Background Cardiomyopathy is the leading cause of death in Duchenne Muscular Dystrophy (DMD), but studies suggest heart failure biomarkers correlate poorly with cardiomyopathy severity. DMD clinical trials have used troponin I (cTnI) as a biomarker of toxicity but it is unclear if asymptomatic DMD patients have elevated cTnI. We longitudinally evaluated cTnI, brain natriuretic peptide (BNP), and N-terminal proBNP (NT-proBNP) in a DMD cohort. Methods DMD patients were prospectively enrolled and followed for three years. Serum was drawn at time of cardiac magnetic resonance (CMR). Normal biomarker values were derived from healthy subjects. Biomarkers were correlated with CMR markers. Results All subjects were asymptomatic at time of enrollment. Several DMD subjects had transiently elevated cTnI. Those with elevated cTnI were more likely to have late gadolinium enhancement on baseline CMR. NT-proBNP correlated with indexed left ventricular end diastolic and maximum left atrial volumes. Otherwise, standard cardiac biomarkers did not correlate with CMR markers of cardiomyopathy. Conclusions CTnI, BNP, and NT-proBNP do not correlate with CMR assessment of cardiomyopathy progression. A subset of DMD patients have asymptomatic cTnI leak of uncertain clinical significance, though of critical importance if cTnI is used to assess for cardiac toxicity in future drug trials.
Background and Objective: Improvement in the affordability and convenience of genetic testing has rapidly expanded the understanding of the mechanistic causes of various pediatric cardiomyopathies.Concurrently, new therapies are being developed to better-target specific pathologies as opposed to classic therapies that treat the maladaptive processes of chronic heart failure. This review will discuss the advances in genetic testing and specific therapies that have been shown to benefit or potentially benefit genetically distinct subsets of the pediatric population with heart failure or at risk of developing heart failure.Methods: We undertook a comprehensive database search (January 2000-August 2022) of PubMed, utilizing terms 'pediatric', 'cardiomyopathy', 'heart failure', 'genetics', and 'precision medicine'. Additional notable studies were obtained from ClinicalTrials.gov. Studies published in English that examine genetic basis and treatment modalities of pediatric heart failure.
Introduction: Decline in renal function can impact both the management and outcomes of pediatric heart transplantation (HTx). Initial renal function decline may be subclinical and underappreciated. We sought to identify the time course and predictors of decline in renal function and the impact of these changes on HTx outcomes. Methods: The Pediatric Heart Transplant Society (PHTS) database was queried to identify HTx recipients at participating centers from 1996 to 2019 with at least 1 year of follow-up. Patients with simultaneous or previous kidney transplant were excluded. Renal function was measured by modified Schwartz formula eGFR on annual follow-up forms and stratified into eGFR groups by National Kidney Foundation chronic kidney disease staging guidelines. “Initial renal function decline” was defined as the initial drop by at least one eGFR group relative to stage at 1 year post transplant (“baseline”). Results: Of the 5,250 patients who met inclusion criteria, initial renal function decline occurred, relative to baseline, in 7.4%, 18.7%, and 55.7%, by 1, 5, and 10 years of follow up, respectively (Figure A). eGFR group distribution for the cohort progressively worsened over the follow up period (Figure B). On multivariate Cox modeling, risk factors for renal function decline were increased BSA at 1 year post-transplant (HR 1.24 [1.02, 1.52]), acute rejection with hemodynamic compromise (HR 1.24 [1.10, 1.39]), and Black race (HR 1.21 [1.08, 1.36]) with the use of tacrolimus (vs cyclosporine) being protective (HR 0.77 [0.69, 0.85]). Patients whose eGFR was < 30 mL/min at 1 year follow up had an increased risk of graft loss (P < 0.0001 compared to all other groups). Conclusions: Decline in renal function occurs progressively, affecting over 50% of HTx recipients in long term follow up, independent of renal condition at the time of HTx. Avoidance of potentially nephrotoxic events and medications must be considered at all times in the long term management of pediatric HTx.
Introduction: Cardiomyopathy is the leading cause of death in Duchenne Muscular Dystrophy (DMD), but traditional heart failure biomarkers have limited utility. Cardiac Troponin I (cTnI) has been used in DMD research studies as a marker of toxicity, but little is known about cTnI levels in asymptomatic patients. The goal of this study was to longitudinally evaluate cTnI, NTproBNP, and BNP in an asymptomatic DMD cohort. We hypothesized the biomarkers would not correlate with cardiac function, but some asymptomatic patients would exhibit a cTnI leak, reflecting ongoing myocardial inflammation related to disease progression. Methods: Asymptomatic DMD patients (N=69) and controls with normal cardiac evaluations (N=18) were enrolled. In DMD subjects, biomarker levels were obtained at time of cardiac magnetic resonance imaging (CMR), which included assessment of atrial and ventricular volumes, function, and late gadolinium enhancement (LGE). Normal ranges for biomarkers were created based on control values. Spearman correlation was used for analysis. Results: There was no consistent correlation between biomarkers and disease progression by CMR (Table 1). Several DMD subjects had transiently elevated cTnI (Fig 1). Those with elevated cTnI trended towards being more likely to have LGE on baseline CMR, though this did not reach statistical significance (p= 0.08). Conclusions: CTnI, BNP, and NTproBNP do not correlate with CMR assessment of cardiomyopathy progression. There is a subset of the DMD cohort with asymptomatic cTnI leak. While this cTnI leak is of uncertain clinical significance, it is important to recognize if cTnI is used to assess for cardiac toxicity in future drug trials.
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