Shahrokh Javaheri, MD, sleep physician, TriHealth Sleep, is charting a new course in cardiovascular sleep medicine.
Shahrokh Javaheri, MD, a sleep physician at Bethesda North Hospital and professor emeritus of medicine at the University of Cincinnati College of Medicine in Cincinnati, Ohio, is a man on a mission. “Most cardiologists in this country are not aware of the prevalence of sleep apnea in heart failure,” Javaheri explains. “They are nowhere near where I think they should be.” Through his practice, his research, and his advocacy, he is committed to changing that and, in the process, expanding and advancing the field of cardiovascular sleep medicine.
“Dr Javaheri is not only a national leader but an international leader in clinical and academic research involving congestive heart failure and sleep apnea,” says Lee A. Surkin, MD, founder of the American Academy of Cardiovascular Sleep Medicine (AACSM) and a practicing physician who is board certified in both cardiology and sleep medicine. Surkin established the AACSM in 2012; Javaheri joined its advisory board in 2014. “His passion for the convergence between cardiology and sleep medicine completely resonates with the organization’s goals,” Surkin says.
Javaheri began his career in pulmonology. His research into breathing mechanisms in animals, then humans, led to an exploration of sleep disorders. In 1995, he undertook a study on the prevalence of sleep apnea in ambulatory patients in treatment for heart failure. The results sparked an interest that altered the trajectory of his career.
The study (Annals of Internal Medicine, 1 April 1995, Vol 122, No 7) found that almost 50% of stable, ambulatory heart failure patients had moderate to severe sleep apnea, and about 30% had central sleep apnea (CSA). Yet those patients who had sleep apnea did not report any symptoms that differed from those who did not. “For the first time in this country,” Javaheri says, “we showed that patients with heart failure who do not have any symptoms can be suffering from severe sleep apnea.” He notes similar results from a range of global studies.
Javaheri attributed the patients’ lack of awareness of their sleep apnea to the fact that sleep apnea as a disorder shares many of the symptoms of heart failure. “They wake up short of breath. Is this because they stop breathing or is the shortness of breath related to heart failure? They wake up tired. Is it because they have sleep apnea or heart failure? During the day they feel fatigue, is it heart failure, the beta blocker, or is it sleep apnea?”
This shared symptomatology gave Javaheri insights into poor adherence to CPAP devices often demonstrated by sleep apnea patients with heart failure. “Patients with OSA (obstructive sleep apnea) use the device overnight, they wake up the next morning, they don’t feel sleepy, they love the device,” Javaheri says. “But heart failure patients who use it are not very symptomatic regarding sleep apnea to begin with, and they don’t see an acute benefit from using CPAP.”
Intrigued by the findings, Javaheri shifted the focus of both his research and his practice entirely to sleep medicine. Over the years, he has gained international recognition for his studies in sleep; in particular, those focused on the intersection between cardiovascular disease and sleep disorders. “Javaheri’s research has helped define the association between heart failure and sleep apnea,” Surkin says, “and established the importance for the cardiologist as a partner in the treatment and management of patients who are affected.”
A Prolific Researcher
Javaheri’s avid curiosity sparked an ever-expanding range of inquiry. Over the past 20 years, opioids have become a mainstay of therapy for individuals with chronic pain, and are now among the country’s most prescribed medications. About 10 years ago, Javaheri noted an influx of opioid users whose spouses suspected them of having a sleep disorder. “And wow! When we studied them, almost every single one had sleep apnea,” he says. Javaheri was especially intrigued by the prevalence of CSA among these patients. “That’s rare in the general population, except for those with heart failure or stroke,” he says. “But that was the opioid part.”
He has published several studies on opioids and sleep apnea since then. “Brain centers for breathing and rhythm generation are replete with opioid receptors,” Javaheri says. “When opioids combine with the receptors, they depress breathing and can cause sleep apnea.” He has been struck by cases of premature death in opioid users who were otherwise healthy. He speculates, “A lot of times these patients are also taking benzodiazepines, or other drugs that impair arousal, along with the opioids. Perhaps a terminal apnea is the cause of death in these cases.” Sleep apnea among opioid users is an area of ongoing research for Javaheri.
Another project that has captured his interest is Respicardia’s remed? System, a therapeutic modality for CSA that employs phrenic nerve stimulation. “An electrophysiologist takes this pacemaker, which is tiny, and goes through a vein to where it crosses the phrenic nerve,” Javaheri says. “The phrenic nerve is then stimulated through the wall of the vein and the diaphragm contracts.” The device can be programmed based on a specific algorithm, and is activated when the patient goes to sleep and deactivated when the patient gets up. “During sleep, the diaphragm can be stimulated, say 12 or 15 times a minute,“ Javaheri explains, “so the CSA is prevented.”
