RED CELL DISTRIBUTION WIDTH

Transcription

1 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)

2 PROGNOSTICATORS IN CHF Single-term prognosticators: ER and hospital admissions Symptoms at rest Cachexia Hemoglobin, sodium, troponin, creatinine High natriuretic peptides LVEF High < 20% natriuretic peptides Symptomatic arrhythmia s Complex, multivariate models: Heart Failure Survival Score Seattle Heart Failure Model

3 RED CELL DISTRIBUTION WIDTH (RDW) Red blood cell distribution width, RDW, is a measure of the variation of red blood cell volume (MCV) RDW = Standard deviation of MCV Mean MCV X 100 Reference range %, available as part of the complete blood count Higher RDW values indicate greater variation in size (anisocytosis)

4 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

5 RDW IN CHONIC HEART FAILURE N=1087 Red cell distribution width: an inexpensive and powerful prognostic marker in heart failure. Al-Najjar Y, et al. Eur J Heart Fail 2009; 11:

6 CAUSES OF HIGH RDW VALUES Erythropoiesis Iron deficiency Anemia Iron of deficiency chronic disease B12 Anemia or of folate chronic deficiency disease B12 or folate deficiency Inadequate epo production Inadequate epo production Bone marrow suppression Inflammation Hemoglobinopathies Chronic Heart Failure Elevated RDW RBC Destruction Hemolysis Thrombotic conditions Blood Transfusion

7 EXERCISE INTOLERANCE IN CHF Stroke volume Chronotropic response VO 2 peak = CO x (CaO 2 -CvO 2 ) Blood supply Muscle mass Metabolic alteration in skeletal muscle Deficient oxygen transport in RBC?

8 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

9 PATIENTS Inclusion - LVEF 40% - Ischemic or dilated cardiomyopathy - Stable symptoms and medical therapy for 1 mth Exclusion - Recent ACS/revascularization - Exercise limited by angina or arrythmia - Anemia, epo substitution, recent blood transfusion - Severe renal failure - Chronic inflammatory of malignant disease TRAINING GROUP 71 patients referred for exercise training 118 CHF patients CONTROL GROUP 47 patients followed at Heart Failure Clinic

10 STUDY DESIGN Baseline Maximal cardiopulmonary exercise test (Treadmill) Blood sampling (RDW, Hb, Fe status, NT-proBNP) CONTROL GROUP Sedentary TRAINING GROUP Endurance training (+/- resistive exercises) Target HR 90% of HR at AT In hospital, 3x/week, 1h 6-months Follow-up Maximal cardiopulmonary exercise test (Treadmill) Blood sampling (RDW, Hb, Fe status, NT-proBNP)

11 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 ( ) EXERCISE CAPACITY VO 2 peak (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 ( ) RDW (%) 13.6 ( ) Leukocytes (x 10 9 /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

12 RELATION OF RDW WITH EXERCISE CAPACITY PEARSON R P-VALUE AGE (YEARS) BODY MASS INDEX (KG/M 2 ) HEART FAILURE CHARACTERISTICS NYHA class LVEF (%) EXERCISE CAPACITY VO 2 peak (ml.kg -1.min -2 ) < VO 2 peak at VT2 (ml.kg -1.min -2 ) Maximal Workload (Watt) < VE/VCO2slope Heart rate at maximum (bpm) < Oxygen pulse (mlvo 2.kg -1.min -2 /beat) Circulatory Power (mmhg. mlvo 2.kg -1.min -2 ) < LABORATORY PARAMETERS r = ; p< lognt-probnp < Hemoglobin (g/dl) < logmcv Serum Fe (µg/dl) TIBC (µg/dl) Transferrin saturation (%)

13 PREDICTOR OF EXERCISE CAPACITY VO 2 PEAK VE/VCO 2 SLOPE BETA P-VALUE BETA P-VALUE Age LogRDW NYHA class lognt-probnp Hemoglobin Creatinine Clearance Serum Fe Transferrin saturation Age LogRDW NYHA class lognt-probnp Hemoglobin Creatinine Clearance Serum Fe Transferrin saturation Multiple regression analysis based on significant parameters in the bivariate model RDW is a strong and independent predictor of VO 2 peak RDW is not a predictor of VE/VCO 2 slope

14 VO 2 peak (ml/kg/min) Maximal Workload (Watt) TRAINING Effect on exercise capacity P=0.005 P= Baseline Follow-up 90 Baseline Follow-up Control Training

15 RDW(%) TRAINING Effect on RDW values P= months exercise training significantly reduces RDW values Baseline Follow-up Control Training

16 TRAINING Effect on Hemoglobin and Fe status CONTROL GROUP TRAINING GROUP P-Value Baseline Follow-up Baseline Follow-up HEMATOLOGICAL PARAMETERS RDW (%) 13.6 ± ± ± ± MCV (%) 92.2 ± ± ± ± Hemoglobin (g/dl) 13.6 ± ± ± ± FE STATUS Serum Fe (ug/ml) ± ± ± ± TIBC (ug/ml) ± ± ± ± Transferrin saturation (%) 31.4 ± ± ± ± P-values based on ANOVA repeated measures of log transformed data

17 TRAINING Improved VO 2 peak correlates with decreased RDW Total Group r=-0.248; p=0.009 Trained Group r=-0.242; p=0.048 Control Training

18 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