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Circulation. 2007;115:2376-2378
doi: 10.1161/CIRCULATIONAHA.107.697037
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(Circulation. 2007;115:2376-2378.)
© 2007 American Heart Association, Inc.

Editorial

Is Ventilatory Classification Preferable to Peak Oxygen Consumption for Risk Stratification in Heart Failure?

Donna Mancini, MD; Thierry H. LeJemtel, MD

From the Division of Cardiology (D.M.), Columbia University, New York, NY, and the Division of Cardiology (T.H.L.), Tulane University Medical School, New Orleans, La.

Correspondence to Donna Mancini, MD, Columbia Presbyterian Medical Center, 622 West 168th St, New York, NY 10032. E-mail dmm31{at}columbia.edu


Key Words: Editorials • exercise • heart failure

Since the 1980s, cardiopulmonary exercise testing has been applied to patients with congestive heart failure (CHF) to objectively assess exercise capacity, to risk stratify patients, and to assess the response to therapeutic interventions.1 Subsequently, peak oxygen consumption (VO2) was reported to be a reliable prognostic index and to be particularly useful for the timing of cardiac transplantation in patients with advanced CHF caused by left ventricular systolic dysfunction.2 As peak VO2 is derived from the Fick equation and as most patients achieve comparable arterial-venous oxygen differences when they give maximal effort, peak VO2 has provided a noninvasive marker for peak cardiac output response and thus cardiac reserve. However, peak VO2 is affected not only by the cardiac output response to exercise as observed in healthy subjects but also by limited skeletal muscle mass and perfusion in patients with advanced CHF. Thus the usefulness of peak VO2 to predict prognosis in patients with CHF also results from an objective quantification of the derangements that the failing heart causes in the periphery. Not unexpectedly, CHF patients with severe skeletal muscle wasting and low peak VO2 have a worse prognosis than patients with little or no muscle wasting and moderately reduced peak VO2. Numerous studies before and after the advent of ß-blocker therapy have repeatedly demonstrated the effectiveness of peak VO2 to predict outcome in patients with heart failure.3–5 The prognostic power of ancillary data collected during cardiopulmonary testing, such as VO2 at anaerobic threshold, percentage predicted peak VO2 and ventilatory parameters have also been examined.6–10 Among the ventilatory variables that are derived from respiratory gas exchange analysis during exercise testing, ventilatory efficiency has received the most attention in CHF patients.8–10 Ventilatory efficiency is commonly assessed by the minute ventilation (VE) carbon dioxide production (VCO2) slope. Ventilatory efficiency depends on pulmonary hemodynamics and the resulting ventilation-perfusion mismatch, skeletal muscle ergoreceptor and peripheral chemoreceptor sensitivity, and heightened sympathetic activity.11–15 Ventilation-perfusion mismatch appears to be primarily responsible for the abnormal ventilatory efficiency in CHF patients,11,15 whereas chemo- and ergoreceptor sensitivity and heightened sympathetic activity may play a role in the late stages of CHF.12,13 Ventilatory efficiency, when expressed as a VE/VCO2 slope >34, has repeatedly been reported to be a more accurate prognostic index than peak VO2.8–10

Article p 2410

In the present issue of the Circulation, Arena et al16 review this ventilatory data and go beyond the previous studies with the development of strata to more rigorously predict outcome. Analysis of their data suggests that the ventilatory response may be a more sensitive and specific predictor of outcome than peak VO2. Arena et al16 also propose that the ventilatory classification guide therapy throughout the CHF spectrum and outline an algorithm for clinical management of heart failure on the basis of the ventilatory response. Ventilatory data has often been ignored by the cardiology community despite the fact that valuable prognostic information can be gleaned from these measurements. However, recommendations such as a VE/VCO2 slope of 36 to 44.9 be used as a criteria for chronic resynchronization therapy appear to be premature and speculative at this time. Whether these strata will prove to be clinically useful awaits further testing and validation.

