Digoxin was associated with a significant increase in all-cause mortality in patients with AF after correcting for clinical characteristics and comorbidities, regardless of gender or of the presence or absence of HF. These findings call into question the widespread use of digoxin in patients with AF.

Atheroma formation and restenosis following percutaneous vascular intervention involve the growth and migration of vascular smooth muscle cells (SMCs) into neointimal lesions, in part due to changes in the extracellular matrix. While some clinical studies have suggested that, in comparison to nondiabetics, β3 integrin inhibition in diabetic patients confers protection from restenosis, little is known regarding the role of β3 integrin inhibition on SMC responses in this context. To understand the molecular mechanisms underlying integrin-mediated regulation of SMC function in diabetes, we examined SMC responses in diabetic mice deficient in integrin β3 and observed that the integrin was required for enhanced proliferation, migration and extracellular regulated kinase (ERK) activation. Hyperglycemia enhanced membrane recruitment and catalytic activity of PKCβ in an integrin β3-dependent manner. Hyperglycemia also promoted SMC filopodia formation and cell migration, both of which required αVβ3, PKCβ, and ERK activity. Furthermore, the integrin-kinase association was regulated by the αVβ3 integrin ligand thrombospondin and the integrin modulator Rap1 under conditions of hyperglycemia. These results suggest that there are differences in SMC responses to vascular injury depending on the presence or absence of hyperglycemia and that SMC response under hyperglycemic conditions is largely mediated through β3 integrin signaling

Among patients with AF, QRSd ≥ 120 ms was associated with a substantially increased risk for mortality (all-cause, cardiovascular, and arrhythmic) and hospitalization. Interestingly, an increased mortality was also observed among those with QRS 90-119 ms and concomitant HF.

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Background: Coronary artery calcification (CAC) is common in patients with chronic kidney disease on hemodialysis (CKD-5D) and is an important predictor of mortality. However, cardiac functional links between CAC and mortality have not been well established. This study tested the hypothesis that CAC increases mortality by adversely affecting cardiac function. Methods: Patients were recruited from 37 regional dialysis centers. 2-D and Doppler echocardiographic analyses were performed, and CAC was measured using 64-slice computed tomography. Relationships between CAC and echocardiographic measures of left ventricular (LV) function were analyzed. Survival was assessed with median follow-up of 37 months. Results: There were 157 patients: 59% male, 46% Caucasian, 48% diabetic. Median age was 55 years, and median duration of CKD-5D was 45 months. Agatston CAC scores > 100 were found in 69% of patients, with 51% having a score > 400. CAC was associated with measures of LV systolic and diastolic function (global longitudinal strain (GLS; rho = 0.270, p = 0.004)), peak LV systolic velocity (rho = –0.259, p = 0.004), and estimate of LV filling pressure (E:E’; rho = 0.286, p = 0.001). Multivariate regression confirmed these relationships after adjustment for age, gender, LV ejection fraction, and coronary artery disease. Valvular calcification varied linearly with CAC (p < 0.05). Both LV diastolic and systolic functional measures were significant predictors of mortality, the strongest of which was LV diastolic dysfunction. Conclusions: These findings show a link between CAC, cardiac function, and mortality in CKD-5D. LV diastolic function (E:E’), peak LV systolic velocity, and GLS are independent predictors of mortality. Valvular calcification may be an important marker of CAC in CKD-5D. These effects on cardiac function likely explain the high mortality with CKD-5D and describe a potentially-valuable role for echocardiography in the routine management of these patients.