Diffuse myocardial fibrosis precedes subclinical functional myocardial impairment and provides prognostic information in systemic sclerosis.

Aims: Myocardial involvement is common in patients with systemic sclerosis (SSc) and causes myocardial fibrosis and subtle ventricular dysfunction. However, the temporal onset of myocardial involvement during the progression of the disease and its prognostic value are yet unknown. We used cardiovascular magnetic resonance (CMR) to investigate subclinical functional impairment and diffuse myocardial fibrosis in patients with very early diagnosis of SSc (VEDOSS) and established SSc and examined whether this was associated with mortality.
Methods and Results: One hundred and ten SSc patients (86 established SSc, 24 VEDOSS) and 15 healthy controls were prospectively recruited. The patients were followed-up for a median duration of 7.0 years (interquartile range 6.0-7.3 years). Study subjects underwent CMR including assessment of myocardial fibrosis [native T1 and extracellular volume (ECV)] and measurement of global longitudinal (GLS) and circumferential (GCS) myocardial strain. Native T1 values and ECV were elevated in VEDOSS and SSc patients compared with controls (P < 0.001). GLS was similar in VEDOSS and controls but significantly impaired in patients with established SSc (P < 0.001). GCS was similar over all groups (P = 0.88). There were 12 deaths during follow-up. Elevated native T1 [hazard ratio (HR) 5.8, 95% confidence interval (CI): 1.7-20.4; P = 0.006] and reduced GLS (HR 6.1, 95% CI: 1.3-29.9; P = 0.038) identified subjects with increased risk of death. Only native T1 was predictive for cardiovascular mortality (P < 0.001).
Conclusion: Subclinical myocardial involvement first manifests as diffuse myocardial fibrosis identified by the expansion of ECV and increased native T1 in VEDOSS patients while subtle functional impairment only occurs in established SSc. Native T1 and GLS have prognostic value for all-cause mortality in SSc patients.
Competing Interests: Conflict of interest: B.M. has/had grant/research support from Abbvie, Protagen, Novartis Biomedical Research, received speaker fees from Böhringer Ingelheim as well as congress support from Pfizer, Roche, Actelion, Mepha, and MSD. C.M. has received congress support from Actelion and Roche, and personal fees from Boehringer-Ingelheim, Mepha, and MEDtalks Switzerland, outside the submitted work. R.D. reports grants/research support from Pfizer, Actelion, and personal fees (speaker/consultancy) from Actelion and Boehringer-Ingelheim, outside the submitted work. O.D. has/had consultancy relationship with and/or has received research funding from or has served as a speaker for the following companies in the area of potential treatments for systemic sclerosis and its complications in the last 3 years: Abbvie, Acceleron, Alcimed, Amgen, AnaMar, Arxx, AstraZeneca, Baecon, Blade, Bayer, Boehringer-Ingelheim, ChemomAb, Corbus, CSL Behring, Galapagos, Glenmark, GSK, Horizon (Curzion), Inventiva, iQvia, Kymera, Lupin, Medac, Medscape, Miltenyi Biotec, Mitsubishi Tanabe, Novartis, Prometheus, Roche, Roivant, Sanofi, Serodapharm, Topadur and UCB. Patent issued ‘mir-29 for the treatment of systemic sclerosis’ (US8247389, EP2331143). O.D. and B.M. have a patent for ‘mir-29 for the treatment of systemic sclerosis’ (US8247389, EP2331143). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
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