Abstract 3815: Changes in the Regulation of the Extracellular Matrix Correlate with the Degree of LV Stiffness in Patients with Diastolic Heart Failure
Introduction: Isolated diastolic dysfunction is characterized by a disturbed compliance of the left ventricle (LV). The mechanisms leading to this diastolic dysfunction may include behind changes in the myocyte also in the regulation of the cardiac extracellular matrix. We further investigated LV cardiac stiffness and changes in the cardiac extracellular matrix regulation in patients with heart failure despite normal ejection fraction (HFnlEF).
Methods: 42 patients with exercise intolerance despite normal EF (>50%) were included in this study and compared with 10 control patients. In all patients pressure-volume loops were measured by conductance technique (CDLeicom, Netherlands). As marker for diastolic function the diastolic stiffness constant was analyzed. All patients underwent cardiac biopsies for immunochemestrical analyzation of cardiac fibrosis (Sirius red), MMP2/TIMP1 ratio, MMP9/TIMP1 ratio, TGF-β type 1.
Results: Patients with HFnlEF had increased stiffness (0.0275+0.0036 vs. 0.0107+0.002, p<0.05) showed increased fibrosis (0.029±0.004 vs. 0.012±0.008, %, p<0.05), MMP2/ TIMP1 ratio (97,4±6 vs. 43.2±7, p<0.05) and MMP9/TIMP1 ratio (168.4±16 vs. 123±9, p<0.05), as well as an increase in TGF-β staining (1.25±0.05 vs. 0.03±0.01, area fraction %, p<0.05). Furthermore, increased stiffness correlated with cardiac fibrosis in patients with HFnlEF (R=0.58, p<0.05). In addition MMP2 but not MMP9 corelatetd with LV stiffness and fibrosis (R=0.52, p<0.05).
Conclusion: We demonstrate that HFnlEF is characterized by increased cardiac stiffness measured by conductance technique, which is associated by changes in the extarcellular matrix regulation characterized by an increase in fibrosis most probably due to changes in MMP/TIMP system as well due to changes in profibrotic cytokines like TGF-β.