Normal sinus heart rate: Sinus tachycardia sinus bradycardia redefined David H. Spodick,
MD, DSc Worcester,
Muss.
Heart rate abnormality, often an early clinical sign of disease, is simply and accurately measurable without special instrumentation. Thresholds for tachycardia and bradycardia, 100 beatslmin and 60 beatslmin, respectively, have long been taught as the limits of “normal sinus rhythm.” Leading authorities ascribe these numbers to “general acceptance”1-3 or state them without reference to formal studies.4, 5 Clinical experience suggests that both traditional thresholds are too high. Most physicians would be suspicious of resting heart rates in the range of 90 beatslmin and, particularly in this modern era of physical fitness, not especially suspicious of heart rates in the 50 beats/ min range. Of course, under undue autonomic arousal, disease-free individuals will often increase their heart rates, as for example in anticipation of a stressful procedure. What conductor of exercise tests has not seen the occasional patient with a resting control heart rate well in excess of 100 beats/min whose accelerated sinus rate temporarily slows in spite of the immediate withdrawal of vagal tone and the rapid increase in sympathetic stimulation6 with the onset of exercise? Methodology. We examined the problem of operational definitions for sinus tachycardia and sinus bradycardia in a clinically normal population.7 The subject group was 500 consecutive individuals who had returned repeatedly to a periodic adult screening clinic and who were familiar with that medical environment. All heart rates were measured by routine electrocardiography between 1 and 5 PM. We stressed environmental familiarity because of the cardiocirculatory effects of autonomic arousal in normal persons, epitomized by anticipation of any stressful procedure and by factors such as the well-known From t.he Department of Medicine, School, and the Cardiology Division, Received Reprmt Hospital, 4/1/39887
for publication requests: Worcester,
March
D. H. Spodick, MA 01604.
University St Vincent
2, 1992; MD,
accepted Cardiology
of Massachusetts Hospital. April
and
Medical
20, 1992.
Division.
St. Vincent
“white coat hypertension.” It was also important that the subjects not only be comfortable and not be facing a stressful procedure, but also that they not be invasively instrumented, since invasive instrumentation by its very presence modifies the individual’s physiologic milieu and responsiveness.8 Our 500 consecutive normal subjects happened to include 123 men and 367 women between the ages of 50 and 80 years. These patients were analyzed by quinquennium, with the results shown in Table I. The relation between heart rate and age was analyzed by linear regression analysis with confidence limits and significance testing of the correlation coefficients using Fisher’s Z-transformation: Z = % Ln [l + r)/ 1 - r], where I” is the correlation coefficient. Observations. Results are summarized in Table I. The group mean heart rates were 69.41 beats/min for men and 73.05 beatslmin for women, and all the mean quinquennial rates were between 67.2 and 74.7 beats/min. Regression analysis of heart rate against age yielded a correlation coefficient of 0.014 in men and of 0.063 in women-i.e., showing virtually no dependence of heart rate on age. Finally, in simplified terms, utilizing the 2 standard deviation rule for normal distributions, these results produced extremes of 51 and 95 beatslmin for women and 46 and 93 beats/ min for men.* Rate results in our investigation closely reflect those in the largest single series reporting studies of normal men and women-the Framingham Heart Study.g Participants without demonstrable disease measured by age decile between 35 and 44 years and between 75 and 84 years yielded mean heart rates of 74 to 76 beats/min, with a slight to absent age trend. It is understandable that in a study several times the size of ours the range would be somewhat “tighter,” but the means and the absence of an age trend are remarkably similar. Moreover, in studying a series of resting subjects in an even wider age range, between 20 and 80 years, FleglO reported approximate means between 72 and 68 beats/min, similar to ours without an age trend. Indeed, a number of series of nonin1119
1120
Spodick
Table
I. Heart rates by gender and age (N = 500)
American
~-.-
Male Mean Age br)
i
_---_-.-
Female S.D.
Cbeatslmin)
NO.
October 1992 Hearl Journal
Mean 95c;. Cl
No.
-t
S.D.
