Low Heart-Rate Turbulence Predicts Cardiac Death in Low-Risk Older Adults

February 22, 2011

February 22, 2011 (St Louis, Missouri) — Low heart-rate turbulence, a measure that quantifies the autonomically mediated response to ventricular premature beats, is significantly associated with an increased risk of cardiac death in older adults otherwise considered low risk for cardiovascular events, according to the results of a new study published in the February 2011 issue of the Journal of Cardiovascular Electrophysiology [1].

Abnormal heart-rate turbulence was also associated with a higher risk of cardiac mortality in older adults considered intermediate and high risk, report investigators, although the association wasn't as strong. In contrast, elevated C-reactive protein (CRP) levels were associated with an increased risk of cardiac mortality in low-risk adults, but not to same extent as low-risk older adults who have abnormal heart-rate turbulence.

Although the number of people identified with abnormal heart-rate turbulence and considered low risk for cardiovascular events based on traditional risk-factor scoring is small, lead investigator Dr Phyllis K Stein (Washington University School of Medicine, St Louis, MO) told heartwire that Holter-based monitoring shows that the people aren't healthy and are in fact at an eightfold greater risk of cardiac death compared with low-risk older adults with normal heart-rate turbulence. Still, these early results pose a bit of a conundrum for clinicians.

"The worried well are exposing themselves to colossal amounts of radiation at this point to find out if they're really okay," said Stein in reference to imaging scans using computed tomography (CT). "Except for itchy electrodes, this test is no big deal. Certainly, it would appeal to the worried well. But in our current climate of trying to reign in excessive healthcare costs, is that a good thing? And what would you do if a patient had bad heart-rate turbulence? That's still not known."

Heart-Rate Turbulence Defined

To heartwire , Stein explained that premature ventricular beats are relatively common. As a result of the premature beat, cardiac output for that beat is low, as the heart did not have enough time to fill. With the heart rate regulated on a beat-to-beat basis to match the needs of the body, the heart rate increases. However, as Stein explained, the early ventricular beat also empties the heart early, and as the heart fills passively during diastole, this extra filling time leads to more blood pumped on the next beat to the body than should be pumped. As a result, the heart slows down.

In healthy hearts, said Stein, heart-rate increases and decreases are part of the normal compensation process for this under- and overfilling caused by the ventricular premature beat. Abnormal heart-rate turbulence occurs when the autonomic nervous does not allow the heart to compensate in this manner.

In the present study, Stein, along with Dr Joshua Barzilay (Emory University School of Medicine, Atlanta, GA), analyzed Holter-monitor recordings from 1272 individuals 65 years of age and older. The participants were stratified into three risk categories based on an assessment of their cardiovascular health. Participants in the "clinical" arm had a history of cardiovascular disease, such as MI, angina, PCI or coronary artery bypass graft (CABG) surgery, while those in the subclinical arm had abnormal assessments on carotid ultrasound, ECG, or ankle-brachial index (ABI) testing. The healthy participants had no history of cardiovascular disease.

In all three risk categories, abnormal heart-rate turbulence, as measured by turbulence onset and turbulence slope, was associated with an increased risk of cardiac death, although the association was strongest in healthy people. During long-term follow-up, the "healthy" people with abnormal heart turbulence had worse survival than those who had subclinical disease, report investigators. Of the 357 older adults classified as healthy, 21 had abnormal heart-rate turbulence.

Cardiac Mortality in Patients With Abnormal Heart-Rate Turbulence


Odds ratio (95% CI)

Healthy, low risk

7.9 (2.8–22.5)

Subclinical, intermediate risk

2.7 (1.2–5.9)

Clinical, high risk

2.2 (1.5–4.0)

Investigators also looked at the role of CRP as a predictor of cardiac mortality. They used a cutoff >3.0 mg/L to define elevated CRP levels, higher than was used in other trials, such as the >2.0 mg/L cutoff in the JUPITER trial, but found that elevations in CRP were associated with an increased risk of cardiac death only in low-risk participants. For those considered healthy, an increase in CRP was associated with a 2.5-fold increase in risk compared with healthy individuals with normal CRP levels.

Speaking to the clinical usefulness of these results, Stein said she envisions a test assessing heart-rate turbulence to help make decisions to more aggressively manage patients who might be considered to have "less-than-overwhelming" risk factors, much the way CRP has been proposed to be used. For example, a patient with slightly elevated cholesterol levels but low HDL-cholesterol levels, who also has abnormal heart-rate turbulence, might be more aggressively treated with lifestyle interventions and pharmacotherapy, said Stein.

The authors report they have no conflicts of interest.


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