this ppt gives an overview of iron deficiency in heart failure and the treatment options

1. Diagnosis & Treatment of
Iron Deficiency in Heart Failure
- Latest updates

2. Outline
• Missing Link in HF Management
• Defining Iron Deficiency (ID) in Heart Failure (HF)
• Prevalence of ID in HF
• Clinical Implications of ID in HF patients
• Management of ID in HF
- Role and benefits of FCM
- Oral vs IV iron supplements
• Conclusion

3. B-Blockers Diuretics
ARNI SGLT2
inhibitors
IV (FCM)
Iron
IV FCM - The 5th Pillar in HF treatment
IV Ferric Carboxymaltose is missing link in HF Management

4. To Address Iron Deficiency in Heart Failure
1. DETECT: Diagnosis of ID (Ferritin & TSAT)
2. INJECT: Right dose administration without admission
3. FORGET: Forget worry of patients on Quality of Life Improvement
DETECT INJECT FORGET

5. Defining Iron deficiency in Heart Failure
• ID in the adult general population is defined by the World
Health Organization as plasma ferritin <15 mg/l. However,
a higher cutoff for ferritin is recommended in chronic
inflammatory conditions.
• Accordingly, in chronic HF, absolute ID is defined as
ferritin <100 mcg/l and functional ID is defined as ferritin
between 100 and 300 mcg/l when Transferrin saturation
(TSAT) is <20%.
Bruno M.L. Rocha, Gonçalo J.L. Cunha, Luiz F. Menezes Falcão J Am Coll Cardiol. 2018 Feb, 71 (7) 782-793

6. 6
Parameters Range
Ferritin 15 – 299 ug/l
Transferrin
Saturation [TSAT]
Upto 55% for Males
Upto 50% for
Females
Paramete
r
Range
Ferritin < 100 ug/l
Parameter
s
Range
Ferritin 100-299
ug/l
Transferrin
Saturation
[TSAT]
< 20%
Iron Deficiency: Definition

7. Absolute vs Functional Iron deficiency
Functional ID has been found to be more common in the earlier stages
of HF with absolute ID developing as the disease progresses
European Heart Journal – Cardiovascular Pharmacotherapy (2015) 1, 58–64

8. Iron deficiency vs Iron deficiency Anemia
• Patient can have Iron Deficiency without having
Anaemia
• In an international, pooled cohort of 1506 chronic heart
failure patients, iron deficiency (but not anemia) was an
independent predictor of mortality
• Although anemia is a frequent co-morbidity in HF,
treatment with Erythropoietin-Stimulating agents did
not improve death from any cause nor hospitalization for
worsening HF
Cohen-Solal A, Leclercq C, Deray G, et al. Heart 2014;100: 1414–1420.

9. Iron deficiency: common co-morbidity in HF
• In the absence of any iron treatment, it is estimated that up
to 50% of patients with heart failure have low levels of
available iron.[ Absolute + Functional iron deficiency]
• High prevalence seen in :
 NYHA class III and IV
 Females
 In patients with high levels of inflammatory markers
(such as C-reactive protein) as well as increased levels of
NT-proBNP
Eur J Heart Fail. 2015 ;17(3):248-62

10. Prevalence of ID in HF population
Bruno M.L. Rocha, Gonçalo J.L. Cunha, Luiz F. Menezes Falcão J Am Coll Cardiol. 2018 Feb, 71 (7) 782-793

11. Curr Heart Fail Rep (2017) 144.223-234
Prevalence of ID and Anemia in HF cohorts

12. Clinical & Prognostic consequence of ID in HF
• Reduced peak oxygen consumption (VO2 max)
• lower 6-min walk test (6 MWT)
Exercise intolerance
• Assessed by Minnesota Living with Heart Failure Questionnaire
(MLHFQ)
Decreased Health
related quality of
life(HRQOL)
• In both HFrEF and HFpEF
• Irrespective of presence of anemia
Increased long term
all cause mortality
• Increases the risk for re-hospitalization within 30 days after
discharge
• Combined all-cause death, non-fatal cardiovascular or heart
transplantation
In acute HF
hospitalized patients
HFrEF –Heart failure with reduced ejection fraction, HFpEF-Heart failure with preserved ejection fraction
Am J Cardiovasc Drugs. 2017 Jun;17(3):183-201

13. 3 year event free survival rates in patients
with Systolic CHF with vs without ID
• N= 546 patients
with stable
systolic CHF
• In patients with
systolic CHF, ID
is common and
constitutes a
strong,
independent
predictor of
unfavorable
outcome.
European Heart Journal (2010) 31, 1872–1880

14. ID in HF patients: significant association
with mortality
The increase in mortality risk appears to be in the order of
40–50%
Eur J Heart Fail. 2015 ;17(3):248-62

15. 2021 HF guidelines recommend
Intravenous FCM to treat ID in HFeEF

16. Advantages of Inj. FCM over other i.v. iron
preparations
Safe option at higher dose – 1000
mg of elemental iron in FCM
against 200 mg of elemental iron in
iron sucrose in single infusion
Rapid infusion visits – unlike iron
sucrose with multiple visits for total
dose infusion
Near neutral pH & physiological
osmolality – low rate of injection site
reactions, no test dose needed
Type I, Dextran-free, robust
iron with long half life – 16
hours
Stable complex – does not
release non-transferrin bound
iron
Structure similar to Ferritin,
deposited easily in RES
Low Antigenicity

