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.

Myocardial Involvement Detected Using Cardiac Magnetic Resonance Imaging in Patients with Systemic Sclerosis: A Prospective Observational Study

“…We observed worsening of skin thickness and a decrease in pulmonary diffusing capacity over time in our patients. Contrary to previous studies [11,21,22], only GDF-15 correlated with these changes in our study. GDF-15 expression is induced during fibrosis development, and serum levels correlated strongly with clinical symptoms of lung fibrosis, which was the case in a previous study [25] as well as in our baseline study.…”

“…None of our patients developed pulmonary hypertension. TnI values were increased in the fibrous processes in the heart [11], but TnI levels may be affected by various cardiovascular risk factors, renal pathology, and inflammation [27]. For the reasons given, neither NT-proBNP nor hsTnI showed significant correlations with functional (DLco) or clinical (mRSS) parameters.…”

“…Several biomarkers have been studied concerning myocardial involvement. Values of high sensitivity cardiac troponins and N-terminal pro-brain natriuretic peptides (NT-proBNP) are known to be elevated in SSc patients [10,11] and have been shown to be associated with heart involvement and outcomes [12]. Other biomarkers that could express the severity of the disease and degree of myocardial fibrosis have also been investigated [13,14].…”

“…The published data suggest that the development of myocardial fibrosis is a slow and silent process that can evolve outside the detection limits of standard biochemistry or ECHO [11,15,16]. To the best of our knowledge, no work has been published so far to assess the development of changes detected by CMR over longer times.…”

Cardiovascular outcomes in systemic sclerosis with abnormal cardiovascular MRI and serum cardiac biomarkers

“…We recently reported on one of the largest studies to describe subclinical CMR features of SSc-pHI, demonstrating reduced microvascular perfusion and presence of myocardial focal and diffuse fibrosis in 83 patients with SSc. 18 This subclinical phenotype associated with high-sensitivity (hs)-TnI and NT-proBNP and also SSc disease severity and complicated peripheral vasculopathy. We now report on the clinical and functional outcomes of this cohort.…”