Overview of heart disease in rheumatoid arthritis

INTRODUCTION — Various forms of heart disease occur in patients with rheumatoid arthritis (RA), including pericardial and myocardial disease, coronary artery disease, and disturbances in heart rhythm. Some of these conditions are more common in patients with RA than in the general population and contribute to an increased risk of death in affected patients.

An overview of the cardiac disorders seen in patients with RA is presented here. Coronary artery disease, heart failure (HF), and pericarditis in RA, as well as rheumatoid nodulosis, are discussed in more detail separately, as are noncardiac vascular diseases in patients with RA:

●(See "Coronary artery disease in rheumatoid arthritis: Pathogenesis, risk factors, clinical manifestations, and diagnostic implications" and "Coronary artery disease in rheumatoid arthritis: Implications for prevention and management".)

●(See "Heart failure in rheumatoid arthritis".)

●(See "Pericardial involvement in systemic autoimmune diseases", section on 'Rheumatoid arthritis'.)

●(See "Rheumatoid nodules", section on 'Cardiac nodules'.)

●(See "Overview of the systemic and nonarticular manifestations of rheumatoid arthritis", section on 'Noncardiac vascular disease'.)

FREQUENCY OF HEART DISEASE IN RHEUMATOID ARTHRITIS — There is an increased risk of coronary artery disease and heart failure (HF) in patients with rheumatoid arthritis (RA), and there may be an increased risk of atrial fibrillation (AF) [1,2]. Clinically apparent pericarditis and myocarditis are uncommon disorders in patients with RA. Evidence suggests that the overall risk of cardiac disease among patients with RA has declined since the 1980s, possibly owing, at least in part, to improved management of the underlying systemic inflammation of RA [3].

CORONARY ARTERY DISEASE

Pathogenesis, clinical manifestations, and diagnosis — The risks of sudden death and myocardial infarction appear to be increased in patients with rheumatoid arthritis (RA). Although a higher prevalence of traditional cardiac risk factors may be present in patients with RA than in the general population, epidemiologic data suggest that RA is an independent risk factor for coronary artery disease; the presence of chronic inflammation in RA is thought to enhance the development of atherosclerosis. The pathogenesis, risk, clinical manifestations, and diagnosis of coronary heart disease in patients with RA are presented in detail elsewhere. (See "Coronary artery disease in rheumatoid arthritis: Pathogenesis, risk factors, clinical manifestations, and diagnostic implications".)

Use of antiinflammatory drugs such as glucocorticoids and nonselective and cyclooxygenase (COX) 2 selective nonsteroidal antiinflammatory drugs (NSAIDs) may contribute to increased risk for coronary thrombosis. Some medications used in RA can adversely impact the lipoprotein profile, while simultaneously reducing vascular risk surrogates, including inflammatory markers, although the net effect on cardiovascular morbidity and mortality of such changes is unknown. (See "Coronary artery disease in rheumatoid arthritis: Pathogenesis, risk factors, clinical manifestations, and diagnostic implications", section on 'Risk factors'.)

The clinical manifestations and diagnosis of coronary artery disease are generally similar in patients with or without RA, but tend to be more severe in those with RA, although there is a decreased prevalence of clinical angina pectoris. For patients with RA ≥50 years of age, we perform a yearly assessment for symptoms and findings suggestive of coronary artery disease. (See "Coronary artery disease in rheumatoid arthritis: Pathogenesis, risk factors, clinical manifestations, and diagnostic implications", section on 'Clinical manifestations' and "Coronary artery disease in rheumatoid arthritis: Pathogenesis, risk factors, clinical manifestations, and diagnostic implications", section on 'Diagnosis and screening'.)

Prevention and management — The key elements in the prevention of coronary artery disease in patients with RA are optimization of antiinflammatory and immunomodulatory therapy to achieve effective disease control and aggressive management of traditional risk factors. The prevention and management of coronary artery disease in RA is discussed in detail separately. (See "Coronary artery disease in rheumatoid arthritis: Implications for prevention and management".)

Briefly, the primary prevention strategy in patients with RA is comparable with that for the general population. (See "Coronary artery disease in rheumatoid arthritis: Implications for prevention and management", section on 'General prevention measures'.)

