Bmc Med
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It is now understood that it is the quality rather than the absolute amount of adipose tissue that confers risk for obesity-associated disease. Adipose-derived stem cells give rise to adipocytes during the developmental establishment of adipose depots. In adult depots, a reservoir of progenitors serves to replace adipocytes that have reached their lifespan and for recruitment to increase lipid buffering capacity under conditions of positive energy balance. MAIN: The adipose tissue expandability hypothesis posits that a failure in de novo differentiation of adipocytes limits lipid storage capacity and leads to spillover of lipids into the circulation, precipitating the onset of obesity-associated disease. Since adipose progenitors are specified to their fate during late fetal life, perturbations in the intrauterine environment may influence the rapid expansion of adipose depots that occurs in childhood or progenitor function in established adult depots. Neonates born to mothers with obesity or diabetes during pregnancy tend to have excessive adiposity at birth and are at increased risk for childhood adiposity and cardiometabolic disease. ⋯ In this narrative review, we synthesize current knowledge in the fields of obesity and developmental biology together with literature from the field of the developmental origins of health and disease (DOHaD) to put forth the hypothesis that the intrauterine milieu of pregnancies complicated by maternal metabolic disease disturbs adipogenesis in the fetus, thereby accelerating the trajectory of adipose expansion in early postnatal life and predisposing to impaired adipose plasticity.
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Atrial fibrillation (AF) and heart failure (HF) are frequently associated and can be caused or exacerbated by each other through different mechanisms. AF is particularly common in patients with heart failure with preserved ejection fraction (HFpEF) defined as left ventricular ejection fraction (LVEF) ≥ 50%, with a prevalence ranging around 40-60%. In two recent trials, treatment with SGLT2 inhibitors resulted in a lower risk of worsening heart failure or cardiovascular death than placebo in patients with HFpEF, and SGLT2 inhibitors similarly improved prognosis whether patients had AF or not at enrolment. ⋯ In patients with AF and HF included in the CABANA trial, catheter ablation produced marked improvements in survival, freedom from AF recurrence, and quality of life compared to drug therapy. When strategies aiming at rhythm control eventually fail in patients with AF and HFpEF, a strategy of rate control with atrioventricular junction ablation and cardiac resynchronisation should be discussed since it may also reduce all-cause mortality. Finally, and in conclusion, considering that patients with AF and HFpEF may have a variety of cardiovascular and non-cardiovascular additional comorbidities, they are among those likely to have the highest clinical benefit being adherent to a holistic and integrated care management of AF following the ABC (Atrial Fibrillation Better Care) pathway.