Research Article: Elevated plasma levels of cardiac troponin-I predict left ventricular systolic dysfunction in patients with myotonic dystrophy type 1: A multicentre cohort follow-up study

Date Published: March 21, 2017

Publisher: Public Library of Science

Author(s): Mark J. Hamilton, Yvonne Robb, Sarah Cumming, Helen Gregory, Alexis Duncan, Monika Rahman, Anne McKeown, Catherine McWilliam, John Dean, Alison Wilcox, Maria E. Farrugia, Anneli Cooper, Josephine McGhie, Berit Adam, Richard Petty, Cheryl Longman, Iain Findlay, Alan Japp, Darren G. Monckton, Martin A. Denvir, Ruben Artero.


High sensitivity plasma cardiac troponin-I (cTnI) is emerging as a strong predictor of cardiac events in a variety of settings. We have explored its utility in patients with myotonic dystrophy type 1 (DM1).

117 patients with DM1 were recruited from routine outpatient clinics across three health boards. A single measurement of cTnI was made using the ARCHITECT STAT Troponin I assay. Demographic, ECG, echocardiographic and other clinical data were obtained from electronic medical records. Follow up was for a mean of 23 months.

Fifty five females and 62 males (mean age 47.7 years) were included. Complete data were available for ECG in 107, echocardiography in 53. Muscle Impairment Rating Scale score was recorded for all patients. A highly significant excess (p = 0.0007) of DM1 patients presented with cTnI levels greater than the 99th centile of the range usually observed in the general population (9 patients; 7.6%). Three patients with elevated troponin were found to have left ventricular systolic dysfunction (LVSD), compared with four of those with normal range cTnI (33.3% versus 3.7%; p = 0.001). Sixty two patients had a cTnI level < 5ng/L, of whom only one had documented evidence of LVSD. Elevated cTnI was not predictive of severe conduction abnormalities on ECG, or presence of a cardiac device, nor did cTnI level correlate with muscle strength expressed by Muscle Impairment Rating Scale score. Plasma cTnI is highly elevated in some ambulatory patients with DM1 and shows promise as a tool to aid cardiac risk stratification, possibly by detecting myocardial involvement. Further studies with larger patient numbers are warranted to assess its utility in this setting.

Partial Text

Myotonic dystrophy type 1 (DM1) is a dominantly inherited, multisystem condition affecting approximately 1 in 8,000 of the population.[1] It is caused by expansion of a CTG trinucleotide repeat in the 3′-untranslated region of the DMPK gene. The trinucleotide repeat is genetically unstable in the germline, with offspring frequently inheriting a larger repeat expansion than the transmitting parent.[2] This gives rise to the phenomenon of genetic anticipation, with earlier onset and more severe symptoms often seen in successive generations of an affected family. Cardiac manifestations of DM1 include cardiomyopathy, conducting system disease and arrhythmias.[3, 4] Non-cardiac features include frontal balding, ptosis, skeletal muscle weakness, delayed muscle relaxation, diabetes and cognitive deficits.[5] Premature mortality is most commonly due to cardiac arrhythmias and respiratory failure.[6, 7] Abnormalities of the surface electrocardiogram are common, and include prolongation of the PR interval, axis-deviation and broadening of the QRS complex.[8] Arrhythmias may also occur including atrial fibrillation and flutter, ventricular tachycardia and varying degrees of atrioventricular block. In several case series, advanced cardiac involvement of the conducting system was linked to sudden death and cardiovascular events.[9–11] Overt cardiomyopathy is relatively rare, although cardiac MR studies suggest that more subtle changes in myocardial trabeculation and mass are more common than previously recognized.[8, 12, 13]

In clinical practice, the role of plasma cardiac troponin measurement as a screen for myocardial necrosis in the context of acute chest pain is well established. However, high-sensitivity cardiac troponin assays have also shown promise as prognostic biomarkers of cardiovascular risk in a variety of ambulatory outpatient settings, including among those with known vascular disease,[28, 29] the elderly [30, 31] and in general population-based studies.[27, 32–35] The cause of chronic, low-level troponin elevation in these populations is uncertain, although speculated mechanisms include subclinical ischaemia, microvascular dysfunction or apoptosis of myocytes.[36]

In ambulatory patients with DM1, plasma cTnI level appears to map with the presence of LVSD but does not correlate with advanced conducting system disease on surface ECG. These findings suggest that high sensitivity cTnI holds promise as a tool to aid risk stratification of patients with myotonic dystrophy, possibly adding additional value to surface ECG in identifying those at increased risk of cardiovascular disease or those with manifest cardiac muscle involvement. Further studies of cardiac biomarkers in DM1 involving larger patient numbers and longer-term formal follow-up are therefore warranted.




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