THE CARDIAC BIOMARKERS IN CHILDREN WITH CARDIOMYOPATHY MULTICENTER STUDY: PRELIMINARY RESULTS FOR PEDIATRIC HYPERTROPHIC CARDIOMYOPATHY

1509 JACC April 5, 2016 Volume 67, Issue 13

Heart Failure and Cardiomyopathies THE CARDIAC BIOMARKERS IN CHILDREN WITH CARDIOMYOPATHY MULTICENTER STUDY: PRELIMINARY RESULTS FOR PEDIATRIC HYPERTROPHIC CARDIOMYOPATHY Poster Contributions Poster Area, South Hall A1 Monday, April 04, 2016, 9:45 a.m.-10:30 a.m. Session Title: Beyond the Usual Suspects: The Atypical Cardiomyopathies Abstract Category: 26. Heart Failure and Cardiomyopathies: Clinical Presentation Number: 1250-052 Authors: Steven Lipshultz, James Wilkinson, Ling Shi, Jeffrey Towbin, Charles Canter, Daphne Hsu, Steven Webber, Paul Kantor, Melanie Everitt, Elfriede Pahl, John Jefferies, Joseph Rossano, Linda Addonizio, Debra Dodd, Stephanie Ware, Kimberly Molina, Steven Colan, Wayne State University School of Medicine, Detroit, MI, USA

Background: Few cardiac biomarkers have been validated as surrogate endpoints in children with hypertrophic cardiomyopathy (HCM). The National Heart, Lung and Blood Institute-funded Cardiac Biomarkers in Pediatric Cardiomyopathy study is evaluating cardiac biomarkers in children with HCM and their association with echo and cardiac magnetic resonance (cMRI) measures of cardiac fibrosis and as surrogates for clinical endpoints (heart failure, death, or heart transplant).

Methods: The study is currently enrolling children < 21 years of age at the time of diagnosis of HCM and is collecting cardiac biomarker, echo, cMRI and clinical data. The study aim for HCM patients with a recent cMRI was to determine if collagen metabolism biomarkers of are associated with cardiac fibrosis by cMRI. The other study aim was to determine whether cardiac troponin T (cTnT with a detection level of 0.01ng/ml), and inflammatory biomarkers are associated with echocardiographic and clinical status measures. Results: Preliminary results from the first 22 HCM patients enrolled are shown in the Table. Collagen biomarker ranges exceeded >4 standard deviations and detectable cTnT was found in 3/22 patients.

Conclusions: The observed variability of collagen biomarkers in children with HCM suggests that they may serve as surrogate endpoints for myocardial fibrosis as measured by cMRI. The next step will be to investigate the associations of biomarker results with cardiac imaging and clinical status in the entire study population. Table. Results of Cardiac Biomarker Assays in 22 Children with Hypertrophic Cardiomyopathy Cardiac Biomarker Class

HCM (N=22) Mean ± SD (range)

Normal Values Mean (range)

1.2±0.5 (0.2-2.3)

0.3* (0.02-0.58)

1.Collagen Metabolism (Cardiac Fibrosis) C-Terminal Relopeptide of Type I Collagen (ng/ml) TIMP Metallopeptidase Inhibitor 1 (ng/ml)

66±13.8 (44.6-104.9)

98* (110-966)

Promatrix Metalloprotease 1 (ng/ml)

2.3±2.1 (0.3-9.1)

3.45 (0.91-9.34)

C-Terminal Propeptide of Type I Collagen (ng/ml)

245±146.7 (53.7-636.3)

326 (110-966)

2,152±3,909 (29-17,729)

67.8±83.7*

2.Heart Failure NT-proBNP (pg/ml) Galectin-3 (ng/ml)

5.4±1.8 (2.3-9.9)

6.44* (2.03-15.50)

ST2 (pg/ml)

11,937±6,220 (5,308-26,305)

12.2* (4.90-19.9)

Growth Differentiation Factor-15 (pg/ml)

355±100 (205-499)

534 (289-1096)

Troponin-T (cTnT) (level of detection ≥ 0.01 ng/ml)

0.08±0.06 N=3 (0.04-0.15) [N=19 had non-detectable levels]

<0.01 (level of detection)*

C-Reactive Protein (mg/L)

1.7±2.4 (0.2-8.3)

N/A (0.1-2.8)

3.Cardiac Myocyte Injury

4.Inflammatory TNF-α (pg/ml)

1.2±0.4 (0.4-1.8)

1.04 (non-detectable*-2.14)

IL-6 (pg/ml)

3.1±6.8 (0.6-32.4)

1.49* (0.43-8.87)

*Normal value for adults