The Relationship between QT Interval and Heart Rate During Physiological Exercise and Pacing Fawaz AKHRAS,M.D. and Anthony F. RICKARDS,M.B., M.R.C.P. SUMMAR Conventional doctrine states that the QT interval is related to heart rate in an inverse exponential relationship, so that with increasing rate the QT interval shortens. This relationship has recently been studied in a group of patients undergoing physiological exercise stress tests, atrial pac- ing stress test, and in a further group of patients with complete heart block undergoing exercise at a fixed ventricular rate controlled by cardiac pacemaker. Examinations of recordings made during physiological ex- ercise do show the expected shortening in QT interval, we believe that this shortening is only in part due to the intrinsic effect of increased rate as patients who were atrially paced to similar rates and within the same age group showed only a small decrease in measured QT interval and patients undergoing exercise at fixed ventricular rate showed shortening in QT interval which was related to the independent atrial rate. It ap- pears, therefore, that the QT interval is governed mainly by extrinsic factors and not intrinsically rate related. The physiological control of QT interval is being used now to con- struct a cardiac pacemaker which senses the interval between the de- livered stimulus and the evoked T wave so that the stimulus-evoked T wave interval could be used to set the subsequent escape interval and sub- sequently the overall pacing rate. Physiological control of cardiac pac- ing rate using conventional unipolar lead systems and independent of atrial activity is possible and currently being investigated. Additional Indexing Words: Corrected QT interval Control of cardiac pacemaker Catecho- lamines AZETT1) in 1920 first described a non-linear relationship between the QT interval and the heart rate which has been widely applied to derive the rate corrected QT interval (QTc). Roy et al2) in 1976 reported that in a subject with familial prolongation of the QT interval the QTc actually prolonges with increasing rate during From the National Heart Hospital, London, England. Address for reprint: Dr. F. Akhras, Cardiac Department, King's College Hospital, Denmark Hill, London SE5 9RS, England. This work was supported by a grant from the National Heart and London Chest Hospitals Re- search Fund. Received for publication July 31, 1980. 345 B Jpn. Heart M 346 AKHRAS AND RICKARDS ay 1981 atrial pacing and has led to this re-examination of the rate-QT interval re- lationship in an attempt to define the normal relationship between heart rate and QT interval during physiological exercise and atrial pacing. PATIENTS AND METHODS Physiologicalexercise in sinus rhythm: A group of 25 patients underwent a treadmill exercise and were studied to re- evaluate the rate-QT interval relationship. All subjects were being investigated for ischemic heart disease and were exercised according to Bruce protocol. Twelve lead electrocardiographic recordings were made at a paper speed of 100mm/s us- ing a Cambridge Automatic 3-Channel recorder complying to A.H.A. standards. Recordings were made at rest, at 90s intervals during exercise, immediately post exercise, every 30s for 2min and then every minute until the resting heart rate was reached. The protocol allowed measurement of early as well as late changes in heart rate during recovery, thus allowing frequent measurements of QT interval to be obtained at varying heart rates. Data was analysed as a whole and for the groups sub-divided into those pa- tients taking beta blocking drugs (15 patients) and those on no cardioactive ther- apy (10). Further analysis of the rate-QT relationship with increasing (exercise) and with decreasing rate (recovery) was also made. Atrial pacing: Similar data was obtained from 15 patients who underwent pacing stress test- ing during cardiac catheterization for the evaluation of chest pain. Simultaneous 12 lead cardiograms on a Cambridge Photographic recorder at the resting rate and during atrial pacing from 100 beats/min (b.p.m.) in increments of 10b.p.m. until either: the maximum rate of 180b.p.m. was achieved or the test was terminated due to chest pain or A.V. block. A detailed description of the atrial pacing pro- tocol has been previously reported.3) Exerciseat fixed ventricularrate: Nine patients in complete heart block with ventricular inhibited pacemakers set at 70b.p.m. were exercised according to the Bruce protocol. The relationship between atrial rate and pacing stimulus-T interval was measured during exercise and recovery using the methods described above except that by definition the paced QRS complex was wide and showed a left bundle branch block pattern due to right ventricular endocardial pacing. Fig. 1. An example of measurement of QT interval. Vol.22 No.3 RATE-QT INTERVAL RELATIONSHIP 347 Measurementof QT interval (Fig. 1): The measurement of QT interval was made from the direct recordings of standard lead II as described