Heart failure in rheumatoid arthritis

INTRODUCTION — Various forms of heart disease occur in patients with rheumatoid arthritis (RA), such as heart failure (HF) and other conditions, 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.

The pathogenesis, manifestations, evaluation, and management of HF in patients with RA are described here. Coronary artery disease and other cardiac disorders in RA 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" and "Pericardial involvement in systemic autoimmune diseases", section on 'Rheumatoid arthritis' and "Rheumatoid nodules", section on 'Cardiac nodules' and "Overview of heart disease in rheumatoid arthritis".)

OVERVIEW AND TERMS — There is an increased incidence of heart failure (HF) in patients with rheumatoid arthritis (RA) compared with the general population, and HF may contribute to the shortened life expectancy observed in RA. Symptomatic HF may occur with either a reduced left ventricular (LV) ejection fraction (HFrEF) or a preserved LV ejection fraction (HFpEF); these two forms of HF were previously referred to as LV systolic dysfunction and LV diastolic dysfunction, respectively. HFrEF, HFpEF, and asymptomatic LV systolic dysfunction are more prevalent among patients with RA than in the general population. Attempts to reduce the risk of HF in patients with RA may substantially improve their survival.

Because most studies of HF in RA were performed prior to the distinctions of HFrEF and HFpEF, this topic review largely refers to prior descriptions of undifferentiated HF or HF associated with LV systolic or diastolic dysfunction. While the prior classifications of LV systolic or diastolic dysfunction generally correspond to HFrEF and HFpEF, respectively, these definitions are not entirely interchangeable, as the newer classifications use specific ejection fraction cutoffs to classify patients for each condition, and other features also distinguish these conditions.

The distinctions between HFrEF and HFpEF, as well as differences between the terms HFpEF and diastolic dysfunction, are described in detail separately. (See "Pathophysiology of heart failure with preserved ejection fraction", section on 'Terminology'.)

ETIOLOGY AND PATHOGENESIS — Etiopathogenic mechanisms that can be responsible for an increased risk of heart failure (HF) in rheumatoid arthritis (RA) may include inflammatory mediators, antirheumatic drug therapy, ischemic heart disease, and amyloidosis:

Inflammation — Inflammatory stimuli may be involved in the initiation of HF in RA [1]. In a longitudinal cohort study of 9087 patients with RA, the 10-year incidence of HF was 8.2 percent [2]. Elevated inflammation (defined as an erythrocyte sedimentation rate or C-reactive protein above the upper limit of normal) was associated with an increased risk of HF with preserved ejection fraction (HFpEF; hazard ratio [HR] 1.45) but not HF with reduced ejection fraction (HFrEF). In another longitudinal study of 9889 patients with RA and 9889 controls, a 21 percent increased risk of HF was observed in RA versus controls, with elevated levels of C-reactive protein predicting HFpEF (HR 1.24) and HFrEF (1.17) [3]. Previous studies have also associated laboratory measures of inflammation with the risk of HF [4,5].

Antirheumatic drug therapy — Medications used in the treatment of RA, particularly glucocorticoids and nonsteroidal antiinflammatory drugs (NSAIDs) may contribute to HF, and antimalarials are a rare cause of cardiomyopathy, but tumor necrosis factor (TNF) inhibitors do not appear to increase HF risk in patients with RA:

●Glucocorticoids – Therapeutic use of glucocorticoids has been associated with dose-dependent increased rates of HF, as well as myocardial infarction, stroke, and all-cause mortality [6,7].

In a large observational study, the risk of HF appeared to increase with the daily dose of glucocorticoids prescribed, with a rate ratio of 3.72 (95% CI 2.71-5.12) with ≥7.5 mg/day of prednisone or its equivalent compared with nonusers [6]. The cardiovascular risk was higher for those who had continuing prescriptions than for those who had intermittent prescribing of glucocorticoids, and it was higher for those using glucocorticoids during the six months prior to the cardiovascular event versus those who used glucocorticoids at an earlier time. (See "Major adverse effects of systemic glucocorticoids", section on 'Cardiovascular effects'.)

