The role of sleep-disordered breathing is well recognized as a comorbid condition in heart and vascular patients. Assessment and therapy of sleep apnea is considered part of the “standard of care” for patients with heart failure and atrial fibrillation. In practice, the diagnosis and treatment of sleep-disordered breathing have several distinct obstacles. A limited awareness of the breadth of sleep-disordered breathing and stigma associated with a sleep disorder diagnosis may often limit referrals for evaluation, and result in poor adherence to therapy. Furthermore, the focus on obstructive type sleep apnea, which is certainly more common, may overshadow the diagnosis of central sleep apnea (CSA), which in certain populations has been demonstrated to be under-recognized and hence, undertreated.
Central Sleep Apnea
CSA is a chronic respiratory condition characterized by delayed activation or interruption of neural output from respiratory control centers, resulting in variable respiratory drive and reductions in airflow. Although the incidence of primary central sleep apnea is low, ranging from 3-17%, specific populations are disproportionally affected, including those patients with advanced heart failure, chronic opioid use, and neuromuscular conditions. The diagnosis of central sleep apnea is made through traditional in-laboratory polysomnography. Central apnea is defined by a cessation of airflow for 10 seconds or longer with no respiratory effort in contrast to obstructive sleep apnea, where there is cessation of airflow for 10 seconds or longer but with respiratory effort.6 (Figure 1)
In patients with heart failure, central sleep apnea is present in upwards of 40% of individuals. Transient episodes of apnea and resultant hypoxia activate sympathetic neural pathways, increase systemic inflammation and oxidative stress, and manifest clinically as increased mortality and morbidity for this population.1-3 Therapy has been focused largely on non-invasive devices such as Continuous Positive Airway Pressure (CPAP) machines and more recently, adaptive servo-ventilation (ASV), which has limited consistent adherence and resulted in undertreatment of many patients. Recent evaluations of non-invasive ventilatory strategies for this population have demonstrated an increased mortality for patients, with an ejection fraction of less than 45%.4 Although the exact mechanism by which CPAP and ASV may worsen the prognosis of heart failure patients is unclear, one possibility is the detrimental effect of positive airway pressure on venous return and the resultant decrease in preload and increase in afterload, as well as increased pulmonary arterial pressures.5
Phrenic Nerve Stimulation
The remedē® (Respicardia, Inc.) is a transvenous implanted phrenic nerve stimulator that consists of 1) a phrenic nerve pacing lead placed either in the left paraphrenic vein or in the right brachiocephalic vein if the left paraphrenic vein is not visualized or able to be accessed; 2) a sensing lead placed in an right posterior intercostal vein; and 3) a pulse generator.
Peri-operative management is similar to cardiac device implantation, with the exception that implants cannot be completed under general anesthesia; this is to ensure appropriate assessment of comfort during phrenic nerve stimulation. The leads and generator are delivered using established techniques for the delivery of cardiac resynchronization therapies. The pacing pulse is distinct from a typical biphasic pacing pulse of a cardiac device, and is in the form of low-amplitude, high-frequency bursts. Most commonly, a 20-40 Hz burst delivered with 2-10 mA is utilized with the intent to provide a stimulation of the phrenic nerve in such a way as to initiate a “physiologic” breath (Figure 2). Stimulation is graded for efficacy, comfort, and cadence. A well-implanted device delivers phrenic nerve stimulation without extra respiratory stimulation and triggers a negative pressure respiratory cycle, obviating the detrimental effects of positive pressure ventilation.
A 70-year-old male with a limited medical history notable for only hypertension was diagnosed with central sleep apnea and referred to us for consideration of an implanted phrenic nerve stimulator. Non-invasive therapies, including both CPAP and ASV, failed to significantly reduce his apnea-hypopnea index and central apnea index. Thus, we proceeded with device implant.
