Evaluation of Systemic Sclerosis Primary Heart Involvement and Chronic Heart Failure in the European Scleroderma Trials and Research Cohort

Abstract

Background: Systemic sclerosis (SSc) primary heart involvement (SSc-pHI) is one of the leading causes of mortality in SSc. We aimed to evaluate risk factors for SSc-pHI and its progression and the outcomes in the EUSTAR (European Scleroderma Trials and Research) cohort.

Methods: SSc-pHI was defined according to the World Scleroderma Foundation/Heart Failure Association definition. Data from 5741 patients with SSc in the EUSTAR cohort were analyzed. Additional cardiovascular data were collected from a subcohort of 838 patients with SSc. Lasso regression was used for risk factor analyses. Kaplan-Meier estimator was used for survival analyses. Progression of SSc-pHI was evaluated by a study definition developed by rheumatology and cardiology experts.

Results: Risk factors for the presence of SSc-pHI comprised skeletal muscle atrophy (odds ratio [OR], 2.00 [95% CI, 1.00-2.68]), age (OR, 1.91 [95% CI, 1.73-2.03]), male sex (OR, 1.77 [95% CI, 1.42-2.05]), swollen joints (OR, 1.70 [95% CI, 1.47-1.98]), skeletal muscle weakness (OR, 1.38 [95% CI, 1.00-1.85]), and tendon friction rubs (OR, 1.46 [95% CI, 1.00-1.77]) (n=3276). Telangiectasia (OR, 2.10 [95% CI, 1.38-2.72]), intestinal symptoms (OR, 1.70 [95% CI, 1.04-2.42]), age (OR, 1.47 [95% CI, 1.21-1.62]), and antitopoisomerase I antibodies (OR, 1.37 [95% CI, 1.00-1.77]) were associated with an increased risk for new onset of SSc-pHI (n=1000). Survival rate was significantly lower in patients with SSc-pHI than in those without (P value <0.0001, n=3768). Patients with SSc-pHI had a lower survival rate than patients with interstitial lung disease (n=3365). Swollen joints were associated with an increased risk of progressive SSc-pHI (OR, 2.49 [95% CI, 1.79-3.52]) (n=595). Tendon friction rubs (OR, 1.21 [95% CI, 0.94-1.90]) increased the risk of heart failure with preserved ejection fraction in patients with SSc-pHI.

Conclusions: We defined progressive SSc-pHI and identified risk factors for new onset and progression of SSc-pHI and for SSc-pHI-associated heart failure with preserved ejection fraction in the largest cohort with SSc. These findings may guide patient stratification for diagnostic workup and therapy.

Keywords: EUSTAR cohort; mortality; risk factors; systemic sclerosis; systemic sclerosis primary heart involvement.

Figure 1. Schematic representation of the study design.

At the time of data collection (July 1, 2021), 17 760 patients with SSc had been included in the EUSTAR cohort. Of these patients, 5167 were excluded from further analyses as they fulfilled 1 or more of the exclusion criteria. Another 6852 patients were excluded due to missing data regarding all inclusion criteria of the study. The remaining 5741 patients from the EUSTAR cohort were used for further analyses: 3276 patients were used for the analysis of risk factors for the presence of SSc‐pHI, 1000 patients were used for the analysis of risk factors for the development of SSc‐pHI, and 595 patients were used for the analysis of risk factors for the progression of SSc‐pHI. Survival analyses included 3768 patients. EUSTAR indicates European Scleroderma Trials and Research; NA, Not available; and SSc‐pHI, systemic sclerosis primary heart involvement.

Figure 2. Risk factor analysis for the presence of SSc‐pHI and its distinct clinical entities in the EUSTAR cohort.

Dot plot illustrating the odds of the presence of muscle atrophy, age, male sex, swollen joints, muscle weakness, tendon friction rubs, telangiectasia, antitopoisomerase I antibodies, intestinal symptoms, interstitial lung disease, and digital ulcers for the presence of SSc‐pHI (black dot), cardiac arrhythmias (blue rhombus), cardiac conduction blocks (yellow rhombus), left ventricular diastolic dysfunction (violet rhombus), perimyocarditis (green rhombus), and left ventricular systolic dysfunction (defined as a left ventricular ejection fraction below 50%) (red rhombus). EUSTAR indicates European Scleroderma Trials and Research; ILD, interstitial lung disease; OR, odds ratio; and SSc‐pHI, systemic sclerosis primary heart involvement.

Figure 3. Survival analyses in patients with and without SSc‐pHI in a EUSTAR subcohort and the EUSTAR database.

Kaplan–Meier curves illustrating the survival probabilities of patients with SSc‐pHI (blue curve) and without SSc‐pHI (red curve) in the whole EUSTAR cohort (A) and a EUSTAR sub‐cohort (B). The shaded areas represent the 95% CIs. EUSTAR indicates European Scleroderma Trials and Research; and SSc‐pHI, systemic sclerosis primary heart involvement.

Figure 4. Survival analysis in patients with and without ILD or SSc‐pHI in the EUSTAR cohort.

Kaplan–Meier curves illustrating the survival probabilities of patients without ILD and SSc‐pHI (red curve), patients with SSc‐pHI and without ILD (green curve), patients without SSc‐pHI and with ILD (blue curve), and patients with both ILD and SSc‐pHI (violet curve) in the EUSTAR cohort. Patients meeting the exclusion criteria of the study were not included. The shaded areas represent the 95% CIs. EUSTAR indicates European Scleroderma Trials and Research; ILD, interstitial lung disease; and SSc‐pHI, systemic sclerosis primary heart involvement.

Figure 5. Survival analyses in patients with SSc‐pHI with and without HFpEF and patients with SSc without SSc‐pHI in the EUSTAR cohort.

Kaplan–Meier curves illustrating the survival probabilities of patients with SSc‐pHI with HFpEF (red curve) and without HFpEF (blue curve) as well as patients with SSc without SScpHI (green curve) in the whole EUSTAR cohort. EUSTAR indicates European Scleroderma Trials and Research; HFpEF, heart failure with preserved ejection fraction; SSc, systemic sclerosis; and SSc‐pHI, systemic sclerosis primary heart involvement.