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(Circulation. 2001;103:967.)
© 2001 American Heart Association, Inc.
Clinical Investigation and Reports |
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
From the Cardiac Medicine Department, Imperial College, National Heart & Lung Institute, London, UK (P.P., D.P.F., M.F.P., C.D., T.P.C., C.H.D., V.F., P.A.P.-W., A.J.S.C., S.D.A.); the Cardiology Department, Clinical Military Hospital, Wroclaw, Poland (P.P., W.B.); and the Franz-Volhard-Klinik (Charité, Campus Berlin-Buch) at Max-Delbrück-Centrum, Berlin, Germany (S.D.A.).
Correspondence to Dr Piotr Ponikowski, MD, PhD, Clinical Cardiology, National Heart & Lung Institute, Imperial College School of Medicine, Dovehouse Street, London SW3 6LY. E-mail piotrponikowski{at}hotmail.com
Background—In
patients with chronic heart failure (CHF) and preserved exercise
tolerance, the value of cardiopulmonary exercise testing for risk
stratification is not known. Elevated slope of ventilatory response to
exercise
(
E/CO2)
predicts poor prognosis in advanced CHF. Derangement of cardiopulmonary
reflexes may trigger exercise hyperpnea. We assessed the relationship
between cardiopulmonary reflexes and
E/CO2
and investigated the prognostic value of
E/CO2
in CHF patients with preserved exercise
tolerance.
Methods and
Results—Among 344 consecutive CHF patients, we
identified 123 with preserved exercise capacity, defined as a peak
oxygen consumption (peak
O2)
18
mL · kg-1 · min-1
(age 56 years; left ventricular ejection fraction 28%; peak
O2
23.5
mL · kg-1 · min-1).
Hypoxic and hypercapnic chemosensitivity (n=38), heart rate variability
(n=34), baroreflex sensitivity (n=20), and ergoreflex activity (n=20)
were also assessed. We identified 40 patients (33%) with high
E/CO2
(ie, >34.0). During follow-up (49±22 months, >3 years in all
survivors), 34 patients died (3-year survival 81%). High
E/CO2
(hazard ratio 4.3, P<0.0001)
but not peak
O2
(P=0.7) predicted mortality. In
patients with high
E/CO2,
3-year survival was 57%, compared with 93% in patients with normal
E/CO2
(P<0.0001). Patients with high
E/CO2
demonstrated impaired reflex control, as evidenced by augmented
peripheral (P=0.01) and central
(P=0.0006) chemosensitivity,
depressed low-frequency component of heart rate variability
(P<0.0001) and baroreflex
sensitivity (P=0.03), and
overactive ergoreceptors
(P=0.003) compared with
patients with normal
E/CO2.
Conclusions—In CHF
patients with preserved exercise capacity, enhanced ventilatory
response to exercise is a simple marker of a widespread derangement of
cardiovascular reflex control; it predicts poor prognosis, which peak
O2
does not.
Key Words: heart failure • ventilation • respiration • prognosis
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
R. Wolk, B. D. Johnson, and V. K. Somers Leptin and the ventilatory response to exercise in heart failure J. Am. Coll. Cardiol., November 5, 2003; 42(9): 1644 - 1649. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
 |
|
 A S Androne, K Hryniewicz, R Goldsmith, A Arwady, and S D Katz Acetylcholinesterase inhibition with pyridostigmine improves heart rate recovery after maximal exercise in patients with chronic heart failure Heart, August 1, 2003; 89(8): 854 - 858. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. C. Scott, D. P. Francis, A. J.S. Coats, and M. F. Piepoli Reproducibility of the measurement of the muscle ergoreflex activity in chronic heart failure Eur J Heart Fail, August 1, 2003; 5(4): 453 - 461. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
T Tomita, H Takaki, Y Hara, F Sakamaki, T Satoh, S Takagi, Y Yasumura, N Aihara, Y Goto, and K Sunagawa Attenuation of hypercapnic carbon dioxide chemosensitivity after postinfarction exercise training: possible contribution to the improvement in exercise hyperventilation Heart, April 1, 2003; 89(4): 404 - 410. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
P. Agostoni, M. Guazzi, M. Bussotti, S. De Vita, and P. Palermo Carvedilol Reduces the Inappropriate Increase of Ventilation During Exercise in Heart Failure Patients Chest, December 1, 2002; 122(6): 2062 - 2067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|