Autoimmune rheumatic diseases (ARDs) such as systemic lupus erythematosus, rheumatoid arthritis (RA), and systemic sclerosis carry an excess risk of cardiovascular morbidity and mortality due to conventional cardiovascular risk factors, antirheumatic drug-related cardiotoxicity, disease-related inflammation, and autoimmune dysregulation.1,2  Patients with lupus have demonstrated mortality and cardiovascular disease (CVD) event hazards double those of age- and sex-matched controls.3 In patients with RA, approximately 50% of premature deaths are related to CVD.4 RA confers a risk of CVD comparable to that seen with type 2 diabetes, a disease classically considered as a coronary heart disease equivalent.5

The European League Against Rheumatism (EULAR) guidelines on CVD risk management in patients with RA and other inflammatory joint disorders advocate the use of risk stratification algorithms such as the European Systematic COronary Risk Evaluation (SCORE).6 Because these algorithms do not account for the excess CVD risk present in patients with ARDs, EULAR recommends a 1.5 multiplication factor for all patients with RA.

The guidelines further state that screening for asymptomatic atherosclerotic plaques with carotid ultrasound may be considered as part of the CVD risk evaluation in patients with RA.6 However, some researchers believe that the EULAR-recommended approach is insufficient, and that the expanded use of CV imaging, particularly cardiovascular magnetic resonance (CMR), may improve cardiovascular risk stratification and facilitate the timely initiation of CV therapies.7-10

Rheumatology Advisor conducted an interview with a leading proponent of the use of CMR in rheumatic diseases, Sophie Mavrogeni, MD, PhD, FESC, of the Onassis Cardiac Surgery Center, in Athens, Greece. According to Dr Mavrogeni, the cardio-rheumatic approach using CMR was developed at her hospital in collaboration with professors of rheumatology, Petros Sfikakis, MD, and George Kitas, MD, PhD, FRCP, who strongly supported the idea.


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Rheumatology Advisor: What is the current status of CV imaging in patients with rheumatic diseases? Should rheumatologists be routinely using it for risk assessment?

Dr Mavrogeni: The main noninvasive modalities in CV imaging include echocardiography, nuclear imaging, cardiac computed tomographic imaging, and cardiac magnetic resonance imaging (CMR). Of them, echocardiography remains the bedside inexpensive approach and every patient with systemic ARD must be examined by echocardiography at diagnosis and at annual follow-up, unless new-onset cardiac symptoms appear and demand prompt re-evaluation. However, it is an operator- and acoustic-window-dependent modality with poor reproducibility and that cannot perform tissue characterization.

Nuclear imaging can give information regarding ventricular function and perfusion but at a cost of radiation. Because patients with ARD will need long-term follow-up, radiation-free modalities are recommended for cardiac risk stratification. Furthermore, the low spatial resolution of nuclear imaging does not allow for detection of small subendocardial or intramyocardial lesions, which are frequently found in patients with ARDs.

Cardiac computed tomographic imaging can reliably detect stenotic lesions in the coronary arteries and therefore has an excellent negative predictive value to exclude coronary artery disease. However, it uses radiation and iodinated contrast agents that are harmful in allergic patients or in patients with compromised renal function.

CMR is the only nonradiating modality that can provide reliable and highly reproducible information about myocardial function, perfusion, and fibrosis. Its high spatial resolution and capability of performing tissue characterisation makes this modality ideal for patients with ARDs and facilitates the diagnosis of cardiac involvement at the early preclinical stages.

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Rheumatologists should routinely use echocardiography as a screening tool. However, a normal echocardiogram does not always exclude cardiac disease in patients with ARDs. It is very common to identify cardiac lesions, using CMR, at diagnosis of ARDs in patients without clinical evidence of cardiac involvement. Therefore, we recommend an initial CMR evaluation of patients with systemic ARDs at diagnosis and re-evaluation if patients feel anything unusual such as chest discomfort or pain, fatigue, mild shortness of breath, inability to deal with the usual everyday activities, and episodes of syncope and/or palpitations or other rhythm disturbances.

Rheumatology Advisor: What are the implications of CV imaging for clinical decision-making in rheumatology?

