Variations in subclinical left ventricular dysfunction, functional capacity, and clinical outcomes in different heart failure aetiologies

Aims: Patients with heart failure (HF) risk factors are described as being in Stage A of this condition (SAHF). Management is directed towards prevention of HF progression, but to date, no evidence has been described to align the intensity of this intervention to HF risk. We sought to what extent SAHF of Type 2 diabetes mellitus (T2DM) and other HF risks showed differences in subclinical left ventricular function, exercise capacity, and prognosis.Methods and Results: We recruited 551 elder asymptomatic SAHF patients (age 71 ± 5 years, 49% men, 290 T2DM) with at least one risk factor from a community-based population with preserved ejection fraction. All underwent a comprehensive echocardiogram including global longitudinal strain (GLS) and a 6 min walk test and were followed for 2 years. The primary endpoints were new-onset HF and all-cause mortality. The T2DM group was associated with reduced 6 min walk test distance (451 ± 111 vs. 493 ± 87 m, P P = 0.028), and impaired GLS (-17.7 ± 2.6% vs. -19.0 ± 2.6%, P P = 0.021). In Cox models, obesity [hazard ratio (HR) = 2.46; P = 0.007], atrial fibrillation (HR = 2.39; P = 0.028), 6 min walk distance (HR = 0.99; P = 0.034), and GLS (HR = 1.14; P = 0.033) were independently associated with the primary endpoint in T2DM-SAHF, independent of age and glycaemic control.Conclusions: The T2DM-SAHF has worse subclinical left ventricular function, exercise capacity, and prognosis than other-SAHF. Impaired GLS, atrial fibrillation, exercise capacity, and obesity are associated with a worse prognosis in T2DM-SAHF but not in other-SAHF

The impact of circulating preeclampsia-associated extracellular vesicles on the migratory activity and phenotype of THP-1 monocytic cells

Intercellular communication via extracellular vesicles (EVs) and their target cells, especially immune cells, results in functional and phenotype changes that consequently may play a significant role in various physiological states and the pathogenesis of immune-mediated disorders. Monocytes are the most prominent environment-sensing immune cells in circulation, skilled to shape their microenvironments via cytokine secretion and further differentiation. Both the circulating monocyte subset distribution and the blood plasma EV pattern are characteristic for preeclampsia, a pregnancy induced immune-mediated hypertensive disorder. We hypothesized that preeclampsia-associated EVs (PE-EVs) induced functional and phenotypic alterations of monocytes. First, we proved EV binding and uptake by THP-1 cells. Cellular origin and protein cargo of circulating PE-EVs were characterized by flow cytometry and mass spectrometry. An altered phagocytosis-associated molecular pattern was found on 12.5 K fraction of PE-EVs: an elevated CD47 "don't eat me" signal (p < 0.01) and decreased exofacial phosphatidylserine "eat-me" signal (p < 0.001) were found along with decreased uptake of these PE-EVs (p < 0.05). The 12.5 K fraction of PE-EVs induced significantly lower chemotaxis (p < 0.01) and cell motility but accelerated cell adhesion of THP-1 cells (p < 0.05). The 12.5 K fraction of PE-EVs induced altered monocyte functions suggest that circulating EVs may have a role in the pathogenesis of preeclampsia