Cardiac Involvement in Systemic Sclerosis Beyond the Right Heart: Novel and Conventional Cardiac Magnetic Resonance Phenomics-Based Evaluation

Objectives Systemic sclerosis (SSc) patients can experience a broad range of cardiovascular complications - with cardiomyopathy development posing risks of future major cardiovascular events. We comprehensively investigated cardiovascular phenotypes of SSc patients referred for CMR and compared them to healthy volunteers (HV) using conventional CMR metrics and advanced 4D modeling.

Methods 100 SSc patients and 100 HV were studied from the Cardiovascular Imaging Registry of Calgary. All patients underwent CMR imaging inclusive of cine and late gadolinium enhancement (LGE). Conventional analyses were performed using cvi42 software. A comparison of conventional CMR markers between SSc patients and HV were utilized to identify SSc patients with a cardiomyopathy, defined as an abnormal left ventricular ejection fraction [LVEF] < 55% or LGE presence. SSc cardiomyopathic individuals were processed using 4Deep and age- and sex-matched compared against HV to characterize SSc cardiomyopathy phenotype. 4Deep is a locally developed deep learning-based 4D modeling pipeline which automatically segments cines to deliver spatially registered bi-layer 4D LV meshes, providing regional 3D wall thickness, mass, and principal strain. Patients were followed for a composite outcome of death, heart failure admission, or sustained ventricular tachycardia.

Results Clinical and CMR characteristics of the SSc (median age 57 years old, 67% female) and HV patients (median age of 46 years old, 54% female) are summarized (Table 1). Conventional CMR analysis revealed 30% of SSc patients with a cardiomyopathy (21% abnormal LVEF, 18% abnormal LGE) and 20% with an abnormal right ventricular (RV) EF. 4Deep analysis of 24 age- and sex-matched SSc patients with LV cardiomyopathy to HV revealed SSc patients experienced significant reductions of 14.7% LVEF, 18.8% mean max. principal strain, and increases of 1.3 mm in LV wall thickness and 3.1% mean min. principal strain in comparison to HV. SSc patients with a cardiomyopathy experienced significantly reduced minimum principal strain deformation in septal and apical segments of the heart. Over a median follow-up of 4.1 years, 32% of SSc patients developed a composite primary outcome. In the full cohort, a multivariable model including age, sex, LVEF, LGE fibrosis burden, and RVEF showed RVEF as the only independent predictor (HR 0.95 [0.91-0.99], p=0.006).

Conclusion In this large cohort of SSc patients referred for CMR, one-third demonstrated LV cardiomyopathy with 38% showing LV or RV abnormality. LV disease localized to the septal and apical segments. Larger studies are needed to determine the incremental prognostic value of these features beyond RVEF.