Left Axis Deviation: Prevalence, Associated Conditions, and Prognosis

Transcription

1 Left Axis Deviation: Prevalence, Associated Conditions, and Prognosis An Epidemiologic Study LEON D. OSTRANDER, JR., M.D., F.A.C.P., Ann Arbor, Michigan In Tecumseh, Michigan, 4,678 persons past 20 years of age participated in a series of comprehensive examinations in 1959 and The electrocardiograms of 248 participants showed a mean QRS axis of 30 deg or beyond in the frontal plane. Men had a higher prevalence of left axis deviation than women, and the frequency increased with age among both sexes. Fifty-nine percent of the persons with left axis deviation had other findings that suggested heart disease. Forty-one percent were free of such abnormalities (isolated left axis deviation). Those with isolated left axis deviation had no excess incidence of heart disease morbidity or mortality during an average observation period of 4 years. Their frequency of coronary heart risk factors was similar to that observed in the entire study population. Isolated left axis deviation appears to be a common electrocardiographic finding without unfavorable prognostic implications. LEFT AXIS deviation is usually defined by the mean QRS axis, which must fall between 30 deg and 90 deg in the frontal plane. In the early years of clinical electrocardiography, when only three bipolar extremity leads were recorded, the electrical axis was considered useful for the identification of ventricular hypertrophy. With the introduction of unipolar leads and new criteria for the classification of hypertrophy and bundle-branch block the axis appeared to have little specific diagnostic value. In 1956 Grant renewed clinical interest in left axis deviation as a sign of underlying heart disease when he reported a high prevalence of myocardial lesions From the Center for Research in Diseases of the Heart, Circulation, and Related Disorders, University of Michigan, Ann Arbor, Mich. or left ventricular hypertrophy among autopsied persons whose electrocardiograms had shown left axis deviation within 5 weeks of death (1). In 1965 Watt, Murao, and Pruitt (2) reported that laceration of the anterior division of the left bundle-branch in the baboon heart resulted in delayed activation of the anterior wall of the left ventricle and a leftward shift of the electrical axis of sufficient magnitude to fulfill the criteria for left axis deviation. Other investigators have reported interruption of this conducting pathway in nearly all humans with left axis deviation who came to autopsy (3-5). Most of the myocardial lesions have been infarcts or areas of fibrosis that were attributed to ischemia. This chain of evidence has suggested to many that most left axis deviation is a manifestation of coronary heart disease. Only the reports of Blackburn and associates (6, 7) on electrocardiographic findings among men in countries with very different prevalence rates of coronary heart disease have suggested that left axis deviation in a general population may be a benign concomitant of aging, rather than a sign of any specific etiologic type of heart disease. Because of Blackburn's observation and the biases inherent in autopsy studies, the data from the Tecumseh Community Health Study were analyzed in an effort to determine the relationship of left axis deviation to heart disease or its precursors in a welldefined population. Methods Tecumseh, Michigan, is the site of a prospective epidemiologic study of health and disease among the population of a community of nearly 10,000 persons. During thefirstseries of examinations in 1959 and 1960, 88% of the inhabitants participated, and a similar Annals of Internal Medicine 75:23-28,

2 proportion took part in the second series of examinations from 1962 to Details of the methods and aims of the study have been published (8, 9). Of the 8,641 persons examined in 1959 and 1960, 4,678 were 20 years of age or older. Experienced physicians reviewed and supplemented the comprehensive medical histories obtained from participants by trained lay interviewers and then performed thorough physical examinations. The principal measurements and laboratory studies were a standard 12-lead electrocardiogram, chest roentgenogram, anthropometric measurements, and determination of the serum cholesterol and blood glucose concentrations. During the first series of examinations blood specimens were obtained from 80% of the adults 1 hour after a 100-g oral glucose challenge; almost all other participants gave casual blood samples. Electrocardiograms were recorded without regard for prior meals, smoking, or time of glucose ingestion. During the second series of examinations, from 1962 to 1965, procedures were similar except that nearly all adult participants without known diabetes received the 100-g oral glucose challenge, and all electrocardiograms were recorded before glucose ingestion. The time between examinations varied from 20 to 72 months, with a median interval of 47 months. Eighty percent of those who participated in both examinations were reexamined between 40 and 56 months after entrance to the study. Myocardial infarction, angina pectoris, rheumatic and congenital heart disease, and congestive heart failure were diagnosed according to strict criteria (10). Relative weight was the ratio of the individual's observed weight to a predicted weight derived from a sex-specific equation, which takes into account not only height but the biacromial and bicristal diameters (11). Chest roentgenograms were interpreted