Original Article
Long-Term Outcome in Asymptomatic Men with Exercise-Induced Premature Ventricular Depolarizations
N Engl J Med 2000; 343:826-833September 21, 2000
- Abstract
Background
Exercise testing is widely used in the diagnosis of coronary artery disease, but the long-term outcome for asymptomatic persons with exercise-induced premature ventricular depolarizations remains unclear. We used data from the Paris Prospective Study I to assess the long-term outcome of such persons.
Methods
A total of 6101 asymptomatic French men (42 to 53 years of age) who were free of clinically detectable cardiovascular disease underwent a standardized graded exercise test between 1967 and 1972. Subjects were prospectively classified as having or not having frequent premature ventricular depolarizations (a run of two or more consecutive premature ventricular depolarizations or premature ventricular depolarizations constituting more than 10 percent of all ventricular depolarizations during any of the 30-second electrocardiographic recordings).
Results
During exercise, 138 subjects had frequent premature ventricular depolarizations. After 23 years of follow-up, these subjects had a higher risk of death from cardiovascular causes than the men without frequent premature ventricular depolarizations during exercise (relative risk, 2.67; 95 percent confidence interval, 1.76 to 4.07). In a multivariate model, with adjustment for standard coronary risk factors and the presence or absence of premature ventricular depolarizations before exercise and during recovery from exercise, both exercise-induced ischemia and the occurrence of frequent premature ventricular depolarizations during exercise remained independently associated with an increased risk of death from cardiovascular causes, with similar relative risks (2.63 [95 percent confidence interval, 1.93 to 3.59] and 2.53 [95 percent confidence interval, 1.65 to 3.88], respectively).
Conclusions
The occurrence of frequent premature ventricular depolarizations during exercise in asymptomatic middle-aged men is associated with a long-term increase in the risk of death from cardiovascular causes.
Media in This Article
Figure 1
Percentage without Death from Cardiovascular Causes among Subjects with an Exercise Test That Was Positive for Ischemia, Subjects with Frequent Premature Ventricular Depolarizations during Exercise, and Subjects with Neither a Positive Exercise Test nor Frequent Premature Ventricular Depolarizations.Table 1
Death Rates According to the Frequency of Premature Ventricular Depolarizations Occurring before, during, or after Exercise.Article Activity
- Article
Exercise testing is widely used to detect coronary heart disease and to assess the short- and long-term prognosis in patients with the disease. Numerous studies have shown that an ischemic ST-segment response to exercise is a powerful predictor of major coronary events, including death, in apparently healthy persons.1-7
Whether the occurrence of premature ventricular depolarizations during exercise is useful in the diagnosis of coronary heart disease and in the assessment of prognosis remains controversial. Although an association between the occurrence of premature ventricular depolarizations during exercise and coronary heart disease has been described in patients at high risk for coronary heart disease, it is uncertain whether there is such an association in asymptomatic men.8-13 The short- and long-term prognosis of persons with exercise-induced premature ventricular depolarizations is also uncertain.1,14-19
The occurrence of premature ventricular depolarizations during exercise in asymptomatic subjects raises the question of whether such depolarizations may be a normal response to exercise.20 If so, long-term mortality should not be affected. We used data from 23 years of follow-up in the Paris Prospective Study I to answer this question.
Methods
Subjects
Details of the study have been described elsewhere.21 Briefly, after their oral informed consent was obtained, 7746 Frenchmen who were employed by the Paris Civil Service and who were between 42 and 53 years of age were examined from 1967 through 1972. This sample represented 93.4 percent of all the men employed by the Paris Civil Service in early 1967 who had been born in France between 1917 and 1928. The subjects underwent electrocardiography and physical examinations, provided blood samples for laboratory tests, and supplied information on questionnaires administered by trained interviewers. The means of three measurements of diastolic and systolic blood pressure were used for analysis. The subjects were classified as diabetic if they reported having ever had diabetes, whether or not it was treated.
Subjects could be excluded for technical or medical reasons. Subjects underwent exercise testing unless they had known or suspected cardiovascular disease of any grade or cause, a systolic blood pressure above 180 mm Hg at rest, or any abnormality on 12-lead standard electrocardiography at rest according to the Minnesota code (definite Q waves, atrioventricular block or conduction defects, ST-segment abnormalities, supraventricular tachycardia, or polymorphic premature ventricular depolarizations). No attempt was made to assess ventricular function. Complete data were available for 6456 of 6565 men who completed the exercise test.
Exercise-Test Protocol
The bicycle exercise test was conducted according to a standard protocol.22 It consisted of three successive workloads: 2 minutes at 82 W, 6 minutes at 164 W, and the last 2 minutes at 191 W, for a maximal duration of 10 minutes. Cardiac rhythm was continuously monitored, and 30-second recordings were made from a bipolar lead (V5 and V5R) while the subject was at rest and every 2 minutes during a maximum of 10 minutes of exercise, at maximal effort, and every 1 minute during the 10-minute recovery time, or whenever the monitoring physician observed an arrhythmia. Testing was terminated if the subject had fatigue, dyspnea, leg discomfort, any chest pain, systolic blood pressure above 250 mm Hg, a heart rate of 180 beats per minute or more, ventricular tachycardia, or electrocardiographic changes indicative of ischemia. An ischemic response was defined as a J-point depression of at least 1 mm, with a flat or downsloping ST segment, during exercise or recovery. At the time of each electrocardiographic recording, the frequency of premature ventricular depolarizations was assessed as the maximal number of premature ventricular depolarizations divided by the total number of ventricular depolarizations during any of the 30-second recordings. Subjects with a run of two or more consecutive premature ventricular depolarizations or with premature ventricular depolarizations constituting more than 10 percent of all ventricular depolarizations on any of the electrocardiograms recorded with the subject at rest, during exercise, or during recovery were classified as having had frequent premature ventricular depolarizations during that period. Subjects classified as having infrequent premature ventricular depolarizations were those with premature ventricular depolarizations constituting 10 percent or less of all ventricular depolarizations. These criteria were defined in the study protocol and coded by the physician who conducted the examination.