(beatslmin)
9.5:;
Cl
50-54 55-59 60-64 65-69 70-74 75-80
13 40 21 23 19 I
14.7 67.2 70.1 67.3 71.4 71.4
15.3 10.13 13.0 10.0 12.5 14.3
44.7-104.7 47.3-87.1 44.6-95.6 47.7-86.9 46.9-95.9 43.4-99.4
57 111 88 47 43 21
70.9 73.5 72.7 12.4 76.2 72.8
9.6 10.3 10.7 13 11.3 11.9
62.1-89.7 5X3-93.7 .51.7-93.7 46.9-97.9 54.1-98.3 49.5-96.1
Total
123
69.41
11.86
43.4-92.7
367
73.05
10.90
.51.7-94.4
CI, Confidence
interval.
strumented adult subjects used as normal controls for nonstressful investigations have shown comparable mean resting heart rates averaging about 70 beats/min.‘l-l4 Finally, since 2 standard deviations tend to represent the quite thin “tails” on any distribution curve, it appears that nearly all the subjects in these investigations, like those in our series, fit well into a clinically convenient (i.e., rounded) normal sinus heart rate range of between 50 and 90 beatslmin, rather than into the traditional 60 and 100 beatslmin range. Comments. In the absence of autonomic arousal, which itself could be considered a temporary cardiocirculatory abnormality, resting normal daytime heart rates for both men and women average close to 70 beats/min, a fact of which most, if not all, clinicians have been aware perhaps since the inception of clinical pulse rate measurement. The traditional limits of normal sinus rhythm, established as noted by general acceptance,lm3have been easy to remember, especially the tachycardia threshold, because 100 is a most convenient “round number.” However, traditional beliefs may exercise considerable power as psychologic blocks (think “tachycardia” only at 100 beats/min), a situation that could be ameliorated by more precise redefinition. The results of our investigation, in agreement with the other results cited, strongly indicate that few normal individuals have resting heart rates above 90 beats/min, so that those in that range should be investigated to some reasonable degree. Thus the clinician would be alerted to a possible tachycardia, without waiting for the 100 beat/min traditional threshold. Indeed, for patients with sepsis the definition of t,achycardia has recently been redefined as “over 90 beats/min.“15 Clinicians have similarly become used to seeing healthy individuals with resting heart rates in the 50 beats/min range in whom there would be little or no
indication for special investigation on the basis of heart rate alone. On this end of the scale, a threshold for bradycardia under 50 beatslmin appears to be more appropriate. Conclusions. Heart rate abnormality may be an early or a principal sign of disease or malfunction. The traditional normal sinus heart rate range, 60 to 100 beats/min, has been a matter of consensus (general agreement)le3 rather than the result of formal study. An investigation of 500 consecutive normal adult subjects yielded mean resting afternoon heart rates for men and women approximating 70 beats/ min, with no significant age-related trend, in agreement with epidemiologic and small clinical studies. Two standard deviations yielded rounded extremes of 46 and 93 beatslmin for men and 51 and 95 beats/ min for women. The absence of an age-related trend in our subjects and in others as young as 20 years old now permits proposing more appropriate rate standards for normal sinus rhythms in adults (irrespective of circadian variability). Thresholds for diagnosing sinus tachycardia and sinus bradycardia should be lowered. Clinicians should be alerted to a possible heart rate problem outside the range of 50 to 90 beatslmin rather than outside the range of 60 to 100 beats/min. For clinical purposes and as screening criteria, this shift in the operational definition of the normal sinus heart rate should improve the sensitivity of the tachycardia threshold and the specificity of the bradycardia threshold. REFERENCES
1. Chung EK. Principles of cardiac arrhythmias. Baltimore: Williams & Wilkins, 198956. 2. Zipes DP. Specific arrhythmias. In: Braunwald E, ed. Heart disease. ed. 3. Philadelphia: WB Saunders, 1988:663. 3. Chou T-C. Electrocardiography in clinical practice. ed. 3. Philadelphia: WB Saunders, 1991:299.
