The overarching goals of the newest ACC/AHA guidelines for heart failure (HF) center on available data of the risks and benefits of cardiovascular therapies and procedures, their impact on health related quality of life (HRQOL, QOL), patient outcomes, and health economic profiles. Per the guidelines, the “writing committees are charged with regularly reviewing and evaluating all available evidence to develop balanced, patient-centric recommendations for clinical practice.”¹ As such, the ACC and AHA have resolved to use guideline-directed medical therapy (GDMT) for this and future guidelines in how best to manage patients from a comprehensively effective perspective.

In this light, it was clear and prudent that the societies updated this recent HF guideline with incorporation of comprehensive approach to managing ancillary cumbersome comorbidities. Since the 19th century, sleep-disordered breathing (e.g. Cheyne-Stokes, Biot) and sleep apnea (SA) has been associated with advanced disease and nearing the end of life. However, elucidation of its pathology in HF became clear in the 1990’s into the past decades.² A venerable undertaking, a SA-incorporated guideline sets the stage to significantly improve on all quality indicators of HF management, owing to the influence of SA on other cardiovascular risk, systemic and pulmonary hypertension, dyslipidemia, and sudden death.^3,4 The new guidelines have incorporated specifics in management of SA in HF stemming from new insights on outcomes, treatment and prognosis. Appropriately, apnea is first mentioned with discussion on health related quality of life (QOL). Moreover, SA is recognized as a risk factor for hospitalization and likely explains a significant proportion of potentially reversible HF readmission. 

It has been suggested that HF and SA coexist in at least 60% of patients in an evidence-based cohort study.⁶ A review article published in the Journal of American College of Cardiology by Kasai et al. discusses the cardiovascular effects of obstructive sleep apnea (OSA) on the cardiovascular system.⁴ Increased negative intrathoracic pressure caused by chronic OSA increases left ventricular (LV) transmural pressure, resulting in increased afterload. OSA-induced hypoxic pulmonary vasoconstriction increases RV afterload, consequently causing RV distension and leftward septal displacement during diastole, thus impairing LV filling. The combination of increased afterload and reduced left ventricular preload reduces both stroke volume and cardiac output. This hemodynamic stress is particularly detrimental in for HF patients with already compromised myocardial mechanics as evidenced by the delayed recovery after an apneic episode.  

It is known that independent of heart failure, SA is associated with increased sympathetic activity as measured by an increase in plasma and urinary catecholamines, heart rate variability and muscle sympathetic nerve activity.⁸  This may be due to intermittent hypoxia and CO₂ retention caused by apneic episodes that stimulate central and peripheral chemoreceptors, thus augmenting the sympathetic nervous system. Reduced stroke volume and blood pressure during these events also unload carotid sinus baroreceptors and reflexively augment the sympathetic nervous system. The resultant sympathetic surge is particularly exaggerated in patients with heart failure as they are likely to have prolonged reduction in stroke volume as described above. Parallels in mechanism call to question correlation and causation versus association in HF. Nonetheless, OSA and HF overlay in pathophysiology and exert synergistic comorbidity.

The evidence draws support for, and caution in, using conventional medicines. As an example, despite the proven hypertensive benefit of ACE inhibition in management of SA, a subset of patients with associated cough may have worsened airway inflammation and SA severity.⁹ SA may also be a cause of fatigue in patients on beta blockers rather than the medicine dose, thus to avoid suboptimal GDMT. Care is advised in the use of diuretics which, aside from usual concerns of hypotension, may have an exaggerated effect in the preload-dependent SA patient and ultimately exaggerate the elevated catecholamine levels.

The guidelines highlight the treatment and potential reversibility of systolic dysfunction with continuous positive airway pressure (CPAP) therapy.¹⁰ Specifically, Continuous positive airway pressure (CPAP) can be beneficial to increase LVEF and improve functional status in patients with HF and sleep apnea. Hence, there is a dual effect of anatomical and functional benefit. As underscored in the guidelines, “ CPAP for obstructive sleep apnea was effective in decreasing the apnea hypopnea index, improving nocturnal oxygenation, increasing LVEF, lowering norepinephrine levels, and increasing the distance walked in six minutes; these benefits were sustained for up to two years. Smaller studies suggest that CPAP can improve cardiac function, sympathetic activity, and HRQOL in patients with HF and obstructive sleep apnea.”