Follow-up
The administrative department in charge of the study population provided an annual list of all subjects not yet retired who had died during the year. All available data relevant to the cause of death were obtained from hospital records or from the subjects' general practitioners, as identified by their relatives. The data were then reviewed by an independent medical committee. For subjects who died after retirement, the cause of death was obtained from death certificates. The cause of death was coded according to the eighth revision of the International Classification of Diseases. 23 Sudden death was defined as a natural death occurring within one hour after the onset of acute symptoms. Death was coded as due to myocardial infarction only if the death was found to be definitely related to myocardial infarction.
The follow-up period ended on January 1, 1994. Vital status could not be determined for 355 (5.5 percent) of the 6456 subjects for whom complete exercise-test data were available. Their characteristics at base line and during exercise were not significantly different from those of the remaining 6101 men whom we studied.
Statistical Analysis
Analysis of variance and chi-square analysis were used for comparisons between groups. Because of the skewed distribution of triglyceride values, log-transformed values were used in the analysis of this factor. Analysis of variance and logistic regression were used to identify factors associated with an exercise test that was positive for ischemia and factors associated with the occurrence of frequent premature ventricular depolarizations, after mutual adjustment. The relative risks of death were adjusted for confounding factors and estimated by the Cox proportional-hazards model. SAS software (SAS Institute, Cary, N.C.) was used for analysis.
Results
There were no serious complications of exercise testing (such as death, myocardial infarction, or ventricular fibrillation). The test was positive for ischemia in 271 of 6101 subjects (4.4 percent). Frequent premature ventricular depolarizations occurred in 48 subjects (0.8 percent) before exercise, in 138 (2.3 percent) during exercise, and in 174 (2.9 percent) during recovery. The mean (±SD) heart rate at the end of exercise was 167±16 beats per minute (96±9 percent of the predicted maximal heart rate). During the 23 years of follow-up, 1635 subjects (26.8 percent) died, including 435 from cardiovascular causes (7.1 percent).
Rates of Death among Subjects with Premature Ventricular Depolarizations
Forty-eight of the 6101 subjects (0.8 percent) had frequent premature ventricular depolarizations before exercise, 121 (2.0 percent) had infrequent premature ventricular depolarizations, and 5932 (97.2 percent) had none (Table 1Table 1
Death Rates According to the Frequency of Premature Ventricular Depolarizations Occurring before, during, or after Exercise.). There were no significant differences among these three groups in the rates of death from all causes, death from noncardiovascular causes, or death from cardiovascular causes (which included sudden death, fatal myocardial infarction, and death from other cardiovascular causes).During exercise, 138 subjects (2.3 percent) had frequent premature ventricular depolarizations, 520 (8.5 percent) had infrequent premature ventricular depolarizations, and 5443 (89.2 percent) had none. The rates of death from all causes and death from cardiovascular causes were significantly (P<0.001) higher in subjects with frequent premature ventricular depolarizations than in the other two groups (death from all causes: 41.3 percent, vs. 27.9 percent in the group with infrequent premature ventricular depolarizations and 26.3 percent in the group with none; death from cardiovascular causes: 16.7 percent, vs. 7.3 percent and 6.8 percent). The rate of death from noncardiovascular causes did not differ significantly among the three groups. There were no significant differences in the rates of death from all causes, death from noncardiovascular causes, or death from cardiovascular causes between subjects with infrequent premature ventricular depolarizations and those without such depolarizations.
During recovery from exercise, 174 subjects (2.9 percent) had frequent premature ventricular depolarizations, 448 (7.3 percent) had infrequent premature ventricular depolarizations, and 5479 (89.8 percent) had none. The rates of death from all causes and from noncardiovascular causes were significantly higher among subjects with frequent premature ventricular depolarizations during recovery than in the other two groups. The rates of death from cardiovascular causes were similar in the three groups.
Occurrence of Premature Ventricular Depolarizations during Exercise
There were no significant differences in cardiovascular risk factors between the subjects with infrequent premature ventricular depolarizations and those without premature ventricular depolarizations during exercise. The 271 subjects (4.4 percent) with a positive exercise test were equally distributed among the three groups. The exercise test was stopped because of chest pain in 8 subjects (0.1 percent), none of whom had premature ventricular depolarizations; the test was stopped because of runs of two or more premature ventricular depolarizations in 16 subjects (0.3 percent).
Premature Ventricular Depolarizations before, during, and after Exercise
Among the 48 subjects with frequent premature ventricular depolarizations before exercise, 3 (6 percent) continued to have frequent premature ventricular depolarizations during exercise and 15 (31 percent) had a recurrence of frequent premature ventricular depolarizations during recovery from exercise. Among the 138 subjects who had frequent premature ventricular depolarizations during exercise, 3 (2.2 percent) also had frequent premature ventricular depolarizations before exercise, 125 (90.6 percent) had no premature ventricular depolarizations before exercise, 21 (15.2 percent) continued to have frequent premature ventricular depolarizations during recovery, and 96 (69.6 percent) had none during recovery.
