The pathophysiological mechanisms underlying preserved left ventricular (LV) ejection fraction (EF) in patients with heart failure and preserved ejection fraction (HFpEF) remain incompletely understood. We hypothesized that transmural variations in myofiber contractility with existence of subendocardial dysfunction and compensatory increased subepicardial contractility may underlie preservation of LVEF in patients with HFpEF. We quantified alterations in myocardial function in a mathematical model of the human LV that is based on the finite element method. The fiber-reinforced material formulation of the myocardium included passive and active properties. The passive material properties were determined such that the diastolic pressure-volume behavior of the LV was similar to that shown in published clinical studies of pressure-volume curves. To examine changes in active properties, we considered six scenarios: (1) normal properties throughout the LV wall; (2) decreased myocardial contractility in the subendocardium; (3) increased myocardial contractility in the subepicardium; (4) myocardial contractility decreased equally in all layers, (5) myocardial contractility decreased in the midmyocardium and subepicardium, (6) myocardial contractility decreased in the subepicardium. Our results indicate that decreased subendocardial contractility reduced LVEF from 53.2 to 40.5%. Increased contractility in the subepicardium recovered LVEF from 40.5 to 53.2%. Decreased contractility transmurally reduced LVEF and could not be recovered if subepicardial and midmyocardial contractility remained depressed. The computational results simulating the effects of transmural alterations in the ventricular tissue replicate the phenotypic patterns of LV dysfunction observed in clinical practice. In particular, data for LVEF, strain and displacement are consistent with previous clinical observations in patients with HFpEF, and substantiate the hypothesis that increased subepicardial contractility may compensate for subendocardial dysfunction and play a vital role in maintaining LVEF.
Background:
Progressive thinning and dilation of the LV due to ischemic heart failure (IHF) increases wall stress and myocardial oxygen consumption. Injectable biopolymers implanted in the myocardial wall have been used to increase wall thickness to reduce chamber volume, decrease wall stress, and improve cardiac function. We sought to evaluate the efficacy of a biopolymer (Algisyl-LVR) to prevent left ventricular (LV) remodeling in a swine model of IHF.
Methods:
IHF was induced in 11 swine by occluding the marginal obtuse branches of the left circumflex artery. Eight weeks later, Algisyl-LVR was injected into the LV myocardial free wall in five of the 11 animals. Echocardiographic examinations were done every 2 weeks for 16 weeks.
Results:
Within eight weeks of treatment, the ejection fraction increased from 30.5% ± 7.7% to 42.4% ± 3.5% (treated group) vs. 37.3% ± 3.8% to 34.3% ± 2.9% (control), p < 0.01. Stroke volume increased from 18.5 ± 9.3 mL to 41.3 ± 13.3 mL (treated group) vs. 25.4 ± 2.3 mL to 31.4 ± 5.3 mL (control), p < 0.05. Wall thickness in end-diastole of the infarcted region changed from 0.69 ± 0.06 cm to 0.81 ± 0.13 cm (treated group) vs. 0.73 ± 0.09 cm to 0.68 ± 0.11 cm (control), p < 0.05. Sphericity index remained almost unchanged after treatment, although differences were found at the end of the study between both groups (p < 0.001). Average myofiber stress changed from 16.3 ± 5.8 kPa to 10.2 ± 4.0 kPa (treated group) vs. 15.2 ± 4.8 kPa to 17.9 ± 5.6 kPa (control), p < 0.05.
Conclusions:
Algisyl-LVR is an effective strategy that serves as a micro-LV assist device to reduce stress and hence prevent or reverse maladaptive cardiac remodeling caused by IHF in swine.
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