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The majority of patients with heart failure with preserved ejection fraction (HFpEF) develop secondary pulmonary hypertension (PH) and subsequent right ventricular (RV) failure. The underlying mechanisms are not well understood, but involve passive congestion, active vascular remodeling with impaired pulmonary gas exchange and systemic activation of the immune system. Here, we propose a mechanistic interdependence of these processes, in that active recruitment of immune cells into the lung´s perivascular space drives lung vascular remodeling thus impairing pulmonary gas exchange. The ensuing systemic hypoxemia will in turn promote systemic inflammation and accelerate the decline in left ventricular (LV) and right ventricular (RV) function.
Graphical Abstract: Previously, HFpEF has been linked to comorbidities via systemic inflammation, and to RV failure via congestion (thin black arrows). Here, we propose a novel concept of cardio-pulmonary interaction in HFpEF that is driven by a triangular maladaptive feed-forward loop mutually promoting inflammation, lung vascular remodeling, and hypoxemia in a reciprocal manner (thick arrows) with each component negatively impacting on ventricular function (thin arrows pointing towards LV and RV, respectively).
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