Background: Cardiac resynchronization therapy (CRT) is an established treatment for selected patients with heart failure (HF); however, a substantial proportion of patients do not derive clinical or echocardiographic benefit. Systemic inflammation has been implicated in adverse myocardial remodeling and may influence response to CRT. This study aimed to evaluate the association between the systemic immune-inflammation index (SII) and CRT response.

Methods: This retrospective, single-center study included 110 patients with HF who underwent CRT implantation. Clinical, echocardiographic, and laboratory parameters, including SII, were assessed at baseline and at 6-month follow-up. Cardiac resynchronization therapy response was defined using combined echocardiographic and clinical criteria. Associations between inflammatory markers and CRT response were analyzed.

Results: Nonresponders demonstrated significantly higher baseline SII levels compared with responders. During follow-up, SII values increased significantly in nonresponders, whereas no significant change was observed in responders. Baseline C-reactive protein (CRP) levels were similar between groups. Chronic ischemic heart disease and elevated baseline SII were independently associated with CRT nonresponse. The discriminatory ability of baseline SII for CRT nonresponse was moderate.

Conclusion: Elevated SII was associated with an increased likelihood of CRT nonresponse and persistent inflammatory activity during follow-up. These findings suggest that SII reflects an unfavorable inflammatory and biological milieu related to impaired CRT response, rather than a direct causal mechanism. Systemic immune-inflammation index may serve as a complementary biomarker for risk stratification in patients undergoing CRT.