BACKGROUND: Heart failure (HF) is characterized by heightened sensitivities of the CO2 chemoreflex and the ergoreflex which promote increased ventilatory drive manifested as increased minute ventilation per volume of expired CO2 (VE/VCO2). The aims of this study were to evaluate the effects of cardiac resynchronization therapy (CRT) on carbon dioxide (CO2) chemosensitivity and the arterial CO2 setpoint. METHODS AND RESULTS: Consecutive HF patients (n = 35) who underwent clinically indicated CRT were investigated by means of cardiopulmonary exercise testing and CO2 chemosensitivity evaluation with the use of a rebreathe method before and 4-6 months after CRT. Pre- and post-CRT measures were compared with the use of either paired t test or Wilcoxon test. Decreased peak VE/VCO2 (44 ± 10 vs 40 ± 8; P < .01), CO2 chemosensitivity (2.2 ± 1.1 vs 1.7 ± 0.8 L min(-1) mm Hg(-1); P = .04), and increased peak end-tidal CO2 (29 ± 5 vs 31 ± 5 mm Hg; P < .01) were also observed after CRT. Multivariate analysis adjusted for age and sex showed the decrease of peak VE/VCO2 from before to after CRT to be most strongly associated with the increase of peak end-tidal CO2 (β = -0.84; F = 21.5; P < .0001). CONCLUSIONS: Decrease of VE/VCO2 after CRT is associated with decreased CO2 chemosensitivity and increase of the arterial CO2 setpoint, which is consistent with decreased activation of both the CO2 chemoreflex and the ergoreflex.

Department of Biomedical Statistics and Informatics Mayo Clinic Rochester Minnesota

Division of Cardiovascular Diseases Mayo Clinic Rochester Minnesota

International Clinical Research Center and Department of Anesthesiology and Intensive Care St Anne's University Hospital Brno Czech Republic

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Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med. 2002 Jun 13;346(24):1845–53. PubMed

Auricchio A, Stellbrink C, Sack S, Block M, Vogt Jurge, Bakker P, et al. long-term clinical effect of hemodynamically optimized cardiac resynchronization therapy in patients with heart failure and ventricular conduction delay. J Am Coll Cardiol. 2002;39(12):2026–33. erven. PubMed

De Marco T, Wolfel E, Feldman AM, Lowes B, Higginbotham MB, Ghali JK, et al. Impact of cardiac resynchronization therapy on exercise performance, functional capacity, and quality of life in systolic heart failure with QRS prolongation: COMPANION trial sub-study. J Card Fail. 2008 Feb;14(1):9–18. PubMed

Cleland JGF, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, et al. The effect of cardiac resynchronization on morbidity and mortality in heart failure. N Engl J Med. 2005 Apr 14;352(15):1539–49. PubMed

Abraham WT, Hayes DL. Cardiac Resynchronization Therapy for Heart Failure. Circulation. 2003;108(21):2596–2603. Listopad. PubMed

Fanfulla F, Mortara A, Maestri R, Pinna GD, Bruschi C, Cobelli F, et al. The Development of Hyperventilation in Patients With Chronic Heart Failure and Cheyne-Stokes Respiration A Possible Role of Chronic Hypoxia. Chest. 1998 Oct 1;114(4):1083–90. PubMed

Woods PR, Olson TP, Frantz RP, Johnson BD. Causes of breathing inefficiency during exercise in heart failure. J Card Fail. 2010 Oct;16(10):835–42. PubMed PMC

Arena R, Myers J, Aslam SS, Varughese EB, Peberdy MA. Peak VO2 and VE/VCO2 slope in patients with heart failure: a prognostic comparison. Am Heart J. 2004 Feb;147(2):354–60. PubMed

Johnson RL. Gas Exchange Efficiency in Congestive Heart Failure. Circulation. 2000;101(24):2774–2776. erven. PubMed

Lloyd TC., Jr Effect of increased left atrial pressure on breathing frequency in anesthetized dog. J Appl Physiol. 1990 Dec;69(6):1973–80. PubMed

Olson TP, Frantz RP, Snyder EM, O'Malley KA, Beck KC, Johnson BD. Effects of acute changes in pulmonary wedge pressure on periodic breathing at rest in heart failure patients. Am Heart J. 2007 Jan;153(1):104.e1–7. PubMed PMC