An association of glucocorticoid-related risk was illustrated in a population-based study from the Rochester Epidemiology Project that reported that rheumatoid factor (RF)-positive patients, particularly those with high cumulative exposure to glucocorticoids, high average daily dose, and recent use, were at increased risk of cardiovascular events, including myocardial infarction, HF, and death from cardiovascular causes [8]. The RF-positive patients with high cumulative exposure had a threefold increased risk (hazard ratio [HR] 3.06, 95% CI 1.81-5.18), which persisted after adjustments for demographic features, baseline cardiovascular risk factors, and RA characteristics. By contrast, RF-negative patients were not at increased risk of cardiovascular events, regardless of glucocorticoid exposure. The observed association between glucocorticoids and HF remain challenging to study. While glucocorticoids can reduce inflammation, they can also exacerbate HF, thus confounding the association.

●NSAIDs – Nonsteroidal antiinflammatory drug (NSAID) use is rarely associated with a first occurrence of HF; however, it can cause a worsening of preexisting HF. The major mechanism for HF exacerbation is an increase in afterload resulting from NSAID-induced systemic vasoconstriction, which can lead to a further reduction in cardiac contractility and cardiac output in advanced HF. The risk of HF in patients using NSAIDs is discussed in detail separately. (See "NSAIDs: Adverse cardiovascular effects", section on 'NSAIDs and heart failure'.)

●Antimalarial drugs – Antimalarial drugs such as chloroquine and hydroxychloroquine can cause a drug-induced cardiomyopathy. This complication of antimalarial drugs is discussed in detail elsewhere. (See "Drug-induced myopathies", section on 'Chloroquine/hydroxychloroquine'.)

●TNF inhibitors – Tumor necrosis factor (TNF) inhibitors may increase the risk of HF in patients with RA, but in patients without moderate to severe HF, these agents are generally well tolerated. The risk of HF from use of TNF inhibitors is described in detail separately. (See "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects", section on 'Heart failure'.)

Ischemic heart disease — Ischemic cardiomyopathy is the most common cause of HF due to systolic dysfunction in the general population. HF is also likely to result from an ischemic cardiomyopathy in a significant percentage of patients with RA, given that the prevalence of coronary disease is increased in patients with RA compared with the general population [9]. (See "Epidemiology of heart failure" and "Coronary artery disease in rheumatoid arthritis: Pathogenesis, risk factors, clinical manifestations, and diagnostic implications", section on 'Epidemiology'.)

However, among a cohort of patients with RA with a high incidence of HF, the cumulative incidence of symptomatic ischemic heart disease, including angina and hospitalization for myocardial infarction, was not significantly different from that of age- and sex-matched controls [10]. The 30-year incidence among patients with RA was 38 versus 35 percent in the control group. (See "Coronary artery disease in rheumatoid arthritis: Implications for prevention and management".)

Nonselective NSAIDs and cyclooxygenase 2 (COX-2) selective inhibitors can also have adverse effects on the cardiovascular system, leading to ischemic heart disease. At least two NSAIDs can interfere with the cardioprotective effects of aspirin. (See "NSAIDs: Adverse cardiovascular effects".)

Amyloidosis — AA (secondary) amyloidosis due to RA can cause HF due to an infiltrative cardiomyopathy. This complication of RA is now extremely rare. (See "Causes and diagnosis of AA amyloidosis and relation to rheumatic diseases" and "Cardiac amyloidosis: Epidemiology, clinical manifestations, and diagnosis".)

EPIDEMIOLOGY

Population-based studies — The incidence of heart failure (HF) in patients with rheumatoid arthritis (RA) is increased compared with a population of similar age and sex distribution without RA and is independent of other cardiovascular risk factors [8,10-12]. A number of population- and registry-based studies have provided estimates of the incidence, prevalence, and prognosis of HF in RA [10-16].

One of the largest case-control studies, from Denmark, involving 51,859 patients with RA and 256,653 age- and sex-matched controls without RA, observed an increased risk of HF for patients with incident RA both with and without ischemic heart disease over a 10-year follow-up period (hazard ratio [HR] 2.06, 95% CI 1.90-2.24, and 1.23, 95% CI 1.20-1.23, respectively) [16]. A persistent increased risk of HF was observed up to 10 years following RA onset in this large cohort, which may not have been observed in smaller cohorts [15] due to decreased sensitivity.