volume
124
Number
4
Normal
4. Marriott HJL. Practical electrocardiography. ed. 8. Baltimore: Williams & Wilkins, 1987:353. 5. Dunn MI, Lipman BS. Lipousa-Massie clinical electrocardiography. ed. 8. Chicago: Year Book Medical Publishers, 1989:345. 6. Xenakis A, Quarry VM, Spodick DH. Immediate cardiac response to exercise. AM HEART J 1975;89:178-85. 7. Spodick DH, Raju P, Bishop RL, Rifkin RD. Operational definition of normal sinus heart rate. Am J Cardiol 1992;69: 1245-6. 8. Spodick DH. Physiologic and prognostic implications of invasive monitoring. Am J Cardiol 1980;46:173-5. 9. Kannel WB, Kannel C, Paffenbarger RS Jr, Cupples LA. Heart rate and cardiovascular mortality: the Framingham Study. AM HEART J 1987;113:1489-94. 10. Fleg JC. Correlations in cardiovascular structure and function with advancing age. Am J Cardiol 1986;57:33C-44C.
The values and limitations clinical practice
sinus heart rate
11. Remes J, Helen M, Vaino P, Rautio P. Clinical outcome and left ventricular function 23 years after acute Coxsackie virus myopericarditis. Eur Heart J 1990;11:182-8. 12. Harrison MR, Clifton GD, Pennell AT, DeMaria AN. Effect of heart rate on left ventricular diastolic transmitral flow velocity patterns assessed by Doppler echocardiography in normal subjects. Am J Cardiol 1991;67:622-7. 13. Hayano J, Sakakibara Y, Yamada A, Yamada M, Mukai S, Fujinami T, Yokoyama K, Watanabe Y, Takata K. Accuracy of assessment of cardiac vagal tone by heart rate variability in normal subjects. Am J Cardiol 1991;67:199-204. 14. Vybiral T, Bryg RJ, Maddens ME, Boden WE. Effect of passive tilt on sympathetic and parasympathetic components of heart rate variability in normal subjects. Am J Cardiol 1989;63:117-20. 15. Bone RC. Gram-negative sepsis: background, clinical features, and interaction. Chest 1991;100:802-8.
of the QT interval
in
Paul Schweitzer, MD New York, N.Y.
The QT interval encompasses both depolarization and repolarization of the ventricular muscle. According to Burchell,’ the QT interval was first measured in the frog heart. by Burdo-Sanderson and Page in 1880, and the term “QT interval” was introduced by Einthoven. In 1920, Bazett? showed that the QT interval is related to ventricular systole and that its duration is influenced by the heart rate. His work led to the development of the formula to correct the QT interval for the heart rate (QT,).3 It is still in use today, although other equations have been developed and the search for the “best” one continues.4-11 Clinical interest in the QT interval started with the description of the congenital long QT syndrome (LQTS) 12-14and because of the role of the QT interval in drug-induced ventricular tachycardia.15s i6 More recently, it was suggested that a prolonged QT interval could be a marker for increased risk of sud-
From the Division of Cardiology, Department of Medicine, Bronx Veterans Affairs Medical Center, and Division of Cardiology, Department of Medicine, Mount Sinai School of Medicine. Received for publication Feb. 28, 1992; accepted April 16, 1992. Reprint requests: Paul Schweitzer, MD, Division of Cardiology, Bronx VAMC, Bronx NY 10468. 4/1/39686
den death in patients with ischemic heart disease17, l8 and diabetic neuropathy.lgl 2o Finally, some studie& 22 have evaluated the relationship between the QT interval and mortality in the general population with and without heart disease. Despite increased interest, the role of the QT interval in clinical electrocardiography is not completely settled. Among the controversial issues are the accuracy of the QT measurement,23-26 the usefulness of the Bazett formula for calculating the QTc,27-32 the normal value of the QTc,33 and the role of the QT interval in patients with polymorphic ventricular tachycardia (PVT)34s 35 and myocardial infarction.17, ls The purpose of this article is to review the values and limitations of the QT interval in clinical practice. Electrophysiologic basis for the QT interval. The ST segment corresponds to phase 2 (the plateau phase) of the action potential. Its duration is dependent on the heart rate and on the extracellular concentration of Ca and catecholamines. The T wave corresponds to phase 3 (rapid phase) of the action potential. Its duration, amplitude, and morphology are influenced by myocardial diseases, the autonomic nervous system, the potassium concentration, and by various drugs.36 Measurement of the QT interval. The lead or leads in 1121
MD, DSc Worcester,
Muss.
