Skip to main content

Left ventricular remodeling in rheumatoid arthritis patients without clinical heart failure


Rheumatoid arthritis (RA) patients have a 1.5- to twofold higher risk of developing heart failure (HF) and a twofold increased risk of HF-associated mortality compared to those without RA. HF is preceded subclinically by left ventricular (LV) remodeling in the general population. There is a relative absence of prospective studies following RA patients from pre-clinical to clinical HF as well as prospective studies of LV remodeling in RA without clinical HF. In our study, 158 RA patients without clinical HF were enrolled and underwent transthoracic echocardiography (TTE) at baseline and on follow-up between 4 and 6 years. Extensive characterization of RA disease activity and cardiovascular risk factors were performed. LV remodeling was prevalent at 40% at baseline and increased to 60% over time. Higher levels of interleukin-6 (IL 6) were associated with concentric LV remodeling on follow-up. The use of tocilizumab was also significantly associated with baseline LV remodeling (relative wall thickness). These findings suggest a role for IL-6 as a biomarker for LV remodeling in RA patients without clinical HF. Future research should focus on prospective follow-up of LV remodeling and the effects of IL-6 inhibition on LV remodeling in RA patients.


People with rheumatoid arthritis (RA) have a 1.5- to twofold higher risk of developing heart failure (HF) and a twofold increased risk of HF-associated mortality compared with people without RA. Emerging data suggest that the dominant clinical HF phenotype in RA appears to be HF with preserved ejection fraction (HFpEF) [1]. In the general population, HFpEF is thought to be preceded subclinically by the development of LV diastolic dysfunction and concentric remodeling, while HF with reduced ejection fraction (HFrEF) is more typically preceded by systolic dysfunction and eccentric remodeling [2,3,4,5]. While there are no prospective studies that have followed RA patients from pre-symptomatic phase to clinical HF, numerous reports confirm that RA patients without clinical HF have a higher rate of subclinical diastolic dysfunction compared to age- and gender-matched controls [6]. However, reports on LV remodeling and its determinants in RA patients without clinical HF are few. Several cross-sectional studies [7,8,9] confirm a higher prevalence of concentric hypertrophy and remodeling in RA vs age- and gender-matched non-RA controls. However, there are few data to date on the rate of progression of subclinical LV remodeling and its determinants. We evaluated not only the baseline prevalence of LV remodeling but also its progression, in an RA cohort without clinical HF. Furthermore, we hypothesized that measures of RA disease activity would convey risk for baseline and/or progression of LV concentric remodeling.


The RHYTHM cohort (n = 158) was designed as a cross-sectional study in 2011 to identify myocardial phenotypes in RA patients without clinical cardiovascular disease (CVD). Patients were subsequently re-recruited for a follow-up visit 4–6 years later to investigate changes in LV structure and function over time; 60 participants completed the follow-up visit. Detailed inclusion/exclusion criteria have been published previously [10]. The baseline visit consisted of clinical questionnaires, joint examination, biospecimen collection, echocardiography, and cardiac PET-CT scan. Echocardiography was repeated at follow-up. The study was approved by the Columbia University Irving Medical Center Institutional Review Board. All subjects provided written informed consent prior to enrollment.

Clinical characteristics

Demographic and cardiovascular characteristics

The assessment of demographics, lifestyle characteristics, CV risk factors, and medications was performed as previously described [10]. Forty-four joints were examined for swelling and tenderness by the same trained joint assessor. RA disease activity was calculated with the Disease Activity Score for 28 joints using C-reactive protein (DAS28-CRP) and with the Clinical Disease Activity Index (CDAI). The Health Assessment Questionnaire (HAQ) was used as a measure of self-reported disability.



