Exercise Oscillatory Ventilation in Systolic Heart Failure: An Indicator of Impaired Hemodynamic Response to Exercise

Background— Exercise oscillatory ventilation (EOV) is a noninvasive parameter that potently predicts outcomes in systolic heart failure (HF). However, mechanistic insights into EOV have been limited by the absence of studies relating EOV to invasive hemodynamic measurements and blood gases performed during exercise. Methods and Results— Fifty-six patients with systolic HF (mean±SEM age, 59±2 years; left ventricular ejection fraction, 30±1%) and 19 age-matched control subjects were studied with incremental cardiopulmonary exercise testing. Fick cardiac outputs, filling pressures, and arterial blood gases were measured at 1-minute intervals during exercise. We detected EOV in 45% of HF (HF+EOV) patients and in none of the control subjects. The HF+EOV group did not differ from the HF patients without EOV (HF−EOV) in age, sex, body mass index, left ventricular ejection fraction, or origin of HF. Univariate predictors of the presence of EOV in HF, among measurements performed during exercise, included higher right atrial pressure and pulmonary capillary wedge pressure and lower cardiac index (CI) but not PaCO2 or PaO2. Multivariate logistic regression identified that low exercise CI is the strongest predictor of EOV (odds ratio, 1.39 for each 1.0-L · min−1 · m−2 decrement in CI; 95% confidence interval, 1.14–1.70; P=0.001). Among HF patients with EOV, exercise CI was inversely related to EOV cycle length (R=−0.71) and amplitude (R=−0.60; both P<0.001). In 11 HF+EOV subjects treated with 12 weeks of sildenafil, EOV cycle length and amplitude decreased proportionately to increases in CI. Conclusion— Exercise oscillatory ventilation is closely related to reduced CI and elevated filling pressures during exercise and may be an important surrogate for exercise-induced hemodynamic impairment in HF patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00309790.

[1]  Andrea Giordano,et al.  Sleep and Exertional Periodic Breathing in Chronic Heart Failure: Prognostic Importance and Interdependence , 2005, Circulation.

[2]  R. Casaburi,et al.  Evidence that circulatory oscillations accompany ventilatory oscillations during exercise in patients with heart failure. , 1992, The American review of respiratory disease.

[3]  Andrea Giordano,et al.  Oscillatory ventilation during exercise in patients with chronic heart failure: clinical correlates and prognostic implications. , 2002, Chest.

[4]  A. Xie,et al.  Cycle length of periodic breathing in patients with and without heart failure. , 1996, American journal of respiratory and critical care medicine.

[5]  V. Somers,et al.  Differential Effects of Theophylline on Sympathetic Excitation, Hemodynamics, and Breathing in Congestive Heart Failure , 2004, Circulation.

[6]  Piergiuseppe Agostoni,et al.  Mechanisms of periodic breathing during exercise in patients with chronic heart failure. , 2008, Chest.

[7]  H R Figulla,et al.  Role of hyperventilation in the pathogenesis of central sleep apneas in patients with congestive heart failure. , 1994, American journal of respiratory and critical care medicine.

[8]  Adelaide M. Arruda-Olson,et al.  Exercise oscillatory ventilation: instability of breathing control associated with advanced heart failure. , 2008, Chest.

[9]  K. Dickstein,et al.  Six-Minute Walk Test and Cardiopulmonary Exercise Testing in Patients With Chronic Heart Failure: A Comparative Analysis on Clinical and Prognostic Insights , 2009, Circulation. Heart failure.

[10]  G. Lewis,et al.  Sildenafil Improves Exercise Hemodynamics and Oxygen Uptake in Patients With Systolic Heart Failure , 2006, Circulation.

[11]  P. Ponikowski,et al.  Peripheral Chemoreceptor Hypersensitivity: An Ominous Sign in Patients With Chronic Heart Failure , 2001, Circulation.

[12]  A Berghold,et al.  Pulmonary arterial pressure during rest and exercise in healthy subjects: a systematic review , 2009, European Respiratory Journal.

[13]  R. Christie,et al.  Periodic changes in respiratory depth, produced by changes in the lung , 1943, The Journal of physiology.

[14]  Mary Ann Peberdy,et al.  Prognostic value of timing and duration characteristics of exercise oscillatory ventilation in patients with heart failure. , 2008, The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation.

[15]  A. Guyton,et al.  Basic oscillating mechanism of Cheyne-Stokes breathing. , 1956, The American journal of physiology.

[16]  S. Andreas,et al.  Cheyne-Stokes respiration and prognosis in congestive heart failure. , 1996, The American journal of cardiology.

[17]  J. E. Hansen,et al.  Predicted values for clinical exercise testing. , 2015, The American review of respiratory disease.

