Cardiac magnetic resonance imaging in rheumatoid arthritis: promising or misleading? Sophie Mavrogeni MD FESC

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Cardiac magnetic resonance imaging in rheumatoid arthritis: promising or misleading? Sophie Mavrogeni MD FESC Onassis Cardiac Surgery Center Athens Greece

Nothing to disclose Financial disclosure

Cardiac involvement in RA Rheumatoid arthritis (RA) affects 1% of the population. RA has twice the risk of CHF, compared to normals Reduction in life expectancy in RA (+) for rheumatoid factor Heart disease is clinically silent and can be manifested as CHF after a long preclinical phase.

Currently used imaging techniques in Cardiology Echocardiography (inexpensive, widely available, operator depended) Single photon emission computed tomography (SPECT) (low spatial resolution, radiation) Positron emission tomography (PET) (not widely available, expensive, radiation, low spatial resolution) Multislice computed tomography (CT)/Coronary artery CT angiography (CCTA) (Indication only if there is low probability for CAD) Cardiovascular magnetic resonance (CMR) (noninvasive, nonradiating, high spatial resolution, expensive)

Why CMR in CTD and specifically in RA? CTD usually have a silent or oligosymptomatic cardiac presentation Myocardial inflammation, assessed by pathology studies in CTD/RA, can not be detected by echo, before deterioration of cardiac function. Acuity of heart involvement can not be detected by echo, nuclear, CT Tissue characterization can not be performed by echo, nuclear, CT Great vessels angiography can not be assessed by echo, nuclear CMR is operator independent, reproducible, nonradiating= ideal for serial evaluation Most patients are female unable to exercise. Stress CMR, offering a nonradiative option, without the limitations of acoustic window and/or breast artifacts, is ideal for CAD and microvascular disease Mavrogeni S et al. Curr Cardiovasc Imag Reports 2015

Edema and fibrosis imaging by CMR: How can the experience of Cardiology be best utilized in rheumatological practice? Transmitting experience from Cardiology into Rheumatology: (a) heart involvement with atypical clinical presentation is common in autoimmune connective tissue diseases (CTDs). (b) CMR can detect early myocardial tissue changes. (c) CMR can identify disease acuity and detect various patterns of heart involvement in CTDs, including myocarditis, myocardial infarction and vasculitis. (d) CMR can assess heart lesion severity and aid therapeutic decisions in CTDs. CMR experience, transferred from Cardiology into Rheumatology, may facilitate early and accurate diagnosis of heart involvement in these diseases and potentially targeted heart treatment. Mavrogeni S et al. Semin Arthritis Rheum. 2014

Which sequences?

Horizontal, vertical and SA SSFP for function, valvular and wall motion assessment (SIMPSON S RULE) 3D technique (in deformed ventricles) Less partial volume effect in short axis imaging RV assessed simultaneously Pohost G et al. MR of the CV system 1995

Study of inflammation/fibrosis by CMR T2STIR images: T2ratio h/sm<2 Early gadolinium enhancement (EGE) <4 Late gadolinium enhancement (LGE) Subendocardial/transmural following the CA= myocardial infarction due to CAD Subepicardial/intramural= myocarditis/cardiomyopathy Friedrich MG et al. JACC 2009

Cardiovascular magnetic resonance in myocarditis: A JACC White Paper. Cine imaging Edema. Increase T2: sens 84%, spec 74%, accur 79% Early gadolinium enhancement (EGE) : sens 80%, spec 68%, accur 74.5% Late gadolinium enhancement (LGE): sens 44%, spec 95.5%, accur 71% Combined any two: sens 76%, spec 95.5%, accur 85% Friedrich MG et al JACC 2009

T2-W, T2 mapping and native T1 for oedema imaging

Early (EGE) gadolium enhancement for assessment of inflammation

BRIGHT IS DEAD TTC MRI Ex vivo comparison of TTC and Gd-enhanced MRI in infarcted myocardium

Late (LGE) gadolium enhancement for assessment of inflammation and fibrosis

T1 gadolinium first pass perfusion during adenosine stress for differentiation between CAD and microvascular disease

Frequent Detection Of Myocardial Inflammation In Autoimmune Diseases Autoimmune diseases with myocarditis: SLE, RA, Takayasu s art, SSC, thyroid disease. Assess by T2-w, EGE, LGE. Positive histology and PCR in agreement with 50% and 87.5% of positive CMR. Herpes virus, Adeno, Coxsackie B6, Echo, Parvo-B19, CMV, Chlamydia trachomatis or coexistence CMR can early diagnose myocardial inflammation Mavrogeni S et al. Inflam Allergy and DT 2009

Myopericarditis, as the first sign of rheumatoid arthritis relapse, evaluated by CMR Myopericarditis with atypical presentation, diagnosed by CMR in RA under remission and may precede the development of RA relapse. In 1-year follow-up RA patients with history of myocarditis have a higher frequency of disease relapse and may develop HF. Mavrogeni S et al. Inflam Allergy DT 2013