Heart rate abnormality, often an early clinical sign of disease, is simply and accurately measurable without special instrumentation. Thresholds for tachycardia and bradycardia, 100 beatslmin and 60 beatslmin, respectively, have long been taught as the limits of “normal sinus rhythm.” Leading authorities ascribe these numbers to “general acceptance”1-3 or state them without reference to formal studies.4, 5 Clinical experience suggests that both traditional thresholds are too high. Most physicians would be suspicious of resting heart rates in the range of 90 beatslmin and, particularly in this modern era of physical fitness, not especially suspicious of heart rates in the 50 beats/ min range. Of course, under undue autonomic arousal, disease-free individuals will often increase their heart rates, as for example in anticipation of a stressful procedure. What conductor of exercise tests has not seen the occasional patient with a resting control heart rate well in excess of 100 beats/min whose accelerated sinus rate temporarily slows in spite of the immediate withdrawal of vagal tone and the rapid increase in sympathetic stimulation6 with the onset of exercise? Methodology. We examined the problem of operational definitions for sinus tachycardia and sinus bradycardia in a clinically normal population.7 The subject group was 500 consecutive individuals who had returned repeatedly to a periodic adult screening clinic and who were familiar with that medical environment. All heart rates were measured by routine electrocardiography between 1 and 5 PM. We stressed environmental familiarity because of the cardiocirculatory effects of autonomic arousal in normal persons, epitomized by anticipation of any stressful procedure and by factors such as the well-known From t.he Department of Medicine, School, and the Cardiology Division, Received Reprmt Hospital, 4/1/39887
for publication requests: Worcester,
March
D. H. Spodick, MA 01604.
University St Vincent
2, 1992; MD,
accepted Cardiology
of Massachusetts Hospital. April
and
Medical
20, 1992.
Division.
St. Vincent
“white coat hypertension.” It was also important that the subjects not only be comfortable and not be facing a stressful procedure, but also that they not be invasively instrumented, since invasive instrumentation by its very presence modifies the individual’s physiologic milieu and responsiveness.8 Our 500 consecutive normal subjects happened to include 123 men and 367 women between the ages of 50 and 80 years. These patients were analyzed by quinquennium, with the results shown in Table I. The relation between heart rate and age was analyzed by linear regression analysis with confidence limits and significance testing of the correlation coefficients using Fisher’s Z-transformation: Z = % Ln [l + r)/ 1 - r], where I” is the correlation coefficient. Observations. Results are summarized in Table I. The group mean heart rates were 69.41 beats/min for men and 73.05 beatslmin for women, and all the mean quinquennial rates were between 67.2 and 74.7 beats/min. Regression analysis of heart rate against age yielded a correlation coefficient of 0.014 in men and of 0.063 in women-i.e., showing virtually no dependence of heart rate on age. Finally, in simplified terms, utilizing the 2 standard deviation rule for normal distributions, these results produced extremes of 51 and 95 beatslmin for women and 46 and 93 beats/ min for men.* Rate results in our investigation closely reflect those in the largest single series reporting studies of normal men and women-the Framingham Heart Study.g Participants without demonstrable disease measured by age decile between 35 and 44 years and between 75 and 84 years yielded mean heart rates of 74 to 76 beats/min, with a slight to absent age trend. It is understandable that in a study several times the size of ours the range would be somewhat “tighter,” but the means and the absence of an age trend are remarkably similar. Moreover, in studying a series of resting subjects in an even wider age range, between 20 and 80 years, FleglO reported approximate means between 72 and 68 beats/min, similar to ours without an age trend. Indeed, a number of series of nonin1119
1120
Spodick
Table
I. Heart rates by gender and age (N = 500)
American
~-.-
Male Mean Age br)
i
_---_-.-
Female S.D.
Cbeatslmin)
NO.
October 1992 Hearl Journal
Mean 95c;. Cl
No.
-t
S.D.