The protocol for transthoracic 2-dimensional (2D) echocardiography was detailed in prior manuscripts [10,11,12]. Using apical 2 and 4-chamber views, as well as real-time 3-dimensional (3D) echocardiography, left ventricular (LV) structural measures (LV mass (LVM), end-diastolic volume index (EDVI), end-systolic volume index (ESVI), and relative wall thickness (RWT)) were measured according to the most recent American Society of Echocardiography (ASE) guidelines [13]. LVM/EDV was evaluated as an alternate measure for RWT [13, 14]. LV mass (LVM) was calculated as per ASE convention [13], using LV internal diameter at end-diastole (LVIDd) and at end-systole (LVIDs) and the interventricular septal (IVSd) and posterior wall thickness (PWd) obtained in the long axis view. LVM index (LVMI) was defined as LVM indexed to height (2.7 m2). Baseline scans (n = 158) were re-read side by side with the follow-up scans (n = 60) by the same echocardiographer (KI) without blinding to time sequence.

Sex-neutral as well as sex-specific cut offs for LV structure derived from the general population were utilized: LVMI (51 g/m2.7 sex neutral; 50 g/m2.7 for men and 47 g/m2.7 for women) [15, 16], ESVI (31 mL/m2 for men and 24 mL/m2 for women), RWT (< 0.42) [17,18,19,20], LVM indexed to EDV (LVM/EDV) (< 1.23 in women; < 1.22 in men) [14].

Definitions of remodeling

LV remodeling states are defined in the general population using standardized cut-off values of LVMI and RWT. General population cut-offs for elevated LVMI are > 115 g/m2 for men and > 95 g/m2 for women, and the sex independent cut off is 51 g/ht2.7 and RWT > 0.42 [15]. Concentric hypertrophy (CH) is defined as LVM > 95 g/m2or LVMI > 115 g/m2 and RWT > 0.42. Concentric remodeling (CRM) is defined as LVM < 95 g/m2 or LVMI < 115 g/m2 and RWT > 0.42. Eccentric hypertrophy (EH) is defined as LVM > 95 g/m2 or LVMI > 115 g/m2 and RWT < 0.42. However, because the RA patients in this study did not have clinical HF, we utilized LVMI > 90 percentile indexed to height2.7 with RWT > 0.42 to define LV remodeling categories. Categories were constructed without regard to sex, as 84% of our cohort was female and there were no statistical differences in LVMI ht2.7 in male vs female (p = 0.52) within our cohort. Thus, the following cut-offs were utilized to define remodeling states in this RA cohort: (1) normal geometry, LVMI < 90 percentile and RWT < 0.42 and (2) CRM, LVMI < 90 percentile and RWT > 0.42; (3) CH, LVMI > 90 percentile and RWT > 0.42; and (4) EH, LVMI > 90 percentile and RWT < 0.42.

Cardiac FDG PET-CT

Cardiac PET-CT scans were performed at baseline to measure myocardial 18F-fluorodeoxyglucose (FDG) uptake, rest and stress myocardial perfusion using 13N-ammonia, and coronary artery calcium (CAC). These methods have been described extensively in prior publications [11, 12].

Laboratory measurements

Phlebotomy was performed on the morning of each visit after an overnight fast. Details of laboratory measurements have been previously published [10]. Cholesterol (HDL, LDL, triglycerides), C-reactive protein (CRP), glucose, insulin, IL (interleukin)-6, BNP, and galectin-3 levels were measured in the Biomarkers Core Laboratory of the Columbia University Clinical and Translational Research Center. Troponin-I levels were measured by the Quanterix SimoaTM Human Troponin-I 2.0 immunoassay.

Statistical analysis

Means and standard deviations (SDs) for normally distributed variables, and counts and percentages for categorical variables, were calculated. For continuous variables, differences were compared using Student’s t-tests or the Wilcoxon-Mann–Whitney test/signed ranks. Categorical variables were compared using the chi-squared goodness of fit test, Fisher’s exact test, or McNemar’s test, as appropriate. Linear regression was used to model the associations of clinical and laboratory characteristics with the primary outcomes, CRM and RWT. Univariable and multivariable models were constructed to identify variables associated with these LV structural outcomes. Multivariable models were constructed by including any variable associated with the outcome (p < 0.25) in univariable models, and a p-value of < 0.05 was considered significant for final models. All multivariable models were examined for co-linearity, omitted variables, and outliers. All analyses were performed using Stata version 16 (StataCorp, College Station, TX).


