Adv. Cardiol., vol. 18, pp. 208-216 (Karger, Basel 1976)
Epidemiology and Prevention of Ventricular Ectopic Rhythms 1 H. BLACKBURN, G. DE BACKER, R. CROW, R. PRINEAS and D. JACOBS Laboratory of Physiological Hygiene, School of Public Health, University of Minnesota, Minneapolis, Minn.
1 Supported in part by National Heart and Lung Institute grants: HL 16573-01 'Studies Related to the Prevention of Sudden Death', and NOI HL 22976 'Multiple Risk Factor Intervention Trial'.
Downloaded by: University of Cambridge 131.111.164.128 - 1/31/2019 6:12:04 PM
Little more is known today about the ultimate significance of ventricular premature beats (VPB) than that known by LEWIS [4] in 1912, whose classic Disorders of the Heartbeat will be quoted frequently herein. Nevertheless, information has been collected in recent years about the longer term prognostic importance of ectopic ventricular rhythms, both in coronary care units and in free-living populations. Most of the information to date suggests that VPB in ambulant coronary heart disease patients are probably important harbingers of future risk of death or sudden death. It is not yet entirely clear whether this contribution to risk is independent of the clinical state and whether lethal cardiac rhythms are directly and causally related to the frequency or the nature of ectopic beats. Particularly it is not established whether intervention on ectopic beats is effective in reducing risk. Current information also suggests that there is little or no predictive information in the frequency and nature of simple uniform VPB in general popUlations or groups of individuals without clinically manifest ischemic myocardial disease. It is also not known whether VPB are important among that intermediate category of individuals having only subclinical or electrocardiographically manifest myocardial ischemia. Finally, with the exception of one encouraging report on the effect of beta-blockade therapy from Sweden, there is no evidence that long-term arrhythmia-suppressive therapy is effective or appropriately safe in reducing the risk of reinfarction or sudden death. The experience of this Laboratory is summarized briefly for the Paavo Nurmi Symposium.
BLACKBURN/DE BACKER/CROW/PRINEAS/JACOBS
209
Premature beats are: '... responses of the heart to new and isolated impulses formed in the musculature; contractions which occur before the anticipated time and which consequently disturb the normal order of the heart mechanism' [4]. A systematic effort is underway in the Laboratory of Physiological Hygiene and elsewhere to describe the frequency, distribution, and characteristics associated with VPB in populations outside hospital, to determine their independent prognostic importance and to test the potential of physiological hygiene in modifying their frequency. The experience of this laboratory is outlined here with the intention to illustrate an epidemiological and community approach to an interesting cardiovascular phenomenon and a controlled hygienic approach to intervention on the characteristic. Studies on the frequency, associations, prognostic importance, and prevention ofVPB proceed in parallel in several populations under observation. Because findings are not complete, this presentation will concern itself with the rationale and the methodology as prominently as with the preliminary results.
Census tracts in the Twin Cities of Minnesota were preselected for residential stability as the local catchment area for a large multicenter national prevention trial (MRFIT) sponsored by the National Heart, Lung and Blood Institute. Approval of a special VPB study as an ancillary project of MRFIT resulted in addition of an arrhythmia detection procedure as the last station in the first phase population screening in the community. VPB screening was carried out in 10,880 men, aged 35-57, representing a 95% response rate to accepted invitations of age-eligible men and approximately an 80% response rate of all men of these ages in the community catchment area. A 2 min, lead I electrocardiogram (ECG) was recorded in a semirecumbent position at 10 mm/sec paper speed for each man while seated in a large comfortable chair under quiet testing conditions. The ECG station was preceded by explanations and signed consent, a demographic and health questionnaire, blood pressure measurements and venipuncture. In the standard rhythm strip, a technician was trained to identify, count and classify VPB as well as other Minnesota Code findings in the single lead ECG. Ectopic beat classifications were based on special Minnesota criteria avail-
Downloaded by: University of Cambridge 131.111.164.128 - 1/31/2019 6:12:04 PM
VP B Detection: Population Screening
BLACKBURN/DE BACKER/CROW/PRINEAS/JACOBS
210
able from this Center. Technician coding was done systematically in duplicate and disagreements resolved by an electrocardiographer. Serum cholesterol determinations were performed in a standard fashion using a Technicon Autoanalyzer II under rigid internal and external quality control. Blood pressure values used in analysis were based on the mean of the last two seated blood pressure readings recorded by technicians certified in population blood pressure survey techniques. A coronary risk score was computed based on multiple regression coefficients from experience in men of appropriate age in the Framingham study, as applied to the MRFIT screening values found for second phase diastolic blood pressure, serum cholesterol level, and the number of cigarettes currently smoked daily.
