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Iron Deficiency in Heart Failure Linked to GI Causes or Cancer

MANCHESTER— Iron deficiency in patients with heart failure is associated with a significant risk for hospitalisation or death due to non-cardiovascular causes, notably gastrointestinal bleeding or cancer, suggest new findings from the Hull LifeLab cohort.

After a 2-year follow up, "GI bleeding or cancer accounted for around 1 in 8 of all deaths and about 1 in 3 of all non-cardiovascular deaths", Dr Joe Cuthbert of Hull York Medical School reported at the British Cardiovascular Society Annual Meeting.

The risk for death or hospitalisation was apparent regardless of the definition of iron deficiency applied and regardless of heart failure phenotype.

"These data really support something that I think we all suspect – patients who are iron deficient are at greater risk of adverse outcome," Dr Cuthbert said. 

"The relevance, though, is that the guidelines currently recommended to screen patients for iron deficiency, but there's no clue as to what we should do when we find it," he told Medscape News UK

"If you say, iron deficiency to a heart failure specialist, they will say, 'Okay, I'll give this person IV iron', but if you said it any other medical practitioner, they might say, 'GI lesion or cancer'," he pointed out.

"If it is the case, in practice, that we are giving intravenous iron to people who actually have a GI lesion or a cancer, then really, we're refilling the dam without ever plugging the hole," Dr Cuthbert added.

Iron Deficiency Prevalence by Definition

Iron deficiency is a common finding among heart failure patients, and in the analysis of 4446 patients that he presented, the prevalence ranged from 21% when National Institute for Health and Care Excellence (NICE) criteria were used up to 68% when European Society of Cardiology (ESC) criteria were used. 

Both NICE and the ESC base their criteria on measuring serum ferritin levels alone or with transferrin saturations (TSAT). They differ by the thresholds which they set, NICE sets the bar for iron deficiency at a ferritin level of less than 30µg/L, or less than 45µg/L if TSAT is measured. The ESC sets the bar for iron deficiency at a lower level at 100 µg/L for ferritin alone or 100-299 µg/L if using TSAT. The latter should be below 20% in both cases. 

At Hull, they use another definition, which relies on measuring serum iron levels; these need to be below 13 µmol/L or there needs to be a TSAT of less than 20%. Using this definition, 47% of the study population were deemed iron deficient. The reasoning for using serum iron levels is that this has been shown to be associated with a risk for adverse outcomes in prior studies. 

"We would prefer to use serum iron as a marker of iron deficiency," Dr Cuthbert said in response to being quizzed on which definition might be the best. "If you want to know what the iron status is just measure the iron and not the surrogates,” he suggested. 

However, this is not what guidelines recommend and when referring patients to a gastroenterologist, the ferritin levels will be wanted. 

Hospitalisations, Deaths, and Deficiency

Over a median follow up of 1840 days, there were 1820 deaths. Out of the 4446 patients, 1899 either died of any cause or were hospitalised with GI bleeding – out of which, 266 were due to GI bleeding or cancer. A further 231 patients had required hospitalisation for GI bleeding. 

Death due to GI bleeding or cancer accounted for approximately 14% of all deaths and 33% of all non-cardiovascular deaths.

Iron deficiency versus no iron deficiency was associated with 22% (ESC), 61% (NICE), or 41% (Hull) significant increased risk for hospitalisation for GI bleeding, or death due to GI bleeding or cancer. Patients with anaemia in addition to iron deficiency were at the highest risk for these adverse outcomes, although upon multivariable adjustment the association was lost. 

"Thank you so much for giving me a task to screen my patients for cancer now," quipped one audience member. 

However, in an interview, Dr Cuthbert said that it's time for heart failure specialists to think more holistically about the care of their patients.

"As patients with heart failure are diagnosed later in life, because treatment for the conditions that cause heart failure has improved, and as we improve our treatments for patients with heart failure, they live longer, they accrue more comorbidities, and they are at risk of other non-heart failure related events," he explained. 

"I think we need to broaden our horizons as heart failure specialists to think about the patient as a whole and I would encourage people that you need to look, look at reasons why this person might be iron deficient, rather than just giving the IV iron."

He added that if a patient meets referral criteria, then that is mandated by NICE guidelines if that is a route that patient wants to go down. "It doesn't mean you can't give intravenous iron for what you might see the symptomatic or outcome benefit in the meantime. But the process shouldn't stop there."

Dr Cuthbert reported no conflicts of interest.