Coronary microvascular dysfunction in systemic sclerosis: insights from PET-derived myocardial flow reserve

Objectives Cardiovascular death is the second leading cause in systemic sclerosis (SSc), with coronary microvascular dysfunction (CMVD) playing a key role. PET-derived myocardial blood flow (MBF) and flow reserve (MFR) offer a validated, noninvasive way to assess CMVD. We studied the prevalence of impaired MFR in SSc and its association with vasodilator or immunomodulatory therapy. Methods SSc patients who underwent dynamic 82-Rubidium PET myocardial perfusion imaging (MPI) at Yale New Haven Hospital (July 2016 to April 2025) were studied. Patients were matched 3:1 with controls without autoimmune rheumatologic disease based on age, sex, body mass index, and cardiovascular comorbidities. Abnormal MFR was defined as < 2.0. Results The cohort included 67 SSc patients (87% female, age : 61 ± 11 years, 21% diffuse cutaneous SSc, SSc duration : 12 ± 10 years) and 201 controls. Rest MBF was higher in SSc (1.14 [IQR 0.91–1.39] ml/g/min) vs controls (1.00 [IQR 0.78–1.25]; p= 0.01), while MFR was lower (2.17 [IQR 1.84–2.57] vs 2.44 [IQR 1.96–2.96]; p= 0.01). Stress MBF was similar (2.47 [IQR 1.99–2.82] vs 2.43 [IQR 1.91–3.04]; p= 0.85). Multivariable analysis showed mycophenolate mofetil (MMF) use linked to lower odds of abnormal MFR (OR 0.09 [95% CI 0.01–0.56]; p= 0.017), while calcium-channel blockers (OR 7.77 [1.93–42.53]; p= 0.008) and statins (OR 7.14 [1.86–36.87]; p= 0.008) increased odds. Conclusions PET MPI reveals reduced MFR in SSc. Treatment associations, including MMF, should be interpreted cautiously given the retrospective design. PET-derived MFR may serve as a noninvasive marker of vascular involvement, warranting prospective validation.