Anemia, insuficiencia cardíaca y transfusión. Talavera 2016

Insuficiencia Cardiaca:
anemia y transfusión.

POSTGRADO UNIVERSITARIO EN BLOOD
Conflictos de interés
Asesor externo
- AMGEN Oncología 2010/2012
- Roche Anemia 2009
- Ditassa-Ferrer 2004
Charlas, estudios investigación y ayudas a congresos
-Vifor-Uriach/Ferralinze
-Janssen-Cilag/Braun
-Astra-Tech de Aztra Zeneca/Well-Health?/GSK
-Sanofi Aventis/Esteve/Novartis/Octapharma
-Cobe-Caridian/Roche Oncología/AMGEN Oncologia
Miembro del CAT 2002-2005
Miembro del Documento de Sevilla “Alternativas a la Transfusión”
Miembro del Documento LatinoAmericano de la Anemia
Miembro de GIEMSA/ Secretario AWGE/Socio SETS/AEHH/NATA
Editor Asociado Revista ANEMIA www.revistaanemia.org
Miembro Comité Científico NATA y TATM
Representante de la SEHH en la ONT
Coordinador del Grupo de Trabajo de la SETS
“Hemoterapia basada en el sentido común”

INSUFICIENCIA CARDIACA, ANEMIA Y TRANSFUSIÓN
Agradecimientos
Prof. Manolo Muñoz Gómez
GIEMSA. Facultad de Medicina
Universidad de Málaga
Dr Manuel Quintana Díaz
Coordinador del Servicio de Urgencias de Adultos. Servicio de Cuidados
Intensivos. Hospital Universitario La Paz. Madrid. IdiPaz-49
Dra Ana I. Peral García
Servicio de Anestesiología y Reanimación -Hospital Puerta de Hierro
Majadahonda – Madrid
Dr Josep Comín Colet
Unidad de Insuficiencia Cardiaca. Servicio de cardiologia. Hospital del mar (IMAS)
Barcelona

Anemia e insuficiencia cardíacaAnemia e insuficiencia cardíaca
II Jornadas Pirenaicas de Cardiología
Jaca 28 de Febrero de 2005

II Jornadas Pirenaicas de Cardiología
Jaca 28 de Febrero de 2005
- La ANEMIA sería frecuente en pacientes con Insuficiencia
Cardíaca.
- ANEMIA de origen multifactorial. ¿Infra o mal
diagnosticada? ¿Tratada?
- La ANEMIA sería un factor predictivo de gravedad,
pronóstico y mortalidad.
- Posible papel del metabolismo del HIERRO.
INTRODUCCIÓN

INTRODUCCIÓN

INSUFICIENCIA
CARDIACA
ANEMIA
TRANSFUSIÓN
SANGUÍNEA
INTRODUCCIÓN

INSUFICIENCIA CARDIACA
• Prevalencia e incidencia en
aumento
• Alta mortalidad
• Alta morbilidad
• Elevado coste sanitario
• Afecta a población de edad
avanzada
• Comorbilidades
!Problema de Salud Pública!
Permanyer G et al. Rev Esp Cardiol 2002;55(6):57
Agradeciemiento. Modificada Dr Comín

ANEMIA
INSUFICIENCIA
CARDIACA
TRANSFUSIÓN
SANGUÍNEA
INTRODUCCIÓN

1.0 2.0 3.0 4.0 5.0 6.0
0
10
20
30
Male Female
6.0%
8.7%
1.5%
12.2%
4.4%
6.8%
7.8%
8.5%
15.7%
10.3%
26.1%
20.1%
1-16 17- 49 50 - 64 65 - 74 75 - 84 85+
Age group (years)
Percentwhohaveanemia
26,372 individuals
WHO criteria
Prevalencia de anemia
Cortestía/Modifiicada Prof. M. Muñoz

ANEMIA
Hipoxia tisular
vasodilatación
Reducción TA + SNS
vasoconstricción
Hipoperfusión renal
+ SRAA
IRC
Retención
hidrosalina
taquicardia
IC DESCOMPENSADA
* J Am Coll Cardiol 2000;35:1737
Postcarga
EPO
Performance
cardiaca
Factor precipitante de descompensación de la IC crónica*
¿CÓMO LA ANEMIA PROVOCA INSUFICIENCIA CARDÍACA?

ANEMIA
ACTIVACIÓN
NEUROHORMONAL
HIPERTROFIA
necrosis fibrosis apoptosis
DILATACIÓN +
DISFUNCIÓN VI
REMODELADO VI
Factor promotor de la progresión de la IC crónica*
¿CÓMO LA ANEMIA PROVOCA INSUFICIENCIA CARDÍACA?
* J Am Coll Cardiol 2000;35:1737
Hipoxia tisular vasodilatación
Reducción TA
+ SNS
+ SRAA

ETIOPATOGENIA DE LA ANEMIA en I. CARDÍACA
I) Malabsorción por bajo gasto: Disminución de la absorción intestinal
de Hierro, Vitamina B12, Ácido fólico, vitamina D, etc
II) Hipoperfusión renal: Disfunción y descenso de la síntesis de
eritropoyetina (EPO) +
III) Hipoperfusión médula ósea: disminución de la maduración de
proeritrobastos.
IV) Hemodilución: Activación del sistema renina-angiotensina-
aldosterona: Retención de Na y H2O.
V) Pérdidas por sangrado gastrointestinal (antiagregantes,
anticoagulantes, hipertensión portal, etc).
VI) Tratamiento con IECA y ARAII: peor respuesta EPO.
VII) Diabetes: Proteinuria y pérdida de EPO y transferrina con la orina.
VIII) Bloqueo hierro: Citoquinas TNF alfa, Hepcidicina