Occurrence of Ischemia or Frequent Premature Ventricular Depolarizations during Exercise
Because of their similar characteristics and mortality rates, the groups with infrequent and with no premature ventricular depolarizations during exercise were combined and compared with the group with frequent premature ventricular depolarizations during exercise. Older age and higher levels of total cholesterol and triglycerides were significantly associated with a positive exercise test, but not with frequent premature ventricular depolarizations during exercise (Table 2Table 2
Characteristics of Subjects According to the Presence or Absence of Ischemia and Frequent Premature Ventricular Depolarizations (PVDs) during Exercise.). The body-mass index (the weight in kilograms divided by the square of the height in meters) was significantly lower and tobacco consumption was significantly higher among subjects with frequent premature ventricular depolarizations, but neither was associated with a positive exercise test. The maximal heart rate and the percentage of the predicted maximal heart rate achieved during exercise were significantly higher in subjects with evidence of ischemia on the exercise test. The duration of the exercise test was significantly shorter among subjects with a positive exercise test and among those with frequent premature ventricular depolarizations. Diabetic status, extent of physical activity, heart rate at rest, systolic blood pressure at rest, and maximal systolic blood pressure were not significantly associated with either the exercise-test result or with the presence or absence of frequent premature ventricular depolarizations.Death Rates and Relative Risks of Death from Cardiovascular Causes
Subjects with evidence of ischemia on exercise testing or with frequent premature ventricular depolarizations during exercise had significantly higher rates of death from all causes and from cardiovascular causes, but not from noncardiovascular causes (Table 3Table 3
Rates and Relative Risks of Death from Cardiovascular Causes Associated with the Presence or Absence of Ischemia or Frequent Premature Ventricular Depolarizations (PVDs) during Exercise.). Those with a positive exercise test had significantly higher rates of death from myocardial infarction and of sudden death, but not of deaths due to other cardiovascular causes. Those with frequent premature ventricular depolarizations during exercise had significantly higher rates of death due to myocardial infarction and other causes of cardiovascular death, but not of sudden death. There was no significant interaction between the exercise-test result and the presence or absence of frequent premature ventricular depolarizations during exercise.As Figure 1Figure 1
Percentage without Death from Cardiovascular Causes among Subjects with an Exercise Test That Was Positive for Ischemia, Subjects with Frequent Premature Ventricular Depolarizations during Exercise, and Subjects with Neither a Positive Exercise Test nor Frequent Premature Ventricular Depolarizations. shows, the proportion that did not die from cardiovascular causes did not differ markedly between subjects with an exercise test that was positive for ischemia and those with frequent premature ventricular depolarizations during exercise.A multivariate analysis was performed with adjustment for age, body-mass index, heart rate at rest, systolic blood pressure, tobacco use, level of physical activity, diabetic status, total cholesterol level, the occurrence of premature ventricular depolarizations before exercise, and the occurrence of premature ventricular depolarizations during recovery. The results showed that a positive exercise test and the occurrence of frequent premature ventricular depolarizations during exercise were independently associated with a higher mortality rate from cardiovascular causes, with similar relative risks (Table 3). The relative risks were 2.63 (95 percent confidence interval, 1.93 to 3.59) for ischemia and 2.53 (95 percent confidence interval, 1.65 to 3.88) for frequent premature ventricular depolarizations.
Runs of Premature Ventricular Depolarizations
Runs of two or more consecutive premature ventricular depolarizations were induced in 16 subjects during exercise and in 6 other subjects during recovery, and they all resolved spontaneously. The characteristics of these subjects did not differ significantly from those of subjects who had frequent pre-mature ventricular depolarizations without complex runs. When data from the subjects with complex runs were excluded from the preceding analysis, the results did not change significantly: the occurrence of frequent premature ventricular depolarizations during exercise remained independently associated with higher mortality from cardiovascular causes, with a relative risk of 2.17 and a 95 percent confidence interval of 1.34 to 3.50.
Discussion
The occurrence of premature ventricular depolarizations during exercise may be related to exercise-induced myocardial ischemia.15-19 However, subjects with an exercise test that was positive for ischemia and subjects with frequent premature ventricular depolarizations during exercise do not share the same pattern of risk factors. It is striking that among the 271 subjects with a positive exercise test, only 3 percent had frequent premature ventricular depolarizations during exercise. Conversely, among the 138 subjects with frequent premature ventricular depolarizations during exercise, only 6 percent had an exercise test that was positive for ischemia.
The occurrence of premature ventricular depolarizations during exercise may be mediated by the increase in plasma catecholamines related to exercise,24 and both epinephrine and norepinephrine levels have been shown to continue to increase during the first three minutes after exercise.25 Only 21 of 138 subjects (15.2 percent) had frequent premature ventricular depolarizations both during and after exercise. The outcome for this group was not different from that of subjects who had frequent premature ventricular depolarizations only during exercise, but the numbers were too small for any firm conclusions to be drawn.
The higher rate of death from noncardiovascular causes among subjects who had frequent premature ventricular depolarizations during the period of recovery from exercise than in those without such depolarizations remains difficult to explain. It is likely that different mechanisms cause premature ventricular depolarizations before, during, and after exercise. It appears that the occurrence of frequent premature ventricular depolarizations during exercise identifies only subjects at higher risk of death from cardiovascular causes.
