CLINICAL RESEARCH: HEART FAILURE
Periodic breathing during incremental exercise predicts mortality in patients with chronic heart failure evaluated for cardiac transplantation
Joao J. Leite, MD, PhD*,*,
Alfredo J. Mansur, MD, PhD*,
Humberto F. G. de Freitas, MD*,
Paulo R. Chizola, MD*,
Edimar A. Bocchi, MD, PhD*,
Mario Terra-Filho, MD, PhD*,
J. Alberto Neder, MD, PhD and
Geraldo Lorenzi-Filho, MD, PhD*
* Division of Respiratory Disease–Heart Institute (InCor), University of São Paulo Medical School, São Paulo, Brazil
Centre for Exercise Science and Medicine (CESAME), Institute of Biomedical & Life Sciences (IBLS), University of Glasgow, Glasgow, United Kingdom
Manuscript received August 19, 2002;
revised manuscript received November 11, 2002,
accepted November 27, 2002.
* Reprint requests and correspondence: Dr. Joao J. Leite, Instituto do Coração, Rua Dr. Eneas Carvalho de Aguiar 44, CEP: 05403-000, São Paulo-SP, Brazil.
pnejoao{at}incor.usp.br
OBJECTIVES: We hypothesized that exercise-related periodic breathing (EPB) would be associated with poor prognosis in advanced chronic heart failure (CHF).
BACKGROUND: Patients with CHF might present instability of the ventilatory control system characterized by cyclic waxing and waning of tidal volume (periodic breathing [PB]). This condition is associated with several deleterious circulatory and neuro-endocrine responses; in fact, PB in awake and asleep patients has been identified as an independent risk factor for cardiac death. During exercise, however, the prognostic value of PB is still unknown in CHF patients awaiting heart transplantation.
METHODS: Eighty-four patients with established CHF (65 male, 19 female) were submitted to clinical evaluation, echocardiogram, ventricular scintigraphy, determination of resting serum norepinephrine levels, and an incremental cardiopulmonary exercise test on cycle ergometer. Patients were followed for up to 49.7 months (median = 15.3), and 26 patients (30.9%) died during this period.
RESULTS: Twenty-five of 84 patients presented EPB (29.7%). The following variables were related to mortality according to Kaplan-Meier and univariate Cox regression analysis: EPB (p = 0.004), New York Heart Association class (p = 0.04), serum norepinephrine (p = 0.06), peak oxygen uptake (ml·min–1·kg–1 and % predicted; p = 0.085 and p = 0.10, respectively), slope of the ratio of change in minute ventilation to change in carbon dioxide output during exercise (p = 0.10), and scintigraphic left ventricular ejection fraction (p = 0.10). Cox multivariate analysis identified EPB as the only independent variable for cardiac death prediction (p = 0.007). Therefore, EPB alone was associated with a 2.97-fold increase in risk of death in this population (95% confidence interval = 1.34 to 6.54).
CONCLUSIONS: Exercise-related periodic breathing independently predicts cardiac mortality in CHF patients considered for heart transplantation.
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Abbreviations and Acronyms
| | CHF | = chronic heart failure | | CSR | = Cheyne-Stokes respiration | | EPB | = exercise-related periodic breathing | | LVEF | = left ventricular ejection fraction | | NYHA | = New York Heart Association | | PaCO2 | = arterial carbon dioxide pressure | | PB | = periodic breathing | | PETCO2 | = end-tidal partial pressure for carbon dioxide |  CO2 | = carbon dioxide output | | Vds | = dead space volume | | E | = minute ventilation | | O2 | = oxygen uptake | | VT | = tidal volume |
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