Peripheral microvascular function is linked to cardiac involvement on CMR in systemic sclerosis-related pulmonary arterial hypertension patients

Abstract

Abstract Background Systemic sclerosis (SSc) is characterized by vasculopathy, inflammation and fibrosis, and carries one of the worst prognosis in patients who also develop pulmonary arterial hypertension (PAH). Although PAH is a known prognosticator, SSc-PAH patients demonstrate disproportionately high morbidity and mortality, presumably due to cardiac involvement. Purpose To determine the pathophysiology of cardiac involvement in SSc, cardiovascular magnetic resonance (CMR) measures of perfusion, inflammation and fibrosis were compared between SSc-PAH and idiopathic PAH (IPAH) patients. In addition, the correlation between myocardial involvement on CMR and known markers of peripheral microvascular function was assessed. Methods Consecutive patients with SSc-PAH and IPAH of similar age and gender, consecutively underwent CMR imaging, and nailfold capillaroscopy (NC) with post-occlusive reactivity hyperaemia-test (PORH-test). CMR imaging included T2 mapping (inflammation), pre- and postcontrast T1 mapping to calculate the extracellular volume fraction (ECV, fibrosis), and adenosine-stress perfusion imaging to measure the relative myocardial upslope (microvascular perfusion), all measurements were performed on the left ventricle. These CMR markers were related to peripheral microvascular function by NC and PORH-test. Results Twenty SSc-PAH patients (71 [62–77] years, 14% male) and 5 IPAH patients (69 [47–77] years, 20% male) were included. SSc-PAH patients had higher ECV and T2 values than IPAH patients. NC showed lower average capillary density and reduced recruitment of capillaries after PORH in SSc-PAH patients, corresponding to impaired microvascular structure and function. Both higher ECV and T2 values correlated with lower average capillary density (r=−0.454 and −0.583, respectively, p<0.05 for both). Additionally, higher T2 values and lower relative myocardial upslope correlated with worse peripheral microvascular function measured by PORH-test (r=−0.471 and r=0.421, respectively, p<0.05 for both). Conclusion SSc-PAH patients showed higher markers of cardiac fibrosis and inflammation, compared to IPAH patients. These markers correlated well with worse peripheral microvascular function, suggesting that SSc-driven inflammation and vasculopathy concurrently affect peripheral microcirculation and the heart. This may have important therapeutic implications, for which future studies are warranted evaluating the role of anti-inflammatory/anti-fibrotic therapy. Funding Acknowledgement Type of funding sources: None.