Dr Mavrogeni: The results of CV imaging can seriously affect both cardiac and antirheumatic treatment. If any ventricular dysfunction is observed on echocardiography, adequate cardiac medication should be started. However, echocardiography cannot detect the acuity of cardiac disease. This is the role of CMR – it gives information about edema, which is indicative of acute lesions and fibrosis that can occur during acute or chronic inflammation or as the result of myocardial infarction. The detection of acute myocardial inflammation demands modification of antirheumatic treatment even if the patient is asymptomatic. CMR is the only way to detect early cardiac involvement, because blood biomarkers of systemic inflammation may be negative or will be increased later, when a severe myocardial lesion will occur. Furthermore, the presence of fibrosis will change the cardiac approach. Evidence of subendocardial or transmural scar following the distribution of coronary arteries demands further assessment with cardiac catheterization. In contrast, if there is an intramyocardial or subepicardial scar, it is due to inflammation or vasculitis and coronary angiography is not needed. In any case, the presence of myocardial scarring demands clinical evaluation for cardiac arrhythmia and early start of angiotensin-converting enzyme inhibitors and/or beta-blockers to avoid evolution to heart failure and/or cardiac death.

After all, it is clear that CV imaging is not a luxury, but rather is a useful, absolutely necessary adjunct in the evaluation of cardiac involvement in ARDs that can change both the cardiac and antirheumatic treatment of these diseases.

Rheumatology Advisor: What else should rheumatologists know about CV imaging?

Dr Mavrogeni: Echocardiography and CMR are the cornerstones of CV imaging in rheumatology. Echocardiography should be used as an inexpensive, routine bedside modality both at diagnosis of ARDs and during annual follow-up. However, operator and acoustic-window dependency and inability to perform tissue characterization are serious limitations of echocardiography. Therefore, CMR should be considered as routine evaluation at diagnosis of every patient with a systemic ARD, because cardiac involvement with or without reduced left ventricular ejection fraction may occur years before the diagnosis of the systemic disease and should be treated before evolution to heart failure or development of life-threatening rhythm disturbances. The holistic approach offered by CMR can provide reliable and reproducible information about cardiac disease acuity, type of myocardial perfusion disturbances, and fibrosis. After the initial evaluation following diagnosis of an ARD, CMR is recommended for every patient who presents with typical or atypical cardiac symptoms including shortness of breath, rhythm disturbances, syncope, or persistent fatigue or weakness, particularly those patients with quiescent systemic disease and normal echocardiogram. Heart involvement, as detected by CMR, can completely change both cardiac and antirheumatic treatment leading to cardiovascular complications, such as life-threatening rhythm disturbances and heart failure. Use of CMR can also potentially lead to improvement in the increased morbidity and mortality seen in patients with ARD that is mainly due to cardiovascular involvement.

References

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  2. Zegkos T, Kitas G, Dimitroulas T. Cardiovascular risk in rheumatoid arthritis: assessment, management and next steps.Ther Adv Musculoskelet Dis. 2016;8:86-101.
  3. Bartels CM, Buhr KA, Goldberg JW, et al. Mortality and cardiovascular burden of systemic lupus erythematosus in a US population-based cohort. J Rheumatol. 2014;41:680-687.
  4. Aviña-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum. 2008;59:1690-1697.
  5. Peters MJL, van Halm VP, Voskuyl AE, et al. Does rheumatoid arthritis equal diabetes mellitus as an independent risk factor for cardiovascular disease? A prospective study. Arthritis Rheum. 2009;61:1571-1579.
  6. Agca R, Heslinga SC, Rollefstad S, et al. EULAR recommendations for cardiovascular disease risk management in patients with rheumatoid arthritis and other forms of inflammatory joint disorders: 2015/2016 update. Ann Rheum Dis. 2017;76:17-28.
  7. Giles JT. Cardiovascular disease in rheumatoid arthritis: current perspectives on assessing and mitigating risk in clinical practice. Best Pract Res Clin Rheumatol. 2015;29:597-613.
  8. Mavrogeni SI, Sfikakis PP, Dimitroulas T, et al. Can cardiovascular magnetic resonance prompt early cardiovascular/rheumatic treatment in autoimmune rheumatic diseases? Current practice and future perspectives [published March 7, 018]. Rheumatol Int. doi:10.1007/s00296-018-4004-6
  9. Fent GJ, Greenwood JP, Plein S, Buch MH. The role of non-invasive cardiovascular imaging in the assessment of cardiovascular risk in rheumatoid arthritis: where we are and where we need to be. Ann Rheum Dis. 2017;76(7):1169-1175.
  10. Gerster M, Peker E, Nagel E, Puntmann VO. Deciphering cardiac involvement in systemic inflammatory diseases: noninvasive tissue characterisation using cardiac magnetic resonance is key to improved patients’ care. Expert Rev Cardiovasc Ther. 2016;14(11):1283-1295.