VPB Frequency: Screening Results
540 men, or 4.96% of the 10,880 men screened, had one or more VPB in the screening detection procedure. Uniform simple VPB occurred in 459 (4.21 %) and complex forms were detected in 0.7%. Complex forms included 0.5% of men with multiform VPB, 0.2% with pairs, runs, or R/T ectopic beats. Simple frequent VPB (10 or more VPB within the 2 min monitoring strip) occurred with the frequency of 0.9% [3].
' ... if the age distribution of the populace is considered ... , it becomes evident that essentially they [VPB] are a phenomenon of advancing years. It is probable that the majority of people who live to middle life or advanced years are affected in this manner at some time or other. Of the factors which appear to be predominantly associated with them [VPB], gross lesions of the heart stand first. Otherwise, an inquiry into the habits, history and state of the patients throws but an obscure light upon the causation. In young adults, excessive tobacco smoking is recognized as an exciting cause of their temporary appearance. There are also clinical associations between premature contractions, raised arterial pressure and digestive disturbances, but these are not fully understood at the present time. Fatigue, subsequent to exertion, is provocative in those who are predisposed. The influence of heart rate is especially noteworthy. Hearts beating at 100/min and over are often not disturbed, and premature contractions are very rare when the heart rate
Downloaded by: University of Cambridge 131.111.164.128 - 1/31/2019 6:12:04 PM
VP B Associations
VPB Epidemiology and Prevention
211
exceeds 120. No factor is more potent than posture. Patients who exhibit numerous premature contractions while standing, may soon lose them in recumbency, and this despite a slight decrease of heart rate in the last position' [4]. Analysis in this series reveals a strong relationship between the occurrence and the frequency of uniform simple VPB, age and systolic blood pressure. Relationship with diastolic blood pressure was not as clear and there was no significant relationship with smoking habit or serum cholesterol level. An important positive relationship was found between VPB and other electrocardiographic findings, particularly negative T waves at rest on the screening strip. A coronary risk score was computed from the three primary coronary risk variables of diastolic blood pressure, serum cholesterol, and cigarettes smoked. These were found unrelated to VPB in univariate analyses. VPB were also found unrelated to a multivariate risk score calculated from these items [3]. In conclusion, screening for individuals with frequent ectopic ventricular rhythms is feasible using simple equipment in a rapid screening situation associated with a primary coronary risk factor screening station. A 2-min rhythm strip is two thirds repeatable and has a sufficient yield with respect to later more detailed monitoring measures. Something on the order of 5% of free-living men in general populations will exhibit some VPB in such a screening situation. These manifestations are strongly related to the duration of monitoring period, the individual's age and systolic blood pressure level, and to the presence of non-specific electrocardiographic findings.
The second stage of a community approach to VPB screening and detection was an invitation to the central laboratory of those men having any VPB during the primary resting 2-min screen, to ascertain: (1) the efficacy of the primary screening strip to detect those having frequent or complex VPB under standard and more complete VPB monitoring; (2) the repeat variability of the 2-min rhythm strip, and (3) the response rate to the invitation of age eligibles in the population. In each of two extra visits to the central laboratory, the following tests were administered to all those having VPB in the primary screening center: (1) a repeat two-minute single-lead rhythm strip; (2) a conventional resting
Downloaded by: University of Cambridge 131.111.164.128 - 1/31/2019 6:12:04 PM
VPB Detection: Second Stage
BLACKBURN/DE BACKER/CRow/PRlNEAS/JAcoBs
212
12-lead ECG; (3) a VPB induction test to be described, and (4) a 24-hour Holter monitoring tape in a subsample. The identical procedure was administered to a subsample of men having no VPB at the primary screen, but this experience will be reported elsewhere. The VPB induction test consists of: (1) carotid sinus pressure; (2) mental stress in the form of mirror drawing; (3) cold stress in the form of hand immersion in ice water; (4) isometric stress in the form of a handgrip exercise, and (5) progressive treadmill stress to voluntary maximal capacity.
