Letter by Guazzi Regarding Article “Sleep and Exertional Periodic Breathing in Chronic Heart Failure: Prognostic Importance and Interdependence”
To the Editor:
I read with interest the article by Corrà and associates1 that appeared in a recent Circulation issue. In 133 chronic heart failure patients, the authors elegantly demonstrated that those (n=22) who exhibit both central sleep apnea (CSA; apnea/hypopnea index ≥30) and exercise oscillatory ventilation (EOV) have a very unfavorable prognosis. The negative survival expectation is, however, primarily driven by CSA, a recognized prognostic marker, rather than by EOV, a disorder found to be prognostic irrespective of CSA coexistence.2 Accordingly, patients with isolated EOV had clinical data and survival rates similar to those without oscillatory kinetics. This observation suggests that EOV may not hold clinical importance and weakens the argument for interdependent pathways in the genesis of EOV and CSA. As an overall comment, any reasoning on this category of patients is likely flawed by the small number of subjects investigated (n=6).
This is the first study in which EOV was tested against exercise V̇e/V̇co2 slope, a powerful prognosticator in chronic heart failure patients with intermediate performance.3 Statistical comparison is not reported, and at the multivariate Cox analysis, CSA, peak V̇o2, and β-blocker therapy emerged as prognostic, whereas V̇e/V̇co2 slope, in contrast with established evidence, did not. The information may be misleading in some instances and can be explained by technical difficulties related to the calculation of V̇e/V̇co2 slope in the setting of oscillatory gas kinetics, including the definition of its linear relationship from the beginning of exercise to the isocapnic compensatory point. The concern is strengthened by the discrepancies among the few studies available. In 25 similar patients, Leite et al2 reported an average V̇e/V̇co2 slope of 48.7, which is similar to the 46.6 reported in another study involving 10 patients.4 Both studies appear far from the V̇e/V̇co2 slopes of 30 (EOV alone) and 40 (CSA and EOV) reported by Corrà et al.
Thus, in the presence of EOV, a correct V̇e/V̇co2 slope measure and interpretation should require further mathematical elaboration.
These are questions that Corrà et al may help to interpret to further expand our knowledge on the complex and fascinating relationships among exercise ventilation inefficiency, sleep disorders, and life expectancy across different chronic heart failure populations.
Corrà U, Pistono M, Mezzani A, Braghiroli A, Giordano A, Lanfranchi P, Bosimini E, Gnemmi M, Giannuzzi P. Sleep and exertional periodic breathing in chronic heart failure: prognostic importance and interdependence. Circulation. 2006; 113: 44–50.
Leite JJ, Mansur AJ, de Freitas HFG, Chizola PR, Bocchi EA, Terra-Filho M, Neder JA, Lorenzi-Filho G. Periodic breathing during incremental exercise predicts mortality in patients with chronic heart failure evaluated for cardiac transplantation. J Am Coll Cardiol. 2003; 41: 2175–2181.
Guazzi M, Reina G, Tumminello G, Guazzi MD. Exercise ventilation inefficiency and cardiovascular mortality in heart failure: the critical independent prognostic value of the arterial CO2 partial pressure. Eur Heart J. 2005; 26: 472–480.
Agostoni P, Cattadori G, Bianchi M, Wasserman K. Exercise-induced pulmonary edema in heart failure. Circulation. 2003; 108: 2666–2671.