According to our clinical findings, hypertensive cardiomyopathy is unlikely to be the cause of premature ventricular depolarizations, although other types of subclinical nonischemic cardiomyopathy could be involved. Hypertrophic cardiomyopathy is usually a familial disorder with a variable clinical course26 that frequently includes premature ventricular depolarizations.27,28 Left ventricular hypertrophy may be absent or mild, and the disease may be asymptomatic and clinically undetectable at an early stage. Arrhythmogenic right ventricular dysplasia is characterized by the replacement of right ventricular myocardium by fibrous tissue and fat,29 a change that is usually responsible for frequent premature ventricular depolarizations associated with left bundle-branch block.30 Early diagnosis can be quite difficult, since there may be only minor signs of disease on the electrocardiogram. Premature ventricular depolarizations may also be due to dilated cardiomyopathy,31 which may not be detectable at early stages, or to mitral-valve prolapse. The latter condition is associated with an increased frequency of premature ventricular depolarizations32 and usually has few adverse effects.33
The occurrence of frequent premature ventricular depolarizations during exercise is associated with an increase in the rate of death from cardiovascular causes, which is related to an increase in various cardiovascular causes of death. A greater increase in the rate of sudden death was expected in this group, but the number of patients was too small to allow precise conclusions.
The higher mortality rate from cardiovascular causes that is associated with frequent premature ventricular depolarizations during exercise in asymptomatic men has consequences for clinical practice. Such subjects should certainly be evaluated and treated for cardiovascular risk factors, and it should be strongly recommended that they quit smoking. Regular clinical follow-up is advisable.
The presence or absence of premature ventricular depolarizations before exercise was determined from the analysis of one conventional electrocardiogram recorded at entry into the study and one 30-second electrocardiogram recorded before the beginning of exercise. The occurrence of premature ventricular depolarizations in an individual patient is highly variable.34 Therefore, two electrocardiograms taken at rest are clearly insufficient for us to conclude that a subject has no premature ventricular depolarizations. It is likely that some subjects were wrongly classified as having infrequent premature ventricular depolarizations or none, but such misclassification would have had only a small effect on our results.
Evidence of ischemia on the exercise electrocardiogram and a run of consecutive premature ventricular depolarizations were both reasons for termination of the test. We cannot exclude the possibility that frequent premature ventricular depolarizations might have occurred in some subjects who had ischemia if the test had been prolonged and, conversely, that the exercise test might have been positive for ischemia in subjects who had premature ventricular depolarizations during exercise.
The study population consisted of healthy men without symptoms of cardiovascular disease who were employed by the Paris Civil Service; these men may have differed from the general population in socioeconomic status, use of alcohol and tobacco, or other characteristics. Therefore, caution must be used in extending the results to the general population. The study included only men, but there is no reason to expect that different conclusions would have been reached if the study had included women.
In order to achieve the maximal predicted heart rate in asymptomatic subjects as rapidly as possible, an unusual protocol of exercise tests was used. The rapidity with which the workload was advanced may have influenced the results, and it is possible that the conclusions may not be applicable to subjects who undergo testing according to the standard Bruce protocol, which is now routinely used.
The occurrence of frequent premature ventricular depolarizations during exercise in asymptomatic middle-aged men is associated with increased long-term mortality from cardiovascular causes. The relative risk is similar to that associated with an exercise test that is positive for ischemia, even after adjustment for confounding variables. For this population, additional examinations and regular medical follow-up should be encouraged, and patients should be urged to modify risk factors and particularly to quit smoking. Further studies are required to identify the causes and mechanisms of the association between frequent premature ventricular depolarizations during exercise and death from cardiovascular causes.
We are indebted to Beverley Balkau and Professor Claude Guérot for their support.
Source Information
From the Service de Cardiologie, Université Paris V, Faculté Necker–Enfants Malades, Hôpital Européen Georges Pompidou, Paris (X.J., M.D.); and INSERM Unité 258 (Epidémiologie Cardiovasculaire et Métabolique), Hôpital Paul Brousse, Villejuif, France (X.J., M.Z., D.C., P.D.).
Address reprint requests to Dr. Jouven at the Service de Cardiologie, Hôpital Européen Georges Pompidou, 20 rue Le Blanc, 75015 Paris, France, or at xavier.jouven@bcc.ap-hop-paris.fr.