Findings in these studies have also included evidence of a higher incidence of HF among patients with RA compared with patients without RA after adjustment for cardiovascular risk factors (adjusted incidence ratio 1.61, 95% CI 1.43-1.83) [14]; and another after adjustment for age, sex, known cardiovascular risk factors, and the presence of ischemic heart disease (1.99 versus 1.16 cases per 100 person-years, respectively) [11,12]. Others showed a higher cumulative incidence of HF but not ischemic heart disease in those with RA (37 versus 28 percent, at 30 years of follow-up) [10], and that RA patients have a higher risk of nonischemic compared with ischemic HF in the year after RA onset, although the frequency of HF was not increased in RA prior to disease onset [15].

LV systolic dysfunction/HFrEF — Left ventricular (LV) systolic dysfunction and heart failure with reduced LV ejection fraction (HFrEF) may be severalfold more common in patients with RA than in the general population, although they appear to be less common in RA than diastolic dysfunction [17]. However, few data exist concerning the prevalence of LV systolic dysfunction in patients with RA.

In one cross-sectional study that compared 226 patients with RA with 3960 members of the general population, LV systolic dysfunction, defined as an LV ejection fraction (LVEF) <40 percent on echocardiography, was more common in patients with RA (5.3 versus 1.8 percent) [18]; even after adjustment for hypertension, diabetes, and exposure to cigarette smoke, all of which were greater among the RA patients, LV systolic dysfunction was still 3.2 times more common in the RA group.

In another cross-sectional study, involving 157 RA patients, the prevalence of HFrEF was much lower than heart failure with preserved LV ejection fraction (HFpEF; slightly over 1 versus 23 percent) [5].

Diastolic dysfunction/HFpEF — Diastolic dysfunction and heart failure with preserved LV ejection fraction (HFpEF) are more frequent in patients with RA than in healthy controls [19-22] and are much more common than systolic dysfunction [17]. Increased risk is associated with advancing age and with disease severity and duration [5,17].

●Frequency and risk of diastolic dysfunction – Typically, epidemiologic studies have used Doppler echocardiography to assess diastolic heart function. Such measurements usually consist of transmitral blood flow velocity measured in early diastole (E) and late diastole corresponding to atrial contraction (A), and the ratio of these velocities (E/A ratio); or measurements of the velocity of septal myocardium adjacent to the mitral valve annulus during systole (Sa), early diastole (Ea or E'), and atrial contraction (Aa or A') using tissue Doppler assessments (see "Heart failure with preserved ejection fraction: Clinical manifestations and diagnosis"). As an example of such studies, a higher prevalence of impaired LV diastolic relaxation was found in a group of 47 patients with RA of at least five years' duration compared with healthy age- and sex-matched controls (66 versus 43 percent) [22]. Similarly, in another cross-sectional study, the prevalence of at least mild diastolic dysfunction was increased in patients with RA versus age- and sex-matched controls (59 versus 39 percent) [5].

As in the general population, the prevalence of diastolic dysfunction increases with age. While some studies suggested that RA disease duration is a risk factor that is independent of patient age [19,21], another study showed that the prevalence of HF, predominantly diastolic, was significantly related in patients with RA to both age and disease duration [5]. In a series of 100 RA patients, the presence of LV diastolic dysfunction was more prevalent than LV systolic dysfunction (55 versus 9 patients), and LV dysfunction overall was related to both RA disease severity and disease duration [17]. Over a five-year period, the rate of progression of diastolic dysfunction was more rapid in a cohort of 160 patients with RA compared with 1391 non-RA controls [23].

Consistent with the high risk of progression in this population, a prospective cohort of 217 RA patients without diastolic dysfunction at baseline demonstrated a 24 percent incidence of new echocardiographic diastolic dysfunction at one year [24]. Multivariate analysis revealed that decreased E/A ratios in transmitral Doppler flow waveforms (but not meeting criteria for diastolic dysfunction), age, and elevated systolic pressures were independent predictors of incident diastolic dysfunction. It has been suggested that these risk factors could be used to monitor high-risk subpopulations with RA for early intervention, with the notion that subclinical LV diastolic dysfunction may represent an early risk factor for the development of HFpEF and, potentially, HFrEF in RA.

