Yonsei Med J.  2014 May;55(3):635-643. 10.3349/ymj.2014.55.3.635.

Red Cell Distribution Width as an Independent Predictor of Exercise Intolerance and Ventilatory Inefficiency in Patients with Chronic Heart Failure

• Hong SJ
• Youn JC
• Oh J
• Hong N
• Lee HS
• Park S
• Lee SH
• Choi D
• Kang SM

• KMID: 2068672
• DOI: http://doi.org/10.3349/ymj.2014.55.3.635

Abstract

PURPOSE
Peak oxygen uptake (peak VO2) and ventilatory inefficiency (VE/VCO2 slope) have proven to be strong prognostic markers in patients with chronic heart failure (CHF). Recently increased red cell distribution width (RDW) has emerged as an additional predictor of poor outcome in CHF. We sought to evaluate the relationship between RDW and cardiopulmonary exercise test (CPET) parameters in CHF patients and healthy controls.
MATERIALS AND METHODS
85 ambulatory CHF patients (68 men, 54+/-10 years) and 107 healthy controls, who underwent a symptom-limited CPET on a treadmill according to the modified Bruce ramp protocol, were enrolled. CHF patients and healthy controls were divided into RDW tertile groups and laboratory, echocardiographic, and CPET results were analyzed.
RESULTS
For patients with CHF, compared with patients in the lowest RDW tertile, those in the highest tertile had lower peak VO2 (22 mL/kg/min vs. 28 mL/kg/min, p<0.001) and higher VE/VCO2 slope (31 vs. 25, p=0.004). Multivariate regression analysis revealed RDW to be an independent predictor for peak VO2 (beta=-0.247, p=0.035) and VE/VCO2 slope (beta=0.366, p=0.004). The optimal cutoff value of RDW for predicting peak VO2 < or =20 mL/kg/min and VE/VCO2 slope > or =34 was 13.6% (sensitivity 53%, specificity 89%) and 13.4% (sensitivity 75%, specificity 82%), respectively. In contrast, for healthy controls, RDW was not related to both peak VO2 and VE/VCO2 slope.
CONCLUSION
Higher RDW is independently related to peak VO2 and VE/VCO2 slope only in patients with CHF. RDW assessment, an inexpensive and simple method, might help predict functional capacity and ventilatory efficiency in these patients.

Keyword

Cardiopulmonary exercise test; heart failure; red cell distribution width

MeSH Terms

Adult
Erythrocyte Indices/*physiology
Exercise Test
Female
Heart Failure/*physiopathology
Humans
Male
Middle Aged
Oxygen Consumption/physiology
Retrospective Studies

Figure

• 

  Fig. 1 Receiver operating characteristic curve of RDW for the determination of peak VO2 ≤20 mL/kg/min and VE/VCO2 slope ≥34. ROC curve indicated a good power of RDW in identifying patients with peak VO2 ≤20 mL/kg/min (A) and VE/VCO2 slope ≥34 (B) (AUC 0.717, 95% CI=0.556-0.878 for peak VO2 and AUC 0.858, 95% confidence interval=0.747-0.970). The optimal cutoff value of RDW for predicting peak VO2 ≤20 mL/kg/min and VE/VCO2 slope ≥34 was 13.6% (sensitivity 53%, specificity 89%) and 13.4% (sensitivity 75%, specificity 82%). RDW, red cell distribution width; ROC, receiver operating characteristic; CI, confidence interval; AUC, area under the curve.

Reference

1. Mancini DM, Eisen H, Kussmaul W, Mull R, Edmunds LH Jr, Wilson JR. Value of peak exercise oxygen consumption for optimal timing of cardiac transplantation in ambulatory patients with heart failure. Circulation. 1991; 83:778–786.

2. Chua TP, Ponikowski P, Harrington D, Anker SD, Webb-Peploe K, Clark AL, et al. Clinical correlates and prognostic significance of the ventilatory response to exercise in chronic heart failure. J Am Coll Cardiol. 1997; 29:1585–1590.

3. Kleber FX, Vietzke G, Wernecke KD, Bauer U, Opitz C, Wensel R, et al. Impairment of ventilatory efficiency in heart failure: prognostic impact. Circulation. 2000; 101:2803–2809.

4. Felker GM, Allen LA, Pocock SJ, Shaw LK, McMurray JJ, Pfeffer MA, et al. Red cell distribution width as a novel prognostic marker in heart failure: data from the CHARM Program and the Duke Databank. J Am Coll Cardiol. 2007; 50:40–47.

5. Al-Najjar Y, Goode KM, Zhang J, Cleland JG, Clark AL. Red cell distribution width: an inexpensive and powerful prognostic marker in heart failure. Eur J Heart Fail. 2009; 11:1155–1162.

6. Förhécz Z, Gombos T, Borgulya G, Pozsonyi Z, Prohászka Z, Jánoskuti L. Red cell distribution width in heart failure: prediction of clinical events and relationship with markers of ineffective erythropoiesis, inflammation, renal function, and nutritional state. Am Heart J. 2009; 158:659–666.

7. Oh J, Kang SM, Won H, Hong N, Kim SY, Park S, et al. Prognostic value of change in red cell distribution width 1 month after discharge in acute decompensated heart failure patients. Circ J. 2012; 76:109–116.

