Therapeutic fibrinolysis is ineffective in 40 % of ST-segment elevation acute myocardial infarction (STEMI) patients, but understanding of the mechanisms is incomplete. It was our aim to compare the composition of coronary thrombus in lysis-resistant STEMI patients with that of lysis-sensitive patients. Intracoronary thrombi (n=64) were obtained by aspiration in consecutive STEMI patients. Of them, 20 had received fibrinolysis and underwent rescue percutaneous coronary intervention (r-PCI, lysis-resistant patients) and 44 underwent primary PCI (p-PCI). Lysis-sensitivity was determined in vitro by clot permeability measurements and turbidimetric lysis in plasma of 44 patients undergoing p-PCI and 20 healthy donors. Clot-lysis sensitivity was defined as a clot-lysis time not greater than 1 SD over the mean of healthy donors. Coronary thrombus composition in 20 lysis-resistant and in 20 lysissensitive patients was analysed by immunofluorescence with confocal microscopy. Plasma biomarkers (P-selectin, VWF, PAI-1, t-PA, D-dimer, TF pathway markers, plasmin and CD34⁺) were measured simultaneously on peripheral blood. Lysis-resistant clots had higher levels of fibrin (p=0.02), P-selectin (p=0.03) and VWF (p=0.01) than lysis-sensitive clots. Among thrombi obtained ≤ 6 hours after onset of symptoms, those from lysis-resistant patients showed a higher content in fibrin than those from p-PCI patients (p=0.01). Plasma PAI-1 (p=0.02) and D-dimer levels were significantly higher (p=0.003) in lysis-resistant patients, whereas plasmin levels were lower (p=0.03). Multivariate analysis showed the content of fibrin and VWF within thrombus as predictors of thrombolysis resistance. In conclusion, coronary thrombi in STEMI patients resistant to fibrinolysis are characterised by higher fibrin, P-selectin and VWF content than lysis-sensitive thrombi.

Proper treatment of hypoxic myoclonic status is not clearly determined. Induced hypothermia is improving prognosis and a more aggressive treatment might be beneficial in some patients. Among the new options of antiepileptic drugs, perampanel (PER) is a drug with a novel mechanism, and it might be a promising drug for myoclonic status or as an antimyoclonic drug. We describe the use of PER in one patient with hypoxic super-refractory myoclonic status. A 51-year-old patient presented after an out-of-hospital cardiac arrest due to an acute myocardial infarction. The patient was diagnosed with clinical and electrical (EEG) myoclonic status at the rewarming phase. Several treatments were used, starting with clonazepam, valproate, sedation (midazolam, propofol), and subsequently barbiturate-induced coma with persistent myoclonic status. Finally, we decided to try PER (dose: 6-8 mg) through a nasogastric tube, resulting in a marked improvement of EEG activity and myoclonus decrease. The patient had a progressive clinical improvement, with a CPC (Cerebral Performance Category) scale score of 1. This case shows the potential utility of PER as a therapeutic option in super-refractory hypoxic status and even its potential use before other aggressive alternatives considering their greater morbidity.

Background: The long-term cardiovascular (CV) outcomes of COVID-19 have not been fully explored. Methods: This was an international, multicenter, retrospective cohort study conducted between February and December 2020. Consecutive patients ≥18 years who underwent a real-time reverse transcriptase-polymerase chain reaction (RT-PCR) for SARS-CoV2 were included. Patients were classified into two cohorts depending on the nasopharyngeal swab result and clinical status: confirmed COVID-19 (positive RT-PCR) and control (without suggestive symptoms and negative RT-PCR). Data were obtained from electronic records, and clinical follow-up was performed at 1-year. The primary outcome was CV death at 1-year. Secondary outcomes included arterial thrombotic events (ATE), venous thromboembolism (VTE), and serious cardiac arrhythmias. An independent clinical event committee adjudicated events. A Cox proportional hazards model adjusted for all baseline characteristics was used for comparing outcomes between groups. A prespecified landmark analysis was performed to assess events during the post-acute phase (31–365 days). Results: A total of 4,427 patients were included: 3,578 (80.8%) in the COVID-19 and 849 (19.2%) control cohorts. At one year, there were no significant differences in the primary endpoint of CV death between the COVID-19 and control cohorts (1.4% vs. 0.8%; HR_adj 1.28 [0.56–2.91]; p = 0.555), but there was a higher risk of all-cause death (17.8% vs. 4.0%; HR_adj 2.82 [1.99–4.0]; p = 0.001). COVID-19 cohort had higher rates of ATE (2.5% vs. 0.8%, HR_adj 2.26 [1.02–4.99]; p = 0.044), VTE (3.7% vs. 0.4%, HR_adj 9.33 [2.93–29.70]; p = 0.001), and serious cardiac arrhythmias (2.5% vs. 0.6%, HR_adj 3.37 [1.35–8.46]; p = 0.010). During the post-acute phase, there were no significant differences in CV death (0.6% vs. 0.7%; HR_adj 0.67 [0.25–1.80]; p = 0.425), but there was a higher risk of deep vein thrombosis (0.6% vs. 0.0%; p = 0.028). Re-hospitalization rate was lower in the COVID-19 cohort compared to the control cohort (13.9% vs. 20.6%; p = 0.001). Conclusions: At 1-year, patients with COVID-19 experienced an increased risk of all-cause death and adverse CV events, including ATE, VTE, and serious cardiac arrhythmias, but not CV death. Study registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT04359927.

Background Bleeding risk scores have shown a limited predictive ability in elderly patients with acute coronary syndromes (ACS). No study explored the role of a comprehensive geriatric assessment to predict in-hospital bleeding in this clinical setting. Methods The prospective multicentre LONGEVO-SCA registry included 532 unselected patients with non-ST segment elevation ACS (NSTEACS) aged 80 years or older. Comorbidity (Charlson index), frailty (FRAIL scale), disability (Barthel index and Lawton–Brody index), cognitive status (Pfeiffer test) and nutritional risk (mini nutritional assessment-short form test) were assessed during hospitalization. CRUSADE score was prospectively calculated for each patient. In-hospital major bleeding was defined by the CRUSADE classification. The association between geriatric syndromes and in-hospital major bleeding was assessed by logistic regression method and the area under the receiver operating characteristic curves (AUC). Results Mean age was 84.3 years (SD 4.1), 61.7% male. Most patients had increased troponin levels (84%). Mean CRUSADE bleeding score was 41 (SD 13). A total of 416 patients (78%) underwent an invasive strategy, and major bleeding was observed in 37 cases (7%). The ability of the CRUSADE score for predicting major bleeding was modest (AUC 0.64). From all aging-related variables, only comorbidity (Charlson index) was independently associated with major bleeding (per point, odds ratio: 1.23, p = 0.021). The addition of comorbidity to CRUSADE score slightly improved the ability for predicting major bleeding (AUC: 0.68). Conclusion Comorbidity was associated with major bleeding in very elderly patients with NSTEACS. The contribution of frailty, disability or nutritional risk for predicting in-hospital major bleeding was marginal.