Patient characteristics

Characteristics of the full cohort (n = 158) and the longitudinal subset (n = 60) at baseline were previously reported [10] and are re-summarized in Table 1. The longitudinal subset was largely similar to the full cohort except for shorter RA duration, higher frequency of methotrexate use, and higher mean CRP level. Statistically significant changes from baseline to follow-up in the longitudinal subset included decreases in DAS28CRP and IL-6 levels, less frequent use of methotrexate, and an increase in mean systolic blood pressure (SBP).

Table 1 Baseline characteristics of the RHYTHM full cohort and subset

LV structure

LV structural measures are summarized in Table 1. The following mean baseline levels for the full RA cohort were statistically significantly lower than published cut-off values for the general population: mean baseline LVMI of 29.2 ± 5.06 (vs 51 g/m2.7 (p < 0.01) sex neutral; 50 g/m2.7 for men (p < 0.01) and 47 g/m2.7 for women (p < 0.01)) [15, 16]; mean baseline EDVI of 47.2 ± 11.0 (vs 74 mL/m2 for men (p < 0.01), 61 mL/m2 for women (p < 0.01)); mean baseline ESVI of 17.7 + 5.06 (vs 31 mL/m2 for men (p < 0.01) and 24 mL/m2 for women (p < 0.01)), mean baseline RWT of 0.34 ± 0.09 (vs < 0.42 (p < 0.01)) [17,18,19,20].

Mean baseline LVM indexed to EDV (LVM/EDV) of 1.33 ± 0.24 was above established cut-off values (< 1.23 in women; < 1.22 in men) [14]. Fifty-eight of the 60 patients enrolled in the longitudinal follow-up had complete echocardiographic data for both time points. At follow-up, both RWT and LVM/EDV increased significantly over time (p < 0.01 and p < 0.05, respectively) while mean LVMI, EDVI and ESVI were not significantly different from baseline (p = 0.82).

The percentages of patients fulfilling LV remodeling criteria are shown in Table 2. At baseline, 60% of the longitudinal cohort had normal geometry (normal LVMI and RWT), but only 40% retained normal geometry at follow-up. The predominant abnormal geometry at follow-up was CRM which increased significantly from 10% at baseline to 31% at follow-up. There were no significant changes in the prevalence of CH or EH from baseline to follow-up. Lastly, 4 patients with CRM at baseline reverted to normal on follow-up and 1 patient with EH at baseline reverted to normal on follow-up.

Table 2 Baseline and follow-up changes in LV remodeling categories

Determinants of LV remodeling

Demographic and CV risk factors and RA-associated disease variables were examined as determinants of CRM at baseline and at follow-up (other remodeling states were not examined due to small numbers). Similar analyses were performed for individual measures of wall thickness (RWT and LVM/EDV) (Tables 3 and 4; Supplementary Tables 2 and 3). In multivariable analyses with CRM as outcome, there was a trend in association of higher IL-6 levels with having CRM at follow-up (OR 2.55; 95% CI 0.99–6.58; p = 0.053) but not with baseline CRM (Tables 5 and  6; Supplementary Table 1). In multivariable analyses with RWT as outcome, age (β = 0.0043; p = 0.023) and tocilizumab use (β = 0.50; p = 0.043) were associated with higher baseline RWT (Table 3). In multivariable analyses with LVM/EDV as outcome, higher BMI at baseline was associated with higher LVM/EDV (β = 0.012; p = 0.010) (Supplementary Table 2). In multivariable analyses with LVMI as outcome, SBP was marginally associated with a higher likelihood of baseline 3D LVMI > 90% (OR = 1.07; 95% CI 1.02–1.12; p = 0.009) (Supplementary Table 4) as well as increasing RWT over time (β = 0.00035; p = 0.028) (Table 4).

Table 3 Univariable and multivariable regression table for baseline RWT
Table 4 Univariable and multivariable regression table for annualized rate of change RWT
Table 5 Univariable and multivariable regression table for baseline CRM
Table 6 Univariable and multivariable regression table for follow-up CRM

There were no significant associations (univariable or multivariable analyses) between measures of myocardial inflammation and perfusion vs baseline/follow-up LV structure, including CRM and RWT. Additionally, there were no significant associations (univariable or multivariable analyses) between BNP, troponin-I, and galectin-3 and baseline/follow-up LV structure, including CRM and RWT.