[18]  A S Slutsky,et al.  Factors inducing periodic breathing in humans: a general model. , 1982, Journal of applied physiology: respiratory, environmental and exercise physiology.

[19]  P. Ponikowski,et al.  Clinical characteristics of chronic heart failure patients with an augmented peripheral chemoreflex. , 1997, European heart journal.

[20]  James E. Hansen,et al.  Oscillatory breathing and exercise gas exchange abnormalities prognosticate early mortality and morbidity in heart failure. , 2010, Journal of the American College of Cardiology.

[21]  R. Whalen,et al.  Cheyne-Stokes respiration. A review of clinical manifestations and critique of physiological mechanisms. , 1971, Archives of internal medicine.

[22]  T. D. Bradley,et al.  Relationship of carbon dioxide tension in arterial blood to pulmonary wedge pressure in heart failure , 2002, European Respiratory Journal.

[23]  R. Maestri,et al.  Association between hemodynamic impairment and Cheyne-Stokes respiration and periodic breathing in chronic stable congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. , 1999, The American journal of cardiology.

[24]  H. Hecht,et al.  The mechanism of Cheyne-Stokes respiration. , 1962, The Journal of clinical investigation.

[25]  S. Javaheri,et al.  Effect of theophylline on sleep-disordered breathing in heart failure. , 1996, The New England journal of medicine.

[26]  Cheyne-Stokes breathing. An instability in physiologic control. , 1974, The New England journal of medicine.

[27]  P. Ponikowski,et al.  Oscillatory breathing patterns during wakefulness in patients with chronic heart failure: clinical implications and role of augmented peripheral chemosensitivity. , 1999, Circulation.

[28]  J S Haldane,et al.  The causes of periodic or Cheyne‐Stokes breathing , 1909, The Journal of physiology.

[29]  S. Silver,et al.  Heart Failure , 1937, The New England journal of medicine.

[30]  M. Naughton,et al.  The effect of successful heart transplant treatment of heart failure on central sleep apnea. , 2003, Chest.

[31]  M. Kryger,et al.  The entrainment of low frequency breathing periodicity. , 1990, Chest.

[32]  T. Chua,et al.  Relation between chemosensitivity and the ventilatory response to exercise in chronic heart failure. , 1996, Journal of the American College of Cardiology.

[33]  Ross Arena,et al.  Exercise oscillatory ventilation may predict sudden cardiac death in heart failure patients. , 2007, Journal of the American College of Cardiology.

[34]  G. Lewis,et al.  Determinants of Ventilatory Efficiency in Heart Failure: The Role of Right Ventricular Performance and Pulmonary Vascular Tone , 2008, Circulation. Heart failure.

[35]  R. Gerszten,et al.  Sildenafil Improves Exercise Capacity and Quality of Life in Patients With Systolic Heart Failure and Secondary Pulmonary Hypertension , 2007, Circulation.

[36]  S. Javaheri A mechanism of central sleep apnea in patients with heart failure. , 1999, The New England journal of medicine.

[37]  C. Kremser,et al.  Oscillatory hyperventilation in severe congestive heart failure secondary to idiopathic dilated cardiomyopathy or to ischemic cardiomyopathy. , 1987, The American journal of cardiology.

[38]  M. Piepoli,et al.  Contribution of muscle afferents to the hemodynamic, autonomic, and ventilatory responses to exercise in patients with chronic heart failure: effects of physical training. , 1996, Circulation.

[39]  J. Ribeiro,et al.  Periodic breathing during exercise in severe heart failure. Reversal with milrinone or cardiac transplantation. , 1987, Chest.

[40]  A. Giordano,et al.  Response to Letter Regarding Article “Sleep and Exertional Periodic Breathing in Chronic Heart Failure: Prognostic Importance and Interdependence” , 2006 .

[41]  M. Naughton,et al.  Influence of pulmonary capillary wedge pressure on central apnea in heart failure. , 1999, Circulation.

[42]  K. J. Osterziel,et al.  Baroreflex sensitivity and cardiovascular mortality in patients with mild to moderate heart failure. , 1995, British heart journal.

[43]  H. Coleridge,et al.  Stimulation of Pulmonary Vagal Afferent C‐Fibers by Lung Edema in Dogs , 1986, Circulation research.

[44]  A. Giordano,et al.  Exercise haemodynamic variables rather than ventilatory efficiency indexes contribute to risk assessment in chronic heart failure patients treated with carvedilol. , 2009, European heart journal.

[45]  A. Mansur,et al.  Periodic breathing during incremental exercise predicts mortality in patients with chronic heart failure evaluated for cardiac transplantation. , 2003, Journal of the American College of Cardiology.