RA drug therapy requires particular attention. NSAIDs should be used with particular caution in patients with RA, with attention to presence or absence of cardiovascular disease, the degree of risk for gastroduodenal damage, and the need for long-term oral anticoagulation or antiplatelet therapy. The risk of atherosclerosis associated with glucocorticoid use should be minimized by using the minimum effective dose of a glucocorticoid for the shortest possible time. (See "Coronary artery disease in rheumatoid arthritis: Implications for prevention and management", section on 'Nonsteroidal antiinflammatory drugs' and "Coronary artery disease in rheumatoid arthritis: Implications for prevention and management", section on 'Limiting glucocorticoid exposure'.)

Strict control of inflammation due to RA with both nonbiologic disease-modifying antirheumatic drugs (DMARDs; eg, methotrexate) and/or biologic DMARDs (eg, tumor necrosis factor [TNF] inhibitors) reduces the increased cardiovascular risk seen in patients with RA. While in general, control of inflammation is considered beneficial for cardiovascular risk, in 2021, the US Food and Drug Administration (FDA) issued a black box warning for the targeted synthetic DMARDs, Janus kinase (JAK) inhibitors, regarding concern for higher cardiovascular events compared with TNF inhibitors [4]. (See "Coronary artery disease in rheumatoid arthritis: Implications for prevention and management", section on 'DMARDs for control of inflammation due to RA' and "Overview of the Janus kinase inhibitors for rheumatologic and other inflammatory disorders", section on 'Restrictions' and "Overview of the Janus kinase inhibitors for rheumatologic and other inflammatory disorders", section on 'Cardiovascular'.)

HEART FAILURE AND LEFT VENTRICULAR DYSFUNCTION — There is an increased incidence of heart failure (HF) in patients with rheumatoid arthritis (RA) compared with the general population. HF may contribute to the shortened life expectancy observed in RA, while efforts to reduce the risk of HF in patients with RA may substantially improve survival. HF in RA is discussed in detail separately. (See "Heart failure in rheumatoid arthritis".)

Briefly, symptomatic HF may occur with either a reduced left ventricular (LV) ejection fraction (HFrEF) or a preserved LV ejection fraction (HFpEF). HFrEF was historically identified as LV systolic dysfunction and HFpEF as LV diastolic dysfunction. LV systolic dysfunction may be severalfold more common in patients with RA than in the general population, although it appears less common in RA than diastolic dysfunction; diastolic dysfunction is also more frequent in patients with RA than in healthy controls. (See "Heart failure in rheumatoid arthritis", section on 'Overview and terms' and "Heart failure in rheumatoid arthritis", section on 'Epidemiology'.)

Etiopathogenic mechanisms that can be responsible for an increased risk of HF in RA may include inflammatory mediators, antirheumatic drug therapy (eg, glucocorticoids, nonsteroidal antiinflammatory drugs [NSAIDs], and antimalarials), ischemic heart disease, and amyloidosis. (See "Heart failure in rheumatoid arthritis", section on 'Etiology and pathogenesis'.)

The clinical manifestations, diagnosis, and management of HF in RA are similar to that in patients without RA, but particular consideration also needs to be given to RA drug therapy, which may impact risk and management. (See "Heart failure in rheumatoid arthritis" and "Heart failure in rheumatoid arthritis", section on 'Clinical manifestations' and "Heart failure in rheumatoid arthritis", section on 'Evaluation and diagnosis' and "Heart failure in rheumatoid arthritis", section on 'Prevention' and "Heart failure in rheumatoid arthritis", section on 'Management'.)

MYOCARDITIS

Types of myocarditis in rheumatoid arthritis — Clinically evident myocarditis can be either granulomatous or interstitial, is rare in rheumatoid arthritis (RA), and is usually associated with active articular disease and with other nonarticular manifestations [5]. Granulomatous myocarditis has higher specificity for RA, while the interstitial form is much less frequent in RA than in systemic lupus erythematosus (SLE). Direct granulomatous involvement of the endocardium can produce mitral insufficiency, while involvement of the conduction system can induce atrioventricular block.

Imaging evidence of myocardial inflammation in rheumatoid arthritis — Studies using cardiac magnetic resonance imaging (MRI) and 18-fluorodeoxyglucose (FDG) positron emission tomography (PET) imaging have revealed frequent imaging evidence of myocardial inflammation. In a study of 39 patients with RA without known heart disease, who were under age 65, and 39 matched controls, 46 percent of the patients with RA but none of the controls had evidence of focal fibrosis on cardiac MRI, which included T1-mapping, with T2-weighted and late gadolinium enhancement imaging [6]. Diffuse myocardial fibrosis and inflammation were also evident among the patients with RA, and the fibrotic and inflammatory changes were associated with impaired strain and RA disease activity. Similarly, in a study of 119 patients with RA, 18 and 39 percent of patients had visually or quantitatively enhanced myocardial uptake of 18-FDG on PET imaging, respectively, as evidence of myocardial inflammation [7]. PET evidence of myocardial inflammation was associated with higher clinical disease activity scores, and was reduced among those treated with tumor necrosis factor (TNF) alpha inhibitors, and non-TNF alpha targeted biologics, compared with patients treated with conventional disease-modifying antirheumatic drugs (DMARDs) [7,8].

