1519: Using Galacetin-3 (Gal-3) and Cardiotrophin-1 (CT-1) for Early Detection of Primary Heart Involvement in Systemic Sclerosis as Seen on Cardiac MRI

Erin Chew¹, Sarah Wood¹, Bibin Varghese¹, Christopher Chew², erin wilfong¹ and Tracy Frech¹, ¹Vanderbilt University Medical Center, Nashville, TN, ²University of North Carolina at Chapel Hill, Chapel Hill, NC

Background/Purpose: Primary heart involvement in systemic sclerosis (SSc-pHI) is characterized by myocardial inflammation with resultant fibrosis that is not secondary to ischemic heart disease or pulmonary hypertension. SSc-pHI clinically manifests with arrhythmia and/or heart failure and is a significant contributor to mortality in SSc patients. Cardiac magnetic resonance imaging (cMRI) is the gold standard for comprehensive cardiac evaluation and can detect subclinical fibrosis with greater sensitivity than the routine practice of serial echocardiogram (TTE). Serum biomarkers (hs-TnT and NT-proBNP) are known to be elevated in SSc with cardiac involvement but are not specific for myocardial fibrosis. Thus, there is a need for specific biomarkers that define primary cardiac involvement. Serum cardiotrophin-1 (CT-1) is a member of the IL-6 cytokine family and induces myocyte hypertrophy and collagen synthesis. Galacetin-3 (Gal-3) has previously been shown to play a role in myocardial fibrosis and remodeling. CT-1 and Gal-3 are thought to mediate the proinflammatory and profibrotic myocardial effects in SSc-pHI and may serve as biomarkers for the early detection of SSc-pHI. We hypothesize CT-1 and Gal-3 levels correlate to SSc-pHI detected by cMRI.

Methods: SSc patients enrolled in the longitudinal Vanderbilt University Medical Center Myositis and Scleroderma Treatment Initiative Center (VUMC IRB 141415) who had a cMRI, TTE, and banked plasma were included in this analysis. Demographic and clinical information were reviewed. Serum levels of Ga1-3, CT-1, NT-proBNP, and hs-TnT were measured. Abnormal cutoffs for Gal-3 and CT-1 levels were determined based on prior prognostic studies in patients with heart failure.

Results: Of the 100 SSc patients in MYSTIC, 7 patients met inclusion criteria. All patients were white, 5 were female, median age of 67 (range 60-71 years). Average disease duration was 17.5 years (1-42 years) from first non-Raynaud's symptom onset. Serum biomarkers, cMRI, and TTE findings are shown in Table 1. No SSc patient had normal cardiac parameters in all categories. Six patients had elevated NT-proBNP and 4 patients had elevated hs-TNT. Of the 5 patients who had an abnormal cMRI, only one had an abnormal TTE. Only 3 cMRI were performed with parametric mapping which allows for improved tissue characterization and quantitative evaluation of myocardial inflammation and fibrosis. CT-1 was normal in 2 patients who had abnormal cMRI. Gal-3 was abnormal in all SSc patients. The 2 patients with normal myocardium on cMRI had the lowest Gal-3 levels with one patient on myocophenolate mofetil and the other on prednisone.

Conclusion: NT-proBNP, hs-TNT and routine TTEs are not sufficient for the detection of the myocardial fibrosis in SSc-pHI. Specific cardiac biomarkers that correspond to fibrotic change on cMRI are necessary for early detection of SSc-pHI and to guide immunosuppressive treatment. In our study, Gal-3 was abnormal in all patients and those with lowest Gal-3 levels had normal myocardium on cMRI. Given the correlation, future studies validating the relationship between Gal-3 levels and myocardial fibrosis on cMRI are needed.

Disclosures: E. Chew, None; S. Wood, None; B. Varghese, None; C. Chew, None; e. wilfong, Boehringer-Ingelheim, Boehringer-Ingelheim, Health and Human Services; T. Frech, None.