Background: Heart failure with recovered ejection fraction (HFrecEF) has been proposed as a new subset of HF, clinically distinct from HF with persistently reduced EF (HFrEF). However, what factors will determine the recovery of EF in non-ischemic dilated cardiomyopathy (NICM) has not been clarified. We focused on myocardial expression of tenascin-C (TNC), extracellular matrix protein which regulates tissue remodeling.
Methods: A total of 139 patients (51+14 years, 28 female), who had successfully undergone follow-up echocardiography around 1 year after diagnosis of NICM, were investigated. Cardiac catheterization including endomyocardial biopsy was performed in all patients at diagnosis. Inclusion criteria for LV dilatation and reduced contraction were LV diastolic diameter >117% of the predicted value and LVEF ≤45%, respectively. Patients were classified into 2 groups: continued HFrEF with follow-up LVEF of ≤45% and HFrecEF who had LVEF improved to >45%. Patients’ clinical data were obtained from their medical records. We performed immunohistochemical staining using specific antibody to TNC on RV endomyocardial biopsy specimens and TNC-positive area was semi-quantitatively measured by densitometric method.
Results: Fifty patients (36%) exhibited HFrecEF aspect with LVEF improved from 30±10% to 53±6%. According to the survival analysis with the mean follow-up period of 5.0±2.3 years, continued HFrEF group showed worse outcome for all-cause death, cardiac transplantation, or LVAD implantation compared to HFrecEF group (p=0.006). HFrecEF was associated with higher prevalence of hypertension history (54% vs. 28%, p=0.003), lower baseline LV diastolic diameter (65±8 vs. 68±10 mm, p=0.026), and higher baseline LVEF (30±10% vs. 25±9%, p=0.003). TNC area was significantly lower in HFrecEF group than continued HFrEF group (0.8±0.8% vs. 1.7±2.1%, p=0.007). Multivariate logistic regression analysis identified lower TNC area (p=0.012, OR 0.68 per 1%) as an independent correlate of HFrecEF.
Conclusions: HFrecEF patients showed a more favorable outcome with lower myocardial TNC expression. Myocardial deposition of TNC might have some inhibitory role against recovery of contractile function in patients with NICM.