Assessment of sub clinical right ventricular ischemia using oxygen sensitive cardiac magnetic resonance imaging in patients with systemic sclerosis: mechanistic insights from advanced cardiac imaging
Authors: Egberts B , Ananthakrishna R , Shah R J , Regalado J J , Sutton A , Mcwilliams L , Walker J , Pasculpathy S , Proudman S , Selvanyagam J B 
Published: October 2024

Abstract

Background
Cardiac involvement in Systemic Sclerosis (SSc) is common, with manifestations ranging from subclinical to life-threatening 1. Cardiopulmonary complications, including, right ventricular (RV) dysfunction is the leading cause of SSc-related mortality2. Pulmonary arterial hypertension (PAH) occurs in 8-12% of SSc patients and remains a leading cause of death, with a 3-year survival rate around 50%2. The progressive decline in RV function in PAH is often attributed to RV ischemia3. Oxygen Sensitive Cardiac Magnetic Resonance imaging (OS-CMR) has been previously used by our group to assess RV myocardial oxygenation in patients with PAH3, including SSc-associated PAH 3. The objective of this study was to use OS-CMR to assess RV myocardial oxygenation in SSc patients prior to the onset of PAH.

Methodology
In this prospective, multicentre study, three study groups were established. Group 1 comprised SSc patients without PAH or known cardiac disease. Group 2 included stable PAH patients confirmed by right heart catheterization, matched for age and sex, but without SSc. Group 3 comprised healthy normal volunteers (NV), matched for age and sex. All patients underwent a 3T CMR which included: cine images, rest cine OS-CMR, stress cine OS-CMR, native T1 mapping, stress perfusion, and late gadolinium enhancement (LGE). The primary outcome was change in inferior RV myocardial signal intensity (SI) in diastole, measured by the change in OS-CMR between rest and stress within each group. Two experienced independent reviewers performed the CMR analysis with an inter-assessor correlation coefficient of 0.8, 95% Cl [0.3, 0.9].

Results
A total of 44 patients were enrolled. Of these, n=26 group 1 (SSc), n=8 group 2 (PAH), n=10 group 3 (NV). Study results are listed in Table 1. Mean age within the SSc, PAH, and NV groups were 59±10, 67±12 and 57 ±7 years respectively (p=0.482). The RV OS-CMR SI was significantly lower in the SSc group when compared to the NV group (p=0.017). In contrast, there was no significant difference between the PAH and SSc groups (p=0.426), indicating a similar degree of RV ischemia in the established PAH patients and the SSc patients. All SSc patients exhibited inferior and anterior RV insertion fibrosis, with no perfusion defects noted. Five (19%) of SSc patients presented with LGE hyperenhancement in the LV. Eighteen (69%) of SSc patients obtained at least 1 abnormal T1 mapping segment in the LV.

Conclusion
SSc patients without overt PAH had a similar degree of RV ischemia when compared to patients with overt PAH from other causes. Our findings imply that in SSc, RV adverse effects occur prior to the onset of PAH, and that this effect is mediated by RV ischemia secondary to changes in the microvasculature. Our findings may have screening and/or therapeutic implications.