Heart rate variability in patients with stable angina pectoris

The rate and modulation of the heart beat (i.e. heart rate variability; HRV) are controlled by the autonomic nervous system. Cardiac sympathetic activation decreases and parasympathetic increases HRV. Measurements of HRV can be performed in the frequency domain or the time domain; also simple geometric methods are used for time domain measurements. HRV has provided important prognostic information in patients following an acute myocardial infarction and in heart failure patients.

The aims of these studies in patients with stable angina pectoris were (1) to develop and validate a graphical method for the assessment of HRV, (2) to examine the long term stability of HRV measurements, and changes after an acute myocardial infarction, (3) to study the prognostic information of HRV, and (4) to evaluate the effects of beta-adrenoceptor blockade (metoprolol) and calcium antagonist treatment (verapamil) on HRV.

We evaluated 24 h ambulatory ECG recordings in the Angina Prognosis Study in Stockholm (APSIS). HRV was evaluated before and during double-blind treatment with metoprolol or verapamil in 678 patients with stable angina pectoris with a median follow-up of 40 months. The results showed that the differential index (DI) a novel and simple graphical method fore HRV measurements, mainly reflects cardiac parasympathetic control and agrees well with conventional indices of HRV. The DI and conventional indices in the frequency domain and time domain appeared stable over 3 years. An acute myocardial infarction was associated with indices of increased cardiac sympathetic activity, while changes in parasympathetic activity appeared to be small. A low HRV in both the frequency and time domains predicted cardiovascular mortality, independently of conventional risk factors, whereas no such relation was seen for non-fatal myocardial infarction. Thus, a cardiac autonomic imbalance seems to be of importance for fatal arrhythmic events, but not for the atherosclerotic process and plaque vulnerability. The DI appeared to predict cardiovascular death somewhat better than traditional time domain indices of HRV. The best sensitivity and specificity was obtained with a DI of approximately 320 ms. The results indicate that reduced cardiac parasympathetic activity is a major factor associated with a poor prognosis in stable angina pectoris. In addition, diabetic patients had a lower HRV and a worsened prognosis. Metoprolol increased HRV somewhat, whereas verapamil had no effects. However, these short term influences on HRV did not seem to relate to prognosis.

In conclusion, HRV is a valuable method for the evaluation of cardiac autonomic control. The DI is a simple and robust method that shows good agreement with established, more complicated measurements. The DI and other indices of HRV which reflect parasympathetic cardiac control may be useful predictors of the future risk of suffering a fatal cardiovascular event in patients with stable angina pectoris.

List of scientific papers

I. Forslund L, Björkander I, Ericson M, Held C, Kahan T, Rehnqvist N, Hjemdahl P (2002). "Prognostic implications of autonomic function assessed by analyses of catecholamines and heart rate variability in stable angina pectoris." Heart 87(5): 415-22
https://pubmed.ncbi.nlm.nih.gov/11997407

II. Björkander I, Kahan T, Ericson M, Held C, Forslund L, Rehnqvist N, Hjemdahl P (2005). "Differential index, a novel graphical method for measurements of heart rate variability." Int J Cardiol 98(3): 493-9
https://pubmed.ncbi.nlm.nih.gov/15708185

III. Bjorkander I, Forslund L, Kahan T, Ericson M, Held C, Rehnqvist N, Hjemdahl P (2008). "Differential index: a simple time domain heart rate variability analysis with prognostic implications in stable angina pectoris." Cardiology 111(2): 126-33. Epub 2008 Mar 31
https://pubmed.ncbi.nlm.nih.gov/18376124

IV. Björkander I, Forslund L, Ericson M, Rehnqvist N, Hjemdahl P, Kahan T (2009). "Long term stability of heart rate variability in chronic stable angina pectoris, and the impact of an acute myocardial infarction." (Submitted)