Insuficiencia
cardíaca
Fisiopatología de la anemia en el paciente
con insuficiencia cardíaca
Función
renal
Enterocito
Macrófagos
Hepcidina
EPO
Anemia
Disponibilidad
de hierro
Perfusión
Activación SRA
Tono simpático
IECAs
Médula
ósea
TNF
Perfusión
Resistencia
EPO
Hemo-
dilución
Diabetes
(Proteinuria)

Déficit nutricional
(Fe, B12, Fólico)
Pérdidas
de sangre
Disponibilidad
de hierro
Insuficiencia
cardíaca
Función
renal
Médula
ósea
TNF
Perfusión
Resistencia
EPO
Enterocito
Macrófagos
Hepcidina
EPO
Anemia
Perfusión
Activación SRA
Tono simpático
IECAs
Hemo-
dilución
Proteinuria
(EPO)

Isquemia
Apoptosis
HVI
Tono
Simpático
Insuficiencia
cardíaca
Función
renal
Médula
ósea
TNF
Perfusión
Resistencia
EPO
Enterocito
Macrófagos
Hepcidina
(Fe, B12, Fólico)
Pérdidas
de sangre
EPO
Anemia
Disponibilidad
de hierro
Perfusión
Activación SRA
Tono simpático
IECAs
Hemo-
dilución
Proteinuria
(EPO)

Clases III, IV
Clase II
Clase I
(Fe, B12, Fólico)
Pérdidas
de sangre
Disponibilidad
de hierro
Insuficiencia
cardíaca
Función
renal
Médula
ósea
TNF
Perfusión
Resistencia
EPO
Enterocito
Macrófagos
Hepcidina
EPO
Anemia
Perfusión
Activación SRA
Tono simpático
IECAs
Hemo-
dilución
Proteinuria
(EPO)

ANEMIA
INSUFICIENCIA
CARDIACA
INSUFICIENCIA
RENAL
CRÓNICA
ETIOPATOGENIA

DIAGNÓSTICO ANEMIA

Saturación transferrina < 20% Saturación transferrina > 20%
1. Evaluación GI
2. Reticulocitos, EPO, creatinina, PCR
AF1
Ferritina <30 µg/L
+ HCM <27 pg
ATC + F3
Ferritina
30-100 µg/L
ATC2
Ferritina
>100 µg/L
Hb <13 g/dL
Vitamina B12 y Folato
Bajo
VCM >100 fL
Anemia
macrocítica4
Tratamiento con
B12 / Folato
Normal
AOD SMD 4
3. sTfR/log Ft, hipocromía, CHr
4. Evaluación hematológica (Alcoholismo?)
Hb <13 g/dL
Tratamiento con
Fe oral o IV
Paciente IC con Hb <12 g/dL♀ o <13 g/dL ♂
Evaluar comorbilidad y tratamiento farmacológico
Tratamiento con
AEEs

Causas de anemia en insuficiencia cardíaca
Hussein y cols. J Card Failure 2003; 9: S19
Anémicos FE<40* FE>40
(n=125) (n=46) (n=71)
IRC (CrCL<60) 44 (35%) 20 (43%) 23 (32%)
Déficit Fe/fólico/B12 38 (30%) 13 (28%) 23 (32%)
Cirugía/sangrado 12 (10%) 4 (9%) 7 (10%)
Alt. Hematológica 17 (13%) 5 (11%) 10 (14%)
Otras 14 (11%) 4 (9%) 8 (11%)
604 pacientes IC ambulatorios consecutivos
125 pacientes anémicos (Hb<12 g/dL) (21%)
*Solo 117 tenían determinada la FE

ANEMIA Y CIRUGÍA CARDÍACA
210/576 patients (36.5%) presented with preoperative anemia

HIERRO E INSUFICIENCIA CARDÍACA
.....................................................................................................................................................................................
Iron deficiency isa key determinant of health-
related quality of life in patientswith chronic heart
failure regardlessof anaemia status
Josep Comıń-Colet 1,2,3*, Cristina Enjuanes1,2,3, Gina Gonza´lez1,2,4, Ainhoa Torrens1,2,3,
Merce` Cladellas2,3, Oona Meronõ1,2,3, Nuria Ribas1,2,3, Sonia Ruiz1, Miquel Go´mez1,2,3,
Jose´ Maria Verdu´2,3,5, and Jordi Bruguera1,2
1
Heart Failure Programme, Department of Cardiology, Hospital del Mar, Barcelona, Spain; 2
Heart DiseasesBiomedical Research Group, Program of Research in Inflammatory and
Cardiovascular Disorders, IMIM (Hospital del Mar Medical Research Institute), Barcelona, Spain; 3
Department of Medicine, Universitat Auto`nomade Barcelona. Barcelona, Spain;
4
Department of Cardiology, Fundacioń SantaFe, Bogota´, Colombia; and 5
Jordi Gol Primary Care Research Institute, Catalan Institute of Heath, Barcelona, Spain
Received 3 February 2013; revised 9 April 2013;accepted 26 April 2013; onlinepublish-ahead-of-print 22 May2013
A im s To evaluate the effect of iron deficiency (ID) and/or anaemiaon health-related quality of life (HRQoL) in patientswith
chronic heart failure (CHF).
Met hods
and result s
Weundertook apost-hoc analysisof acohort of CHFpatientsin asingle-centrestudy evaluatingcognitivefunction. At
recruitment, patients provided baseline information and completed the Minnesota Living with Heart Failure question-
naire(MLHFQ) for HRQoL(higher scoresreflect worseHRQoL).At thesametime,bloodsamplesweretakenfor sero-
logical evaluation. ID wasdefined asserum ferritin levels , 100 ng/mL or serum ferritin , 800 ng/mL with transferrin
saturation, 20%.Anaemiawasdefinedashaemoglobin ≤ 12 g/dL.A totalof552CHFpatientswereeligiblefor inclusion,
with anaverageageof 72 yearsand 40%in NYHA classIII or IV.TheMLHFQ overall summary scoreswere41.0+ 24.7
amongthosewithID,vs.34.4+ 26.4for non-ID patients(P¼ 0.003),indicatingworseHRQoL.Whenadjustedfor other
factors associated with HRQoL, ID wassignificantly associated with worse MLHFQ overall summary (P¼ 0.008) and
physical dimension scores(P¼ 0.002),whereasanaemiawasnot (bothP. 0.05).Increased levelsof solubletransferrin
receptor werealso associatedwithimpaired HRQoL(P≤ 0.001). Adjustingfor haemoglobinandC-reactiveprotein,ID
European Journal of Heart Failure (2013) 15,1164–1172
doi:10.1093/eurjhf/hft083
Conclusion:
“In patients with CHF, IRON DEFICIT but not anaemia was associated
with reduced HRQoL, mostly due to physical factors”.

