Periodic Limb Movements of Sleep Tied to Ventricular Tachycardia

Batya Swift Yasgur, MA, LSW

August 27, 2019

Periodic limb movements during sleep (PLMS) with arousals are associated with subsequent nonsustained ventricular tachycardia (NSVT), new research suggests.

Investigators assessed temporal associations between PLMS and NSVT in older men in their 70s and 80s with PLMS and apnea-hypopnea and found that PLMS without arousal was not significantly associated with NSVT.

However, PLMS with arousal (PLMA) was associated with a threefold increased risk for NSVT shortly after the episode.

"There are multiple lines of evidence that people with coronary artery disease, which is the most common cause of ventricular tachycardia, and atrial fibrillation/flutter should get sleep studies to evaluate for sleep-disordered breathing," lead author Anna M. May, MD, physician at the VA Northeast Ohio Health System, Cleveland, told Medscape Medical News.

However, "links between periodic limb movements and cardiovascular disease are an active area of research, and a causal link is not yet established," she cautioned. "Interventional trials to provide support for a causal link are needed before considering a change to current medical practice," she said.

The results were published online July 17 in Sleep.

"Granular" Analysis

"Accumulating data support an association of sleep disruption and adverse cardiovascular outcomes," the investigators write.

May noted that her group had previously studied associations between respiratory events and arrhythmia and had evaluated new-onset atrial fibrillation (AF) and flutter in those with higher levels of periodic limb movements.

"The main analysis did not find an association between PLMS with or without arousal and AF. However, in prespecified analyses stratified by age, in the oldest of the old, we found an association between PLMS, both with and without arousal, with incident AF," she said.

For the current analysis, the investigators wanted to assess the temporal relationship between PLMS and arrhythmia "in a more granular way," May said.

To assess temporal associations between PLMS and NSVT during sleep, the researchers examined 49 older men with NSVT (n = 141 episodes) who were participating in the Osteoporotic Fractures in Men Sleep Study (n = 2911).

NSVT was defined as three or more consecutive heartbeats originating below the atrioventricular node with a rate of 100 or more beats per minute and lasting less than 30 seconds. To be included, NSVT episodes had to occur at least 5 minutes apart.

A bidirectional time-stratified case-crossover study design was used. Each individual served as their own control, with a hazard period directly preceding NSVT and control periods sampled at regular intervals from both before and after the event.

"This approach is well-suited to determine relationships between outcomes with a discrete onset (NSVT) and exposures with intermittent timing and immediate and transient effects on risk (PLMs)," the investigators explain.

"Because both hazard and control periods are taken from the same person, each participant serves as his own control for variables which remain constant throughout the night (e.g. age, sex, comorbidities, medications)," they write.

The sleep period, defined as sleep onset to last epoch of sleep, was divided into approximately equal 30-minute segments.

At the sleep visit, participants provided information regarding demographics, medical history, smoking status, alcohol consumption, and medications used in the past month.

Sympathetic Activation

Key characteristics of the 49 male participants with NSVT included the following: ethnicity, 98% white; average age, 79.5 years; mean body mass index, 26.5 kg/m2; PLMI, 32.1; PLMA index, 2.2; and apnea-hypopnea index, 17.1

Compared with those in the overall study who did not have NSVT, participants with NSVT were significantly older (mean age, 79.5 years vs 76.3 years). In addition, for patients with NSVT, CAD was more prevalent (47.9% vs 25.9%), heart failure was more prevalent (14.3% vs. 5.8%), and weekly alcohol consumption was lower.

Among those with NSVT, 30 reported having had one NSVT event, nine had had two events, four participants had had three to five events, and the other six had had five or more events.

PLMS with or without associated arousal occurred in 34 of the 141 hazard periods (24.1%) and in 90 of the 423 control periods (21.3%).

Of 124 PLMS events, 36 (29.0%) were PLMA, which occurred in 9.9% of hazard periods and 5.2% of control periods.

PLMS without arousal was not significantly associated with NSVT (odds ratio [OR], 0.80, 95% confidence interval [CI], 0.41 – 1.59).

However, PLMA was associated with NSVT in both unadjusted and adjusted analyses (OR, 2.50; 95% CI, 1.11 – 5.65; and OR, 2.31; 95% CI, 1.02 – 5.25, respectively).

Similarly, arousals associated with PLMS were associated with NSVT in unadjusted and adjusted analyses (ORs, 2.84 and 2.61, respectively).

Respiratory events, which included apneas and hypopneas, and minimum oxygen saturation were not associated with NSVT events in either unadjusted or adjusted models.

"PLMS are associated with sympathetic activation, and PLMA more so," May said.

"The parasympathetic system is supposed to predominate during sleep; sympathetic nervous system activation during sleep may increase risk of arrhythmia, especially in people with subclinical cardiac disease," she added.

Broadening the Spectrum

Calling the study "interesting," Virend K. Somers, MD, PhD, professor of cardiovascular medicine, Mayo Clinic, Rochester, Minnesota, told Medscape Medical News that it "adds to the body of evidence implicating PLMs and arousals in CVD."

In addition, the research "specifically broadens the spectrum of possible arrhythmic consequences of PLMs and arousals to include not just AF but now also NSVT, at least in older men," said Somers, who was not involved with the study.

There are several take-home messages from the findings, he noted.

"Patients with NSVT occurring during sleep — noted, for example, on Holter monitoring — should potentially be evaluated for PLMs," Somers said.

"However, whether treatment of PLMs attenuates NSVT or improves any measurable clinically significant cardiovascular outcomes remains to be determined," he added.

The researchers note that further investigation addressing the impact of PLMS on arrhythmia risk should be conducted in other populations, including women and younger people.

"Clarification of the relationship between PLMA and cardiac structural changes via echocardiography may further characterize the pathophysiology of PLMA-induced arrhythmogenesis," they write.

Additional research is also needed to "clarify whether targeted PLMA-directed interventions mitigate cardiac arrhythmogenesis," the investigators conclude.

The Osteoporotic Fractures in Men study is supported by the National Institutes of Health (NIH). The following institutes provided additional support: the National Institute on Aging, the National Institute of Arthritis and Musculoskeletal and Skin Diseases, the National Center for Advancing Translational Sciences, the NIH Roadmap for Medical Research, and the National Heart, Lung, and Blood Institute. May and Somers report no relevant financial relationships. Disclosures for the other study authors are listed in the original article.

Sleep. Published online July 17, 2019. Abstract

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