LV structure is assessed by LVM and RWT on two or three-dimensional TTE. Several proxy measures for RWT exist, including LVM indexed to EDV dimensions. Generally, increased LVM and RWT indicate abnormal LV geometry.

In this study, we confirmed that CRM, defined by increased RWT but normal LVM, is prevalent in RA patients without HF and, importantly, showed for the first time that the prevalence increases over time. Furthermore, our data suggest several inflammatory determinants of LV remodeling and its progression including higher IL-6 levels or use of an IL-6 inhibitor (tocilizumab), as well as demographic and CV determinants including age, BMI, and SBP.

In our prospective sub-cohort, CRM was the most prevalent form of remodeling at baseline (13%) and increased significantly to 31% on follow-up. RWT and LVM/EDV also both increased significantly over time (p < 0.05 for both), consistent with the overall increasing prevalence of CRM. Other individual LV structural parameters such as LVMI, EDVI, and ESVI did not change significantly on follow-up.

Our findings are in agreement with prior cross-sectional RA studies which also demonstrate that concentric geometry is the most prevalent remodeling form [ 8, 9] . This is notable as concentric geometry (remodeling and/or hypertrophy) has been linked to increased CV events including HF in the general population [21,22,23]. Whether this increase in CRM in RA is a risk factor for future clinical HF needs to be explored in prospective studies. Several other prospective RA studies reported statistically significant declines in LVMI, wall thickness, EDV, and ESV in RA patients without clinical HF [24], diverging from our results. This could be attributable to differences in demographics, RA disease features (duration, disease activity, treatment), sample size, conventional CV risk factors, or other variables.

Beyond the usual demographic and CV variables discussed above, higher rates of LV remodeling in RA vs non-RA controls have been hypothesized to be due to the higher levels of inflammation in RA. Indeed, we observed an association between inflammatory measures- IL6- and LV structure. Namely, every logged unit (mg/L) increase in IL-6 was associated with 2.5 times higher odds of CRM on follow-up. These findings are consistent with the hypothesis that higher levels of IL-6 induce adverse LV structure/geometry, likely mediated by activation of pro-fibrotic and myocyte hypertrophy pathways [25,26,27]. Tocilizumab use at baseline was also associated with higher baseline RWT. As use of anti-inflammatory medications, particularly biologic DMARDs in RA, is associated with higher burden of inflammation, this could be considered a marker of those with severe RA disease and possibly LV remodeling.

In as far as the association between tocilizumab and IL-6 levels are concerned, given the small numbers of patients on tocilizumab at baseline (n = 3) and on follow-up (n = 6), meaningful statistical differences in IL-6 levels could not be inferred. However, IL-6 levels were consistently higher in those on tocilizumab vs those not on tocilizumab (results not shown), which may reflect an accumulation of free/unmetabolized IL-6 in circulation resulting from uptake of IL-6 receptors after tocilizumab treatment.

In our multivariable analyses, older age at baseline was associated with higher baseline RWT, which parallels findings in both RA [7, 28] and non-RA studies [29,30,31]. This reinforces the idea that aging remains an independent risk factor for LV remodeling.

Additionally, baseline BMI was associated with adverse remodeling/geometry, including higher baseline LVM/EDV, and baseline LVMI > 90%. This is in line with at least one RA study in which BMI was significantly associated with higher baseline LVMI [7]. It is also consistent with an array of non-RA studies which demonstrated BMI independently associating with higher LV mass [29, 31,32,33].

Baseline SBP was associated with baseline LVMI > 90% as well as increasing RWT over time. While many studies in non-RA patients demonstrate significant associations between SBP and higher/increasing LVMI [29, 32], the majority of RA studies do not support this association. In our current study, the prevalence of hypertension was low (mean SBP = 117.7; 1/3 on BP medications); therefore, any possible associations between BP and LV structure could have been attenuated.

There were no associations with troponin-I and BNP and LV structure. Given that both are released as a response to myocyte injury/necrosis, it is possible that our patients were too early in the course of myocardial/LV damage and remodeling to be able to detect these markers.