CONSECUENCIAS DE LA ANEMIA

REC 2005
INSUFICIENCIA CARDIACA Y ANEMIA

• Influye negativamente en la calidad de vida relacionada
con la salud (Rev Esp Cardiol 2004;57(2):155 )
• Es un factor predictivo independiente de mayores gastos
derivados de la hospitalización (Am J Cardiol 2003;92(11):1300 SOLVD
substudy)
• Se relaciona con una peor capacidad funcional : la
prevalencia de anemia en pacientes con IC se incrementa
con la gravedad de la CF NYHA) (J Am Coll Cardiol 2000;35(7):1737)*
*% de pacientes en una cohorte de 142 pacientes con IC controlados en una UIC con Hb < 12 g%
Agradeciemiento. Modificada Dr Comín
Consecuencias de la anemia en el
paciente con insuficiencia cardíaca

• Factor predictivo independiente de mortalidad elevada.
• Mayores gastos derivados de hospitalización.
• Empeoramiento de la sintomatología.
• Puede precipitar isquemia miocárdica.
• Remodelado negativo del VI.
Horwich. J Am Coll Cardiol 2002;39:1780
Ezekowitz. Circulation 2003;107:223
SOLVD substudy. Am J Cardiol 2003;92:1300
Agradeciemiento. Modificada Prof Muñoz
Consecuencias de la anemia en el
paciente con insuficiencia cardíaca

• Factor predictivo independiente de mayor mortalidad
– 2281 pacientes. Kosiborod M et al. Am J Med 2003;114(2):112
– 1130 pacientes. Mozaffarian D et al. J Am Coll Cardiol 2003;
41(11):1933
– 12605 pacientes. Ezekowitz JA et al. Circulation 2003;107(2):223
– 176 pacientes. Szachniewicz J et al. Int J Cardiol 2003;90(2-3):303
– Felker GM et al. Am J Cardiol 2003;92(5):625
– 665 pacientes. McClellan WM et al. J Am Soc Nephrol 2002;13(7):1928
– 1061 pacientes. Horwich TB et al. J Am Coll Cardiol 2002;39(11):1780

ANEMIA Y TRANSFUSIÓN Y CIRUGÍA CARDÍACA
(Ann Thorac Surg 2012;94:1134–42)

25%
Al año de seguimiento, el 34,5% de los pacientes con anemia nosocomial
habían sufrido complicaciones cardiovasculares y/o muerte, frente al 9% de los
que se mantuvieron sin anemia (p < 0,001).
La anemia nosocomial resulta ser un predictor potente de mortalidad total y
de complicaciones cardiovasculares (hazard ratio = 2,47; intervalo de confianza
del 95%, 1,23-4,96; p = 0,01).
PATOLOGÍA CARDIACA Y ANEMIA

ANEMIA
INSUFICIENCIA
CARDIACA
TRANSFUSIÓN
SANGUÍNEA

¿TRATAMIENTO DE LA ANEMIA?
Compromiso
del aporte de
oxígeno
Instaurar
tratamiento
ANEMIA
Transfusional
NIVEL DE
HEMOGLOBINA

