CVD in Rheumatoid Arthritis: How Can We Improve Diagnosis?

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A significant challenge is that CVD often remains clinically silent in patients with RA, only manifesting as cardiac dysfunction after an extended preclinical phase.
A significant challenge is that CVD often remains clinically silent in patients with RA, only manifesting as cardiac dysfunction after an extended preclinical phase.

Patients with rheumatoid arthritis (RA) have a significantly higher risk for cardiovascular disease (CVD), including coronary artery disease, valvular heart disease, heart failure, and pulmonary arterial hypertension, than persons without RA, increasing their risk for morbidity and mortality.1 Life expectancy has been reported to be 10 years shorter in patients with RA than in healthy individuals, with cardiovascular disease being the leading cause of death and mortality rate linked to clinical severity.2,3

A significant challenge is that CVD often remains clinically silent in patients with RA, only manifesting as cardiac dysfunction after an extended preclinical phase,2 making early recognition of cardiovascular abnormalities difficult unless thorough cardiovascular examinations are performed. Yet no diagnostic algorithms are currently available to guide assessment for CVD in patients with RA with no signs or symptoms of CVD, adding to the challenge of making an early diagnosis.

Various imaging modalities can be used to assess cardiovascular health in patients with RA, but because patients are often asymptomatic and have a complex cardiovascular pathophysiology, early diagnosis requires use of an imaging modality that can identify more subtle pathology. This is where cardiac magnetic resonance (CMR) imaging is showing considerable promise, and many rheumatologists are advocating its use in the early diagnosis of CVD in patients with RA.

Rheumatology Advisor had the opportunity to discuss CMR imaging with Sophie Mavrogeni, MD, FESC, from the Onassis Cardiac Surgery Centre, Athens, Greece, who has written extensively on the subject and organized numerous international workshops dedicated to advancing knowledge on the use of CMR imaging, including in individuals with RA.

Rheumatology Advisor: Why is CMR imaging ideal for assessing cardiovascular health in patients with RA?

Dr Mavrogeni: CMR imaging is the ideal technique because it can perform tissue characterization and detect cardiovascular structural and functional abnormalities in the very early preclinical stage. For example, in a recently published Finnish study, patients with active RA who had no signs of clinical cardiac disease were found to have numerous cardiovascular abnormalities, including prolonged myocardial T1 relaxation times, suggestive of diffuse inflammation or fibrosis; late gadolinium enhancement, indicative of local myocardial scars and inflammation; and impairments in left ventricular systodiastolic function.4

Furthermore, adenosine stress CMR can be useful for the early detection of perfusion defects. When such defects are identified, it is essential to encourage further cardiac assessment and treatment. It remains to be proven whether very early diagnosis of abnormalities identified on CMR imaging can be lead to successful treatment and improved outcomes.

Rheumatology Advisor: At what point should CMR imaging be used in assessing patients with RA and other connective tissue diseases?

Dr Mavrogeni: There are currently no internationally proposed guidelines to define which patients should receive CMR imaging. On the basis of our experience, a baseline study including biventricular function assessment, T2 mapping for myocardial edema, late gadolinium enhancement, and T1 mapping (native, postcontrast, and extracellular volume fraction) should be performed at diagnosis.

Subsequent CMR should be recommended in the following situations: if there is a mismatch between clinical findings and imaging/laboratory findings; in new-onset heart failure; when there is any arrhythmia; if the rheumatologist plans to change the rheumatic treatment, especially if there is a plan to use biologic agents; when there is any increase in troponin, brain natriuretic peptide, or D-dimer, even if patient has only subtle symptoms; and if the patient is being treated with hydroxychloroquine or biologic agents, which can have cardiotoxic effects.

Rheumatology Advisor: Are there situations in which other imaging modalities would be preferred over CMR imaging?

Dr Mavrogeni: CMR has great versatility, providing diagnostic information in almost all cases of CVD; however, echocardiography is preferred for valvular disease evaluation and cardiac computed tomography for coronary artery and pulmonary embolism evaluation.

