The Effect of Iron Deficiency on Cardiac Resynchronization Therapy: Results from the RIDE-CRT Study

AIMS: Cardiac resynchronization therapy (CRT) improves functional status, induces reverse left ventricular remodelling, and reduces hospitalization and mortality in patients with symptomatic heart failure, left ventricular systolic dysfunction, and QRS prolongation. However, the impact of iron deficiency on CRT response remains largely unclear. The purpose of the study was to assess the effect of functional and absolute iron deficiency on reverse cardiac remodelling, clinical response, and outcome after CRT implantation. METHODS AND RESULTS: The relation of iron deficiency and cardiac resynchronization therapy response (RIDE-CRT) study is a prospective observational study. We enrolled 77 consecutive CRT recipients (mean age 71.3 ± 10.2 years) with short-term follow-up of 3.3 ± 1.9 months and long-term follow-up of 13.0 ± 3.2 months. Primary endpoints were reverse cardiac remodelling on echocardiography and clinical CRT response, assessed by change in New York Heart Association classification. Echocardiographic CRT response was defined as relative improvement of left ventricular ejection fraction ≥ 20% or left ventricular global longitudinal strain ≥ 20%. Secondary endpoints were hospitalization for heart failure and all-cause mortality (mean follow-up of 29.0 ± 8.4 months). At multivariate analysis, iron deficiency was identified as independent predictor of echocardiographic (hazard ratio 4.97; 95% confidence interval 1.15-21.51; P = 0.03) and clinical non-response to CRT (hazard ratio 4.79; 95% confidence interval 1.30-17.72, P = 0.02). We found a significant linear-by-linear association between CRT response and type of iron deficiency (P = 0.004 for left ventricular ejection fraction improvement, P = 0.02 for left ventricular global longitudinal strain improvement, and P = 0.003 for New York Heart Association response). Iron deficiency was also significantly associated with an increase in all-cause mortality (P = 0.045) but not with heart failure hospitalization. CONCLUSIONS: Iron deficiency is a negative predictor of effective CRT therapy as assessed by reverse cardiac remodelling and clinical response. Assessment of iron substitution might be a relevant treatment target to increase CRT response and outcome in chronic heart failure patients.