Washington, DC - Abnormal heart-rate turbulence (HRT) as measured on Holter monitoring predicts mortality, including sudden-death mortality, in patients with heart failure, independently of ventricular systolic function, according to a large, prospective cohort-based study [1].

The authors of the Muerte Subita en Insuficiencia Cardiaca (MUSIC) study, led by Dr Iwona Cygankiewicz (Catalan Institute of Cardiovascular Sciences, Barcelona, Spain and University of Rochester, NY) say theirs is the largest-yet evaluation of HRT as a risk stratifier in heart failure and probably the first to show in that setting that conventionally defined HRT parameters can predict sudden cardiac death (SCD) along with all-cause mortality and death from progressive heart failure.

More studied as a risk marker after acute MI, abnormal HRT reflects impairment of the autonomic response to blood-pressure changes caused by ventricular premature beats, has been observed in different forms of cardiomyopathy, and is "an excellent marker of neurohormonal activity in congestive heart-failure patients," according to the group's report in the August 2008 issue of Heart Rhythm.

Hopes are that when combined with other risk stratifiers, such as (for example) T-wave alternans, it will help single out patients most likely to benefit from primary-prevention ICDs from the broader population currently eligible for them based on clinical and LVEF criteria.

It also might help identify heart-failure patients with preserved ejection fractions who are at increased SCD risk. "Even patients without a very impaired ejection fraction might have a severely impaired autonomic nervous system, and it will be reflected in these ECG measurements such as heart-rate turbulence," Cygankiewicz told heartwire.

About 44% of the 607 patients in MUSIC had LV ejection fractions >35; the entire cohort had predominantly NYHA class 2 heart failure and evaluable HRT data. About half had ischemic and half nonischemic heart-failure etiologies.

Per convention, HRT abnormalities were defined in terms of the two HRT components, turbulence onset (TO), representing the start of heart-rate acceleration, and turbulence slope (TS), referring to subsequent heart-rate deceleration.

In the current study, 43% of patients were classified as HRT0 (neither TO nor TS abnormal) and 36% and 21% of patients, respectively, were classified as HRT1 or HRT2 (one or both of the components abnormal).

In multivariate analysis, abnormal TS and HRT2 were both significantly predictive of total mortality (p<0.001 for both), SCD (p=0.033 and 0.021, respectively), and heart-failure mortality (p<0.001 for both).

TO and HRT1 were less consistent as predictors, with HRT1 reaching significance for heart-failure death only (p=0.042).

The group highlighted two findings in particular. The HRT hazard ratios were highest for prediction of death from progressive heart failure. Also, in a separate analysis, TS emerged as predictive of mortality in patients with QRS complexes wider than 120 ms, but not in the remainder (hazard ratios 3.55 [p<0.001] and 1.37 [p=0.224], respectively).

The latter observation was novel, according to Cygankiewicz. "We don't know what the exact physiologic link is between wide QRS and the predictive value. Probably those patients are just sicker, so that's why the turbulence slope works better in patients with wide QRS," she said.

"The study by Cygankiewicz et al is an important step toward identifying heart-failure patients at high risk for SCD or heart-failure progression. However, risk stratification probably cannot be entrusted to a single parameter," according to an accompanying editorial from Drs Leonardo Calo and Ermenegildo de Ruvo (Policlinico Casilino, Rome, Italy) [2].

"In our opinion," they write, "combining measures of autonomic tone (HRT, baroreflex sensitivity, heart-rate variability, etc) with measures of electrical substrate (T-wave alternans, signal-averaged ECG, etc) may help to identify patients at high risk for SCD and improve the selection of ICD candidates in order to optimize the cost-effectiveness of therapies."