Multimorbidity Risk Tool Incorporating Gut Microbiome Predicts HF Rehospitalization and Mortality

Overview

A novel 11-variable risk model including gut microbiome metabolites was developed and validated to predict one-year mortality and rehospitalization in heart failure (HF) patients. This model demonstrated good diagnostic performance (C-statistic ~0.70) and stratified patients into distinct risk groups with significantly different outcomes.

Background

Heart failure is a complex syndrome influenced by cardiovascular, renal, metabolic, and neurohormonal factors, with emerging evidence implicating the gut microbiome in its pathophysiology. Existing HF risk scores primarily focus on traditional cardiovascular markers and often overlook the impact of multimorbidity and gut-heart axis contributions. Non-cardiac comorbidities such as chronic obstructive pulmonary disease (COPD) and diabetes are associated with worse HF outcomes but are underrepresented in current risk stratification tools. Incorporating gut microbiome metabolites like trimethylamine N-oxide (TMAO) and related compounds may enhance prognostic accuracy.

Data Highlights

The model showed a C-statistic of 0.71 in the training cohort and 0.70 in the validation cohort (P < 0.001). Patients stratified into low-, mid-, and high-risk groups demonstrated significantly increasing incidence of death or HF rehospitalization (P < 0.001).

Key Findings

• An 11-variable risk model was developed incorporating clinical, biochemical, comorbidity, and gut microbiome factors to predict 1-year death or rehospitalization in HF patients.
• The model included traditional HF markers (age, NT-proBNP, NYHA class), comorbidities (COPD, diabetes), medication use (loop diuretics, beta-blockers), renal function (creatinine), and gut metabolites (TMAO and related compounds).
• The risk score demonstrated good discrimination with C-statistics of 0.71 (training) and 0.70 (validation), comparable to existing HF risk scores.
• Risk stratification into low-, mid-, and high-risk groups showed a stepwise increase in adverse outcomes, validating clinical utility.
• The inclusion of gut microbiome metabolites added incremental prognostic value beyond traditional risk factors.

Clinical Implications

This multimorbidity risk score incorporating gut microbiome factors provides clinicians with a practical tool to better stratify HF patients at risk of death or rehospitalization within one year. It highlights the importance of considering non-cardiac comorbidities and the gut–heart axis in HF management. Use of this risk calculator may guide more personalized treatment strategies and closer monitoring for high-risk patients.

Conclusion

The study presents a validated, clinically applicable risk model that integrates multimorbidity and gut microbiome metabolites to improve prognostication in heart failure. This novel approach advances risk stratification beyond traditional cardiovascular parameters, potentially enhancing patient outcomes through tailored care.

References

1. Tang WHW 2023 -- Editorial on Multimorbid Risk Calculator in Heart Failure