Clinical manifestations and diagnosis — Myocarditis should be suspected in patients with or without cardiac signs and symptoms (table 1) who present with a rise in cardiac biomarker levels, change in electrocardiogram (ECG) suggestive of acute myocardial injury, arrhythmia, or abnormalities of ventricular systolic function, particularly if these clinical findings are new and unexplained. (See "Clinical manifestations and diagnosis of myocarditis in adults", section on 'When to suspect myocarditis'.)

The approach to evaluation and diagnosis of myocarditis is the same as in patients without RA. It generally involves a careful history and examination, laboratory studies, and imaging. Patients may also require cardiac catheterization and endomyocardial biopsy, as described separately. (See "Clinical manifestations and diagnosis of myocarditis in adults".)

Treatment — Because of the rarity of clinically evident rheumatoid myocarditis, optimal treatment is uncertain. In one reported case of heart failure (HF) due to rheumatoid vasculitis with myocardial involvement that was detected by right ventricular biopsy, a favorable response to glucocorticoid therapy was noted [9]. High-dose methylprednisolone (pulse therapy 500 to 1000 mg/day for three days or 80 mg daily) may be beneficial as initial therapy. The general approach to the treatment of myocarditis is described separately. (See "Treatment and prognosis of myocarditis in adults".)

Immunosuppressive therapies such as azathioprine and cyclophosphamide, as used for the treatment of systemic rheumatoid vasculitis, are other options for patients who do not respond to glucocorticoids. The role of biologic therapies in the management of rheumatoid myocarditis is uncertain. (See "Treatment of rheumatoid vasculitis".)

Use of a TNF inhibitor or non-TNF alpha targeted biologic could be considered for a patient with mild HF or with other manifestations of myocarditis, and there is evidence that such treatments may reduce imaging evidence of myocardial inflammation and fibrosis [7,8]. However, high doses of anti-TNF agents have been associated with increased severity and mortality when used in patients with severe HF (New York Heart Association [NYHA] class III or IV HF) of other etiologies, and their use in RA patients with moderate to severe HF should probably be avoided in this setting. (See "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects", section on 'Heart failure'.)

Subclinical myocardial disease observed on imaging or biomarker elevation — Subclinical myocardial disease is relatively common in patients with RA [6,10], while clinical myocarditis with or without left ventricular (LV) dysfunction is a rarer manifestation. While there are no recommendations for treating asymptomatic myocardial inflammation detected by these modalities, the presence of subclinical myocarditis may signify underlying disease activity and could prompt consideration of targeted biologic therapy, although not in the presence of LV dysfunction. Even less common, asymptomatic myocardial inflammation in the presence of asymptomatic LV dysfunction should prompt further evaluation and treatment of HF with a reduced LV ejection fraction (HFrEF) with guideline-directed medical therapy. (See "Heart failure in rheumatoid arthritis", section on 'Evaluation and diagnosis'.)

ATRIAL FIBRILLATION — Risk factors for atrial fibrillation (AF), including heart failure (HF), ischemic heart disease, and cigarette smoking, are increased in patients with rheumatoid arthritis (RA). However, there are limited studies on AF and RA, and results of the analyses are inconsistent. A nationwide cohort study in Denmark involving 18,247 patients with RA followed for a median of 4.8 years found a significant increase in the risk of AF in patients with RA, compared with age- and sex-matched controls from the general population (event rates of 8.2 versus 6 per 1000 person-years) [2]. This represented a greater than 40 percent increase in the incidence of AF in RA (adjusted incidence rate ratio 1.41, 95% CI 1.31-1.51). By contrast, a United States-based cohort study of 20,852 RA and 104,260 non-RA patients found no difference in risk of AF after adjusting for comorbidities, medications, and health care utilization [11].

The incidence of stroke was also increased in the Danish cohort of patients with RA. The relative risks of both AF and stroke were increased to a greater extent in younger patients, while the absolute differences in risk were higher in older patients. (See "Overview of the systemic and nonarticular manifestations of rheumatoid arthritis", section on 'Stroke'.)

