RED CELL DISTRIBUTION WIDTH

A NEW MARKER OF EXERCISE INTOLERANCE

IN PATIENTS WITH CHRONIC HEART FAILURE

Emeline Van Craenenbroeck, Paul Beckers, Nadine Possemiers,

Christiaan Vrints, Viviane Conraads

Cardiology Department, Antwerp University Hospital, Belgium

Disclosure information: This study is supported by the Fund for Scientific Research (FWO-Flandres)

PROGNOSTICATORS IN CHF

Single-term prognosticators:

• ER and hospital admissions

• Symptoms at rest

• Cachexia

• Hemoglobin, sodium, troponin, creatinine

• High natriuretic peptides

• LVEF < 20%

• Symptomatic arrhythmia’s

………

Complex, multivariate models:

• Heart Failure Survival Score

• Seattle Heart Failure Model

High natriuretic peptides

• Red blood cell distribution width, RDW, is a measure of the variation of red blood

cell volume (MCV)

• Reference range 11.6 - 14.6 %, available as part of the complete blood count

• Higher RDW values indicate greater variation in size (anisocytosis)

RED CELL DISTRIBUTION WIDTH (RDW)

RDW =

Standard deviation of MCV

Mean MCV

X 100

RDW IN CHONIC HEART FAILURE

Red cell distribution width as a novel prognostic marker in chronic heart failure.

Felker M, et al. J Am Coll Cardiol 2007; 50:40-47

RDW IN CHONIC HEART FAILURE

Red cell distribution width: an inexpensive and powerful prognostic marker in heart failure.

Al-NajjarY, et al. Eur J Heart Fail 2009; 11:1155-1162

N=1087

CAUSES OF HIGH RDW VALUES

Erythropoiesis

Iron deficiency

Anemia of chronic disease

B12 or folate deficiency

Inadequate epo production

Bone marrow suppression

Inflammation

Hemoglobinopathies

RBC Destruction

Hemolysis

Thrombotic conditions

Blood Transfusion

Elevated

RDW

Chronic Heart FailureIron deficiency

Anemia of chronic disease

B12 or folate deficiency

Inadequate epo production

Bone marrow suppression

Inflammation

EXERCISE INTOLERANCE IN CHF

VO2peak = CO x (CaO2-CvO2)

Blood supply

Metabolic alteration in skeletal muscle

Deficient oxygen transport in RBC ?

Muscle mass

Stroke volume

Chronotropic response

AIMS OF THE STUDY

1.To study the relation between objective parameters of

exercise intolerance and RDW in CHF

2.To investigate the effect of exercise training on RDW

measures in relation to improved exercise capacity

PATIENTS

Exclusion

- Recent ACS/revascularization

- Exercise limited by angina or arrythmia

- Anemia, epo substitution, recent blood

transfusion

- Severe renal failure

- Chronic inflammatory of malignant disease

Inclusion

- LVEF ≤ 40%

- Ischemic or dilated cardiomyopathy

- Stable symptoms and medical therapy for 1 mth

118 CHF patients

TRAINING GROUP

71 patients referred for exercise training

CONTROL GROUP

47 patients followed at Heart Failure Clinic

STUDY DESIGN

BaselineMaximal cardiopulmonary exercise test (Treadmill)

Blood sampling (RDW, Hb, Fe status, NT-proBNP)

TRAINING GROUP

Endurance training (+/- resistive exercises)

Target HR 90% of HR at AT

In hospital, 3x/week, 1h

CONTROL GROUP

Sedentary

6-months Follow-upMaximal cardiopulmonary exercise test (Treadmill)

Blood sampling (RDW, Hb, Fe status, NT-proBNP)

PATIENT CHARACTERISTICS

AGE (YEARS) 60.6 ± 1.0

GENDER (% MALE) 72

HEART FAILURE CHARACTERISTICS

NYHA class I-II (%) 47.5

NYHA class III-IV (%) 52.5

LVEF (%) 25.3 ± 8.7

Etiology (% ischemic) 67.8

NT-proBNP (pg/ml) 860 (427-2264)

EXERCISE CAPACITY

VO2peak (ml.kg -1.min-2) 19.1 ± 5.3

Percentage predicted VO2peak (%) 74.9 ± 1.7

Maximal Workload (Watt) 103 ± 3.23

HAEMATOLOGICAL PARAMETERS

Hemoglobin (g/dl) 13.3 ± 0.13

MCV (fl) 90.7 (88.6-94.7)

RDW (%) 13.6 (12.8-14.6)