by experienced radiologists, and the cardiothoracic ratios were calculated from direct measurements. High values for systolic and diastolic blood pressure, relative weight, serum cholesterol, and cardiothoracic ratio were arbitrarily defined according to the upper quintile of the age- and sex-specific distributions of these variables. The blood glucose was treated similarly, except that the type of test, casual or postchallenge, was taken into account in the calculation (12). The known diabetics were added to the upper quintile so that slightly more than 20% of the participants were classified as hyperglycemic. Death certificates were obtained for all previously examined persons who died, but few autopsies were performed in the community. All electrocardiograms recorded from adults were classified according to the Minnesota coding system (13). Persons 20 years of age or older whose electrocardiograms were classified as II X (QRS axis, 30 deg or beyond) at the first examination constituted the study population. They were divided into one group who had no other major electrocardiographic finding or any historical or physical evidence of heart disease (isolated left axis deviation) and another group with other abnormalities suggestive of heart disease. The electrocardiographic abnormalities among the latter group included Minnesota classifications I a. 8 (suspicious or abnormal Q waves), III a (high-amplitude R waves), IV^ (RST-segment depression), V 1>2 (T-wave inversion), VI 12 (second or third degree atrioventricular block), and VII 1)2, 3, (complete left bundle-branch block and complete and incomplete right bundle-branch block). Results PREVALENCE OF LEFT AXIS DEVIATION During the 1959 to 1960 examinations electrocardiograms were recorded from 2,235 men and 2,443 women 20 years of age or older (Table 1). The electrocardiograms of 147 men and 101 women were classified Hi, according to the Minnesota system. Of the 248 persons with left axis deviation, 69 men and 34 women had no other historical, physical, or electrocardiographic evidence of heart disease (isolated left axis deviation). Men had a higher prevalence of left axis deviation in every decade age group. The prevalence rates for both sexes increased progressively with age. In general, the age and sex distribution of isolated left axis deviation was similar to that of the entire Hi classification. The mean age of women with isolated left Table 1. Prevalence of Left Axis Deviation According to Age and Sex Age Range, yr Men no. Population , Total LAD* Rate per 1, Isolated LAD Rate per 1, Women Population ,443 Total LAD Rate per 1, Isolated LAD Rate per 1, * Left axis deviation. Ju, y 1971 * Annals of Internal Medicine Volume 75 Number 1 Total

3 Table 2. Age and Sex Characteristics of Persons with Isolated Left Axis Deviation Sex Number Age Range Men Women Mean Age Median Age axis deviation was 5 years older than that of men,?nd the median age was 11 years older (Table 2). RELATIONSHIP OF LEFT AXIS DEVIATION TO OTHER CONDITIONS Of the 145 persons with other findings suggestive of heart disease, 92 had RST-segment depression or T-wave inversion, and 22 had high-amplitude R waves. The other 31 had a variety of abnormalities, which included histories of angina pectoris or myocardial infarction, electrocardiographic evidence of bundle-branch block or myocardial infarction, or physical findings indicative of rheumatic or congenital heart disease. Because each of these conditions is either known or suspected to be associated with excess morbidity or mortality from heart disease, only persons with isolated left axis deviation were analyzed further (14-16). The prevalence of systolic and diastolic hypertension, high relative weight, hypercholesterolemia, hyperglycemia, and cardiomegaly did not differ significantly from the expected frequency for the 103 persons with isolated left axis deviation (Table 3). Similarly, the prevalence of those characteristics among men, women, persons less than 50 years of age, and participants 50 years of age or older was generally unremarkable, although persons less than 50 years of age and women tended to have hyperglycemia more frequently than others with left axis deviation. When the 19 persons less than 40 years of age were analyzed separately, hyperglycemia was significantly more frequent than expected (9 persons or 47.4%, P < 0.01). The percentage of cigarette smokers among the persons with isolated left axis deviation was slightly less than that of all participants of like age and sex. Among persons with isolated left axis deviation the proportion with none, one, two, or three or more coronary heart disease risk factors was similar to that of the entire examined adult population (Table 4). The factors included were systolic and diastolic hypertension, overweight, hypercholesterolemia, and hyperglycemia. MORBIDITY AND MORTALITY AMONG PERSONS WITH ISOLATED LEFT AXIS DEVIATION Seventy-seven of the 103 persons (75%) with left axis deviation at entrance to the study in 1959 or 1960 were reexamined during the period from 1962 to The proportion reexamined was similar to the 76% reexamination rate for all participants past 20 years of age. Three of the 77 developed symptoms or signs of heart disease between examinations. A 48-year-old man gave a history of myocardial infarction, although confirmatory electrocardiographic findings were not present at the time of the second examination. A 47-year-old woman developed angina pectoris, and a 63-year old woman suffered a myocardial