Background/Purpose: Cardiac manifestations significantly impact the prognosis of patients with systemic sclerosis (SSc), underscoring the need for early risk stratification. While gastrointestinal (GI) symptoms are common and impair quality of life, their role as predictors of cardiac involvement remains unclear. Emerging data suggest a link between GI and cardiac manifestations, possibly through shared mechanisms like dysautonomia and immune-mediated damage to mesodermally derived neurons. This study explores whether baseline GI symptoms could serve as early indicators of future cardiac events, aiming to identify high-risk phenotypes for personalized management.

Methods: We analyzed data from 459 patients with early SSc enrolled in a prospective cohort. GI and cardiac manifestations were comprehensively evaluated both at baseline and during follow-up. GI involvement was defined as the presence of one or more of the following symptoms: dysphagia, peptic ulcer, bloating, diarrhea, malabsorption, constipation, or pseudo-obstruction. To assess whether any of these early GI symptoms could predict the later development of cardiac complications—specifically conduction abnormalities or cardiomyopathy—we applied multivariable logistic regression and Cox models, adjusting for key confounders such as age, sex, and disease duration.

Results: At baseline, GI involvement was present in 60% of patients with early systemic sclerosis. During follow-up, 26% of these patients developed cardiac complications, mainly conduction defects (24%) and less frequently cardiomyopathy (5%). A significant association was found between GI manifestations and cardiac involvement, with bloating showing the strongest association (OR 3.3, 95% CI 1.7–6.2), even after adjustment in the multivariable model (Tab.1). We then examined the strength of the association between individual GI symptoms and the two cardiac complications. Notably, upper GI symptoms like dysphagia (OR 3.3; 95% CI: 1.8–6.0) and peptic ulcers (OR 3.2; 95% CI: 1.5–7.2) were specifically associated with conduction defects, while malabsorption was strongly associated with cardiomyopathy (OR 4.6; 95% CI: 1.4–15.0). These associations remained robust even in the multivariable model. Cox regression was then applied to identify baseline GI symptoms in SSc patients that predict cardiac complications. Interestingly, malabsorption and bloating emerged as the strongest predictors of subsequent cardiac complication with malabsorption in particular conferring the highest risk, with a hazard ratio (HR) of 33.6 (95% CI: 15.8–71.1), after adjusting for potential confounders (Fig.1) (Tab.2).

Conclusion: Upper GI symptoms were selectively associated with cardiac conduction defects, suggesting that autonomic nervous system dysfunction may contribute to this relationship. In contrast, lower GI involvement—particularly malabsorption—was linked to cardiomyopathy in early SSc, pointing to a possible shared mechanism. If confirmed in other early SSc cohorts, these findings support the integration of early GI symptoms into cardiac risk stratification and highlight the importance of targeting these patient subgroups in future translational research.

Table 1. Associations between GI manifestations and cardiac complications* in SSc patients over time: results from logistic models.

Definition of GI manifestations:(a) Dysphagia, defined as pain or difficulty in swallowing or passing food;(b) Peptic ulcer, documented; (c) Bloating;(d) Diarrhea;(e) Malabsorption, confirmed by diarrhea associated with >10% weight loss or by abnormal chemical studies. Symptoms from (c) to (d) were self-reported by patients.

*Cardiac complications refers to the following domains: cardiomyopathy and conduction defects.

§ Refers to the age at the time of the first cardiac complication (if applicable) or the maximum age reached during the study period (if no cardiac complication occurred).

# Refers to disease duration from the first non-Raynaud symptom to the time of the first cardiac complication (if applicable), or to the maximum disease duration reached during the study period (if no cardiac complication occurred).

Values are Odds Ratio (95% confidence interval).

† Statistically significant.

Table 2. Baseline GI predictors of cardiac complications*in patients with systemic sclerosis.

Definition of GI predictors:(a) Dysphagia, defined as pain or difficulty in swallowing or passing food;(b) Bloating;(c) Diarrhea;(d) Malabsorption, confirmed by diarrhea associated with >10% weight loss or by abnormal chemical studies. Symptoms (b) and (c) were self-reported by patients.

*Cardiac complications refers to cardiomyopathy and/or conduction defects.

Values are Hazard Ratios (95% confidence interval).

§ Refers to the age at baseline.

# Refers to the disease duration from the first non-Raynaud symptom at baseline.

† Statistically significant.

Figure 1. Kaplan-Meier analysis of time to cardiac complications* onset according to baseline bloating and malabsorption.

*Cardiac complications refers to cardiomyopathy and/or conduction defects.

Log-rank test: Bloating at baseline, p < 0.001; Malabsorption at baseline, p < 0.001.

« Back to ACR Convergence 2025

ACR Meeting Abstracts - https://acrabstracts.org/abstract/the-gut-heart-axis-in-systemic-sclerosis-evidence-from-the-genisos-cohort/