Clinical research
Valvular heart disease
Is pre-operative anaemia a risk marker for in-hospital
mortality and morbidity after valve replacement?
Merce` Cladellas1
*, Jordi Bruguera1
, Josep Comıń1
, Joan Vila2
, Elisabeth de Jaime3
,
Julio Martı´1
, and Miquel Gomez1
1
Department of Cardiology, Hospital del Mar (IMAS-UAB), Passeig Marı´tim 25– 29, E-08003 Barcelona, Spain; 2
Institut
Municipal d’Investigacio´ Me` dica (IMIM); and 3
Department of Geriatrics, Institut Municipal d’Investigacio´ Me` dica (IMIM),
Barcelona, Spain
Received 19 April 2005; revised 18 January 2006; accepted 23 February 2006; online publish-ahead-of-print 14 March 2006
Aims To assess the level of pre-operative haemoglobin (HB) as a risk marker for morbidity and mortality
in the early post-operative period of patients who underwent elective valve replacement.
Methods and results Between January 1998 and March 2004, clinical and outcomes data were collected
for the 201 patients who had elective valve replacement. For each gender, the criterion to choose the
best cut-off point wasthat which achieved the maximum likelihood after several General Additive Model
models performed in a Bootstrap procedure. The best cut-off point obtained for pre-operative HB was
12 g/ dL. Overall peri-operat ive mortality (deaths occurring during hospital period or within 30 days) was
9.5%. After adjusting well-known independent pre-operative risk factors for operative mortality, pre-
operative HB , 12 g/ dL was identified as an independent predictor for in-hospital mortality (OR,
3.23; 95%CI, 1.09– 9.55; P¼ 0.03). Also adjusting for EuroScore, pre-operative HB remained significant
(OR, 3.64; 95%CI, 1.32– 10.06; P¼ 0.01). The same model was applied to post-operat ive morbidity, and
pre-operative HB , 12 g/ dL was identified as an independent predictor with and without EuroScore (OR,
4.67; 95%CI, 2.03– 10.71; P, 0.001), (OR, 5.18; 95%CI, 2.18– 12.3; P, 0.001), respectively.
KEYWORDS
Anaemia;
Heart valve prosthesis;
Cardiac valve
European Heart Journal (2006) 27, 1093– 1099
doi:10.1093/ eurheartj/ ehi830
http://eurheartj.oxfordjoDownloadedfrom
Increasing patient age, female sex, lower preoperative haemoglobin levels, as well as the urgency
of the CABG surgery were associated with higher transfusion rates.

Unadjusted odds of 30-day operative mortality for patients with preoperative
hemoglobin level less than 10 g/dL were 2.37 times higher than for patients
with hemoglobin levels of 10 g/dL or greater (95% confidence interval: 1.84 to
3.05; p < 0.0001).
Ann Thorac Surg 2008;86:1415–23

Muñoz M, Ariza D, Leal Noval SR, García Erce JA CIRUGÍA CARDÍACA EN EL ANCIANO: PREVALENCIA
Y CONSECUENCIAS DE LA ANEMIA PREOPERATORIA. Med Clin (Barc). 2008;131(7):276-9

ANEMIA Y TRANSFUSIÓN Y PATOLOGÍA CARDÍACA
Am J Cardiol 2008;102:115–119)

J Am Coll Cardiol 2015;66:2510–8

ANEMIA
INSUFICIENCIA
CARDIACA
TRANSFUSIÓN
SANGUÍNEA
PROBLEMAS DE LA

Transfusion 2008
EFECTOS ADVERSOS O RIESGOS DE LA TRANSFUSIÓN

JAMA, October 13, 2010—Vol 304, No. 14

JAMA April 2014. Vol 311

Adverse effects of RBC transfusion contrasted with other risks
Carson JL et al. Red Blood Cell Transfusion: A Clinical Practice Guideline From the AABB
Ann Intern Med. 2012 Jul 3; 157(1): 49-58

DIAGNÓSTICO DIFERENCIAL: “TACO”
TRALI: “Lesión pulmonar aguda asociada a transfusión“
INSUFICIENCIA RESPIRATORIA Y TRANSFUSIÓN
“EDEMA PULMONAR SECUNDARIO A SOBRECARGA
DURANTE LA TRANSFUSION ó TRANSFUSION ACUTE
CIRCULATORY OVERLOAD”

DIAGNÓSTICO DIFERENCIAL: “TACO”
TRALI: “Lesión pulmonar aguda asociada a transfusión“
Modificada. Cortesía Dr Lea
TAC
O
TACO Aumento
presión
hidrostática
Historia
cardiopatía
Fallo
circulatorio
Aumento BNP,
PCP elevada
Aumento de proteínas en líquido
alveolar
TRALI Daño Endotelial No historia
cardiopatía
No fallo
circulatorio
BNP normal,
PCP no aumentada
No aumento proteínas en líquido
alveolar

TRALI vs TACO

Fatalities Reported to FDA Following Blood Collection and
Transfusion
Período 2009-2013: 190 fallecimientos documentados
2009: 44; ’10: 40; ’11: 30; ’12: 38; y ’13: 38
72 29 13 45 9 3
19
MORTALIDAD ASOCIADA A TRANSFUSIÓN

MORTALIDAD ASOCIADA A TRANSFUSIÓN
Sistemas de Hemovigilancia: REINO UNIDO(sin
Escocia)

Am J Cardiol 2008;102:115–119)

¿TRATAMIENTO DE LA ANEMIA?
Compromiso
del aporte de
oxígeno
Instaurar
tratamiento
ANEMIA
Transfusional
NIVEL DE
HEMOGLOBINA
Enfermedad
Sustitutos
Farmacológico

Silverberg y cols. JACC 2000; 35: 1737-1744
 26 pacientes con FCC y Hb <12 g/dL, NYHA >3 y FEVI <35%
 EPO: 2000 UI/semana sc (hasta Hb >12 g/dL)
 Venofer: 200 mg/semana iv (hasta FRT 400 mg/L; Sat TFR 40% o
Hb 12 g/dL)
 Duración del tratamiento: 4-12 meses
Hb ( g/dL) 10.1 ± 0.9 12.1 ± 1.2*
Ferritina (mg/L) 177 ± 114 347 ± 207*
Hierro (mg/dL) 60 ± 19 75 ± 21*
SatTRF (%) 20 ± 6 26 ± 5*
FEVI (%) 27.7 ± 4.8 35.4 ± 7.6*
Hospitalización/pte 2.7 ± 1.2 0.2 ± 0.5*
NYHA (0-4) 3.7 ± 0.5 2.7 ± 0.7*
PostPreParámetro

