The Gut-Heart Axis in Systemic Sclerosis: Evidence from the GENISOS cohort

Background

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.

Methods

We analyzed 459 patients from the prospective GENISOS cohort. GI involvement at baseline was defined by one or more of the following: dysphagia, 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.

Results

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 [HR 12.38 (95% CI: 4.4 – 34.6)]. Interestingly, dysphagia and peptic ulcers were significantly associated with conduction defects, while malabsorption was significantly associated with systolic dysfunction, even after adjustment for potential confounders.

Conclusions

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 SSc patients, potentially indicating a distinct biological mechanism. These findings may support integrating early GI symptoms into cardiac risk stratification, and provide a foundation for future translational studies.

Key messages

• Distinct cardiac phenotypes in SSc patients associate with distinct types of GI involvement.

• Upper GI manifestations were significantly associated with conduction defects, possibly reflecting shared dysautonomia, affecting both GI motility and cardiac rhythm.

• Lower GI involvement was significantly associated with systolic dysfunction, suggesting that a distinct mechanism may underlie this clinical phenotype.