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

Abstract

ObjectiveHigh 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).Methods117 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.ResultsFifty 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.ConclusionsPlasma 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.

SERUM cardiac‐specific biomarkers and atrial fibrillation in myotonic dystrophy type I

“…On multivariable analysis, NT‐proBNP and CP were independently associated with incident paroxysmal AF in DM1 population. Increased levels of cardiac‐specific serum biomarkers in DM1 patients compared with controls have been previously reported . In a recent case‐control study, Valperta et al suggested that the hs‐cTnT might represent a helpful serum biomarker to predict cardiac risk in DM disease, below our ability to detect it with conventional measures.…”

“…In a recent case‐control study, Valperta et al suggested that the hs‐cTnT might represent a helpful serum biomarker to predict cardiac risk in DM disease, below our ability to detect it with conventional measures. More recently, Hamilton et al in a multicenter study including 117 DM1 patients followed for a mean of 23 months demonstrated that elevated serum hs‐cTnI levels were associated with left ventricular systolic dysfunction, but did not correlate with advanced conducting system disease on surface ECG. These findings suggest that high sensibility troponins might be a useful tool to aid risk stratification in DM1 patients, adding value to surface ECG in identifying those at increased risk of cardiovascular disease or those with manifest cardiac muscle involvement.…”

“…Increased levels of cardiac-specific serum biomarkers in DM1 patients compared with controls have been previously reported. [11][12][13][14][15] In a recent case-control study, Valperta et al 14 Abbreviations: CI, confidence interval; CP, copeptin; HR, hazard ratio; LAD, left atrium diameter; NT-proBNP, N terminal pro-B-type natriuretic peptide.…”

TNNT2 Missplicing in Skeletal Muscle as a Cardiac Biomarker in Myotonic Dystrophy Type 1 but Not in Myotonic Dystrophy Type 2

“…Cardiac involvement is an important cause of premature death in DM patients and one possible molecular explanation to cardiac dysfunctions is the misregulation of alternative splicing of TNNT2 and SCN5A pre-mRNA in cardiac tissue (25, 26). Recently, several authors have reported that DM patients show elevated serum levels of cTnT, cTnI, and NT-pro-BNP, suggesting that these serum cardiac biomarkers could be used to identify DM patients at increased risk of developing myocardial conduction abnormalities and for stratification of subjects in clinical trials (34, 43, 46). However, to date, no cardiac biomarkers have been identified that may serve as an accurate biomarker of cardiac involvement that could be used in clinical trials.…”

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

“… 22–24 hs-cTnI levels in DM type I were highly elevated in ambulatory subjects and predictive of cardiac dysfunction (Architect Stat Troponin Assay, Abbott). 25 Elevated cTnI levels were observed in patients with Friedreich’s ataxia. 26 Elevated troponin levels also occur in patients with spinal muscular atrophy (SMA), and transient increases in cTnI levels (up to 0.176 µg/L; assay and normal limit not reported) of unclear significance were observed following Zolgensma infusion in clinical trials.…”