Cardiac structural remodeling in hypertensive cardiomyopathy

Heart failure with preserved ejection fraction (HFpEF), which is a primary driver of morbidity and mortality, accounts for approximately half of all heart failure cases. Therefore, it is essential to develop preclinical animal models for HFpEF pharmacological treatment strategies. We created a porcine model of severe hypertension and hyperlipidemia by using a combination of deoxycorticosterone acetate (DOCA, 100 mg kg^-1), Western diet (WD) and angiotensin II infusion. Systolic blood pressure, echocardiography and invasive pressure-volume loop were assessed at baseline, 12 weeks and 18 weeks. A detailed histological assessment was also performed to determine the cardiac structural remodeling. Compared with controls (n=10), hypertensive animals (n=10) showed markedly higher systolic blood pressure (181 vs. 86 mm Hg) at 18 weeks. Concentric remodeling, characterized by a normal chamber size with a thicker wall, was observed in hypertensive animals. Left ventricle diastolic function showed a tendency toward decline, according to the echocardiographic data. Hemodynamic data showed that the end-diastolic pressure-volume relationship was elevated without changes in the end-systolic pressure-volume relationship. Histological results revealed that the fibrotic area in hypertensive animals (P<0.05 vs. controls) and the fibrotic area in the posterior wall of hypertensive animals' left atria were larger than other sites of the left atria (P<0.05 vs. other sites). This model can mimic clinical HFpEF to some degree. We found that the posterior wall of the left atrium is more susceptible to atrial remodeling associated with hypertension compared with other regions of the left atrium.