Heart Failure In Rheumatoid Arthritis Research Articles

Associations between rheumatoid arthritis, incident heart failure, and left ventricular ejection fraction

Rheumatoid arthritis (RA) is an independent risk factor for heart failure (HF). Yet, the association between RA and left ventricular ejection fraction (LVEF) in incident HF is not well studied, nor are outcomes of HF in RA by LVEF. We identified incident HF patients between 2003 and 2018 through the Swedish Heart Failure Registry, enriched with data from national health registers. Using logistic regression, associations between a prior diagnosis of RA and LVEF among HF patients and vs age, sex, and geographical area matched general population controls without HF were assessed. Additionally, associations between HF with vs without a prior diagnosis of RA, by LVEF, and outcomes up to 5 years after HF diagnosis were investigated using Cox regression. LVEF was primarily dichotomized at 40% and secondarily categorized as <40%, 40% to 49%, and ≥50%. Covariates included demographics and cardiovascular comorbidities. Among 20,916 incident HF patients, 331 (1.6%) had RA vs 1,047/103,501 (1.0%) of HF-free controls. The odds ratio (OR) for RA was 1.4 (95% CI: 1.1-1.8) in LVEF<40% vs HF-free controls and 1.6 (95% CI: 1.3-2.0) in LVEF≥40% vs HF-free controls. Among HF patients, RA was more common in HF with LVEF ≥40% (1.9%) vs LVEF<40% (1.3%), corresponding to OR 1.4 (95% CI: 1.1-1.7). No associations between RA and cardiovascular outcomes were observed across LVEF. An association between RA and all-cause mortality was observed only for patients with LVEF<40% (hazard ratio: 1.4; 95% CI: 1.1-1.8). RA was independently associated with incident HF, particularly HF with LVEF≥40%. RA did not associate with cardiovascular outcomes following HF diagnosis but was associated with increased risk of all-cause mortality in HF with LVEF<40%.

Myocardial Dysfunction and Heart Failure in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) patients have almost twice the risk of heart failure (HF) as individuals without RA, even with adjustment for the presence of ischemic heart disease. Moreover, RA patients remain at a 2-fold higher risk of mortality from HF compared to non-RA patients. These observations suggest that RA-specific inflammatory pathways are significant contributors to this increased risk of HF. Herein we summarize the epidemiology of HF in RA patients, the differences in myocardial structure or function between RA patients and non-RA patients without clinical signs of HF, and data on the role of systemic and local inflammation in RA HF pathophysiology. We also discuss the impact of subduing inflammation through the use of RA disease-modifying therapies on HF and myocardial structure and function, emphasizing gaps in the literature and areas needing further research.

Use of Hydroxychloroquine and Risk of Heart Failure in Patients With Rheumatoid Arthritis.

To examine the relationship between the use of hydroxychloroquine (HCQ) and risk of developing heart failure (HF) in rheumatoid arthritis (RA). In this nested case-control study, cases were Olmsted County, Minnesota residents with incident RA (based on 1987 American College of Rheumatology criteria) from 1980 to 2013 who developed HF after RA incidence. Each case was matched on year of birth, sex, and year of RA incidence with an RA control who did not develop HF. Data on HCQ use including start and stop dates, as well as dose changes, were reviewed and used to calculate HCQ duration and cumulative dose. Age-adjusted logistic regression models were used to examine the association between HCQ and HF. The study identified 143 RA cases diagnosed with HF (mean age 65.8 yrs, 62% females) and 143 non-HF RA controls (mean age 64.5, 62% female). HCQ cumulative dose was not associated with HF (OR 0.96 per 100-g increase in cumulative dose, 95% CI 0.90-1.03). Likewise, no association was found for patients with a cumulative dose ≥ 300 g (OR 0.92, 95% CI 0.41-2.08). The HCQ duration of intake in years prior to index was not associated with HF (OR 0.98, 95% CI 0.91-1.05). Use of HCQ was not associated with development of HF in patients with RA in this study. Further studies are needed to understand the effect of higher doses of HCQ on the development of HF in RA.

Trends in mortality, co-morbidity and treatment after acute myocardial infarction in patients with rheumatoid arthritis 1998-2013.

