Impaired Cardiac Function in Juvenile Mixed Connective Tissue Disease Compared with Controls

Birgit Nomeland Witczak¹, Siri Opsahl Hetlevik², Zoltan Barth^1,3, Thomas Schwartz^4,5, Berit Flatø^2,6, Vibke Lilleby^2,6 and Ivar Sjaastad^1,6,7, ¹Institute for Experimental Medical Research, Oslo University Hospital, Oslo, Norway, Oslo, Norway, ²Department of Rheumatology, Oslo University Hospital, Rikshospitalet, Oslo, Norway, Oslo, Norway, ³Department of Pathophysiology and Gerontology, Medical School, University of Pècs, Pècs, Hungary, Pècs, Hungary, ⁴Oslo University Hospital and University of Oslo, Institute for Experimental Medical Research, Oslo, Norway, ⁵Department of Infectious Diseases, Oslo University Hospital, Oslo, Norway, Oslo, Norway, ⁶Institute for Clinical Medicine, University of Oslo, Oslo, Norway, Oslo, Norway, ⁷Department of Cardiology, Oslo University Hospital, Oslo, Norway, Oslo, Norway

Meeting: 2017 ACR/ARHP Annual Meeting

Date of first publication: September 18, 2017

Keywords: Cardiovascular disease, Disease Activity, Lipids, mixed connective tissue disease (MCTD) and ribonucleoprotein (RNP)

Session Information

Date: Monday, November 6, 2017

Title: Pediatric Rheumatology – Clinical and Therapeutic Aspects Poster II: Lupus and Related Disorders, Myositis, Scleroderma and Vasculitis

Session Type: ACR Poster Session B

Session Time: 9:00AM-11:00AM

Background/Purpose: Juvenile MCTD (JMCTD) is a heterogenic autoimmune disease, with SLE-, SSc- and PM/DM and RA like manifestations. Cardiac involvement is known in juvenile SLE, SSc, JDM and JIA, but data is limited in JMCTD. Adult MCTD is more benign than other CTDs, and cardiac involvement is mainly subclinical. Mortality, however, is mostly related to cardiac causes. Aim of study was to compare cardiac function in JMCTD patients with controls, and explore associations between cardiac function and disease characteristics.

Methods: 50 patients and 50 matched controls were examined median 14.9 years after disease onset. Cardiac function was assessed by echocardiography; LV systolic function was assessed by biplane ejection fraction (EF) and normalized mitral annulus displacement (long axis strain (LAS)); LV diastolic function was assessed by early diastolic tissue velocity (E’), early diastolic transmitral flow (MV E), and early/ late diastolic transmitral flow ratio (MV E/A ratio). LV dysfunction was defined as EF≤61.6%, LAS≤15.3%, or E’≤9.3m/s, all defined by mean values -2 standard deviations in controls. Disease activity was assessed by SLEDAI, Juvenile Arthritis Disease Activity Score (JADAS), anti-RNP-levels and positive rheumatoid factor (RF). Patients were classified with SLE-like, SSc-like or PM-like findings.

Results: Table 1 shows characteristics and cardiovascular parameters in patients and controls. 86% were female; Mean age in patients was 27.4 years.

EF and LAS were lower in patients than controls (P≤0.001 and P=0.045), but within normal range. MV E and MV E/A ratio were also impaired in patients (P ≤0.029). LV dysfunction was present in 16% patients versus 4% controls (P=0.046).

At follow-up, JADA was associated with lower EF (rsp= -0.283, p0.049); Positive RF and higher SLEDAI at follow-up were associated with higher LAS (rsp=0.318, P=0.026 and rsp=0.281, P=0.048). Long duration of prednisolone treatment was associated with EF≤61.6% (rsp=0.340, P=0.016).

In final multivariable regression models (table 2), PM-like findings at diagnosis was an independent predictor of impaired EF (P=0.001), male sex was independent predictor of impaired LAS (P=0.002), and long disease duration was independent predictor of impaired E’ (P≤0.001).

Conclusion: LV cardiac function was impaired in JMCTD patients compared with controls. Subclinical LV dysfunction was present in 16% of the patients. PM-like manifestation at diagnosis, male sex and long disease duration predicted impaired cardiac function. Our results suggest that cardiac involvement in JMCTD varies among the different clinical phenotypes.

