adapted for Journal presentation from International Journal of Cardiology, August 2019

1. Dr. Samanta Rahman
D.Card student, SSMC&MH

2.  Gianluigi Savarese
 Åsa Jonsson
 Ann-Charlotte Hallberg
 Ulf Dahlström
 Magnus Edner
 Lars H. Lund
Published in International Journal of Cardiology;
August,2019.

3.  Heart failure (HF) affects 2–3% of the population
and up to 20% of the elderly.
 Anemia is common and associated with poor
outcomes in HF.
 A comprehensive assessment of the independent
predictors of anemia, and of the independent
association between anemia and outcomes in
HFpEF vs. HFmrEF vs. HFrEF is lacking.

4. According to the 2016 European Society of
Cardiology (ESC) HF guidelines,
 EF categorized as <40% is defined as HFrEF,
 EF categorized as 40-49% is defined as HFmrEF,
 EF categorized as ≥50% is defined as HFpEF.

5.  In women: hemoglobin <120 g/L and
 In men: hemoglobin <130 g/L.

6.  Study Method: Observational prospective study.
 Study population: after applying exclusion criteria,
42,985 patients.
 Inclusion criteria: age ≥18 and clinician-judged HF,
regardless of EF.
 Exclusion criteria: death during hospitalization.
 Duration of study: from 11 May,2000 to 31
December,2012

7.  Statistical analyses:
Baseline characteristics of patients
according to the presence of concomitant anemia
were compared by using Kruskal-Wallis test for
continuous variables and by Chi-square for
categorical variables.
Crude outcomes were assessed by Kaplan-
Meier analysis.
A p-value <0.05 was considered as
statistically significant.

8. Anemia has been extensively studied in patients with
chronic and acute HF. Specifically,
41% of patients with HFpEF,
35% of those with HFmrEF and
32% of those with HFrEF had anemia.

9. HFpEF HFmrEF HFrEF
Anemia
No
Anemia
yes
Anemia
No
Anemia
yes
Anemia
No
Anemia
Yes
Sex
Male
Female
Age, years,
mean
Duration of
HF
<6 months
≥6 months
NT-Pro BNP
(pg/ml)
41.2%
58.8%
76
50%
50%
1641
51.4%
48.6%
79
45.3%
54.7%
2832
58.3%
41.7%
73
52.3%
47.7%
1698
65.2%
34.8%
77
44.4%
55.6%
3442
69.4%
30.6%
70
54.3%
45.7%
2557
75.2%
24.8%
75
44.6%
55.4%
5039
(P value <0.001)

10. HFpEF HFmrEF HFrEF
Anemia
No
Anemia
yes
Anemia
No
Anemia
yes
Anemia
No
Anemia
Yes
NYHA class
I
II
III
IV
eGFR,
ml/min/1.73
m2, median
≥60
30-59
<30
18.7%
45.3%
33.1%
3.0%
51.7%
43.1%
5.2%
12.3%
44.2%
39.1%
4.4%
34.6%
50.3%
15.0%
16.6%
55.3%
26.6%
1.5%
57.3%
38.2%
4.5%
11.9%
48.1%
35.9%
4.0%
39.3%
47.5%
13.2%
10.3%
48.2%
37.9%
3.6%
58.9%
37.1%
4.0%
5.7%
37.8%
49.3%
7.1%
39.8%
45.8%
14.4%
(P value <0.001)

11. HFpEF HFmrEF HFrEF
Comorbidities Anemia
No
Anemia
yes
Anemia
No
Anemia
yes
Anemia
No
Anemia
Yes
Current smoker
Obesity
HTN
DM
IHD
Stroke/TIA
AF
Pulmonary Dis.
10.6%
31.1%
70.1%
24.9%
43.5%
17.8%
62.9%
28.3%
8.4%
26.1%
71.9%
33.1%
50.9%
22.6%
64.9%
32.7%
12.8%
28.6%
61.5%
23.0%
53.4%
15.6%
57.4%
23.4%
9.8%
22.8%
66.3%
34.3%
64.3%
19.1%
59.9%
28.6%
16.3%
23.5%
52.5%
23.7%
52.3%
13.9%
50.9%
21.3%
13.5%
15.4%
58.2%
33.8%
69.9%
19.6%
52.1%
27.9%
(P value <0.001)

12.  Age is a strong independent predictor of anemia
within each HF phenotype.
 Notably, DM is associated with a 48% increased
risk of anemia in HFpEF, 51% in HFmrEF and 44% in
HFrEF, independently of renal function and all the
other patients' characteristics.
 Chronic kidney disease (CKD) is an independent
predictor of anemia. There is interplay between
anemia, CKD and diabetes in both HFpEF and
HFmrEF, and support a key role for comorbidities
in HFpEF.

13.  Important predictors which differed across the EF
spectrum were NYHA class and ischemic heart
disease, with higher NYHA class and history of
ischemic heart disease being associated with
concomitant anemia in HFrEF and HFmrEF but not
in HFpEF.

14. These results may be explained by
 Anemia as consequence of the cardiorenal
syndrome and hypoxemic status due to low output
in patients with more advanced HFrEF (i.e. NYHA
III-IV vs I-II) and those with HFmrEF transiting
toward HFrEF, and
 Coronary artery disease more frequent in HFrEF vs.
HFmrEF vs. HFpEF and thus anemia more likely to
contribute to type 2 myocardial infarctions in
patients with lower EF.

15.  Anemia is a predictor of all-cause mortality
regardless of EF.
 Anemia is associated with mortality independently
of HF phenotype.
 In patients with HFpEF and HFmrEF, anemia may
exacerbate HF-related symptoms more than in
HFrEF, leading to higher risk of HF hospitalization.
 Treating anemia may be beneficial regardless of
the EF phenotype, may even more heavily
contribute to reduce hospital admissions in
patients with higher EF.

17. In this comprehensive assessment of anemia in
patients with HFpEF vs. HFmrEF vs. HFpEF it is
found that:
 Anemia is common regardless of EF, but with
higher prevalence in HFpEF (41%) vs. HFmrEF
(35%) vs. HFrEF (32%).
 Anemia is independently associated with several
other patients' characteristics such as higher age,
male sex, worse renal function, comorbidities,
frailty and severity of HF.

18.  Over long-term follow-up, anemia is
independently associated with increased risk of
death or HF hospitalization and of death alone in
both HFpEF, HFmrEF and HFrEF, but with higher
risk of all-cause death or HF hospitalization in
HFpEF and HFmrEF vs. HFrEF.
 No differences in risk across the EF spectrum for
all-cause mortality.

19.  Laboratory data needed for the diagnosis of iron
deficiency were not available, and thus the
relationship/interaction among iron deficiency,
anemia and HF has not been captured in the
analyses.
 Potential underlying causes of anemia in these
patients were not considered.
 Hemoglobin levels were obtained as a single
measurement at the hospital discharge/clinical
visit, and therefore did not exclude if patients had
only transitory anemia or hemodilution.

20. These findings suggest that while anemia may be
one among many other comorbidities contributing
to HFpEF and, although to a lesser extent, to
HFmrEF pathogenesis, it may be a risk marker in
HF, leading to identify those patients with more
severe HF and cardiorenal syndrome who are more
likely to experience adverse outcomes.