Rheumatoid arthritis may influence the outcome after an acute myocardial infarction. We aimed to compare trends in one-year mortality, co-morbidities and treatments after a first acute myocardial infarction in patients with rheumatoid arthritis versus non-rheumatoid arthritis patients during 1998-2013. Furthermore, we wanted to identify characteristics associated with mortality. Data for 245,377 patients with a first acute myocardial infarction were drawn from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions for 1998-2013. In total, 4268 patients were diagnosed with rheumatoid arthritis. Kaplan-Meier analysis was used to study mortality trends over time and multivariable Cox regression analysis was used to identify variables associated with mortality. The one-year mortality in rheumatoid arthritis patients was initially lower compared to non-rheumatoid arthritis patients (14.7% versus 19.7%) but thereafter increased above that in non-rheumatoid arthritis patients (17.1% versus 13.5%). In rheumatoid arthritis patients the mean age at admission and the prevalence of atrial fibrillation increased over time. Congestive heart failure decreased more in non-rheumatoid arthritis than in rheumatoid arthritis patients. Congestive heart failure, atrial fibrillation, kidney failure, rheumatoid arthritis, prior diabetes mellitus and hypertension were associated with significantly higher one-year mortality during the study period 1998-2013. The decrease in one-year mortality after acute myocardial infarction in non-rheumatoid arthritis patients was not applicable to rheumatoid arthritis patients. This could partly be explained by an increased age at acute myocardial infarction onset and unfavourable trends with increased atrial fibrillation and congestive heart failure in rheumatoid arthritis. Rheumatoid arthritis per se was associated with a significantly worse prognosis.

Prevalence, risk factors and proteomic bioprofiles associated with heart failure in rheumatoid arthritis: The RA-HF study

BackgroundRheumatoid arthritis (RA) patients have high risk of heart failure (HF). AimsIdentifying the risk factors and mechanistic pathways associated with HF in patients with RA. MethodsCohort study enrolling 355 RA patients. HF was defined according to the ESC criteria. 93 circulating protein-biomarkers (91CVDIIOlink®+troponin-T+c-reactive protein) were measured. Regression modeling (multivariate and multivariable) were built and network analyses were performed - based on the identified relevant protein biomarkers. Results115 (32.4%) patients fulfilled the ESC criteria for HF, but only 24 (6.8%) had a prior HF diagnosis. Patients with HF were older (67 vs. 55yr), had a longer RA duration (10 vs. 14yr), had more frequently diabetes, hypertension, obesity, dyslipidemia, atrial fibrillation, and ischemic arterial disease. Several protein-biomarkers remained independently associated with HF, the top (FDR1%) were adrenomedullin, placenta-growth-factor, TNF-receptor-11A, and angiotensin-converting-enzyme-2. The networks underlying the expression of these biomarkers pointed towards congestion, apoptosis, inflammation, immune system signaling and RAAS activation as central determinants of HF in RA. Similar HF-associated biomarker-pathways were externally found in patients without RA. Having RA plus HF increased the risk of cardiovascular events compared to RA patients without RF; adjusted-HR (95%CI)=2.37 (1.07-5.30), p=0.034 ConclusionAge, cardiovascular risk factors, and RA duration increase the HF odds in patients with RA. Few RA patients had a correct prior HF diagnosis, but the presence of HF increased the patients` risk. RA patients with HF largely share the mechanistic pathways of HF patients without RA. Randomized HF trials should include patients with RA. ClinicalTrials.gov IDNCT03960515

Incidence of congestive heart failure in rheumatoid arthritis: a review of literature and meta-regression analysis.

AimsRheumatoid arthritis (RA) is a systemic inflammatory autoimmune disorder that not only affects peripheral joints but also increases the risk for cardiovascular disease (CVD) and mortality. Heart failure (HF) appears to be one of the most important contributors to the excess mortality risk among patients with RA. We assessed the incidence of HF in patients with RA compared with age‐matched and sex‐matched non‐RA subjects, after accounting for traditional cardiovascular risk factors and clinical ischemic heart disease.Methods and resultsWe performed an aggregate analysis on three studies of RA patients having listed manifestations of HF. We performed a meta‐regression analysis to evaluate the incidence of HF in RA patients with increased age and noted for any gender correlation. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using both fixed‐effects and random‐effects models. In the cumulative analysis of 5, 220, 883 patients, the incidence of HF was noted to be almost two‐fold higher in patients with RA compared with a matched control population (OR 1.78, 95% CI 1.22–2.60, P < 0.003), HTN (OR 1.66, 95% CI 1.24–2.23, P < 0.001), and diabetes (OR 1.57, 95% CI 1.36–1.81, P < 0.001). Women had three‐fold higher incidence of HF with RA (OR 3.38, 95% CI 2.59–4.40, P < 0.001). On meta‐regression, the incidence of HF increased further with older age (coefficient = 0.12, P = 0.0004).ConclusionsOur systematic review that included over 5 million subjects confirms the suspected increased incidence of HF in RA patients. Women have the greatest risk for HF. Our analysis advocates the need for updating the current guidelines to incorporate screening and preventive methods for HF in RA patients.