Leukocytes (x 109/L) 6.8 ± 0.17

BIOCHEMICAL PARAMETERS

Creatinine Clearance (ml/min) 65.6 ± 2.5

Serum Fe (µg/dl) 98.5 ± 3.8

TIBC (µg/dl) 325 ± 6.8

Transferrin saturation (%) 31 ± 1.4

MEDICATION

ACE/ARB (%) 81.4

Beta-blockers (%) 80.5

Diuretics (%) 83.1

Spironolactone (%) 54.2

RELATION OF RDW WITH EXERCISE CAPACITY

PEARSON R P-VALUE

AGE (YEARS) 0.172 0.062

BODY MASS INDEX (KG/M2) 0.004 0.967

HEART FAILURE CHARACTERISTICS

NYHA class 0.193 0.036

LVEF (%) -0.094 0.31

EXERCISE CAPACITY

VO2peak (ml.kg -1.min-2) -0.449 < 0.00001

VO2peak at VT2 (ml.kg -1.min-2) -0.374 0.001

Maximal Workload (Watt) -0.524 < 0.00001

VE/VCO2slope 0.287 0.002

Heart rate at maximum (bpm) -0.362 < 0.0001

Oxygen pulse (mlVO2.kg-1.min -2/beat) -0.201 0.029

Circulatory Power (mmHg. mlVO2.kg-1.min -2) -0.471 < 0.00001

LABORATORY PARAMETERS

logNT-proBNP 0.319 < 0.001

Hemoglobin (g/dl) -0.343 < 0.00001

logMCV -0.163 0.079

Serum Fe (µg/dl) -0.127 0.184

TIBC (µg/dl) 0.054 0.596

Transferrin saturation (%) -0.09 0.381

r = -0.449; p<0.0001

PREDICTOR OF EXERCISE CAPACITY

VO2PEAK

BETA P-VALUE

Age - 0.325 0.001

LogRDW - 0.305 0.001

NYHA class - 0.170 0.065

logNT-proBNP - 0.031 0.761

Hemoglobin - 0.071 0.513

Creatinine Clearance 0.186 0.076

Serum Fe 0.275 0.215

Transferrin saturation - 0.087 0.669

RDW is a strong and independent predictor of VO2peak

VE/VCO2 SLOPE

BETA P-VALUE

Age - 0.124 0.265

LogRDW 0.125 0.250

NYHA class 0.211 0.052

logNT-proBNP 0.224 0.066

Hemoglobin 0.176 0.172

Creatinine Clearance - 0.190 0.124

Serum Fe 0.064 0.807

Transferrin saturation - 0.250 0.393

RDW is not a predictor of VE/VCO2 slope

Multiple regression analysis based on significant parameters in the bivariate

model

TRAINING

Baseline Follow-up

VO

2p

eak (

ml/

kg

/m

in)

18

19

20

21

22

23

Baseline Follow-upM

axim

al W

orklo

ad

(W

att

)90

100

110

120

130

140

Effect on exercise capacity

Control Training

P=0.005 P=0.00001

TRAINING

Baseline Follow-up

RD

W(%

)

13.0

13.2

13.4

13.6

13.8

14.0

14.2

14.4

Control Training

Effect on RDW values

6-months exercise training significantly reduces

RDW values

P=0.0003

TRAINING

P-values based on ANOVA repeated measures of log transformed data

CONTROL GROUP TRAINING GROUP P-Value

Baseline Follow-up Baseline Follow-up

HEMATOLOGICAL PARAMETERS

RDW (%) 13.6 ± 0.2 13.7 ± 0.2 14.0 ± 0.2 13.3 ± 0.1 0.0003

MCV (%) 92.2 ± 1.0 91.2 ± 1.1 91.8 ± 0.7 92.2 ± 0.6 0.022

Hemoglobin (g/dl) 13.6 ± 0.2 13.4 ± 0.2 13.1 ± 0.2 13.3 ± 0.2 0.126

FE STATUS

Serum Fe (ug/ml) 102.4 ± 6.8 98.1 ± 6.5 95.9 ± 4.6 94.5 ± 3.1 0.498

TIBC (ug/ml) 340.1 ± 11.4 342.2 ± 10.2 313.8 ± 8.2 325.4 ± 6.7 0.608

Transferrin saturation (%) 31.4 ± 2.3 29.1± 1.8 30.9 ± 1.8 30.2 ± 1.2 0.236

Effect on Hemoglobin and Fe status

TRAINING

Total Group Trained Group

r=-0.248;

p=0.009

r=-0.242;

p=0.048

Improved VO2peak correlates with decreased RDW

Control Training

CONCLUSION

Red cell distribution width (RDW) is related to objective parameters of exercise intolerance in CHF patients. This relation is independent of hemoglobin or markers of disease severity

A 6-months exercise training program significantly reduces RDW values

The decrease in RDW values following exercise training is correlated with an increase

in aerobic capacity

The causal role of high RDW values in exercise intolerance deserves further

investigation