Heart rate turbulence assessed through ergometry after myocardial infarction: a feasibility study

ABSTRACT BACKGROUND: Coronary artery disease is an important cause of morbidity and mortality. The impact of ventricular arrhythmias with impaired cardiac vagal activity is one of the most recently studied prognostic factors. However, there are no studies evaluating the phenomenon of heart rate turbulence (HRT) during physical exertion. OBJECTIVE: To study the behavior of HRT during exercise testing, among individuals after myocardial infarction. DESIGN AND SETTING: Feasibility study conducted in a university hospital among individuals 4-6 weeks after myocardial infarction. METHODS: All subjects underwent 24-hour Holter monitoring and ergometric stress testing. We considered that abnormal HRT was present if the turbulence onset was ≥ 0% or turbulence slope was ≤ 2.5 mm/relative risk interval. RESULTS: All 32 subjects were asymptomatic. Their median age was 58 years (interquartile range 12.8) and 70% were male. Abnormal HRT was associated with ventricular dysfunction in this population. We found no differences regarding the behavior of HRT, in relation to age, gender, smoking, systemic arterial hypertension, diabetes mellitus or dyslipidemia. Ergometric stress testing detected premature ventricular beats (PVB) in approximately 44% of the examinations, and these occurred both during the active phase of effort and in the recovery period. The low occurrence of several isolated PVB in beta-blocked subjects made it difficult to perform statistical analysis to correlate HRT between ergometric and Holter testing. CONCLUSION: The data obtained in this study do not support performing HRT through ergometric stress testing among patients who remain on beta-blockers post-myocardial infarction, for the purpose of assessing cardiac vagal activity.

The low clinical use of HRT as a risk predictor, which was first put forward by Schmidt et al., 5 may be related to the low sensitivity that it has been perceived to have in some studies. 8 It may also be because 24-hour Holter monitoring is not routinely indicated after myocardial infarction, considering that HRT is determined and analyzed in Holter monitoring. 10 Ergometric stress testing assists in risk assessments on coronary events through analysis on clinical, electrocardiographic and hemodynamic parameters. Modulation of autonomous tonus takes place during physical exertion, which gives rise to increased sympathetic activity during the active phase of effort, while cardiac vagal activity increases in the recovery period. 11 Thus, vagal activity may increase during physical exercise. Hence, ergometric stress testing is already incorporated in regular monitoring for patients with coronary artery disease.

OBJECTIVE
The aim of our study was to evaluate the behavior of post-myocardial infarction HRT during ergometric stress testing.

METHODS
This was an observational, prospective study using primary data to estimate changes in HRT during ergometric stress testing among individuals who had recently had a myocardial infarction episode. The study was conducted in the "Professor Luiz Tavares" Cardiological Emergency Service (Pronto Socorro Cardiológico Universitário de Pernambuco Professor Luiz Tavares), which is affiliated with the University of Pernambuco, between 2018 and 2019. All the patients met the criteria for myocardial infarction, in accordance with the fourth universal definition of myocardial infarction. 12 We excluded individuals with a history of previous events relating to coronary disease, those who could not undergo the ergometric stress testing (due to orthopedic/neurological problems, balance deficits or peripheral vascular alterations) and those who presented factors that precluded the possibility of HRT (atrial fibrillation, cardiac pacemaker and artifacts in the examination recordings).
All of the individuals included in this study had become asymptomatic by the time that they reached four to eight weeks after the ischemic event and they were continuing to use of beta-blockers regularly. All of them underwent 24-hour Holter monitoring (CardioLight 3-channel recorder; Cardios, São Paulo, Brazil) and ergometric stress testing using the Naughton protocol (KT 10200 AT multi-programmable treadmill; Inbramed, Porto Alegre, Brazil).
Turbulence onset (TO) ≥ 0% or turbulence slope (TS) ≤ 2.5 mm/ relative risk interval in 24-hour Holter monitoring was considered to be the gold standard for abnormal HRT.
The analysis on the HRT parameters was standardized in accordance with the study by Bauer et al. 11 In order to eliminate errors in the analysis, we excluded the following: interpolated premature ventricular beats (PVBs); PVB with prematurity less than 20%; PVB with compensation pause below 120% of the average of the last five previous relative risk ( RR) or PVB values; and very short (< 300 ms) or very long (> 2000 ms) PVB tachograms.
TO was calculated based on the last two sinus RR intervals immediately before the PVB-coupling interval, and the two sinus RR intervals immediately after the compensatory pause. TO (as a percentage) has negative values for patients with low cardiovascular risk since there is an immediate heart rate acceleration after PVB.
Where RR = R-to-R wave interval in electrocardiogram On the other hand, TS was calculated using the slope of the line formed by five RR intervals after the PVB, which were obtained from among the first 15 sinus RR intervals that followed the PVB.
TS is expressed in milliseconds per RR interval, and the heart rate of patients with a low cardiovascular risk is decreased by up to 8 beats/min following the initial acceleration caused by the PVB.
Thus, the reference value is > 2.5 ms/RR, which translates as the maximum variation in sinus RR intervals (ms) among the five sinus RR intervals to be analyzed.
Where Y = maximum positive regression slope assessed after the PVB; and X = five consecutive sinus rhythm R-R intervals after PVB. This extremely low number did not allow us to undertake any statistical treatment of associations of HRT parameters between the ergometric test and 24-hour Holter test.

DISCUSSION
In our study, it was not possible to adequately perform analysis on HRT using ergometric stress testing due to the low density of ventricular arrhythmia. All the individuals analyzed were making  This first response is usually ephemeral, since baroreceptors will also detect an elevation in blood pressure and consequently recruit the vagal stimulus that is responsible for heart rate deceleration. 10 Later on, they will return to the hemodynamic situation patients after myocardial infarction, over a mean follow-up of three years, and showed that HRT parameters were strong predictors of cardiac mortality (heart rate, HR 5.7; 95% confidence interval, CI 2.1-15.9; P = 0.0008). 13  The major limitation of our study was the fact that the small sample size precluded observation of any statistical difference regarding the behavior of HRT involving demographic data and cardiovascular risk factors. Likewise, this did not enable assessment of the possible association of the HRT parameters obtained through ergometry with the gold standard obtained through the 24-hour Holter monitoring.

CONCLUSION
The data obtained in this study do not support assessment of HRT through ergometric stress testing in patients who remain on beta-blockers post-myocardial infarction, for the purpose of assessing cardiac vagal activity, as a replacement for 24-hour Holter monitoring.