- References
References
1
Bruce RA ,DeRouen TA ,Hossack KF . Value of maximal exercise tests in risk assessment of primary coronary heart disease events in healthy men: five years' experience of the Seattle Heart Watch study. Am J Cardiol 1980;46:371-378
CrossRef | Web of Science | Medline2
Giagnoni E ,Secchi MB ,Wu SC , et al. Prognostic value of exercise EKG testing in asymptomatic normotensive subjects: a prospective matched study. N Engl J Med 1983;309:1085-1089
Full Text | Web of Science | Medline3
Gianrossi R ,Detrano R ,Mulvihill D , et al. Exercise-induced ST depression in the diagnosis of coronary artery disease: a meta-analysis. Circulation 1989;80:87-98
CrossRef | Web of Science | Medline4
Gordon DJ ,Ekelund LG ,Karon JM , et al. Predictive value of the exercise tolerance test for mortality in North American men: the Lipid Research Clinics Mortality Follow-up Study. Circulation 1986;74:252-261
CrossRef | Web of Science | Medline5
Michaelides AP ,Psomadaki ZD ,Dilaveris PE , et al. Improved detection of coronary artery disease by exercise electrocardiography with the use of right precordial leads. N Engl J Med 1999;340:340-345
Full Text | Web of Science | Medline6
Rywik TM ,Zink RC ,Gittings NS , et al. Independent prognostic significance of ischemic ST-segment response limited to recovery from treadmill exercise in asymptomatic subjects. Circulation 1998;97:2117-2122
Web of Science | Medline7
Shaw LJ ,Peterson ED ,Shaw LK , et al. Use of a prognostic treadmill score in identifying diagnostic coronary disease subgroups. Circulation 1998;98:1622-1630
Web of Science | Medline8
McHenry PL ,O'Donnell J ,Morris SN ,Jordan JJ . The abnormal exercise electrocardiogram in apparently healthy men: a predictor of angina pectoris as an initial coronary event during long-term follow-up. Circulation 1984;70:547-551
CrossRef | Web of Science | Medline9
Nair CK ,Aronow WS ,Sketch MH , et al. Diagnostic and prognostic significance of exercise-induced premature ventricular complexes in men and women: a four year follow-up. J Am Coll Cardiol 1983;1:1201-1206
CrossRef | Web of Science | Medline10
Weiner DA ,Ryan TJ ,McCabe CH , et al. Prognostic importance of a clinical profile and exercise test in medically treated patients with coronary artery disease. J Am Coll Cardiol 1984;3:772-779
CrossRef | Web of Science | Medline11
Sami M ,Chaitman B ,Fisher L ,Holmes D ,Fray D ,Alderman E . Significance of exercise-induced ventricular arrhythmia in stable coronary artery disease: a Coronary Artery Surgery Study project. Am J Cardiol 1984;54:1182-1188
CrossRef | Web of Science | Medline12
Froelicher VF Jr ,Thomas MM ,Pillow C ,Lancaster MC . Epidemiologic study of asymptomatic men screened by maximal treadmill testing for latent coronary artery disease. Am J Cardiol 1974;34:770-776
CrossRef | Medline13
Vedin JA ,Wilhelmsson CE ,Wilhelmsen L ,Bjure J ,Ekstrom-Jodal B . Relation of resting and exercise-induced ectopic beats to other ischemic manifestations and to coronary risk factors: men born in 1913. Am J Cardiol 1972;30:25-31
CrossRef | Medline14
Califf RM ,McKinnis RA ,McNeer JF , et al. Prognostic value of ventricular arrhythmias associated with treadmill exercise testing in patients studied with cardiac catheterization for suspected ischemic heart disease. J Am Coll Cardiol 1983;2:1060-1067
CrossRef | Web of Science | Medline15
Udall JA ,Ellestad MH . Predictive implications of ventricular premature contractions associated with treadmill stress testing. Circulation 1977;56:985-989
Web of Science | Medline16
Drory Y ,Pines A ,Fisman EZ ,Kellermann JJ . Persistence of arrhythmia exercise response in healthy young men. Am J Cardiol 1990;66:1092-1094
CrossRef | Web of Science | Medline17
Faris JV ,McHenry PL ,Jordan JW ,Morris SN . Prevalence and reproducibility of exercise-induced ventricular arrhythmias during maximal exercise testing in normal men. Am J Cardiol 1976;37:617-622
CrossRef | Web of Science | Medline18
Fleg JL ,Lakatta EG . Prevalence and prognosis of exercise-induced nonsustained ventricular tachycardia in apparently healthy volunteers. Am J Cardiol 1984;54:762-764
CrossRef | Web of Science | Medline19
Morrow K ,Morris CK ,Froelicher VF , et al. Prediction of cardiovascular death in men undergoing noninvasive evaluation for coronary artery disease. Ann Intern Med 1993;118:689-695
Web of Science | Medline20
Toff WD ,Joy M ,Camm AJ . Exercise-induced arrhythmia. Eur Heart J 1988;9:Suppl G:119-126
Medline21
Ducimetiere P ,Richard JL ,Cambien F ,Rakotovao R ,Claude JR . Coronary heart disease in middle-aged Frenchmen: comparison between Paris Prospective Study, Seven Countries Study and Pooling Project. Lancet 1980;1:1346-1350
CrossRef | Web of Science | Medline22
Filipovsky J ,Ducimetiere P ,Safar ME . Prognostic significance of exercise blood pressure and heart in middle-aged men. Hypertension 1992;20:333-339
Web of Science | Medline23
List of three-digit categories. In: International classification of diseases: manual of the international statistical classification of diseases, injuries, and causes of death. 1965 revision. Vol. 1. Geneva: World Health Organization, 1967:3-41.
24
Fleg JL ,Tzankoff SP ,Lakatta EG . Age-related augmentation of plasma catecholamines during dynamic exercise in healthy males. J Appl Physiol 1985;59:1033-1039
Web of Science | Medline25
Dimsdale JE ,Hartley LH ,Guiney T ,Ruskin JN ,Greenblatt D . Postexercise peril: plasma catecholamines and exercise. JAMA 1984;251:630-632
CrossRef | Web of Science | Medline26
Maron BJ . Hypertrophic cardiomyopathy. Lancet 1997;350:127-133[Erratum, Lancet 1997;350:1330.]
