within 24h of presentation with AMI, and underwent serial imaging of the two non-infarct-related arteries at baseline and after 52 weeks. The primary endpoint was percent atheroma volume (PAV) by intravascular ultrasound (IVUS). Powered secondary endpoints were maximal lipid core burden index (maxLCBI4mm) by near-infrared spectroscopy (NIRS) and minimum fibrous cap thickness (FCTmin) by optical coherence tomography (OCT). Results Of 300 randomized patients (mean age 58.5±9.8 years, 18.7% women, baseline LDL-C 3.94±0.87 mmol/L), IVUS was serially performed in 265 patients (537 arteries). LDL-C levels decreased to 1.92±0.79 mmol/L with placebo and 0.61±0.61 mmol/L with alirocumab (p Conclusion In this study of intensive LDL-C lowering treatment initiated in the acute AMI setting, more favorable plaque changes were observed in patients with lower on-treatment LDL-C levels and in lesions with more adverse baseline plaque characteristics. Whether AMI patients with high-risk plaque features might derive greater clinical benefit from early initiation of intensive LDL-C-lowering therapies requires further investigation. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Sanofi, Regeneron

Stroke associated with transcatheter aortic valve replacement (TAVR) is a potentially devastating complication. Until recently, the Sentinel™ Cerebral Protection System (CPS; Boston Scientific) has been the only commercially available device for mechanical prevention of TAVR-related stroke. However, its effectiveness is still undetermined. Methods Between January 2019 and August 2020 consecutive patients were randomly assigned to TAVR with or without Sentinel™ in a 1:1 fashion. We defined as primary endpoint clinically detectable cerebrovascular events within 72 hours after TAVR, and as secondary endpoints LOS and 12-month mortality. Logistic and linear regression analyses were used to assess associations of Sentinel™ use with endpoints. Results Of 411 patients (80±7 y/o, 47.4% female, EuroSCORE II 6.3±5.9%), Sentinel™ was used in 213 (51.8%), with both filters correctly deployed in 189 (46.0%). 20 (4.9%) cerebrovascular events were recorded, 10 (2.4%) of which were disabling strokes. Sentinel™ reduced cerebrovascular events in univariate analysis by 71% (OR 0.29, 95% CI 0.11–0.82; p=0.02) and after multivariate adjustment by 75% (adj. OR 0.25; 95% CI 0.08–0.80; p=0.02). Sentinel™ use was also significantly associated with shorter LOS (8.4±9.6 versus 6.7±6.1 days; p=0.03) and lower 12-month all-cause mortality (15.7% versus 7.5%, p=0.01). Conclusions In the present prospective all-comers TAVR cohort, Sentinel™ significantly 1) reduced cerebrovascular events, 2) shortened LOS, and 3) improved 12-month survival. These data promote the use of a CPS when implanting TAVR valves. Funding Acknowledgement Type of funding sources: None.

A patient with a three-year history of recurrent pulmonary embolism is presented. Thromboembolic pulmonary hypertension was proven in the final stage of disease in the presence of repeated episodes of systemic embolic events. Paradoxical embolism was assumed to be present on the basis of blood-gas analysis and contrast echocardiography that demonstrated a right-to-left shunt at atrial level. Autopsy revealed a patent foramen ovale and provided strong evidence for the accuracy of the clinical diagnosis.