Reliability of Cardiac Troponins for the Diagnosis of Myocardial Infarction in the Presence of Skeletal Muscle Disease

Heart&Muscle Study

Visits to the emergency department (ED) for chest pain are extremely common and require a safe, rapid and efficacious treatment algorithm to exclude a possible AMI. These diagnostic algorithms are partly based on an important laboratory value, which showed growing utility in the diagnostic and prognostic of many cardiovascular diseases in the last years : cardiac troponin.

However, some patients with muscle disease often present with unexplained elevated high-sensitive cardiac Troponin T (hs-cTnT) levels in the absence of cardiac disease. The investigators aim at the characterization of the behaviour of this biomarker and its alternative (high-sensitive cardiac Troponin I), which will have important clinical implications on patients management.

Introduction: The detection of cardiomyocyte injury as quantified by blood concentrations of cardiac troponin T (cTnT) or I (cTnI) is central in the diagnosis of acute myocardial infarction (AMI). While multiple cardiac disorders other than AMI may also lead to cardiomyocyte injury and therefore elevations in cTnT and cTnI, latest generations of cTnT and cTnI assays are considered to have near exclusive cardiac-specificity. Overall, both analytes (cTnT and cTnI) seem to have comparable diagnostic accuracy among patients presenting with suspected AMI to the emergency department (ED). However, their use in the diagnosis of AMI in patients with a skeletal muscle disease is questioned, as especially cTnT was found to be elevated in this setting. These increased cTnT levels have been successively attributed to a possible re-expression of cTnT isoforms in the diseased muscle, to a primary cardiac involvement associated with the muscle disease or to a cross-reaction of the hs-cTnT assay with TnT of muscle origin.

Aim: To characterize cTn levels in patients with a skeletal muscle disease to assess their utility in the field of cardiology (through their implication in AMI diagnosis and their diagnostic and prognostic accuracy regarding a possible cardiac involvement) and in the field of neurology (for the detection and risk-stratification of the muscle disorder itself).

Methodology: This study will be conducted at the University Hospital of Basel, at the Kantonsspital Aarau, both in Switzerland, and at the University Hospital of Innsbruck, Austria. A prospective cohort patient will be recruited through the neurology, rheumatology and cardiology clinics of these three hospitals. This prospective cohort of patients presenting with skeletal muscle disease will allow us to systematically screen patients for cTn increases, to investigate the prevalence and characteristics of a possible primary cardiac involvement (as documented by electrocardiogram, echocardiography, magnetic resonance imaging, cTnI, NT-proBNP (N-terminal pro-B-type Natriuretic Peptide) and any available further cardiac testing) and to explore the origins of the elevated cTn levels using muscle biopsies. Furthermore, this prospective cohort will document the role of these biomarkers in the diagnosis, prognosis and risk-stratification of the muscle disease. Patients will receive a 1- and 3-year follow-up visit with blood draw in order to measure cTn and other biomarkers and record the impact of the evolution and treatment of the muscle disease on these levels. Major adverse cardiac events including cardiovascular death, AMI, hospitalization for heart failure, and the development of clinical or subclinical heart failure as quantified by elevated blood concentrations of NT-proBNP will be recorded during follow-up.

Potential significance: Elevated cTnT levels do not only have consequences regarding the diagnosis of AMI but also raise many questions regarding their possible use as a diagnostic, prognostic and risk-stratification marker regarding the different muscle injuries and their possible primary cardiac involvement.

Inclusion Criteria:

• Diagnostic or suspicion of muscle disease as presence of specified keyword in patient's file or as screened by colleagues of the rheumatology, neuromuscular or other medical clinics.
• Patient consent available

Exclusion Criteria:

• Patient's refusal
• Age <18 years old
• Terminal kidney insufficiency with need for dialysis.
• Temporary exclusion criteria : Acute health condition such as myocardial infarction, patients presenting with a major trauma, a sepsis, patients shortly after cardiac surgery, and patients in shock (>100 bpm, <90 systolic BP, evidence of organ dysfunction).