400 Br Heart3' 1993;70:400-402

FOR DEBATE

Chronotropic incompetence: a proposal for Br J: first published as 10.1136/hrt.70.5.400 on 1 November 1993. Downloaded from definition and diagnosis

Demosthenes Katritsis, A John Camm

Between 1958 and 1960 Astrand docu- exercise testing that is <75%16 or <80%"7 of mented the normal heart rate response to the predicted MPHR. Other arbitrary defini- exercise in healthy individuals and noted that tions such as a maximum exercise the maximum heart rate decreased with age.' 2 <100 beats/min" or <120 beats/min'8 have A reduced cardiac chronotropic response to also been used. However, the achievement of has been reported in elderly sub- maximum exercise is not always possible. jects and alterations in catecholamine- Elderly cardiac patients, especially those interactions may be disabled by chronotropic incompetence, are responsible for this change of cardiovascular unable to perform sufficient exercise on the regulation in the elderly.35 In addition the treadmill. Furthermore, everyday life activi- parasympathetic innervation of the sinus ties of these patients usually correspond to node is currently under investigation.6 Over low work loads up to 6 metabolic equivalents the years it has also been recognised that corresponding to the first stage of the stan- an inadequate chronotropic response dard Bruce protocol. In addition, not much is (chronotropic incompetence) at maximal known about the patterns of heart rate accel- exercise is common in patients with cardiac eration and deceleration in the presence of disease78 and much interest has centred chronotropic incompetence. on the pathophysiological mechanism(s) Wilkoff et al,'9 using exercise testing with involved in chronotropic incompetence.910 respiratory gas analysis and employing a Despite this, no universally accepted defini- less demanding protocol, the so-called tion of chronotropic incompetence exists and Chronotropic Assessment Exercise Protocol the criteria for its diagnosis are not defined. (CAEP), recently established a method by

However, a precise diagnosis of this condition which the chronotropic response during sub- http://heart.bmj.com/ is of clinical importance. First, adaptive-rate maximal exercise can be assessed. This was pacing may be beneficial in patients who achieved by comparing relative metabolic clearly demonstrate chronotropic incompe- levels with relative heart rates-that is, by tence."'''4 Secondly, chronotropic incompe- normalising the change in heart rate from rest tence has also been documented in patients to maximal exertion as a linear function of with chronic heart failure and may contribute the change in metabolic workload. The to the impairment of physical capacity seen in normal predicted heart rate at some sub- these patients.7 '5 maximal stage of exercise, regardless of on October 1, 2021 by guest. Protected copyright. the protocol used, is given by the formula: Terminology and definitions HRstage = [(220-age-HRret) x The term chronotropic incompetence implies (METSstage-1) I (METSpeak1)] + HRrest the inability of the heart to increase its rate in proportion to metabolic demand. where METS = Vo2(ml/kg/min)/3 5, and Consequently, it refers either to inadequacy METSpeak = the peak functional capacity of the sinus node or, in the case of complete achieved during the test. heart block, of the lower escape pacemaker to This formula is proposed as a guide to the respond to exercise or other autonomic expected heart rate at various stages of exer- changes. Unfortunately in published reports a cise in normal subjects able to exercise to maxi- clear distinction is not always made between mum workload, but it gives no idea as to the of the sinus node expectation in patients who are unable to Department of chronotropic incompetence Cardiological and of the lower escape pacemaker. achieve anaerobic peak exercise. In these Sciences, St George's The current definitions of chronotropic patients the application of the formula will Hospital Medical incompetence usually rely on the heart rate produce an exaggerated estimate of School, London D Katritsis response achieved at maximal exercise. The chronotropic incompetence during submaxi- A J Camm expression which was formulated by Astrand mal exercise because of its reliance on Correspondence to: to predict the age dependent maximum sinus METSpeak as a denominator in the equation. Dr D Katritsis, Department rate to exercise Wilkoffs methodology has been used of Cardiological Sciences, St response (maximum pre- recently Georges's Hospital Medical dicted heart rate, MPHR) was MPHR = by Kay20 in a proposed model for assessment School, Cranmer Terrace, incom- of the rates offered London SW17 ORE. (220-age) beats/min and chronotropic pacing by adaptive-rate defined as a pacemakers from the of exercise to Accepted for publication petence has been arbitrarily beginning 26 April 1993 maximum exercise heart rate achieved during complete recovery. Chronotropic incompetence: a proposalfor definition and diagnosis 401

