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Atrial and ventricular arrhythmias in asymptomatic active elderly subjects: Correlation with left atrial size and left ventricular mass
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Atrial and ventricular arrhythmias in asymptomatic active elderly subjects: Correlation with left atrial size and left ventricular mass Elderly normal subjects have an increased prevalence of cardiac arrhythmias compared with young and middle-aged subjects. The objective of this study was to test the hypothesis that the incidence and complexity of atrial and ventricular arrhythmlas may be related to either left atrial enlargement or to increased left ventricular mass, respectively. From 146 asymptomatic volunteers older than 60 years, 86 subjects were considered to be free of cardiovascular abnormalities and had adequate M-mode echocardiograms and 24-hour ambulatory electrocardiograms. The mean age was 72 ___ 7 years, with a range of 60 to 96 years. There were 37 men and 49 women. During 1415 • 73 minutes of ambulatory electrocardiography, the average heart rate was 72 • 8 beats/min in men and 76 ___6 beats/min in women (p < 0.05). Atrial arrhythmias were present in 64 subjects (74%); the frequency and complexity of these arrhythmias correlated with left atrial size (p < 0.01). Ventricular arrhythmias were present in 55 subjects (64%); the frequency and complexity of ventricular arrhythmias did not correlate with left ventricular mass index. These results suggest that left atrial dilatation, a normal development in healthy elderly subjects, plays a significant role in the pathophysiology of the increased incidence of atrial arrhythmias. Increased left ventricular mass, which also occurs normally in the aging heart, is not, on the other hand, associated with an increased frequency a n d / o r complexity of ventricular arrhythmias. (AM HEART J 1 9 9 0 ; 1 1 9 : 1 0 6 9 . )
D a n t e E. Manyari, MD, Christopher P a t t e r s o n , MD, David Johnson, MD, L i b a r d o Melendez, MD, William J. Kostuk, MD and Ronald D.T. Cape, MD.
London, Ontario, Canada
A high prevalence of cardiac a r r h y t h m i a s has been r e p o r t e d in a p p a r e n t l y healthyl-Tand normal 8 elderly persons. T h i s suggests t h a t r h y t h m disorders m a y be related to intrinsic changes in the aging heart, indep e n d e n t of disease. In patients with various cardiac and p u l m o n a r y diseases, atrial a r r h y t h m i a s are associated with atrial enlargement, 9,10 and increased ventricular ectopic activity has been f o u n d in subjects with systemic h y p e r t e n s i o n with increased left ventricular mass. 11 Since m o d e s t increases of b o t h left atrial size and left ventricular mass have been described in elderly subjects, 12,13 we p o s t u l a t e d t h a t these anatomic characteristics could be related to the From the Sectionsof Cardiologyand GeriatricMedicine,Departmentof Medicine,Universityof Western OntarioHospitals. Supported in part by a grant fromthe OntarioHeart and StrokeFoundation, Toronto,Canada. Receivedfor publicationSept. 8, 1989;acceptedJan. 2, 1990. Reprint requests: Dr. Dante E. Manyari, Foothills Hospital, 1403-29th Street N.W., Calgary,Alberta Canada T2N 2T9. 4/1/19077
increased prevalence of atrial and ventricular arrhythmias, respectively. T h e objective of this s t u d y was to correlate the presence a n d complexity of cardiac a r r h y t h m i a s with left atrial size and left ventricular mass in a p p a r e n t l y healthy, active elderly subjects. METHODS Study population. One hundred forty-six asymptomatic volunteers 60 years of age or older were screened for participation in a large prospective study on the cardiovascular function in a healthy elderly population. 13,14 This report is part of that study. After history taking and physical examination, all subjects had the following investigations: hemoglobin concentration, zeta sedimentation rate, 15 serum electrolytes including phosphorus and calcium, blood urea nitrogen, serum creatinine and glucose, urinalysis, chest x-ray film, electrocardiogram, M-mode echocardiogram, and spirometry (forced expiratory volume and forced expiratory volume in the first second). Subjects were included if they met the following criteria: (1) absence of cardiorespiratory or systemic disease known to affect 1069
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cardiac structure or function such as hypertension, diabetes mellitus, obstructive lung disease, thyroid dysfunction, etc.; (2) normal 12-lead electrocardiogram, apart from minor non-specific repolarization abnormalities or right bundle branch block; (3) normal cardiac shadow and lungs on chest x-ray film; (4) normal hematologic and biochemical studies; (5) no evidence of myocardial, pericardial, or valvular heart disease on echocardiogram (not considering left ventricular mass); and (6) normal spirometry. We also excluded all subjects who were taking cardiovascular medication, but some subjects were taking simple analgesics or minor tranquilizers. Volunteers meeting these criteria were judged to be free of overt heart disease and were considered appropriate candidates for arrhythmia monitoring. Thirty-three of the 146 volunteers were excluded because of hypertension (blood pressure >160/95 mm Hg on at least two occasions), chronic obstructive pulmonary disease, left ventricular hypertrophy on the electrocardiogram, cardiomegaly on chest x-ray film, diabetes mellitus, asymmetric septal hypertrophy, evidence of old myocardial infarction, mitral valve prolapse, hyperthyroidism, and electrolyte abnormalities. Three subjects who were taking major tranquilizers were also excluded. In 18 subjects, the echocardiograms were technically inadequate to assess left atrial size and left ventricular dimensions or wall thickness. Thus, 92 volunteers were judged to be healthy. Eighty-six subjects completed the study; two had technically inadequate ambulatory electrocardiogram recordings and four subjects refused to carry the tape recorder. Mean age of the 86 participants was 72 _+ 7 years. There were 37 men, age 71 __+6 years (range 60 to 87) and 49 women, mean age 73 ___8 years (range 60 to 96). Results were analyzed in arbitrary subgroups of subjects aged 60 to 69, 70 to 75, and 76 to 96 years. Ambulatory electrocardiography. Ambulatory monitoring was carried out with a two-channel 24-hour portable electrocardiogram tape recorder (Model 445, Del Mar Avionics, Irvine, Calif.) and a bipolar electrode lead system for each channel (modified V5 and II). We encouraged subjects to continue normal, everyday activities. We analzed the tapes using a rapid scanner with audiovisual superimposed electrocardiogram imaging and an arrhythmiagraph trace of R-R intervals (Model 660A computerized electrocardioscanner, Del Mar Avionics). At high speed (• a histogram of heart rate versus time for the entire 24 hours was recorded. Two independent observers (an experienced technologist and a cardiologist) then reviewed each tape at a slower speed (• to detect all abnormalities. Hard copies of all arrhythmic events were recorded for detailed analysis. Changes of ST segment were not analyzed because of lack of calibration during recording. Definitions. Average heart rate was defined as the number of beats recorded divided by the recording time in minutes. T h e longest pause was defined by the greatest R-R interval excluding episodes of second-degree atrioventricular (AV) block or postextrasystolic depolarizations. Sinus tachycardia, sinus bradycardia, and severe sinus bradycardia were defined by rates greater than 100 beats/ min, less than 60 beats/min, and less than 40 beats/min,
AmericanHeartJournal