(beatslmin)
9.5:;
Cl
50-54 55-59 60-64 65-69 70-74 75-80
13 40 21 23 19 I
14.7 67.2 70.1 67.3 71.4 71.4
15.3 10.13 13.0 10.0 12.5 14.3
44.7-104.7 47.3-87.1 44.6-95.6 47.7-86.9 46.9-95.9 43.4-99.4
57 111 88 47 43 21
70.9 73.5 72.7 12.4 76.2 72.8
9.6 10.3 10.7 13 11.3 11.9
62.1-89.7 5X3-93.7 .51.7-93.7 46.9-97.9 54.1-98.3 49.5-96.1
Total
123
69.41
11.86
43.4-92.7
367
73.05
10.90
.51.7-94.4
CI, Confidence
interval.
strumented adult subjects used as normal controls for nonstressful investigations have shown comparable mean resting heart rates averaging about 70 beats/min.‘l-l4 Finally, since 2 standard deviations tend to represent the quite thin “tails” on any distribution curve, it appears that nearly all the subjects in these investigations, like those in our series, fit well into a clinically convenient (i.e., rounded) normal sinus heart rate range of between 50 and 90 beatslmin, rather than into the traditional 60 and 100 beatslmin range. Comments. In the absence of autonomic arousal, which itself could be considered a temporary cardiocirculatory abnormality, resting normal daytime heart rates for both men and women average close to 70 beats/min, a fact of which most, if not all, clinicians have been aware perhaps since the inception of clinical pulse rate measurement. The traditional limits of normal sinus rhythm, established as noted by general acceptance,lm3have been easy to remember, especially the tachycardia threshold, because 100 is a most convenient “round number.” However, traditional beliefs may exercise considerable power as psychologic blocks (think “tachycardia” only at 100 beats/min), a situation that could be ameliorated by more precise redefinition. The results of our investigation, in agreement with the other results cited, strongly indicate that few normal individuals have resting heart rates above 90 beats/min, so that those in that range should be investigated to some reasonable degree. Thus the clinician would be alerted to a possible tachycardia, without waiting for the 100 beat/min traditional threshold. Indeed, for patients with sepsis the definition of t,achycardia has recently been redefined as “over 90 beats/min.“15 Clinicians have similarly become used to seeing healthy individuals with resting heart rates in the 50 beats/min range in whom there would be little or no
indication for special investigation on the basis of heart rate alone. On this end of the scale, a threshold for bradycardia under 50 beatslmin appears to be more appropriate. Conclusions. Heart rate abnormality may be an early or a principal sign of disease or malfunction. The traditional normal sinus heart rate range, 60 to 100 beats/min, has been a matter of consensus (general agreement)le3 rather than the result of formal study. An investigation of 500 consecutive normal adult subjects yielded mean resting afternoon heart rates for men and women approximating 70 beats/ min, with no significant age-related trend, in agreement with epidemiologic and small clinical studies. Two standard deviations yielded rounded extremes of 46 and 93 beatslmin for men and 51 and 95 beats/ min for women. The absence of an age-related trend in our subjects and in others as young as 20 years old now permits proposing more appropriate rate standards for normal sinus rhythms in adults (irrespective of circadian variability). Thresholds for diagnosing sinus tachycardia and sinus bradycardia should be lowered. Clinicians should be alerted to a possible heart rate problem outside the range of 50 to 90 beatslmin rather than outside the range of 60 to 100 beats/min. For clinical purposes and as screening criteria, this shift in the operational definition of the normal sinus heart rate should improve the sensitivity of the tachycardia threshold and the specificity of the bradycardia threshold. REFERENCES
1. Chung EK. Principles of cardiac arrhythmias. Baltimore: Williams & Wilkins, 198956. 2. Zipes DP. Specific arrhythmias. In: Braunwald E, ed. Heart disease. ed. 3. Philadelphia: WB Saunders, 1988:663. 3. Chou T-C. Electrocardiography in clinical practice. ed. 3. Philadelphia: WB Saunders, 1991:299.
