A Western diet combined with DOCA for 20 weeks in minipigs successfully induced a translational model of HFpEF characterized by paroxysmal AF, concentric LV hypertrophy, and multi-organ fibrosis.
A novel porcine model using a Western diet and DOCA successfully recapitulates the clinical and pathophysiological features of HFpEF and associated atrial fibrillation.
Abstract Background Heart failure with preserved ejection fraction (HFpEF) accounts for nearly 50% of all heart failure cases. It is a multi-organ syndrome driven by a chronic inflammatory state resulting from metabolic disorders. Its prevalence continues to rise with an aging population and the surge in comorbidities such as obesity, arterial hypertension and type 2 diabetes mellitus. Patients with HFpEF typically present an exercise intolerance owing to an adverse cardiac remodeling that increases diastolic stiffness and left ventricular filling pressures. In addition, atrial fibrillation (AF) is common and can further exacerbate symptoms by reducing atrial contribution to ventricular filling, worsening hemodynamics, and increasing the risk of hospitalization and morbidity. The pathophysiological mechanisms underlying HFpEF remains poorly understood, and the factors contributing to the development and progression of AF in this setting are likewise incompletely elucidated. Purpose We therefore developed a translational porcine model of HFpEF to identify cellular mechanisms driving atrial remodeling and the development of AF. Methods Eleven-month-old, female Göttingen Minipigs were fed a "Western diet" (high in fat, cholesterol, fructose and salt) for 20 weeks, while sustained-release deoxycorticosterone acetate (DOCA) induced a primary aldosteronism. Animals were compared to a control group receiving a standard diet. Implantable loop recorders allowed for continuous ECG monitoring in freely moving minipigs. Transthoracic echocardiography and cardiac MRI were performed to assess cardiac structure and function. Left ventricular filling pressures were measured invasively. Organs were collected for histopathological assessment. Results HFpEF minipigs developed paroxysmal AF on ECG. Cardiac imaging studies showed concentric LV hypertrophy with normal ejection fraction. Left atria were dilated and left ventricular filling pressures increased. Masson's trichrome staining revealed an extensive fibrofatty infiltration of the atria. Fibrosis was detected in the ventricles and in multiple organs, including the lungs, liver and kidneys. Conclusions We have developed a porcine model of HFpEF that recapitulates the complexity of the clinical syndrome. This animal model will allow to identify key mechanisms and novel therapeutic strategies for the treatment of HFpEF and associated AF.
Edaes et al. (Fri,) conducted a other in Heart failure with preserved ejection fraction (HFpEF). Western diet and sustained-release deoxycorticosterone acetate (DOCA) vs. Standard diet was evaluated on Development of HFpEF, atrial remodeling, and atrial fibrillation. A Western diet combined with DOCA for 20 weeks in minipigs successfully induced a translational model of HFpEF characterized by paroxysmal AF, concentric LV hypertrophy, and multi-organ fibrosis.