Rheumatology Advisor: How do you envision CMR imaging being used in clinical practice?

Dr Mavrogeni: Excellent collaboration between a cardiologist familiar with rheumatic diseases and CMR imaging and a rheumatologist specialized in RA is a prerequisite. For this reason, at the Onassis Cardiac Surgery Centre, we established a dedicated outpatient clinic for patients with rheumatic diseases. After long-term training in rheumatic diseases, clinical cardiology, and CMR, I oversee this clinic. We perform very well in both clinical assessments and research because we work as a team with our referral cardiologists and rheumatologists. Furthermore, we organize common educational activities to explain to both clinical cardiologists and rheumatologists the indications and benefits of CMR imaging in diagnosing and assisting with decision-making regarding rheumatic diseases.           

Rheumatology Advisor: What are the limitations of CMR?

Dr Mavrogeni: CMR is contraindicated in patients with non-MRI-compatible devices or metallic clips and in claustrophobic patients. However, all coronary artery stents, currently implanted valves, and MRI-conditional devices can be safely scanned. In patients with renal failure, use of paramagnetic agent gadolinium is contraindicated because of the risk for nephrogenic fibrosis. In these patients, we can apply non-contrast-enhanced imaging protocols and perform both function and tissue characterization evaluation. In addition, CMR performs less well in patients with severe arrhythmia and/or an inability to hold their breath.

Rheumatology Advisor: Anything else rheumatologists should know about CMR imaging or addressing cardiovascular health in patients with RA?

Dr Mavrogeni: The pathophysiology of RA is multifaceted, being a combination of myopericardial inflammation, microvascular and macrovascular coronary artery disease, and valvular disease. Because these patients are at high risk of developing heart failure with or without coronary artery disease, close collaboration between cardiologists and rheumatologists is necessary.

A cardiac evaluation should be part of the routine annual evaluation of rheumatic patients and should include detailed clinical and imaging assessments. Electrocardiogram and echocardiography are cornerstones of routine cardiovascular assessment; however, CMR has a special place in ischemia/fibrosis assessment (adenosine stress CMR) because of its capability to detect myocardial perfusion defects missed by other imaging techniques.

This technique is of special value in obese women and those who are unable to perform exercise. The detection of perfusion defects can prompt further assessment by coronary angiography and potentially lead to more timely use of angioplasty and cardiac medications. Even detection of a small fibrotic area should motivate clinicians to prescribe cardiac medication to prevent the development of heart failure in the future. Finally, the detection of active myocardial inflammation after CMR tissue characterization should lead to modifications in both rheumatic and cardiac treatments. By offering an integrated, noninvasive, nonradiating assessment of the cardiovascular system, CMR imaging can be an excellent diagnostic adjunct for the early diagnosis, treatment, and follow-up of rheumatic patients.

References

  1. Mavrogeni S, Markousis-Mavrogenis G, Kolovou G. The Sphinx's riddle: cardiovascular involvement in autoimmune rheumatic disease. BMC Cardiovasc Disord. 2016;16:204. doi: 10.1186/s12872-016-0381-5
  2. Kobayashi H, Kobayashi Y, Ode S, et al. The diagnostic role of cardiac magnetic resonance imaging in rheumatoid arthritis [published online September 13, 2010]. Int J Immunol Immunother. doi: 10.1186/ar3131
  3. Wolfe F, Mitchell DM, Sibley JT, et al. The mortality of rheumatoid arthritis. Arthritis Rheum. 1994;37(4):481-494. doi: 10.1002/art.1780370408
  4. Holmström M, Koivuniemi R, Korpi K, et al. Cardiac magnetic resonance imaging reveals frequent myocardial involvement and dysfunction in active rheumatoid arthritis [published online April 6, 2016]. Clin Exp Rheumatol. 34(3):416-423.
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