volume
124
Number
4
Normal
4. Marriott HJL. Practical electrocardiography. ed. 8. Baltimore: Williams & Wilkins, 1987:353. 5. Dunn MI, Lipman BS. Lipousa-Massie clinical electrocardiography. ed. 8. Chicago: Year Book Medical Publishers, 1989:345. 6. Xenakis A, Quarry VM, Spodick DH. Immediate cardiac response to exercise. AM HEART J 1975;89:178-85. 7. Spodick DH, Raju P, Bishop RL, Rifkin RD. Operational definition of normal sinus heart rate. Am J Cardiol 1992;69: 1245-6. 8. Spodick DH. Physiologic and prognostic implications of invasive monitoring. Am J Cardiol 1980;46:173-5. 9. Kannel WB, Kannel C, Paffenbarger RS Jr, Cupples LA. Heart rate and cardiovascular mortality: the Framingham Study. AM HEART J 1987;113:1489-94. 10. Fleg JC. Correlations in cardiovascular structure and function with advancing age. Am J Cardiol 1986;57:33C-44C.
The values and limitations clinical practice
sinus heart rate
11. Remes J, Helen M, Vaino P, Rautio P. Clinical outcome and left ventricular function 23 years after acute Coxsackie virus myopericarditis. Eur Heart J 1990;11:182-8. 12. Harrison MR, Clifton GD, Pennell AT, DeMaria AN. Effect of heart rate on left ventricular diastolic transmitral flow velocity patterns assessed by Doppler echocardiography in normal subjects. Am J Cardiol 1991;67:622-7. 13. Hayano J, Sakakibara Y, Yamada A, Yamada M, Mukai S, Fujinami T, Yokoyama K, Watanabe Y, Takata K. Accuracy of assessment of cardiac vagal tone by heart rate variability in normal subjects. Am J Cardiol 1991;67:199-204. 14. Vybiral T, Bryg RJ, Maddens ME, Boden WE. Effect of passive tilt on sympathetic and parasympathetic components of heart rate variability in normal subjects. Am J Cardiol 1989;63:117-20. 15. Bone RC. Gram-negative sepsis: background, clinical features, and interaction. Chest 1991;100:802-8.
of the QT interval
in
Paul Schweitzer, MD New York, N.Y.
The QT interval encompasses both depolarization and repolarization of the ventricular muscle. According to Burchell,’ the QT interval was first measured in the frog heart. by Burdo-Sanderson and Page in 1880, and the term “QT interval” was introduced by Einthoven. In 1920, Bazett? showed that the QT interval is related to ventricular systole and that its duration is influenced by the heart rate. His work led to the development of the formula to correct the QT interval for the heart rate (QT,).3 It is still in use today, although other equations have been developed and the search for the “best” one continues.4-11 Clinical interest in the QT interval started with the description of the congenital long QT syndrome (LQTS) 12-14and because of the role of the QT interval in drug-induced ventricular tachycardia.15s i6 More recently, it was suggested that a prolonged QT interval could be a marker for increased risk of sud-
From the Division of Cardiology, Department of Medicine, Bronx Veterans Affairs Medical Center, and Division of Cardiology, Department of Medicine, Mount Sinai School of Medicine. Received for publication Feb. 28, 1992; accepted April 16, 1992. Reprint requests: Paul Schweitzer, MD, Division of Cardiology, Bronx VAMC, Bronx NY 10468. 4/1/39686
den death in patients with ischemic heart disease17, l8 and diabetic neuropathy.lgl 2o Finally, some studie& 22 have evaluated the relationship between the QT interval and mortality in the general population with and without heart disease. Despite increased interest, the role of the QT interval in clinical electrocardiography is not completely settled. Among the controversial issues are the accuracy of the QT measurement,23-26 the usefulness of the Bazett formula for calculating the QTc,27-32 the normal value of the QTc,33 and the role of the QT interval in patients with polymorphic ventricular tachycardia (PVT)34s 35 and myocardial infarction.17, ls The purpose of this article is to review the values and limitations of the QT interval in clinical practice. Electrophysiologic basis for the QT interval. The ST segment corresponds to phase 2 (the plateau phase) of the action potential. Its duration is dependent on the heart rate and on the extracellular concentration of Ca and catecholamines. The T wave corresponds to phase 3 (rapid phase) of the action potential. Its duration, amplitude, and morphology are influenced by myocardial diseases, the autonomic nervous system, the potassium concentration, and by various drugs.36 Measurement of the QT interval. The lead or leads in 1121