The management of AF in patients with RA does not differ from patients without RA. (See "Atrial fibrillation: Overview and management of new-onset atrial fibrillation".)

OTHER CARDIAC DISORDERS

Pericarditis — Clinical episodes of pericarditis are uncommon in rheumatoid arthritis (RA), but asymptomatic disease is more often detected by echocardiography or on autopsy. Restrictive pericarditis with tamponade physiology is very uncommon. Pericarditis occurs most frequently in patients with active seropositive RA and other extraarticular manifestations. Rheumatoid pericarditis and its management are discussed separately. (See "Pericardial involvement in systemic autoimmune diseases", section on 'Rheumatoid arthritis' and "Pericardial effusion: Approach to diagnosis".)

Rheumatoid nodules — Rheumatoid nodules may develop in the pericardium, myocardium, and valvular structures; although symptoms related to the presence of nodules are rare, syncope or death due to heart block from a lesion situated in the conduction system can occur. Stroke or other manifestations of arterial embolization, as well as valvular insufficiency, may result from nodules on a heart valve. Nodules may be detected echocardiographically. (See "Rheumatoid nodules", section on 'Cardiac nodules'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Rheumatoid arthritis" and "Society guideline links: Heart failure in adults" and "Society guideline links: Assessment of cardiovascular risk".)

SUMMARY AND RECOMMENDATIONS

●The risks of sudden death and myocardial infarction appear to be increased in patients with rheumatoid arthritis (RA). In addition to traditional cardiac risk factors, data suggest that RA is an independent risk factor for coronary artery disease, probably due to the chronic inflammation that can be present in RA and its effects upon atherosclerotic disease. Some medications may increase risk (eg, nonsteroidal antiinflammatory drugs [NSAIDs]), while others may decrease such risk. The clinical manifestations and diagnosis of coronary artery disease in RA are generally similar to patients without RA, but manifestations generally tend to be more severe in those with RA, although there is a decreased prevalence of clinical angina pectoris. (See 'Pathogenesis, clinical manifestations, and diagnosis' above and "Coronary artery disease in rheumatoid arthritis: Pathogenesis, risk factors, clinical manifestations, and diagnostic implications".)

●The key elements in the prevention of coronary artery disease in patients with RA are optimization of antiinflammatory and immunomodulatory therapy to achieve effective disease control and aggressive management of traditional risk factors. The primary prevention strategy in patients with RA is comparable with that for the general population. Strict control of inflammation due to RA with both nonbiologic disease-modifying antirheumatic drugs (DMARDs; eg, methotrexate) and/or biologic DMARDs (eg, tumor necrosis factor [TNF] inhibitors) reduces the increased cardiovascular risk. (See 'Prevention and management' above and "Coronary artery disease in rheumatoid arthritis: Implications for prevention and management".)

●There is an increased risk of heart failure (HF) in patients with RA compared with the general population. Symptomatic HF may occur with either a reduced left ventricular (LV) ejection fraction (HFrEF; LV systolic dysfunction) or a preserved LV ejection fraction (HFpEF; LV diastolic dysfunction). Both are more common in patients with RA than in the general population; in RA, systolic dysfunction is less common than diastolic dysfunction, unlike in the general population. (See 'Heart failure and left ventricular dysfunction' above and "Heart failure in rheumatoid arthritis".)

●The clinical manifestations, diagnosis, and management of HF in RA are similar to that in patients without RA, but particular consideration also needs to be given to RA drug therapy, which may impact risk and management. (See 'Heart failure and left ventricular dysfunction' above and "Heart failure in rheumatoid arthritis".)

●Clinically evident myocarditis can be either granulomatous or interstitial, is rare in RA, and is usually associated with active articular disease and with other nonarticular manifestations. Myocarditis should be suspected in patients who present with a rise in cardiac biomarker levels, change in ECG suggestive of acute myocardial injury, arrhythmia, or abnormalities of ventricular systolic function, particularly if these clinical findings are new and unexplained. (See 'Myocarditis' above.)

●Risk factors for atrial fibrillation (AF), including HF, ischemic heart disease, and cigarette smoking, are increased in patients with RA. (See 'Atrial fibrillation' above.)

●Clinically apparent pericarditis and the presence of rheumatoid nodules in the pericardium, myocardium, or valvular structures are uncommon in patients with RA, but may occur. (See 'Pericarditis' above and 'Rheumatoid nodules' above.)