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Central Sleep Apnea in Heart Failure
Adaptive Pressure Support Servo Ventilation Respiratory Stimulants
This is a new modality of ventilatory support that delivers baseline- Respiratory stimulants such as theophylline have been suggested
positive airway pressure along with machine-generated breaths for the treatment of CSA in heart failure. Proposed mechanisms
during central apneas. These devices are equipped with sensitive include increased ventilatory responsiveness below eupnea, resulting
sensors that can detect central apneas. They deliver several breaths, in increased proximity between eupneic PaCO
2
and the apnea
a tidal volume, and respriratory rate previously determined to match threshold. Other potential mechanisms include a stimulatory effect on
the patient’s minute ventilation during stable breathing. Therefore, the cardiac function, which is a concern. This has limited the use
mechanism of effect of this modality is by preventing the increase in of  theophylline in clinical practice. Only one double-blinded cross-
PaCO
2
during the apnea and subsequently preventing the over study has examined the short-term effects of theophylline on
hyperventilation that follows the apnea, in effect breaking CSA in 15 patients with stable heart failure. Compared with placebo,
the periodic breathing cycle. Several small trials have demonstrated theophylline decreased the central events and the severity of oxygen
significant benefit of adaptive pressure support servo ventilation desaturation, but without improvement in  left ventricular ejection
(ASV) in eliminating central events, increasing left ventricular ejection fraction.
101
Overall, the cardiac-stimulatory effects of theophylline limit
fraction, and improving quality of life.
12,90
These studies are promising its use in clinical practice until adequately powered studies can
but will require confirmation with an adequately powered randomized demonstrate its safety and efficacy.
controlled trial.
Acetazolamide induces metabolic acidosis and has a stimulatory effect on
Bilevel-positive airway pressure has also been used effectively in small ventilation, increasing the proximity between the eupneic PaCO
2
and the
trials to treat CSA. In this setting, bilevel-positive airway pressure was apnea threshold.
102
In a recent short-term (six-night) placebo-controlled,
administered with a back-up rate effectively as a form of ventilation with cross-over trial, Javaheri found a decrease in respiratory events and
predetermined minute ventilation that corresponds to the patient’s severity of nocturnal desaturation with acetazolamide compared with
minute ventilation during stable breathing.
91
ASV is a very promising placebo, with an improvement in subjective sleep quality.
103
There were no
treatment modality for CSA and is rapidly becoming widely used.
Oxygen Therapy
The distinction between central and
Given that the primary lesion in CSA responsible for the cardiovascular
consequences is intermittent hypoxia, it is logical to expect that
obstructive disorders in patients with heart
nocturnal oxygen may be an effective treatment in preventing
failure may be difficult due to the complex
sympathetic activation. Moreover, supplemental oxygen will improve the
oxygen store in patients with heart failure, subsequently dampening
physiological interaction between the
the ventilatory response to the increase in PaCO
2
during apnea.
mechanisms leading to either disorder.
Another possible mechanism of action would be a direct effect on the
peripheral chemoreceptors, decreasing their background chemosensitivity changes in objective measures of sleep quality and  left ventricular
(to PaCO
2
), and dampening the ventilatory overshoot following apnea- ejection fraction with acetazolamide. The potential for urinary potassium
induced hypercapnea.
92–94
Indeed, nocturnal oxygen was effective in wasting leading to hypokalemia and increased arrhythmia risk with
decreasing the number of central events in several small trials.
92,95
acetazolamide remains a serious concern. The role of acetazolamide in
Moreover, a beneficial effect was also noted on  left ventricular ejection the long-term treatment of CSA has yet to be determined.
fraction
95,96
and sympathetic tone.
97
Other longer-term trials have also
supported the beneficial role of nocturnal oxygen in the treatment of CSA Administration of small doses of exogenous CO
2
directly or indirectly by
in heart failure patients.
98,99
A major concern regarding nocturnal oxygen increased dead space is another intriguing treatment modality for CSA.
compared with positive airway pressure is its inability to eliminate the CO
2
is a respiratory stimulator that can stabilize the breathing pattern.
upper airway obstruction that co-exists with central apneas.
100
Again, long-term adequately powered trials are lacking and preclude
consideration of this modality. Furthermore, the practicalities of delivery
Similar to ASV, nocturnal oxygen is a promising therapy but has not yet and safety remain cardinal concerns with this treatment option.
104,105
been sufficiently studied in adequately-powered, randomized controlled
trials for the treatment of CSA in patients with heart failure. Subsequently, Hypnotics
oxygen therapy is not the standard of care for these patients. Hypnotics, such as benzodiazepines, have been studied in patients with
CSA. The mechanism of action was presumed to be a decrease in arousal-
Experimental (Phase I and II) Therapeutics for related ventilatory overshoot. Early pilot reports showed a decrease in the
Central Sleep Apnea number of nocturnal arousals, but no change in the severity of respiratory
These are modalities that target different components of the events or nocturnal oxygen desaturation was found.
106,107
pathophysiology of CSA. The effectiveness of these modalities was
demonstrated in small human trials, but safety and efficacy have not yet Conclusion
been evaluated in randomized controlled trials. These approaches, The distinction between central and obstructive disorders in patients
therefore, are not all part of current clinical practice. with heart failure may be difficult due to the complex physiological
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