Limitations of this study include the absence of non-RA controls, which does not allow for direct comparisons and establish whether such changes in LV structure are unique/specific to RA. While only a limited number of patients returned for follow-up (about 1/3 of baseline cohort), we were still able to detect significant changes in key parameters of LV structure.


In conclusion, LV remodeling is prevalent in RA patients without clinical HF and increases to 60% over time. Adverse LV structure/remodeling at baseline and follow-up are associated with higher IL-6 levels and use of tocilizumab. These findings suggest that inflammatory cytokines such as IL-6 could serve as biomarkers for LV remodeling in RA patients and possibly future development of HF. Investigating whether LV remodeling leads to clinical HF in RA patients and whether LV remodeling is reversible or attenuated by IL-6 inhibition (tocilizumab) remain key future research objectives, ultimately to reduce the twofold higher HF mortality rate associated with RA vs non-RA [34].

Availability of data and materials

The datasets used and analyzed during the current study are included in this published article (and its supplementary information files) or otherwise available from the corresponding author on request.







American Society of Echocardiography


Body mass index


Coronary artery calcium


Clinical Disease Activity Index


Concentric hypertrophy


Concentric remodeling


C-reactive protein




Cardiovascular disease


Disease Activity Score for 28 joints using CRP


End-diastolic volume index


Eccentric hypertrophy


End-systolic volume index


Myocardial 18F-fluorodeoxyglucose


Health Assessment Questionnaire


Heart failure


HF with preserved ejection fraction


HF with reduced ejection fraction




Interventricular septal


Low-density lipoprotein


Left ventricular

LVIDs and LVIDs:

LV internal diameter at end-diastole and end-systole


LV mass index


Posterior wall thickness


Rheumatoid arthritis


RHeumatoid Arthritis studY of THe Myocardium


Relative wall thickness


Systolic blood pressure


Standard deviation


Standardized uptake Value


  1. Ahlers MJ, Lowery BD, Farber-Eger E, Wang TJ, Bradham W, Ormseth MJ, et al. Heart failure risk associated with rheumatoid arthritis–related chronic inflammation. JAHA. 2020;9(10). Available from: . [Cited 21 Jun 2020].

  2. Sharma K, Kass DA. Heart failure with preserved ejection fraction: mechanisms, clinical features, and therapies. Circ Res. 2014;115(1):79–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Kosmala W, Marwick TH. Asymptomatic left ventricular diastolic dysfunction. JACC: Cardiovascular Imaging. 2019 Apr;S1936878X19302578.

  4. Kane GC, Karon BL, Mahoney DW, Redfield MM, Roger VL, Burnett JC, et al. Progression of left ventricular diastolic dysfunction and risk of heart failure. JAMA. 2011;306(8). Available from: [Cited 17 Mar 2021].

  5. Kuznetsova T, Thijs L, Knez J, Cauwenberghs N, Petit T, Gu YM, et al. Longitudinal Changes in left ventricular diastolic function in a general population. Circ Cardiovasc Imaging. 2015;8(4). Available from: [Cited 8 Nov. 2020]

  6. Aslam F, Bandeali SJ, Khan NA, Alam M. Diastolic dysfunction in rheumatoid arthritis: a meta-analysis and systematic review. Arthritis Care Res. 2013;65(4):534–43.