infarction, with diagnostic electrocardiographicfindings.the age-adjusted incidence of nonfatal new events of coronary heart disease among persons with left axis deviation was similar to that of all participants in the first and second examinations. Nine of the 26 participants with isolated left axis deviation who were not reexamined died before their Table 3. Persons with Isolated Left Axis Deviation Who Had Upper Blood Glucose, and Cardiothoracic Ratio Category Total Systolic Diastolic Relative Serum Blood Cardio- Blood Blood Weight Cholesterol Glucose thoracic Pressure Pressure Ratio no. % no. % no. ~% no. ~% no. ~% no. % All persons with isolated left axis deviation Men with isolated left axis / / / / deviation / / / / Women with isolated left axis deviation / / / Persons less than 50 years of age (28 men, 10 women) / Persons past 50 years of age (41 men, 24 women) / / / / Persons less than 40 years of age (15 men, 4 women) * 5/ * Significant P < Ostrander Left Axis Deviation 25

4 Table 4. Distribution of Persons with Isolated Left Axis Deviation and All Adult Tecumseh Participants According to the Number of Coronary Heart Disease Risk Factors Number of Factors * Isolated LAD f Adult Participants None One Two Three or more % * Systolic hypertension, diastolic hypertension, high relative weight, hypercholesterolemia, and hyperglycemia as defined in the text. t Left axis deviation. scheduled second examination (Table 5). The ageadjusted mortality rate for persons with isolated left axis deviation was no greater than the rate for the total Tecumseh population. There was no excess of cardiovascular disease among the nine fatalities. Discussion Left axis deviation can be produced in primates by interruption of the anterior division of the left bundle branch (2). Postmortem studies of hospital patients with left axis deviation have shown areas of myocardial infarction or fibrosis that involve the anterior division of the left bundle branch in almost every instance (3-5). Most of these lesions have been attributed to ischemia because of the frequency of associated severe coronary arterial atherosclerosis. The age and sex distribution of left axis deviation in epidemiologic studies, which closely parallels that of myocardial infarction, is a further clue linking this electrocardiographicfindingto coronary heart disease (6, 17, 18). Other considerations must be taken into account before attributing nearly all left axis deviation to coronary heart disease. Autopsy studies are inevitably biased toward lethal diseases such as myocardial infarction and are unlikely to reveal benign conditions that might also cause left axis deviation. The age distribution of atrioventricular and intraventricular block also coincides fairly closely, with that of myo- myocardial infarction (17, 19), but current evidence Table 5. Deaths Among Persons with Isolated Left Axis Deviation Sex Age Cause of Death yr 51 Myocardial infarction 52 Carcinoma of the esophagus Cerebrovascular accident Septicemia from urinary tract infection Bronchial carcinoma Gastrointestinal hemorrhage 74 Myocardial infarction Female 65 Gastrointestinal hemorrhage Female 67 Cerebrovascular accident suggests that coronary heart disease is not the sole or even the major cause of these conduction disturbances (20). Rosenbaum believes that leftward shift of the electrical axis beyond 45 deg is almost always caused by interruption of the anterior division of the left bundle and implies that lesser degrees of left axis deviation are unreliable signs of "left anterior hemiblock" (21). Such criteria are rarely fulfilled in the general population. Among the 248 Tecumseh participants with left axis deviation only 8 exceeded 45 deg, and each had other evidence of heart disease. Very strict criteria eliminate almost all false positive diagnoses, but experimental and clinical observations suggest that "left anterior hemiblock" may be overlooked if the diagnosis is only considered in the presence of extreme left axis deviation (2-5). Several reports have attempted to clarify the significance of left axis deviation in defined population samples, but not all the conclusions seem justified by the data. In a study of supposedly uncomplicated left axis deviation among military men without cardiovascular disease, Eliot, MilUion, and Millhon (22) included men with angina pectoris or positive electrocardiographic exercise tests. In commenting on the higher 22-month incidence of angina pectoris, coronary insufficiency, and myocardial infarction among men with left axis deviation than occurred in a control group, they did not indicate the proportion of the new events occurring among men free of any evidence of coronary heart disease at initial examination and among those with detected disease. Recently Borden and Ibrahim (23) reported a higher prevalence of coronary heart disease risk factors among men with a "leftward" mean QRS axis ( 30 deg to +30 deg) than among men with a "rightward" axis (+45 deg to +120 deg). Only 27 of these 257 middle-aged men with a "leftward" QRS axis had true left axis deviation, and the authors did not indicate whether they differed from the men with a lesser degree of leftward rotation of the mean QRS axis. They suggested that the mean electrical axis might be a useful predictor of future coronary events because the leftward group was significantly fatter, more hypertensive, and had a higher mean cholesterol concentration than the rightward group. The leftward group was also significantly older, which may have accounted in part for other unfavorable traits. The authors did not mention the prevalence of other historical, physical, or electrocardiographic cardiography signs of cardiac disease in the two groups. Such information is essential before one can 26 July 1971 Annals of Internal Medicine Volume 75 Number 1

