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Aims To evaluate the impact of the COVID-19 pandemic on patient admissions to Italian cardiac care units (CCUs). Methods and Results We conducted a multicentre, observational, nationwide survey to collect data on admissions for acute myocardial infarction (AMI) at Italian CCUs throughout a 1 week period during the COVID-19 outbreak, compared with the equivalent week in 2019. We observed a 48.4% reduction in admissions for AMI compared with the equivalent week in 2019 (P < 0.001). The reduction was significant for both ST-segment elevation myocardial infarction [STEMI; 26.5%, 95% confidence interval (CI) 21.7–32.3; P = 0.009] and non-STEMI (NSTEMI; 65.1%, 95% CI 60.3–70.3; P < 0.001). Among STEMIs, the reduction was higher for women (41.2%; P = 0.011) than men (17.8%; P = 0.191). A similar reduction in AMI admissions was registered in North Italy (52.1%), Central Italy (59.3%), and South Italy (52.1%). The STEMI case fatality rate during the pandemic was substantially increased compared with 2019 [risk ratio (RR) = 3.3, 95% CI 1.7–6.6; P < 0.001]. A parallel increase in complications was also registered (RR = 1.8, 95% CI 1.1–2.8; P = 0.009). Conclusion Admissions for AMI were significantly reduced during the COVID-19 pandemic across Italy, with a parallel increase in fatality and complication rates. This constitutes a serious social issue, demanding attention by the scientific and healthcare communities and public regulatory agencies.

BACKGROUNDConflicting evidence exists on the efficacy and safety of bivalirudin administered as part of percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome. METHODSWe randomly assigned 7213 patients with an acute coronary syndrome for whom PCI was anticipated to receive either bivalirudin or unfractionated heparin. Patients in the bivalirudin group were subsequently randomly assigned to receive or not to receive a post-PCI bivalirudin infusion. Primary outcomes for the comparison between bivalirudin and heparin were the occurrence of major adverse cardiovascular events (a composite of death, myocardial infarction, or stroke) and net adverse clinical events (a composite of major bleeding or a major adverse cardiovascular event). The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events. RESULTSThe rate of major adverse cardiovascular events was not significantly lower with bivalirudin than with heparin (10.3% and 10.9%, respectively; relative risk, 0.94; 95% confidence interval [CI], 0.81 to 1.09; P = 0.44), nor was the rate of net adverse clinical events (11.2% and 12.4%, respectively; relative risk, 0.89; 95% CI, 0.78 to 1.03; P = 0.12). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (11.0% and 11.9%, respectively; relative risk, 0.91; 95% CI, 0.74 to 1.11; P = 0.34). CONCLUSIONSIn patients with an acute coronary syndrome, the rates of major adverse cardiovascular events and net adverse clinical events were not significantly lower with bivalirudin than with unfractionated heparin. The rate of the composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion. (Funded by the Medicines Company and Terumo Medical; MATRIX ClinicalTrials.gov number, NCT01433627.)

Background-Serum C-reactive protein (CRP) levels are good predictors of the development of cardiovascular events in apparently healthy men and women. CRP has been believed to be produced exclusively by hepatocytes during the acute-phase response. Several lines of evidence have suggested that atherosclerotic arteries can also produce CRP. However, the cell types that produce CRP locally in the atherosclerotic arterial wall have not been clearly identified. Methods and Results-Human coronary artery smooth muscle cells (HCASMCs) and human umbilical vein endothelial cells (HUVECs) were incubated with interleukin-1␤ (IL-1␤), IL-6, their combination, tumor necrosis factor-␣ (TNF-␣), or lipopolysaccharide (LPS) at different concentrations. The supernatants were concentrated and analyzed by a high-sensitivity enzyme-linked immunosorbent assay specific for human CRP. RNA was extracted from the HCASMCs for reverse transcriptase-polymerase chain reaction (RT-PCR) using specific primers for the CRP. Maximal CRP production was observed in HCASMCs after 48 hours of incubation with the combination of 25 ng/mL of IL-1␤ and 10 ng/mL of IL-6, whereas incubation with IL-1␤ or IL-6 alone only modestly induced CRP. Incubation with TNF-␣ (50 ng/mL) or LPS (1000 EU/mL) resulted in an increase in CRP production comparable to the IL-1␤ and IL-6 combination. [1][2][3][4] and could directly participate in the pathogenesis of atherosclerosis through activation of endothelial cells. 5-9 CRP, named for its capacity to bind to the C-polysaccharide of Streptococcus pneumoniae, was the first acute-phase protein to be described. 10 CRP, like other acute-phase proteins, is synthesized by the liver in response to microbial infection, tissue injury, and autoimmune disorders. It had been shown that interleukin-1␤ (IL-1␤) and IL-6 strongly induced the expression of CRP in human hepatocytes 11 and hepatoma cells. 12 Recently, human neuronal cells were found to produce CRP in Alzheimer's disease. 13 In addition, renal cortical tubular epithelial cells were shown to produce CRP after inflammatory stimuli. 14 Interestingly, CRP has also been found in human atherosclerotic plaques, 15 which could be the result of indirect deposit from circulating cells or direct production by cells in the arterial wall. We show that human coronary artery smooth muscle cells (HCASMCs), but not human umbilical vein endothelial cells (HUVECs), can synthesize CRP after stimulation by inflammatory cytokines. Methods Cell CultureHCASMCs, HUVECs, and endothelial cell supplements were purchased from Cascade Biologics; penicillin, streptomycin, medium 231, medium 199, and smooth muscle cell growth supplement were from Gibco BRL; and fetal bovine serum, human serum, heparin, and gelatin were obtained from Sigma. HCASMCs were plated onto 0.1% gelatin-coated culture dishes from Corning, Inc, and grown in 231 medium with growth supplement and 1% penicillin/streptomycin; HUVECs were plated onto 0.1% gelatin-coated culture dishes and grown in 199 medium with endothelial growth suppleme...

