Rebuttal to Javaheri, Brown and Khayat

摘要

Drs. Javaheri, Brown, and Khayat highlight the controversy about the pathophysiological concepts associated with Hunter-Cheyne-Stokes breathing (HCSB) in the setting of heart failure (HF) with reduced ejection fraction.1 Debate over such matters is healthy and should lead to further research in what is a fascinating overlap between cardiology, pulmonary, sleep, and autonomic function.Simply put, it is my view that HF-related HCSB (1) is simply a reflection of HF severity, (2) may recede if cardiac function improves, and (3) has physiological advantages when the failing heart is leading to dyspnea.2,3 If identified, HCSB should not be ignored! Indeed, a search for reversible causes should be undertaken. Note that HF is not always reversible: it can be malignant. In this context, a plethora of therapies (including continuous positive airway pressure [CPAP]) may assist cardiac function in some patients and attenuate HCSB. Whereas other treatments directed solely at controlling the ventilatory pattern of HCSB, without regard for cardiac function, may disguise rather than treat the cause of HCSB and in my opinion require carefully performed clinical trials before becoming mainstream treatments.Four physiological effects were raised for debate by Javaheri et al.1The first issue they highlighted was that hyperventilation-related increase in end-expiratory lung volume and associated rise in end-expiratory pressure may be detrimental. I concur that changes in intrathoracic pressure (ITP) and lung volume may have differing effects on right and left ventricular function dependent on filling pressure (preload) and upstream resistance (afterload). In cases of acute heart failure (AHF), the Forrester plot is a helpful clinical guide, based on filling pressure and cardiac index, to guide treatments.4 Patients presenting with AHF can be either wet or dry (ie, high or low filling pressures). Patients with HCSB are generally wet5 and usually increase their stroke volume acutely with CPAP.6 Such patients with HCSB also have a restrictive ventilatory defect that predisposes to greater oscillations in ventilatory drive and reduced oxygen stores (half the body's oxygen stores are kept in a gaseous mixture within the lungs). Thereby reversal of this restriction with large tidal volumes during the hyperventilation phase with HCSB (or more continuously with CPAP) should increase oxygen stores and reduce HCSB. Episodic rises in SpO2 during sleep in patients with HCSB is caused by the increase in tidal volume and increase in end-expiratory lung volume. Lung inflation with CPAP is best illustrated when applied in AHF with a virtually immediate rise in SpO2 and a slowing of respiratory rate.In contrast to prolonged elevations of ITP ( 10 seconds as with the Valsalva maneuver) which reduce preload and stroke volume in healthy normal individuals, short swings in ITP related to periodic hyperventilation during sleep ( 5 seconds) increase stroke volume as measured by echocardiography7 and digital photoplethysmography8 techniques. Criley et al. showed that intermittent swings in ITP caused by voluntary coughing could maintain cardiac output in asystolic humans,9 supporting the concept that the chest wall can in some circumstances augment stroke volume (ie, similar to a second heart). Moreover, the elevations in end-expiratory ITP proposed with HCSB ( 5 mmHg3) are similar to that seen with intrinsic positive end-expiratory pressure, which might prevent alveolar collapse.The second issue is related to the relationship between disturbed HF, autonomic dysregulation, and HCSB. It is correct that we observed muscle sympathetic nerve activity (MSNA) inversely correlated with tidal volume in a group of patients with HF during wakefulness.10 This was a correlation and does not confirm causation. The beauty of MSNA activity is that it accurately follows short-term changes in sympathetic activity (SNA). If one carefully examines Figure 1 of our paper10 it can be seen that the large tidal breaths were associated with a more cyclic pattern of MSNA compared with rapid shallow breaths. As with the study by van de Borne,11 MSNA during HCSB was decreased during the periods of hyperventilation compared with the central apneic period. As with a yawn, sympathetic activity is attenuated by inspiration.Based on our group's observation that HF severity explained most of the variance of elevated SNA (measured by tritiated norepinephrine spillover), the contribution from HCSB was minimal.12 Limitations of this study were that the tritiated norepinephrine spillover was measured while awake and HCSB occurred during sleep. However, HCSB can occur during wakefulness (eg, at rest or during exercise) when there is an absence of hypoxemia and arousals. Moreover, we have observed that markers of SNA do not increase across the night in patients with HCSB,13 which would support the concept that HCSB is not adding to SNA. My hypothesis is that HF leads to increased SNA,