Silverberg y cols. JACC 2001; 37: 1775-80
 32 pacientes con FCC y Hb <12 g/dL, NYHA 3 - 4 y FEVI ≤ 40%
 Grupo estudio: EPO 4000 UI/s sc (hasta Hb >12,5 g/dL) +
Venofer 200 mg/s iv (hasta FRT 400 mg/L; Sat 40% o Hb 12,5 g/dL).
 Grupo control: No tratamiento
 Duración del estudio: 8.2 ± 2.7 meses
Mortalidad: 25% vs. 0%
Hb (g/dL) Pre 10.9 ± 0.8 10.3 ± 1.2
Post 10.8 ± 0.8 12.9 ± 1.1*
FEVI (%) Pre 28.4 ± 7.6 30.8 ± 12.6
Post 23.0 ± 6.9 36.3 ± 11.9*
Hospital (días) Pre 9.9 ± 4.8 13.8 ± 7.2
Post 15.6 ± 9.8 9.8 ± 2.9*
NYHA Pre 3.5 ± 0.7 3.8 ± 0.4
Post 3.9 ± 0.3 2.2 ± 0.7*
Grupo
tratamiento
Grupo
control
Parámetro
estudiado

 23 ptes con ICC II-IV (Htc <35, Cr<2.5 mg/dL, Epo<100 mU/L)
 Grupo estudio: EPO 5000 UI/semana sc (10000 U/I semana)
+ hierro y folato oral diario (n=15)
 Grupo control: placebo EPO (n=8)
 Duración del tratamiento: 3 meses o Htc >45
Mancini y cols. Circulation 2003; 107: 294-9
Hb (g/dL) Pre 10.9 ± 1.3 11.0 ± 0.6
Post 11.5 ± 1.3 14.3 ± 1.2*
Peak VO2 Pre 10.0 ± 1.9 11.0 ± 0.8
Post 9.5 ± 1.6 12.7 ± 2.8*
MLWHFQ Pre 56 46
Post 66* 37*
Distancia 6 min Pre 929 ± 356 1187 ± 279
(pies) Post 1052 ± 403 1328 ± 254*
Grupo
tratamiento
Grupo
control
Parámetro
estudiado

• 319 pacientes con IC sintomática, FEVI ≤ 40% y
Hb entre 9.0 g/dL y 12.5 g/dL.
• Placebo (n=157) or darbepoetin alfa (0.75 µg/kg;
n=162) sc cada 2 semanas más hierro oral diario
durante un año (Hb objetivo: 14.0 ± 1.0 g/dL).
• Variable principal:
• Cambio en la capacidad de ejercicio a las 27
semanas de tto.
• Variables secundarias:
• Clase NYHA
• Calidad de vida
• Mortalidad por cualquier causa
• Hospitalizacion por IC en un aňo.
Ghali y cols. Circulation 2008; 117: 526-35

• 7 estudios aleatorizados y controlados
- 363 pacientes tratados con AEEs
- 287 pacientes con placebo
• Corrección de la anemia
• Mayor tolerancia al ejercicio y calidad de vida
• Menor riesgo de hospitalizacion
(RR 0.59, [95%CI 0.41-0.86];p= 0.006)
• No diferencias en mortalidad
(RR 0.69, [95%CI 0.39-1.23]; p=0.21).
• No diferencia en HTA o trombosis
Heart. 2009 Jan 23. [Epub ahead of print]
Erythropoietin Treatment in Patients with Chronic
Heart Failure: a meta-analysis.
Van der Meer P, Groenveld H, Januzzi JL, Van Veldhuisen DJ.

Erythropoiesis Stimulating Agents in Heart Failure
Patients with Anemia: A Meta-Analysis
Faramarz Tehrani &Pavittarpaul Dhesi &
Daniel Daneshvar &Anita Phan &Asim Rafique&
Robert J. Siegel &Bojan Cercek
# Springer Science + Business Media, LLC 2009
Abstract
Background Anemia is prevalent in patients with heart
failure and an independent prognostic sign of poor
outcome. The current report is a meta-analysis of published
clinical trials assessing the use of erythropoeisis stimulating
agents (ESA) in heart failure (HF) patients with anemia.
Methods Literature and Medline search was performed to
identify studies with control groups (case-control, cohort or
randomized controlled trials) that examined the effect of
ESA therapy in patients with HF and anemia.
Results Seven prospective controlled trials met inclusion
criteria (n=663 subjects). TheESA studied was darbepoetin
in 4 trials and erythropoietin in 3 trials. Mean follow up
period ranged from 12 to 27 weeks. Compared to placebo
ESA therapy was associated with improvement in six
cardiovascular parameters assessed by at least three of the
analyzed trials, including increase in hemoglobin levels
2.35(95% confidence interval [Cl], 1.76–2.93, P<0.00001),
increase in exercise duration 0.91(95% Cl, 0.08–1.73,
P=0.03), improvement in New York Heart Association
functional class −1.46(95% Cl, −2.32 to −0.60, P=0.0009),
improvement in 6-minute walk test 1.42(95% Cl, 0.31–2.54,
eters, compared to control therapy. Large prospective
randomized controlled trials are warranted to comprehen-
sively evaluate the potential effects of erythropoiesis
stimulating agents on clinical outcomes in heart failure
patients with anemia.
Key words Heart failure. Anemia.Erythropoietin
Introduction
Current research has shown that anemia is prevalent in
patients with heart failure (HF) [1–4]. A recent prospective
analysis evaluating the Study of Anemia in a Heart Failure
Population (STAMINA-HFP) registry reported that anemia
was present in 34% of the patients with heart failure [5],
though other, similar studies have demonstrated prevalence
as high as 55% [6, 7].
Recently there has been much debate regarding presence
of anemiabeing causally related to HF or if it is amarker of
more advanced disease. While the etiology is likely multi-
factorial and has not been clearly discerned, potential
Cardiovasc Drugs Ther
DOI 10.1007/s10557-009-6203-6
Hb
6 min test
Pro-BNP
NYHA

