Background-Congestive heart failure (CHF) is a disease that is characterized by progressive left ventricular (LV) dysfunction and dilatation. Oxidative stress is thought to contribute to the progression of CHF, and antioxidants have been shown to have beneficial effects when started early after myocardial infarction (MI). In this study, we tested whether the powerful antioxidant probucol would attenuate progression of CHF once it was established after MI in the rat. Methods and Results-Ligation of a coronary artery was used to create an MI in rats (nϭ266). Survivors were then randomized 20 days after MI to either probucol 61 mg · kg Ϫ1 · d Ϫ1 or vehicle and followed up for a total of 100 days after MI. Studies of cardiac hemodynamics, LV remodeling, cardiac apoptosis and morphology, systemic neurohumoral activation, oxidative stress, and renal function were then evaluated. Probucol improved LV function (LV maximum rate of pressure rise from 3103 to 4250 mm Hg/s, PϽ0.05, and LV end-diastolic pressure decrease from 28 to 24 mm Hg, PϽ0.05), reduced pulmonary weights, prevented right ventricular systolic hypertension, and preserved renal function compared with vehicle. Probucol also prevented LV dilatation, prevented wall thinning (1.70 versus 1.42 mm, PϽ0.05), reduced cardiac fibrosis and cardiac apoptosis, attenuated increased myocardial cell cross-sectional area, and increased scar thickness. Conclusions-In

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BackgroundThoracic ascending aorta aneurysms (TAA) are an important cause of mortality in adults but are a relatively less studied subject compared to abdominal aortic aneurysms (AAA). The purpose of this review is to explain the main aspects (etiology, pathophysiology, diagnosis) of this disease and to summarize the most recent developments in its management.MethodologyLiterature was obtained through online health related search engines (PubMed, MEDLINE) by including the following keywords: ascending aorta aneurysm, thoracic aneurysms, Marfan syndrome, bicuspid aortic valve, familial thoracic syndrome, aortic dissection, aorta imaging and aortic aneurysm guidelines. We included articles dating from 1980 to 2014.FindingsLiterature revealed how lethal this disease can be and how simple steps such as follow-up and prophylactic surgery can significantly reduce morbidity and mortality. This review also allowed us to realize the many developments that have been made in recent years in the understanding of pathologic mechanisms of this disease.ConclusionTAA is a silent disease that needs to be recognized early in its course and followed closely in order to recommend appropriate preventive and prophylactic therapy in a timely manner.

This study indicates that the anti-oxidant probucol markedly improves post-MI survival in rats despite few demonstrable effects on cardiac remodeling or hemodynamics. Its beneficial effects may, however, be associated with reduced cardiac fibrosis, oxidative stress and expression of pro-inflammatory cytokines.

The period following heart failure hospitalization (HFH) is a vulnerable time with high rates of death or recurrent HFH.OBJECTIVE To evaluate clinical characteristics, outcomes, and treatment response to vericiguat according to prespecified index event subgroups and time from index HFH in the Vericiguat Global Study in Subjects With Heart Failure With Reduced Ejection Fraction (VICTORIA) trial. DESIGN, SETTING, AND PARTICIPANTSAnalysis of an international, randomized, placebo-controlled trial. All VICTORIA patients had recent (<6 months) worsening HF (ejection fraction <45%). Index event subgroups were less than 3 months after HFH (n = 3378), 3 to 6 months after HFH (n = 871), and those requiring outpatient intravenous diuretic therapy only for worsening HF (without HFH) in the previous 3 months (n = 801). Data were analyzed between May 2, 2020, and May 9, 2020.INTERVENTION Vericiguat titrated to 10 mg daily vs placebo. MAIN OUTCOMES AND MEASURESThe primary outcome was time to a composite of HFH or cardiovascular death; secondary outcomes were time to HFH, cardiovascular death, a composite of all-cause mortality or HFH, all-cause death, and total HFH. RESULTS Among 5050 patients in the VICTORIA trial, mean age was 67 years, 24% were women, 64% were White, 22% were Asian, and 5% were Black. Baseline characteristics were balanced between treatment arms within each subgroup. Over a median follow-up of 10.8 months, the primary event rates were 40.9, 29.6, and 23.4 events per 100 patient-years in the HFH at less than 3 months, HFH 3 to 6 months, and outpatient worsening subgroups, respectively. Compared with the outpatient worsening subgroup, the multivariable-adjusted relative risk of the primary outcome was higher in HFH less than 3 months (adjusted hazard ratio, 1.48; 95% CI, 1.27-1.73), with a time-dependent gradient of risk demonstrating that patients closest to their index HFH had the highest risk. Vericiguat was associated with reduced risk of the primary outcome overall and in all subgroups, without evidence of treatment heterogeneity. Similar results were evident for all-cause death and HFH. Addtionally, a continuous association between time from HFH and vericiguat treatment showed a trend toward greater benefit with longer duration since HFH. Safety events (symptomatic hypotension and syncope) were infrequent in all subgroups, with no difference between treatment arms.CONCLUSIONS AND RELEVANCE Among patients with worsening chronic HF, those in closest proximity to their index HFH had the highest risk of cardiovascular death or HFH, irrespective of age or clinical risk factors. The benefit of vericiguat did not differ significantly across the spectrum of risk in worsening HF.