' ... they [VPB] are abolished during exercise and for a short period afterwards, but during the period of slow heart action which often follows exercise, they are frequent. As we shall subsequently see, this knowledge may often be used advantageously to induce premature beats in patients predisposed to them' [4]. Only preliminary results on the second stage testing are available from the first 210 men having VPB at the first stage screen. These men were issued a single mail plus telephone invitation to an orientation meeting, to explain the question of VPB and the scientific study being made of them. 100 men appeared from whom 70 volunteered for the study and in which 54 were determined medically eligible. In this first group, the repeatability of the 2-min screening strip in the same posture and conditions was 66% for any VPB and 67% for the same frequency class of VPB. Thus, a rapid community screening process for ectopic rhythms is repeatable in about two thirds of instances. Test-retest repeatability of the VPB induction test, including all the stress procedures, is approximately 90% for the presence of any VPB, 66% for any complex VPB, and very low (8%) for runs of ventricular tachycardia. The yield of VPB from each facet of the VPB induction test was complementary to that from the other. The progressive treadmill exercise gave the largest independent fraction of the total VPB yield. The mental stress used was largely ineffective in inducing VPB. Each aspect of the test except for the mirror image drawing revealed some extra information. There was a unique yield of VPB in each phase of standing rest, progressive exercise and recovery. It was more frequent that exercise suppressed VPB than that it induced VPB. Complex VPB or very frequent VPB were more likely to occur in those who had frequent uniform VPB during the resting state.
Downloaded by: University of Cambridge 131.111.164.128 - 1/31/2019 6:12:04 PM
Results of Second Stage VP B Detection
VPB Epidemiology and Prevention
213
Table 1. VPB and prognosis for CHD death. Ten-year experience in the Seven Countries Study [2]
NoVPB
Rest ECG Exercise ECG
VPB Present
N
CHD deaths
%
N
CHD deaths
%
10,621 10,546
323 324
(3.04) (3.07)
149 245
9 8
(6.04) (3.26)
' ... our inquiries are as to whether a heart, which presents no other sign, can be regarded as healthy and as to whether, in the case of an unhealthy heart, the prospect [of VPB] has an added gloom. A number of people are temporarily affected by premature beats which do not reappear, while the heart manifests no sign of further damage, either at the time or afterwards. It may be said, therefore, that in themselves premature beats cannot be regarded as evidence of serious involvement of the heart muscle, although such involvement is often found in conjunction with them. It follows that of hearts seen today, some of which show premature contractions and some of which show none, the incidence of grave irregularities will in later years be greater in the former than in the latter' [4]. Table I represents 10 years follow-up in 10,770 men aged 40-59 free of manifest coronary heart disease at entry into the previously reported Seven Countries Study [5]. The crude relationship shown here between VPB and CHD incidence becomes weak and inconsistent when age, blood pressure and coronary risk scores are accounted for. It is concluded that there is no significant independent predictive information in VPB at rest or induced by exercise for coronary disease risk in middle-aged men clinically free of coronary disease. This is not to say that there is absolutely no possible relationship, nor that an occasional case of sudden death may be directly related to events precipitated by a series of VPB. Furthermore, it does not say that effective intervention on ectopic beats might not modify risk in some clinical groups. It does suggest, however, that the predictive relationship is overall weak and that intervention on VPB is unlikely to have a powerful effect on the frequency of sudden coronary death in persons at high risk due to primary coronary risk factors.
