Abstract
Myocardial fibrosis leads to a restrictive diastolic filling pattern of the left ventricle which is associated with a poor prognosis in patients with heart failure. We investigated the relationship between cardiac fibrosis and restrictive filling pattern of the left ventricle measured by Tc99m left ventriculography in patients with chronic symptomatic heart failure. Serum cardiac extracellular matrix markers including type I and III aminoterminal propeptide of procollagen (PINP and PIIINP), matrix metalloproteinase-2,9 (MMP-2,9), and tissue inhibitor of MMP-1 (TIMP-1) were analyzed. Fifty-one (39 males) patients were enrolled. Their median age was 51.8 years, and median left ventricular ejection fraction was 31.9%. Time to peak filling rate of the left ventricle was significantly correlated with serum levels of the three cardiac extracellular matrix markers (TIMP-1, PIIINP, and MMP-2). The patients with a restrictive diastolic filling pattern of the left ventricle (time to peak filling rate = 154 ms) had significantly higher levels of these extracellular matrix markers. In receiver operating characteristic curve analysis, areas under the curve of PIIINP, TIMP-1, and MMP-2 were 0.758, 0.695, and 0.751 to predict the presence of a restrictive pattern. In C-statistics, all three cardiac extracellular matrix markers significantly increased the area under the curve after adding creatinine. In net reclassification improvement and integrated discrimination improvement models, PIIINP and MMP-2 significantly improved the predictive power of age, creatinine and brain natriuretic peptide. In conclusion, serum extracellular matrix markers are significantly correlated with restrictive diastolic filling pattern of the left ventricle in patients with heart failure.
Highlights
Heart failure (HF) is a major health problem affecting more than 23 million patients worldwide [1]
We divided the patients into two groups based on the presence of a restrictive pattern in technetium 99m (Tc99m) radionuclide ventriculography
The patients with a restrictive LV pattern in Tc99m radionuclide ventriculography had significantly higher levels of serum fibrosis markers including tissue inhibitor of matrix metalloproteinases (MMPs)-1 (TIMP-1) (p = 0.019), PIIINP (p = 0.002), and MMP-2 (p = 0.002) (Table 2)
Summary
Heart failure (HF) is a major health problem affecting more than 23 million patients worldwide [1]. Systolic function has been reported to be a prognostic predictor in HF with reduced ejection fraction (HFrEF) [3]. Compared to the New York Heart Association functional classification, left ventricular ejection fraction (LVEF) has been reported to be a less reliable marker, especially in patients with atrial fibrillation [4, 5]. Many tools can estimate diastolic function, including echocardiography, cardiac magnetic resonance imaging (MRI), electrocardiography-gated myocardial perfusion single photon emission computed tomography (SPECT), and technetium 99m (Tc99m) left ventriculography. Tc99m left ventriculography has recently been reported to be a useful method to assess LV diastolic dysfunction due to more stable parameters and because it is independent of the influence of systolic function, age and sex [7]. Data on LV diastolic function in patients with HF are limited
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