Prevalence the sinus node to accelerate in response to The prevalence of this condition in most metabolic demands secondary to intrinsic dis- patient populations is not known and the ease or negative chronotropic . inconsistency in defining chronotropic incom- Functional chronotropic incompetence mani- petence in the various reported studies makes fests itself either as atrial tachyarrhythmias or Br Heart J: first published as 10.1136/hrt.70.5.400 on 1 November 1993. Downloaded from comparative analysis of the existing data diffi- as retrograde ventriculoatrial conduction cult. It has been suggested that approximately resulting in sinus node reset, pacemaker- 40% of the pacemaker population exhibit mediated tachycardia, or the so-called atri- some degree of chronotropic incompetence oventricular desynchronisation arrhythmia and might benefit from rate-adaptive pacing2l (that is, unsensed retrograde P waves fol- and that this percentage increases with time lowed by ineffectual atrial stimulation during after implantation.'7 The prevalence of atrial refractoriness26). In such cases there is chronotropic incompetence in sick sinus interference with sinus node activity prevent- syndrome (due to inadequate response of the ing an appropriate sinus node rate response sinus node), defined as <120 beats/min at to exercise or autonomic changes. maximum exercise, has been reported to Jrunctional chronotropic incompetence in range from 28% to 57%.18 Characteristically, patients with permanent atrial fibrillation the definition of chronotropic incompetence implies inability of the heart rate to achieve in the published series is not always clear.22 In 80% of the predicted values owing to the atri- atrial fibrillation (usually due to inadequate oventricular conduction defect. Also in response of the conduc- patients with complete heart block it refers to tion) the chronotropic response to exercise the inability of the escape junctional pace- may be impaired in up to 60% of the maker to achieve at least 80% of the pre- patients.23 In patients with acquired complete dicted value. In cases of an intra-hisian or heart block (usually due to inadequate infra-hisian block the term ventricular response of the His-Purkinje pacemaker) chronotropic incompetence is more appropri- chronotropic incompetence is almost univer- ate-to denote incompetence of the escape sal. Chronotropic incompetence is not only focus. important in patients with primary conduc- tion disease but is also common in patients DIAGNOSIS with heart failure whether this is caused by Ideally, cardiopulmonary exercise testing with ischaemic heart disease'5 or dilated or hyper- respiratory gas analysis is required for a trophic cardiomyopathy.2' Studies are cur- proper assessment of the chronotropic rently underway to determine the true response, though this facility is not univer- prevalence of chronotropic incompetence in sally available. We propose the following such patients and to assess whether the practical scheme: restoration of chronotropic competence is of (1) If patients achieve more than 80% of therapeutic benefit. their predicted maximum heart rate during an ordinary exercise test chronotropic incompe- http://heart.bmj.com/ tence is not present. Proposals (2) In patients unable to achieve at least DEFINITIONS 80% of their predicted maximum heart rate A standard definition of chronotropic incom- on exercise, exercise testing with respiratory petence is proposed based ott an anatomical gas analysis should be performed, particularly and a physiological differentiation. From an in patients with abnormal left ventricular anatomical perspective chronotropic incom- function. petence is divided into sinus nodal, junc- (a) Patients who achieve the anaerobic on October 1, 2021 by guest. Protected copyright. tional, or ventricular. Whereas from a threshold are chronotropically incompetent. physiological perspective we have proposed25 (b) In those patients who do not reach the a distinction between two varieties: specific or anaerobic threshold at peak exercise, submax- functional. imal chronotropic incompetence at any stage of submaximal exercise can be assessed Chronotropic incompetence is the inability of the according to Wilkoffs formula. Since the heart rate to achieve at least 80% (an arbi- "METSpeak" value available will be necessarily trary percentage for the time being) of the smaller than the one that corresponds to the predicted value according to Astrand's for- anaerobic threshold, chronotropic incompe- mula (220- age) at peak exercise-that is, tence can be excluded if the heart rate achievement of the anaerobic threshold. response is higher than 80% of that predicted Inability of the heart rate to achieve at least according to the formula. If the achieved 80% of the predicted value according to heart rate response is less than 80% of that Wilkoff's formula at any stage of submaximal predicted, chronotropic incompetence cannot exercise may also denote a form of be excluded. chronotropic incompetence that at present is particularly relevant to the pacing rate modu- lation offered by adaptive-rate pacemakers.20 1 Astrand I. The physical work capacity of workers 50-64 years old. Acta Physiol Scand 1958;42:73-86. 2 Astrand I. Aerobic work capacity in men and women with Sinus node chronotropic incompetence is the special reference to age. Acta Physiol Scand 1960;49: inability of the sinus node to achieve at least 1-92. 3 Buhler FR, Bolli P. Changes in cardiovascular responsive- 80% of the predicted rate. Specific sinus node ness caused by age and high : chronotropic incompetence is the inability of Implications for therapy. J Cardiovasc Pharmacol 1985; 402 Katritsis, Camm