    Article  Google Scholar 

  7. Rudominer RL, Roman MJ, Devereux RB, Paget SA, Schwartz JE, Lockshin MD, et al. Independent association of rheumatoid arthritis with increased left ventricular mass but not with reduced ejection fraction. Arthritis Rheum. 2009;60(1):22–9.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Cioffi G, Ognibeni F, Dalbeni A, Giollo A, Orsolini G, Gatti D, et al. High prevalence of occult heart disease in normotensive patients with rheumatoid arthritis. Clin Cardiol. 2018;41(6):736–43.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Myasoedova E, Davis JM, Crowson CS, Roger VL, Karon BL, Borgeson DD, et al. Brief Report: Rheumatoid arthritis is associated with left ventricular concentric remodeling: results of a population-based cross-sectional study: abnormal left ventricular remodeling in RA. Arthritis Rheum. 2013;65(7):1713–8.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Park E, Ito K, Iqbal R, Amigues I, Bokhari S, Van Eyk J, et al. Prospective changes in diastolic function in patients with rheumatoid arthritis. Arthritis Res Ther. 2022;24(1):184.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Amigues I, Tugcu A, Russo C, Giles JT, Morgenstein R, Zartoshti A, et al. Myocardial inflammation, measured using 18-fluorodeoxyglucose positron emission tomography with computed tomography, is associated with disease activity in rheumatoid arthritis. Arthritis Rheumatol. 2019;71(4):496–506.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Amigues I, Russo C, Giles JT, Tugcu A, Weinberg R, Bokhari S, et al. Myocardial microvascular dysfunction in rheumatoid arthritis: quantitation by 13 N-ammonia positron emission tomography/computed tomography. Circ: Cardiovascular Imaging. 2019;12(1). Available from: [Cited 6 Dec 2019].

  13. Lang RM, Badano LP, Mor-Avi V, Afilalo J, Armstrong A, Ernande L, et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr. 2015;28(1):1-39.e14.

    Article  PubMed  Google Scholar 

  14. Lembo M, Santoro C, Sorrentino R, Trimarco B, Galderisi M, Esposito R. Impact of left ventricular mass/end-diastolic volume ratio by three-dimensional echocardiography on two-dimensional global longitudinal strain and diastolic function in native hypertensive patients. J Hypertens. 2019;37(10):2041–7.

    Article  CAS  PubMed  Google Scholar 

  15. de Simone G, Daniels SR, Devereux RB, Meyer RA, Roman MJ, de Divitiis O, et al. Left ventricular mass and body size in normotensive children and adults: assessment of allometric relations and impact of overweight. J Am Coll Cardiol. 1992;20(5):1251–60.

    Article  PubMed  Google Scholar 

  16. Konstam MA, Kramer DG, Patel AR, Maron MS, Udelson JE. Left ventricular remodeling in heart failure. JACC: Cardiovasc Imaging. 2011;4(1):98–108.

    PubMed  Google Scholar 

  17. Aune E, Baekkevar M, Roislien J, Rodevand O, Otterstad JE. Normal reference ranges for left and right atrial volume indexes and ejection fractions obtained with real-time three-dimensional echocardiography. Eur J Echocardiogr. 2009;10(6):738–44.

    Article  PubMed  Google Scholar 

  18. Fukuda S, Watanabe H, Daimon M, Abe Y, Hirashiki A, Hirata K, et al. Normal values of real-time 3-dimensional echocardiographic parameters in a healthy Japanese population: – The JAMP-3D Study –. Circ J. 2012;76(5):1177–81.

    Article  PubMed  Google Scholar 

  19. Chahal NS, Lim TK, Jain P, Chambers JC, Kooner JS, Senior R. Population-based reference values for 3D echocardiographic LV volumes and ejection fraction. JACC: Cardiovasc Imaging. 2012;5(12):1191–7.

    PubMed  Google Scholar 

  20. Muraru D, Badano LP, Peluso D, Dal Bianco L, Casablanca S, Kocabay G, et al. Comprehensive analysis of left ventricular geometry and function by three-dimensional echocardiography in healthy adults. J Am Soc Echocardiogr. 2013;26(6):618–28.

    Article  PubMed  Google Scholar 

  21. Verma A, Meris A, Skali H, Ghali JK, Arnold JMO, Bourgoun M, et al. Prognostic implications of left ventricular mass and geometry following myocardial infarction. JACC: Cardiovasc Imaging. 2008;1(5):582–91.

    PubMed  Google Scholar 

  22. Pugliese NR, Fabiani I, La Carrubba S, Conte L, Antonini-Canterin F, Colonna P, et al. Classification and prognostic evaluation of left ventricular remodeling in patients with asymptomatic heart failure. Am J Cardiol. 2017;119(1):71–7.