Downloaded by: University of Cambridge 131.111.164.128 - 1/31/2019 6:12:04 PM
Prognosis of VP B
BLACKBURN/DE BACKER/CRow/PRINEAS/JACOBS
214
Long-term VPB suppressive drug therapy, at sufficient levels to reduce ectopic activity significantly, has not yet been demonstrated to be safe or efficacious. However, because of many anecdotal reports and clinical impressions which relate cardiac excitability and VPB to poor physiological hygiene, to debauche, to coffee drinking, stimulants and smoking, a crossover controlled trial was designed to test the hypothesis that hygienic intervention might suppress VPB. Men recruited in the earlier screening stages with VPB detection, described earlier, and having consistent demonstrations of ectopic activity at rest and in VPB stress induction tests, are now actively enrolled in the hygienic intervention trial depicted in figure 1. Eligible men, free of clinically manifest cardiac disease and demonstrated to have persistent quantifiable ectopic activity under these standard testing conditions, have been randomly assigned to three groups. Group A is advised to make no change in their lifestyle. Group B is advised and provided supportive counselling therapy to stop smoking entirely, to avoid coffee, tea, and chocolate as sources of stimulants, to abstain from more than two drinks daily or four drinks total per week, to avoid all stimulant over-the-counter drugs and to get a comfortable amount of sleep every night during the six-week experimental period. Group C receives the same hygienic interventions plus progressive conditioning exercise in three hourly sessions per w~ek at the local YM CA facility. To strengthen the design, the control group is offered the complete intervention program, including physical conditioning, in a cross-over procedure after the first six weeks. The initial experimental groups are also requested to cross-over and to resume previous lifestyles (with the exception of recommencing cigarette smoking which is not recommended). Another six-week experimental period is followed by complete retesting. Experience to date reveals remarkable collaboration of the participants and almost total adherence to the experimental program, with little contamination of controls behavior. Participants are now in the cross-over stage of the design and results are not ready for reporting. Reports from an earlier pilot project exposed 196 men, aged 45-54 to a 15- to 18-month conditioning program, also based on three times a week hourly exercise sessions. VPB in that study were measured by a standard progressive exercise test. Significant physical conditioning was achieved based on changes in submaximal heart rate at a given external work load [1]. The statistical power of that study was not large to demonstrate a clearcut effect of hygiene and physical conditioning due to the method of measure-
Downloaded by: University of Cambridge 131.111.164.128 - 1/31/2019 6:12:04 PM
VPB Suppression by Physiological Hygiene
215
VPB Epidemiology and Prevention Randomization I
A I Control
I
Randomization
I
C
I
Hygiene plus conditioning
Six-week examination and VPB tests
Hygiene plus conditioning
I I
Control
Control
Twelve-week examination and VPB tests
Fig. 1. Partial cross-over design of VPB intervention trial.
ment and the numbers of individuals. However, the findings were sufficiently suggestive that more definitive studies were felt indicated. Among those who adhered effectively to the exercise session, there was a reduction in the number of men having exercise-induced VPB, as well as in the number of VPB per man. There seemed also to be an elevation of the threshold of exercise at which VPB were induced. Results of the current controlled cross-over experiment are eagerly awaited. Irrespective of the results in these healthy men, it may be that the potential for reducing cardiac excitability, frequency and seriousness ofVPB in manifest coronary disease patients is sufficient to recommend a similar randomized trial among such patients. The mechanisms of VPB may be different in them; certainly, their need for safe suppressant therapy is great.
Current work of the Laboratory of Physiological Hygiene is reviewed on the epidemiology and prevention of ectopic ventricular rhythms (VPB). The evidence suggests that uniform simple VPB at rest, or exercise-induced, are prognostically important only in those having clinically manifest coronary disease. A simple rhythm strip is an effective first screen method for detecting individuals having rather frequent VPB, and frequency of VPB is correlated with complex ectopic rhythms. A multifaceted stress induction test induces VPB and does it consistently. Hygienic intervention, in which cardiac stimulants are removed and conditioning exercises given, is being tested as VPB suppressive therapy.
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Summary
BLACKBURN/DE BACICER/CROW/PruNEAS/JACOBS
216
References
2
3
4 5
BLACKBURN, H.; TAYLOR, H. L.; HAMRELL, B.; BUSKIRK, E.; NICHOLAS, W. c., and THORSEN, R. D.: Premature ventricular complexes induced by stress testing. Am. J. Cardiol. 31,' 441-449 (1973). BLACKBURN, H.; KEyS, A.; ARAVANIS, C.; BUCHEM, F. S. P. VAN; BUZINA, R.; DJORDJEVIC, B. S.; FIDANZA, F.; KARVONEN, M.; MENOTTI, A.; PUNSAR, S., and TAYLOR, H. L.: The ECG in population studies. Prediction (in preparation). CROW, R.; PRlNEAS, R.; DIAS, V.; TAYLOR, H. L.; JACOBS, D., and BLACKBURN, H.: Ventricular premature beats in a population sample. Frequency and association with coronary risk characteristics. Circulation Suppl. III 51/52,' 211-215 (1975). LEWIS, T.: Clinical disorders of the heartbeat (Shaw & Sons, London 1912). KEYS, A.: Coronary heart disease in seven countries. Circulation 41,' suppl.l (1970).
