Diastolic dysfunction persists 3 months after surgical revascularization in a large animal model of hibernating myocardium

OBJECTIVE Diastolic heart failure with preserved ejection fraction (HFpEF) secondary to coronary artery disease is associated with a significant morbidity and mortality. Diastolic dysfunction due to chronic myocardial ischemia is an important clinical entity though recovery of diastolic relaxation with revascularization is poorly understood. A swine model of hibernating myocardium (HM) was used to assess systolic and diastolic myocardial recovery following coronary artery bypass grafting (CABG). METHODS Study animals included 18 juvenile pigs who underwent placement of a constrictor around the left anterior descending artery (LAD) to gradually create chronic ischemia without infarction. Study groups included 5 healthy age and weight-matched controls, 6 HM animals without revascularization, 7 HM+CABG+1 month recovery and 5 HM+CABG+3 months recovery. Cardiac MRI was used to assess global systolic and diastolic function at rest and with dobutamine stress. Histopathology assessed tissue structural and molecular changes. RESULTS Systolic and diastolic myocardial function were significantly depressed in HM. Both improved with CABG, however, diastolic relaxation remained significantly impaired even at 3 months post-CABG compared to controls. Histological analysis showed interstitial fibrosis in HM tissue with residual fibrosis seen post-CABG. α-SMA stain identified myofibroblasts in both HM and post-CABG animals. CONCLUSIONS In a large animal model of HM, diastolic dysfunction persists under stress despite CABG and is present even after three months recovery. Persistent fibrosis and diastolic stiffness prevent full recovery. These findings highlight a therapeutic need for pharmacologic or regenerative adjunctive therapies at the time of revascularization.