●LV hypertrophy – LV hypertrophy (LVH) is a recognized cause of diastolic HF, but it is unclear whether LV mass is higher or lower in RA patients compared with controls. In a study of 89 RA patients without clinical cardiovascular disease and 89 healthy matched controls who were examined echocardiographically, the prevalence of LVH was significantly greater in those with RA than in controls (18 versus 6.7 percent, respectively) [25].

By contrast, a study of 75 RA patients and 225 matched controls, also without clinical cardiovascular disease, found that LV mass was lower in RA patients than in controls when measured using cardiac magnetic resonance imaging (MRI), with the mean LV mass in RA patients being 18 percent lower than in controls [26]; similar findings were observed in a subsequent study performed in an independent cohort [27]. End diastolic volumes did not significantly differ between the two groups. When a population of 157 patients with RA and 77 matched controls (not selected for the presence or absence of cardiovascular disease) was analyzed, the echocardiographic LV mass index was significantly greater among women with RA compared with controls (95 versus 83 g/m²) but not significantly changed in men with RA compared with controls [5].

●Preclinical right-sided diastolic dysfunction – There is some evidence that preclinical right-sided diastolic dysfunction may exist in the RA population as a possible sign of increased risk for cardiopulmonary disease. In one study, 35 RA patients and 30 healthy subjects, all without HF, were examined with Doppler echocardiography [28]. Impaired right ventricular (RV) filling, an index of RV diastolic function, was noted in 34 percent of the RA patients but only 7 percent of the controls.

CLINICAL MANIFESTATIONS — There are two major categories of symptoms and physical findings in heart failure (HF) (see "Heart failure: Clinical manifestations and diagnosis in adults"):

●Those due to excess fluid accumulation, including dyspnea, edema, hepatic congestion, and ascites.

●Those caused by reductions in cardiac output, including fatigue and weakness, which are most pronounced with exertion. Patients with rheumatoid arthritis (RA) and HF may experience fewer exertional symptoms than patients with HF who do not have RA, at least in part because RA patients have impaired mobility [29].

EVALUATION AND DIAGNOSIS — The evaluation and diagnosis of heart failure (HF) in patients with rheumatoid arthritis (RA) generally does not differ from that in persons without RA. Several key considerations include the following:

●Clinical suspicion of symptomatic heart failure – Patients suspected of HF based upon symptoms and findings suggesting excess fluid accumulation and reduced cardiac output should be evaluated for HF. (See 'Clinical manifestations' above.)

●Similar approach to patients without rheumatoid arthritis – The approach to the patient with HF with or without RA uses the history, physical examination, laboratory studies, chest radiograph, electrocardiography (ECG), and echocardiogram to establish the diagnosis, determine the etiology, and assess severity. (See "Heart failure: Clinical manifestations and diagnosis in adults" and "Determining the etiology and severity of heart failure or cardiomyopathy".)

●Rheumatoid arthritis-specific considerations – There are additional issues related to etiology that are particularly relevant in patients with RA:

•The potential role of some antirheumatic drugs, which may cause and/or exacerbate HF. (See 'Etiology and pathogenesis' above and "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects", section on 'Heart failure'.)

•The possible role of AA (secondary) amyloidosis as a cause of infiltrative cardiomyopathy, although the frequency is much lower than in other common forms of amyloidosis. If present, other systemic involvement due to AA amyloid usually accompanies HF, particularly renal disease. Biopsy is required for pathologic diagnosis, while T1-weighted cardiac magnetic resonance imaging (MRI) and technetium-99m-pyrophosphate scintigraphy may also be helpful. (See "Causes and diagnosis of AA amyloidosis and relation to rheumatic diseases" and "Cardiac amyloidosis: Epidemiology, clinical manifestations, and diagnosis".)

●Screening for asymptomatic LV dysfunction generally not needed – In general, screening for asymptomatic left ventricular (LV) dysfunction is not recommended in patients with or without RA. Thus, the diagnosis of asymptomatic LV dysfunction is usually made by echocardiography or other cardiac imaging performed for another indication.

