SCLERAXIS AS A PROGNOSTIC MARKER OF MYOCARDIAL FIBROSIS IN HYPERTROPHIC CARDIOMYOPATHY (SPARC) STUDY
CCC ePoster Library. Zhu A. 10/26/19; 280533; 298
Antonia Zhu
Antonia Zhu
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Abstract
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BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death (SCD) in young adults ≤ 40 years of age. Myocardial fibrosis is a well-known histological marker of the disease. Numerous studies have assessed this parameter using cardiac magnetic resonance (CMR) and serum biomarkers of extracellular matrix (ECM) including collagen and matrix metalloproteinases. Although ECM biomarkers are overexpressed in HCM patients with left ventricular tract obstruction and myocardial fibrosis, they do not strongly correlate with an increased risk of SCD. Advancing our understanding of early biomarkers in ECM remodeling, specifically scleraxis (transcription factor for cardiac fibrosis), would be highly advantageous in the HCM population. The objective of the study is to determine whether scleraxis is a detectable biomarker of cardiac fibrosis that correlates with disease burden in the HCM population.

METHODS AND RESULTS: Between 2017-2018, adults with HCM were recruited from a single tertiary care centre. Baseline characteristics including age, cardiovascular risk factors, medication use, and 12-lead EKG were obtained. SCD risk for each HCM patient was calculated using the HCM Risk-SCD prediction model. Systolic function, diastolic function, and myocardial fibrosis were assessed using transthoracic echocardiography (TTE) and CMR. Serum scleraxis levels were quantified using an enzyme-linked immunosorbent assay (ELISA). A control population of 20 healthy adults was recruited to compare serum scleraxis levels to the HCM cohort. A total of 46 HCM patients were enrolled in the SPARC study [58±14 years (31 males)]. Cardiovascular risk factors included: hypertension (57%), smoking (43%), and hyperlipidemia (37%). The mean 5-year SCD risk was 2.3±1.3%. Only 3 individuals (7%) had underlying atrial fibrillation. TTE confirmed HCM with asymmetric hypertrophy, preserved left ventricular (LV) ejection fraction, and increased left atrial (LA) volumes. Systolic anterior motion of the mitral valve was present in 15 (33%) individuals. On CMR, late gadolinium enhancement (LGE) was present in 32 (70%) study participants and occupied 18±7% of the LV myocardium (Figure 1A). ELISA analysis demonstrated a significant increase of serum scleraxis levels in the HCM group as compared to control (0.76±0.06 ng/ml vs. 0.32±0.02 ng/ml; p < 0.05) (Figure 1B). No correlation was demonstrated between serum scleraxis levels and markers of disease severity in HCM patients, including maximum LV wall thickness, %LGE, and SCD risk factors.

CONCLUSION: Scleraxis is a detectable biomarker of myocardial fibrosis in HCM. Future studies are warranted to evaluate scleraxis as a prognostic biomarker for identifying high-risk HCM patients who require aggressive management, including ICD insertion for the prevention of SCD.
BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death (SCD) in young adults ≤ 40 years of age. Myocardial fibrosis is a well-known histological marker of the disease. Numerous studies have assessed this parameter using cardiac magnetic resonance (CMR) and serum biomarkers of extracellular matrix (ECM) including collagen and matrix metalloproteinases. Although ECM biomarkers are overexpressed in HCM patients with left ventricular tract obstruction and myocardial fibrosis, they do not strongly correlate with an increased risk of SCD. Advancing our understanding of early biomarkers in ECM remodeling, specifically scleraxis (transcription factor for cardiac fibrosis), would be highly advantageous in the HCM population. The objective of the study is to determine whether scleraxis is a detectable biomarker of cardiac fibrosis that correlates with disease burden in the HCM population.

METHODS AND RESULTS: Between 2017-2018, adults with HCM were recruited from a single tertiary care centre. Baseline characteristics including age, cardiovascular risk factors, medication use, and 12-lead EKG were obtained. SCD risk for each HCM patient was calculated using the HCM Risk-SCD prediction model. Systolic function, diastolic function, and myocardial fibrosis were assessed using transthoracic echocardiography (TTE) and CMR. Serum scleraxis levels were quantified using an enzyme-linked immunosorbent assay (ELISA). A control population of 20 healthy adults was recruited to compare serum scleraxis levels to the HCM cohort. A total of 46 HCM patients were enrolled in the SPARC study [58±14 years (31 males)]. Cardiovascular risk factors included: hypertension (57%), smoking (43%), and hyperlipidemia (37%). The mean 5-year SCD risk was 2.3±1.3%. Only 3 individuals (7%) had underlying atrial fibrillation. TTE confirmed HCM with asymmetric hypertrophy, preserved left ventricular (LV) ejection fraction, and increased left atrial (LA) volumes. Systolic anterior motion of the mitral valve was present in 15 (33%) individuals. On CMR, late gadolinium enhancement (LGE) was present in 32 (70%) study participants and occupied 18±7% of the LV myocardium (Figure 1A). ELISA analysis demonstrated a significant increase of serum scleraxis levels in the HCM group as compared to control (0.76±0.06 ng/ml vs. 0.32±0.02 ng/ml; p < 0.05) (Figure 1B). No correlation was demonstrated between serum scleraxis levels and markers of disease severity in HCM patients, including maximum LV wall thickness, %LGE, and SCD risk factors.

CONCLUSION: Scleraxis is a detectable biomarker of myocardial fibrosis in HCM. Future studies are warranted to evaluate scleraxis as a prognostic biomarker for identifying high-risk HCM patients who require aggressive management, including ICD insertion for the prevention of SCD.
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