The role of heart rate variability, heart rate turbulence, and deceleration capacity in predicting cause-specific mortality in chronic heart failure.

BACKGROUND The volume of regional denervated myocardium (D-M) on positron emission tomography has been recently suggested as a strong independent predictor of cause-specific mortality from sudden cardiac arrest (SCA) in chronic heart failure. We sought to evaluate whether ECG indices of global autonomic function predict risk of SCA to a similar degree as regional D-M. METHODS Subjects enrolled in the Prediction of Arrhythmic Events using Positron Emission Tomography (PAREPET) study were included in this study. Patients completed a 24-hour Holter ECG at enrollment and were followed up at 3-month intervals. SCA events were adjudicated by two board-certified cardiologists. Other cardiovascular death events were classified as nonsudden cardiac death (NSCD). Eight measures of heart rate variability were analyzed: SDNN, RMSSD, low-frequency (LF) and high-frequency (HF) power, heart rate turbulence onset and slope, and acceleration and deceleration capacity. We used competing risk regression to delineate cause-specific mortality from SCA versus NSCD. RESULTS Our sample included 127 patients (age 67 ± 12, 92% male). After a median follow-up of 4.1 years, there were 22 (17%) adjudicated SCA and 18 (14%) adjudicated NSCD events. In multivariate Cox-regression, LF power was the only HRV parameter to predict time-to-SCA. However, in competing risk analysis, reduced LF power was preferentially associated with NSCD rather than SCA (HR = 0.92 [0.85-0.98], p = 0.019). CONCLUSION Depressed LF power might indicate impaired vagal reflex, which suggests that increasing vagal tone in these patients would have a protective effect against NSCD beyond that achieved by the mere slowing of heart rate using β-blockers.

[1]  K. P. Anderson,et al.  Sudden Cardiac Death Unresponsive to Implantable Defibrillator Therapy: An Urgent Target for Clinicians, Industry and Government , 2005, Journal of Interventional Cardiac Electrophysiology.

[2]  Douglas L Packer,et al.  Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure. , 2005, The New England journal of medicine.

[3]  A. Moss,et al.  The Effect of ICD Programming on Inappropriate and Appropriate ICD Therapies in Ischemic and Nonischemic Cardiomyopathy: The MADIT‐RIT Trial , 2015, Journal of cardiovascular electrophysiology.

[4]  Douglas P Kiel,et al.  Competing Risk of Death: An Important Consideration in Studies of Older Adults , 2010, Journal of the American Geriatrics Society.

[5]  T. Young,et al.  Sleep apnea and cardiovascular disease: an American Heart Association/american College Of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Coun , 2008, Circulation.

[6]  Michael R Gold,et al.  Limitations of ejection fraction for prediction of sudden death risk in patients with coronary artery disease: lessons from the MUSTT study. , 2007, Journal of the American College of Cardiology.

[7]  Roberto Maestri,et al.  Prognostic implications of baroreflex sensitivity in heart failure patients in the beta-blocking era. , 2009, Journal of the American College of Cardiology.

[8]  A. Malliani,et al.  Heart rate variability. Standards of measurement, physiological interpretation, and clinical use , 1996 .

[9]  Marmar Vaseghi,et al.  The role of the autonomic nervous system in sudden cardiac death. , 2008, Progress in cardiovascular diseases.

[10]  Takashi Morita,et al.  Cardiac iodine-123 metaiodobenzylguanidine imaging predicts sudden cardiac death independently of left ventricular ejection fraction in patients with chronic heart failure and left ventricular systolic dysfunction: results from a comparative study with signal-averaged electrocardiogram, heart rate v , 2009, Journal of the American College of Cardiology.

[11]  L. Mulder,et al.  The utility of low frequency heart rate variability as an index of sympathetic cardiac tone: a review with emphasis on a reanalysis of previous studies. , 2013, Psychophysiology.

[12]  J. Canty,et al.  High‐Risk Electrocardiographic Parameters are Ubiquitous in Patients with Ischemic Cardiomyopathy , 2012, Annals of noninvasive electrocardiology : the official journal of the International Society for Holter and Noninvasive Electrocardiology, Inc.