HENRY BLACKBURN, MD, Laboratory of Physiological Hygiene, School of Public Health, University of Minnesota, Minneapolis, MN 55455 (USA)
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1
Epidemiology and Prevention of Ventricular Ectopic Rhythms 1 H. BLACKBURN, G. DE BACKER, R. CROW, R. PRINEAS and D. JACOBS Laboratory of Physiological Hygiene, School of Public Health, University of Minnesota, Minneapolis, Minn.
1 Supported in part by National Heart and Lung Institute grants: HL 16573-01 'Studies Related to the Prevention of Sudden Death', and NOI HL 22976 'Multiple Risk Factor Intervention Trial'.
Downloaded by: University of Cambridge 131.111.164.128 - 1/31/2019 6:12:04 PM
Little more is known today about the ultimate significance of ventricular premature beats (VPB) than that known by LEWIS [4] in 1912, whose classic Disorders of the Heartbeat will be quoted frequently herein. Nevertheless, information has been collected in recent years about the longer term prognostic importance of ectopic ventricular rhythms, both in coronary care units and in free-living populations. Most of the information to date suggests that VPB in ambulant coronary heart disease patients are probably important harbingers of future risk of death or sudden death. It is not yet entirely clear whether this contribution to risk is independent of the clinical state and whether lethal cardiac rhythms are directly and causally related to the frequency or the nature of ectopic beats. Particularly it is not established whether intervention on ectopic beats is effective in reducing risk. Current information also suggests that there is little or no predictive information in the frequency and nature of simple uniform VPB in general popUlations or groups of individuals without clinically manifest ischemic myocardial disease. It is also not known whether VPB are important among that intermediate category of individuals having only subclinical or electrocardiographically manifest myocardial ischemia. Finally, with the exception of one encouraging report on the effect of beta-blockade therapy from Sweden, there is no evidence that long-term arrhythmia-suppressive therapy is effective or appropriately safe in reducing the risk of reinfarction or sudden death. The experience of this Laboratory is summarized briefly for the Paavo Nurmi Symposium.
BLACKBURN/DE BACKER/CROW/PRINEAS/JACOBS
209
Premature beats are: '... responses of the heart to new and isolated impulses formed in the musculature; contractions which occur before the anticipated time and which consequently disturb the normal order of the heart mechanism' [4]. A systematic effort is underway in the Laboratory of Physiological Hygiene and elsewhere to describe the frequency, distribution, and characteristics associated with VPB in populations outside hospital, to determine their independent prognostic importance and to test the potential of physiological hygiene in modifying their frequency. The experience of this laboratory is outlined here with the intention to illustrate an epidemiological and community approach to an interesting cardiovascular phenomenon and a controlled hygienic approach to intervention on the characteristic. Studies on the frequency, associations, prognostic importance, and prevention ofVPB proceed in parallel in several populations under observation. Because findings are not complete, this presentation will concern itself with the rationale and the methodology as prominently as with the preliminary results.
Census tracts in the Twin Cities of Minnesota were preselected for residential stability as the local catchment area for a large multicenter national prevention trial (MRFIT) sponsored by the National Heart, Lung and Blood Institute. Approval of a special VPB study as an ancillary project of MRFIT resulted in addition of an arrhythmia detection procedure as the last station in the first phase population screening in the community. VPB screening was carried out in 10,880 men, aged 35-57, representing a 95% response rate to accepted invitations of age-eligible men and approximately an 80% response rate of all men of these ages in the community catchment area. A 2 min, lead I electrocardiogram (ECG) was recorded in a semirecumbent position at 10 mm/sec paper speed for each man while seated in a large comfortable chair under quiet testing conditions. The ECG station was preceded by explanations and signed consent, a demographic and health questionnaire, blood pressure measurements and venipuncture. In the standard rhythm strip, a technician was trained to identify, count and classify VPB as well as other Minnesota Code findings in the single lead ECG. Ectopic beat classifications were based on special Minnesota criteria avail-
Downloaded by: University of Cambridge 131.111.164.128 - 1/31/2019 6:12:04 PM
VP B Detection: Population Screening
BLACKBURN/DE BACKER/CROW/PRINEAS/JACOBS
210
able from this Center. Technician coding was done systematically in duplicate and disagreements resolved by an electrocardiographer. Serum cholesterol determinations were performed in a standard fashion using a Technicon Autoanalyzer II under rigid internal and external quality control. Blood pressure values used in analysis were based on the mean of the last two seated blood pressure readings recorded by technicians certified in population blood pressure survey techniques. A coronary risk score was computed based on multiple regression coefficients from experience in men of appropriate age in the Framingham study, as applied to the MRFIT screening values found for second phase diastolic blood pressure, serum cholesterol level, and the number of cigarettes currently smoked daily.