Moreover, there are several concerns regarding the study itself and the measurement of ventilatory efficiency. Arena et al16 studied a heterogeneous patient population whose data were collected over a 13-year period and included patients with both left ventricular systolic and diastolic dysfunction. Therapy for heart failure has evolved over the past 13 years, and the prognostic value of peak VO2 in patients with CHF caused by left ventricular diastolic dysfunction remains uncertain.17,18 The study referenced by the authors to validate the use of peak VO2 in patients with diastolic dysfunction included only 46 patients with an ejection fraction >50%, of whom 83% were men, which is quite unusual for left ventricular diastolic dysfunction.18 Lastly only 9% of patients had undergone implantation of a cardiac defibrillator or cardiac resynchronization therapy, whereas 45% of deaths were sudden. Exercise testing with respiratory gas exchange analysis does not, to our knowledge, predict sudden death. Some concerns with the study have to do with the nature of the methodology. Although peak VO2 differs during treadmill and bicycle exercise, the authors did not standardize the mode of exercise and protocol in this study. Both VO2 and the ventilatory response will vary depending on the type of exercise, ie, treadmill versus bicycle as well as incremental versus ramp testing.19,20 The VE/VCO2 slope is linear only to the respiratory compensation period; the slope steeply increases thereafter (Figure, A). Some investigators have defined the VE/VCO2 slope as the relationship to anaerobic threshold. Arena et al16 measured the slope throughout exercise. Such an approach accentuates the slope. Also, it has been observed that many patients with heart failure have an oscillatory ventilatory pattern to exercise (Figure, B), which itself is a poor prognostic marker but whose presence is overlooked in this study. Other investigators have quantified ventilatory efficiency as the VE/VCO2 slope at anaerobic threshold or the greatest threshold measured during exercise.19,20 There is no consensus as to the most accurate approach. In contrast, peak VO2 is straightforward measurement if maximal exercise is achieved, with peak VO2 defined as the highest 20- to 30-second average achieved during exercise. However, unlike peak VO2, ventilatory efficiency is independent of maximum effort.


Figure 1183678
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  		A, Ventilation (VE; L/min) versus carbon dioxide production (VCO2; L/min) during exercise. B, Oscillatory ventilation failure (VE L/min) during exercise (min) in a patient with systolic heart failure.

To what degree does the VE/VCO2 slope reflect central cardiac function? VO2 is easily linked to cardiac output via the Fick equation. The connection of the ventilatory efficiency to cardiac function is much more indirect. Increased pulmonary ventilation-perfusion mismatch is a principal mechanism for an increased VE/VCO2 slope.11 As impaired alveolar hypoventilation is infrequent in heart failure patients, the mechanism for the increased ventilation-perfusion mismatch is presumed to be lack of stroke volume increase and impaired pulmonary vasodilatation during exercise. VE/VCO2 is also indirectly linked to chemoreceptor sensitivity, and thus in part reflects sympathetic nervous system activity.13,14

Pulmonary hemodynamics can be greatly and rapidly improved by therapeutic interventions as demonstrated in patients evaluated for cardiac transplantation. Whether improved pulmonary hemodynamics immediately translates into enhanced ventilatory efficiency and how reproducible is the measurement of ventilatory response in patients with CHF are questions that have not been thoroughly examined. In contrast, determination of peak VO2 has been consistently shown to be reproducible in numerous therapeutic trials as, contrary to pulmonary hemodynamics, skeletal muscle mass and perfusion do not acutely change in patients with CHF.

Clearly and simply, patients with reduced VO2 and high ventilatory response are sicker with a worse prognosis. Should the ventilatory response to exercise alone guide the management of patients with heart failure? No. The study by Arena et al16 indicates that ventilatory efficiency may be superior to determination of peak VO2 to predict life expectancy in CHF patients. However, the clinical usefulness of peak VO2 was established by a large body of data acquired over 2 decades. Such a body of data is not presently available to support the routine measurement of ventilatory efficiency in clinical settings.


*    Acknowledgments
 
Disclosures

None.


*    Footnotes
 
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.


*    References
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 *References
 

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Can Ventilatory Efficiency Be Used to Classify Patients with Heart Failure?
Journal Watch Cardiology, June 6, 2007; 2007(606): 3 - 3.
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