Serial venograms were unable to define the left paraphrenic vein. Right-sided lead placement is indicated in approximately 35% of implants, owing largely to an inability to cannulate/identify the left paraphrenic vein. Several factors need to be fully considered when placing a right-sided phrenic nerve stimulation lead, including longer maturation times, higher pacing thresholds, and lower impedances, which in turn result in higher system current drain. The right-sided lead has 6 electrodes with a helical shape designed to be positioned within the brachiocephalic trunk, and may often require a very proximal position to ensure stability. In addition to stimulation, the lead can also serve as a combination sensing lead. In our patient, a brachiocephalic lead positioned proximally resulted in excellent pacing thresholds, and phrenic nerve capture was rated physiologic without extra-respiratory stimulation. The patient’s device is demonstrated in Figure 3. In follow-up, he has demonstrated marked improvement in his clinical symptoms of fatigue and daytime drowsiness, and continues to undergo device therapy titration.
Interrogation of the system occurs through a dedicated programmer and allows the operator to evaluate pacing vectors and titrate output as well as visualize system longevity, much like any cardiac implantable device. In addition to pacing parameters, the total hours of daily therapy delivered are available along with unique programmable variables, such as the time at which to begin therapy and the sleep angle (Figure 4). The device is activated after 1 month post implant, and subsequent visits are used to titrate therapy based on clinical symptoms. An in-laboratory polysomnogram is often performed to objectively define efficacy. Annual evaluations are required following full titration of therapy.
Developing a central sleep apnea program can be challenging. Establishing a diagnosis requires a high degree of suspicion as well as continued assessment of patients, even after obstructive sleep patterns have been eliminated. A successful program relies on a close collaboration between heart failure, sleep medicine, and electrophysiology providers. Provider champions are required to facilitate education of the entire care team in both the pathophysiology of central sleep apnea and the merits of therapy. These efforts can be further supported by recognizing the barriers to adequate sleep-disordered breathing evaluation and developing streamlined workflows to guide patients through the process.
Our program has fostered these relationships through awareness campaigns specifically targeting heart failure providers, electrophysiology lab staff, and device staff, with an emphasis on standardized evaluation to assess for sleep-disordered breathing of any kind. We have recognized that the primary issues relate to understanding the sleep referral process and completing that evaluation in a timely manner. We also recognize the difficulty in maintaining clear communication paths and delegation of responsibilities between providers and their respective teams. To that end, we sought to engage the physician providers in heart failure, sleep medicine, and electrophysiology. We then focused on integrating our care pathway through a transparent discussion with advanced practice providers, clinical nurses, and scheduling and device staff to create a clear process to care for these patients (Figure 5).
Central sleep apnea is an under-recognized and difficult to diagnose condition with significant morbidity and mortality. Early detection and therapy can improve patient outcomes and potentially reduce healthcare resource utilization. Implanted nerve stimulators to manage sleep-disordered breathing offer significant improvement in sleep characteristics and ensure high levels of therapy adherence. A multidisciplinary team dedicated to building streamlined workflows is required to manage this group of patients. Successful program deployment is incredibly rewarding to providers, patients, and caregivers.
Disclosures: The authors have no conflicts of interest to report regarding the content herein.
- Peppard PE, Young T, Barnet JH, Palta M, Hagen EW, Hla KM. Increased prevalence of sleep-disordered breathing in adults. Am J Epidemiol. 2013;177:1006-1014.
- Paulino A, Damy T, Margarit L, et al. Prevalence of sleep-disordered breathing in a 316-patient French cohort of stable congestive heart failure. Arch Cardiovasc Dis. 2009;102:169-175.
- Khayat R, Jarjoura D, Porter K, et al. Sleep disordered breathing and post-discharge mortality in patients with acute heart failure. Eur Heart J. 2015;36:1463-1469.
- Cowie MR, Woehrle H, Wegscheider K, et al. Adaptive servo-ventilation for central sleep apnea in systolic heart failure. N Engl J Med. 2015;373:1095-1105.
- Liston R, Deegan PC, McCreery C, Costello R, Maurer WT, McNicholas WT. Haemodynamic effects of nasal continuous positive airway pressure in severe congestive heart failure. Eur Respir J. 1995;8:430-435.
- Muza RT. Central sleep apnea — a clinical review. J Thorac Dis. 2015;7(5):930-937.
- Becker K, Mosenifar Z. Central sleep apnea syndromes. Medscape. Published September 21, 2018. Available at https://emedicine.medscape.com/article/304967-overview. Accessed on November 15, 2019.