- Iron deficiency is highly prevalent in Asian patients with heart failure, ranging from 37-61% in different regions. It is associated with increased risk of death and poorer outcomes. - A study of over 750 heart failure patients and 600 controls in Singapore found iron deficiency to be common, even in controls without heart failure. Concomitant iron deficiency and anemia predicted the worst prognosis. - Contributing factors to iron deficiency in Asians may include dietary differences like vegetarianism and black tea consumption, as well as possible genetic differences in iron regulation. Future research includes randomized trials of intravenous iron replacement in Asian heart failure patients.

1. IMPORTANCE OF IRON DEFICIENCY IN
ASIAN PATIENTS WITH HEART FAILURE
Tee Joo YEO, MBBS, MRCP (UK)
Associate Consultant, National University Heart Centre Singapore
Advances in the Care of Patients With Heart Failure: International Perspective from the Singapore Cardiac Society

2. Heart Failure and Iron Deficiency: What do we know?
olneymywellness.com life-dance.blogspot.ca

3. Iron is crucial
• Cellular activity
• Tissue metabolism
• Functional capacity
van Veldhuisen, D.J. et al. Anemia and Iron Deficiency in Heart Failure: Mechanisms and Therapeutic Approaches. Nat Rev Cardiol. 8,485-493 (2011)

4. Iron deficiency
• The most widespread and
common nutritional disorder
in the world

5. Mechanisms for Iron Deficiency
Jankowska et al. Iron deficiency and heart failure: diagnostic dilemmas and therapeutic perspectives Eur Heart J (2013) 13: 816-826

6. Iron Deficiency + Heart Failure = BAD combination
Iron deficiency
( ):
- Increased risk of death
or heart transplant
- Adjusted HR 1.58
(95% CI 1.14–2.17, p < 0.01)
E. Jankowska, P. Rozentryt, A. Witkowska, J. Nowak, O. Hartmann, B. Ponikowska, L. Borodulin-Nadzieja, W. Banasiak, L. Polonski, G. Filippatos, J.
McMurray, S. Anker and P. Ponikowski, "Iron Deficiency: an Ominous Sign in Patients with Systolic Heart Failure," Eur Heart J, no. 31, pp. 1872-1880, 2010

7. Current Guidelines Recommend Screening
For Iron Deficiency In Heart Failure
European Society of Cardiology 2012 –
Recommendations for the diagnostic investigations in ambulatory patients
suspected of having heart failure
•Measurement of blood chemistry is recommended to detect co-morbidities (eg. iron
deficiency) – Class I, Level of Evidence C
National Heart Foundation of Australia 2011 –
Recommendations for pharmacological treatment of symptomatic CHF
•Iron deficiency should be looked for and treated in CHF patients to improve
symptoms, exercise tolerance and quality of life – Grade B recommendation
McMurray JJ, Adamopoulos S, Anker SD et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: The Task Force for
the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Developed in collaboration with the Heart
Failure Association (HFA) of the ESC. European heart journal. 2012;33(14):1787-847.
Krum H, Jelinek MV, Stewart S et al. 2011 update to National Heart Foundation of Australia and Cardiac Society of Australia and New Zealand Guidelines
for the prevention, detection and management of chronic heart failure in Australia, 2006. The Medical journal of Australia. 2011;194(8):405-9

8. Prevalence of Iron Deficiency in Heart Failure
• North America: up to 61%
• Europe: 37 to 50%
• Asia: no available studies
E. Jankowska, P. Rozentryt, A. Witkowska, J. Nowak, O. Hartmann, B. Ponikowska, L. Borodulin-Nadzieja, W. Banasiak, L. Polonski, G. Filippatos, J. McMurray, S. Anker and P. Ponikowski, "Iron Deficiency: an
Ominous Sign in Patients with Systolic Heart Failure," Eur Heart J, no. 31, pp. 1872-1880, 2010
Parikh A, Natarajan S, Lipsitz SR, Katz SD. Iron deficiency in community-dwelling US adults with self-reported heart failure in the National Health and Nutrition Examination Survey III: prevalence and associations
with anemia and inflammation. Circ Heart Fail 2011;4:599–606
Klip IT, Comin-Colet J, Voors AA, Ponikowski P, Enjuanes C, BanasiakW, Lok DJ, Rosentryt P, Torrens A, Polonski L, van Veldhuisen DJ, van der Meer P, Jankowska EA. Iron deficiency in chronic heart failure: an
international pooled analysis. Am Heart J 2013;165:575–582 e3

9. Heart Failure in Asia
• Huge unmet public health burden
• Heart failure affects Asians at a younger age (~66
years) than Europeans (~70 years) or Americans (~75
years)
• Increasing hospitalisation rates
• Longer length of stay, higher in-hospital mortality
Sakata Y, Shimokawa H. Epidemiology of heart failure in Asia. Circulation Journal (Japanese Circulation Society) 2013;77:2209-17
World Health Organization. Global atlas on cardiovascular disease prevention and control, 2011
Atherton JJ, Hayward CS, Wan Ahmad WA et al. Patient characteristics from a regional multicenter database of acute decompensated heart failure in
Asia Pacific (ADHERE International-Asia Pacific). Journal of cardiac failure 2012;18:82-8.
Lam CS, Anand I, Zhang S et al. Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry. European journal of heart failure 2013;15:928-36.

