Sporadic inclusion body myositis: no specific cardiac involvement in cardiac magnetic resonance tomography

Patients with histologically proven inclusion body myositis [ 20] were screened for enrollment into the study. All patients underwent skeletal muscle biopsy for histopathological diagnosis of the underlying disease. The European Neuromuscular Center (ENMC) research criteria were used to make a clinico-pathologically defined diagnosis or a clinically defined IBM.

Medical charts were reviewed for clinical and laboratory data. Exclusion criteria were contraindication for CMR, gadolinium-based contrast agent, pregnancy, or no secured contraception. All included patients gave informed written consent. The study was approved by the local ethics committee (reference no. 13/10).

Blood levels of creatine kinase (CK), myocardial creatine kinase (CK-MB), troponin I and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) were analyzed for each patient (normal range: CK < 171 U/l, CK-MB < 25 U/l, NT-proBNP 0–125 pg/ml).

As controls, a cohort of age- and gender-matched patients from the ongoing multicenter study for the assessment of age- and gender-specific reference values for cardiac imaging markers (USAGE) was implemented. Within this study, healthy subjects lacking any cardiac comorbidity underwent a comprehensive CMR examination.

Transthoracic echocardiography (2D and Doppler) was performed using a CX 50 Ultrasound (Philips Healthcare Germany). Left ventricular (LV) cavity dimensions, mass and wall thickness, and diastolic dysfunction were assessed in accordance with the recommendations of the European Association of Echocardiography [ 20].

An abnormal echocardiography was defined by a left ventricular end-diastolic diameter (LVEDD) > 56 mm, an interventricular septum (IVS) > 11 mm and a left ventricular end-systolic diameter > 40 mm. The ejection fraction was visually evaluated. Additionally, echocardiography was used to assess valve disease and fractional shortening.

All patients were examined in a 1.5 T whole-body scanner (Intera, Philips Medical Systems, Best, the Netherlands) using a 32-channel phased-array cardiac surface coil. Steady-state free precession cine sequences were acquired in contiguous short axis orientation covering the left and right ventricle for volumetric and functional analysis of both ventricles (repetition time 3.4 ms, echo time 1.7 ms, slice thickness 8 mm, no interslice gap, acquisition in end-expiration breath-holds) as previously reported [ 21].

A non-breath-hold T1-weighted fast spin-echo sequence was performed in three axial slices using the body coil (echo time 25 ms, flip angle 90°, repetition time 1xRR). This sequence was acquired before and 30 s after intravenous application of 0.1 mmol gadolinium-based contrast agent (Dotarem, Guerbet, Villepinte, France). After acquisition of T1-weighted images, a second bolus of 0.1 mmol contrast agent was injected [ 21]. Ten minutes later, an inversion-recovery gradient-echo sequence for evaluation of late gadolinium enhancement (LGE) was acquired in contiguous short-axis orientation covering the entire left ventricle (repetition time 7.1 ms, echo time 3.2 ms, slice thickness 8 mm, respiratory navigator, inversion time was individually adjusted for complete nulling of the myocardium) [ 21].

CMR images were anonymized and transferred as DICOM images to a dedicated workstation. Two blinded and experienced readers evaluated all images in consensus using commercially available software (cmr42, Circle, Cardiovascular Imaging, Calgary, Canada). End-diastolic and end-systolic endocardial contours of the left and right ventricle were drawn manually for evaluation of end-diastolic and end-systolic volumes. Ejection fractions were calculated, and end-diastolic left-ventricular epicardial contours were drawn for assessment of left ventricular myocardial mass. Stroke volumes and myocardial mass were also reported as indexes (relation to body surface area as a matter of body weight).

Regions of interest covering the left ventricular myocardium were drawn in the pre-contrast T1-weighted images and copied to the postcontrast images. Early myocardial enhancement was calculated in accordance to the Lake Louis Criteria as increase of signal intensity in percent [ 16]. For T1 ratio, values > 4 were considered pathological. These criteria are well established and suggested for CMR diagnostic work-up of inflammatory myocardial disease [ 16].

The inversion-recovery gradient-echo sequence was evaluated for presence of hyperenhancement consistent with myocardial fibrosis. LGE volume was quantified as percentage of left ventricular myocardial using a cutoff signal intensity increase of more than five standard deviations of remote myocardium [ 22].

All data are reported as median value and interquartile range [Q1, Q3] in case of normal distributed values with mean and standard deviation. Mann–Whitney U test was used for non-normal distributed variables. A p value ≤ 0.05 was regarded to be statistically significant.

Results from all tests were considered exploratory, in keeping with the study design and therefore, no adjustment for multiple testing was done.

The study group consisted of 20 patients with histologically proven IBM. 14 patients were scored as clinico-pathologically defined diagnosis and 6 patients as clinically defined IBM. Thirteen patients were treated with immunoglobulins (IVIG) every 6–8 weeks during the CMR acquisition, one of the patients was on therapy with corticosteroids and mycophenolate mofetil during the 3 months before CMR. All patients fulfilled the diagnostic ENMC criteria [ 7] at the time of CMR. There were no other autoimmune disorders reported from all of the IBM patients. Mean age of the study patients was 61 years, 35% were female. Patients’ characteristics including cardiovascular risk factors, blood levels of CK, CKMB and NT-pro BNP, and myopathy symptoms are provided in Table 1.

Echocardiography revealed normal diameters of the ventricles in all patients. The systolic function was not diminished in the visual evaluation with normal values of fractional shortening in 16/17 patients. Slight insufficiencies of the valves were reported in several patients. No pericardial effusions were reported. All other documented values were in the normal range despite an increase of left atrium diameter in 4/17 patients (Table 2).

CMR was completed in 20 IBM patients and 20 controls. Mean left and right ventricular ejection fractions (LVEF, RVEF) were in the normal range (Table 3), but myocardial stroke volumes were significantly reduced in IBM patients compared to the control group (both left and right ventricular stroke volume and indexes, respectively). The mean left ventricular ejection fraction was 63% (range 47–73). Early myocardial gadolinium enhancement in T1 could be observed in 8/18 (44%) of IBM patients and in 1/19 controls, resulting in a significant difference (Fig.  1). LGE patterns consistent with a myocardial fibrosis were detected in 7 (35%) patients, but this abnormality did not reach significance, since 4 controls also had a pathological LGE. In IBM patients, LGE was distributed in the inferior and inferolateral segments (Fig.  2). These LGE patterns are not characteristic for an ischemic origin, but are commonly reported in inflammatory myocarditis or cardiac involvement in systemic diseases [ 18, 23].

Patients with and without LGE did not differ significantly for all other variables.

Patients with increased early myocardial enhancement or LGE did not show any statistical correlation with any reported laboratory value, echocardiographic parameters or any of the reported CMR analyses.

Pericardial effusion without a hemodynamic restriction were detected in the same frequency as in healthy controls. The detected pericardial effusions in the CMR were not visible in the echocardiography.