Modifying the structural substrate and progression of heart failure with preserved ejection fraction using a regular...

Area of Science:

• Cardiovascular Physiology
• Exercise Science
• Heart Failure Research

Background:

• Heart failure with preserved ejection fraction (HFpEF) is linked to persistent left ventricular pressure overload (LVPO).
• This overload increases myocardial stiffness and collagen content (fibrosis), impairing LV filling and elevating pressures.
• The impact of exercise combined with LVPO on HFpEF progression is not well understood.

Purpose of the Study:

• To investigate whether an exercise program can prevent the development of HFpEF in the presence of progressive LVPO.
• To determine the structural and molecular mechanisms underlying any observed effects of exercise on LV remodeling.

Main Methods:

• Pigs underwent progressive LVPO for 5 weeks, with one group receiving daily exercise and another serving as a control.
• Left ventricular (LV) mass, myocardial stiffness (Km), pulmonary capillary wedge pressure (PCWP), and left atrial area (LAA) were assessed.
• LV collagen content and collagen type 1a mRNA expression were analyzed.

Main Results:

• LV mass increased similarly in both LVPO groups, but the exercise group showed reduced Km, PCWP, and LAA compared to LVPO alone.
• LV collagen percentage area was significantly lower in the LVPO exercise group.
• Collagen type 1a mRNA expression returned to normal levels in the LVPO exercise group.

Conclusions:

• Concomitant exercise prevented the HFpEF phenotype despite LV hypertrophy, indicating exercise's protective role.
• Reduced collagen content and expression appear to be the structural and molecular basis for this prevention.
• Regular exercise may serve as a preventive strategy for individuals at risk of developing HFpEF.