Long-term risk of recurrent cerebrovascular events after patent foramen ovale closure: Results from a real-world stroke cohort.

INTRODUCTION: Patent foramen ovale (PFO)-closure is recommended for stroke prevention in selected patients with suspected PFO-associated stroke. However, studies on cerebrovascular event recurrence after PFO-closure are limited by relatively short follow-up periods and information on the underlying aetiology of recurrent events is scarce. PATIENTS AND METHODS: All consecutive patients with a cerebral ischaemic event and PFO-closure at the University Hospital Graz were prospectively identified from 2004 to 2021. Indication for PFO-closure was based on a neurological-cardiological PFO board decision. Patients underwent standardized clinical and echocardiographic follow-up 6 months after PFO-closure. Recurrent cerebrovascular events were assessed via electronical health records. RESULTS: PFO-closure was performed in 515 patients (median age: 49 years; Amplatzer PFO occluder: 42%). Over a median follow-up of 11 years (range: 2-18 years, 5141 total patient-years), recurrent ischaemic cerebrovascular events were observed in 34 patients (ischaemic stroke: n = 22, TIA: n = 12) and associated with age, hyperlipidaemia and smoking in multivariable analysis (p < 0.05 each). Large artery atherosclerosis and small vessel disease were the most frequent aetiologies of recurrent stroke/TIA (27% and 24% respectively), and only two events were related to atrial fibrillation (AF). Recurrent ischaemic cerebrovascular event rates and incident AF were comparable in patients treated with different PFO occluders (p > 0.1). DISCUSSION AND CONCLUSION: In this long-term follow-up-study of patients with a cerebral ischaemic event who had received PFO-closure with different devices, rates of recurrent stroke/TIA were low and largely related to large artery atherosclerosis and small vessel disease. Thorough vascular risk factor control seems crucial for secondary stroke prevention in patients treated for PFO-related stroke.

VA-ECMO and thrombus aspiration in a pulmonary embolism patient with cardiac arrest and contraindications to thrombolytic therapy.

A 57-year-old male patient with a history of proximal deep vein thrombosis on vitamin K antagonist therapy, suffered a recent hypertensive intracranial hemorrhage without significant neurological deficit. Three weeks later he presented with bilateral central pulmonary embolism. He had witnessed cardiac arrest and was put on veno-arterial extracorporeal membrane oxygenation (VA-ECMO). Endovascular thrombectomy with an Aspirex device led to a significant improvement of hemodynamics. VA-ECMO was terminated after one day, an IVC filter was inserted, and he was discharged from ICU after 15 days. In conclusion, VA-ECMO and endovascular therapy are rescue strategies in patients with contraindications for thrombolysis.

Personalization of electro-mechanical models of the pressure-overloaded left ventricle: fitting of Windkessel-type afterload models.

Computer models of left ventricular (LV) electro-mechanics (EM) show promise as a tool for assessing the impact of increased afterload upon LV performance. However, the identification of unique afterload model parameters and the personalization of EM LV models remains challenging due to significant clinical input uncertainties. Here, we personalized a virtual cohort of N = 17 EM LV models under pressure overload conditions. A global-local optimizer was developed to uniquely identify parameters of a three-element Windkessel (Wk3) afterload model. The sensitivity of Wk3 parameters to input uncertainty and of the EM LV model to Wk3 parameter uncertainty was analysed. The optimizer uniquely identified Wk3 parameters, and outputs of the personalized EM LV models showed close agreement with clinical data in all cases. Sensitivity analysis revealed a strong dependence of Wk3 parameters on input uncertainty. However, this had limited impact on outputs of EM LV models. A unique identification of Wk3 parameters from clinical data appears feasible, but it is sensitive to input uncertainty, thus depending on accurate invasive measurements. By contrast, the EM LV model outputs were less sensitive, with errors of less than 8.14% for input data errors of 10%, which is within the bounds of clinical data uncertainty. This article is part of the theme issue 'Uncertainty quantification in cardiac and cardiovascular modelling and simulation'.

Diurnal Variability of On-Treatment Platelet Reactivity in Clopidogrel versus Prasugrel Treated Acute Coronary Syndrome Patients: A Pre-Specified TROPICAL-ACS Sub-Study.

Long-term evidence supports a clustering of cardiovascular events in the early morning and smaller mechanistic studies in aspirin-treated patients have shown increased platelet reactivity at the end of the dosing interval. Comparative pharmacodynamic analyses for different adenosine diphosphate (ADP) receptor inhibitors in percutaneous coronary intervention-treated acute coronary syndrome (ACS) patients are lacking and this pre-specified analysis from the randomized Testing Responsiveness To Platelet Inhibition On Chronic Antiplatelet Treatment For Acute Coronary Syndromes (TROPICAL-ACS) trial aimed for the first time at investigating diurnal variability of on-treatment platelet reactivity in clopidogrel versus prasugrel treated patients. TROPICAL-ACS randomized 2,610 ACS patients to either treatment with prasugrel (control group) or to a platelet function testing-guided de-escalation of anti-platelet treatment with a switch to clopidogrel (guided de-escalation group). This study design enabled a diurnal comparison of on-prasugrel versus on-clopidogrel treatment platelet reactivity under steady-state conditions. For 2,526 patients (97%), both the exact time of blood sampling and the ADP-induced platelet aggregation value (in units, Multiplate analyser) were available. Platelet reactivity in patients on clopidogrel (n = 1,265) was higher and subject to significant diurnal variability (p = 0.019) with a peaking of platelet reactivity in the early morning (5-10 a.m.). In prasugrel-treated patients (n = 1,261), there was no sign for diurnal variability (p = 0.174) or a peaking of platelet reactivity in the morning. The potent ADP receptor inhibitor prasugrel is not subject to diurnal variability while we observed a significant diurnal variability of on-clopidogrel platelet reactivity. The clinical impact of this observation may differ for patients with and without an adequate response to clopidogrel treatment and the issue of diurnal variability of platelet reactivity in ACS patients warrants further investigation.