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Background <p>Neoadjuvant immunotherapy has transformed the management of resectable non-squamous cell lung cancer (NSCLC). However, the specific arrhythmogenic potential of immune checkpoint inhibitors (ICIs) in the postoperative setting remains poorly characterized. This study aimed to isolate the independent impact of neoadjuvant immunotherapy on postoperative atrial fibrillation (POAF) and quantify its clinical consequences.</p> Methods <p>We analyzed 1,610 patients undergoing anatomic lung resection for Stage II–III NSCLC between 2020 and 2025. To decouple the ICI effect from chemotherapy and eliminate selection bias, a 1:1:1 propensity score-matched (PSM) analysis based on baseline clinical and demographic characteristics was performed to create three balanced cohorts (n = 400 each, Total N = 1,200): (1) upfront surgery (Control), (2) isolated neoadjuvant chemotherapy (nCT), and (3) neoadjuvant chemo-immunotherapy (nCIT).</p> Results <p>Following PSM, all baseline cardiac risk factors achieved statistical parity (<i>p</i> &gt; 0.05). A significant stepwise escalation in POAF incidence was observed: 11.5% in the Control group, 15.1% in the nCT group, and 23.5% in the nCIT group (<i>p</i> &lt; 0.001). Multivariable analysis isolated the specific immunotherapy effect, revealing that the addition of ICIs independently increased POAF odds by 2.28-fold (95% CI: 1.45–3.65, <i>p</i> &lt; 0.001) compared to chemotherapy alone. Clinically, POAF development in the immunotherapy cohort resulted in a significant extension of the median hospital stay (10.4 vs. 5.6&#xa0;days, <i>p</i> &lt; 0.001) and ICU stay (3.2 vs. 1.4&#xa0;days, p &lt; 0.001). This specific ICI effect appeared to correlate with an enhanced systemic inflammatory response and increased surgical complexity observed during hilar dissection.</p> Conclusion <p>Modern neoadjuvant protocols suggest that the immunotherapy component contributes to a higher likelihood of POAF. Consequently, integrating careful perioperative cardiac monitoring and tailored management approaches for these patients could be beneficial in improving clinical outcomes and optimizing the use of hospital resources.</p>

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Neoadjuvant immunotherapy and the stepwise risk of postoperative atrial fibrillation: a propensity score-matched analysis isolating surgical and biological triggers

  • 期刊论文

  • 发表日期：

    2026年5月30日

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  • Ersin Kaya,
  • Tarık Şimşek,
  • İnan Mutlu

摘要

Background

Neoadjuvant immunotherapy has transformed the management of resectable non-squamous cell lung cancer (NSCLC). However, the specific arrhythmogenic potential of immune checkpoint inhibitors (ICIs) in the postoperative setting remains poorly characterized. This study aimed to isolate the independent impact of neoadjuvant immunotherapy on postoperative atrial fibrillation (POAF) and quantify its clinical consequences.

Methods

We analyzed 1,610 patients undergoing anatomic lung resection for Stage II–III NSCLC between 2020 and 2025. To decouple the ICI effect from chemotherapy and eliminate selection bias, a 1:1:1 propensity score-matched (PSM) analysis based on baseline clinical and demographic characteristics was performed to create three balanced cohorts (n = 400 each, Total N = 1,200): (1) upfront surgery (Control), (2) isolated neoadjuvant chemotherapy (nCT), and (3) neoadjuvant chemo-immunotherapy (nCIT).

Results

Following PSM, all baseline cardiac risk factors achieved statistical parity (p > 0.05). A significant stepwise escalation in POAF incidence was observed: 11.5% in the Control group, 15.1% in the nCT group, and 23.5% in the nCIT group (p < 0.001). Multivariable analysis isolated the specific immunotherapy effect, revealing that the addition of ICIs independently increased POAF odds by 2.28-fold (95% CI: 1.45–3.65, p < 0.001) compared to chemotherapy alone. Clinically, POAF development in the immunotherapy cohort resulted in a significant extension of the median hospital stay (10.4 vs. 5.6 days, p < 0.001) and ICU stay (3.2 vs. 1.4 days, p < 0.001). This specific ICI effect appeared to correlate with an enhanced systemic inflammatory response and increased surgical complexity observed during hilar dissection.

Conclusion

Modern neoadjuvant protocols suggest that the immunotherapy component contributes to a higher likelihood of POAF. Consequently, integrating careful perioperative cardiac monitoring and tailored management approaches for these patients could be beneficial in improving clinical outcomes and optimizing the use of hospital resources.