respectively, with normal P wave morphology and adjacent cycle lengths varying by less than 10% for at least four consecutive beats. Mild, moderate, and marked sinus arrhythmias were defined as irregular sinus rhythm with adjacent R-R intervals varying by 10% to 50%, by 50% to 100%, and by more than 100%, respectively. Benign slow atrial tachycardia, an atrial rhythm described by Stemple et al., 16was defined as an abrupt decrease in the R-R interval of greater than 30% that persisted for at least three consecutive beats and was characterized by irregular P-P intervals, variable P wave morphology and P-R intervals, normal QRS configuration, and a rate between 80 and 140 beats/min. Ventricular arrhythmias were described as unifocal, multiform, ventricular couplets (two consecutive ventricular premature depolarizations), ventricular tachycardia (three or more consecutive ventricular premature depolarizations), and R-on-T phenomena. All other arrhythmias were defined by standard electrocardiographic criteria. 17 Echocardiographic studies. M-mode echocardiograms were recorded using a Unirad Series C echocardiograph unit equipped with a 2.5 MHz transducer and interfaced to a Honeywell 1858 strip chart recorder (PPG Biomedical Systems, Medical Electronics Division, Pleasantville, N.Y.). To avoid measurement errors in wall thickness that may occur when the ultrasound beam passes obliquely through the left ventricular cavity, the T-scan technique described by Henry et al. Is was used. Measurements were made according to the recommendations of the American Society of EchocardiographyJ9 Left ventricular mass was calculated using Woythaler's modification2~of the mathematical model described by Devereux and Reichek. 21 Statistical analysis. Results are expressed as group mean _+ standard deviation. We used Students' t test (two groups) or analysis of variance (more than two groups) to assess the significance of the differences between groups. Statistical significance was set at 5 % (p < 0.05). To assess the relationship between atrial arrhythmias and left atrial size, the complexity of atrial arrythmias was arbitrarily graded as follows: 0 = absence of atrial arrhythmias; I = less than 100 atrial premature depolarizations in 24 hours; II = more than 100 atrial premature depolarizations in 24 hours, with or without couplets; I I I = benign slow atrial tachycardia; and IV = atrial fibrillation. To assess the relationship between ventricular arrhythmias and left ventricular mass, the complexity of ventricular arrhythmias was arbitrarily graded as follows: 0 = absence of ventricular arrhythmias; I = isolated (<50) ventricular premature depolarizations in 24 hours; II = >50 ventricular premature depolarizations in 24 hours; I I I = multiform ventricular premature depolarizations; and IV = early ventricular premature depolarizations (R-on-T phenomenon), couplets, ventricular tachycardia, and accelerated idioventricular rhythm. RESULTS
T h e group d u r a t i o n of the a m b u l a t o r y electrocardiogram recording was 1415 _+ 73 minutes. T h e av-
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Arrhythmias in the elderly
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Arrhythmias observed at different age groups in 86 asymptomatic elderly subjects All s u ~ e c t s =8~
Sinus node function Sinus tachycardia Sinus bradycardia Severe sinus bradycardia Mild sinus a r r h y t h m i a Moderate sinus arrhythmia Marked sinus a r r h y t h m i a Atrial premature depolarizations <100/24 hours >100/24 hours Couplets Benig n slow atrial tachycardia Paroxysmal atrial fibrillation Ventricular premature depolarizations <50/24 hours >50/24 hours Multiform R-on-T p h e n o m e n o n Couplets Ventricular tachycardia Accelerated idioventricular r h y t h m Atrioventricular block First-degree Second-degree, type 1 Intraventricular conduction defect
60-69 years ~ =3~
7 0 - ~ years ~ =2~
~ years ~ =21)
No.
%
No.
%
No.
%
No.
%
74 63 0 37 40 9
86 73 0 43 47 10
34 27 0 16 16 5
92 73 0 43 43 14
24 17 0 10 17 1
88 61 0 36 61 4
16 19 0 11 7 3
76 90 0 52 33 14
21 11 3 26 3
24 13 3 30 3
6 6 1 10 2
16 16 3 27 5
10 3 0 10 0
36 11 0 36 0
5 2 2 6 1
24 10 10 29 5
30 8 9 3 2 2 1
35 9 10 3 2 2 1
17 3 1 0 1 1 0
46 8 3 0 3 3 0
S 4 4 2 1 0 1
29 14 14 7 4 0 4
5 1 4 1 0 1 0
24 5 19 5 0 5 0
6 1 4
7 1 5
1 0 1
3 0 3
1 1 0
4 4 0
4 0 3
19 0 14
erage heart rate during 24 hours was higher (p < 0.05) in women than in men. In nine subjects, the longest sinus pause was equal to or more than 1.50 seconds, and in one subject the longest pause was more than 1.75 seconds (1.8:t seconds). Mild sinus arrhythmia was present in all participants, moderate sinus arrhythmia was present in 49 (18 men and 31 women), and marked sinus arrhythmia was found in nine (three men and six women). Atrial arrhythrnias (Table I.) Thirty-five subjects had atrial premature depolarizations. They were isolated and fewer than 100/24 hours in 21 (24 % ) a n d exceeded 100/24 hours (range 110 to 960, mean 370 _+ 115) in 11 patients (13%). Couplets were present in three (3 %) in whom the total number of atrial premature depolarizations was greater than 100 in 24 hours. Benign slow atrial tachycardia was present in 26 persons (30%); the number of episodes per patient was 7 _+ 8 in 24 hours (range 1-35). During episodes of benign slow atrial tachycardia, to the number of ectopic beats per episode ranged from 3 to 24 beats (mean 8 +_ 5 beats). Transient atrial fibrillation was present in three subjects (3%). The ventricular rate varied between 120 and 160 beats/min. One subject
experienced one episode of atrial fibrillation lasting for 17 minutes while asleep; another had two episodes during restful periods while awake, lasting 2 and 4 minutes; and the third subject had four episodes while awake lasting 2 to 6 minutes. No subject was aware of palpitations or other symptoms. The 29 subjects with benign slow atrial tachycardia or paroxysmal atrial fibrillation had, in addition, frequent (more than 100/24 hours ) atrial premature depolarizations. All 64 subjects with atrial arrhythmias had <100 atrial premature depolarizations/24 hours. No significant differences in the incidence of atrial arrhythmias were noted between gender, or between age groups (Table I). Ventricular arrhythmias (Table I). Ventricular premature depolarizations were present in 52 subjects. They were isolated and were less than 50/24 hours in 30 (35 % ). The total number in 24 hours exceeded 50 (range 64 to 745, mean 197 _+ 232) in eight persons (9%). Nine subjects (10%) had multiform ventricular premature depolarizations. The R-on-T phenomenon was observed in three subjects (3 % ). Ventricular couplets were seen in two persons (2 % ). The total number of ventricular premature depolarizations in
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ATRIAL ARRHYTHMIAS Fig. 1. Relationship between left atrial size, measured by M-mode echocardiography, and atrial arrhythmias in 86 elderly subjects without apparent heart disease. A significant (p < 0.01) correlation was found between left atria] size and the presence and complexity of atrial arrhythmias (grade 0 reflects no atrial arrhythmias, grade IV reflects the presence of the most complex atrial arrhythmias; see text for amplification). Bars represent mean +_ standard deviation.
24 hours was greater than 50 in each subject with ventricular couplets and early or multiform ventricular premature depolarizations. Ventricular tachycardia was detected in two (2 % ) subjects (three episodes in one subject and one in the other). The episodes included three, three, four, and seven consecutive beats at rates between 120 and 165 beats/min. No episode occurred during sleep and all were asymptomatic. One subject had, in addition, only isolated ventricular premature depolarizations, while the other had more than 50 multiform ventricular premature depolarizations in 24 hours. Accelerated idioventricular rhythm was seen in one subject (1% ) at a rate of approximately 60 beats/min. Twelve episodes were observed, and all of them occured during sleep. In addition, this subject had frequent (>50 in 24 hours) ventricular premature depolarizations, which were multiform and often coupled. No significant differences were found in the prevalence of ventricular arrhythmias between genders or between various age subgroups (Table I). Arrhythmias versus left atrial size and left ventricular
Left atrial size was less than 30 mm in nine subjects, was 30 to 39 mm in 51 subjects, and was 40 mm or more in 26 subjects, with a group mean of 36 • 5 mm (range 24 to 48 mm). Left ventricular mass.