7(suppl 3):206-15. 15 Yamabe H, Kobayashi K, Takata T, Fukuzaki H. 4 Vestal RE, Wood AJJ, Shand DG. Reduced 3-adrenore- Reduced chronotropic reserve to the metabolic require- ceptor sensitivity in the elderly. Clin Pharmacol Ther ment during exercise in advanced heart failure with old 1979;26:181-6. myocardial infarction. Jpn CircJ 1987;51:259-64. 5 Van Brummelen P, Buhler FR, Kiowski W, Amann FW. 16 Isaeff DM, Jutzy RV, Florio J. Programming of rate Age-related decrease in cardiac and peripheral vascular responsive pacemakers. JT Electrophysiol 1989;3: responsiveness to isoproterenol: Studies in normal sub- 2102-216. Br Heart J: first published as 10.1136/hrt.70.5.400 on 1 November 1993. Downloaded from jects. Clin Sci 1981;60:571-7. 17 Gwinn N, Leman R, Zile M, et al. Pacemaker patients 6 Carlson MD, Geha AS, Hsu J, Martin PJ, Levy MN, become chronotropic incompetent with time [abstr]. Jacobs G, Waldo AL. Selective stimulation of parasym- PACE 1990;13:535. pathetic nerve fibers to the human . 18 Rosenqvist M. Atrial pacing for sick sinus syndrome. Clin Circulation 1992;85:1311-7. Cardiol 1990;13:43-47. 7 Colucci WS, Ribeiro JP, Rocco MB, et al. Impaired 19 Wilkoff BL, Corey J, Blackburn G. A mathematical model chronotropic response to exercise in patients with of the exercise cardiac chronotropic response to exer- congestive heart failure. Role of postsynaptic beta- cise. J Electrophysiol 1989;3:176-80. adrenergic desensitization. Circulation 1989;80:314-23. 20 Kay GN. Quantitation of chronotropic response: compari- 8 Katritsis D, Jones S, Camm AJ: A rational choice of pace- son of methods for rate-modulating permanent pace- maker mode. Eur J Cardiac Pacing Electrophysiol makers. JAm Coll Cardiol 1992;20:1533-41. 1991;1:132-7. 21 McBride JW, Reyes WJ, Medellin L. What is the need for 9 Brown JE, McLeod AA, Shand DG. In support of cardiac rate modulated pacemakers? [abstr]. PACE 1990;13: chronotropic beta 2 adrenoceptors. Am J Cardiol 504. 1986;57:1 lf-16f. 22 Ryden L. Atrial inhibited pacing-An underused mode of 10 Hammond HK, Ransnas LA, Insel PA. Noncoordinate cardiac stimulation. PACE 1988;1 1:1375-9. regulation of cardiac Gs protein and beta-adrenergic 23 Corbelli R, Masterson M, Wilkoff BL. Chronotropic receptors by a physiological stimulus, chronic dynamic response to exercise in patients with atrial fibrillation. exercise. J Clin Invest 1988;82:2168-71. PACE 1990;13:179-85. 11 Batey R, Sweesy M, Scala G, Forney RC. Comparison of 24 Keeling P, Haywood G, Klare E, Jennison S, Bent S, low rate dual chamber pacing to activity responsive rate McKenna W. Chronotropic incompetence in chronic variable ventricular pacing. PACE 1990;13:646-52. heart failure and its association with reduced exercise 12 Higano ST, Hayes DL, Eisinger G. Hemodynamic impor- capacity in patients with dilated cardiomyopathy [abstr]. tance of AV synchrony during low levels of exercise Proceeding of the 13th Annual Scientific Session of the [abstr]. PACE 1989;12:1565. North American Society of Pacing and 13 Cazzin R, Capucci A, Zarbo F, Artusi L, Boriani G, Electrophysiology. PACE 1992;15:575. Zanuttini D, Pascotto P, Piccolo E. Evaluation of rate- 25 Camm AJ, Katritsis D. VVIR pacing is preferable to VDD responsiveness benefit in patients with and without pacing: when and why? In: Santini M, Pistolese M, chronotropic incompetence [abstr]. PACE 1991;14:684. Alliegro A, eds. Progress in clinical pacing. Amsterdam: 14 Haywood G, Katritsis D, Ward J, Leigh-Jones M, Ward Excerpta Medica, 1990:66-82. DE, Camm AJ. Atrial adaptive rate pacing in sick sinus 26 Barold SS. Repetitive reentrant and non-reentrant ven- syndrome: effects on exercise capacity and atrial triculoatrial synchrony in dual chamber pacing. Clin arrhythmias. BrHeart3 1993;69:174-8. Cardiol 1991;14:754-63. http://heart.bmj.com/ on October 1, 2021 by guest. Protected copyright.