Abstract Objectives The aim of the study was to analyse LV systolic function and mechanical energetics in asymptomatic patients with severe aortic regurgitation (AR) to seek a new hemodynamic concept for timing for surgery. Background Current guidelines suggest surgery for patients with severe AR including clinical symptoms, subnormal LV ejection fraction (EF), or markedly abnormal left ventricular dimensions. However, the optimal measure to detect intrinsic myocardial systolic dysfunction in the presence of normal LVEF remains elusive. Methods Strain and echo-derived single beat pressure-volume analyses were performed in cohorts with severe AR without indication for surgery (ARNS; LVEDD <70mm, EF >50%, n=41), with indication for surgery (ARS; n=19) and in healthy, age-matched controls (C; n=20). Additionally, end-systolic elastance (Ees=LV contractility), stroke work (SW) and total energy (PVA) were calculated. Results Patients with ARNS demonstrated significant depression of LV contractility vs. C: Ees (1.5mmHg/ml ±0.7 vs. 2.25mmHg/ml ±0.7; p<0.001), despite comparable ejection fractions (EF: 0.56±0.05 vs. 0.60±0.07; p=0.10). Accordingly, global longitudinal strain (GLS) was decreased (−16.0±2.5% vs. −21.5±2%; p<0.001), end-diastolic volume markedly enlarged (236ml ±90 vs. 136ml ±30; p<0.001), as were PVA and SW indicating waste of energy. The correlation of GLS vs. Ees was good (r=−0.68; p<0.001). Results of ARS-patients were consistently worse. Conclusion Patients with severe AR and normal LVEF showed depressed LV contractility and waste of energy when assessed by Ees and GLS, both correlating well with each other. Hence, GLS may outperform LV dimensions for predicting timing for surgery and clinical outcomes in AR patients. Funding Acknowledgement Type of funding source: None
Abstract Introduction While modern P2Y12-inhibitors and drug eluting stents (DES) have changed therapeutic options in patients with ST-elevation mycoardial infarctions (STEMI) during the last decade, there is few data on their impact in real world registries. Aim of the present study was to analyze changes in mortality and major adverse cardiac and cererobrovascular event rates (MACCE: death, reinfarction,stroke) during the last 13 years in patients with uncomplicated STEMI after successful percutaneous coronary intervention (PCI). Methods All consecutive STEMI-patients, admitted between 2006 and 2018 and successfully treated with PCI (TIMI flow ≥2) in a large German heart center entered analysis. To reduce confounding pts. with STEMI complicated by heart failure and pts. >70 yrs. of age were excluded. Results A STEMI-cohort of 5016 pts. was analysed, with a mean age of 55.9±8 yrs., 19% females, 16% diabetics and 59% smokers. At the beginning of the study period (2006) no patient was treated with ticagrelor/prasugrel and only 5% had a DES implanted. In 2018 92% were treated with prasugrel or ticagrelor and 96% with a DES. The reduction in 1-year-mortality during the study period was not significant: 2006–11: 3.4%, 2012–19: 3.1%, p=0.4, however the reduction in 1-year-MACCE was: 2006–11: 8.3%, 2012–18: 5.7%, p<0.01. This could mainly be attributed to a reduction in reinfarctions: 2006–11: 4.9%, 2012–18: 2.8%, p<0.01. Subgroup analysis revealed that with the exception of diabetics all subgroups showed a significant decline in MACCE-rates during the study period. It was more pronounced in women, non-smokers and patients with a high socioeconomic status (SES) (Table). Analysis of 5-year-data revealed a significant reduction in both 5-year-mortality (2006–09: 9.1%, 2010–13: 6.8%, p<0.01) and 5-year-MACCE-rates: 2006–09: 19.3%, 2010–13: 14.5%, p<0.01. Conclusions This analysis of registry data over a study period of 13 years reveals, that for patients with uncomplicated STEMI and successful PCI a significantly better 1- and 5-year-outcome could be achieved during the last years. This improvement of prognosis was more pronounced in specific subgroups, such as women, non-diabetics and patients with higher SES. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Stiftung Bremer Herzen, Gesundheit Nord
Abstract Platelet activation plays a critical role in thrombosis. Inhibition of platelet activation is a cornerstone in treatment of acute organ ischemia. Platelet ACKR3 surface expression is independently associated with all-cause mortality in CAD patients. In a novel genetic mouse strain, we show that megakaryocyte/platelet-specific deletion of ACKR3 results in enhanced platelet activation and thrombosis in vitro and in vivo. Further, we performed ischemia/reperfusion experiments (transient LAD-ligation and tMCAO) in mice to assess the impact of genetic ACKR3 deficiency in platelets on tissue injury in ischemic myocardium and brain. Loss of platelet ACKR3 enhances tissue injury in ischemic myocardium and brain and aggravates tissue inflammation. Activation of platelet-ACKR3 via specific ACKR3 agonists inhibits platelet activation and thrombus formation and attenuates tissue injury in ischemic myocardium and brain. Here we demonstrate that ACKR3 is a critical regulator of platelet activation, thrombus formation and organ injury following ischemia/reperfusion.