mass index was less than 100 gm/m 2 in 22 subjects, 100 to 134 gm/m 2 in 43 subjects, and 135 gm/m 2 or more in 21 subjects, with a group mean of 117 _+ 25 gm/m 2 (range 72 to 173 gm/m2). A significant correlation was noted between left atrial size and the incidence and complexity of atrial arrhythmias (p < 0.01), as noted in Fig. 1, using the grading system described in the Methods section. The correlation was still significant (p < 0.05) when left atrial size was corrected for body size. Mean left atrial size was 31 • 4, 35 • 4, 38 • 4, 40 • 4, and 38 • 8 mm in subgroups with atrial arrhythmias graded 0, I, II, III, and IV, respectively (p < 0.01). Two of the three patients with atrial fibrillation had a left atrial size of 40 mm or more. The complexity of ventricular arrhythmias, graded as described in the Methods section, did not correlate significantly (p > 0.05) with left ventricular mass or with left ventricular mass index (Fig. 2). Furthermore, the incidence and complexity of ventricular arrhythmias in subjects with normal left ventricular mass 2~ (265 gm or lower) or normal left ventricular mass index 21 (134 gm/m2or lower) were similar to those in subjects with left ventricular mass greater than 265 gm or left ventricular mass index greater than 134 gm/m 2. We recognized that the arbitrary grading system used may not reflect the real arrhythmogenic properties of the left ventricle. Thus we correlated the absolute number of ventricular premature depolarizations in 24 hours with left ventricular mass (n = 55), using linear regression analysis. The correlation coefficient was 0.48 (p > 0.05). Lastly, since it is postulated that the increased left atrial size seen in the elderly population 12, 13 may be due to a diminished left ventricular compliance, 22, 23 we correlated the incidence and complexity of atrial arrhythmias with left ventricular mass and left ventricular mass index and found no statistical signifi: cance (p > 0.1). The relationship between atrial and ventricular arrhythmias, left atrial size, and left ventricular mass index is summarized in Table II, Atrioventricular block and intraventricular conduction
(Table I). First-degree AV block was detected in six subjects (7 % ). One episode of seconddegree AV block was present in one subject (1% ) who also had many episodes of first-degree AV block. Transient widening of the QRS complex to 0.12 and 0.13 second occurred in four subjects (5%). In the modified V5 lead, the appearance was that of right bundle branch block in three subjects and of left bundle branch block in one subject. In eight of the nine episodes, the widening of the QRS complex (with normal P waves and PR intervals) was tachycardia-dependent. abnormalities
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Arrhythmias in the elderly
DISCUSSION
Aging is associated with an increased prevalence of cardiac arrhythmias 1-s and characteristic morphologic changes in the heart such as an increased left atrial size and left ventricular wall thickness. 12, !3 The results of this study indicate that in an apparently healthy elderly population, a significant correlation exists between the frequency and complexity of atrial arrhythmias and left atrial size. However, the frequency and complexity of ventricular arrhythmias does not correlate significantly with left ventricular mass. Atrial arrhythmias and left atrial size. The subjects in this study had a higher prevalence of atrial arrhythmias in general and of benign slow atrial tachycardia in particular than that reported in young 24, 25 and middle-age 26populations. Furthermore, in those subjects with atrial arrhythmias, the grade of complexity was higher in the elderly subjects of our study than in younger subjects. 24-26 While transient atrial fibrillation was detected in 3% of subjects in the present study, agreeing with the findings of previous investigations,i, 2, 4, s ,27 this arrhythmia was not observed in studies of younger peopleY -26 Various atrial arrhythmias have been attributed to atrial dilatation, both in clinical and in laboratory settings.9, 10,2s Since cross-sectional studies have shown left atrial size to be relatively larger in the elderly than in younger subjects, 12' 13 we postulated that the increased frequency of atrial arrhythmias in the elderly may be in part related to an increased left atrial size. To test this hypothesis, it was necessary to select a population free of obvious cardiovascular disease or conditions known to produce cardiac abnormalities. Although our subjects underwent screening tests that excluded obvious cardiac conditions, we did not perform exercise tests or stress myocardial perfusion studies. 29 Thus clinically silent coronary artery disease could not be excluded. While it is possible that asymptomatic coronary artery disease was present in some of our subjects, the prevalence of arrhythmias in this study was similar to that reported by Fleg and Kennedy. s Their study only included subjects with normal exercise tests. The results of this investigation demonstrate a significant relationship between the frequency and complexity of atrial arrhythmias and left atrial size, suggesting that atrial dilatation plays a significant role in the pathogenesis of atrial tachyarrhythmias. This is in agreement with observations that atrial arrhythmias are commonly seen in clinical settings associated with right or left atrial dilatation, such as chronic pulmonary disease and mitral valve disease.9, I0,1~, ~0 In spite of a significant group relation-
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VENTRICULAR ARRHYTHMIAS Fig. 2. Relationship between left ventricular mass index, as assessed by M-mode echocardiography, and ventricular arrhythmias in 86 elderly subjects without apparent heart disease. No significant correlation (p > 0.20) was found between left ventricular mass and the presence or complexity of ventricular arrhythmias (grade 0 reflects no ventricular arrhythmias, grade IV reflects the presence of the most complex ventricnlar arrhythmias; see text for amplification). Bars represent mean _+ standard deviation.
ship between atrial arrhythmias and left atrial size, our data showed wide scatter. This scatter most likely reflects the finding that atrial dilatation is only one of several factors that may contribute to the pathophysiology of atrial arrhythmias. 1~ 2s Ventricular arrhythmias and left ventricular mass. The prevalence of simple and complex ventricular arrhythmias in this study was similar to that previously reported in young 24, 25, middle-aged % and elderly subjects 1, 2, s, 27 without obvious heart disease. Non-complex ventricular arrhythmias have been found more frequently in subjects with left ventricular hypertrophy due to arterial hypertension.11, 31, 32 Since the elderly without obvious heart disease have increased left ventricular wall thickness and mass, 12' 13, 33 we postulated that the incidence and complexity of ventricular arrhythmias could be directly related to left ventricular mass. Our results do not support this hypothesis. We found no significant relationship between ventricular arrhythmias and left ventricular mass index. Moreover, in this population of apparently healthy elderly individuals, the frequency and complexity of ventricular arrhythmias were similar in subjects with and without echocardiographically defined left ventricular hypertrophy.
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Table II. Arrhythmias, left atrial size, and left ventricular mass in 86 apparently healthy elderly subjects
Atrial arrhythmias
Ventricular arrhythmias
Number of subjects (men~women)
Age (yr)
0 I
---
67 74 71 76 73 75
Left ventricular mass index (gm/m 2)
II
--
III
--
IV --
-0
10/12 7/14 6/8 13/13 1/2 12/19
--
I
13/17
7 0 _+ 5
--
II
3/5
6 8 +_ 9
36 + 6
1 2 9 +_ 2 9
--
III
5/4 4/4
71 _+ 7 69 • 6
37 -+ 5 38 • 7
105 +_ 23 134 • 25
IV
_+ _+ +_ _+ • •
Left atrial size (ram) 8 6 8
31 • 4 35 • 4 38 _+ 4
7
4 0 _+ 4
9 5
38 +_ 8 34 • 3 3 8 -+ 4
113 118 117 121 117 114 117
_+ _+ + _+ • + _+
25 21 24 27 39 21 24
G r o u p results are given as m e a n + s t a n d a r d deviation. Atrial a n d ventricular a r r h y t h m i a s were graded from 0 (no a r r h y t h m i a ) to IV (most complex a r r h y t h mia); see text for further description.
