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).

BACKGROUND Patients with chronic heart failure (CHF) have a continuing high mortality. Autonomic dysfunction may play an important role in the pathophysiology of cardiac death in CHF. UK-HEART examined the value of heart rate variability (HRV) measures as independent predictors of death in CHF. METHODS AND RESULTS In a prospective study powered for mortality, we recruited 433 outpatients 62+/-9.6 years old with CHF (NYHA functional class I to III; mean ejection fraction, 0.41+/-0.17). Time-domain HRV indices and conventional prognostic indicators were related to death by multivariate analysis. During 482+/-161 days of follow-up, cardiothoracic ratio, SDNN, left ventricular end-systolic diameter, and serum sodium were significant predictors of all-cause mortality. The risk ratio for a 41.2-ms decrease in SDNN was 1.62 (95% CI, 1.16 to 2.44). The annual mortality rate for the study population in SDNN subgroups was 5.5% for >100 ms, 12.7% for 50 to 100 ms, and 51.4% for <50 ms. SDNN, creatinine, and serum sodium were related to progressive heart failure death. Cardiothoracic ratio, left ventricular end-diastolic diameter, the presence of nonsustained ventricular tachycardia, and serum potassium were related to sudden cardiac death. A reduction in SDNN was the most powerful predictor of the risk of death due to progressive heart failure. CONCLUSIONS CHF is associated with autonomic dysfunction, which can be quantified by measuring HRV. A reduction in SDNN identifies patients at high risk of death and is a better predictor of death due to progressive heart failure than other conventional clinical measurements. High-risk subgroups identified by this measurement are candidates for additional therapy after prescription of an ACE inhibitor.

[1]  W. Stevenson,et al.  Diverse mechanisms of unexpected cardiac arrest in advanced heart failure. , 1989, Circulation.

[2]  W G Stevenson,et al.  Prognostic Significance of Atrial Fibrillation in Advanced Heart Failure: A Study of 390 Patients , 1991, Circulation.

[3]  F Boomsma,et al.  Prognostic value of heart rate variability during long-term follow-up in patients with mild to moderate heart failure. The Dutch Ibopamine Multicenter Trial Study Group. , 1996, Journal of the American College of Cardiology.

[4]  P. Grayburn,et al.  Does digoxin provide additional hemodynamic and autonomic benefit at higher doses in patients with mild to moderate heart failure and normal sinus rhythm? , 1997, Journal of the American College of Cardiology.

[5]  D J van Veldhuisen,et al.  Prognostic value of heart rate variability in chronic congestive heart failure secondary to idiopathic or ischemic dilated cardiomyopathy. , 1997, The American journal of cardiology.

[6]  F. Tristani,et al.  Ejection Fraction, Peak Exercise Oxygen Consumption, Cardiothoracic Ratio, Ventricular Arrhythmias, and Plasma Norepinephrine as Determinants of Prognosis in Heart Failure , 1993, Circulation.

[7]  G. Parati,et al.  Spectral analysis of blood pressure and heart rate variability in evaluating cardiovascular regulation. A critical appraisal. , 1995, Hypertension.

[8]  H. Crijns,et al.  Heart rate variability in left ventricular dysfunction and heart failure: effects and implications of drug treatment. , 1994, British heart journal.

[9]  A. Moss,et al.  Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators. , 1996, The New England journal of medicine.

[10]  Bertram Pitt,et al.  Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE) , 1997, The Lancet.

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

[12]  R Maestri,et al.  Scopolamine Improves Autonomic Balance in Advanced Congestive Heart Failure , 1994, Circulation.

[13]  N Engl,et al.  Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. , 1997, Circulation.

[14]  J. Sanderson The SWORD of Damocles , 1996, The Lancet.

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

[16]  Guidelines for the diagnosis of heart failure , 2022 .

[17]  J. Cohn,et al.  Mild systolic dysfunction in heart failure (left ventricular ejection fraction >35%): baseline characteristics, prognosis and response to therapy in the Vasodilator in Heart Failure Trials (V-HeFT) , 1996, Journal of the American College of Cardiology.

[18]  J. Miller,et al.  Decreased heart rate variability and its association with increased mortality after acute myocardial infarction. , 1987, The American journal of cardiology.

[19]  P. Ponikowski,et al.  Depressed heart rate variability as an independent predictor of death in chronic congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy. , 1997, The American journal of cardiology.

[20]  J. Cohn,et al.  Influence of prerandomization (baseline) variables on mortality and on the reduction of mortality by enalapril. Veterans Affairs Cooperative Study on Vasodilator Therapy of Heart Failure (V-HeFT II). V-HeFT VA Cooperative Studies Group. , 1993, Circulation.