Atherosclerosis represents the most common pathological substrate of coronary heart disease (CHD), and the characterization of the disease as a chronic low-grade inflammatory condition is now largely accepted. A number of mediators of inflammation have been widely studied, both as surrogate biomarkers and as causal agents, in the pathophysiological network of atherogenesis and plaque vulnerability. The epidemiological observation that biomarkers of inflammation are associated with clinical cardiovascular risk supports the theory that targeted anti-inflammatory treatment appears to be a promising strategy in reducing residual cardiovascular risk on the background of traditional medical therapy. A large number of randomized controlled trials have shown that drugs commonly used in cardiovascular disease (CVD), such as statins, may be effective in the primary and secondary prevention of cardiovascular events through an anti-inflammatory effect. Moreover, several anti-inflammatory drugs are being tested for their potential to reduce residual cardiovascular risk on the background of validated medical therapy for atherosclerotic disease. In this paper, we review relevant evidence with regard to the relationship between inflammation and CVD, from pathogenesis to therapeutic strategies.

Background-Accurate echocardiographic parameters to predict maintenance of sinus rhythm in patients with atrial fibrillation (AF) are poorly defined. This study was conducted to assess the atrial myocardial properties during AF through myocardial velocity, strain rate, and strain and to compare their prognostic value in maintaining sinus rhythm in patients with lone AF with standard transthoracic (TTE) and transesophageal echocardiography (TEE). Methods and Results-Sixty-five consecutive patients with lone AF for Յ3 months underwent TTE, TEE, and myocardial velocity and strain and strain rate imaging examinations before successful external cardioversion. Maintenance of sinus rhythm was assessed during a 9-month follow-up. Atrial myocardial velocity, strain, and strain rate values in AF patients were compared with those of age-and sex-matched referents. Moreover, clinical and echocardiographic parameters of patients with maintenance of sinus rhythm (MSR patients) over the 9-month follow-up period (nϭ25) were compared with those from patients with AF recurrence (AFR patients; nϭ40). Atrial myocardial properties assessed by myocardial velocity, strain rate, and strain were significantly reduced (PϽ0.0001) in patients (velocity, 3.2Ϯ1.4 cm/s; strain, 23.3Ϯ19%; strain rate, 2Ϯ0.9 seconds Ϫ1 ) compared with referents (velocity, 5.7Ϯ1.3 cm/s; strain, 92Ϯ26%; strain rate, 4.2Ϯ1.8 seconds

Background-Resistin, a novel adipokine, is elevated in patients with type 2 diabetes and may play a role in the vascular complications of this disorder. One recent study has shown that resistin has a proinflammatory effect on endothelial cells. However, there is no information on whether resistin could also affect vascular smooth muscle cells (SMCs). Thus, the purpose of this study was to assess whether resistin could induce SMC proliferation and to study the mechanisms whereby resistin signals in SMCs. Methods and Results-Human aortic smooth muscle cells (HASMCs) were stimulated with increasing concentrations of resistin for 48 hours. Cell proliferation was induced by resistin in a dose-dependent manner as assessed by direct cell counting. To gain more insights into the mechanism of action of resistin, we investigated the extracellular signal-regulated kinase (ERK) and/or phosphatidylinositol 3-kinase (PI3K) signaling pathways. Transient phosphorylation of the p42/44 mitogen-activated protein kinase (ERK 1/2) occurred after addition of resistin to HASMCs. U0126, a specific inhibitor of ERK phosphorylation, significantly inhibited ERK 1/2 phosphorylation and reduced resistinsimulated proliferation of HASMCs. LY294002, a specific PI3K inhibitor, also significantly inhibited HASMC proliferation after resistin stimulation. Conclusions-Our results demonstrate that resistin induces HASMC proliferation through both ERK 1/2 and Akt signaling pathways. The proliferative action exerted by resistin on HASMCs may account in part for the increased incidence of restenosis in diabetes patients.

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