Objective-Intraplaque hemorrhage (IPH) is an important progression event in advanced atherosclerosis, in large part because of the delivery of prooxidant hemoglobin in erythrocytes. We have previously defined a novel macrophage phenotype (hemorrhage-associated-mac) in human advanced plaques with IPH. These may be atheroprotective in view of raised heme oxygenase 1 (HO-1), CD163, and interleukin-10 expression and suppressed oxidative stress. Methods and Results-We have used a combination of small interfering RNA and pharmacological reagents, protein analysis, and oxidative stress measurements to dissect the pathway leading to the development of this phenotype. We found that erythrocytes, hemoglobin, or purified heme similarly induced CD163 and suppressed human leukocyte antigen and reactive oxygen species. HO-1 was required for the development of each of these features. Challenge of macrophages with purified heme provoked nuclear translocation of Nrf2, and Nrf2 small interfering RNA resulted in significant inhibition of the ability of heme to induce HO-1 protein. Furthermore, tert-butyl-hydroquinone, which activates Nrf2, upregulated CD163, suppressed human leukocyte antigen, and induced interleukin-10, further supporting a role for Nrf2-mediated signaling. However, an inducible protein transactivator is also probably necessary, as heme-induced HO-1 mRNA expression was fully inhibited by the protein synthesis inhibitor cycloheximide. Conclusion-Our

Aims We assessed the outcome of hospitalized coronavirus disease 2019 (COVID‐19) patients with heart failure (HF) compared with patients with other cardiovascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia). We further wanted to determine the incidence of HF events and its consequences in these patient populations. Methods and results International retrospective Postgraduate Course in Heart Failure registry for patients hospitalized with COVID‐19 and CArdioVascular disease and/or risk factors (arterial hypertension, diabetes, or dyslipidaemia) was performed in 28 centres from 15 countries (PCHF‐COVICAV). The primary endpoint was in‐hospital mortality. Of 1974 patients hospitalized with COVID‐19, 1282 had cardiovascular disease and/or risk factors (median age: 72 [interquartile range: 62–81] years, 58% male), with HF being present in 256 [20%] patients. Overall in‐hospital mortality was 25% ( n = 323/1282 deaths). In‐hospital mortality was higher in patients with a history of HF (36%, n = 92) compared with non‐HF patients (23%, n = 231, odds ratio [OR] 1.93 [95% confidence interval: 1.44–2.59], P < 0.001). After adjusting, HF remained associated with in‐hospital mortality (OR 1.45 [95% confidence interval: 1.01–2.06], P = 0.041). Importantly, 186 of 1282 [15%] patients had an acute HF event during hospitalization (76 [40%] with de novo HF), which was associated with higher in‐hospital mortality (89 [48%] vs. 220 [23%]) than in patients without HF event (OR 3.10 [2.24–4.29], P < 0.001). Conclusions Hospitalized COVID‐19 patients with HF are at increased risk for in‐hospital death. In‐hospital worsening of HF or acute HF de novo are common and associated with a further increase in in‐hospital mortality.

S-ICD screening failure occurs in up to 13% of patients with inherited primary arrhythmia syndromes. Patients with BrS present a higher rate of screening failure as compared with other cardiac channelopathies.

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Menstrual pain is consequent to intense uterine contraction aimed to expel menstrual flow through downstream uterine cervix. Herein it was evaluated whether characteristics of uterine cervix are associated with intensity of menstrual pain. Ultrasound elastography was used to analyze cervix elasticity of 75 consecutive outpatient women. Elasticity was related to intensity of menstrual pain defined by a Visual Analogue Scale (VAS). Four regions of interest (ROI) were considered: internal uterine orifice (IUO), anterior (ACC) and posterior cervical (PCC) compartment and middle cervical canal (MCC). Tissue elasticity, evaluated by color score (from 0.5 = blue/violet (low elasticity) to 3.0 = red (high elasticity), and percent tissue deformation was analyzed. Elasticity of IUO was lower (p = 0.0001) than that of MCC or ACC, and it was negatively related (R2 = 0.428; p = 0.0001) to menstrual VAS (CR −2.17; 95%CI −3.80, −0.54; p = 0.01). Presence of adenomyosis (CR 3.24; 95% CI 1.94, 4.54; p = 0.0001) and cervix tenderness at clinical examination (CR 2.74; 95% CI 1.29, 4.20; p = 0.0004), were also independently related to menstrual VAS. At post hoc analysis, women with vs. without menstrual pain had lower IUO elasticity, expressed as color score (0.72 ± 0.40 vs. 0.92 ± 0.42; p = 0.059), lower percent tissue deformation at IUO (0.09 ± 0.05 vs. 0.13 ± 0.08; p = 0.025), a higher prevalence of cervical tenderness at bimanual examination (36.2% vs. 9.5%; p = 0.022) and a higher prevalence of adenomyosis (46.5% vs. 19.9%; p = 0.04). These preliminary data indicate that IUO elasticity is associated with the presence and the intensity of menstrual pain. Mechanisms determining IUO elasticity are useful to be explored.