Unveiling the Gut–Heart Axis in Cardiac Amyloidosis: A Systematic Review of Emerging Evidence

Background: Cardiac amyloidosis is an underdiagnosed infiltrative cardiomyopathy caused by the extracellular deposition of misfolded proteins. The two principal subtypes—light-chain (AL) amyloidosis and transthyretin (ATTR) amyloidosis—differ in pathogenesis and clinical course. Growing evidence implicates the gut microbiota in cardiovascular diseases through immune, inflammatory, and metabolic pathways. However, its potential role in cardiac amyloidosis remains unexplored.Methods: This systematic review was conducted in accordance with the PRISMA 2020 and PRISMA-S guidelines. A comprehensive search of PubMed, EMBASE, and Web of Science was performed from inception to April 2025. Eligible studies included original human research evaluating the gut microbiota in the context of AL or ATTR cardiac amyloidosis via validated molecular techniques such as 16S rRNA sequencing. Titles, abstracts, and full texts were screened by two reviewers, and key variables were extracted and synthesised narratively.Results: Three studies met the inclusion criteria. In a case–control study of hereditary ATTR (ATTRv), patients presented increased microbial α diversity and enrichment of Clostridia-class taxa, particularly those with increased myocardial amyloid burden. A cross-sectional study of ATTRv patients carrying the V142I mutation revealed that Streptococcus and Hungatella were associated with elevated cardiac biomarkers, whereas Intestinimonas was linked to increased left ventricular mass and impaired physical performance. Conversely, in AL amyloidosis, patients showed enrichment of Akkermansia and Bifidobacterium alongside depletion of Faecalibacterium—microbial signatures suggestive of impaired gut barrier integrity and systemic inflammation. A machine learning classifier based on gut microbial taxa achieved a diagnostic accuracy with an AUC of 0.95 in distinguishing AL patients from controls. Across studies, specific genera correlated with cardiac markers such as NT-proBNP, troponin, and left atrial volume.Conclusion: Despite limited sample sizes and methodological heterogeneity, current evidence supports a potential link between gut dysbiosis and cardiac amyloidosis. Microbial signatures may serve as non-invasive biomarkers of disease severity and progression. Further research in larger, multiethnic, and longitudinal cohorts is warranted to validate these associations and explore their therapeutic implications.