CrossRef | Web of Science | Medline27
Kuck KH . Arrhythmias in hypertrophic cardiomyopathy. Pacing Clin Electrophysiol 1997;20:2706-2713
CrossRef | Web of Science | Medline28
Spirito P ,Chiarella F ,Carratino L ,Berisso MZ ,Bellotti P ,Vecchio C . Clinical course and prognosis of hypertrophic cardiomyopathy in an outpatient population. N Engl J Med 1989;320:749-755
Full Text | Web of Science | Medline29
Marcus FI ,Fontaine G ,Guiraudon G , et al. Right ventricular dysplasia: a report of 24 cases. Circulation 1982;65:384-398
CrossRef | Web of Science | Medline30
Fontaine G ,Fontaliran F ,Frank R . Arrhythmogenic right ventricular cardiomyopathies: clinical forms and main differential diagnoses. Circulation 1998;97:1532-1535
Web of Science | Medline31
Pogwizd SM ,McKenzie JP ,Cain ME . Mechanisms underlying spontaneous and induced ventricular arrhythmias in patients with idiopathic dilated cardiomyopathy. Circulation 1998;98:2404-2414
Web of Science | Medline32
La Vecchia L ,Ometto R ,Centofante P , et al. Arrhythmic profile, ventricular function, and histomorphometric findings in patients with idiopathic ventricular tachycardia and mitral valve prolapse: clinical and prognostic evaluation. Clin Cardiol 1998;21:731-735
CrossRef | Web of Science | Medline33
Freed LA ,Levy D ,Levine RA , et al. Prevalence and clinical outcome of mitral-valve prolapse. N Engl J Med 1999;341:1-7
Full Text | Web of Science | Medline34
Janssen MJA ,Swenne CA ,Manger Cats V ,van Bemmel JH ,Bruschke AVG . Autonomic, ischaemic, circadian and rhythmic factors as causes of the spontaneous variability of ventricular arrhythmias. Eur Heart J 1995;16:674-681
Web of Science | Medline
- Citing Articles (51)
Citing Articles
1
MIO UCHIDA, TETSUJI SHINOHARA, NAOHIKO TAKAHASHI, TETSUNORI SAIKAWA. (2011) Interventricular Septal Mass in a Patient with Cardiac Sarcoidosis. Journal of Cardiovascular Electrophysiologyno-no
CrossRef2
R. Perelló, M. Calvo, O. Miró, M. Castañeda, N. Saubí, S. Camón, A. Foix, J.M. Gatell, M. Masotti, J. Mallolas, M. Sánchez, E. Martinez. (2011) Clinical presentation of acute coronary syndrome in HIV infected adults: A retrospective analysis of a prospectively collected cohort. European Journal of Internal Medicine 22:5, 485-488
CrossRef3
ANNUKKA MARJAMAA, ANITA HIIPPALA, BIANCA ARRHENIUS, ANNUKKA M. LAHTINEN, KIMMO KONTULA, LAURI TOIVONEN, JUHA-MATTI HAPPONEN, HEIKKI SWAN. (2011) Intravenous Epinephrine Infusion Test in Diagnosis of Catecholaminergic Polymorphic Ventricular Tachycardia. Journal of Cardiovascular Electrophysiologyno-no
CrossRef4
A. Raviele, F. Giada, L. Bergfeldt, J. J. Blanc, C. Blomstrom-Lundqvist, L. Mont, J. M. Morgan, M. J. P. Raatikainen, G. Steinbeck, S. Viskin, , P. Kirchhof, F. Braunschweig, M. Borggrefe, M. Hocini, P. D. Bella, D. C. Shah. (2011) Management of patients with palpitations: a position paper from the European Heart Rhythm Association. Europace 13:7, 920-934
CrossRef5
Amar Jadhav, Apeksha Ingole, Anand Chockalingam. (2011) Ventricular Ectopic Beats: An Overview of Management Considerations. The American Journal of the Medical Sciences1
CrossRef6
2011. Active Ventricular Arrhythmias. , 181-229.
CrossRef7
Khursheed Jeejeebhoy, Farida Jeejeebhoy. 2010. Clinical Assessment of Athletes. , 377-393.
CrossRef8
R. Berent, J. Auer, S.P. Duvillard, H. Sinzinger, P. Schmid. (2010) Komplikationen bei der Ergometrie. Herz 35:4, 267-272
CrossRef9
Ross Arena, Jonathan Myers, Marco Guazzi. (2010) The future of aerobic exercise testing in clinical practice: is it the ultimate vital sign?. Future Cardiology 6:3, 325-342
CrossRef10
Jeremy S. Windsor, George W. Rodway, Hugh E. Montgomery. (2010) A Review of Electrocardiography in the High Altitude Environment. High Altitude Medicine & Biology 11:1, 51-60
CrossRef11
CYNTHIA M. DOUGHERTY, ROBB W. GLENNY, PETER J. KUDENCHUK, TODD E. MALINICK, GAYLE L. FLO. (2010) Testing an Exercise Intervention to Improve Aerobic Conditioning and Autonomic Function after an Implantable Cardioverter Defibrillator (ICD). Pacing and Clinical Electrophysiology
CrossRef12
Bojko Bjelakovic, Stevan Ilic, Konstantinos Chouliaras, Branislav Milovanovic, Vladislav Vukomanovic, Tijana Bojic, Ljiljana Bjelakovic, Tatjana Zaharov. (2010) Heart Rate Variability in Children with Exercise-Induced Idiopathic Ventricular Arrhythmias. Pediatric Cardiology 31:2, 188-194
CrossRef13
I. Kesoi, B. Sagi, T. Vas, T. Kovacs, I. Wittmann, J. Nagy. (2010) Heart rate recovery after exercise is associated with renal function in patients with a homogenous chronic renal disease. Nephrology Dialysis Transplantation 25:2, 509-513
CrossRef14
(2009) An Association of Changed Levels of Inflammatory Markers with Hematological Factors during One-time Aerobic Exercise in Twenty-aged Young Men. Journal of Life Science 19:11, 1658-1665
CrossRef15
Birna Bjarnason-Wehrens, Olaf Schulz, Stephan Gielen, Martin Halle, Martin Dürsch, Rainer Hambrecht, Heinz Lowis, Wilfried Kindermann, Robin Schulze, Bernhard Rauch. (2009) Leitlinie körperliche Aktivität zur Sekundärprävention und Therapie kardiovaskulärer Erkrankungen. Clinical Research in Cardiology Supplements 4:S3, 1-44
CrossRef16
FREDERICK E. DEWEY, MARCO PEREZ, DAVID HADLEY, JAMES V. FREEMAN, PAUL WANG, EUAN A. ASHLEY, JONATHAN MYERS, VICTOR F. FROELICHER. (2009) Statin Use and Ventricular Arrhythmias During Clinical Treadmill Testing. Journal of Cardiovascular Electrophysiology 20:2, 193-199
CrossRef17
Kan Takayanagi, Yoshihiko Sakai. (2009) Mechanism of Ventricular Premature Contraction Showing Interpolated Bigeminy —Strong Modulation Hypothesis—. Journal of Arrhythmia 25:4, 177-192
CrossRef18
Rei-Yeuh Chang, Malcolm Koo, Zer-Ran Yu, Chung-Ben Kan, I-Tseng Chu, Chen-Tung Hsu, Cheng-Yun Chen. (2008) The Effect of T'ai Chi Exercise on Autonomic Nervous Function of Patients with Coronary Artery Disease. The Journal of Alternative and Complementary Medicine 14:9, 1107-1113
CrossRef19
Myrvin H. Ellestad. (2008) Unconventional Electrocardiographic Signs of Ischemia During Exercise Testing. The American Journal of Cardiology 102:7, 949-953
CrossRef20
Jerome L. Fleg, Edward G. Lakatta. 2008. Normal Aging of the Cardiovascular System. , 1-44.
