Rafail Angelos Kotronias

Aims: Iron deficiency (ID) is common amongst patients with ST-elevation myocardial infarction (STEMI). Its impact on outcomes remains contested. Previous studies reported favourable or adverse impacts depending on outcome measures, sampling timepoints, ID definition and follow-up duration. This study systematically characterises the prognostic impact of iron status on short-term, mid-term and long-term outcomes, and evaluates the effect of sampling timepoint and ID definition on these prognostic relationships. Methods & Results: We performed an observational cohort study in patients with acute STEMI (n = 167) and no prior heart failure (HF). Iron markers were sampled at presentation, and successive timepoints thereafter. Cardiac Magnetic Resonance was performed at 2 days and 6 months. Major adverse cardiovascular events (MACE), consisting of new-onset HF, recurrent MI or cardiac death were recorded over 4.5 years. Mechanisms were evaluated in a preclinical model of MI. ID was common at presentation, affecting between 44.9% and 67%, depending on ID definition. Tsat <20%, serum iron<13μM, or European Society of Cardiology’s definition, but not ferritin<100μg/L, independently predicted lower risk of MACE. Lower Tsat at presentation predicted attenuated infarct and non-infarct T1, and smaller left ventricular volumes at 2 days. This prognostic effect was weakened by delayed sampling. Lower Tsat and serum iron in the post-acute timepoints, but not at presentation, predicted lower myocardial salvage at 6 months. In mice, MI triggered an acute myocardial labile iron storm and early LV remodelling, progressing to HF. Baseline ID and acute iron chelation averted these effects. Conclusions: This study gives rise to the hypothesis that ID at presentation with STEMI improves long-term outcomes by attenuating myocardial injury. It reconciles previous conflicting reports by revealing the confounding effects of delayed sampling, and non-interchangeability of different ID definitions. It suggests iron chelation in the acute stage, followed by post-acute iron repletion might improve long-term outcomes.

Primary percutaneous coronary intervention (pPCI) has revolutionized the prognosis of ST-segment elevation myocardial infarction (STEMI) and is the gold standard treatment. As a result of its success, the number of pPCI centres has expanded worldwide. Despite decades of advancements, clinical outcomes in STEMI patients have plateaued. Out-of-hospital cardiac arrest and cardiogenic shock remain a major cause of high in-hospital mortality, whilst the growing burden of heart failure in long-term STEMI survivors presents a growing problem. Many elements aiming to optimize STEMI treatment are still subject to debate or lack sufficient evidence. This review provides an overview of the most contentious current issues in pPCI in STEMI patients, with an emphasis on unresolved questions and persistent challenges.

Primary percutaneous coronary intervention (pPCI) has revolutionized the prognosis of ST-segment ele-vation myocardial infarction (STEMI) and is the gold standard treatment. As a result of its success, the number of pPCI centres has expanded worldwide. Despite decades of advancements, clinical outcomes in STEMI patients have plateaued. Out-of-hospital car-diac arrest and cardiogenic shock remain a major cause of high in-hospital mortality, whilst the growing burden of heart failure in long-term STEMI survivors presents a growing problem. Many elements aiming to optimize STEMI treatment are still subject to debate or lack sufficient evidence. This review provides an overview of the most contentious current issues in pPCI in STEMI patients, with an emphasis on unresolved questions and persistent challenges.

A 69-year-old, asymptomatic, and haemodynamically stable male was admitted 48 h following chest pain with lateral ST-segment elevation acute coronary syndrome (STEACS).

Introduction: Analysis of small-molecule metabolites in plasma has the potential for development as a clinical diagnostic and prognostic tool. Atmospheric solids analysis probe mass spectrometry (ASAP-MS) is capable of providing rapid metabolite and small molecule fingerprinting and has the potential for use in a cinical setting. Such an approach could provide clinicians with a rapid patient risk metric, predicting disease progression and response to treatment, and thereby aiding in treatment decisions. Objectives: To develop a robust experimental protocol for performing ASAP-MS measurements on plasma samples. Methods: We performed ASAP-MS measurements on plasma samples from patients recruited for two prospective clinical studies: the Oxford Acute Myocardial Infarction (OxAMI) study; and the Oxford Abdominal Aortic Aneurysm (OxAAA) study. Over the course of a carefully designed series of measurements, we optimised the method of sample introduction, together with a number of key instrument and data acquisition parameters. Results: Following the optimisation process, we are consistently able to record high quality mass spectra for plasma samples. Typical coefficients of variation for individual mass peaks are in the range from 20-50%, in line with those obtained by other researchersresearchers [1, 2] using more sophisticated LC-MS approaches. Conclusions: We have developed a measurement protocol for ASAP-MS measurements on plasma samples which optimises mass spectral quality and reproducibility, while still retaining the simplicity of measurement required for use in a clinical setting. While tested on samples from two specific cohorts of patients, the protocol can be employed in measurements on any blood plasma samples.

Background: Venous thromboembolism (VTE) is common among patients with severe coronavirus disease 2019 (COVID-19). Anticoagulation in hospitalized COVID-19 patients has been associated with survival benefit; however, the optimal thromboprophylaxis strategy has not yet been defined. Objective: To identify published guidance reports by national and international societies regarding thromboprophylaxis strategies in COVID-19 patients in different settings (outpatients, hospitalized, post-discharge). Methods: A systematic review of the literature (Pubmed/EMBASE) was conducted independently by two investigators. Results: Among 1942 initially identified articles, 33 guidance documents were included: 20 published by national and 13 by international societies. These documents provide recommendations mainly for hospitalized (97% of reports) and post-discharge (75%) COVID-19 patients, and less so for outpatients (34%). Thrombotic and bleeding risk stratification prior to any treatment decision is the cornerstone of all suggested thromboprophylaxis strategies; 81% of the documents recommend thromboprophylaxis for all hospitalized patients with a prophylactic dosage of low molecular weight heparin irrespective of VTE risk. Intermediate or therapeutic dose intensity is recommended in high VTE risk patients by 56% and 28% of documents, respectively. Mechanical thromboprophylaxis is suggested in case of high bleeding risk or contraindication to pharmacological thromboprophylaxis (59% of documents). Extended pharmacological thromboprophylaxis is recommended for patients with high VTE risk after hospital discharge (63% of documents). For non-hospitalized outpatients, 28% of documents recommend pharmacological thromboprophylaxis for high VTE risk. Conclusion: The current guidance identifies thromboprophylaxis in COVID-19 patients, especially during hospitalization, as of major importance for the prevention of VTE. Recommendations are derived from limited evidence from observational studies.