In a previous study, McLenachan et al. "~1found a direct and significant relationship between the prevalence of complex ventricular arrhythmias and left ventricular mass index. Similarly, Messerli et al. 11 also reported a positive correlation between complex ventricular arrhythmias and electrocardiographically defined left ventricular hypertrophy. Our results that showed no correlation between ventricular arrhythmias and left ventricular mass may be attributed to the different populations studied. McLenachan et al. 31 and Messerli et al. 11 studied exclusively patients with arterial hypertension and obvious left ventricular hypertrophy on the electrocardiogram. We, on the other hand, excluded subjects with either of these two features and defined, by additional criteria, an apparently normal elderly population. The difference of the study populations is illustrated further by the values of left ventricular mass index: 193 _+ 71 gm/m 2 in the study of McLenachan et al. 31 (group showing increased ventricular arrhythmias) and 117 + 25 gm/m 2 (our study). Several explanations for our results are possible. First in the absence of a cardiovascular abnormality, an increased left ventricular mass in the elderly may be due to extracellular amyloid deposition 33, 34 and not to myofibrillar hypertrophy. Alternatively, in hypertensive patients with left ventricular hypertrophy, the "strain" pattern on the electrocardiogram may reflect subendocardial ischemia, 35 which may be responsible for the ventricular arrhythmias. The aging heart has been characterized by a modest increase in cardiac mass and a reduction in left ventricular compliance, changes that are similar to those seen in hypertension. The results of our investigation are in agreement with the concept that myocardial hypertrophy "per Se" does not appear to be the common link between cellular changes due to aging and those due to hypertension. 36 It is of interest
also to note t h a t the increased left ventricular mass that occurs in well-trained endurance athletes was not associated with ventricular arrhythmias. 37 Limitations. First, we used M-mode and not twodimensional echocardiography to estimate left ventricular mass. However, previous studies have shown that both techniques are equally accurate to estimate left ventricular mass. 21 The addition of Doppler studies would have given us the opportunity to study the correlation of cardiac arrhythmias with left ventricular diastolic function. Second, we could not exclude the possibility that some patients had asymptomatic coronary artery disease, since none of them underwent exercise testing or cardiac catherization. Third, comparison of the prevalence of cardiac arrhythmias in this study with t h a t in younger Subjects was made using historical controls. Our main conclusions, however, do not depend on accurate prevalence comparisions between the two populations. Fourth, classification of atrial and ventricular arrhythmias based on their frequency and complexity, although widely used, 1-8,24-27 is arbitrary and may reflect poorly the underlying pathophysiology. Additional observations. In this study the incidence of AV block was similar to that in younger24-26 populations. Transient intraventricular conduction defects have not been reported in younger subjects. 2426 whereas this abnormality was present in 5 % of our elderly subjects. This could be a manifestation of the known histologic changes of the conduction pathways of the normal aging heart. 3s Another interesting finding was the higher 24-hour average heart rate in women, which extends to the elderly previous observations made in young24, 25 and middle-aged26 subjects. In only 1% of elderly subjects was the longest sinus pause greater than 1.75 seconds, which is in contrast to the 28 % incidence of this finding reported in
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young men. 24 This may reflect on enhanced vagal tone in the young compared with that in the elderly. In addition, the lower incidence of sinus arrhythmia, sinus tachycardia, and sinus bradycardia and the absence of severe sinus bradycardia in the present investigation compared with the findings reported in younger persons 2224 may be due to lesser autonomic nervous system swings or to a less responsive sinus node in the elderly. Conclusions. The results of this study suggest that the high prevalence of atrial arrhythmias in the elderly without apparent heart disease may be explained in part by the larger left atrial size, which characterizes the normal aging heart. While greater left ventricular mass has been associated with increased cardiovascular events and ventricular arrhythmias in other clinical settings, 39, 40 we detected no such association in an elderly population free of obvious cardiovascular disease. Whether an increased left ventricular mass is associated with other morbid events in this population remains to be assessed by longitudinal studies. Our findings support the concept that myocardial hypertrophy does not appear to be the common link between cellular changes due to aging and those due to hypertension. 36
Arrhythmias in the elderly
12. 13.
14.
15. 16. 17. 18.
19.
20.
We acknowledge the invaluable help of Peter Martin, Marlene Johnson, and Patricia Cape. We are also grateful to Delores Fleming and Debbie Woelke for their assistance in manuscript preparation.
21.
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1. Raftery EB, Cashman PMM. Long-term recording of the electrocardiogram in a normal population. Postgrad Med J 1976:52 (suppl 7):32-8. 2. Glasser SP, Clark PI, Applebaum HJ. Occurrence of frequent complex arrhythmias detected by ambulatory monitoring in an apparently healthy asymptomatic population. Chest 1979; 75:565-8. 3. Clee MD, Smith N, McNeill GP, Wright DS. Dysrhythmias in apparently healthy elderly subjects. Age Ageing 1979;8:173-6. 4. Dos Santos RAG, Lye M. Transient cardiac arrhythmias in healthy elderly individuals: how relevant are they? J Clin Exp Gerontol 1980;2:245-58. 5. Camm AJ, Evans KE, Ward DE, Martin A. The rhythm of the heart in active elderly subjects. AM HEARTJ 1980;99:598-603. 6. Martin A, Benbow LJ, Butrous GS, Leach C, Camm AJ. Fiveyear follow up of 101 elderly subjects by means of long-term ambulatory cardiac monitoring. Eur Heart J 1984;5:592-6. 7. Kantelip JP, Sage E, Duchene-Marullaz P. Findings on ambulatory electrocardiographic monitoring in subjects older than 80 years. Am J Cariol 1986;57:398-401. 8. Fleg J, Kennedy HL. Cardiac arrhythmias in a healthy elderly population. Chest 1982:81:302-7. 9. Smith WM, Gallagher JJ. Mechanisms of arrhythmis and conduction abnormalities. In: Hurst JW, ed. The Heart. 6th ed. New York: McGraw-Hill Book Co.: 1986:415. 10. Davies MJ, Anderson RH, Becket AE. Pathology of atrial arrhythmias. In: The conduction system of the heart. London: Butterworth Scientific Publications, 1983:203-15. 11. Messerli FH, Ventura H, Elizardi D, Dunn F, Frohlich ED. Hypertension and sudden death. Increased ventricular ectopic
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30. 31. 32.