P4433Equal cardiovascular risk in patients with diabetes mellitus versus rheumatoid arthritis?

Abstract Purpose To examine whether the risk of cardiovascular disease (heart failure (HF), ischemic heart disease (IHD), myocardial infarction (MI), and coronary revascularization) in patients with rheumatoid arthritis (RA) is comparable to the risk in patients with diabetes mellitus (DM) and general population. Methods The study included the entire Danish population encompassing about 5.7 million inhabitants. Through individual record linkage of nationwide administrative health registries, the authors identified subjects who developed RA and DM and compared these to a matched general population. The cohorts were followed from 1 January 1995 until December 2016. Results The study population consisted of a cohort of 15,491 RA patients, 309,698 DM patients, and a general population cohort of 77,455 subjects matched by age, sex, and year of diagnosis with the RA cohort. Cumulative incidence for HF, IHD, MI, PCI (percutaneous coronary intervention) and CABG (coronary artery bypass grafting) are shown in figure 1. The adjusted hazard ratio (HR) for diagnosis of HF within the 10-year observational period for RA (1.46; 95% CI 1.34–1.59) and DM (1.86; 95% CI 1.78–1.95) were increased compared to the general population. Comparing the risk of HF within the follow-up period a 21% relative risk (HR 0.79, 95% CI 0.73–0.85) reduction of HF in RA compared to DM patients was observed. The HR for IHD development during the follow-up period for RA (1.36; 95% CI 1.25–1.48) and DM (1.64; 95% CI 1.58–1.72) were increased compared to control group. Comparing the risk of IHD within the follow-up period a 17% relative risk (HR 0.83, 95% CI 0.77–0.89) reduction for IHD development in RA compared to DM patients. The HR for MI was increased both in RA (1.48; 95% CI 1.34–1.63) and DM (1.57; 95% CI 1.49–1.65) compared to the control group, without any statistical difference within RA and DM. According to the coronary revascularization, comparable increased numbers of PCI were observed in RA (1.37; 95% CI 1.22–1.54) and DM (1.50; 95% CI 1.41–1.59) patients compared to control subjects. Interestingly, the HR of coronary by-pass grafting (CABG) for RA (1.20; 95% CI 0.98–1.49) and DM (1.99; 95% CI 1.80–2.19) resulting in an adjusted 39% relative risk (0.61 95% CI 0.50–0.74) reduction for CABG in RA compared to DM patients. Figure 1 Conclusions Patients with RA are at increased risk of cardiovascular disease when compared to the general population although slightly lower than observed among patients with DM. Revascularization with CABG was only increased among DM patients, which likely reflects physician compliance to guidelines recommending CABG in case of multivessel disease among DM patients. Patients with RA should be considered for prophylactic strategies in the same way as recommended for patients with DM.

Myocardial Microvascular Dysfunction in Rheumatoid ArthritisQuantitation by 13N-Ammonia Positron Emission Tomography/Computed Tomography.

