BACKGROUND

The possibility of using HRV as a prognostic indicator in patients with cardiac failure, as reported for postmyocardial infarction patients,1 stems directly from the compelling evidence that has been accumulated over the past few years about the importance of the derangement of autonomic nervous control of the cardiovascular system as one of the mechanisms involved in the occurrence of cardiac—particularly sudden—death. Experimental and clinical studies have reported that both increased sympathetic and decreased parasympathetic tone may interact with the electrophysiological mechanisms underlying arrhythmogenesis. Nevertheless, as other factors such as abnormal ventricular wall stretch, electrolyte disorders, and proarrhythmic effects of drugs may play an important role in the genesis of life threatening ventricular arrhythmias and sudden death in cardiac failure patients, the role of autonomic nervous system dysfunction in the pathogenesis of fatal events is less clear than in patients with coronary artery disease. However, the fact that reduced HRV in postmyocardial infarction patients appears to predict not only sudden death but also total cardiac mortality,1 suggests that, at clinical level, sympathetic hyperactivity in addition to increased electrical instability may combine and have multiple deleterious effects on all abnormal substrates leading to cardiac events.

CLINICAL DATA

The most relevant studies that have addressed the role of HRV in risk stratification of patients with cardiac failure will be considered. They differ profoundly in terms of number of patients enrolled, selection of parameters, and statistical methods. As a result, it is currently not known whether measures of HRV are useful and independent predictors of outcome in patients with cardiac failure.

In 1992, Binder et al reported for the first time that reduced HRV was associated with a 20-fold increased risk of death.8 In the following years this observation was confirmed by other reports.9-13 However, the populations included in these studies were often very small with a limited number of events, and correct multivariate regression analysis was not always applied.

Among the HRV parameters selected to stratify cardiac failure patients, an altered non-parametric measure such as the Poincare plot was also proposed.10 ,12 The main limitation of this index is the subjective criteria of the investigator in the classification of the plots as normal or abnormal, particularly in the absence of any quantification of the data.

Recently, two other studies14 ,15 that focused on the value of HRV in the prediction of cardiac death, found that a decreased 24 hour standard deviation of normal RR intervals (SDNN) (nearly below 100 ms) was related to an increased risk of cardiac death. However, only in the study by Ponikowski et al was this index independent of other clinical factors such as peak oxygen consumption, NYHA class, left ventricular ejection fraction, and occurrence of ventricular tachycardia during Holter recording.15 The main limitation of these studies, besides the small number of events, is the choice of the cut off value defining normal and reduced HRV. These two studies14 ,15 used a cut off of 100 ms, which included about 40% of the enrolled population and was at variance with the indication of the task force on HRV,1 which suggested lower values for patients with a depressed HRV.

A value of SDNN < 50 ms was reported to distinguish a subgroup of severe congestive heart failure patients with a shorter event free survival time, even when conventional measures such as ejection fraction, cardiothoracic ratio, and number of extrasystoles did not differ between patients with and without cardiac events.16Unfortunately the size of the study was small.

As to the possible predictive value of the LF component, it is worth recalling that Ponikowski and colleagues15 reported an increased risk of death only in patients with a reduced LF, whereas Szabo and colleagues14 reported a multivariate risk of death 2.5 times higher in patients with increased LF. These contrasting results reflect the poor applicability of spectral decomposition data obtained by automatic commercial Holter systems.1

The first prospective study on the prognostic implications of HRV in patients with cardiac failure (UK-HEART study) has been presented only in a preliminary form.17 In 433 ambulant outpatients with mild to moderate cardiac failure, 24 hour SDNN was significantly reduced in patients who died compared to those who survived. At multivariate analysis an arbitrary cut off value of < 100 ms emerged as a significant predictor of cardiac death but it failed to predict sudden death independently. This high cut off value was partially justified by the type of patients enrolled in the study (mean (SD) ejection fraction 42(17)%) but it remained far superior to that commonly used to stratify risk after myocardial infarction.

Although the results of this prospective study are not applicable to the usual cardiac failure population that often has more severe impairment of left ventricular function, they demonstrate that a simple HRV measure may contribute to better stratification of out-of-hospital patients with moderate cardiac failure when cardiac death is considered a primary end point. The lack of association between reduced HRV and sudden death once again confirms that depressed HRV predisposes more to an unfavourable progression of cardiac failure rather than to increased electrical instability of the myocardium.