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activity in left ventricular hypertrophy. Am J Med 1984;77: 18-22. Gerstrenblith G, Frederuksen J, Yin FCP, Fortuin NJ, Lakatta EG, Weisfeldt ML. Echocardiographic assessment of a normal adult aging population. Circulation 1977;56:273-8. Manyari D, Patterson C, Johnson D, Meledez L, Boughner D, Kostuk W, Cape R. An echocardiographic study on resting left ventricular function in healthy elderly subjects. J Clin Exp Gerontol 1982;4:403-21. Patterson C, Manyari DE, Johnson D, Cape R. Occult cardiac arrhythmias in healthy aged subjects. In: Proceedings of the XII International Congress of Gerontology. Hamburg: July 12-17, 1981:106. Morris NW, Skrobzi Z, Nelson DA. Zeta sedimentation ratio "ZRS." A replacement for the erythrocyte sedimentation rate "ERS." Am J Clin Pathol 1975;64:254-65. Stemple DR, Fitzgerald JW, Winkle RA. Benign slow atrial tachycardia. Ann Intern Med 1977;87:44-8. Criteria Committee, New York Heart Association. Nomenclature and criteria for diagnosis of disease of the heart and great vessels. 8th ed. Boston: Little, Brown & Co., 1979;:188-250. Henry WL, Clark CE, Epstein SE. Asymmetric septal hypertrophy: echocardiographic identification of the pathognomonic anatomic abnormality of IHSS, Circulation 1973;47: 225-31. Sahn D J, DeMaria A, Kisslo J, Weyman A. Recommendations regarding quantitation in M-mode echocardiography: results of a survey of echocardiographic measurements. Circulation 1978;58:1072-83. Woythaler JN, Singer SL, Kwan 0, Meltzer R, Reubner B, Bommer W, DeMaria A. Accuracy of echocardiography versus electrocardiography in detecting left ventricular hypertrophy: Comparison with postmortem mass measurements. J Am Coll Cardiol 1983;2:305-11. Devereux RB, Reichek N. Echocardiographic determination of left ventricular mass in man: Anatomic validation of the method. Circulation 1977;55:613-8. Manyari DE, Patterson C, Johnson D, Belenkie I, Anderson P, Melendez L, Cape R. Left ventricular diastolic function in a population of healthy elderly subjects: an echocardiographic study. J Am Geriatr Soc 1985;33:758-63. Bonow RO, Vitale DF, Bacharach SL, Maron BJ, Green MV. Effects of aging on asynchronous left ventricular regional function and global ventricular filling in normal human subjects. J Am Coll Cardiol 1988;11:50-8. Brodsky M, Wu D, Denes P, Kanakis C, Rosen KM. Arrhythmias documented by 24-hour continuous electrocardiographic monitoring in 50 male medical students without apparent heart disease. Am J Cardiol 1977;39:390-5. Sobotka PA, Mayer JH, Bauernfeind RA, Kanakis C, Rosen KM. Arrhythmias documented by 24-hour continuous ambulatory electrocardiographic monitoring in young women without apparent heart disease. AM HEARTJ 1981;101:753-9. Clarke JM, Hamer J, Shelton JR, Taylor S, Venning GR. The rhythm of the normal human heart. Lancet 1976;2:508-12. Rossi A. Twenty-four-hour electrocardiographic study in the active very elderly. Cardiology 1987;74:159-66. Wyndham CRC. What's wrong with the atrium in patients with atrial fibrillation? Int J Cardiol 1982;2:199-202. Gerstenblith G, Fleg JL, Van Tosh A, Becker B, Kallman C, Andres R, Weisfeldt M, Lakatta EG. Stress testing redefines the prevalence of coronary artery disease in epidemiologic studies [Abstract]. Circulation 1980;62(suppl III ):III-308. Shine KI, Kastor JA, Yurchak PM. Multifocal atrial tachycardia. Clinical and electrocardiographic features in 32 patients. N Engl J Med 1968;279:344-9. McLenachan JM, Henderson E, Morris KI, Dargie HJ. Ventricular arrhythmias in patients with hypertensive left ventricuiar hypertrophy. N Engl J Med 1987:317:787-92. Levy D, Savage DD, Garrison RJ, Balkus S, Anderson K, Kannel W, Castelli WP. The association of left ventricular hypertrophy with ventricular arrhythmias: the Framingham
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Heart Study [Abstract]. Circulation 1985;72(suppl 3):III-46. 33. Lakatta EG, Mitchell JH, Promerance A, Rowe GG. Human aging: changes in structure and function. J Am Cull Cardiol 1987;10:(suppl A):42A-7A. 34. Hodkinson HM, Promerance A. The clinical significance of senile cardiac amyloidosis: a prospective clinico-pathological study. Q J Med 1977;46:381-7. 35. Rembert JC, Kleinman LH, Fedor JM, Wechsler A, Greenfield JC. Myocardial blood flow distribution in concentric left ventricular hypertrophy. J Clin Invest 1978;62:379-86. 36. Lakatta EG. Do hypertension and aging have a similar effect on the myocardium. Circulation t987;75(suppl I ):I-69~I-77. 37. Kelly P, Thigpen T. Ginzton L. Ventricular hypertrophy in
May 1990 American Heart Journal
endurance athletes is not associated with complex ventricular ectopy [Abstract]. Circulation 1985;72 (suppl 3): III-46. 38. Fujino M, Okada R, Arakawa K. The relationship of aging to histological changes in the conduction system of the normal human heart. Jpn Heart J 1983;24:13-20. 39. Casale P, Devereux R, Milner M, Zullo G, Harshfield G, Pickering T, Laragh J. Value of echocardiographic measurement of left ventricular mass in predicting cardiovascular morbid events in hypertensive men. Ann Intern Med 1986; 105:173- 8. 40. Kannel WB, Gordon T, Offutt D. Left ventricular hypertrophy by electrocardiogram: Prevalence, incidence, and mortality in the Framingham Study. Ann Intern Med 1969;71:89-105.
I
Atrial and ventricular arrhythmias in asymptomatic active elderly subjects: Correlation with left atrial size and left ventricular mass Elderly normal subjects have an increased prevalence of cardiac arrhythmias compared with young and middle-aged subjects. The objective of this study was to test the hypothesis that the incidence and complexity of atrial and ventricular arrhythmlas may be related to either left atrial enlargement or to increased left ventricular mass, respectively. From 146 asymptomatic volunteers older than 60 years, 86 subjects were considered to be free of cardiovascular abnormalities and had adequate M-mode echocardiograms and 24-hour ambulatory electrocardiograms. The mean age was 72 ___ 7 years, with a range of 60 to 96 years. There were 37 men and 49 women. During 1415 • 73 minutes of ambulatory electrocardiography, the average heart rate was 72 • 8 beats/min in men and 76 ___6 beats/min in women (p < 0.05). Atrial arrhythmias were present in 64 subjects (74%); the frequency and complexity of these arrhythmias correlated with left atrial size (p < 0.01). Ventricular arrhythmias were present in 55 subjects (64%); the frequency and complexity of ventricular arrhythmias did not correlate with left ventricular mass index. These results suggest that left atrial dilatation, a normal development in healthy elderly subjects, plays a significant role in the pathophysiology of the increased incidence of atrial arrhythmias. Increased left ventricular mass, which also occurs normally in the aging heart, is not, on the other hand, associated with an increased frequency a n d / o r complexity of ventricular arrhythmias. (AM HEART J 1 9 9 0 ; 1 1 9 : 1 0 6 9 . )
D a n t e E. Manyari, MD, Christopher P a t t e r s o n , MD, David Johnson, MD, L i b a r d o Melendez, MD, William J. Kostuk, MD and Ronald D.T. Cape, MD.
London, Ontario, Canada
A high prevalence of cardiac a r r h y t h m i a s has been r e p o r t e d in a p p a r e n t l y healthyl-Tand normal 8 elderly persons. T h i s suggests t h a t r h y t h m disorders m a y be related to intrinsic changes in the aging heart, indep e n d e n t of disease. In patients with various cardiac and p u l m o n a r y diseases, atrial a r r h y t h m i a s are associated with atrial enlargement, 9,10 and increased ventricular ectopic activity has been f o u n d in subjects with systemic h y p e r t e n s i o n with increased left ventricular mass. 11 Since m o d e s t increases of b o t h left atrial size and left ventricular mass have been described in elderly subjects, 12,13 we p o s t u l a t e d t h a t these anatomic characteristics could be related to the From the Sectionsof Cardiologyand GeriatricMedicine,Departmentof Medicine,Universityof Western OntarioHospitals. Supported in part by a grant fromthe OntarioHeart and StrokeFoundation, Toronto,Canada. Receivedfor publicationSept. 8, 1989;acceptedJan. 2, 1990. Reprint requests: Dr. Dante E. Manyari, Foothills Hospital, 1403-29th Street N.W., Calgary,Alberta Canada T2N 2T9. 4/1/19077
increased prevalence of atrial and ventricular arrhythmias, respectively. T h e objective of this s t u d y was to correlate the presence a n d complexity of cardiac a r r h y t h m i a s with left atrial size and left ventricular mass in a p p a r e n t l y healthy, active elderly subjects. METHODS Study population. One hundred forty-six asymptomatic volunteers 60 years of age or older were screened for participation in a large prospective study on the cardiovascular function in a healthy elderly population. 13,14 This report is part of that study. After history taking and physical examination, all subjects had the following investigations: hemoglobin concentration, zeta sedimentation rate, 15 serum electrolytes including phosphorus and calcium, blood urea nitrogen, serum creatinine and glucose, urinalysis, chest x-ray film, electrocardiogram, M-mode echocardiogram, and spirometry (forced expiratory volume and forced expiratory volume in the first second). Subjects were included if they met the following criteria: (1) absence of cardiorespiratory or systemic disease known to affect 1069
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Man yari et al.