Olson TP, Joyner MJ, Johnson BD. Influence of locomotor muscle metaboreceptor stimulation on the ventilatory response to exercise in heart failure. Circ Heart Fail. 2010 Mar;3(2):212–9. PubMed PMC

Jaussaud J, Blanc P, Bordachar P, Roudaut R, Douard H. Response to Cardiac Resynchronization Therapy: The Muscular Metabolic Pathway. Cardiol Res Pract. 2010 Dec 20;2011 PubMed PMC

Laveneziana P, O'Donnell DE, Ofir D, Agostoni P, Padeletti L, Ricciardi G, et al. Effect of biventricular pacing on ventilatory and perceptual responses to exercise in patients with stable chronic heart failure. Journal of Applied Physiology. 2009 May;106(5):1574–1583. PubMed

Piepoli MF, Villani GQ, Corrà U, Aschieri D, Rusticali G. Time Course of Effects of Cardiac Resynchronization Therapy in Chronic Heart Failure: Benefits in Patients with Preserved Exercise Capacity. Pacing and Clinical Electrophysiology. 2008 Jun 1;31(6):701–8. PubMed

Read DJ. A clinical method for assessing the ventilatory response to carbon dioxide. Australas Ann Med. 1967 Feb;16(1):20–32. PubMed

Miller MR, Crapo R, Hankinson J, Brusasco V, Burgos F, Casaburi R, et al. General Considerations for Lung Function Testing. Eur Respir J. 2005 Jul 1;26(1):153–61. PubMed

Ponikowski P, Francis DP, Piepoli MF, Davies LC, Chua TP, Davos CH, et al. Enhanced ventilatory response to exercise in patients with chronic heart failure and preserved exercise tolerance: marker of abnormal cardiorespiratory reflex control and predictor of poor prognosis. Circulation. 2001 Feb 20;103(7):967–72. PubMed

Giannoni A, Emdin M, Bramanti F, Iudice G, Francis DP, Barsotti A, et al. Combined Increased Chemosensitivity to Hypoxia and Hypercapnia as a Prognosticator in Heart Failure. J Am Coll Cardiol. 2009 May 26;53(21):1975–80. PubMed

Piepoli M, Clark AL, Volterrani M, Adamopoulos S, Sleight P, Coats AJ. Contribution of muscle afferents to the hemodynamic, autonomic, and ventilatory responses to exercise in patients with chronic heart failure: effects of physical training. Circulation. 1996 Mar 1;93(5):940–52. PubMed

Franciosa JA, Leddy CL, Wilen M, Schwartz DE. Relation between hemodynamic and ventilatory responses in determining exercise capacity in severe congestive heart failure. The American Journal of Cardiology. 1984;53(1):127–34. Leden. PubMed

Agostoni P, Pellegrino R, Conca C, Rodarte JR, Brusasco V. Exercise hyperpnea in chronic heart failure: relationships to lung stiffness and expiratory flow limitation. J Appl Physiol. 2002 Apr;92(4):1409–16. PubMed

Boggs DF, Frappell PB, Kilgore DL., Jr Ventilatory, cardiovascular and metabolic responses to hypoxia and hypercapnia in the armadillo. Respir Physiol. 1998 Aug;113(2):101–9. PubMed

Gabor JY, Newman DA, Barnard-Roberts V, Korley V, Mangat I, Dorian P, et al. Improvement in Cheyne-Stokes respiration following cardiac resynchronisation therapy. European Respiratory Journal. 2005;26(1):95–100. ervenec. PubMed

Tanabe Y, Suzuki M, Takahashi M, Oshima M, Yamazaki Y, Yamaguchi T, et al. Acute Effect of Percutaneous Transvenous Mitral Commissurotomy on Ventilatory and Hemodynamic Responses to Exercise. Pathophysiological Basis for Early Symptomatic Improvement. Circulation. 1993 Oct 1;88(4):1770–8. PubMed

McSwain SD, Hamel DS, Smith PB, Gentile MA, Srinivasan S, Meliones JN, et al. End-tidal and arterial carbon dioxide measurements correlate across all levels of physiologic dead space. Respir Care. 2010 Mar;55(3):288–93. PubMed PMC

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