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Follistatin-Like 1 in Chronic Systolic Heart Failure: A Marker of Left Ventricular Remodeling
Study Questions:
Are levels of serum and myocardial follistatin-like I (FSTL1), an extracellular glycoprotein that regulates the transforming growth factor-beta superfamily proteins, associated with chronic heart failure (HF)?
Methods:
This was a two part study. First, a prospective study of 86 outpatients with chronic systolic HF (left ventricular ejection fraction [LVEF] <40%) and 21 healthy age- and sex-matched controls was conducted to compare serum FSTL1 levels obtained through western blotting. In addition, FSTL1 levels were examined in relation to echocardiographic measurements, serum B-type natriuretic peptide (BNP) levels, and death. From a separate pool of heart donors, tissue western blot analysis of myocardial FTSL1 levels was then compared amongst failing ventricles (n = 9 nonischemic and n = 9 ischemic) and nonfailing ventricles (n = 7).
Results:
In the HF cohort, the mean ± standard deviation age and LVEF was 60 ± 13 years and 21 ± 9%, respectively; 36% had an ischemic etiology for HF; 80% had a history of hypertension; and 75% were New York Heart Association class II or III. Compared with controls, mean FSTL1 levels were higher in HF patients (19.8 ± 7.2) than controls (12.5 ± 5, Student’s t p < 0.01). In patients with chronic HF, higher FSTL1 levels were associated with higher BNP levels, larger LV end-diastolic and end-systolic dimensions, and greater LV mass. For each unit increase in FSTL1, the LV mass index (95% confidence interval) increased by 6.7 (95% confidence interval, 4.8-8.5) g/m2. Of the 86 patients, 51% died. Each unit increase in FSTL1 was associated with an adjusted hazard ratio of 2.8 (95% confidence interval, 2.0-7.7) increased risk of death. In the post-mortem study, tissue FSTL1 levels were higher in failing hearts (dilated cardiomyopathy = 2.4 ± 0.5; ischemic cardiomyopathy = 2.7 ± 0.5) than nonfailing hearts (1.0 ± 0.2, ANOVA p < 0.05).
Conclusions:
The authors concluded that elevated FTSL1 is associated with LV hypertrophy in HF, and confers an increased risk of death.
Perspective:
This is a novel study demonstrating the presence of elevated serum and myocardial FSTL1 levels in patients with chronic HF compared with that of healthy controls. Further, serum FSTL1 levels appear to correlate with the severity of LV hypertrophy, and are associated with worse survival in HF. What remains to be explained is why FSTL1 is elevated in HF, and if it is a marker or an instigator of disease. The authors mention the fact that FSTL1 has anti-inflammatory properties in humans and it reduces matrix metalloproteinase 1 and 3 expression in vitro, hypothesizing that FSTL1 levels reflect a response to a high inflammatory state. Whether this test will provide use in the diagnosis or management of HF (above what is already available) remains to be examined.
Keywords: Biomarkers, Heart Failure, Ventricular Remodeling, Follistatin, New York, Cardiomyopathy, Dilated, Echocardiography
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