cardiac structure or function such as hypertension, diabetes mellitus, obstructive lung disease, thyroid dysfunction, etc.; (2) normal 12-lead electrocardiogram, apart from minor non-specific repolarization abnormalities or right bundle branch block; (3) normal cardiac shadow and lungs on chest x-ray film; (4) normal hematologic and biochemical studies; (5) no evidence of myocardial, pericardial, or valvular heart disease on echocardiogram (not considering left ventricular mass); and (6) normal spirometry. We also excluded all subjects who were taking cardiovascular medication, but some subjects were taking simple analgesics or minor tranquilizers. Volunteers meeting these criteria were judged to be free of overt heart disease and were considered appropriate candidates for arrhythmia monitoring. Thirty-three of the 146 volunteers were excluded because of hypertension (blood pressure >160/95 mm Hg on at least two occasions), chronic obstructive pulmonary disease, left ventricular hypertrophy on the electrocardiogram, cardiomegaly on chest x-ray film, diabetes mellitus, asymmetric septal hypertrophy, evidence of old myocardial infarction, mitral valve prolapse, hyperthyroidism, and electrolyte abnormalities. Three subjects who were taking major tranquilizers were also excluded. In 18 subjects, the echocardiograms were technically inadequate to assess left atrial size and left ventricular dimensions or wall thickness. Thus, 92 volunteers were judged to be healthy. Eighty-six subjects completed the study; two had technically inadequate ambulatory electrocardiogram recordings and four subjects refused to carry the tape recorder. Mean age of the 86 participants was 72 _+ 7 years. There were 37 men, age 71 __+6 years (range 60 to 87) and 49 women, mean age 73 ___8 years (range 60 to 96). Results were analyzed in arbitrary subgroups of subjects aged 60 to 69, 70 to 75, and 76 to 96 years. Ambulatory electrocardiography. Ambulatory monitoring was carried out with a two-channel 24-hour portable electrocardiogram tape recorder (Model 445, Del Mar Avionics, Irvine, Calif.) and a bipolar electrode lead system for each channel (modified V5 and II). We encouraged subjects to continue normal, everyday activities. We analzed the tapes using a rapid scanner with audiovisual superimposed electrocardiogram imaging and an arrhythmiagraph trace of R-R intervals (Model 660A computerized electrocardioscanner, Del Mar Avionics). At high speed (• a histogram of heart rate versus time for the entire 24 hours was recorded. Two independent observers (an experienced technologist and a cardiologist) then reviewed each tape at a slower speed (• to detect all abnormalities. Hard copies of all arrhythmic events were recorded for detailed analysis. Changes of ST segment were not analyzed because of lack of calibration during recording. Definitions. Average heart rate was defined as the number of beats recorded divided by the recording time in minutes. T h e longest pause was defined by the greatest R-R interval excluding episodes of second-degree atrioventricular (AV) block or postextrasystolic depolarizations. Sinus tachycardia, sinus bradycardia, and severe sinus bradycardia were defined by rates greater than 100 beats/ min, less than 60 beats/min, and less than 40 beats/min,
AmericanHeartJournal
respectively, with normal P wave morphology and adjacent cycle lengths varying by less than 10% for at least four consecutive beats. Mild, moderate, and marked sinus arrhythmias were defined as irregular sinus rhythm with adjacent R-R intervals varying by 10% to 50%, by 50% to 100%, and by more than 100%, respectively. Benign slow atrial tachycardia, an atrial rhythm described by Stemple et al., 16was defined as an abrupt decrease in the R-R interval of greater than 30% that persisted for at least three consecutive beats and was characterized by irregular P-P intervals, variable P wave morphology and P-R intervals, normal QRS configuration, and a rate between 80 and 140 beats/min. Ventricular arrhythmias were described as unifocal, multiform, ventricular couplets (two consecutive ventricular premature depolarizations), ventricular tachycardia (three or more consecutive ventricular premature depolarizations), and R-on-T phenomena. All other arrhythmias were defined by standard electrocardiographic criteria. 17 Echocardiographic studies. M-mode echocardiograms were recorded using a Unirad Series C echocardiograph unit equipped with a 2.5 MHz transducer and interfaced to a Honeywell 1858 strip chart recorder (PPG Biomedical Systems, Medical Electronics Division, Pleasantville, N.Y.). To avoid measurement errors in wall thickness that may occur when the ultrasound beam passes obliquely through the left ventricular cavity, the T-scan technique described by Henry et al. Is was used. Measurements were made according to the recommendations of the American Society of EchocardiographyJ9 Left ventricular mass was calculated using Woythaler's modification2~of the mathematical model described by Devereux and Reichek. 21 Statistical analysis. Results are expressed as group mean _+ standard deviation. We used Students' t test (two groups) or analysis of variance (more than two groups) to assess the significance of the differences between groups. Statistical significance was set at 5 % (p < 0.05). To assess the relationship between atrial arrhythmias and left atrial size, the complexity of atrial arrythmias was arbitrarily graded as follows: 0 = absence of atrial arrhythmias; I = less than 100 atrial premature depolarizations in 24 hours; II = more than 100 atrial premature depolarizations in 24 hours, with or without couplets; I I I = benign slow atrial tachycardia; and IV = atrial fibrillation. To assess the relationship between ventricular arrhythmias and left ventricular mass, the complexity of ventricular arrhythmias was arbitrarily graded as follows: 0 = absence of ventricular arrhythmias; I = isolated (<50) ventricular premature depolarizations in 24 hours; II = >50 ventricular premature depolarizations in 24 hours; I I I = multiform ventricular premature depolarizations; and IV = early ventricular premature depolarizations (R-on-T phenomenon), couplets, ventricular tachycardia, and accelerated idioventricular rhythm. RESULTS
T h e group d u r a t i o n of the a m b u l a t o r y electrocardiogram recording was 1415 _+ 73 minutes. T h e av-
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Arrhythmias in the elderly
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T a b l e I.
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Arrhythmias observed at different age groups in 86 asymptomatic elderly subjects All s u ~ e c t s =8~
Sinus node function Sinus tachycardia Sinus bradycardia Severe sinus bradycardia Mild sinus a r r h y t h m i a Moderate sinus arrhythmia Marked sinus a r r h y t h m i a Atrial premature depolarizations <100/24 hours >100/24 hours Couplets Benig n slow atrial tachycardia Paroxysmal atrial fibrillation Ventricular premature depolarizations <50/24 hours >50/24 hours Multiform R-on-T p h e n o m e n o n Couplets Ventricular tachycardia Accelerated idioventricular r h y t h m Atrioventricular block First-degree Second-degree, type 1 Intraventricular conduction defect
60-69 years ~ =3~
7 0 - ~ years ~ =2~
~ years ~ =21)
No.
%
No.
%
No.
%
No.
