HEART RATE TURBULENCE IN PATIENTS WITH CORONARY ARTERY DISEASE

I.Cygankiewicz¹, JK.Wranicz¹, H.Bolinska¹, J.Zaslonka¹, W.Zareba²
¹ Institute of Cardiology, Medical University of Lodz, Poland,
Sterlinga 1/3, 91-425 Lodz, POLAND
²Cardiology Unit, University of Rochester, Rochester NY

Abstract: The aim of this study was to evaluate the association between heart rate turbulence (HRT) parameters and clinical characteristics of coronary artery disease (CAD) patients. In 158 pts (33 F, 125 M; mean age 62±9 years) with angiographically documented CAD, 24-hour Holter monitoring with HRT analysis was performed to evaluate turbulence onset (To) and turbulence slope (Ts).

HRT parameters showed broad spectrum of values, To ranging from –8,3% to +4,45%; av -1,32%±1,64 and Ts ranging from 0,42 to 54,7 ms/RR; av.10,67 ±10,36 ms/RR. According to quartile values To ³ - 0,38% and Ts £4,22 ms/RR were considered as abnormal.

Average values of To were higher and Ts lower in patients over 60 yrs, with past MI and in those with EF<40%. Considering pharmacotheraphy, higher values of Ts were observed in patients on statins, nitrates and beta-blockers while lower Ts values were noted in patients on calcium blockers. Multivariate analysis revealed that abnormal HRT parameters were significantly and independently associated with age>60yrs (OR 1,26; p=0,002) and EF<40% (OR 1,37; p=0,001). In conclusion, HRT parameters are dependent on clinical characteristics of studied patients and on pharmacotherapy. Abnormal Ts more than abnormal To depends on clinical characteristics of patients.

INTRODUCTION

Heart rate turbulence (HRT) is a novel, noninvasive predictor of sudden cardiac death [1]. This biphasic response of sinus rhythm to a premature ventricular beat (VPB) is believed to reflect baroreceptors function [2]. Little is known about the association between HRT parameters and clinical characteristics of patients with coronary artery disease (CAD). Thus, the aim of this study was to establish the relationship between HRT parameters and clinical characteristics of CAD patients (pts).

METHODS

In 158 pts (33F, 125 M aged 38-78 yrs, av. 62±9 years) with angiographically documented CAD, 24-hour ECG Holter monitoring (Oxford Medilog Excel 2) with HRT analysis was performed. Two numeric HRT parameters were calculated : turbulence onset (To) and turbulence slope (Ts). To was defined as the difference between the mean of the first two sinus RR intervals after a VPB and the last two sinus RR intervals before VPB divided by the mean of the last two sinus RR intervals before VPB, while Ts was described as the steepest positive slope of a regression line assessed over any sequence of 5 subsequent sinus RR intervals within the first 20 sinus RR intervals after VPB.

In all the patients clinical characteristics (age, sex, past MI, EF) and CAD risk factors (diabetes, hypertension, obesity, smoking, family history) as well as pharmacotherapy were evaluated.

Then, patients were dichotomized into high-risk groups according to quartiles HRT values: the first quartile for Ts and the fourth quartile for To.

Univariate and multivariate analysis was performed to correlate the clinical characteristics of pts with HRT parameters. P value <0.05 was considered statistically significant.

RESULTS

There were 34 pts with diabetes, 81 pts with hypertension and 102 pts with a past MI history in a studied group. EF varied from 33-74%, av.54% (in this 10 pts with EF<40%). None of them presented heart failure symptoms ³III NYHA.

During Holter monitoring ventricular arrhythmia necessary for HRT calculation was found in 132 pts ( 83%)

HRT parameters showed broad spectrum of values, To ranging from –8,3% to +4,45%; av -1,32%±1,64 and Ts ranging from 0,42 to 54,7 ms/RR; av.10,67±10,36 ms/RR. According to quartile values To ³ - 0,38% and Ts £4,22 ms/RR were considered as abnormal.

In 32 pts (24%) abnormal To or Ts was found, while in 17 pts (13%) both To and Ts were abnormal. In remaining 82pts (62%) both HRT parameters were normal. To correlated significantly with Ts (r=-0,31, p=0,0004)

Patients with abnormal parameters of HRT compared to a group with normal HRT values were older and characterized by feature of more advanced CAD: age over 60 yrs (79% vs 50%), past MI (76% vs. 64%) and EF<40% (25% vs. 4%). Multivariate analysis revealed that abnormal HRT parameters were significantly and independently associated with age>60yrs (OR 1,26; p=0,002) and EF<40% (OR 1,37; p=0,001).

DISCUSSION

Heart rate turbulence, described for the first time as a new ECG predictor in 1999, was found to reflect baroreflex response [3,4]. Baroreceptors localized in aortic arch and carotid sinus constitute one of the basic mechanism of heart rate and blood pressure control. They are constantly stimulated by tonic arterial blood pressure. They are more likely to response to sudden hypotonia, than an increase in blood pressure [5]. Baroreceptors sensitivity is studied by means of two types of methods: invasive and non-invasive. The phenylephrine test, stimulating alpha receptors, is the method of choice, although its use in clinical practice remains limited due to its methodological complexity [6]. Heart rate turbulence, as a noninvasive method of BRS evaluation, is believed to become more commonly utilized.

In our study, HRT parameters were evaluated in 132 CAD patients. Abnormal HRT parameters were found in 38 % pts, that indicates a high incidence of BRS dysfunction in this group of patients. HRT parameters significantly worsened with age. This observation is confirmed by publications of Barthel and Yap who observed similar correlation in a population of EMIAT study [7,8]. Age-related decrease in BRS sensitivity is considered to be an effect of a reduced arterial compliance [9]. Diabetes, past MI history and decreased ejection fraction have also predisposed to altered HRT parameters. When analyzing pharmacotherapy HRT parameters showed better values in patients treated with beta-blockers, statins and nitrates. It was postulated that comparing to HRV parameters HRT remains a significant stratifier in pts on beta-blockers. The favorable effect of beta-blockers on HRT may be explained by its influence on sympathovagal balance [10]. The positive influence of statins on HRT might be mediated by an increase of arterial walls compliance, while the influence of nitrates by its direct endothelial effect and blood pressure decrease.

Heart rate turbulence is a new method, thus it is very difficult to define abnormal HRT values. To and Ts correlate with each other that makes this decision even more difficult. In our studied group we considered high-risk quartile as abnormal values. Abnormal values were observed in 38% of pts. While dichotomizing according to values considered as abnormal by authors of this method abnormal values of HRT were found in 23% pts [1].

Among two HRT parameters Ts is more dependent on clinical characteristics of patients and seems to better reflect baroreceptors sensitivity. It is supported by data of Davies who also considered Ts as the predominant HRT parameter [2]. It might be explained by a fact that Ts better than To reflects dynamicity of RR changes.

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