Homeostasis del hierro: inflamación
20-30
mg/day
Liver & Muscles
(1000 mg)
Bone marrow
(300 mg)
Erythrocytes
(2.500 mg)
Intestinal absorption
(1-2 mg/day)
Transferrin
(4 mg)
Iron losses
(1-2 mg/day)
Macrophages RES
(500 mg)
IV iron
Macrophages RES
(750-1500 mg)

Bolger y cols. JACC 2006; 48: 1225-7
 16 pacientes con IC estable II-III, Hb ≤12 g/dL y FEVI 26 ± 13%
 Venofer: 200 mg/bolo iv (max. 1 g en 12 días en régimen ambulatorio)
 Duración del seguimiento: 92 ± 6 días
Hb ( g/dL) 11.2 ± 0.7 12.6 ± 1.2*
Ferritina (mg/L) 87 ± 113 217 ± 185*
SatTRF (%) 16 ± 9 25 ± 8*
Hierro (µmol/L) 9.2 ± 4,4 13.7 ± 4.8*
MLWHFQ 33 ± 19 19 ± 14*
6MW (m) 242 ± 78 286 ± 72*
NYHA (II/III) 9/7 16/0
Post -ttoPre-ttoParámetro

 40 ptes con ICC II-IV e IRC (Hb <12.5 g/dL, ferritina <100 ng/mL
y/o Sat ≤20%, CrCl <90 mL/min y FEVI ≤ 35%)
 Grupo estudio: Hierro sacarosa 200 mg/semana iv (n=20)
 Grupo control: placebo (n=20)
 Duración del tratamiento: 5 semanas. Seguimiento: 6 meses
Toblli y cols. JACC 2007; 50: 1657-65
Hb (g/dL) Basal 10.2 ± 0.5 10.3 ± 0.6
6 meses 9.8 ± 0.6 11.8 ± 0.7*#
Clase NYHA Basal 2.9 ± 0.6 2.9 ± 0.7
6 meses 3.3 ± 0.6* 2.0 ± 0.2*#
MLWHFQ Basal 58 ± 6 60 ± 5
6 meses 59 ± 8 41 ± 57*#
Distancia 6 min Basal 191 ± 56 192 ± 61
(metros) 6 meses 184 ± 58 240 ± 51*#
Grupo
tratamiento
Grupo
control
Parámetro
estudiado
*P<0.05 vs. basal; #
P<0.05 vs. control

No hubo diferencias en los niveles de Hb entre los grupos

TRATAMIENTO DE ANEMIA CIRUGÍA CARDÍACA

Am J Cardiol 2012;110:1021–1026
TRATAMIENTO DE ANEMIA CIRUGÍA CARDÍACA

TRATAMIENTO DE ANEMIA INSUFICIENCIA CARDÍACA

.....................................................................................................................................................................................
CLINICAL RESEARCH
Heart failure/cardiomyopathy
The effect of intravenous ferric carboxymaltose
on health-related quality of life in patients
with chronic heart failure and iron deficiency:
a subanalysis of the FAIR-HF study
Josep Comin-Colet 1,2*, Mitja Lainscak3,4, Kenneth Dickstein5,6,
Gerasimos S. Filippatos7, Patrick Johnson8, Thomas F. Lu¨scher 9, Claudio Mori8,
Ronnie W illenheimer 10,11, Piotr Ponikowski12,13, and Stefan D. Anker 4,14
1
Heart Failure Programme, Department of Cardiology, and Research in Inflammatory and Cardiovascular Disorders Programme, IMIM–Hospital del Mar (Parc de Salut Mar), Passeig
Maritim, 25–29, 08003, Barcelona, Spain; 2
Department of Medicine, Universitat Autonoma de Barcelona, Barcelona, Spain; 3
Division of Cardiology, University Clinic of Respiratory
and Allergic Diseases, Golnik, Slovenia; 4
Applied Cachexia Research, Department of Cardiology, Charite´ Campus Virchow-Klinikum, Berlin, Germany; 5
Stavanger University
Hospital, Stavanger, Norway; 6
University of Bergen, Bergen, Norway; 7
Athens University Hospital Attikon, Athens, Greece; 8
Vifor Pharma Ltd., Glattbrugg, Switzerland;
9
Department of Cardiology, Cardiovascular Center, University Hospital Zu¨rich, Zurich, Switzerland; 1 0
Heart Health Group, Malmo¨, Sweden; 1 1
Lund University, Malmo¨, Sweden;
1 2
Wroclaw Medical University, Wroclaw, Poland; 1 3
Military Hospital, Wroclaw, Poland; and 1 4
Centre for Clinical and Basic Research, IRCCSSan Raffaele, Rome, Italy
Received 8 August 2011; revised 5 December 2011; accepted 20 December 2011; online publish-ahead-of-print 31 January 2012
This paper was guest-edited by W illiam T. Abraham, Professor of Medicine, Physiology and Cell Biology, The Ohio State University,
Columbus, OH 43210-1252, USA
A im s Patients with chronic heart failure (CHF) show impaired health-related quality of life (HRQoL), an important target
for therapeutic intervention. Impaired iron homeostasis may be one mechanism underlying the poor physical condi-
tion of CHFpatients. This detailed subanalysis of the previously published FAIR-HFstudy evaluated baseline HRQoL
in iron-deficient patients with CHF and the effect of intravenous ferric carboxymaltose (FCM) on HRQoL.
Met hods FAIR-HFrandomized 459 patients with reduced left ventricular ejection fraction and iron deficiency, with or without
European Heart Journal (2013) 34, 30–38
doi:10.1093/eurheartj/ehr504
byguestonhttp://eurheartj.oxfordjournals.org/Downloadedfrom
HRQoL is impaired in iron-deficient patients with CHF. Intravenous FCM significantly
improved HRQoL after 4 weeks, and throughout the remaining study period.
The positive effects of FCM were independent of anaemia status.