Aspirin resistance is often defined as failure to demonstrate an inhibitory effect of aspirin on standard platelet function assays. Although many studies have been published on this phenomenon, the performance of individual assays to detect actual aspirin effects is poorly defined. The aim of this study is to define the sensitivity and potential limitations of five different assays of platelet function on detecting aspirin effects. A prospective cohort of 45 healthy volunteers consented to taking 80 mg of non-coated aspirin for 8–10 days. Participants were selected if they were non-smokers, did not present any significant medical condition and were excluded if they had ingested any potential drug / supplement known to effect platelet function in the past 10 days or were found to have abnormal blood counts. Samples were collected immediately prior to the first aspirin dose and repeated after 8 to 10 days of aspirin therapy. The study population consisted of 16 males and 29 females, 19 to 59 years of age without acquired cardiovascular risk factors and a mean BMI of 24,1 (range: 18,8–32,5). Study drug intake was carefully monitored by patient questionnaire and unused pill count at the second study visit. Partial non compliance was identified in 4 participants (1–2 missed doses) although no missed doses occurred in the last 3 days of the study. Mean delay between the last aspirin dose and the post study sample was 221 minutes (range 60 to 720 min, 5 patients with delays over 6 hours). Test characteristics and performances in detecting aspirin intake in our population are resumed in the table below. Conclusion: Although aspirin clearly has an effect in all the assays tested, the broad distribution of values with LTA-ADP, platelet count drop, TEG-MA(AA) and urinary dTxB2 does not allow accurate discrimination of aspirin effects in healthy individuals. Considering their adequate distinction between subjects on and off aspirin, we suggest that LTA-AA and the VerifyNow assay should be preferred in studies evaluating aspirin effect and potential resistance to this drug. Findings such as ours should serve to better define the limitations of laboratory studies of platelet function for the assessment of aspirin effects. Table 1. Test performance characteristics LTA-AA 1,6 mM (%) LTA-ADP 10 umol (%) VerifyNow (ARU) Platelet count drop (%) TEG-MAAA(%) dTxB2 (pg/ml) * 95% confidence intervals; **paired t-test, ***as suggested by Gum et al, ¤as suggested by manufacturer, 2best fit on ROC curve Prior to ASA 61,2 (33,9;88,4)* 74,2 (35,1;113,3) 634,5 (564,8;704,3) 74,9 (35,3;114,4) 100,6 (27,2;174) 240,8 (0;821) After ASA 2,4 (0;7,9) 40,4 (0;85,8) 407,9 (355,7;460,1) 41,5 (8,8;74,3) 53,2 (−44,4;150,8) 115 (0;407,9) p value** <10e-29 <10e-13 <10e-32 <10e-10 <10e-7 <10e-6 Proposed cut-off values < 20%*** < 70%*** <550 ARU¤ <55%2 < 90%2 < 602 Sensitivity 100 % 84,4 % 100 % 82,2 % 82,9 % 62,2% Specificity 95,6 % 77,8 % 95,6 % 86,7 % 75,8 % 82,2%

Extracorporeal life support (ECLS) is a means to support patients with acute respiratory failure. Initially, recommendations to treat severe cases of pandemic coronavirus disease 2019 (COVID‐19) with ECLS have been restrained. In the meantime, ECLS has been shown to produce similar outcomes in patients with severe COVID‐19 compared to existing data on ARDS mortality. We performed an international email survey to assess how ECLS providers worldwide have previously used ECLS during the treatment of critically ill patients with COVID‐19. A questionnaire with 45 questions (covering, e.g., indication, technical aspects, benefit, and reasons for treatment discontinuation), mostly multiple choice, was distributed by email to ECLS centers. The survey was approved by the European branch of the Extracorporeal Life Support Organization (ELSO); 276 ECMO professionals from 98 centers in 30 different countries on four continents reported that they employed ECMO for very severe COVID‐19 cases, mostly in veno‐venous configuration (87%). The most common reason to establish ECLS was isolated hypoxemic respiratory failure (50%), followed by a combination of hypoxemia and hypercapnia (39%). Only a small fraction of patients required veno‐arterial cannulation due to heart failure (3%). Time on ECLS varied between less than 2 and more than 4 weeks. The main reason to discontinue ECLS treatment prior to patient’s recovery was lack of clinical improvement (53%), followed by major bleeding, mostly intracranially (13%). Only 4% of respondents reported that triage situations, lack of staff or lack of oxygenators, were responsible for discontinuation of ECLS support. Most ECLS physicians (51%, IQR 30%) agreed that patients with COVID‐19‐induced ARDS (CARDS) benefitted from ECLS. Overall mortality of COVID‐19 patients on ECLS was estimated to be about 55%. ECLS has been utilized successfully during the COVID‐19 pandemic to stabilize CARDS patients in hypoxemic or hypercapnic lung failure. Age and multimorbidity limited the use of ECLS. Triage situations were rarely a concern. ECLS providers stated that patients with severe COVID‐19 benefitted from ECLS.

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