The frequency with which this occurs was evaluated in a study of 226 consecutive patients with RA who underwent clinical evaluation, ECG, echocardiography, and measurements of plasma levels of brain natriuretic peptide (BNP) [18]. Eight patients (3.5 percent) had asymptomatic LV dysfunction with an LV ejection fraction (LVEF) ≤50 percent. Most such patients had an abnormal ECG.

A study examining incident cases of LV diastolic dysfunction in RA patients suggested that risk factors of diminished E/A ratios in mitral valve inflow waveforms, advanced age, and elevated systolic blood pressure may identify patients that would benefit from early screening and intervention [24]. It is not known if similar criteria might be applied to identify individuals with high risk for LV dysfunction. (See "Approach to diagnosis of asymptomatic left ventricular systolic dysfunction" and "Management and prognosis of asymptomatic left ventricular systolic dysfunction".)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis includes disorders in patients with rheumatoid arthritis (RA) that can produce symptoms, signs, and/or imaging findings similar to those observed with heart failure (HF). These include:

●Interstitial lung disease – Symptoms and signs of interstitial lung disease, caused by either active alveolitis or fibrosis due to previous lung inflammation, can be confused with the manifestations of HF. Rales may be audible, and the interstitial fibrosis demonstrated by chest radiography may be difficult to distinguish from interstitial edema caused by HF.

In this setting, echocardiography provides important diagnostic information related to ventricular size and function. A high-resolution computed tomography (CT) scan of the chest is useful in assessing the lung disease. (See "Interstitial lung disease in rheumatoid arthritis".)

●Pericardial disease – Pericardial disease, particularly effusion without tamponade, is a common finding in RA. Both HF and a pericardial effusion without tamponade can be associated with an enlarged cardiac silhouette on chest radiography. The signs and symptoms of constrictive pericardial disease and/or cardiac tamponade can be confused with HF (see "Cardiac tamponade" and "Constrictive pericarditis: Diagnostic evaluation"). These disorders can be distinguished by findings on echocardiography, which is the method of choice for evaluating most pericardial diseases. (See "Echocardiographic evaluation of the pericardium".)

PREVENTION — Attention to risk factors for heart failure (HF) that have been identified in the general population, and to some factors more specific to those with rheumatoid arthritis (RA), may reduce the risk of HF. Interventions addressing these risk factors for HF are appropriate for those with RA. Prevention of HF in the general population is discussed in detail elsewhere. (See "Epidemiology of heart failure", section on 'Prevention of heart failure'.)

●Role of risk factors also seen in general population – Some data suggest a higher prevalence of established risk factors for HF in patients with RA compared with the general population. These risk factors include longstanding hypertension, coronary artery disease, diabetes mellitus, cigarette smoking, obesity, and left ventricular (LV) hypertrophy (LVH) [18]. (See "Coronary artery disease in rheumatoid arthritis: Implications for prevention and management".)

●Role of rheumatoid arthritis drug therapy – In addition to risk factor modification, effective treatment of RA may also reduce the incidence of HF. As examples, large observational studies have shown reduced risk of hospitalization for HF in patients receiving conventional synthetic disease-modifying antirheumatic drugs (DMARDs) and in those receiving tumor necrosis factor (TNF) inhibitors [30]; TNF inhibitors have been shown to reduce the elevated risk of HF in patients with RA compared with patients not receiving such therapy (3.1 versus 3.8 percent) [31]; and TNF inhibitor use in patients with active RA but no clinical signs of HF was associated with reduced levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) [32].

If TNF inhibitor therapy has a beneficial cardiac effect in RA, it is most likely to be due to control of the inflammatory process. Randomized trials of such therapy in patients with HF have found either no effect or a possible effect. In addition, new-onset HF has been described in a small number of patients on such treatment in the absence of major cardiovascular risk factors. The labels of etanercept, infliximab, and adalimumab contain the following disease-related concern: "Use with caution in patients with HF or decreased LV function; worsening and new-onset HF has been reported." The supportive data are discussed elsewhere. (See "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects", section on 'Heart failure'.)