[13]  M. Malik,et al.  Deceleration capacity of heart rate as a predictor of mortality after myocardial infarction: cohort study , 2006, The Lancet.

[14]  L E Hinkle,et al.  Clinical Classification of Cardiac Deaths , 1982, Circulation.

[15]  J. Canty,et al.  Electrocardiographic predictors of sudden and non-sudden cardiac death in patients with ischemic cardiomyopathy. , 2014, Heart & lung : the journal of critical care.

[16]  A. Hutson,et al.  Prediction of arrhythmic events with positron emission tomography: PAREPET study design and methods. , 2006, Contemporary clinical trials.

[17]  K. Lee,et al.  Electrophysiologic testing to identify patients with coronary artery disease who are at risk for sudden death. Multicenter Unsustained Tachycardia Trial Investigators. , 2000, The New England journal of medicine.

[18]  R. Prescott,et al.  Prospective study of heart rate variability and mortality in chronic heart failure: results of the United Kingdom heart failure evaluation and assessment of risk trial (UK-heart). , 1998, Circulation.

[19]  S. Boveda,et al.  Depressed low frequency power of heart rate variability as an independent predictor of sudden death in chronic heart failure. , 2000, European heart journal.

[20]  A Malliani,et al.  A Cardiocardiac Sympathovagal Reflex in the Cat , 1973, Circulation research.

[21]  R. Maestri,et al.  Short-Term Heart Rate Variability Strongly Predicts Sudden Cardiac Death in Chronic Heart Failure Patients , 2003, Circulation.

[22]  D. Goldstein,et al.  Low‐frequency power of heart rate variability is not a measure of cardiac sympathetic tone but may be a measure of modulation of cardiac autonomic outflows by baroreflexes , 2011, Experimental physiology.

[23]  Peter J. Schwartz,et al.  Sympathetic–parasympathetic interaction in health and disease: abnormalities and relevance in heart failure , 2011, Heart Failure Reviews.

[24]  Barry J Maron,et al.  American Heart Association/American College of Cardiology Foundation/Heart Rhythm Society Scientific Statement on Noninvasive Risk Stratification Techniques for Identifying Patients at Risk for Sudden Cardiac Death. A scientific statement from the American Heart Association Council on Clinical Cardi , 2008, Journal of the American College of Cardiology.

[25]  A. Camm,et al.  Heart-rate turbulence after ventricular premature beats as a predictor of mortality after acute myocardial infarction , 1999, The Lancet.

[26]  J. O'Quigley,et al.  Cox's regression model: computing a goodness of fit statistic. , 1986, Computer methods and programs in biomedicine.

[27]  A. Curtis,et al.  Regional myocardial sympathetic denervation predicts the risk of sudden cardiac arrest in ischemic cardiomyopathy. , 2014, Journal of the American College of Cardiology.

[28]  Mark E. Anderson,et al.  Sudden Cardiac Death Prediction and Prevention: Report From a National Heart, Lung, and Blood Institute and Heart Rhythm Society Workshop , 2010, Circulation.

[29]  Martin Borggrefe,et al.  Vagus Nerve Stimulation for the Treatment of Heart Failure: The INOVATE-HF Trial. , 2016, Journal of the American College of Cardiology.

[30]  W. Zareba,et al.  Risk stratification of mortality in patients with heart failure and left ventricular ejection fraction >35%. , 2009, The American journal of cardiology.

[31]  P. Schwartz,et al.  Exercise-Induced Increase in Baroreflex Sensitivity Predicts Improved Prognosis After Myocardial Infarction , 2002, Circulation.

[32]  F Lombardi,et al.  Sudden cardiac death: role of heart rate variability to identify patients at risk. , 2001, Cardiovascular research.

[33]  G. Breithardt,et al.  Heart rate variability: standards of measurement, physiological interpretation and clinical use. Task Force of the European Society of Cardiology and the North American Society of Pacing and Electrophysiology. , 1996 .

[34]  R. L. Carter,et al.  Denervated Myocardium Is Preferentially Associated With Sudden Cardiac Arrest in Ischemic Cardiomyopathy: A Pilot Competing Risks Analysis of Cause-Specific Mortality , 2017, Circulation. Cardiovascular imaging.