Juvenile-Onset Mixed Connective Tissue Disease Associated With Systolic Dysfunction

Human heart, computer artwork.
Patients with juvenile mixed connective tissue disease had impaired left and right ventricular function compared with matched controls after a median of 15 years disease duration.

At 15 years post-onset, patients with juvenile mixed connective tissue disease (MCTD) had mostly subclinical left ventricle (LV) and right ventricle (RV) systolic dysfunction (LVD and RVD) but no diastolic dysfunction compared with healthy controls, according to a report published in The Journal of Rheumatology. Higher disease activity and longer prednisolone treatment were significantly associated with LVD.

Much of the mortality associated with adult mixed CTD is a result of cardiovascular disease; however, cardiac function has not been studied in juvenile MCTD populations. Investigators aimed to compare cardiac function in patients with juvenile MCTD vs healthy controls and to identify potential associations between cardiac dysfunction and disease variables and related cardiovascular risk factors in a first of its kind study.

Related Articles

Between March 2013 and June 2015, a prospective case-control study enrolled 50 patients with juvenile MCTD (median age, 27.2 years; 86% women; median disease duration, 14.9 years) and 50 age- and sex-matched controls at Oslo University Hospital. Electrocardiogram and echocardiogram were performed in blinded fashion on all participants, with diastolic dysfunction marked by e’ and systolic dysfunction identified by long-axis strain (LAS) and LV ejection fraction (LVEF). Low LVEF, low e’ or low LAS identified those with LVD. Tricuspid annular plane systolic excursion was used to assess RVD.

As there is no accepted activity measure for juvenile MCTD, a variety of indices used for related conditions was employed. Clinical remission was achieved when patients demonstrated inactive disease for ≥6 months.

At follow-up, 35 (70%) patients had active disease and 36 (72%) were prescribed immunosuppressive medications. Of the 37 participants with electrocardiogram data available, a total of 7patients with juvenile MCTD and 2controls had pathologic electrocardiogram findings. Evidence of LVD was seen in 8 patients with juvenile MCTD and 2 controls (P =.035), with both LAS and LVEF lower in patients with juvenile MCTD vs controls (4% and 6% lower, respectively; P =.044 and P <.001, respectively). There was an 8% difference in tricuspid annular plane systolic excursion between groups, with patients with juvenile MCTD registering lower scores than controls (P =.008). Patients with juvenile MCTD exhibited longer corrected QT times compared with controls (P =.012).

No pulmonary hypertension was detected in the patient group, and no diastolic dysfunction differences existed between the groups.

Higher apolipoprotein B levels (P =.023), higher systolic (P =.032) and diastolic (P =.045) blood pressures, longer prednisolone therapy duration (P =.015), higher activity by physician’s global assessment (P =.019), and greater organ damage according to the Myositis Damage Index (P =.047) were associated with LVD. There was no difference in antibody profiles or other disease characteristics between patients with or without LVD. Erythrocyte sedimentation rate was also higher in patients (P <.001), while apolipoprotein A-I was higher in controls (P <.001).

Study strengths included a representative juvenile MCTD cohort, state-of-the-art methodologies, and comparable demographic characteristics between groups. Study limitations included small sample size, lack of validated measures for MCTD, and the possibility that some P values might be the result of chance.

“Our study revealed impaired systolic function measured by LAS and EF in patients with [juvenile MCTD compared to controls, despite their young age,” noted the authors, adding, “Further prospective studies are needed to evaluate the prognostic implication of subclinical LVD in [juvenile MCTD].”


Witczak BN, Hetlevik SO, Sanner H, et al. Effect on cardiac function of longstanding juvenile-onset mixed connective tissue disease: a controlled study [published online March 15, 2019]. J Rheumatol. doi:10.3899/jrheum.180526