Intake of hemoglobin by the hemoglobin-haptoglobin receptor CD163 leads to a distinct alternative non-foam cell antiinflammatory macrophage phenotype that was previously considered atheroprotective. Here, we reveal an unexpected but important pathogenic role for these macrophages in atherosclerosis. Using human atherosclerotic samples, cultured cells, and a mouse model of advanced atherosclerosis, we investigated the role of intraplaque hemorrhage on macrophage function with respect to angiogenesis, vascular permeability, inflammation, and plaque progression. In human atherosclerotic lesions, CD163+ macrophages were associated with plaque progression, microvascularity, and a high level of HIF1α and VEGF-A expression. We observed irregular vascular endothelial cadherin in intraplaque microvessels surrounded by CD163+ macrophages. Within these cells, activation of HIF1α via inhibition of prolyl hydroxylases promoted VEGF-mediated increases in intraplaque angiogenesis, vascular permeability, and inflammatory cell recruitment. CD163+ macrophages increased intraplaque endothelial VCAM expression and plaque inflammation. Subjects with homozygous minor alleles of the SNP rs7136716 had elevated microvessel density, increased expression of CD163 in ruptured coronary plaques, and a higher risk of myocardial infarction and coronary heart disease in population cohorts. Thus, our findings highlight a nonlipid-driven mechanism by which alternative macrophages promote plaque angiogenesis, leakiness, inflammation, and progression via the CD163/HIF1α/VEGF-A pathway.

OBJECTIVES Right ventricular (RV) failure after left ventricular assist device (LVAD) implantation continues to be a morbid complication. In this study, we hypothesized that a less invasive approach to implantation would preserve RV function relative to a conventional sternotomy (CS) approach. METHODS All patients (2013–2017) who underwent LVAD implantation were reviewed. Patients were stratified by surgical approach: less invasive left thoracotomy with hemi-sternotomy (LTHS) and CS. The primary outcome was severe RV failure. RESULTS Eighty-three patients (LTHS: 37, CS: 46) were identified. The median Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) score was significantly worse in the LTHS compared to the CS cohort, and there was a trend towards higher RV failure scores and HeartMate II mortality scores. Preoperative RV dysfunction, in pulmonary artery pulsatility index and RV stroke work index were similar between the 2 groups. Though operative time did not significantly differ between the 2 groups, cardiopulmonary bypass time was significantly shorter in the LTHS group (61 vs 95 min, P < 0.001). The incidence of postoperative severe RV failure was significantly reduced in the LTHS group (16% vs 39%, P = 0.030), along with the need for temporary right ventricular assist device (3% vs 26%, P = 0.005). Improvement in RV function, along with a change in pulmonary artery pulsatility index, was significantly greater in the LTHS cohort. There was a trend towards improved Kaplan–Meier 1-year survival in the LTHS cohort (91% vs 56%, P = 0.056). CONCLUSIONS In this cohort, less invasive LVAD implantation appears to be associated with reduced postoperative RV failure, and equivalent or improved survival compared to conventional LVAD implantation.

Background Statins have anti-inflammatory and immunomodulatory effects that may reduce the severity of coronavirus disease 2019 (COVID-19), in which organ dysfunction is mediated by severe inflammation. Large studies with diverse populations evaluating statin use and outcomes in COVID-19 are lacking. Methods and results We used data from 10,541 patients hospitalized with COVID-19 through September 2020 at 104 US hospitals enrolled in the American Heart Association’s COVID-19 Cardiovascular Disease (CVD) Registry to evaluate the associations between statin use and outcomes. Prior to admission, 42% of subjects (n = 4,449) used statins (7% on statins alone, 35% on statins plus anti-hypertensives). Death (or discharge to hospice) occurred in 2,212 subjects (21%). Outpatient use of statins, either alone or with anti-hypertensives, was associated with a reduced risk of death (adjusted odds ratio [aOR] 0.59, 95% CI 0.50–0.69), adjusting for demographic characteristics, insurance status, hospital site, and concurrent medications by logistic regression. In propensity-matched analyses, use of statins and/or anti-hypertensives was associated with a reduced risk of death among those with a history of CVD and/or hypertension (aOR 0.68, 95% CI 0.58–0.81). An observed 16% reduction in odds of death among those without CVD and/or hypertension was not statistically significant. Conclusions Patients taking statins prior to hospitalization for COVID-19 had substantially lower odds of death, primarily among individuals with a history of CVD and/or hypertension. These observations support the continuation and aggressive initiation of statin and anti-hypertensive therapies among patients at risk for COVID-19, if these treatments are indicated based upon underlying medical conditions.

Aims Vascular calcification is routinely encountered in percutaneous coronary intervention (PCI) and severe coronary calcification is a known predictor of in-stent restenosis and stent thrombosis. However, the histopathologic mechanisms behind such events have not been systematically described. Methods and results From our registry of 1211 stents, a total of 134 newer-generation drug-eluting stents (DES) (Xience, Resolute-Integrity, PROMUS-Element, and Synergy) with duration of implant ≥30 days were histologically analysed. The extent of calcification of the stented lesions was evaluated radiographically and divided into severe (SC, n = 46) and non-severely calcified lesions (NC, n = 88). The percent-uncovered struts per section {SC vs. NC; median 2.4 [interquartile range (IQR) 0.0–19.0] % vs. 0.0 (IQR 0.0–4.6) %, P = 0.02} and the presence of severe medial tears (MTs) (59% vs. 44%, respectively, P = 0.03) were greater in SC than NC. In addition, SC had a higher prevalence of ≥3 consecutive struts lying directly in contact with surface calcified area (3SC) (52% vs. 8%, respectively, P &lt; 0.0001). Multivariate analysis demonstrated that sections with duration of implantation ≤6 months [odds ratio (OR): 7.7, P &lt; 0.0001], 3SC (OR: 6.5, P &lt; 0.0001), strut malapposition (OR: 5.0, P &lt; 0.0001), and lack of MTs (OR: 2.5, P = 0.0005) were independent predictors of uncovered struts. Prevalence of neoatherosclerosis was significantly lower in SC than that of NC (24% vs. 44%, P = 0.02). Conclusion Severe calcification, especially surface calcified area is an independent predictor of uncovered struts and delayed healing after newer-generation DES implantation. These data expand of knowledge of the vascular responses of stenting of calcified arteries and suggests further understand of how best to deal with calcification in patients undergoing PCI.

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