[21]  D. Ewing,et al.  Cardiac parasympathetic activity in severe uncomplicated coronary artery disease. , 1994, British heart journal.

[22]  J. Bigger,et al.  Baroreflex sensitivity and heart-rate variability in prediction of total cardiac mortality after myocardial infarction , 1998, The Lancet.

[23]  S. Dubner,et al.  Nonsustained ventricular tachycardia in severe heart failure. Independent marker of increased mortality due to sudden death. GESICA-GEMA Investigators. , 1996, Circulation.

[24]  Z. You-hua,et al.  Sympathetic inhibition with clonidine improves autonomic balance in congestive heart failure. , 1997, International journal of cardiology.

[25]  T. Cesario Introduction—Cardiovascular disease in the elderly: Etiology, diagnosis, prevention and treatment , 1989 .

[26]  J. Cohn,et al.  Erratum: Mild systolic dysfunction in heart failure (left ventricular ejection fraction > 35%): Baseline characteristics, prognosis and response to therapy in the Vasodilator in Heart Failure Trials (V-HeFT) (J Am Coll Cardiol (1996), 27:642-9) , 1996 .

[27]  J. Fleiss,et al.  Frequency Domain Measures of Heart Period Variability and Mortality After Myocardial Infarction , 1992, Circulation.

[28]  Australia. Randomised, placebo-controlled trial of carvedilol in patients with congestive heart failure due to ischaemic heart disease , 1997, The Lancet.

[29]  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.

[30]  H L Greene,et al.  Classification of deaths after myocardial infarction as arrhythmic or nonarrhythmic (the Cardiac Arrhythmia Pilot Study). , 1989, The American journal of cardiology.

[31]  J. Cohn,et al.  Influence of Prerandomization (Baseline) Variables on Mortalit and on the Reduction of Mortalit by Enalapril Veterans Affairs Cooperative Study on Vasodilator Therapy of Heart Failure (V‐HeFT II) , 1993 .

[32]  J. Cohn,et al.  The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. , 1996, The New England journal of medicine.

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

[34]  J M Neilson,et al.  Measurement of parasympathetic activity from 24-hour ambulatory electrocardiograms and its reproducibility and sensitivity in normal subjects, patients with symptomatic myocardial ischemia, and patients with diabetes mellitus. , 1996, The American journal of cardiology.

[35]  G D Pinna,et al.  Abnormal awake respiratory patterns are common in chronic heart failure and may prevent evaluation of autonomic tone by measures of heart rate variability. , 1997, Circulation.

[36]  I Ford,et al.  Mortality in heart failure: clinical variables of prognostic value. , 1987, British heart journal.

[37]  S Capewell,et al.  Decreased cardiac parasympathetic activity in chronic heart failure and its relation to left ventricular function. , 1992, British heart journal.

[38]  A. Camm,et al.  Selection of dichotomy limits for multifactorial prediction of arrhythmic events and mortality in survivors of acute myocardial infarction. , 1997, European heart journal.

[39]  R. Sexton Prognosis in congestive heart failure. , 1952, The Journal of the Tennessee State Medical Association. Tennessee State Medical Association.

[40]  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 .

[41]  P. Ponikowski,et al.  Detection and significance of a discrete very low frequency rhythm in RR interval variability in chronic congestive heart failure. , 1996, The American journal of cardiology.

[42]  Salim Yusuf,et al.  Effect of enalapril on survival in patients with reduced left ventricular ejection fractions and congestive heart failure. , 1991, The New England journal of medicine.

[43]  E. J. Brown,et al.  The effect of digoxin on mortality and morbidity in patients with heart failure. , 1997, The New England journal of medicine.

[44]  G. PORENTA,et al.  Prognostic Value of Heart Rate Variability in Patients Awaiting Cardiac Transplantation , 1992, Pacing and clinical electrophysiology : PACE.

[45]  P. Ponikowski,et al.  Circadian pattern of heart rate variability in chronic heart failure patients. Effects of physical training. , 1995, European heart journal.

[46]  J. Le Heuzey,et al.  Effects of bisoprolol on heart rate variability in heart failure. , 1996, The American journal of cardiology.

[47]  J. Oss,et al.  IMPROVED SURVIVAL WITH AN IMPLANTED DEFIBRILLATOR IN PATIENTS WITH CORONARY DISEASE AT HIGH RISK FOR VENTRICULAR ARRHYTHMIA , 1996 .