Doxorubicin (Dox) is an effective anti-neoplasm drug, but its cardiac toxicity limits its clinical use. Endothelial-to-mesenchymal transition (EndMT) has been found to be involved in the process of heart failure. It is unclear whether EndMT contributes to Dox-induced cardiomyopathy (DoIC). Calcitriol, an active form Vitamin D3, blocks the growth of cancer cells by inhibiting the Smad pathway. To investigate the effect of calcitriol via inhibiting EndMT in DoIC, C57BL/6 mice and endothelial-specific labeled mice were intraperitoneally administered Dox twice weekly for 4 weeks (32 mg/kg cumulative dose) and were subsequently treated with or without calcitriol for 12 weeks. Echocardiography revealed diastolic dysfunction at 13 weeks following the first Dox treatment, accompanied by increased myocardial fibrosis and up-regulated pro-fibrotic proteins. Calcitriol attenuated Dox-induced myocardial fibrosis, down-regulated pro-fibrotic proteins and improved diastolic function. Endothelial fate tracing revealed that EndMT-derived cells contributed to Dox-induced cardiac fibrosis. In vitro, human umbilical vein endothelial cells and mouse cardiac fibroblasts were treated with Transforming growth factor (TGF)-β with or without calcitriol. Morphological, immunofluorescence staining, and Western blot analyses revealed that TGF-β-induced EndMT and fibroblast-to-myofibroblast transition (FMT) were attenuated by calcitriol by the inhibition of the Smad2 pathway. Collectively, calcitriol attenuated DoIC through the inhibition of the EndMT and FMT processes.

Infective endocarditis (IE) is a severe disease with a hospital mortality rate of 17%–25%. Early identification of IE patients with high risk of mortality may improve their clinical outcomes. Patients with diabetes mellitus (DM) who develop infective diseases are associated with worse outcomes. This study aimed to define the impact of DM on long-term mortality in IE patients. A total of 412 patients with definite IE from February 1999 to June 2012 were enrolled in this observational study and divided into 2 groups: group 1, patients with DM (n = 72) and group 2, patients without DM (n = 340). The overall in-hospital mortality rate for both groups combined was 20.2% and was higher in group 1 than in group 2 (41.7% vs. 16.5%, p < 0.01). Compared to patients without DM, patients with DM were older and associated with higher incidence of chronic diseases, less drug abuse, higher creatinine levels, and increased risk of Staphylococcus aureus infection (all p < 0.05). Moreover, they were more likely to have atypical clinical presentation and were associated with longer IE diagnosis time (all p < 0.05). In multivariable analysis, DM is an independent and significant predictor of mortality. The prognosis of IE patients with DM is still poor. Early identification and more aggressive treatment may be considered in IE patients with DM.

SummaryThis study evaluated the association between atrial fibrillation (AF) and 30-day clinical outcome in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Between January 2005 and October 2009, 783 consecutive patients with acute STEMI undergoing primary PCI were enrolled. Of these patients, 85 (10.9%) with AF during admission were categorized into group 1, while the remaining 698 (89.1%) with sinus rhythm during admission served as group 2. The results demonstrated that the incidence of advanced Killip score (defined as ≥ score 3) and advanced congestive heart failure (defined as ≥ NYHA class 3) were significantly higher, whereas the left ventricular ejection fraction (LVEF) was notably lower in group 1 than in group 2 (all P < 0.003). Additionally, the normal blood flow in the infarct-related artery was notably lower in group 1 than in group 2 (P = 0.003). Moreover, the incidences of new-onset stroke and 30-day mortality were remarkably higher in group 1 than in group 2 (all P < 0.003). Furthermore, Kaplan-Meier analysis demonstrated that the 30-day survival rate was markedly lower in AF patients than in those with sinus rhythm. However, multivariate stepwise Cox regression analysis demonstrated that the advanced Killip score and low LVEF were significantly and independently predictive of 30-day mortality (all P < 0.004). In conclusion, AF was significantly associated with 30-day mortality. (Int Heart J 2011; 52: 153-158)