Myocardial performance improvement after iron replacement in heart failure patients with LVEF &lt;50% and TSAT &lt;20%: The IRON-PATH II echo-substudy
Authors: Ramos Polo R , Pons Riverola A , Miguel Martinez J , Cabarrocas I De Llanos A , Ras-Jimenez M , Basalo M , Garcia-Pinilla J , Cobo-Marcos M , De Juan-Baguda J , Fonseca C , Yun-Viladomat S , Jovells-Vaque S , Enjuanes-Grau C , Comin-Colet J 
Published: October 2024

Abstract

Background
Iron deficiency (ID) is a prevalent comorbidity in patients with heart failure (HF) and left ventricular ejection fraction (LVEF) &lt;50%. ID leads to impaired myocardial global function. Some echocardiographic parameters have demonstrated an additive value in advanced assessment of cardiac performance, like global longitudinal strain (GLS), myocardial work (MW) and its derivatives constructive work (CW), wasted work (WW) and work efficiency (WE). The usual definition of ID may have limitations in rightly identifying systemic iron status, especially those with isolated hypoferritinemia. However, the impact on cardiac function measured by echocardiography after intravenous iron replacement according to TSAT values has never been explored.

Purpose
Describe the myocardial performance associated with systemic ID defined as TSAT &lt;20% in patients with HF compared to patients with HF without ID (TSAT ≥20%). Afterwards, we aimed to explore changes in myocardial function after iron replacement by echocardiography.

Methods
The IRON-PATH II was a multicenter, prospective, observational study. The total number of patients to be recruited was 210 in 7 centers across Spain and Portugal. Patients with HF and LVEF ≤50%, without signs of fluid overload or low cardiac output, and haemoglobin ≥11 g/dL were included. The IRON-PATH II echo-substudy included 100 patients who undergone a specific pilot evaluation of echocardiographic. All patients undergone an echocardiography at baseline, ID-patients received a second echocardiography three months after ID replenishment.

Results
The final study cohort included in the echo-substudy consisted of 98 patients, 41 (42%) were classified in the ID group (TSAT &lt;20%). Regarding the usual definition of ID, 7 patients (15%) in the ID group had TSAT ≥20%, while 4 (7%) in the non-ID group showed TSAT &lt;20%.
Mean age was 72±10 years, 22 (22%) were women and most were in NYHA functional class II (71%). Ischemic was the main etiology of HF (50%). The ID group presented worse LV function expressed by LVEF (34% vs. 38%), WW (302[235.5-439,75] mmHg% vs. 209.5[136-297.25] mmHg%) and WE (74±10% vs. 80±10%) (Figure 1). Right ventricle function was also worse in the ID group when measured by fractional area change (FAC) (41.76[33.26-50.33] % vs 46.79[39.23 – 54.94] %) and RV coupling ratio (0.52±0.21 vs 0.64±0.24) but not by TAPSE. Strikingly, no differences were observed in any echocardiographic parameter of myocardial function between the non-ID patients compared with the ID-patients after iron replenishment (Table 1).

Conclusions
TSAT &lt;20% identified ID status that causes impaired myocardial performance in HF patients. This can be reversed with intravenous iron repletion. This reversible damage to cardiac function can be detected by advanced echocardiographic parameters, both for LV (GLS, WE, MW, WW) and for RV (RVFW strain, RV coupling), but not by LVEF or TAPSE.Figure 1Table 1