Iron deficiency impacts prognosis but less exercise capacity in heart failure with preserved ejection fraction

Abstract

Aims Whether and how iron deficiency (ID) impacts patients with heart failure (HF) with preserved ejection fraction (HFpEF) remain unclear. The aim of our study was to investigate the impact of ID on functional status, exercise capacity, and prognosis in HFpEF. Methods and results The study population consisted of 300 HFpEF patients. ID was defined as serum ferritin <100 μg/L or 100-300 μg/L and transferrin-saturation <20%. Baseline functional status, quality of life (HADS score and EQ 5D index), 6 min walking test, echocardiography, and outcome (all-cause mortality and combined all cause-mortality and HF hospitalization) were evaluated. ID was found in 159 (53%) patients. Patients with ID had a worse prognosis with a higher combined endpoint of all-cause mortality and HF hospitalization after 4 years of follow-up (log rank = 0.008). Pulmonary hypertension, depression, and thyroid disease were more prevalent in the ID group. Multivariable analysis showed that ID was independently associated with body mass index (P = 0.003), pulmonary hypertension (P = 0.008), and thyroid disease (P = 0.01). Although patients with ID had a lower exercise capacity compared with patients without ID (393 m [294-455] vs. 344 m [260-441], P = 0.008), there was no significant correlation after multivariable correction for age, BMI, NT-proBNP, DM, and depression. Conclusions Heart failure with preserved ejection fraction patients with ID have a worse prognosis and impaired exercise capacity compared with those without ID. However, although a trend was observed, after multivariable correction ID was no longer significantly associated with a reduced exercise capacity. This reflects that impaired exercise capacity in HFpEF is complex and seems multifactorial. Interestingly, pulmonary hypertension was an independent predictor of both ID and exercise capacity.

Iron Deficiency Impacts Diastolic Function, Aerobic Exercise Capacity, and Patient Phenotyping in Heart Failure With Preserved Ejection Fraction: A Subanalysis of the OptimEx-Clin Study

“…In multivariable regression, the relationship between iron parameters and peak V̇O 2 was minor. This confirms findings from a recent analysis in 300 patients with HFpEF ( Barandiarán Aizpurua et al, 2021 ). Previously, smaller studies found more important relationships between iron parameters and peak V̇O 2 ( Núñez et al, 2016 ; Martens et al, 2018 ).…”

Iron Deficiency in Heart Failure: Mechanisms and Pathophysiology

“…Psychological disorders such as depression are very common in HF patients [ 264 ]. Several studies reported a higher prevalence of depression in iron-deficient HF [ 26 , 265 , 266 ]. Whether systemic ID is associated with brain ID in HF patients is unknown.…”

“…ID impairs thyroid hormone metabolism by different mechanisms, including ineffective erythropoiesis, reduced thyroid peroxidase activity (haeme-containing enzyme) and increased hepatic inactivation of thyroid hormones [ 269 , 270 ]. Iron deficient HFpEF patients have a significantly higher prevalence of thyroid disease [ 265 ]. The therapeutic consequence of replenishing iron on thyroid function in HF has not been studied yet.…”

A year in heart failure: an update of recent findings

“…Treatment of iron deficiency with ferric carboxymaltose (FCM) infusion improved symptoms, functional capacity, and QOL in chronic HFrEF 139–141 . Efficacy on symptoms may be slightly larger in patients with HFrEF than with HFpEF 142 . In the Study to Compare Ferric Carboxymaltose With Placebo in Patients With Acute Heart Failure and Iron Deficiency (AFFIRM‐HF), the use of intravenous FCM in patients hospitalized for acute HF, an LVEF < 50%, and with evidence of iron deficiency reduced HF hospitalization at a 52 week follow‐up (risk ratio, 0.74; 95% CI, 0.58 to 0.94, P = 0.013) 143 .…”