VPB Frequency: Screening Results
540 men, or 4.96% of the 10,880 men screened, had one or more VPB in the screening detection procedure. Uniform simple VPB occurred in 459 (4.21 %) and complex forms were detected in 0.7%. Complex forms included 0.5% of men with multiform VPB, 0.2% with pairs, runs, or R/T ectopic beats. Simple frequent VPB (10 or more VPB within the 2 min monitoring strip) occurred with the frequency of 0.9% [3].
' ... if the age distribution of the populace is considered ... , it becomes evident that essentially they [VPB] are a phenomenon of advancing years. It is probable that the majority of people who live to middle life or advanced years are affected in this manner at some time or other. Of the factors which appear to be predominantly associated with them [VPB], gross lesions of the heart stand first. Otherwise, an inquiry into the habits, history and state of the patients throws but an obscure light upon the causation. In young adults, excessive tobacco smoking is recognized as an exciting cause of their temporary appearance. There are also clinical associations between premature contractions, raised arterial pressure and digestive disturbances, but these are not fully understood at the present time. Fatigue, subsequent to exertion, is provocative in those who are predisposed. The influence of heart rate is especially noteworthy. Hearts beating at 100/min and over are often not disturbed, and premature contractions are very rare when the heart rate
Downloaded by: University of Cambridge 131.111.164.128 - 1/31/2019 6:12:04 PM
VP B Associations
VPB Epidemiology and Prevention
211
exceeds 120. No factor is more potent than posture. Patients who exhibit numerous premature contractions while standing, may soon lose them in recumbency, and this despite a slight decrease of heart rate in the last position' [4]. Analysis in this series reveals a strong relationship between the occurrence and the frequency of uniform simple VPB, age and systolic blood pressure. Relationship with diastolic blood pressure was not as clear and there was no significant relationship with smoking habit or serum cholesterol level. An important positive relationship was found between VPB and other electrocardiographic findings, particularly negative T waves at rest on the screening strip. A coronary risk score was computed from the three primary coronary risk variables of diastolic blood pressure, serum cholesterol, and cigarettes smoked. These were found unrelated to VPB in univariate analyses. VPB were also found unrelated to a multivariate risk score calculated from these items [3]. In conclusion, screening for individuals with frequent ectopic ventricular rhythms is feasible using simple equipment in a rapid screening situation associated with a primary coronary risk factor screening station. A 2-min rhythm strip is two thirds repeatable and has a sufficient yield with respect to later more detailed monitoring measures. Something on the order of 5% of free-living men in general populations will exhibit some VPB in such a screening situation. These manifestations are strongly related to the duration of monitoring period, the individual's age and systolic blood pressure level, and to the presence of non-specific electrocardiographic findings.
The second stage of a community approach to VPB screening and detection was an invitation to the central laboratory of those men having any VPB during the primary resting 2-min screen, to ascertain: (1) the efficacy of the primary screening strip to detect those having frequent or complex VPB under standard and more complete VPB monitoring; (2) the repeat variability of the 2-min rhythm strip, and (3) the response rate to the invitation of age eligibles in the population. In each of two extra visits to the central laboratory, the following tests were administered to all those having VPB in the primary screening center: (1) a repeat two-minute single-lead rhythm strip; (2) a conventional resting
Downloaded by: University of Cambridge 131.111.164.128 - 1/31/2019 6:12:04 PM
VPB Detection: Second Stage
BLACKBURN/DE BACKER/CRow/PRlNEAS/JAcoBs
212
12-lead ECG; (3) a VPB induction test to be described, and (4) a 24-hour Holter monitoring tape in a subsample. The identical procedure was administered to a subsample of men having no VPB at the primary screen, but this experience will be reported elsewhere. The VPB induction test consists of: (1) carotid sinus pressure; (2) mental stress in the form of mirror drawing; (3) cold stress in the form of hand immersion in ice water; (4) isometric stress in the form of a handgrip exercise, and (5) progressive treadmill stress to voluntary maximal capacity.