8. Hong N, Oh J, Kang SM, Kim SY, Won H, Youn JC, et al. Red blood cell distribution width predicts early mortality in patients with acute dyspnea. Clin Chim Acta. 2012; 413:992–997.

9. Allen LA, Felker GM, Mehra MR, Chiong JR, Dunlap SH, Ghali JK, et al. Validation and potential mechanisms of red cell distribution width as a prognostic marker in heart failure. J Card Fail. 2010; 16:230–238.

10. Chiari MM, Bagnoli R, De Luca PD, Monti M, Rampoldi E, Cunietti E. Influence of acute inflammation on iron and nutritional status indexes in older inpatients. J Am Geriatr Soc. 1995; 43:767–771.

11. Deswal A, Petersen NJ, Feldman AM, Young JB, White BG, Mann DL. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation. 2001; 103:2055–2059.

12. Uthamalingam S, Kandala J, Daley M, Patvardhan E, Capodilupo R, Moore SA, et al. Serum albumin and mortality in acutely decompensated heart failure. Am Heart J. 2010; 160:1149–1155.

13. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. Modification of Diet in Renal Disease Study Group. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Ann Intern Med. 1999; 130:461–470.

14. Quinones MA, Waggoner AD, Reduto LA, Nelson JG, Young JB, Winters WL Jr, et al. A new, simplified and accurate method for determining ejection fraction with two-dimensional echocardiography. Circulation. 1981; 64:744–753.

15. Folland ED, Parisi AF, Moynihan PF, Jones DR, Feldman CL, Tow DE. Assessment of left ventricular ejection fraction and volumes by real-time, two-dimensional echocardiography. A comparison of cineangiographic and radionuclide techniques. Circulation. 1979; 60:760–766.

16. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography's Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005; 18:1440–1463.

17. Appleton CP, Hatle LK, Popp RL. Relation of transmitral flow velocity patterns to left ventricular diastolic function: new insights from a combined hemodynamic and Doppler echocardiographic study. J Am Coll Cardiol. 1988; 12:426–440.

18. Thierer J, Acosta A, Vainstein N, Sultan M, Francesia A, Marino J, et al. Relation of left ventricular ejection fraction and functional capacity with metabolism and inflammation in chronic heart failure with reduced ejection fraction (from the MIMICA Study). Am J Cardiol. 2010; 105:977–983.

19. Gardin JM, Leifer ES, Fleg JL, Whellan D, Kokkinos P, Leblanc MH, et al. Relationship of Doppler-Echocardiographic left ventricular diastolic function to exercise performance in systolic heart failure: the HF-ACTION study. Am Heart J. 2009; 158:4 Suppl. S45–S52.

20. Weber KT, Janicki JS. Cardiopulmonary exercise testing for evaluation of chronic cardiac failure. Am J Cardiol. 1985; 55:22A–31A.

21. Karnad A, Poskitt TR. The automated complete blood cell count. Use of the red blood cell volume distribution width and mean platelet volume in evaluating anemia and thrombocytopenia. Arch Intern Med. 1985; 145:1270–1272.

22. Thompson WG, Meola T, Lipkin M Jr, Freedman ML. Red cell distribution width, mean corpuscular volume, and transferrin saturation in the diagnosis of iron deficiency. Arch Intern Med. 1988; 148:2128–2130.

23. Aslan D, Gümrük F, Gürgey A, Altay C. Importance of RDW value in differential diagnosis of hypochrome anemias. Am J Hematol. 2002; 69:31–33.

24. Anker SD, von Haehling S. Inflammatory mediators in chronic heart failure: an overview. Heart. 2004; 90:464–470.

25. Won H, Kang SM, Shin MJ, Oh J, Hong N, Park S, et al. Plasma adiponectin concentration and its association with metabolic syndrome in patients with heart failure. Yonsei Med J. 2012; 53:91–98.

26. van de Weert-van Leeuwen PB, Slieker MG, Hulzebos HJ, Kruitwagen CL, van der Ent CK, Arets HG. Chronic infection and inflammation affect exercise capacity in cystic fibrosis. Eur Respir J. 2012; 39:893–898.

27. Gläser S, Ittermann T, Koch B, Völzke H, Wallaschofski H, Nauck M, et al. Airflow limitation, lung volumes and systemic inflammation in a general population. Eur Respir J. 2012; 39:29–37.

28. Van Craenenbroeck EM, Pelle AJ, Beckers PJ, Possemiers NM, Ramakers C, Vrints CJ, et al. Red cell distribution width as a marker of impaired exercise tolerance in patients with chronic heart failure. Eur J Heart Fail. 2012; 14:54–60.

29. Oh J, Kang SM, Hong N, Choi JW, Lee SH, Park S, et al. Relation between red cell distribution width with echocardiographic parameters in patients with acute heart failure. J Card Fail. 2009; 15:517–522.

30. Guazzi M, Myers J, Peberdy MA, Bensimhon D, Chase P, Pinkstaff S, et al. Echocardiography with Tissue Doppler Imaging and cardiopulmonary exercise testing in patients with heart failure: a correlative and prognostic analysis. Int J Cardiol. 2010; 143:323–329.