For non-TNF inhibitor biologic therapies, limited data exist. The US Food and Drug Administration (FDA) issued a black box warning in September 2021 for increased risk of serious heart-related events in patients taking Janus kinase (JAK) inhibitor compared with a TNF inhibitor. We are awaiting publication for detailed information on the heart-related events. By contrast, anakinra and tocilizumab may have beneficial effects; both have been shown to reduce NT-proBNP levels, a measure of myocardial stretch used to assess HF [33,34].

MANAGEMENT — There are two management issues that must be addressed in rheumatoid arthritis (RA) patients with heart failure (HF): avoidance of exacerbation of HF while treating RA and specific therapy of the HF.

Approaches particular to rheumatoid arthritis patients with heart failure — In patients with RA and HF we take the following approach to avoid exacerbation of HF:

●General approach to selecting antirheumatic therapy – Drugs without significant risk of cardiotoxicity, such as antimalarial drugs (except in severe HF), methotrexate, rituximab, and abatacept, are preferred as initial therapy for patients with RA and HF, rather than tumor necrosis factor (TNF) inhibitors, nonsteroidal antiinflammatory drugs (NSAIDs), and glucocorticoids, which all can have adverse effects in RA patients with HF.

We suggest not administering TNF inhibitors at any dose in patients with symptomatic systolic left ventricular (LV) dysfunction. (See 'Etiology and pathogenesis' above and "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects", section on 'Heart failure'.)

In patients with severe HF, we also avoid antimalarials. (See "General principles and overview of management of rheumatoid arthritis in adults".)

We do not avoid interleukin (IL) 6 inhibitors, Janus kinase (JAK) inhibitors, or rituximab in patients with HF, as problems with these agents have not been described, but specific data regarding their safety in HF is lacking.

●Mild heart failure – For patients with RA and mild HF (New York Heart Association [NYHA] functional class I or II) (table 1) whose arthritis is refractory to other disease-modifying antirheumatic drugs (DMARDs) or biologic agents, targeted TNF inhibition might be considered but requires close monitoring. If the use of TNF inhibitor treatment is entertained, we suggest the following (see "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects", section on 'Heart failure'):

•Cardiology consultation

•Baseline echocardiography, with repeat echocardiography to be obtained based on changes in clinical status and current heart failure guidelines (see "Overview of the management of heart failure with reduced ejection fraction in adults", section on 'Follow-up and preventive care' and "Determining the etiology and severity of heart failure or cardiomyopathy", section on 'Echocardiography')

•Close follow-up

•Avoidance of high TNF inhibitor doses (eg, more than infliximab 3 mg/kg, adalimumab 40 mg every two weeks, or etanercept 50 mg/week)

•Prompt discontinuation of TNF inhibitor therapy if HF worsens

●Patients with known LV dysfunction – We suggest avoiding NSAIDs (except low-dose aspirin being used for cardioprotection) and selective cyclooxygenase 2 (COX-2) inhibitors in patients with known symptomatic LV dysfunction (see "NSAIDs: Adverse cardiovascular effects", section on 'NSAIDs and heart failure'). Glucocorticoids should also be used in the lowest possible dose for the shortest time in such patients. Caution is required in the use of DMARDs that are excreted primarily by the kidneys (eg, methotrexate and antimalarial drugs) because glomerular filtration may be reduced in HF.

●New heart failure during treatment for rheumatoid arthritis – For patients who develop HF while receiving treatment for RA, we discontinue any TNF inhibitors and NSAIDs. In addition, we reduce glucocorticoid gradually as tolerated to the lowest possible dose and discontinued when feasible. (See "Glucocorticoid withdrawal".)

General approach to heart failure management — The treatment of HF itself in patients with RA is similar to that in those without RA and is discussed in detail separately. (See "Treatment and prognosis of heart failure with preserved ejection fraction" and "Overview of the management of heart failure with reduced ejection fraction in adults".)

PROGNOSIS — Rheumatoid arthritis (RA) is associated with an increased mortality rate compared with individuals from the general population of the same age and sex, and several studies indicate that deaths are attributed to heart failure (HF) more often for patients with RA than for the general population. This difference appears to be the result of an increased incidence of HF in RA rather than a worse prognosis once HF develops [10,35].

