Evaluating the diagnostic and prognostic value of biomarkers for heart disease and major adverse cardiac events in patients with muscular dystrophy

Abstract

Aims Heart disease is recognized as the leading cause of morbidity and mortality in patients with muscular dystrophy (MD). Our study demonstrates the clinical utility of cardiac biomarkers to improve the diagnosis of cardiomyopathy and prognostication of major adverse cardiac events (MACE) in these vulnerable patients. Methods and Results We prospectively followed 117 patients (median age, 42 (interquartile range [IQR], 26-50) years; 49 [41.9%] women) at the Neuromuscular Multidisciplinary clinic diagnosed with a dystrophinopathy, limb-girdle MD, type 1 myotonic dystrophy, or facioscapulohumeral MD. We determined that B-type natriuretic peptide (BNP) and high-sensitive troponin I (hsTnI) were effective diagnostic markers of cardiomyopathy (area under the curve [AUC], 0.64; P=0.017; and AUC, 0.69; P=0.001, respectively). Patient risk stratification for MACE was based on cutoff values of BNP and hsTnI defined a priori as 30.5000 pg/mL and 7.6050 ng/L, respectively. Over a median follow-up period of 2.09 (IQR, 1.17-2.81) years there were 36 confirmed MACE. Multivariate regression analyses showed that patients with BNP and hsTnI levels above the respective cutoff values had a 3.70-fold (P=0.001) and 3.24-fold (P=0.002) greater risk of MACE, respectively, compared to patients with biomarker levels below. Furthermore, patients with biomarker levels above both cutoff values had a 4.08-fold (P=0.001) greater risk of MACE. Inflammatory biomarkers did not show clinical utility for heart disease in these patients. Conclusion Our study demonstrates important diagnostic and prognostic value of BNP and hsTnI as part of a comprehensive cardiac assessment to augment the management and treatment of heart disease in patients with MD.

Predictors of mortality and cardiovascular outcomes in Emery-Dreifuss muscular dystrophy in a long-term follow-up

“…When stroke was analyzed as a separate endpoint, a trend in older patients suffering from stroke (40 [27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] vs. 25 [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34] years; P = 0.08) was observed. Those patients more frequently had atrial standstill (AS) (50% vs. 5%; P = 0.02) and atrio-ventricular (AV) block (83% vs. 15%; P = 0.002) at baseline.…”

Clinical utility of 12‐lead electrocardiogram in evaluating heart disease in patients with muscular dystrophy: Assessment of left ventricular hypertrophy, conduction disease, and cardiomyopathy

“…Heart disease is highly prevalent in patients with MD and is a major determinant of their clinical outcomes. (Nikhanj et al, 2020 ; Nikhanj, Yogasundaram, et al, 2020 ) 12‐lead electrocardiogram assessment is easily accessible, requires minimal training, and is of negligible burden on healthcare resources, making it a convenient and feasible method of assessing heart disease. Our investigation evaluated the use of conventional ECG‐LVH criteria in patients with MD.…”

“…Although we were not able to capture the association between cardiac biomarkers and anatomical LVH in this cohort due the low prevalence, we support the proposed prognostic value of comparable B‐type natriuretic peptide and hsTnI for MACE in these patients, independent of LVH. (Nikhanj, Nichols, et al, 2020 ) We acknowledge that ECG‐LVH could be representative of interstitial and ion channel remodeling in the absence of myocyte hypertrophy. (Aro Aapo & Chugh, 2016 ) With regard to the indication of LA enlargement by ECG, previous studies have shown that the level of specificity could prove useful for confirmation of indications by imaging but not for diagnosis, similar to our findings with ECG‐LVH.…”

Current state of cardiac troponin testing in Duchenne muscular dystrophy cardiomyopathy: review and recommendations from the Parent Project Muscular Dystrophy expert panel

“…A recent study of 117 patients with DMD, Becker muscular dystrophy (BMD), DMD/BMD carrier, limb-girdle muscular dystrophy (LGMD), facioscapulohumeral dystrophy (FSHD) and myotonic dystrophy (DM) type I found a threefold increased risk of cardiac disease in subjects with an hs-cTnI level greater than 7.6 ng/L (Access High Sensitivity Troponin I Assay, Beckman-Coulter; normal <2.3 ng/L). 15 In a study of 53 subjects with dystrophic myopathies (including DMD, DMD carrier, BMD, LGMD 2A, FSHD), DM types I and II, and Becker/Thomsen myotonias, only three subjects, two with DMD and one with DM, had elevated cTnI levels and all three had evidence of cardiac disease. 13 Other studies have also demonstrated increases in cTnI levels in DMD and BMD.…”