5 ascribe diagnostic or predictive power to the electrical axis. In broad population studies Blackburn, Vasquez, and Keys (6) found that left axis deviation was a common and apparently nonspecific abnormality that was associated with aging in three populations with very different incidence rates of coronary heart disease. More recently Blackburn, Taylor, and Keys (7) reported only equivocal evidence that left axis deviation had prognostic value among cohorts of working men, without apparent coronary heart disease, who were drawn from total populations in the United States and six other countries. The Tecumseh findings may help to reconcile the conflicting impressions of these different investigators. Coronary heart disease probably accounts for most of the left axis deviation identified in hospitalized patients and much of that found among the general population as well. Fifty-nine percent of the Tecumseh participants with left axis deviation had other signs of heart disease. Although some of the 41% with isolated left axis deviation undoubtedly had subclinical coronary heart disease too, there is little to suggest that they had more coronary heart disease than unaffected Tecumseh participants of like age and sex. They suffered no excess morbidity or mortality from cardiovascular disease during the period of observation nor did they differ significantly from other members of the Tecumseh population in their frequency of cardiomegaly on chest roentgenogram. The prevalence of coronary heart disease precursors among the participants with isolated left axis deviation was not significantly greater than expected except among the 19 persons less than 40 years of age. Nine had hyperglycemia, but there was no excess of hypertension, overweight, or hypercholesterolemia. Although no conclusions should be drawn from this small number, isolated left axis deviation may be a more important sign of latent coronary disease among younger persons. The unfavorable prognosis attributed to left axis deviation does not appear to depend as much on the electrocardiographic abnormality as on the conditions associated with it. The benignity of isolated left axis deviation should be kept in mind in interpreting electrocardiograms and explaining electrocardiographic findings to patients. Left axis deviation is a frequent finding in tracings that have been recorded for such purposes as periodic health examinations, preoperative checks, or insurance requirements. The Tecumseh results do not justify an unfavorable prognosis based on this electrocardiographic abnormality alone. ACKNOWLEDGMENTS: The author is grateful to Mr. Jacob B. Keller for his statistical analyses and constructive suggestions and to Drs. Frederick H. Epstein, Norman S. Hayner, Millicent W. Higgins, and Benjamin C. Johnson for their many helpful suggestions. The entire staff of the Tecumseh Community Health Study, under the supervision of Dr. Frederick H. Epstein, Director, and Mr. John A. Napier, Associate Director for Operations, participated in the collection of the data used in this report. Received 21 December 1970; revision accepted 12 February Requests for reprints should be addressed to Leon D. Ostrander, Jr., M.D., Tecumseh Health Study, University of Michigan, 130 S. 1st St., Ann Arbor, Mich References 1. GRANT RP: Left axis deviation. An electrocardiographicpathologic correlation study. Circulation 14: , WATT TB JR, MURAO S, PRUITT RD: Left axis deviation induced experimentally in a primate heart. Amer Heart J 70: , CORNE RA, PARKIN TW, BRANDENBURG RO, et al: Significance of marked left axis deviation. Electrocardiographicpathologic correlative study. Amer J Cardiol 15: , PRYOR R, BLOUNT SG JR: The clinical significance of true left axis deviation. Left intraventricular blocks. Amer Heart J 72: , BAHL OP, WALSH TJ, MASSIE E: Left axis deviation. An electrocardiographic study with postmortem correlation. 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6 Electrocardiographic findings among the total adult popu- 21. ROSENBAUM MB: The hemiblocks: diagnostic criteria and lation of a large religious isolate. Circulation 41: , clinical significance. Mod Cone Cardiovasc Dis 39: , PERLMAN LV, OSTRANDER LD JR, KELLER JB, et al: An 22. ELIOT RS, MILLHON WA, MILLHON J: The clinical signifiepidemiologic study of first degree atrioventricular block in cance of uncomplicated marked left axis deviation in men Tecumseh, Michigan. Chest 59:40-46, 1971 without known disease. Amer J Cardiol 12: , LEV M: Anatomic basis for atrioventricular block. Amer J 23. BORDEN HH, IBRAHIM MA: The epidemiology of the QRS Med 37: , 1964 axis measurement. Amer J Public Health 60: , 1970 Medical Footnotes to Literary History IN Holland v. Metalious 38 the author of the best-selling novel Peyton Place, perhaps seeking to atone for her prose style, had willed her body to either of two medical schools "for purposes of experimentation in the interest of medical science." Nothing much came of her effort, however; both schools declined to accept the body A.2d 654 (S. Ct. N.H. 1964). JON R. WALTZ and FRED E. INBAU Medical Jurisprudence. New York, The Macmillan Co., 1971, p Ju/ y *9 7 1 Annals of Internal Medicine Volume 75 Number 1