CrossRef21
Borys Surawicz, Morton Tavel. 2008. Stress Test. , 221-255.
CrossRef22
I. A. Brouwer. 2008. Fish, omega-3 fatty acids and heart disease. , 165-181.
CrossRef23
C. W. Israel. (2007) Non-invasive risk stratification: Prognostic implications of exercise testing. Herzschrittmachertherapie & Elektrophysiologie 18:1, 17-29
CrossRef24
Vijay S Chauhan, Raja J Selvaraj. (2007) Utility of microvolt T-wave alternans to predict sudden cardiac death in patients with cardiomyopathy. Current Opinion in Cardiology 22:1, 25-32
CrossRef25
Takanori Ikeda, Satoru Yusu, Kentaro Nakamura, Hideaki Yoshino. (2007) Risk Stratification for Sudden Cardiac Death. Circulation Journal 71:SupplementA, A106-A114
CrossRef26
(2006) Guías de Práctica Clínica del ACC/AHA/ESC 2006 sobre el manejo de pacientes con arritmias ventriculares y la prevención de la muerte cardiaca súbita.Versión resumida. Revista Española de Cardiología 59:12, 1328.e1-1328.e51
CrossRef27
Sandra D??Amore, Samia Mora. (2006) Gender-Specific Prediction of Cardiac Disease. Cardiology in Review 14:6, 281-285
CrossRef28
Elizabeth S. Kaufman, Daniel M. Bloomfield, Richard C. Steinman, Pearila B. Namerow, Ottorino Costantini, Richard J. Cohen, J. Thomas Bigger. (2006) “Indeterminate” Microvolt T-Wave Alternans Tests Predict High Risk of Death or Sustained Ventricular Arrhythmias in Patients With Left Ventricular Dysfunction. Journal of the American College of Cardiology 48:7, 1399-1404
CrossRef29
Douglas P. Zipes, A. John Camm, Martin Borggrefe, Alfred E. Buxton, Bernard Chaitman, Martin Fromer, Gabriel Gregoratos, George Klein, Arthur J. Moss, Robert J. Myerburg, Silvia G. Priori, Miguel A. Quinones, Dan M. Roden, Michael J. Silka, Cynthia Tracy, Sidney C. Smith, Alice K. Jacobs, Cynthia D. Adams, Elliott M. Antman, Jeffrey L. Anderson, Sharon A. Hunt, Jonathan L. Halperin, Rick Nishimura, Joseph P. Ornato, Richard L. Page, Barbara Riegel, Silvia G. Priori, Jean-Jacques Blanc, Andrzej Budaj, A. John Camm, Veronica Dean, Jaap W. Deckers, Catherine Despres, Kenneth Dickstein, John Lekakis, Keith McGregor, Marco Metra, Joao Morais, Ady Osterspey, Juan Luis Tamargo, José Luis Zamorano. (2006) ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death—Executive Summary. Journal of the American College of Cardiology 48:5, 1064-1108
CrossRef30
Douglas P. Zipes, A. John Camm, Martin Borggrefe, Alfred E. Buxton, Bernard Chaitman, Martin Fromer, Gabriel Gregoratos, George Klein, Arthur J. Moss, Robert J. Myerburg, Silvia G. Priori, Miguel A. Quinones, Dan M. Roden, Michael J. Silka, Cynthia Tracy, Sidney C. Smith, Alice K. Jacobs, Cynthia D. Adams, Elliott M. Antman, Jeffrey L. Anderson, Sharon A. Hunt, Jonathan L. Halperin, Rick Nishimura, Joseph P. Ornato, Richard L. Page, Barbara Riegel, Silvia G. Priori, Jean-Jacques Blanc, Andrzej Budaj, A. John Camm, Veronica Dean, Jaap W. Deckers, Catherine Despres, Kenneth Dickstein, John Lekakis, Keith McGregor, Marco Metra, Joao Morais, Ady Osterspey, Juan Luis Tamargo, José Luis Zamorano. (2006) ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death. Journal of the American College of Cardiology 48:5, e247-e346
CrossRef31
M. Kallinen, M. Kauppinen, P. Era, E. Heikkinen. (2006) The predictive value of exercise testing for survival among 75-year-old men and women. Scandinavian Journal of Medicine and Science in Sports 16:4, 237-244
CrossRef32
Ingeborg A. Brouwer, Anouk Geelen, Martijn B. Katan. (2006) n−3 Fatty acids, cardiac arrhythmia and fatal coronary heart disease. Progress in Lipid Research 45:4, 357-367
CrossRef33
Maxime Cournot, Dorota Taraszkiewicz, Michel Galinier, Bernard Chamontin, Henri Boccalon, Hel??ne Hanaire-Broutin, Jacques Puel, Jean Ferri??res. (2006) Is exercise testing useful to improve the prediction of coronary events in asymptomatic subjects?. European Journal of Cardiovascular Prevention & Rehabilitation 13:1, 37-44