The goal of this study was to assess the prevalence of myocardial microvascular dysfunction in rheumatoid arthritis (RA) patients without clinical cardiovascular disease and its association with RA characteristics and measures of cardiac structure and function. Participants with RA underwent rest and vasodilator stress N-13 ammonia positron emission tomography and echocardiography. Global myocardial blood flow was quantified at rest and during peak hyperemia. Myocardial flow reserve (MFR) was calculated as peak stress myocardial blood flow/rest myocardial blood flow. A small number of asymptomatic and symptomatic non-RA controls were also evaluated. In RA patients, mean±SD MFR was 2.9±0.8, with 29% having reduced MFR (<2.5). Male sex and higher interleukin-6 were significantly associated with lower MFR, while the use of tumor necrosis factor inhibitors was associated with higher MFR. Lower MFR was associated with higher left ventricle mass index and higher left ventricle volumes but not with ejection fraction or diastolic dysfunction. RA and symptomatic controls had comparable MFR (mean±SD: 2.9±0.8 versus 2.55±0.6; P=0.48). In contrast, MFR was higher in the asymptomatic controls (mean±SD: 3.25±0.7) although not statistically different. Reduced MFR was observed in a third of RA patients without clinical cardiovascular disease and was associated with a measure of inflammation and with higher left ventricle mass and volumes. MFR in RA patients was similar to controls referred for clinical scans (symptomatic controls). Whether reduced MFR contributes to the increased risk for heart failure in RA remains unknown.

Development of heart failure in patients with rheumatoid arthritis: A Danish population‐based study

To investigate the incidence of heart failure (HF) and ischaemic heart disease (IHD) in different time spans following incident rheumatoid arthritis (RA) and, furthermore, to investigate the impact of IHD on the development of HF and the impact of different treatment era of RA. This matched cohort study used nationwide, prospectively collected data. From the total Danish population of approximately 5.7 million inhabitants, we identified 51 859 patients (between 1995 and July 2016) with incident RA and a sex- and age-matched cohort from the general population (256 653 persons). The hazard ratio (HR) for HF among RA patients compared with persons from comparison cohort was 2.28 within the first year of index date, 1.39 within the 1-5 years of index date and 1.38 within the 5-10 years of index date. No difference was identified regarding different treatment era of RA. For IHD, the subdistribution hazard ratio (sHR) was 1.93 within the first year of index date, 1.26 within the 1-5 years of index date and 1.31 within the 5-10 years of index date. Coronary revascularization was also more common within the first year after diagnosis of RA. An increased risk of percutaneous coronary intervention and coronary artery bypass grafting within 10 years following the RA diagnosis was observed. HR for new onset of HF in RA without IHD was 1.23, while the HR for new onset of HF in patients with RA and IHD was 2.06. Rheumatoid arthritis patients had higher rates of HF and IHD throughout the entire observation period compared to the comparison cohort. RA was associated with a larger risk of developing HF.

Association Between Rheumatoid Arthritis and Risk of Ischemic and Nonischemic Heart Failure

BackgroundIt is unknown whether the increased risk of heart failure (HF) in rheumatoid arthritis (RA) is independent of ischemic heart disease (IHD). ObjectivesThis study sought to investigate the relative risk of HF overall and by subtype (ischemic and nonischemic HF) in patients with RA and to assess the impact of RA disease factors. MethodsTwo contemporary cohorts of RA subjects were identified from Swedish patient and rheumatology registries and matched 1:10 to general population comparator subjects. A first-ever HF diagnosis (classified as ischemic HF or nonischemic HF based on the presence of IHD) was assessed through registry linkages. Relative risks for a history of HF before RA onset were calculated through odds ratios. Relative risks of incident HF in RA were calculated as hazard ratios (HRs). ResultsBy the time of RA onset, a history of HF was not more common in RA. In the new-onset RA cohort, the overall HRs for subsequent HF (any type), ischemic HF, and nonischemic HF were between 1.22 and 1.27. The risk of nonischemic HF increased rapidly after RA onset, in contrast to the risk of ischemic HF. High disease activity was associated with all HF types but was most pronounced for nonischemic HF. In the cohort of patients with RA of any duration, the HRs were between 1.71 and 1.88 for the different HF subtypes. ConclusionsPatients with RA are at increased risk of HF that cannot be explained by their increased risk of IHD. The increased risk of nonischemic HF occurred early and was associated with RA severity.

