Background-Cardiomyopathy is the leading cause of death in Duchenne muscular dystrophy (DMD). Standard cardiac biomarkers are poor indicators of DMD cardiovascular disease. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) regulate collagen turnover. Given the cardiac fibrosis seen in DMD, we hypothesized that MMPs and TIMPs correlate with severity of DMD cardiomyopathy. Methods and Results-Prospectively enrolled DMD subjects (n=42) underwent cardiac MRI for function and late gadolinium enhancement (LGE), including LGE severity from 0 (no LGE) to 4 (severe). Serum from DMD and healthy male controls (n=15) analyzed for MMP 1, 2, 3, 7, 9, 10 and TIMPs 1-4. MMP1, MMP7, and MMP10 were higher in DMD than control (median 5080pg/ml vs. 2120pg/ml, p=0.007; 2170pg/ml vs. 1420pg/ml, p<0.001; 216pg/ml vs. 140pg/ml, p=0.040); TIMP4 was lower in DMD (124pg/ml vs. 263pg/ml, p=0.046). Within DMD, MMP7 correlated inversely with left ventricular ejection fraction (r=−0.40, p=0.012) and directly with
HGF may be a specific marker that distinguishes AL cardiac amyloidosis from other cardiomyopathies with similar clinical or morphologic characteristics. Further studies are necessary to determine whether HGF levels predict the likelihood of survival.
Retrospective studies suggest that chimeric antigen receptor T-cell (CAR T) therapy may lead to cardiac injury, but this has not been assessed systematically or prospectively. In this prospective study of 40 patients who received CAR T, we systematically measured high-sensitivity troponin T (hsTropT) and N-terminal pro-B natriuretic peptide (NTproBNP) at baseline and on day 1, days 7, and 21 after CAR T. Biomarker elevations with respect to timepoint and cytokine release syndrome (CRS) status were examined using repeated measure analysis of variance. hsTropT did not differ with time or with the presence of grade 2 CRS. Median hsTropT was 12.1 ng/L [interquartile range (IQR): 9.2, 20.1] at baseline, 13.1 ng/L (IQR: 9.6, 24.2) at day 1, 11.9 ng/L (IQR: 9.6, 18.0) at day 7, and 15.3 ng/L (10.8, 20.2) at day 21. In contrast, NTproBNP rose on day 1 (P Wilcox = 0.0002) and day 7 (P Wilcox = 2.7 ´ 10 −5 ), and the degree of elevation differed by the presence of grade 2 CRS (P interaction = 0.002). Median NTproBNP was 179 pg/mL (IQR: 116, 325) at baseline, 357 pg/mL (IQR: 98, 813) at day 1, 420 pg/mL (IQR: 239, 1242) at day 7, and 177 pg/mL (IQR: 80, 278) at day 21. In conclusion, hsTropT l did not differ across timepoints after CAR T therapy, but NTproBNP rose at day 7, the prognostic implications of which should be the target of future research, as the indications for this therapy expand.
Biomarkers are routinely used for noninvasive identification or monitoring of disease
processes in clinical practice, as well as surrogate end points for drug development.
There is a significant lack of data regarding biomarkers in children. An understanding of
biomarker levels in a healthy pediatric cohort is essential as more studies begin to apply
noninvasive biomarkers to pediatric populations. Brain-derived neurotrophic factor (BDNF)
functions in neuronal survival and plasticity and is associated with exercise capacity and
inflammatory disease processes. Osteopontin (OPN) plays a regulatory role in inflammation
and may be a clinically useful biomarker of cardiovascular disease processes, ventricular
remodeling, and skeletal muscle regeneration. This study describes our initial experience
with a cohort of healthy pediatric patients and seeks to provide normal values of BDNF and
OPN with correlation to age, gender, and cardiovascular and fitness measures. Serum BDNF
and plasma OPN were measured using enzyme-linked immunosorbent assay in 33 healthy
pediatric subjects. Subjects underwent complete cardiac evaluation, including
echocardiography, exercise stress testing, and health risk assessment. The 5th–95th
percentile was 5.63–37.86 ng/ml for serum BDNF and 4.9–164.9 ng/ml for plasma OPN. Plasma
OPN correlated with number of days of exercise per week (r = 0.46,
p = 0.008). No other correlations were significant. This study provides
the initial data on serum BDNF and plasma OPN in children and begins to explore the
relationships of BDNF and OPN to cardiovascular health and fitness in the pediatric
population.
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