CrossRef34
E. Perrier, O. Manen, J.F. Paul, M. Lerecouvreux, G. Quiniou, S. Geffroy, J. Deroche, C. Caussin, P. Doireau, C. Plotton, R. Carlioz. (2005) Apport du scanner multicoupes dans le dépistage des lésions coronaires chez des patients asymptomatiques à risque : étude préliminaire. Annales de Cardiologie et d'Angéiologie 54:5, 227-232
CrossRef35
Jouven, Xavier, Empana, Jean-Philippe, Schwartz, Peter J., Desnos, Michel, Courbon, Dominique, Ducimetière, Pierre, . (2005) Heart-Rate Profile during Exercise as a Predictor of Sudden Death. New England Journal of Medicine 352:19, 1951-1958
Full Text36
James Beckerman, Anima Mathur, Stephen Stahr, Jonathan Myers, Sung Chun, Victor Froelicher. (2005) Exercise-Induced Ventricular Arrhythmias and Cardiovascular Death. Annals of Noninvasive Electrocardiology 10:1, 47-52
CrossRef37
James O. O'Neill, James B. Young, Claire E. Pothier, Michael S. Lauer. (2004) Severe frequent ventricular ectopy after exercise as a predictor of death in patients with heart failure. Journal of the American College of Cardiology 44:4, 820-826
CrossRef38
Anouk Geelen, Ingeborg A Brouwer, Peter L Zock, Martijn B Katan. (2004) Antiarrhythmic effects of n-3 fatty acids: evidence from human studies. Current Opinion in Lipidology 15:1, 25-30
CrossRef39
Kristina Juneblad, Anna Näslund, Bert-Ove Olofsson, Ole B Suhr. (2004) Outcome of exercise electrocardiography in familial amyloidotic polyneuropathy patients, Portuguese type, under evaluation for liver transplantation. Amyloid 11:3, 208-213
CrossRef40
(2003) Ventricular Ectopy after Exercise as a Predictor of Death. New England Journal of Medicine 348:23, 2357-2359
Full Text41
Frolkis, Joseph P., Pothier, Claire E., Blackstone, Eugene H., Lauer, Michael S., . (2003) Frequent Ventricular Ectopy after Exercise as a Predictor of Death. New England Journal of Medicine 348:9, 781-790
Full Text42
Curfman, Gregory D., Hillis, L. David, . (2003) A New Look at Cardiac Exercise Testing. New England Journal of Medicine 348:9, 775-776
Full Text43
David Amar, Hao Zhang, Nancy Roistacher. (2002) The Incidence and Outcome of Ventricular Arrhythmias After Noncardiac Thoracic Surgery. Anesthesia & Analgesia 95:3, 537-543
CrossRef44
MARTIN FEJKA, ROBERTO A. CORPUS, JOSEPH ARENDS, WILLIAM W. O'NEILL, BARRY A. FRANKLIN. (2002) Exercise-Induced Nonsustained Ventricular Tachycardia: A Significant Marker of Coronary Artery Disease?. Journal of Interventional Cardiology 15:3, 231-235
CrossRef45
Khursheed Jeejeebhoy. 2002. Clinical Assessment of Athletes. , 373-385.
CrossRef46
TAI-GER HSU, KUANG-MING HSU, CHI-WOON KONG, FUNG-JOU LU, HU CHENG, KELVIN TSAI. (2002) Leukocyte mitochondria alterations after aerobic exercise in trained human subjects. Medicine & Science in Sports & Exercise 34:3, 438-442
CrossRef47
M. Duong, Y. Cottin, L. Piroth, A. Fargeot, I. Lhuiller, M. Bobillier, M. Grappin, M. Buisson, M. Zeller, P. Chavanet, J. E. Wolf, H. Portier. (2002) Exercise Stress Testing for Detection of Silent Myocardial Ischemia in Human Immunodeficiency Virus--Infected Patients Receiving Antiretroviral Therapy. Clinical Infectious Diseases 34:4, 523-528
CrossRef48
(2001) Exercise-Induced Premature Ventricular Depolarizations. New England Journal of Medicine 344:5, 383-384
Full Text49
Maron, Barry J., . (2000) The Paradox of Exercise. New England Journal of Medicine 343:19, 1409-1411
Full Text50
Calkins, Hugh, . (2000) Premature Ventricular Depolarizations during Exercise. New England Journal of Medicine 343:12, 879-880
Full Text51
Ezra A. Amsterdam. (2000) Clinical Implications of Exercise-Induced Ventricular Arrhythmias. Preventive Cardiology 3:4, 183-184
CrossRef