Increased Prevalence of Diastolic Heart Failure in Patients with Rheumatoid Arthritis Correlates with Active Disease, but Not with Treatment Type

Although heart failure (HF) is a major cause of premature mortality, there is little information regarding its prevalence and associated risk factors in patients with rheumatoid arthritis (RA). In this study, we evaluated the prevalence of HF in a community-based RA cohort. Further, we investigated the effect of RA activity and present treatment on HF rate and cardiac structure. A diagnostic workup for HF according to the European Society of Cardiology recommendations was performed in 157 patients with RA fulfilling the American College of Rheumatology/European League Against Rheumatism criteria (68% women, age 61 ± 13 yrs) from our outpatient clinic and in 77 age- and sex-matched controls. The prevalence of HF in patients with RA (24%) was unexpectedly high and differed significantly from the control sample (6%, p = 0.001). Diastolic HF was the dominant type (23% vs 6%), and clinical symptoms alone were of low diagnostic value. Active RA (28-joint Disease Activity Score ≥ 2.6: OR 3.4, 95% CI 1.3-9.8) was an independent risk factor of HF, as well as systemic inflammation (erythrocyte sedimentation rate > 16 mm/h: OR 5.4, 95% CI 2.1-16; C-reactive protein > 10 mg/l: OR 2.6, 95% CI 0.8-8.0) and RA duration > 10 years (OR 2.6, 95% CI 1.2-5.8). HF in RA was associated with concentric hypertrophy (48% vs 17%, p < 0.001) and reduced longitudinal strain (-17.2% vs -19.7%, p < 0.001). However, the prevalence of HF was equivalent between the treatment groups [conventional synthetic disease-modifying antirheumatic drugs (DMARD) 25%, tumor necrosis factor inhibitors 22%, other biological DMARD 27%]. Recognition of all diastolic HF in RA requires a complex diagnostic approach. Active rather than inactive RA places patients at a higher risk for HF, whereas influence of RA treatment on HF risk needs to be elucidated in further studies.

Why currently used diagnostic techniques for heart failure in rheumatoid arthritis are not enough: the challenge of cardiovascular magnetic resonance imaging.

Rheumatoid arthritis (RA) is a multiorgan inflammatory disorder affecting approximately 1% of the population that leads to progressive joint destruction and disability. Patients with RA exhibit a high risk of cardiovascular disease, which results in premature morbidity and mortality and reduced life expectancy, when compared with the general population. Among various guises of myocardial involvement, heart failure (HF) has been recently recognized as an important contributory factor to the excess cardiovascular mortality associated with RA. HF in RA typically presents with occult clinical symptomatology and is mainly associated with structural and functional left ventricular abnormalities leading to diastolic dysfunction, while systolic myocardial performance remains well preserved. As isolated diastolic dysfunction is a predictor of high mortality, the evaluation of patients in early asymptomatic stages, when treatment targeting the heart is more likely to be effective, is of great importance. Although patient history and physical examination remain the cornerstones of HF evaluation, noninvasive imaging of cardiac chambers, coronary arteries, and great vessels may be necessary. Echocardiography, nuclear techniques, and invasive coronary angiography are already established in the routine assessment of HF; however, many aspects of HF pathophysiology in RA remain obscure, due to the limitations of currently used techniques. The capability of cardiovascular magnetic resonance (CMR) to capture early tissue changes allows timely detection of pathophysiologic phenomena of HF in RA, such as myocardial inflammation and myocardial perfusion defects, due to either macrovascular (coronary artery disease) or microvascular (vasculitis) disease. Therefore, CMR may be a useful tool for early, accurate diagnosis and research in patients with RA.

Plasma homoarginine (hArg) and asymmetric dimethylarginine (ADMA) in patients with rheumatoid arthritis: Is homoarginine a cardiovascular corrective in rheumatoid arthritis, an anti-ADMA?

