Predictors of subclinical systemic sclerosis primary heart involvement characterised by microvasculopathy and myocardial fibrosis

Abstract

Objectives: SSc primary heart involvement (SSc-pHI) is a significant cause of mortality. We aimed to characterize and identify predictors of subclinical SSc-pHI using cardiovascular MRI.

Methods: A total of 83 SSc patients with no history of cardiovascular disease or pulmonary arterial hypertension and 44 healthy controls (HCs) underwent 3 Tesla contrast-enhanced cardiovascular MRI, including T1 mapping and quantitative stress perfusion. High-sensitivity troponin I and N-terminal pro-brain natriuretic peptide were also measured.

Results: Cardiovascular MRI revealed a lower myocardial perfusion reserve in the SSc patients compared with HCs {median (interquartile range (IQR)] 1.9 (1.6-2.4) vs 3 (2-3.6), P < 0.001}. Late gadolinium enhancement, indicating focal fibrosis, was observed in 17/83 patients but in none of the HCs, with significantly higher extracellular volume (ECV), suggestive of diffuse fibrosis, in SSc vs HC [mean (s.d.) 31 (4) vs 25 (2), P < 0.001]. Presence of late gadolinium enhancement and higher ECV was associated with skin score [odds ratio (OR) = 1.115, P = 0.048; R2 = 0.353, P = 0.004], and ECV and myocardial perfusion reserve was associated with the presence of digital ulcers at multivariate analysis (R2 = 0.353, P < 0.001; R2 = 0.238, P = 0.011). High-sensitivity troponin I was significantly higher in patients with late gadolinium enhancement, and N-terminal pro-brain natriuretic peptide was associated with ECV (P < 0.05).

Conclusion: Subclinical SSc-pHI is characterized by myocardial microvasculopathy, diffuse and focal myocardial fibrosis but preserved myocardial contractile function. This subclinical phenotype of SSc-pHI was associated with high-sensitivity troponin I, N-terminal pro-brain natriuretic peptide, SSc disease severity and complicated peripheral vasculopathy. These data provide information regarding the underlying pathophysiological processes and provide a basis for identifying individuals at risk of SSc-pHI.

Keywords: SSc primary heart involvement; cardiovascular magnetic resonance; risk stratification.

Fig. 1

Late gadolinium enhancement fibrosis in SSc patients (A) Number of patients with LGE fibrosis as per each cardiac segment (left figure). 17-segment model (right figure) 1: basal anterior; 2: basal anteroseptal; 3: basal inferoseptal; 4: basal inferior; 5: basal inferolateral; 6: basal anterolateral; 7: mid anterior; 8: mid anteroseptal; 9: mid inferoseptal; 10: mid inferior; 11: mid inferolateral; 12: mid anterolateral; 13: apical anterior; 14: apical septal; 15: apical inferior; 16: apical lateral; 17: apex. (B) LGE fibrosis mass in those with focal, linear and diffuse pattern. (C) LGE patterns: a-focal; b-linear; c-diffuse. LGE: late gadolinium enhancement.

Fig. 2

Disease phenotype and cardiovascular MRI parameters (A) Presence or absence of LGE fibrosis and median (IQR) mRSS. (B) Association between ECV and mRSS. (C) Presence or absence of DU and ECV. (D) Presence or absence of DUs and MPR. DU: digital ulceration; ECV: extracellular volume; LGE: late gadolinium enhancement; MPR: myocardial perfusion reserve; mRSS: modified Rodnan skin score; IQR: interquartile range.

Fig. 3

Association between cardiac biomarkers and cardiovascular MRI variables (A) Presence or absence of LGE and hs-TnI. (B) Hs-TnI in focal, linear or diffuse LGE pattern. (C) Association between ECV and NT-proBNP. ECV: extracellular volume; hs-TnI: high-sensitivity troponin I; LGE: late gadolinium enhancement; NT-proBNP: N-terminal pro-brain natriuretic peptide.