# Low Body Mass Index as a Predictor of Amiodarone‐Induced Pulmonary Toxicity

**Authors:** Takuto Zaizen, Hidekazu Kondo, Teruo Noguchi, Reina Tonegawa‐Kuji, Tsukasa Kamakura, Mitsuru Wada, Kohei Ishibashi, Yuko Inoue, Koji Miyamoto, Takeshi Aiba, Naohiko Takahashi, Kengo Kusano

PMC · DOI: 10.1002/joa3.70205 · Journal of Arrhythmia · 2025-10-22

## TL;DR

Low BMI increases the risk of lung damage from amiodarone, a heart medication, and KL-6 levels can help detect this toxicity.

## Contribution

Identifies low BMI as a novel independent risk factor for amiodarone-induced pulmonary toxicity.

## Key findings

- Patients with BMI <22 kg/m² were three times more likely to develop APT.
- A KL-6 cutoff of 444 U/mL showed 70.8% sensitivity and 88.1% specificity for APT detection.
- Higher age and amiodarone dose were also significant risk factors for APT.

## Abstract

Amiodarone‐induced pulmonary toxicity (APT) is one of the major side effects of the medication when used in the treatment of arrhythmia. However, the risk factors for developing APT have yet to be fully understood.

We retrospectively analyzed 454 patients who were treated with amiodarone for arrhythmia between 2016 and 2020 at the National Cerebral and Cardiovascular Center, Osaka, Japan. During the median follow‐up period of 207 days, 24 patients (5.4%) had APT. Using a multivariate analysis of the Cox proportional hazards model, lower body mass index (BMI) (hazard ratio [HR]: 0.81, 95% confidence interval [CI]: 0.71–0.95), higher age (HR: 1.06, 95% CI: 1.02–1.10), and higher amiodarone maintenance dose (HR: 1.01, 95% CI: 1.003–1.02) were risk factors for APT. Specifically, the patients whose BMIs were < 22 kg/m2 were approximately three times more likely to develop APT than the patient whose BMIs were ≥ 22 kg/m2. The cutoff value for maximum KL‐6 levels during amiodarone therapy as an APT screening test was 444 U/mL or higher, with a sensitivity of 70.8% and specificity of 88.1%.

Lower BMI, higher age, and a higher maintenance dose were identified as independent risk factors for APT. KL‐6 levels during administration may be useful in suspecting the development of APT.

This retrospective study analyzing 454 patients who were treated with amiodarone revealed that the patients whose BMIs were < 22 kg/m2 were more likely to develop amiodarone‐induced pulmonary toxicity. The cutoff value for maximum KL‐6 levels during amiodarone therapy as an APT screening test was 444 U/mL.

## Linked entities

- **Chemicals:** amiodarone (PubChem CID 2157)
- **Diseases:** arrhythmia (MONDO:0007263)

## Full-text entities

- **Genes:** MUC1 (mucin 1, cell surface associated) [NCBI Gene 4582] {aka ADMCKD, ADMCKD1, ADTKD2, CA 15-3, CD227, Ca15-3}
- **Diseases:** APT (MESH:D008171), arrhythmia (MESH:D001145)
- **Chemicals:** Amiodarone (MESH:D000638)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

20 references — full list in the complete paper: https://tomesphere.com/paper/PMC12541544/full.md

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Source: https://tomesphere.com/paper/PMC12541544