Among hospitalized patients in the United States, there was an increase in mortality from 2005 to 2014 among individuals with RA and HF that was associated with the presence of age, chronic obstructive pulmonary disease, cerebrovascular disease, and renal disease [36]. An increase in hospitalization rate among individuals with HF and RA compared with HF patients without RA appeared in another study to be driven primarily by noncardiovascular hospitalizations [37].

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: Heart failure in adults".)

SUMMARY AND RECOMMENDATIONS

●The risk of developing heart failure (HF) is increased in patients with rheumatoid arthritis (RA). The prevalence and/or incidence of echocardiographically determined left ventricular (LV) systolic and both LV and right ventricular (RV) diastolic dysfunction is also increased in this population. (See 'Epidemiology' above.)

●The etiology and pathogenesis of HF in RA are not well understood. An increased prevalence of established risk factors (ie, hypertension, diabetes, dyslipidemia) may contribute, but RA itself appears to be an independent risk factor. (See 'Etiology and pathogenesis' above.)

●Patients suspected of HF based upon symptoms and findings suggesting excess fluid accumulation and reduced cardiac output should be evaluated for HF; the diagnosis of HF is made the same way in RA patients as in other patients. (See 'Clinical manifestations' above and 'Evaluation and diagnosis' above and "Heart failure: Clinical manifestations and diagnosis in adults".)

●The approach to the patient with HF with or without RA uses the history, physical examination, laboratory studies, chest radiograph, electrocardiography (ECG), and echocardiogram to establish the diagnosis, determine the etiology, and assess severity. (See 'Evaluation and diagnosis' above and "Heart failure: Clinical manifestations and diagnosis in adults" and "Determining the etiology and severity of heart failure or cardiomyopathy".)

●The differential diagnosis of HF in patients with RA includes interstitial lung disease and pericardial disorders. (See 'Differential diagnosis' above.)

●Antiinflammatory and antirheumatic drug therapies, including nonsteroidal antiinflammatory drugs (NSAIDs), cyclooxygenase 2 (COX-2) selective inhibitors, antimalarial drugs, and glucocorticoids, may play a role in precipitating or exacerbating HF. Tumor necrosis factor (TNF) inhibitors may exacerbate existing HF, but whether they can precipitate new HF remains uncertain. (See 'Etiology and pathogenesis' above.)

●Efforts to prevent HF in RA patients are focused on modifying traditional risk factors for HF and for ischemic heart disease, and on optimizing control of RA disease activity. (See 'Prevention' above and "Epidemiology of heart failure", section on 'Prevention of heart failure' and "Coronary artery disease in rheumatoid arthritis: Implications for prevention and management" and "General principles and overview of management of rheumatoid arthritis in adults".)

●Treatment of HF is similar in patients with and without RA, but attention to the possible adverse cardiovascular effects of antiinflammatory and antirheumatic drug therapy may lead to additional diagnostic studies and/or cessation or gradual withdrawal of certain agents, particularly NSAIDs, COX-2 selective inhibitors, and glucocorticoids. (See 'Approaches particular to rheumatoid arthritis patients with heart failure' above and "NSAIDs: Adverse cardiovascular effects", section on 'NSAIDs and heart failure'.)

●We suggest not administering TNF inhibitors at any dose in patients with symptomatic systolic LV dysfunction (Grade 2C). (See 'Etiology and pathogenesis' above and 'Approaches particular to rheumatoid arthritis patients with heart failure' above and "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects", section on 'Heart failure'.)

However, for patients with active RA whose arthritis is unresponsive to other disease-modifying antirheumatic drugs (DMARDs) or biologic agents (eg, abatacept or rituximab) and who have mild to moderate (New York Heart Association [NYHA] functional class I or II) HF, use of a TNF inhibitor might be considered as an alternative to use of glucocorticoids. If TNF inhibitor therapy is used, we suggest cardiology consultation, initiating at lower doses of TNF inhibitors (eg, infliximab ≤3 mg/kg, adalimumab 40 mg every two weeks, or etanercept 50 mg/week), and prompt discontinuation of TNF inhibitor therapy if HF worsens.

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Peter Schur, MD, and Heidi Connolly, MD, FASE, who contributed to an earlier version of this topic review.