Search for Prognostic Biomarkers for DM Cardiac Conduction Abnormalities

Published on Mon, 12/11/2017

Sudden cardiac death resulting from atrioventricular block or ventricular arrhythmias is major risk factor (2nd leading cause of death after respiratory failure) for patients with DM1. These recommendations include annual ECG and use of electrophysiology testing when there is the potential for serious conduction block and arrhythmias. Developing sensitive biomarkers with the potential for early identification of those at risk for cardiac events is a critically important need for care of patients living with DM1.

Cohort Study Assessing Biomarkers for Cardiac Abnormalities

Prof. Raffaele Bugiardini and colleagues at the IRCCS Policlinico San Donato and University of Bologna evaluated serum biomarkers (high-sensitivity cardiac troponin T (hs-cTnT), high-sensitivity cardiac troponin I (hs-TnI), creatine kinase (CK) and N-terminal pro B-type natriuretic peptide (NT-proBNP) in 60 study subjects, 46 with genetic confirmation of DM1 and 14 with DM2. These serum measures were correlated with ECG and left ventricular ejection fraction (LVEF) determined by echocardiography.

Screening for Prospective Serum Biomarkers

ECG abnormalities were detected in 39% of patients. All but 2 patients had normal LVEF. Elevations of hs-cTnT and CK were observed in 92% of DM subjects, while hs-cTnI levels were within normal limits. Higher levels of hs-cTnT were found in patients with ECG measures above the normative range., but, after adjusting for age, gender, NT-proBNP levels and CK, hs-cTnT levels did not correlate with ECG parameters. Twelve of the 60 subjects (9 DM1 and 3 DM2) had elevated NT-proBNP levels.  Measurements of NTpro-BNP > 125 pg/ml were an independent predictor of ECG abnormalities.

Outcomes

The research team noted that NT-proBNP is released during cardiac repair and that it is not yet known how elevated levels may relate to the development of conduction system abnormalities in DM. They do show that NT-proBNP levels > 125 pg/ml correlates with the presence of conduction abnormalities in DM, regardless whether the molecular diagnosis was DM1 or DM2. Identification and validation of an NT-proBNP level that would trigger stricter clinical monitoring and determination of the relationship between NT-proBNP levels and the severity of ECG abnormalities awaits study of a larger cohort.

Reference:

Cardiac involvement in myotonic dystrophy: The role of troponins and N-terminal pro B-type natriuretic peptide.
Valaperta R, De Siena C, Cardani R, Lombardia F, Cenko E, Rampoldi B, Fossati B, Brigonzi E, Rigolini R, Gaia P, Meola G, Costa E, Bugiardini R.
Atherosclerosis. 2017 Oct 21;267:110-115. doi: 10.1016/j.atherosclerosis.2017.10.020. [Epub ahead of print]