Reduced heart rate variability is associated with disease severity in AL amyloidosis: a retrospective cohort study.

BACKGROUND: Autonomic nervous system involvement is common in systemic amyloidosis, yet the clinical relevance of heart rate variability (HRV) in immunoglobulin light-chain (AL) amyloidosis remains incompletely defined. METHODS: In this retrospective cohort study, 56 patients with biopsy-proven AL amyloidosis and 33 age- and sex-comparable healthy controls underwent 24 h Holter monitoring. Time- and frequency-domain HRV parameters were recorded. Associations of HRV with cardiac involvement assessed by cardiac magnetic resonance (CMR), Mayo 2004 stage, and short-term treatment response were evaluated using group comparisons and multivariable regression. RESULTS: Compared with controls, patients with AL amyloidosis had significantly higher mean heart rate and lower SDNN, total power (TP), and all frequency-domain components (ULF, VLF, LF, and HF) (all P < 0.05). Patients with CMR-defined cardiac involvement showed a higher prevalence of HRV abnormalities and lower SDNN, SDANN, pNN50, TP, ULF, VLF, and LF than CMR-negative patients (all nominal P < 0.05). In multivariable models, troponin remained independently associated with CMR-positive status, whereas HRV indices did not retain independent significance. By Mayo 2004 stage (I/II/III: 11/20/25), SDANN and VLF declined progressively with advancing stage (P < 0.05), and SDANN remained independently associated with higher stage after adjustment for troponin. In the exploratory subset with paired follow-up Holter recordings (n = 33), most HRV parameters did not change significantly after therapy; however, the coefficient of variation (CV) showed a statistically significant increase following treatment (P = 0.037). CONCLUSION: Reduced HRV is a prominent feature of AL amyloidosis and is independently associated with Mayo stage after adjustment for cardiac biomarkers. These findings position HRV as a non-invasive marker of autonomic involvement that complements established cardiac biomarkers in characterising disease severity in AL amyloidosis; whether this translates into independent prognostic value requires evaluation in prospective outcome studies.