The remed? System has completed a successful pilot study let by William T. Abraham, MD, from Ohio State University and is now undergoing a randomized clinical trial with Illinois cardiologist Maria Rosa Costanzo, MD, as principal investigator. Javaheri has been involved in the design of this multicenter study, and awaits the results with great interest, particularly in light of the recent discovery of the increased risk of cardiovascular mortality from use of adaptive servo-ventilation (ASV) for treatment of CSA in patients with heart failure and reduced ejection fraction.
ResMed announced in May of this year that its SERVE-HF Phase III trial did not meet its primary endpoint. ASV, formerly considered an effective treatment for heart failure patients with CSA, is now contraindicated in light of these findings. “We don’t want to start any new patients on ASV,” Javaheri says, “and we’re calling our patients with heart failure who are on ASV to come off the device.”
Javaheri has published on a range of alternative CSA therapies, including CPAP, ASV, oxygen, theophylline, and acetazolamide (Diamox), and continues to explore these and other areas of research. He notes that of these therapies, only CPAP has long-term studies currently available. “There are studies on oxygen that suggest after a few months left ventricular ejection fraction and quality of life may improve,” he says. “We do not yet have mortality data.” Javaheri is pointing his research efforts toward that goal.
“We need more randomized clinical trials for the treatment of sleep apnea,” he says, “in order to prove to cardiologists that if you treat the disorder, survival improves, hospitalization goes down, and quality of life gets better. And these studies are not there yet.” Among these, Javaheri hopes that the National Institutes of Health will approve a long-term study with hard endpoints on oxygen treatment for CSA in heart failure.
“He’s been a very prolific researcher,” Surkin says. “His most significant contribution is the strong link between heart failure and sleep apnea, and guiding different potential treatment modalities, which is obviously ongoing. He’s had direct impact on my clinical practice because of the research he’s done.”
Practice and Outreach
Javaheri’s own sleep medicine practice at Bethesda North Hospital in Cincinnati treats the full range of sleep disorders. In light of the reputation he has earned through his research, patients with comorbid heart disease make up a large segment of his practice. “About a third of my referrals are from cardiologists,” Javaheri says. “Not just heart failure patients, but patients with atrial fibrillation (AFib) as well.” Observational studies indicate that AFib patients with OSA lower their recurrence rate when their apnea is treated, he notes.
In addition to his busy practice and ongoing research activities, Javaheri serves as the section editor for “sleep and cardiovascular disease” in Principles and Practice of Sleep Medicine, by Meir H. Kryger, MD, et al. The sixth edition of this seminal text is currently being readied for publication.
Education has been and continues to be a vital aspect of Javaheri’s professional life. “Most cardiologists have not been educated about sleep apnea and heart failure,” he says, “because when they went to medical school, this wasn’t taught.” He notes that this omission is compounded by time constraints that are intrinsic to today’s busy cardiology practices. “The time they spend with a patient is so limited,” Javaheri says, “cardiologists don’t really have time to think about sleep apnea comorbid with heart failure.”
Javaheri is committed to raising awareness of sleep health among cardiologists, and believes integrated care is vital to effective treatment. “Otherwise, it’s dissociated medicine,” he says. “A patient hears one thing from the sleep doctor, another from the cardiologist. If they are all involved and talking about the problem at the same time, that’s a better approach.”
While Javaheri is serious about his message, his manner is jovial and engaging. When Surkin first met Javaheri and introduced himself as both a sleep specialist and cardiologist, Javaheri responded with an exuberant hug. At another encounter, when Surkin told Javaheri about his plans for the newly formed AACSM, Javaheri’s response was even more enthusiastic. “He said, ‘You know, I could just kiss you,’” Surkin recalls with a laugh. “This is the kind of big-hearted person he is. He has such stature, and yet his humility is infectious.”
That signature enthusiasm is evident as Javaheri urges fellow sleep specialists to reach out to their colleagues and help bridge the education gap. “Get together with cardiologists,” he says, “talk about the prevalence of sleep apnea, the potential cardiovascular complications, and the excess mortality.” He advocates disseminating existing research, and giving lectures on topical issues to keep cardiologists informed. “Education, education is the name of the game,” he says.
Surkin says, “Cardiovascular disease is endemic across the globe, sleep disorders are the same, and they are convergent. Sleep medicine should embrace cardiology, and cardiology should embrace sleep medicine, so they’re bidirectional.” He credits Javaheri as a pioneer in the convergence of these two fields, saying, “His clinical creativity will, I believe, continue to spawn clinical and academic research that will help further refine practice guidelines insofar as the cardiac patient with sleep apnea is concerned.”