    Article  PubMed  Google Scholar 

  23. Shah AM, Claggett B, Loehr LR, Chang PP, Matsushita K, Kitzman D, et al. Heart failure stages among older adults in the community: the Atherosclerosis Risk in Communities study. Circulation. 2017;135(3):224–40.

    Article  PubMed  Google Scholar 

  24. Davis JM, Lin G, Oh JK, Crowson CS, Achenbach SJ, Therneau TM, et al. Five-year changes in cardiac structure and function in patients with rheumatoid arthritis compared with the general population. Int J Cardiol. 2017;240:379–85.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Li Y. Interplay of matrix metalloproteinases, tissue inhibitors of metalloproteinases and their regulators in cardiac matrix remodeling. Cardiovasc Res. 2000;46(2):214–24.

    Article  CAS  PubMed  Google Scholar 

  26. Park E, Griffin J, Bathon JM. Myocardial Dysfunction and heart failure in rheumatoid arthritis. Arthritis  Rheumatol. 2021;art.41979.

  27. Mann DL. Innate immunity and the failing heart: the cytokine hypothesis revisited. Circ Res. 2015;116(7):1254–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Pascale V, Finelli R, Giannotti R, Coscioni E, Izzo R, Rozza F, et al. Cardiac eccentric remodeling in patients with rheumatoid arthritis. Sci Rep. 2018;8(1):5867.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Gidding SS, Liu K, Colangelo LA, Cook NL, Goff DC, Glasser SP, et al. longitudinal determinants of left ventricular mass and geometry: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Circ Cardiovasc Imaging. 2013;6(5):769–75.

    Article  PubMed  Google Scholar 

  30. Lieb W, Gona P, Larson MG, Aragam J, Zile MR, Cheng S, et al. The natural history of left ventricular geometry in the community. JACC Cardiovasc Imaging. 2014;7(9):870–8.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Lee TC, Jin Z, Homma S, Nakanishi K, Elkind MSV, Rundek T, et al. Changes in left ventricular mass and geometry in the older adults: role of body mass and central obesity. J Am Soc Echocardiogr. 2019;32(10):1318–25.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Gardin JM, Brunner D, Schreiner PJ, Xie X, Reid CL, Ruth K, et al. Demographics and correlates of five-year change in echocardiographic left ventricular mass in young black and white adult men and women: the Coronary Artery Risk Development in Young Adults (CARDIA) Study. J Am Coll Cardiol. 2002;40(3):529–35.

    Article  PubMed  Google Scholar 

  33. Kishi S, Reis JP, Venkatesh BA, Gidding SS, Armstrong AC, Jacobs DR, et al. Race–ethnic and sex differences in left ventricular structure and function: the Coronary Artery Risk Development in Young Adults (CARDIA) study. JAHA. 2015;4(3):e001264.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Davis JM, Roger VL, Crowson CS, Kremers HM, Therneau TM, Gabriel SE. The presentation and outcome of heart failure in patients with rheumatoid arthritis differs from that in the general population. Arthritis Rheum. 2008;58(9):2603–11.

    Article  PubMed  PubMed Central  Google Scholar 

Download references


Not applicable.


Joan Bathon is supported by NIH/NIAMS R01 AR050026 and U01 AR068043.

Author information

Authors and Affiliations



KI, CD, JTG, JB: recruitment and data collection. EP, JTG, JB: constructed analysis plan and first draft of manuscript. EP, JTG, JB: substantial modification of manuscript and final approval. All authors read and approved final manuscript.

Corresponding author

Correspondence to Elizabeth Park.

Ethics declarations

Ethics approval and consent to participate

RHYTHM was approved by the CUIMC/New York Presbyterian Hospital Institutional Review Board.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: Table S1.

Follow-up CRM *excluded to those who did not have CRM at baseline*. Table S2. Baseline LVM/EDV. Table S3. Annualized Rate of Change in LVM/EDV. Table S4. Baseline 3D LVMI ht2.7 > 90%. Table S5. Annualized Rate of Change in LVMI2.7

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, E., Ito, K., Depender, C. et al. Left ventricular remodeling in rheumatoid arthritis patients without clinical heart failure. Arthritis Res Ther 25, 124 (2023).

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: