Effect of heart rate correction on pre- and post-exercise heart rate variability to predict risk of mortality—an experimental study on the FINCAVAS cohort

The non-linear inverse relationship between RR-intervals and heart rate (HR) contributes significantly to the heart rate variability (HRV) parameters and their performance in mortality prediction. To determine the level of influence HR exerts over HRV parameters' prognostic power, we studied the predictive performance for different HR levels by applying eight correction procedures, multiplying or dividing HRV parameters by the mean RR-interval (RRavg) to the power 0.5–16. Data collected from 1288 patients in The Finnish Cardiovascular Study (FINCAVAS), who satisfied the inclusion criteria, was used for the analyses. HRV parameters (RMSSD, VLF Power and LF Power) were calculated from 2-min segment in the rest phase before exercise and 2-min recovery period immediately after peak exercise. Area under the receiver operating characteristic curve (AUC) was used to determine the predictive performance for each parameter with and without HR corrections in rest and recovery phases. The division of HRV parameters by segment's RRavg to the power 2 (HRVDIV-2) showed the highest predictive performance under the rest phase (RMSSD: 0.67/0.66; VLF Power: 0.70/0.62; LF Power: 0.79/0.65; cardiac mortality/non-cardiac mortality) with minimum correlation to HR (r = −0.15 to 0.15). In the recovery phase, Kaplan-Meier (KM) survival analysis revealed good risk stratification capacity at HRVDIV-2 in both groups (cardiac and non-cardiac mortality). Although higher powers of correction (HRVDIV-4and HRVDIV-8) improved predictive performance during recovery, they induced an increased positive correlation to HR. Thus, we inferred that predictive capacity of HRV during rest and recovery is augmented when its dependence on HR is weakened by applying appropriate correction procedures.

[1]  M. Lauer,et al.  Heart-rate recovery immediately after exercise as a predictor of mortality. , 1999, The New England journal of medicine.

[2]  B. Geršak,et al.  How Does Successful Off-Pump Pulmonary Vein Isolation for Paroxysmal Atrial Fibrillation Influence Heart Rate Variability and Autonomic Activity? , 2008, Innovations.

[3]  Jari Viik,et al.  Exercise-test-related heart rate variability and mortality: the Finnish Cardiovascular Study. , 2010, International journal of cardiology.

[4]  Arsenio Veicsteinas,et al.  Heart rate variability and autonomic activity at rest and during exercise in various physiological conditions , 2003, European Journal of Applied Physiology.

[5]  Pablo Laguna,et al.  The Integral Pulse Frequency Modulation Model With Time-Varying Threshold: Application to Heart Rate Variability Analysis During Exercise Stress Testing , 2011, IEEE Transactions on Biomedical Engineering.

[6]  Frederick E Dewey,et al.  Autonomic nervous system interaction with the cardiovascular system during exercise. , 2006, Progress in cardiovascular diseases.

[7]  Ti-Ho Wang,et al.  The influence of mean heart rate on measures of heart rate variability as markers of autonomic function: a model study. , 2003, Medical engineering & physics.

[8]  J. Sacha,et al.  Heart rate impact on the reproducibility of heart rate variability analysis. , 2013, International journal of cardiology.

[9]  J. Sacha,et al.  Alterations of an average heart rate change heart rate variability due to mathematical reasons. , 2008, International journal of cardiology.

[10]  P M Okin,et al.  Impaired heart rate response to graded exercise. Prognostic implications of chronotropic incompetence in the Framingham Heart Study. , 1996, Circulation.

[11]  T. Seppänen,et al.  Long-term outcome of patients with chronotropic incompetence after an acute myocardial infarction , 2011, Annals of medicine.

[12]  Jari Viik,et al.  Heart rate variability is dependent on the level of heart rate. , 2007, American heart journal.

[13]  Frederick E Dewey,et al.  Novel predictor of prognosis from exercise stress testing: heart rate variability response to the exercise treadmill test. , 2007, American heart journal.

[14]  Peter J Schwartz,et al.  Heart-rate profile during exercise as a predictor of sudden death. , 2005, The New England journal of medicine.

[15]  G. Schmidt,et al.  How to strengthen or weaken the HRV dependence on heart rate--description of the method and its perspectives. , 2013, International journal of cardiology.

[16]  Mika P. Tarvainen,et al.  Kubios HRV - Heart rate variability analysis software , 2014, Comput. Methods Programs Biomed..

[17]  Ferdinand J. Venditti,et al.  Reduced Heart Rate Variability and Mortalit Risk in an Elderly Cohort: The Framingham Heart Study , 1994, Circulation.

[18]  J. Sacha Interaction between Heart Rate and Heart Rate Variability , 2014, Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc.

[19]  J. Sacha,et al.  Different methods of heart rate variability analysis reveal different correlations of heart rate variability spectrum with average heart rate. , 2005, Journal of electrocardiology.

[20]  P. Sleight,et al.  Physical activity influences heart rate variability and very-low-frequency components in Holter electrocardiograms. , 1996, Cardiovascular research.

[21]  V. Froelicher,et al.  Importance of the first two minutes of heart rate recovery after exercise treadmill testing in predicting mortality and the presence of coronary artery disease in men. , 2004, The American journal of cardiology.

[22]  T. Lehtimäki,et al.  The Finnish Cardiovascular Study (FINCAVAS): characterising patients with high risk of cardiovascular morbidity and mortality , 2006, BMC cardiovascular disorders.

[23]  J. Miller,et al.  The independence of cycle length variability and exercise testing on predicting mortality of patients surviving acute myocardial infarction. The Multicenter Postinfarction Research Group. , 1990, The American journal of cardiology.

[24]  How to select patients who will not benefit from ICD therapy by using heart rate and its variability? , 2013, International journal of cardiology.

[25]  R. E. Mason,et al.  A new system of multiple-lead exercise electrocardiography. , 1966, American heart journal.

[26]  Ian G. Harnik Heart-rate profile during exercise as a predictor of sudden death. , 2005, The New England journal of medicine.

[27]  J. Goldberger,et al.  Assessment of autonomic function in cardiovascular disease: physiological basis and prognostic implications. , 2008, Journal of the American College of Cardiology.

[28]  Jason Ng,et al.  Assessment of parasympathetic reactivation after exercise. , 2006, American journal of physiology. Heart and circulatory physiology.

[29]  T. Seppänen,et al.  Novel spectral indexes of heart rate variability as predictors of sudden and non‐sudden cardiac death after an acute myocardial infarction , 2007, Annals of medicine.

[30]  J. Fleiss,et al.  Frequency domain measures of heart period variability to assess risk late after myocardial infarction. , 1993, Journal of the American College of Cardiology.

[31]  J. Sacha,et al.  Why should one normalize heart rate variability with respect to average heart rate , 2013, Front. Physiol..

[32]  A. Maggioni,et al.  Prognostic significance of heart rate variability in post-myocardial infarction patients in the fibrinolytic era. The GISSI-2 results. Gruppo Italiano per lo Studio della Sopravvivenza nell' Infarto Miocardico. , 1996, Circulation.

[33]  A. Folsom,et al.  Low Heart Rate Variability in a 2-Minute Rhythm Strip Predicts Risk of Coronary Heart Disease and Mortality From Several Causes: The ARIC Study , 2000, Circulation.

[34]  A. Malliani,et al.  Cardiovascular Neural Regulation Explored in the Frequency Domain , 1991, Circulation.

[35]  V. Salomaa,et al.  The validity of the Finnish Hospital Discharge Register and Causes of Death Register data on coronary heart disease , 2005, European journal of cardiovascular prevention and rehabilitation : official journal of the European Society of Cardiology, Working Groups on Epidemiology & Prevention and Cardiac Rehabilitation and Exercise Physiology.