In patients with rheumatoid arthritis (RA), cardiovascular disease(CVD)-related mortality is profoundly increased [1]. The risk of heartfailure in RA is almost twice that of the general population. Theincreasedriskcannotbeentirelyexplainedbytraditionalcardiovascularrisk factors. Instead, blood vessels may be damaged through inflamma-tion and immune-mediated processes [2–4].Asymmetricdimethylarginine(ADMA)isacardiovascularriskfactorandplaysaparticular,notyetfullyunderstoodroleinRA[5–7].ADMAisan endogenous inhibitor of nitric oxide (NO) synthesis, and this mech-anism may be one possible explanation for ADMA's involvement inCVD.However,inacohortof201RApatients,ADMAwasnotassociatedwith subendocardial viability ratio [8], a surrogate marker of coronarymicrovascular perfusion.Recently,homoarginine(hArg),anotherarginineanalogue,emergedas a novel cardiovascular risk factor [9–12], but the underlying mecha-nisms are still unresolved and much less understood than those ofADMA. As circulating hArg and ADMA may have opposing influenceson CVD, we proposed to use the plasma hArg-to-ADMA (hArg/ADMA)molar ratio to improve CVD risk prediction [13].Thus far, hArg has not been investigated in rheumatic diseasesincluding RA. In the present study, we newly determined hArg andADMA concentrations in plasma samples of 100 RA patients (88females, 12 males) collected in a previously reported study involvingcombined add-on supplementation for 12 weeks of omega-3 fattyacids, vitamins E and A, copper, and selenium or placebo (soy oil) [14].Written informed consent was provided by all subjects included in thestudy. The study protocol conformed to the ethical guidelines of the1975 Declaration of Helsinki as reflected in a priori approval by theFreiburg Ethics Committee International (Freiburg, Germany) and theEthics Committee of Charite-University of Medicine (Berlin, Germany).The results of the present study are shown in Figs. 1 and 2. Concentra-tions are reported as mean ± SEM.Plasma hArg concentrations in RA patients were comparable tothose measured by us and others in healthy subjects [13], and did notchange after 12 weeks in the placebo (2858 ± 152 vs. 2950 ±169 nmol/L) and in the verum (2952 ± 158 vs. 2854 ± 185 nmol/L)group. Plasma ADMA concentrations in RA patients were comparableto those in elderly subjects with CVD as measured by us and others[13], and did not change after 12 weeks in the placebo (561 ± 13 vs.566 ± 15 nmol/L) and in the verum (574 ± 21 vs. 576 ± 15 nmol/L)group. The plasma hArg/ADMA ratio was comparable to that measuredinhealthysubjects[13]anddidnotchangeafter12 weeksintheplace-bo (5.17 ± 0.29 vs. 5.32 ± 0.32) and in the verum (5.32 ± 0.33 vs.5.05 ± 0.34) group. At baseline, the plasma hArg/ADMA ratio did notdiffer betweenfemales and males(P = 0.56). There wasnocorrelationbetween the hArg and ADMA plasma concentrations in both groups atbaseline and after 12 weeks. Also, there was no correlation betweenthe hArg or ADMA plasma concentrations and C-reactive protein(CRP) in both groups at the beginning and after 12 weeks (data notshown). In subgroups of patients of both groups, add-on supplementa-tion with omega-3fatty acidsand antioxidants orplacebofor 12 weeksdidnotsignificantlychangethecreatinine-correctedexcretionofnitriteand nitrate, indicators of NO synthesis [20],orof15(S)-8-iso-PGF

FRI0099 Prevalence of Heart Failure in Rheumatoid Arthritis is Doubled in Remission yet Quadrupled in Active Disease

BackgroundRisk of heart failure (HF) is increased in patients with rheumatoid arthritis (RA) and the predominantly prevalent type is diastolic HF with normal ejection fraction (HFNEF). Traditional cardiovascular risk factors...

FRI0124 Increased risk of diastolic heart failure in RA – what should we screening for?

BackgroundPatients with rheumatoid arthritis (RA) share an increased risk of diastolic heart failure with normal ejection fraction (HFNEF), which is often underrecognized. Age, female gender and history of hypertension are...

THU0069 Increased rate of diastolic heart failure in rheumatoid arthritis correlates with systemic inflammation and persistent disease activity, independent from treatment strategy

BackgroundIncreased prevalence of chronic heart failure is observed in patients with rheumatoid arthritis (RA) and heart failure with normal ejection fraction (HFNEF) is the predominant type. Although traditional cardiovascular risk...

Imaging patterns of heart failure in rheumatoid arthritis evaluated by cardiovascular magnetic resonance

Imaging patterns of heart failure in rheumatoid arthritis evaluated by cardiovascular magnetic resonance

Myocardial citrullination in rheumatoid arthritis: a correlative histopathologic study