17. Evidence for use of FCM for treating Iron
Deficiency in Heart Failure

18. CONFIRM HF trial
Primary End Point First Hospitalization due to worsening Heart
Failure
N=304 HF patients with LVEF ≤45%
iron deficiency (ferritin ,100 ng/mL or 100–300 ng/mL if transferrin saturation ,20%).
Conclusion Treatment of symptomatic, iron-deficient HF patients with FCM over a 1-
year period resulted in sustainable improvement in functional capacity, symptoms, and
QoL and may be associated with risk reduction of hospitalization for worsening HF
European Heart Journal (2015) 36, 657–668

19. FAIR HF - Treatment with intravenous ferric carboxymaltose in patients with chronic heart
failure and iron deficiency, with or without anemia, improves symptoms, functional capacity,
and quality of life
N=459 patients with CHF
of NYHA) class II or III
N Engl J Med 2009;361:2436-48

20. AFFIRM-AHF: Primary Composite Endpoint
and Components
Ponikowski. Lancet. 2020;[Epub].
Total HF Hospitalizations
Wks
100
80
60
40
20
0
52
48
24
12
4
0
RR: 0.74 (95% CI: 0.58 – 0.94)
P = 0.013
Wks
CV Death
Proportion
of
Patients
with
Event
1.0
0.8
0.6
0.4
0.2
0
52
48
24
12
4
0
HR: 0.96 (95% CI: 0.70 – 1.32)
P = 0.809
100
80
60
40
20
0
52
48
24
12
4
0
Wks
Primary Outcome: Total HF
Hospitalizations and CV Death
Mean
Cumulative
Events/100
Person-
Yrs
RR: 0.79 (95% CI: 0.62 – 1.01)
P = 0.059
Placebo (mITT n = 550) Ferric Carboxymaltose
(mITT n = 558)
Primary outcome, total heart failure hospitalizations and cardiovascular death within 52 weeks,
occurred in 52.5% of the ferric carboxymaltose group compared with 67.6% of the placebo group (p =
0.059)

21. Interpretation
Among patients with acute heart failure with iron deficiency, intravenous
ferric carboxymaltose was associated with a numerical reduction in total heart
failure hospitalizations and cardiovascular death.
Intravenous ferric carboxymaltose was associated with a significant reduction
in total heart failure hospitalizations compared with placebo.
AFFIRM-AHF support recommendation to administer intravenous ferric
carboxymaltose in patients hospitalized for acute heart failure with
concomitant iron deficiency and with a left ventricular ejection fraction of less
than 50%.
Ferric carboxymaltose benefits patients beyond the correction of anemia.

22. Other Significant Studies
Completed-
• FAIR-HF - (N Engl J Med 2009;361:2436-48)
Ongoing-
• EFFECT-HF (NCT01394562)
• ICHF (NCT01837082)
• FAIR-HF-HFpEF
• PRACTICEASIAHF (NCT01922479)
22

23. Effect of Oral or I.V. Iron on ‘Hepcidin block’
 The rate of iron absorption
from Oral iron therapy is
inadequate to influence this
‘hepcidin block’
 I.V. iron therapy results in
high intracellular iron levels
which overcome the
‘hepcidin block’ by
stimulating overexpression of
ferroportin
European Journal of Heart Failure (2015) 17, 248–262

24. Treatment of ID in HF: Oral Vs IV Iron
Am J Cardiovasc Drugs (2017) 17:183–201 DOI 10.1007/s40256-016-0211-2
Parameters Oral Iron Ferium 1K
Absorption 12–16% 100% systemic availability
Response Suboptimal Optimal
Tolerance
Depends on iron content in
different iron preparations.
No tolerance related issues
Dosage
To be given in divided
doses 2- 3 times a day
Higher doses, less
frequency
Compliance Compliance issues Better compliance
Evidence No clinical benefits in trials Proven Clinical Benefits

25. IV Ferric Carboxymaltose
Dosing Guidelines

26. Conclusion
• Routine diagnosis and management of ID in patients with symptomatic HF,
regardless of anaemia status, and prompt intervention using i.v. iron
therapy should now be considered.
• Available evidence suggests that treatment of symptomatic, Iron-deficient
HF patients with FCM can benefit patients as follows-
- Sustainable improvement in functional capacity
- Improvement in symptoms
- Improvement in QoL
- Risk reduction of hospitalization for worsening HF.

27. Summary
• Prevalence of ID is high in patients with HF
• ID is not same as IDA and Iron Profile [serum Ferritin and TSAT] should
be a routine investigation for all HF patients
• ID is an independent factor for determining outcome and mortality in HF
patients
• Only IV iron and not oral iron have shown clinical benefits in HF
• Ferric Carboxymaltose improves Exercise capacity, Quality of life and
hospitalization due to worsening HF

28. Summary
• Average Dosing of Ferric Carboxymaltose was 1000mg for initial dose in
major RCTs
• Ferric Carboxymaltose can be given as 1000mg bolus [15 min] or as
infusion over 15 min [max dilution with 250ml saline]
• After correction of ID with FCM the iron profile must be done 1-2 times a
year
• Ferric Carboxymaltose is safe, Convenient IV option for correction of ID in
HF

29. To Address Iron Deficiency in Heart Failure
1. DETECT: Diagnosis of ID (Ferritin & TSAT)
2. INJECT: Right dose administration without
admission
3. FORGET: Forget worry of patients on Quality
of Life Improvement
DETECT INJECT FORGET

30. Thank You!!!