10. Role of Singapore

11. Role of Singapore
• Island city-state in South-east Asia
• Land area: 713.8 km2 (277 sq mi)
• Population: 5.5 million
• Population density: 3rd in the world (behind Macau and Monaco)
• Multi-racial population (potential applicability to rest of Asia)
• Public hospitals: 8 (70-80% of population)
• Ranked #1 for most efficient healthcare (Bloomberg 2014)

12. Objectives
• We aimed to study the following aspects of iron deficiency:
- Prevalence
- Clinical correlates
- Functional significance
• HF patients vs. community-based controls without HF
• Multi-ethnic Southeast Asian population

13. Methods
• 751 stable heart failure patients
• 601 community-based controls
(random, asymptomatic)
Santhanakrishnan R, Ng TP, Cameron VA, Gamble GD, Ling LH, Sim D, et al. The Singapore Heart Failure Outcomes and Phenotypes (SHOP) study and
Prospective Evaluation of Outcome in Patients with Heart Failure with Preserved Left Ventricular Ejection Fraction (PEOPLE) study: rationale and design.
Journal of cardiac failure. 2013;19(3):156-62.
Tee Joo Yeo, Poh Shuan Daniel Yeo, Raymond Ching-Chiew Wong, Hean Yee Ong, et al. Iron Deficiency In A Multi-Ethnic Asian Population With And
Without Heart Failure: Prevalence, Clinical Correlates, Functional Significance And Prognosis. European Journal of Heart Failure 2014 Oct;16(10):1125-32.

14. Defining Iron Deficiency
Bradley A Warady. Treating Patients with IV Iron Therapy: Special Considerations ANNA CE Satellite Symposium, April 21, 2005
Serum Ferritin >300 mg/dL 100-300 mg/dL <100 mg/dL
Transferrin saturation >20% <20% <20%

16. Results

17. Results

19. • Poorest prognosis:
concomitant
functional iron
deficiency and
anemia

20. Other contributing factors
• Diet
- Vegetarianism
- Black tea consumption
• Genetics
- regulation of iron homeostasis
- possible genetic predisposition to iron deficiency
Thankachan P, Walczyk T, Muthayya S, Kurpad AV, Hurrell RF. Iron absorption in young Indian women: the interaction of iron status with the influence
of tea and ascorbic acid. The American journal of clinical nutrition. 2008;87(4):881-6.
Nelson M, Poulter J. Impact of tea drinking on iron status in the UK: a review. Journal of human nutrition and dietetics : the official journal of the British
Dietetic Association. 2004;17(1):43-54.
McGregor J, McKie AT, Simpson RJ. Of mice and men: genetic determinants of iron status. The Proceedings of the Nutrition Society. 2004;63(1):11-20

21. • Early, small interventional trials
- No evidence on survival
- Relatively short follow-up periods, heterogeneity, varying statistical significance
• FAIR-HF
- Largest RCT to date investigating effect of IV iron in HF patients
- Improvement in symptoms, functional capacity, QoL
• CONFIRM-HF
- Sustained improvement in 6 minute walk test, symptoms up to 1 year
- Reduced heart failure hospitalization at 1 year
Iron Deficiency – A Therapeutic Target in HF Patients
Anker SD, Comin Colet J, Filippatos G et al. Ferric carboxymaltose in patients with heart failure and iron deficiency. N Engl J Med 2009;361:2436–2448.
Avni T, Leibovici L, Gafter-Gvili A. Iron supplementation for the treatment of chronic heart failure and iron deficiency: systematic review and meta-
analysis. Eur J Heart Fail 2012;14:423–429.
Ponikowski P, van Veldhuisen DJ, Comin-Colet J, et al. Beneficial effects of long-term intravenous iron therapy with ferric carboxymaltose in patients
with symptomatic heart failure and iron deficiency. Eur Heart J 2014; DOI:10.1093/eurheartj/ehu385

22. PRACTICE-ASIA-HF trial
• Pilot Randomized Controlled Trial to
Assess the Role of Intravenous Ferric
Carboxymaltose in Asian Patients with
Heart Failure
• Simple dosing regimen
• 3 major Southeast Asian ethnic
backgrounds
• Inclusion of heart failure patients
regardless of LVEF

23. Summary
• In Southeast Asian patients with heart failure:
- Iron deficiency is highly prevalent, regardless of LVEF
- Iron deficiency is associated with poor outcomes
- Ethnic differences are striking
- Many more contributing factors like diet and genetics are possible
• Future directions:
- Intravenous iron replacement in Asian heart failure patients

24. THANK YOU
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