.....................................................................................................................................................................................
.....................................................................................................................................................................................
CLINICAL RESEARCH
Josep Comin-Colet1,2*, Mitja Lainscak3,4, Kenneth Dickstein5,6,
Ronnie W illenheimer 10,11, Piotr Ponikowski12,13, and Stefan D. Anker4,14
1
9
1 2
Centre for Clinical and Basic Research, IRCCS San Raffaele, Rome, Italy
Met hods
and r esult s
FAIR-HFrandomized 459 patients with reduced left ventricular ejection fraction and iron deficiency, with or without
anaemia, to FCM or placebo (2:1). Health-related quality of life wasassessed at baseline and after 4, 12, and 24 weeks
of therapy using the generic EQ-5D questionnaire and disease-specific Kansas City Cardiomyopathy Questionnaire
(KCCQ). Baseline mean Visual Analogue Scale (VAS) score was 54.3+ 16.4 and KCCQ overall summary score was
52.4+ 18.8. Ferric carboxymaltose significantly improved VASand KCCQ (mean differencesfrom baseline in KCCQ
overall, clinical and total symptom scores, P, 0.001 vs. placebo) at all time points. At Week 24, significant improve-
ment vs. placebo was observed in four of the five EQ-5D dimensions: mobility (P¼ 0.004), self-care (P, 0.001),
pain/discomfort (P¼ 0.006), anxiety/depression (P¼ 0.012), and usual activity (P¼ 0.035). Ferric carboxymaltose
improved all KCCQ domain mean scores from Week 4 onward (P≤ 0.05), except for self-efficacy and social
limitation. Effects were present in both anaemic and non-anaemic patients.
Conclusions HRQoL is impaired in iron-deficient patients with CHF. Intravenous FCM significantly improved HRQoL after 4
weeks, and throughout the remaining study period. The positive effects of FCM were independent of anaemia status.
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Keywor ds Anaemia † Chronic heart failure † Health-related quality of life † Iron deficiency
* Corresponding author. Tel: + 34 932483118, Fax: + 34 932483398, Email: jcomin@hospitaldelmar.cat
byguestonJanuary15,2016http://eurheartj.oxfordjournals.org/Downloadedfrom

.....................................................................................................................................................................................
.....................................................................................................................................................................................
CLINICAL RESEARCH
Josep Comin-Colet1,2*, Mitja Lainscak3,4, Kenneth Dickstein5,6,
Ronnie W illenheimer 10,11, Piotr Ponikowski12,13, and Stefan D. Anker4,14
1
9
1 2
Centre for Clinical and Basic Research, IRCCS San Raffaele, Rome, Italy
Met hods
and r esult s
FAIR-HFrandomized 459 patients with reduced left ventricular ejection fraction and iron deficiency, with or without
anaemia, to FCM or placebo (2:1). Health-related quality of life wasassessed at baseline and after 4, 12, and 24 weeks
of therapy using the generic EQ-5D questionnaire and disease-specific Kansas City Cardiomyopathy Questionnaire
(KCCQ). Baseline mean Visual Analogue Scale (VAS) score was 54.3+ 16.4 and KCCQ overall summary score was
52.4+ 18.8. Ferric carboxymaltose significantly improved VASand KCCQ (mean differencesfrom baseline in KCCQ
overall, clinical and total symptom scores, P, 0.001 vs. placebo) at all time points. At Week 24, significant improve-
ment vs. placebo was observed in four of the five EQ-5D dimensions: mobility (P¼ 0.004), self-care (P, 0.001),
pain/discomfort (P¼ 0.006), anxiety/depression (P¼ 0.012), and usual activity (P¼ 0.035). Ferric carboxymaltose
improved all KCCQ domain mean scores from Week 4 onward (P≤ 0.05), except for self-efficacy and social
limitation. Effects were present in both anaemic and non-anaemic patients.
Conclusions HRQoL is impaired in iron-deficient patients with CHF. Intravenous FCM significantly improved HRQoL after 4
weeks, and throughout the remaining study period. The positive effects of FCM were independent of anaemia status.
- - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - -
Keywor ds Anaemia † Chronic heart failure † Health-related quality of life † Iron deficiency
* Corresponding author. Tel: + 34 932483118, Fax: + 34 932483398, Email: jcomin@hospitaldelmar.cat
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2012.
This isan Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which
permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
byguestonJanuary15,2016http://eurheartj.oxfordjournals.org/Downloadedfrom

Beneficial effects of long term intravenous iron therapy with ferric carboxymaltose in
patients with symptomatic heart failure and iron deficit. CONFIRM .
European Heart Journal. August 2014