' ... they [VPB] are abolished during exercise and for a short period afterwards, but during the period of slow heart action which often follows exercise, they are frequent. As we shall subsequently see, this knowledge may often be used advantageously to induce premature beats in patients predisposed to them' [4]. Only preliminary results on the second stage testing are available from the first 210 men having VPB at the first stage screen. These men were issued a single mail plus telephone invitation to an orientation meeting, to explain the question of VPB and the scientific study being made of them. 100 men appeared from whom 70 volunteered for the study and in which 54 were determined medically eligible. In this first group, the repeatability of the 2-min screening strip in the same posture and conditions was 66% for any VPB and 67% for the same frequency class of VPB. Thus, a rapid community screening process for ectopic rhythms is repeatable in about two thirds of instances. Test-retest repeatability of the VPB induction test, including all the stress procedures, is approximately 90% for the presence of any VPB, 66% for any complex VPB, and very low (8%) for runs of ventricular tachycardia. The yield of VPB from each facet of the VPB induction test was complementary to that from the other. The progressive treadmill exercise gave the largest independent fraction of the total VPB yield. The mental stress used was largely ineffective in inducing VPB. Each aspect of the test except for the mirror image drawing revealed some extra information. There was a unique yield of VPB in each phase of standing rest, progressive exercise and recovery. It was more frequent that exercise suppressed VPB than that it induced VPB. Complex VPB or very frequent VPB were more likely to occur in those who had frequent uniform VPB during the resting state.
Downloaded by: University of Cambridge 131.111.164.128 - 1/31/2019 6:12:04 PM
Results of Second Stage VP B Detection
VPB Epidemiology and Prevention
213
Table 1. VPB and prognosis for CHD death. Ten-year experience in the Seven Countries Study [2]
NoVPB
Rest ECG Exercise ECG
VPB Present
N
CHD deaths
%
N
CHD deaths
%
10,621 10,546
323 324
(3.04) (3.07)
149 245
9 8
(6.04) (3.26)
' ... our inquiries are as to whether a heart, which presents no other sign, can be regarded as healthy and as to whether, in the case of an unhealthy heart, the prospect [of VPB] has an added gloom. A number of people are temporarily affected by premature beats which do not reappear, while the heart manifests no sign of further damage, either at the time or afterwards. It may be said, therefore, that in themselves premature beats cannot be regarded as evidence of serious involvement of the heart muscle, although such involvement is often found in conjunction with them. It follows that of hearts seen today, some of which show premature contractions and some of which show none, the incidence of grave irregularities will in later years be greater in the former than in the latter' [4]. Table I represents 10 years follow-up in 10,770 men aged 40-59 free of manifest coronary heart disease at entry into the previously reported Seven Countries Study [5]. The crude relationship shown here between VPB and CHD incidence becomes weak and inconsistent when age, blood pressure and coronary risk scores are accounted for. It is concluded that there is no significant independent predictive information in VPB at rest or induced by exercise for coronary disease risk in middle-aged men clinically free of coronary disease. This is not to say that there is absolutely no possible relationship, nor that an occasional case of sudden death may be directly related to events precipitated by a series of VPB. Furthermore, it does not say that effective intervention on ectopic beats might not modify risk in some clinical groups. It does suggest, however, that the predictive relationship is overall weak and that intervention on VPB is unlikely to have a powerful effect on the frequency of sudden coronary death in persons at high risk due to primary coronary risk factors.
