Cardiovascular magnetic resonance imaging pattern in systemic lupus erythematosus with cardiac symptoms.

A multicenter study.

Sophie I. Mavrogeni 1, George Markousis-Mavrogenis 1, Loukia Koutsogeorgopoulou 2, …………Theodoros Dimitroulas 3, Gikas Katsifis 4, Genovefa Kolovou 1, George D. Kitas 5, Petros P. Sfikakis 6

1 Onassis Cardiac Surgery Center

2 Department of Pathophysiology, Laikon Hospital, Athens, Greece

3 Department of Rheumatology, Aristotle University of Thessaloniki, Thessaloniki, Greece

4 Rheumatology Department, Naval Hospital, Athens, Greece

5 Arthritis Research UK Epidemiology Unit, Manchester University, Manchester, UK

6 First Department of Propaedeutic and Internal medicine, Laikon Hospital, Athens University Medical School, Athens, Greece

Systemic lupus erythematosus (SLE) is an autoimmune, inflammatory disease involving multiple organs, including the heart (1). It is characterized by a female preponderance (9F:1M), has a prevalence of 15-50/100,000. Symptoms usually appear during the second and/or third decades of life (2). Cardiovascular disease (CVD), including myocarditis, dilated cardiomyopathy, macro/microvascular- coronary artery disease and/or valvular disease, severely contributes to increased mortality (3, 4).

Clinical and echocardiographic evaluation (echo) remains the cornerstone of routine SLE patients’ evaluation. However, this approach may presents important limitations for the assessment of CVD in SLE, due to various reasons including atypical clinical presentation and inherent limitations of echo (3, 4). CMR has been recently proposed as the ideal non-invasive, non-radiating tool to assess the pathophysiologic background of cardiac involvement in SLE, because it is highly reproducible, operator independent and capable of performing tissue characterization, the latter strikingly missing in other imaging techniques (3, 4).

We hypothesized that CMR can identify cardiac pathophysiology in SLE patients referred due to cardiac symptoms including fatigue, chest pain, shortness of breath and/or arrhythmia. Our aim was to use CMR in a cohort of SLE patients with cardiac symptoms to investigate the underlying pathophysiology and detect the substrate of cardiac disease

Patients-Methods

Patients

A number of 100 SLE patients from various centers worldwide with cardiac symptoms/signs will be evaluated using CMR. The study will be prospective and the patients will be consecutively selected. The SLE diagnosis will be based on the American College of Rheumatology (ACR) criteria (5-7). Patients with known contraindications to CMR (claustrophobia, non-CMR conditional pacemakers, etc.) and those with contraindications to paramagnetic contrast agents will be excluded from the study. Informed consent will be obtained from all patients in the form of a signed document of accord and the protocol will be approved by the hospital ethics committee.

Methods

Cardiovascular magnetic resonance imaging

CMR sequences including STIR T2 and late gadolinium enhancement (LGE) will be performed on all patients with a 1.5 Tesla scanner using ECG-triggered steady-state. Steady state free precession breath-hold cines (SSFP) in long-axis planes and sequential 8 mm short-axis slices (3 mm gap) from the atrioventricular ring to the cardiac apex will be also obtained.

Cardiovascular magnetic resonance analysis

Acquired CMR images will be evaluated independently by 2 experienced interpreters blinded to clinical data. Scan parameters including right and left ventricular end systolic and end diastolic volumes (LV/RV-ESV, LV/RV-EDV) as well as regional ventricular function will be evaluated using images from SSFP sequences. T2 ratios will be calculated using the ratios of myocardial to skeletal muscle signal intensity from STIR T2W images (8).

               LGE images will be assessed for subendocardial/transmural enhancement in the distribution of a coronary artery compatible with myocardial infarction (4, 9) for intramural/subepicardial enhancement, compatible with myocarditis (4, 8) and for diffuse subendocardial fibrosis compatible with vasculitis (4). Patients will be further sub-classified as being in an acute (T2 ratio >2) or non-acute (T2 ratio<2) stage (4). A combination of T2>2 with positive LGE will be considered indicative for acute myocardial lesions, whereas one of T2<2 with positive LGE, will be considered indicative of a chronic lesion (1). On the basis of LGE distribution and morphology, patients will be categorized as having: a) diffuse subendocardial LGE, indicative of subendocardial vasculitis, b) intramural/ subepicardial LGE not following the distribution of coronary arteries, indicative of myocarditis (10), or c) subendocardial/transmural LGE following the distribution of coronary arteries, indicative of myocardial infarction (4). Scans with completely normal range volumes and function with no LGE/T2 abnormalities will be considered as normal.

               T1, T2, mapping and ECV woll be also assessed, if they are available at the local imaging system

Image analysis

In T2W images, the signal ratio will be measured from the region of interest covering the left ventricular myocardium as well as a skeletal muscle in the same slice. To assess contrast-enhanced images (LGE), all short-axis slices from base to apex will be inspected visually to identify areas of normal (completely nulled) myocardium. Mean signal intensity and standard deviation (SD) will be derived and a threshold of 0.2 SD exceeding the mean will be used to define areas of LGE. Summing the planimetered areas of LGE in all short-axis slices yielded the total volume, will be expressed as a proportion of total LV myocardium (% LV).

Cine images will be used for the evaluation of LV- and RV-EF. LV-RV endocardial borders will be outlined on the end-systolic and end-diastolic short-axis view images covering the entire LV.  LVEF and RVEF values will be calculated as the ratio of the difference between end-diastolic and end-systolic ventricular volumes (LVEDV/RVEDV-LVESV/RVESV) divided by the end-diastolic volume (LVEDV/RVEDV).

Statistical analyses.

Statistical analyses will be performed with SPSS version 24 (IBM). All continuous variables will be tested for normality through a visual evaluation of individual Q-Q plots and histograms. Additionally descriptive statistics will be obtained; normally distributed measurements will be presented as mean ± standard deviation, not-normally distributed continuous measurements will be presented as median (interquartile range) and nominal variables will be presented as n (%). The presence of a linear relation between blood inflammatory markers (CRP, ESR) and CMR measurements (LV- & RV-EDV/ESV and EF, T2 and LGE) will be investigated by use of Spearman’s rank order correlation. Statistical significance will be considered for p<0.05.

References

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