Diffuse Myocardial Fibrosis and Inflammation in Rheumatoid Arthritis: Insights From CMR T1 Mapping Subclinical CV disease is frequent in RA, including focal and diffuse myocardial fibrosis and inflammation, which are associated with impaired strain and RA disease activity. CMR T1 mapping provides potential added value as a biomarker for disease monitoring and study of therapies aimed at reducing diffuse myocardial fibrosis in RA. Ntutsi et al. JACC Cariovasc Imag 2015

Cardiac tissue characterization and the diagnostic value of CMR in systemic connective tissue diseases Background-Aim. Accurate diagnosis of CV involvement in CTDs remains challenging. Hypothesis: CMR reveals cardiac lesions in symptomatic CTDs with normal echo. Patients-Methods. CMR from 246 CTDs with typical (TCS) (n=146, group A) or atypical (ATCS) (n=100, group B) cardiac symptoms were retrospectively evaluated. Group A included 9 IM, 35 SRC, 30 SSc, 14 SLE, 10 RA and 48 small vessel vasculitis. Group B included 25 RA, 20 SLE, 20 SRC, 15 SSc, 10 IM and 10 small vessel vasculitis. Results. Abnormal CMR in 32 % (chronic 27%) and 15 % (chronic12%) of TCS and ATCS. Lesions due to vasculitis, myocarditis and myocardial infarction in 27.4%, 62.6% and 9.6% of CTDs. Stress studies in CTDs with negative CMR revealed CAD in 20%. Conclusions. CMR in symptomatic CTDs can assess disease acuity and vasculitis, myocarditis and myocardial infarction; therefore, it can be part of CTDs diagnostic algorithm Mavrogeni et al. Arthr Care Research 2014

Imaging patterns of HEART FAILURE in Rheumatoid Arthritis evaluated by CMR In RA with HF, CMR revealed Acute myocarditis Chronic myocarditis Myocardial infarction Dilated Cardiomyopathy Diffuse subendocardial fibrosis. The correlation of LGE with inflammatory indexes and disease activity emphasizes the role of inflammation in HF development in RA. In non RA with HF, CMR revealed Dilated Cardiomyopathy Myocardial infarction Mavrogeni S et al. Int J Cardiol 2013

Imaging patterns of HEART FAILURE in RA evaluated by CMR Mavrogeni S et al. Int J Cardiol 2013

Diffuse, subendocardial vasculitis. A new entity identified by CMR and its clinical implications. Diffuse, subendocardial vasculitis (DSV) can be identified by CMR both in acute and chronic autoimmune diseases. Acute DSV has the potential to be reversed by autoimmune and cardiac treatment modification. Mavrogeni S et al. Int J Cardiol 2013

Noncontrast T1 mapping for the diagnosis of cardiac amyloidosis. Noncontrast T1 mapping has high diagnostic accuracy for detecting cardiac AL amyloidosis, correlates well with markers of systolic and diastolic dysfunction, and is potentially more sensitive for detecting early disease than LGE imaging. Elevated myocardial T1 may represent a direct marker of cardiac amyloid load. Further studies are needed to assess the prognostic significance of T1. Karamitsos TD et al. JACC Cardiovasc Imag 2013

NOT ONLY PATHOPHYSIOLOGY, BUT ALSO RISK STRATIFICATION AND TREATMENT!

Cost-minimization analysis of three decision strategies for cardiac revascularization: results of the "suspected CAD" cohort of the european cardiovascular magnetic resonance registry. The CMR + CXA-strategy reduced costs by 14 %, 34 %, 27 %, and 24 % in the German, UK, Swiss, and US context, respectively, when compared to the CXA + FFR-strategy; and by 59 %, 52 %, 61 % and 71 %, respectively, versus the CXA-only strategy. A CMR + CXA-strategy for patients with suspected CAD provides substantial cost reduction compared to a hypothetical CXA + FFR-strategy in patients with low to intermediate disease prevalence. Moschetti K et al JCMR 2016

Effect of Posterolateral Scar Tissue on Clinical and Echocardiographic Improvement After Cardiac Resynchronization Therapy (CRT) CRT does not reduce LV dyssynchrony in patients with transmural scar tissue in the posterolateral LV segments This results in clinical and echocardiographic nonresponse to CRT. Bleeker G et al Circulation. 2006;113:969-976

Assessment of myocardial scarring improves risk stratification in patients evaluated for cardiac defibrillator implantation (ICD) Myocardial scarring detected by CMR is an independent predictor of adverse outcome in patients being considered for ICD placement. In patients with LVEF >30%, significant scarring (>5% LV) identifies a high-risk cohort similar in risk to those with LVEF 30%. Conversely, in patients with LVEF 30%, minimal or no scarring identifies a low-risk cohort similar to those with LVEF >30%. Klem I et al. JACC 2012

Take Home Message Heart disease in RA is silent, but has high mortality Currently used imaging techniques can not detect cardiac pathophysiology and disease acuity in RA Most patients with RA are female unable to exercise and the classic stress test has low sensitivity in women. Stress CMR is ideal for CAD and microvascular disease differential diagnosis Function, inflammation, ischemia, fibrosis ALL IN ONE BETTER UNDERSTANDING OF PATHOPHYSIOLOGY LEADS TO BETTER RISK STRATIFICATION AND TREATMENT

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