At the official press conference for the anniversary congress “20 Years Cardiology Update”, Prof. Frank Ruschitzka, MD, Cardiology (USZ), presented a worrying balance sheet on heart failure – with 120,000 people affected in Switzerland alone. Because decreased cardiac output is associated with dyspnea, rapid fatigue, fatigue, water retention in the lungs, and peripheral edema, all options for modern management should be exhausted. At a satellite symposium, experts addressed iron deficiency as a recognized comorbidity in heart failure and presented data on successful correction of the deficit with i.v. ferric carboxymaltose.
Given demographic trends, the number of patients with heart failure (CHF) is expected to increase to 200,000 in the next four years, said Prof. Frank Ruschitzka, MD, Zurich. Every year, 10,000 people in Switzerland die as a result of CHF. Overall mortality is 50% at five years, making the prognosis of CHF worse than that of most cancers. Chairman Prof. Georg Noll, MD, Cardiology (USZ), moved on to the management of CHF, pointing out that a meta-analysis of 34 studies [1] (n=150 000) documented not only a high anemia prevalence of 37.8% in patients with CHF, but also significantly increased mortality. Two out of three patients with “anemia of chronic disease” are iron deficient [2], the cardiologist explained. This iron deficiency is responsible for increased morbidity and mortality in CHF, independent of the presence of anemia (Fig. 1) [3, 4]. Therefore, the ESC guidelines also recommend regular monitoring of iron status and consequently correction of the deficit [5].
Fig. 1: Iron deficiency (EM) is associated with increased morbidity and mortality even in the absence of anemia.
Role of iron deficiency in the vicious circle of heart failure.
The prevalence of anemia in patients with CHF was put by Peter van der Meer, MD, Groningen (NL), at 14-79%, depending on the severity of CHF [6]. According to the WHO definition, anemia exists when an Hb <13 g/dl is measured in men and <12 g/dl in women. The speaker referred to a variety of possible etiologies of anemia in CHF, with iron deficiency playing a crucial role. In practice, one must distinguish absolute from functional iron deficiency. In absolute iron deficiency, chronic blood loss usually leads to depletion of iron stores, whereas in functional iron deficiency, inflammation plays the decisive role.
Bone marrow biopsy, the gold standard of anemia diagnosis, showed that iron deficiency anemia was present in nearly three-quarters (73%) of patients (n=37) with advanced CHF (NYHA IV) and an LVEF of 22% [7]. Dr. van der Meer recalled that the following two constellations indicate iron deficiency in CHF [8]:
- Ferritin <100 µg/L, or
- Ferritin between 100 and 299 µg/L with a TSAT<20%.
He referred to a study of CHF patients (n=443) with LVEF of 26%, the majority of whom were classified as NYHA II/III; in this collective, decreased exercise capacity was associated with iron deficiency [9]: Maximal oxygen uptake during exercise was highest in patients without iron deficiency or anemia and lowest in those with iron deficiency anemia. The iron deficit reduces physical endurance on the one hand via the reduced oxygen transport capacity of the blood and on the other hand via the insufficient supply of tissues such as heart and skeletal muscles with energy and oxygen [10]. Because iron deficiency is also associated with significantly increased mortality in CHF, all options should be exhausted to correct iron deficiency in a timely manner [8].
Iron deficiency in HI considered in the 2012 ESC guidelines.
Prof. Stefan Anker, MD, Charité (Berlin), mentioned several studies published between 2006 and 2008 that provided initial evidence of benefit from i.v. iron administration in CHF:
- i.v. iron sucrose improves functional capacity and quality of life in CHF and anemia [11]
- i.v. iron sucrose improves renal function of CHF patients with iron deficiency and anemia [12]
- i.v. iron sucrose improves iron status in CHF patients with and without anemia [13]
- i.v. iron sucrose improves maximal oxygen uptake pVO2 and prolongs endurance exercise [13, 14].
With this in mind, the FAIR-HF study was designed and enrolled 459 CHF patients with iron deficiency (with and without anemia). Patients were randomized 2:1 to treatment with 200 mg Ferinject® i.v. or placebo (saline i.v.) weekly in the correction phase and four weeks thereafter. The primary endpoints chosen were NYHA functional class and patient global assessment (PGA) at 24 weeks. Secondary endpoints included 6-minute walk distance and health-related quality of life, Prof. Anker said.
ESC Guidelines 2012 address iron deficiency
In the verum group, 50% of patients reported significant or moderate improvement vs. 27% on placebo. In addition, 47% were in NYHA class I or II, vs. 30% in the placebo collective. At baseline, more than 80% were in NYHA class III, and these successes were observed whether or not the iron deficiency was associated with anemia. The positive effects at 24 weeks were all statistically significant at four and twelve weeks.
Prof. Anker pointed out that in 2012, iron deficiency was mentioned as a comorbidity in CHF for the first time in the guidelines and should be treated, with the cut-off values mentioned above. For therapy, please refer to the results of the FAIR-HF study [5].
Iron deficiency in heart failure in practice
Finally, PD Dr. med. Otmar Pfister, Cardiology, University Hospital Basel, addressed the management of iron deficiency in CHF in practice. He used a patient example to illustrate how quickly and efficiently the deficit can be corrected with ferric carboxymaltose. A 45-year-old CHF patient was already suffering from fatigue and shortness of breath during daily activities. Iron status confirmed depleted stores. Subjective and objective improvement occurred with Ferinject® administered three times at weekly intervals and a dosage of 200 mg.
Take Home Message
- Iron deficiency is a common comorbidity in patients with CHF.
- Nearly 50% of CHF patients are iron deficient.
- The iron deficiency is responsible for the reduced physical resilience.
- CHF patients with iron deficiency have a significantly increased risk of mortality.
Conclusion of Prof. Anker
- Iron deficiency in CHF is a new therapeutic target in patients with and without anemia.
- The FAIR-HF study was able to show that ferric carboxymaltose improves symptoms, performance and quality of life.
- The new ESC guidelines indicate that iron deficiency can be easily detected by measuring ferritin and TSAT (cut-off values: ferritin <100 µg/l; 100 µg/l <ferritin <299 µg/l and TSAT <20%).
- Ferric carboxymaltose should be considered in these patients.
Source: Press conference on the anniversary congress “20 Years Cardiology Update” and satellite symposium of Vifor Pharma, Davos, February 2013.
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