by Ashman et al and Simonson et al.4)-6) Care was taken to avoid including U or P waves in the measurements.7) Data was excluded if a change in the QRS-T morphology occurred either due to artefact, ischemic changes, conduction defects or ectopic beats. RESULTS Fig. 2 shows the results obtained during exercise for the patients in sinus rhythm. The data for the group as a whole indicate that the rate-QT inter- val relationship can be approximated by a linear regression equation such that QT interval is predicted by QT=522-1.87•~rate. The sub-division of patients on and off beta blocking agents indicates that although the resting and attained rates are necessarily lower for those pa- tients on beta blockers there is no change in the rate-QT relationship. The QT interval does not exhibit hysteresis in relation to rate changes as there is no difference in the rate-QT relationship when the rate is increasing during exercise or decreasing during recovery. Fig. 3 shows data obtained in atrially paced patients to increase heart rate. Although the QT interval decreases with increasing rate the slope of the rate-QT relationship is markedly flatter (QT=-0.66 rate+399). Thus an increase of 100b.p.m. due to atrial pacing would produce a QT decrease of approximately 66ms. Fig. 4 shows that in patients with heart block exercised at a fixed ven- tricular rate controlled by an implanted cardiac pacemaker. The atrial rate Fig. 2. QT plotted against heart rate (HR) during exercise. Dots for the patients taking beta blocking agents (15 patients) and asterisks for the pa- tients not taking beta blocking agents (10 patients). 348 AKHRAS AND RICKARDS Jpn. Heart M ay 1981 Fig. 3a. QT plotted against heart rate (HR) in atrially paced patients. Fig. 3b. Regression lines of rate-QT interval relationship during ex- ercise and atrial pacing. Note that the slope for the atrially paced patients is markedly flatter. was measured from the surface electrocardiogram and used as an indicator of the sympathetic and humoral stimulation occurring due to exercise. Al- though the ventricular rate remains unchanged throughout exercise there is a marked decrease in stimulus-T interval with increasing atrial rate (QT= -0 .95 rate+502) so that for a 100 beat atrial rate increase a decrease in QT interval of 95ms would be predicted. DISCUSSION The dichotomy between the QT interval changes due to physiological exercise and due to pacing induced changes in heart rate has been previously described by ourselves8) and suggested as a technique to determine the sensi- tivity of the sinus node in the sick sinus syndrome. A recent publication from Vol.22 No.3 RATE-QT INTERVAL RELATIONSHIP 349 Fig. 4. Patients with heart block exercised at a fixed ventricular rate. Stimulus-T interval plotted against atrial rate shows marked shortening of the stimulus-T interval with increasing atrial rate. Milne9) studying the changes in QT interval induced by propranolol at fixed atrial pacing rates confirms that the QT interval is not only dependent on rate but is also dependent on the change in catecholamine sensitivity of the heart induced by propranolol. Observations on skinned cardiac muscle using cal- cium pulses to induce contraction demonstrate that the cycle length does not influence the time course of the action potential.10) Thus the time of repolar- isation has no intrinsic relationship to heart rate. Observations on isolated mammalian cardiac muscle11)confirm that ca- techolamines enhance the rate of relaxation independent of heart rate, but ad- ditional and purely rate dependent shortening of the action potential has also been demonstrated,12) both of these observations are responsible for abbrevia- tion of systole necessary in mammalian heart at high heart rate to maintain adequate diastolic filling of the ventricles. The results from the atrial pacing study described here indicate that the intact heart does show some sensitivity of repolarisation time to rate, but of a far smaller magnitude than during physiological exercise. From data obtained from exercising patients in heart block it is apparent that QT interval is shortening independent of heart rate and therefore due to the effect of circulating catecholamines on the ventricular myocardium as there is effectively no direct communication between the autonomic nervous system and ventricular myocardium. The maintenance of the normal rela- tionship between QT interval and rate during exercise under the influence of propranolol implies that the effect of propranolol on blocking the sinus re- Jpn. Heart M 350 AKHRAS AND RICKARDS ay 1981 sponse to circulating catecholamines is accompanied by a similar action in blocking the effect of circulating catecholamines on repolarisation time of the ventricular myocardium. There is little doubt, therefore, that the decrease in QT interval observed during exercise induced changes in heart rate is mainly due to the effect of circulating catecholamines on the ventricular myocardium and not to the increase in heart rate itself.