Title Future of Sleep-Disordered Breathing Therapy Using a Mechanistic Approach Permalink

Sleep disordered breathing (SDB) is highly prevalent among patients with cardiovascular disease (CVD), and the relationship between SDB and CVD may be bidirectional. However, SDB remains underdiagnosed and undertreated. One of the major barriers identified by cardiologists is lack of satisfaction with SDB therapy. This situation could be the result of the discordance between treatment and the pathophysiological characteristics of SDB. This condition is caused by multiple pathophysiological mechanisms, which could be classified into upper airway anatomic compromise, pharyngeal dilator muscle dysfunction, and ventilatory control instability. However, the effective treatment of SDB remains limited, and positive airway pressure therapy is still the mainstay of the treatment. Therefore, we review the pathophysiological characteristics of SDB in this article, and we propose to provide individualized treatment of SDB based on the underlying mechanism. This approach requires further study but could potentially improve adherence and success of therapy. Received for publication November 14, 2014. Accepted February 8, 2015. Corresponding author: Dr Atul Malhotra, 9300 Campus Point Drive, No. 7381, La Jolla, California 92037-7381, USA. Tel. : þ1-858-657-6159; fax: þ1-858-657-7107. E-mail: amalhotra@ucsd.edu See page 885 for disclosure information. http://dx.doi. org/10.1016/j.cjca. 2015.02. 007 0828-282X/ 2015 Canadian Cardiovascular Society. Published by Elsevier Inc. A R ESUM E Les troubles respiratoires du sommeil (TRS) sont très r epandus chez les patients souffrant de maladies cardiovasculaires (MCV). Par cons equent, les TRS et les MCV montreraient un lien bidirectionnel. Cependant, les TRS demeurent sous-diagnostiqu es et sous-trait es. L’un des obstacles majeurs d etermin es par les cardiologues est l’insatisfaction concernant le traitement des TRS. Cette situation pourrait r esulter de la discordance entre le traitement et les caract eristiques physiopathologiques des TRS. Cette affection est caus ee par de multiples m ecanismes physiopathologiques, qui pourraient être classifi es comme suit : le compromis anatomique des voies a eriennes sup erieures, la dysfonction des muscles dilatateurs du pharynx et l’instabilit e de la maîtrise ventilatoire. Cependant, le traitement efficace des TRS etant limit e, leur traitement repose encore sur la th erapie par pression positive expiratoire continue. Par cons equent, dans cet article, nous passons en revue les caract eristiques physiopathologiques des TRS et nous proposons d’offrir un traitement individualis e des TRS reposant sur le m ecanisme sous-jacent. Cette approche n ecessite des etudes plus approfondies, mais pourrait favoriser l’observance et le succès du traitement. Sleep disordered breathing (SDB) with daytime sleepiness was previously estimated to affect 4% of men and 2% of women in North America. However, recent data suggest that SDB is considerably more common at present, affecting approximately 13% of men and 6% of women. This increase is likely the result of increasing rates of obesity, an aging population, and improvements in technology to detect subtle respiratory events. The increasing prevalence is alarming, given the existing knowledge about the role of SDB as a cardiometabolic risk factor. SDB contributes to the development and progression of cardiovascular and cerebrovascular diseases, including heart failure, atrial fibrillation, myocardial infarction, stroke, and mortality. These associations have been explained by multiple proposed mechanisms, although intermittent hypoxemia in SDB has emerged as the most prominent. Specifically, recurrent hypoxemia followed by reoxygenation resembles repetitive ischemia and reperfusion injury, which leads to sympathetic nervous system overactivity, systemic inflammation, metabolic dysfunction, and subsequent endothelial dysfunction. During an obstructive apnea event, strenuous inspiratory effort against an occluded upper airway leads to sympathetic overactivity, and the resultant negative intrathoracic pressure increases left ventricular afterload and right ventricular preload, which chronically increases myocardial oxygen demand and causes ventricular remodelling. Arousal at the end of an apneic episode also increases sympathetic activity and suppresses vagal tone, triggering the surge in blood pressure and heart rate. Emerging evidence suggests a reciprocal relationship in which cardiovascular disease (CVD) also leads to SDB (Fig. 1). Fluid redistributes from the extremities to the neck region