%
74 63 0 37 40 9
86 73 0 43 47 10
34 27 0 16 16 5
92 73 0 43 43 14
24 17 0 10 17 1
88 61 0 36 61 4
16 19 0 11 7 3
76 90 0 52 33 14
21 11 3 26 3
24 13 3 30 3
6 6 1 10 2
16 16 3 27 5
10 3 0 10 0
36 11 0 36 0
5 2 2 6 1
24 10 10 29 5
30 8 9 3 2 2 1
35 9 10 3 2 2 1
17 3 1 0 1 1 0
46 8 3 0 3 3 0
S 4 4 2 1 0 1
29 14 14 7 4 0 4
5 1 4 1 0 1 0
24 5 19 5 0 5 0
6 1 4
7 1 5
1 0 1
3 0 3
1 1 0
4 4 0
4 0 3
19 0 14
erage heart rate during 24 hours was higher (p < 0.05) in women than in men. In nine subjects, the longest sinus pause was equal to or more than 1.50 seconds, and in one subject the longest pause was more than 1.75 seconds (1.8:t seconds). Mild sinus arrhythmia was present in all participants, moderate sinus arrhythmia was present in 49 (18 men and 31 women), and marked sinus arrhythmia was found in nine (three men and six women). Atrial arrhythrnias (Table I.) Thirty-five subjects had atrial premature depolarizations. They were isolated and fewer than 100/24 hours in 21 (24 % ) a n d exceeded 100/24 hours (range 110 to 960, mean 370 _+ 115) in 11 patients (13%). Couplets were present in three (3 %) in whom the total number of atrial premature depolarizations was greater than 100 in 24 hours. Benign slow atrial tachycardia was present in 26 persons (30%); the number of episodes per patient was 7 _+ 8 in 24 hours (range 1-35). During episodes of benign slow atrial tachycardia, to the number of ectopic beats per episode ranged from 3 to 24 beats (mean 8 +_ 5 beats). Transient atrial fibrillation was present in three subjects (3%). The ventricular rate varied between 120 and 160 beats/min. One subject
experienced one episode of atrial fibrillation lasting for 17 minutes while asleep; another had two episodes during restful periods while awake, lasting 2 and 4 minutes; and the third subject had four episodes while awake lasting 2 to 6 minutes. No subject was aware of palpitations or other symptoms. The 29 subjects with benign slow atrial tachycardia or paroxysmal atrial fibrillation had, in addition, frequent (more than 100/24 hours ) atrial premature depolarizations. All 64 subjects with atrial arrhythmias had <100 atrial premature depolarizations/24 hours. No significant differences in the incidence of atrial arrhythmias were noted between gender, or between age groups (Table I). Ventricular arrhythmias (Table I). Ventricular premature depolarizations were present in 52 subjects. They were isolated and were less than 50/24 hours in 30 (35 % ). The total number in 24 hours exceeded 50 (range 64 to 745, mean 197 _+ 232) in eight persons (9%). Nine subjects (10%) had multiform ventricular premature depolarizations. The R-on-T phenomenon was observed in three subjects (3 % ). Ventricular couplets were seen in two persons (2 % ). The total number of ventricular premature depolarizations in
May 1 9 9 0
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ATRIAL ARRHYTHMIAS Fig. 1. Relationship between left atrial size, measured by M-mode echocardiography, and atrial arrhythmias in 86 elderly subjects without apparent heart disease. A significant (p < 0.01) correlation was found between left atria] size and the presence and complexity of atrial arrhythmias (grade 0 reflects no atrial arrhythmias, grade IV reflects the presence of the most complex atrial arrhythmias; see text for amplification). Bars represent mean +_ standard deviation.
24 hours was greater than 50 in each subject with ventricular couplets and early or multiform ventricular premature depolarizations. Ventricular tachycardia was detected in two (2 % ) subjects (three episodes in one subject and one in the other). The episodes included three, three, four, and seven consecutive beats at rates between 120 and 165 beats/min. No episode occurred during sleep and all were asymptomatic. One subject had, in addition, only isolated ventricular premature depolarizations, while the other had more than 50 multiform ventricular premature depolarizations in 24 hours. Accelerated idioventricular rhythm was seen in one subject (1% ) at a rate of approximately 60 beats/min. Twelve episodes were observed, and all of them occured during sleep. In addition, this subject had frequent (>50 in 24 hours) ventricular premature depolarizations, which were multiform and often coupled. No significant differences were found in the prevalence of ventricular arrhythmias between genders or between various age subgroups (Table I). Arrhythmias versus left atrial size and left ventricular
Left atrial size was less than 30 mm in nine subjects, was 30 to 39 mm in 51 subjects, and was 40 mm or more in 26 subjects, with a group mean of 36 • 5 mm (range 24 to 48 mm). Left ventricular mass.
mass index was less than 100 gm/m 2 in 22 subjects, 100 to 134 gm/m 2 in 43 subjects, and 135 gm/m 2 or more in 21 subjects, with a group mean of 117 _+ 25 gm/m 2 (range 72 to 173 gm/m2). A significant correlation was noted between left atrial size and the incidence and complexity of atrial arrhythmias (p < 0.01), as noted in Fig. 1, using the grading system described in the Methods section. The correlation was still significant (p < 0.05) when left atrial size was corrected for body size. Mean left atrial size was 31 • 4, 35 • 4, 38 • 4, 40 • 4, and 38 • 8 mm in subgroups with atrial arrhythmias graded 0, I, II, III, and IV, respectively (p < 0.01). Two of the three patients with atrial fibrillation had a left atrial size of 40 mm or more. The complexity of ventricular arrhythmias, graded as described in the Methods section, did not correlate significantly (p > 0.05) with left ventricular mass or with left ventricular mass index (Fig. 2). Furthermore, the incidence and complexity of ventricular arrhythmias in subjects with normal left ventricular mass 2~ (265 gm or lower) or normal left ventricular mass index 21 (134 gm/m2or lower) were similar to those in subjects with left ventricular mass greater than 265 gm or left ventricular mass index greater than 134 gm/m 2. We recognized that the arbitrary grading system used may not reflect the real arrhythmogenic properties of the left ventricle. Thus we correlated the absolute number of ventricular premature depolarizations in 24 hours with left ventricular mass (n = 55), using linear regression analysis. The correlation coefficient was 0.48 (p > 0.05). Lastly, since it is postulated that the increased left atrial size seen in the elderly population 12, 13 may be due to a diminished left ventricular compliance, 22, 23 we correlated the incidence and complexity of atrial arrhythmias with left ventricular mass and left ventricular mass index and found no statistical signifi: cance (p > 0.1). The relationship between atrial and ventricular arrhythmias, left atrial size, and left ventricular mass index is summarized in Table II, Atrioventricular block and intraventricular conduction
(Table I). First-degree AV block was detected in six subjects (7 % ). One episode of seconddegree AV block was present in one subject (1% ) who also had many episodes of first-degree AV block. Transient widening of the QRS complex to 0.12 and 0.13 second occurred in four subjects (5%). In the modified V5 lead, the appearance was that of right bundle branch block in three subjects and of left bundle branch block in one subject. In eight of the nine episodes, the widening of the QRS complex (with normal P waves and PR intervals) was tachycardia-dependent. abnormalities
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Arrhythmias in the elderly
DISCUSSION
Aging is associated with an increased prevalence of cardiac arrhythmias 1-s and characteristic morphologic changes in the heart such as an increased left atrial size and left ventricular wall thickness. 12, !3 The results of this study indicate that in an apparently healthy elderly population, a significant correlation exists between the frequency and complexity of atrial arrhythmias and left atrial size. However, the frequency and complexity of ventricular arrhythmias does not correlate significantly with left ventricular mass. Atrial arrhythmias and left atrial size. The subjects in this study had a higher prevalence of atrial arrhythmias in general and of benign slow atrial tachycardia in particular than that reported in young 24, 25 and middle-age 26populations. Furthermore, in those subjects with atrial arrhythmias, the grade of complexity was higher in the elderly subjects of our study than in younger subjects. 24-26 While transient atrial fibrillation was detected in 3% of subjects in the present study, agreeing with the findings of previous investigations,i, 2, 4, s ,27 this arrhythmia was not observed in studies of younger peopleY -26 Various atrial arrhythmias have been attributed to atrial dilatation, both in clinical and in laboratory settings.9, 10,2s Since cross-sectional studies have shown left atrial size to be relatively larger in the elderly than in younger subjects, 12' 13 we postulated that the increased frequency of atrial arrhythmias in the elderly may be in part related to an increased left atrial size. To test this hypothesis, it was necessary to select a population free of obvious cardiovascular disease or conditions known to produce cardiac abnormalities. Although our subjects underwent screening tests that excluded obvious cardiac conditions, we did not perform exercise tests or stress myocardial perfusion studies. 29 Thus clinically silent coronary artery disease could not be excluded. While it is possible that asymptomatic coronary artery disease was present in some of our subjects, the prevalence of arrhythmias in this study was similar to that reported by Fleg and Kennedy. s Their study only included subjects with normal exercise tests. The results of this investigation demonstrate a significant relationship between the frequency and complexity of atrial arrhythmias and left atrial size, suggesting that atrial dilatation plays a significant role in the pathogenesis of atrial tachyarrhythmias. This is in agreement with observations that atrial arrhythmias are commonly seen in clinical settings associated with right or left atrial dilatation, such as chronic pulmonary disease and mitral valve disease.9, I0,1~, ~0 In spite of a significant group relation-
1073
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VENTRICULAR ARRHYTHMIAS Fig. 2. Relationship between left ventricular mass index, as assessed by M-mode echocardiography, and ventricular arrhythmias in 86 elderly subjects without apparent heart disease. No significant correlation (p > 0.20) was found between left ventricular mass and the presence or complexity of ventricular arrhythmias (grade 0 reflects no ventricular arrhythmias, grade IV reflects the presence of the most complex ventricnlar arrhythmias; see text for amplification). Bars represent mean _+ standard deviation.
