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Anemia Contributes to Exercise Intolerance in HFpEF, Study Finds


Patients with heart failure with preserved ejection fraction (HFpEF) may experience worsened exercise tolerance if they also have anemia.

A version of this article was published by HCPLive. This version has been lightly edited.

Anemia label on blood test | Image Credit: vchalup – stock.adobe.com

Anemia label on blood test | Image Credit: vchalup – stock.adobe.com

Among individuals with heart failure with preserved ejection fraction (HFpEF), research published in the International Journal of Cardiology Heart & Vasculature suggests that also having anemia can negatively affect exercise tolerance.1

The exercise stress echocardiographic study included nearly 500 patients with and without HFpEF. According to the study, individuals with both anemia and HFpEF had similar cardiac output during exercise but a lower exercise capacity, intensity, and duration than their counterparts in other groups—those with HFpEF alone and those with dyspnea or labored breathing but without HF.

“These data provide new insights into the pathophysiology of anemia in patients with HFpEF,” wrote investigators.

In 2023, the cardiology community—advanced heart failure specialists specifically—witnessed a renewed emphasis on addressing the impact of anemia and iron deficiency in patients with HF. Use of intravenous (IV) iron was centerstage at the European Society of Cardiology (ESC) 2023 Congress, where Robert Mentz, MD, of the Duke University School of Medicine, presented data from the HEART-FID trial, which was billed by investigators as the largest study to assess the long-term safety and efficacy of IV ferric carboxymaltose in HF with reduced ejection fraction (HFrEF) and iron deficiency. During the same session, Piotr Ponikowski, MD, PhD, of Wroclaw Medical University, presented what he described as the largest and most up-to-date analysis of the effect of ferric carboxymaltose in patients with reduced or mildly reduced ejection fraction and iron deficiency in a pooled analysis of data from the CONFIRM-HF, AFFIRM-AHF, and HEART-FID trials.2

In addition to these presentations, the ESC updated their HF guidelines to include a pair of new recommendations related to IV iron supplementation. These updates recommended iron supplementation in symptomatic patients with reduced or mildly reduced ejection fraction, and iron deficiency to alleviate HF symptoms and improve quality of life. The updates also recommended that IV iron supplementation with ferric carboxymaltose or ferrite derisomaltose should be considered in symptomatic patients with reduced or mildly reduced ejection fraction, and iron deficiency, to reduce the risk of HF hospitalization.

The current study sought to develop a greater understanding of exercise capacity, cardiovascular and ventilatory reserve, and the oxygen (O2) pathway in patients with HFpEF and anemia. To do so, the retrospective analysis focused on consecutive patients referred for exercise stress echocardiography for exertion dyspnea at Gunma University Hospital in Japan from October 2019 though January 2023.

For the purpose of analysis, HFpEF was defined using Heart Failure Association criteria, and anemia was defined as a hemoglobin level less than 13 g/dL and less than 12 g/dL in men and women, respectively.

A total of 486 participants were identified for inclusion in the study, including 248 control patients without HF and 238 patients with HFpEF. Anemia was prevalent in 47% of patients with HFpEF, with mean (SD) hemoglobin levels of 13.5 (1.5) g/dL in the control group, 13.7 (1.2) g/dL in patients with HFpEF without anemia, and 10.9 (1.2) g/dL in patients with both HFpEF and anemia.

Results indicated that patients with HFpEF and anemia had worse nutritional status and renal function, lower iron levels, and greater left ventricular (LV) remodeling and plasma volume expansion compared with patients with HFpEF without anemia. Further analysis suggested peak oxygen uptake, exercise intensity, and exercise duration was reduced among those in the anemia and HFpEF group compared with the other groups, with these differences remaining significant after adjustment for age and sex (all P < .01).

Investigators called attention to limitations within their study to consider when interpreting the findings from their study. These limitations included possibility of selection and referral bias as a result of being conducted at a tertiary referral center, inability to exclude the possibility some patients with HFpEF may have been missed, and use of resting hemoglobin levels to estimate arterial O2 content during peak exercise.

“We demonstrated that anemic HFpEF patients were characterized by worse nutritional status, lower renal function, and greater left heart remodeling and plasma volume expansion than those without anemia,” investigators wrote. “Anemia was associated with impaired arterial O2 delivery, which limited the augmentation of peripheral O2 extraction and utilization, contributing to poor exercise capacity.”


  1. Naito A, Obokata M, Kagami K, et al. Contributions of anemia to exercise intolerance in heart failure with preserved ejection fraction-an exercise stress echocardiographic study. Int J Cardiol Heart Vasc. Published online August 20. doi:10.1016/j.ijcha.2023.101255
  2. Campbell P. Role of intravenous iron in spotlight at ESC congress 2023. HCP Live. August 27, 2023. Accessed October 23, 2023. https://www.hcplive.com/view/role-of-intravenous-iron-in-spotlight-at-esc-congress-2023
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