IntroductionThe aim of this study was to explore the presence and localization of myocardial citrullination in samples from rheumatoid arthritis (RA) patients compared to rheumatic and non-rheumatic disease control groups.MethodsArchived myocardial samples obtained during autopsy from 1995 to 2009 were assembled into four groups: RA; scleroderma; fatal myocarditis; and non-rheumatic disease controls. Samples were examined by immunohistochemistry (IHC) for the presence and localization of citrullination and peptidyl arginine deiminase enzymes (PADs) by a single cardiovascular pathologist blinded to disease group and clinical characteristics.ResultsMyocardial samples from seventeen RA patients were compared with those from fourteen controls, five fatal myocarditis patients, and ten scleroderma patients. Strong citrullination staining was detected exclusively in the myocardial interstitium in each of the groups. However, average and peak anti-citrulline staining was 59% and 44% higher, respectively, for the RA group compared to the combined non-RA groups (P < 0.05 for both comparisons). Myocardial fibrosis did not differ between the groups. In contrast to citrullination, PADs 1 to 3 and 6 were detected in cardiomyocytes (primarily PADs 1 and 3), resident inflammatory cells (primarily PADs 2 and 4), and, to a smaller extent, in endothelial cells and vascular smooth muscle cells. PAD staining did not co-localize with anti-citrulline staining in the interstitium and did not vary by disease state.ConclusionsStaining for citrullination was higher in the myocardial interstitium of RA compared to other disease states, a finding that could link autoimmunity to the known increase in myocardial dysfunction and heart failure in RA.

Left ventricular structure and function in patients with rheumatoid arthritis, as assessed by cardiac magnetic resonance imaging

Heart failure is a major contributor to cardiovascular morbidity and mortality in patients with rheumatoid arthritis (RA), but little is known about myocardial structure and function in this population. This study was undertaken to assess the factors associated with progression to heart failure in patients with RA. With the use of cardiac magnetic resonance imaging, measures of myocardial structure and function were assessed in men and women with RA enrolled in the Evaluation of Subclinical Cardiovascular Disease and Predictors of Events in Rheumatoid Arthritis study, a cohort study of subclinical cardiovascular disease in patients with RA, in comparison with non-RA control subjects from a cohort enrolled in the Baltimore Multi-Ethnic Study of Atherosclerosis. Measures of myocardial structure and function were compared between 75 patients with RA and 225 frequency-matched controls. After adjustment for confounders, the mean left ventricular mass was found to be 26 gm lower in patients with RA compared with controls (P < 0.001), an 18% difference. In addition, the mean left ventricular ejection fraction, cardiac output, and stroke volume were modestly lower in the RA group compared with controls. The mean left ventricular end systolic and end diastolic volumes did not differ between the groups. In patients with RA, higher levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies and current use of biologic agents, but not other measures of disease activity or severity, were associated with significantly lower adjusted mean values for the left ventricular mass, end diastolic volume, and stroke volume, but not with ejection fraction. The combined associations of anti-CCP antibody level and biologic agent use with myocardial measures were additive, without evidence of interaction. These findings suggest that the progression to heart failure in RA may occur through reduced myocardial mass rather than hypertrophy. Both modifiable and nonmodifiable factors may contribute to lower levels of left ventricular mass and volume.

The presentation and outcome of heart failure in patients with rheumatoid arthritis differs from that in the general population

To compare the clinical presentation, management, and outcome of heart failure in patients with rheumatoid arthritis (RA) compared with non-RA patients. We conducted a community-based cohort study in the setting of Olmsted County, Minnesota, from 1979 to 2000. One hundred three patients with RA and 852 non-RA patients with incident heart failure (physician diagnosed and Framingham criteria validated) were compared. Age- and sex-adjusted rates/frequencies and multivariable logistic regression models were used to compare the clinical features and mortality of heart failure following its onset in the 2 groups of patients. The patients with RA were more often female and less frequently were obese, were hypertensive, or had ischemic heart disease. Patients with RA and heart failure had fewer typical symptoms and signs and were less likely to undergo echocardiography compared with non-RA patients. After adjusting for differences, the patients with RA and heart failure were more likely to have preserved ejection fraction (>or=50%). Mortality at 1 year following heart failure was higher in patients with RA compared with non-RA patients (35% versus 19%; multivariable hazard ratio 1.89, 95% confidence interval 1.26-2.84). Both the clinical presentation and the outcome of heart failure differ significantly between patients with and those without RA from the same population. Among patients with RA, the presentation of heart failure is more subtle, myocardial function is more likely preserved, while mortality from heart failure is significantly higher. These findings emphasize the importance of more vigilant screening of patients with RA for early signs of heart failure and may represent important insights into the biologic mechanisms underlying heart failure in RA.