Revista Española de Cardiología 2015

WHO 63.12 resolution. Availability, safety and quality of blood products. 2010. 2013.
Patient Blood Management in Europe. Br J Anaesth 2012
EVITAR ANEMIA
Optimización
de eritropoyesis
EVITAR ANEMIA
Optimización
de eritropoyesis
CONTROLAR
HEMORRAGIA
Minimización de pérdidas
sanguíneas
CONTROLAR
HEMORRAGIA
Minimización de pérdidas
sanguíneas
EVITAR
TRANSFUSIÓN
Optimización de la
tolerancia a la anemia
EVITAR
TRANSFUSIÓN
Optimización de la
tolerancia a la anemia
Los Servicios de Salud deben establecer
programas multidisciplinares y multimodales
para el manejo perioperatorio de los pacientes, basados en:
Los Servicios de Salud deben establecer
programas multidisciplinares y multimodales
para el manejo perioperatorio de los pacientes, basados en:
MANEJO INTEGRAL MULTIMODAL DE LA ANEMIA
TRES PILARES DEL PATIENT BLOOD MANAGEMENT

TRES MOMENTOS DEL PATIENT BLOOD MANAGEMENT
Shander A et al. Patient blood management in Europe
British Journal of Anaesthesia 2012; 109 (1): 55–68
PATIENT BLOOD MANAGEMENT Y PATOLOGÍA CARDÍACA

Requirements for implementing
a Patient Blood Management program
M. Muñoz et al. ‘Fit to fly’: overcoming barriers to preoperative haemoglobin
optimization in surgical patients. British Journal of Anaesthesia 2015; 115 (1):
15–24
PATIENT BLOOD MANAGEMENT Y PATOLOGÍA CARDÍACA

“DE UNO EN UNO”
PATIENT BLOOD MANAGEMENT Y CIRUGÍA CARDÍACA

“REDUCCIÓN DEL SANGRADO (IATROGENIA)”

Ultrafilt ration reduces blood transfusions following
cardiac surgery: a meta-analysis
Munir Boodhwani a
, Kathryn Williamsb
, Andrew Babaev a
,
Gurinder Gill a
, Nusrat Saleem a
, Fraser D. Rubensa , *
a
Division of Cardiac Surgery, Universit y of Ottawa Heart Institute, Canada
b
Division of Clinical Research, Universit y of Ottawa Heart Institute, Canada
Received 31 March 2006; received in revised form 18 August 2006; accept ed 15 September 2006
Abstract
Background: Although used routinely in pediatric patients, ultrafiltrat ion techniques that reverse hemodilution are infrequently used in
adults. Data from small, unblinded clinical trials suggest that the use of ultrafiltrat ion can reduce inflammatory mediators, improve cardiac
function, and reduce hemodilution. We conducted a meta-analysis of randomized trials to evaluate the effects of ultrafiltration on blood
transfusions and blood lossfollowing adult cardiac surgery. Methods: Medline, EMBASE, and Cochrane databases were searched and randomized
controlled trials evaluating modified and/ or conventional ultrafiltration, meeting pre-determined selection criteria, were obtained. Quality
evaluation and data extraction were performed by two independent observers blinded to study source. Random effects models were used to
determine pooled effect estimates and sources of heterogeneity were explored using meta-regression. Results: One hundred and thirty two
studies were screened and 10 randomized trials evaluating 1004 patients (control, n = 495; ultrafiltrat ion, n = 509) were identified of which only
two were double-blinded. The use of ultrafiltrat ion was associated with a reduction in postoperat ive blood transfusions (weighted mean
www.elsevier.com/ locat e/ ejcts
European Journal of Cardio-t horacic Surgery 30 (2006) 892—897

Patient Blood Management en Cirugía Cardíaca
Transfusion 2015
MANEJO INTEGRAL MULTIMODAL DE LA ANEMIA

Patient Blood Management
y resultado clínico
WHA 63.12 (resolution). Availability, safety and quality of blood products, 2010.
Available at: http://apps.who.int/gb/ebwha/pdf_files/WHA63/A63_R12-en.pdf.
Optimización
perioperatoria
eritropoyesis
Minimización
del sangrado/
coagulopatía
Tolerancia
a la anemia
postoperatoria
Mejor
resultado
clínico
Insuficiencia
Cardiaca

“The safest blood transfusión is….the one don´t given”
ase!, DO SOMETHING! TREAT THE ANAEMIA WISE AND NICEL

http://www.choosingwisely.org/
Choosing Wisely aims to choose care that is:
-Supported by evidence
-Not duplicative of other tests or procedures already received
-Free from harm
-Truly necessary
In response to this challenge, national organizations representing medical
specialists asked their providers to “choose wisely” by identifying tests or
procedures commonly used in their field whose necessity should be questioned and
discussed.

ANEMIA
INSUFICIENCIA
CARDIACA
TRANSFUSIÓN
SANGUÍNEA
RESUMEN

Recomendación Nº 9: Hemograma completo
La anemia es un factor de riesgo relacionado con la mortalidad, la hospitalización y
la gravedad, pudiendo incluso provocar ICA.
/../ la ferropenia, asociada o no a la anemia, con el empeoramiento clínico de la IC

VIII Curso
Talavera Enero 2016
- La ANEMIA ES frecuente en pacientes con Insuficiencia
Cardíaca.
- ANEMIA ES de origen multifactorial. ¿Infra o mal
diagnosticada? ¿Tratada?
- La ANEMIA ES un factor predictivo de gravedad, pronóstico
y mortalidad.
- PAPEL del metabolismo del HIERRO y de la EPO.
INTRODUCCIÓN
- TRANSFUSIÓN RESTRICTIVA “WISELY”.

Anemia, insuficiencia cardíaca y transfusión. Talavera 2016

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