A summary of the trials incorporated into the writing of the guidelines is presented in table form: http://jaccjacc.cardiosource.com/DataSupp/ACCF/2013_HFGL_Evidence_Tables.pdf for additional data on the treatment of sleep disorder. That the overall level and class of the recommendation is 2A emphasizes both the great progress achieved thus far and the need for directed, large studies in SA in more HF populations. As our care moves from risk stratification to benefit-proven outcomes, we must define the implications of SA-related morbidity and mortality via long term studies to be included in subsequent guidelines. While forthcoming, it is already clear that GDMT is indispensable in the new standard of care HF care. Moreover, care of the HF patient would be remiss to undervalue the credible evaluation and treatment of apnea.

We don’t know whether HF treatment to guideline will completely reverse SA or vice versa. It is unclear whether intensifying therapy through widespread identification and management programs will significantly impact re-hospitalization rates, morbidity or mortality scores, health care costs or delivery. While the guideline addresses obesity and exercise in HF, two important interventions that coincidentally alter SA severity, we cannot measure individual contribution versus synergistic effect in disease process. In addition to the elusive pathophysiologic sequelae, the potential effect of our therapy will likely vary by genomic, socioeconomic or racial strata. However, it is clear is that SA and HF overlaps such that recognition of the reciprocal pathology is crucial in their co-management and substandard attention would undoubtedly yield disparate, unacceptable outcomes. An argument can be made that treatment of each entity is mutually beneficial, yet neither can achieve optimal outcomes in the face of the other. Hopefully, we can quickly develop our understanding of SA, the distinction between central or obstructive, and influence of apnea on other entities (e.g. dysrhythmia, dyslipidemia and atherosclerosis) with the ultimate aims of incorporation into other evidence-based guidelines.

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References

1. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA Guideline for the Management of Heart Failure. J Am Coll Cardiol 2013;62:e147-239.
2. Lieber C, Mohsenin V. Cheyne-Stokes respiration in congestive heart failure. Yale J Biol Med 1992;65:39-50.
3. Wang H, Parker JD, Newton GE, et al. Influence of obstructive sleep apnea on mortality in patients with heart failure. J Am Coll Cardiol 2007; 49:1625-1631.
4. Kasai T, Bradley TD. Obstructive sleep apnea and heart failure: pathophysiologic and therapeutic implications. J Am Coll Cardiol 2011;57:119-27.
5. Khayat R, Abraham W, Patt B, Brinkman V, Wannemacher J, Porter K, Jarjoura D. Central sleep apnea is a predictor of cardiac readmission in hospitalized patients with systolic heart failure. J Card Fail 2012;18:534-40.
6. MacDonald M, Fang J, Pittman SD, et al. The current prevalence of sleep disordered breathing in congestive heart failure patients treated with beta-blockers. J Clin Sleep Med 2008;4:38-42.
7. Yumino D, Takatoshi K, Kimmerly D, Amirthalingam V, Floras J, Bradley TD. Differing Effects of Obstructive and Central Sleep Apneas on Stroke Volume in Patients with Heart Failure. Am J Respir Crit Care Med 2013; 187:433-438.
8. Javaheri S. Basics of Sleep Apnea and Heart Failure. http://apnea.cardiosource.org. February 19, 2013. Accessed January 7, 2014. http://apnea.cardiosource.org/Basics/2013/02/Basics-of-Sleep-Apnea-and-Heart-Failure.aspx.
9. Cicolin A, Mangiardi L, Mutani R, Bucca C. Angiotensin-converting enzyme inhibitors and obstructive sleep apnea. Mayo Clin Proc 2006;81:53-5.
10. Bradley TD, Logan AG, Kimoff RJ, et al. Continuous positive airway pressure for central sleep apnea and heart failure. N Engl J Med 2005;353:2025-33.

Keywords: Disease Management, Economics, Medical, Heart Failure, Quality of Life, Risk, Risk Assessment

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