Downloaded by: University of Cambridge 131.111.164.128 - 1/31/2019 6:12:04 PM
Prognosis of VP B
BLACKBURN/DE BACKER/CRow/PRINEAS/JACOBS
214
Long-term VPB suppressive drug therapy, at sufficient levels to reduce ectopic activity significantly, has not yet been demonstrated to be safe or efficacious. However, because of many anecdotal reports and clinical impressions which relate cardiac excitability and VPB to poor physiological hygiene, to debauche, to coffee drinking, stimulants and smoking, a crossover controlled trial was designed to test the hypothesis that hygienic intervention might suppress VPB. Men recruited in the earlier screening stages with VPB detection, described earlier, and having consistent demonstrations of ectopic activity at rest and in VPB stress induction tests, are now actively enrolled in the hygienic intervention trial depicted in figure 1. Eligible men, free of clinically manifest cardiac disease and demonstrated to have persistent quantifiable ectopic activity under these standard testing conditions, have been randomly assigned to three groups. Group A is advised to make no change in their lifestyle. Group B is advised and provided supportive counselling therapy to stop smoking entirely, to avoid coffee, tea, and chocolate as sources of stimulants, to abstain from more than two drinks daily or four drinks total per week, to avoid all stimulant over-the-counter drugs and to get a comfortable amount of sleep every night during the six-week experimental period. Group C receives the same hygienic interventions plus progressive conditioning exercise in three hourly sessions per w~ek at the local YM CA facility. To strengthen the design, the control group is offered the complete intervention program, including physical conditioning, in a cross-over procedure after the first six weeks. The initial experimental groups are also requested to cross-over and to resume previous lifestyles (with the exception of recommencing cigarette smoking which is not recommended). Another six-week experimental period is followed by complete retesting. Experience to date reveals remarkable collaboration of the participants and almost total adherence to the experimental program, with little contamination of controls behavior. Participants are now in the cross-over stage of the design and results are not ready for reporting. Reports from an earlier pilot project exposed 196 men, aged 45-54 to a 15- to 18-month conditioning program, also based on three times a week hourly exercise sessions. VPB in that study were measured by a standard progressive exercise test. Significant physical conditioning was achieved based on changes in submaximal heart rate at a given external work load [1]. The statistical power of that study was not large to demonstrate a clearcut effect of hygiene and physical conditioning due to the method of measure-
Downloaded by: University of Cambridge 131.111.164.128 - 1/31/2019 6:12:04 PM
VPB Suppression by Physiological Hygiene
215
VPB Epidemiology and Prevention Randomization I
A I Control
I
Randomization
I
C
I
Hygiene plus conditioning
Six-week examination and VPB tests
Hygiene plus conditioning
I I
Control
Control
Twelve-week examination and VPB tests
Fig. 1. Partial cross-over design of VPB intervention trial.
ment and the numbers of individuals. However, the findings were sufficiently suggestive that more definitive studies were felt indicated. Among those who adhered effectively to the exercise session, there was a reduction in the number of men having exercise-induced VPB, as well as in the number of VPB per man. There seemed also to be an elevation of the threshold of exercise at which VPB were induced. Results of the current controlled cross-over experiment are eagerly awaited. Irrespective of the results in these healthy men, it may be that the potential for reducing cardiac excitability, frequency and seriousness ofVPB in manifest coronary disease patients is sufficient to recommend a similar randomized trial among such patients. The mechanisms of VPB may be different in them; certainly, their need for safe suppressant therapy is great.
Current work of the Laboratory of Physiological Hygiene is reviewed on the epidemiology and prevention of ectopic ventricular rhythms (VPB). The evidence suggests that uniform simple VPB at rest, or exercise-induced, are prognostically important only in those having clinically manifest coronary disease. A simple rhythm strip is an effective first screen method for detecting individuals having rather frequent VPB, and frequency of VPB is correlated with complex ectopic rhythms. A multifaceted stress induction test induces VPB and does it consistently. Hygienic intervention, in which cardiac stimulants are removed and conditioning exercises given, is being tested as VPB suppressive therapy.
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Summary
BLACKBURN/DE BACICER/CROW/PruNEAS/JACOBS
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References
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BLACKBURN, H.; TAYLOR, H. L.; HAMRELL, B.; BUSKIRK, E.; NICHOLAS, W. c., and THORSEN, R. D.: Premature ventricular complexes induced by stress testing. Am. J. Cardiol. 31,' 441-449 (1973). BLACKBURN, H.; KEyS, A.; ARAVANIS, C.; BUCHEM, F. S. P. VAN; BUZINA, R.; DJORDJEVIC, B. S.; FIDANZA, F.; KARVONEN, M.; MENOTTI, A.; PUNSAR, S., and TAYLOR, H. L.: The ECG in population studies. Prediction (in preparation). CROW, R.; PRlNEAS, R.; DIAS, V.; TAYLOR, H. L.; JACOBS, D., and BLACKBURN, H.: Ventricular premature beats in a population sample. Frequency and association with coronary risk characteristics. Circulation Suppl. III 51/52,' 211-215 (1975). LEWIS, T.: Clinical disorders of the heartbeat (Shaw & Sons, London 1912). KEYS, A.: Coronary heart disease in seven countries. Circulation 41,' suppl.l (1970).
HENRY BLACKBURN, MD, Laboratory of Physiological Hygiene, School of Public Health, University of Minnesota, Minneapolis, MN 55455 (USA)
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