ship between atrial arrhythmias and left atrial size, our data showed wide scatter. This scatter most likely reflects the finding that atrial dilatation is only one of several factors that may contribute to the pathophysiology of atrial arrhythmias. 1~ 2s Ventricular arrhythmias and left ventricular mass. The prevalence of simple and complex ventricular arrhythmias in this study was similar to that previously reported in young 24, 25, middle-aged % and elderly subjects 1, 2, s, 27 without obvious heart disease. Non-complex ventricular arrhythmias have been found more frequently in subjects with left ventricular hypertrophy due to arterial hypertension.11, 31, 32 Since the elderly without obvious heart disease have increased left ventricular wall thickness and mass, 12' 13, 33 we postulated that the incidence and complexity of ventricular arrhythmias could be directly related to left ventricular mass. Our results do not support this hypothesis. We found no significant relationship between ventricular arrhythmias and left ventricular mass index. Moreover, in this population of apparently healthy elderly individuals, the frequency and complexity of ventricular arrhythmias were similar in subjects with and without echocardiographically defined left ventricular hypertrophy.
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Manyari et al.
Table II. Arrhythmias, left atrial size, and left ventricular mass in 86 apparently healthy elderly subjects
Atrial arrhythmias
Ventricular arrhythmias
Number of subjects (men~women)
Age (yr)
0 I
---
67 74 71 76 73 75
Left ventricular mass index (gm/m 2)
II
--
III
--
IV --
-0
10/12 7/14 6/8 13/13 1/2 12/19
--
I
13/17
7 0 _+ 5
--
II
3/5
6 8 +_ 9
36 + 6
1 2 9 +_ 2 9
--
III
5/4 4/4
71 _+ 7 69 • 6
37 -+ 5 38 • 7
105 +_ 23 134 • 25
IV
_+ _+ +_ _+ • •
Left atrial size (ram) 8 6 8
31 • 4 35 • 4 38 _+ 4
7
4 0 _+ 4
9 5
38 +_ 8 34 • 3 3 8 -+ 4
113 118 117 121 117 114 117
_+ _+ + _+ • + _+
25 21 24 27 39 21 24
G r o u p results are given as m e a n + s t a n d a r d deviation. Atrial a n d ventricular a r r h y t h m i a s were graded from 0 (no a r r h y t h m i a ) to IV (most complex a r r h y t h mia); see text for further description.
In a previous study, McLenachan et al. "~1found a direct and significant relationship between the prevalence of complex ventricular arrhythmias and left ventricular mass index. Similarly, Messerli et al. 11 also reported a positive correlation between complex ventricular arrhythmias and electrocardiographically defined left ventricular hypertrophy. Our results that showed no correlation between ventricular arrhythmias and left ventricular mass may be attributed to the different populations studied. McLenachan et al. 31 and Messerli et al. 11 studied exclusively patients with arterial hypertension and obvious left ventricular hypertrophy on the electrocardiogram. We, on the other hand, excluded subjects with either of these two features and defined, by additional criteria, an apparently normal elderly population. The difference of the study populations is illustrated further by the values of left ventricular mass index: 193 _+ 71 gm/m 2 in the study of McLenachan et al. 31 (group showing increased ventricular arrhythmias) and 117 + 25 gm/m 2 (our study). Several explanations for our results are possible. First in the absence of a cardiovascular abnormality, an increased left ventricular mass in the elderly may be due to extracellular amyloid deposition 33, 34 and not to myofibrillar hypertrophy. Alternatively, in hypertensive patients with left ventricular hypertrophy, the "strain" pattern on the electrocardiogram may reflect subendocardial ischemia, 35 which may be responsible for the ventricular arrhythmias. The aging heart has been characterized by a modest increase in cardiac mass and a reduction in left ventricular compliance, changes that are similar to those seen in hypertension. The results of our investigation are in agreement with the concept that myocardial hypertrophy "per Se" does not appear to be the common link between cellular changes due to aging and those due to hypertension. 36 It is of interest
also to note t h a t the increased left ventricular mass that occurs in well-trained endurance athletes was not associated with ventricular arrhythmias. 37 Limitations. First, we used M-mode and not twodimensional echocardiography to estimate left ventricular mass. However, previous studies have shown that both techniques are equally accurate to estimate left ventricular mass. 21 The addition of Doppler studies would have given us the opportunity to study the correlation of cardiac arrhythmias with left ventricular diastolic function. Second, we could not exclude the possibility that some patients had asymptomatic coronary artery disease, since none of them underwent exercise testing or cardiac catherization. Third, comparison of the prevalence of cardiac arrhythmias in this study with t h a t in younger Subjects was made using historical controls. Our main conclusions, however, do not depend on accurate prevalence comparisions between the two populations. Fourth, classification of atrial and ventricular arrhythmias based on their frequency and complexity, although widely used, 1-8,24-27 is arbitrary and may reflect poorly the underlying pathophysiology. Additional observations. In this study the incidence of AV block was similar to that in younger24-26 populations. Transient intraventricular conduction defects have not been reported in younger subjects. 2426 whereas this abnormality was present in 5 % of our elderly subjects. This could be a manifestation of the known histologic changes of the conduction pathways of the normal aging heart. 3s Another interesting finding was the higher 24-hour average heart rate in women, which extends to the elderly previous observations made in young24, 25 and middle-aged26 subjects. In only 1% of elderly subjects was the longest sinus pause greater than 1.75 seconds, which is in contrast to the 28 % incidence of this finding reported in
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young men. 24 This may reflect on enhanced vagal tone in the young compared with that in the elderly. In addition, the lower incidence of sinus arrhythmia, sinus tachycardia, and sinus bradycardia and the absence of severe sinus bradycardia in the present investigation compared with the findings reported in younger persons 2224 may be due to lesser autonomic nervous system swings or to a less responsive sinus node in the elderly. Conclusions. The results of this study suggest that the high prevalence of atrial arrhythmias in the elderly without apparent heart disease may be explained in part by the larger left atrial size, which characterizes the normal aging heart. While greater left ventricular mass has been associated with increased cardiovascular events and ventricular arrhythmias in other clinical settings, 39, 40 we detected no such association in an elderly population free of obvious cardiovascular disease. Whether an increased left ventricular mass is associated with other morbid events in this population remains to be assessed by longitudinal studies. Our findings support the concept that myocardial hypertrophy does not appear to be the common link between cellular changes due to aging and those due to hypertension. 36
Arrhythmias in the elderly
12. 13.
14.
15. 16. 17. 18.
19.
20.
We acknowledge the invaluable help of Peter Martin, Marlene Johnson, and Patricia Cape. We are also grateful to Delores Fleming and Debbie Woelke for their assistance in manuscript preparation.
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