Table 1. Characteristics and cardiovascular parameters in JMCTD patients and controls
	JMCTD Patients n=50	Controls n=50	P-value
Female sex	43 (86%)	43 (86%)	NA
Variables assessed at diagnosis
SLE-like findings (n=49)	46 (94%)	NA	NA
SSc-like findings (n=49)	12 (25%)	NA	NA
PM-like findings (n=49)	15 (31%)	NA	NA
Anti-RNP, U/L (n=48)	240 (240-999)	NA	NA
Positive RF (n=42)	26 (62%)	NA	NA
Variables assessed at follow-up
Disease duration, years	14.9 (6.6-23.0)	NA	NA
Age, years	27.4 (9.9)	28.5 (9.9)	<0.001
Height, cm (n=49 pairs)	166.0 (7.5)	169.6 (8.6)	0.022
BMI, kg/m²(n=49pairs)	22.8 (3.5)	23.5 (3.0)	0.279
SBP, mmHg (n=47pairs)	111.9 (14.5)	114.8 (11.9)	0.233
DBP, mmHg (n=47pairs)	64.8 (15.0)	67.9 (8.6)	0.177
Total duration of prednisolone (months)	12 (2-40)	NA	NA
SLE-like findings	27 (54%)	NA	NA
SSc-like findings	34 (68%)	NA	NA
PM-like findings	2 (4%)	NA	NA
Disease activity measures at follow-up
CRP, mg/L (n=41pairs)	0.70 (0.50-1.90)	0.60 (0.50-0.90)	0.108
ESR, mm (n=47pairs)	8.5 (5.0-16.0)	4.0 (2.0-7.0)	<0.001
Anti-RNP, U/L (n=49)	199 (38-240)	NA	NA
Positive RF (n=49)	17 (35%)	NA	NA
SLEDAI	0 (0-0)	NA	NA
JADA (n=49)	0 (0-0)	NA	NA
Echocardiography data at follow-up
LV ejection fraction, EF, %	65.8 (4.5)	69.6 (4.0)	<0.001
LV length, mm	77.4 (7.2)	79.6 (6.3)	0.109
MA displacement, mm
MV medial, mm	13.7 (1.9)	14.3 (1.5)	0.094
MV lateral, mm	15.1 (1.7)	16.5 (2.0)	0.001
Long Axis Strain% (LAS%)	18.68 (1.94)	19.40 (2.07)	0.044
MV E velocity, m/s	0.82 (0.12)	0.90 (0.16)	0.015
MV E/A ratio	1.95 (0.46)	2.16 (0.56)	0.029
E’ (cm/s)	12.38 (1.63)	12.86 (1.79)	0.129
Values are mean (SD) or median (IQR) or number (%). Anti-RNP, anti-ribonuceloprotein antibodies; BMI, body mass index; CRP, c-reactive protein; DBP, diastolic blood pressure; E’, early diastolic tissue velocity; ESR, erythrocyte sedimentation rate; JADA, Juvenile Arthritis Disease Activity Score; LA, left atrium; LAS, long axis strain; LV, left ventricular; MA, mitral annulus; MV A, late diastolic transmitral flow; MV E, early diastolic transmitral flow; NA, not applicable; RF, rheumatoid factor; SBP, systolic blood pressure; SLEDAI, systemic lupus erythematosus disease activity index, SLICC, Systemic Lupus International Collaborating Clinics/ACR Damage Index; n=50 pairs or 50 patients or 50 controls unless otherwise stated.

Table 2. Uni-and multivariable linear regression for predictors of cardiac left ventricular function in JMCTD at follow up.
	UNIVARIABLE LINEAR REGRESSION				MULTIVARIABLE LINEAR REGRESSION
		Unstandardized	Standardized		Standardized
	R²	Beta (95% CI)	Beta	P-value	Beta	P-value	R²
EF biplane, % (LV systolic function)							0.120
Predictors at diagnosis
Male sex	0.026	-2.0 (-5.7, 1,6)	-0.160	0.266
Disease duration, years at FU	0.001	0.02 (-0.12, 0.15)	0.036	0.802
RNP, g/l	0.002	0.0 (-0.004, 0.003)	-0.044	0.765
RF positive	0.015	1.1 (-1.8, 4.1)	0.123	0.438
SLE-like findings	0.021	-2.7 (-8.1, 2.7)	-0.145	0.320
SSc-like findings	0.015	-1.3 (-4.3, 1.7)	-0.123	0.400
PM/DM-like findings	0.120	-3.4 (-6.0, -0.7)	-0.347	0.015	-0.347	0.015
LAS, % (LV systolic function)							0.299
Predictors at diagnosis
Male sex	0.206	-2.5 (-3.9, -1.19	-0.454	0.001	–0.445	0.002
Disease duration,years at FU	0.010	0.02 (-0.04, 0.08)	0.101	0.484
RNP, g/l	0.000	0.0 (-0.002, 0.001)	–0.020	0.890
RF positive	0.068	1.1 (-0.2, 2.3)	0.261	0.095
SLE-like findings	0.092	-2.4 (-4.7, -0.2)	-0.303	0.035	-0.267	0.055
SSc-like findings	0.018	-0.6 (-1.9, 0.7)	-0.136	0.353
PM/DM-like findings	0.018	-0.6 (-1.8, 0.6)	-0.136	0.351
E’ m/s (LV diastolic Function)							0.144
Predictors at diagnosis
Male sex	0.009	-0.4 (-1.8, 0.9)	-0.094	0.518
Disease duration, years at FU	0.174	-0.07(-0.11, -0.03)	-0.417	0.003	-0.380	0.008
RNP, g/l	0.091	-0.001 (-0.002, 0.000)	-0.302	0.037
RF positive	0.001	0.1(-1.0, 1.1)	0.022	0.888
SLE-like findings	0.002	-0.3 (-2.2, 1.7)	-0.039	0.791
SSc-like findings	0.074	1.0 (-0.4, 2.1)	0.272	0.058
PM/DM-like findings	0.071	-0.9 (-1.9, 0.1)	-0.266	0.065
Covariates chosen for multivariable linear regression were variables with P ≤ 0.20 in univariable regression and without multicollinearity in the multivariate models. Backward regression based on all potential predictors was performed as sensitivity analysis. P-value for inclusion was 0.05. Variables were removed by backward regression (P=0.10).

Disclosure: B. N. Witczak, None; S. O. Hetlevik, None; Z. Barth, None; T. Schwartz, None; B. Flatø, None; V. Lilleby, None; I. Sjaastad, None.

To cite this abstract in AMA style:

Witczak BN, Hetlevik SO, Barth Z, Schwartz T, Flatø B, Lilleby V, Sjaastad I. Impaired Cardiac Function in Juvenile Mixed Connective Tissue Disease Compared with Controls [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/impaired-cardiac-function-in-juvenile-mixed-connective-tissue-disease-compared-with-controls/. Accessed .

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