The Gut-Heart Axis in Systemic Sclerosis: Evidence From a Large Prospective Early Disease Cohort.

Abstract

Cardiac involvement significantly impacts prognosis in systemic sclerosis (SSc), highlighting the need for early risk stratification. Gastrointestinal (GI) symptoms are common and often manifest early. Emerging data suggest a link between GI and cardiac manifestations, possibly through shared mechanisms like dysautonomia. This study investigates the overall association between GI and cardiac involvement in early SSc and evaluates whether baseline GI symptoms predict future cardiac manifestations. We analyzed 459 patients from the prospective Genetics versus Environment in Scleroderma Outcomes Study cohort. GI involvement at baseline was defined by one or more of the following: dysphagia, gastroesophageal reflux disease, peptic ulcer, bloating, diarrhea, malabsorption, constipation, or pseudo-obstruction. Cardiac manifestations included conduction defects and systolic dysfunction. Cox and multivariable logistic regression models assessed associations, adjusting for potential confounders. The cohort included 459 patients with SSc (82% female), with a median follow-up of 4.1 years (interquartile range 0.8-8.1). At baseline, 59% of patients had GI involvement. During follow-up, 26% of patients developed cardiac manifestations-mainly conduction defects (24%) and less commonly systolic dysfunction (5%). Baseline malabsorption and bloating were strong predictors of future cardiac involvement, with malabsorption showing the highest risk (hazard ratio 10.01 [95% confidence interval 3.7-26.9]). Interestingly, dysphagia and peptic ulcers were significantly associated with conduction defects, whereas malabsorption was significantly associated with systolic dysfunction, even after adjustment for potential confounders. Upper GI dysfunction was associated specifically with conduction defects, suggesting that autonomic dysfunction contributes. In contrast, lower GI involvement, particularly malabsorption, was linked to systolic dysfunction in patients with SSc, potentially indicating a distinct biologic mechanism. These findings may support integrating early GI symptoms into cardiac risk stratification, and they provide a foundation for future translational studies.