prevalence and prognosis of third-degree atrioventricular conduction block: the Reykjavik Study. J

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1 Journal of Internal Medicine 1999; 246: 81±86 The prevalence and prognosis of third-degree atrioventricular conduction block: the Reykjavik Study E. M. KOJIC 1, T. HARDARSON 1, N. SIGFUSSON 2 & H. SIGVALDASON 2 From the 1 Department of Medicine, National University Hospital; and the 2 Heart Preventive Clinic, Reykjavik, Iceland Abstract. Kojic EM, Hardarson T, Sigfusson N, Sigvaldason H (National University Hospital and Heart Preventive Clinic, Reykjavik, Iceland). The prevalence and prognosis of third-degree atrioventricular conduction block: the Reykjavik Study. J Intern Med 1999; 246: 81±86. Objectives. The objectives of this study were to find the prevalence of third-degree atrioventricular block in representative population sample and to estimate its prognostic significance. Most earlier studies have been performed on hospital patients and some professional groups. Setting and subjects. In the Reykjavik Study, a prospective cardiovascular population study, 9139 men and 9773 women aged 33±79 years were examined in 1967±91. Electrocardiograms were taken and coded according to the Minnesota code. Third-degree atrioventricular block was found in 11 persons, seven male and four female, an overall prevalence of 0.04%. All of these individuals had signs of dysrhythmia on electrocardiograms taken later, and in addition some other heart disease. The heart block was temporary in seven individuals (64%); six (55%) needed a pacemaker. Conclusions. The prevalence of third-degree atrioventricular block in this general population was low. The block was temporary in the majority of subjects. All had some underlying heart disease, which may affect the prognosis more than the heart block. Fewer subjects than expected were found to need a pacemaker. Keywords: the Reykjavik Study, third-degree A-V block. Introduction Temporary or permanent damage to the conduction system of the heart can lead to total or third-degree atrioventricular (A-V) block [1]. The incidence and prevalence of this abnormality have most frequently been studied amongst patients with known heart disease, and screening studies of normal cohorts have with one exception been confined to certain professional groups. Although most investigators agree that the prevalence is low [2±6], third-degree A-V conduction block has usually been regarded as a serious condition requiring prompt therapy. The Reykjavik Study, a continuing prospective population study starting in 1967, has provided a very convenient data base for studying the prevalence, incidence and prognostic significance of various electrocardiographic abnormalities. We have previously reported such studies on atrial fibrillation [7], left bundle branch block [8] and right bundle branch block [9]. In the study reported in this paper, third-degree A-V conduction block was similarly examined. Methods People invited to participate in the Reykjavik Study were all the legal residents in the Reykjavik area on 1 December 1966 [10, 11]. The men were born in the following years: 1907, 1910, 1912, 1914, 1916, 1917, 1918, 1919, 1920, 1921, 1922, 1924, 1926, 1928, 1931 and 1934; the women 1 year later, i.e. 1908, 1911, etc. Both sexes were divided into groups A, B and C according to date of birth: i.e. those in group B were born on the 1st, 4th, 7th, etc., of each month, those in group C were born on the 2nd, 5th, 8th, etc., of each month, and those in group A were born on the 3rd, 6th, 9th, etc., of each month (Fig. 1). Groups D and E comprised people born in the years previously omitted in the # 1999 Blackwell Science Ltd 81

2 82 E. M. KOJIC et al. Fig. 1 A schematic diagram of the study plan of the Reykjavik Study, including the number of participants divided into study groups, the number examined at each stage, and the time of invitation of each study group to examination in five stages. period 1907±35, excluding those years listed above. The study population thus comprised all men born in the years 1907±34 and all women born in the years 1908±35 living in the Reykjavik area on 1 December 1966: altogether persons. The study was performed in five stages. The first took place in 1968±69, the second in 1970±72, the third in 1974±79, the fourth in 1979±84 and the fifth in 1983±91. Group B was invited to participate in all stages of the study, group C in stages 2 and 3, group A in stage 3, group D in stage 4 and group E in stage 5. Figure 1 shows the years for follow-up for each group: the largest number of follow-up visits was for group B. The mean response was approximately 70%. In all, 9139 men and 9773 women participated in the study. For each stage, the participants came to the clinic on two occasions. On the first occasion a 12-lead electrocardiogram (ECG) was recorded, a chest X-ray was taken and several blood and urine investigations performed. On the second occasion the participant was interviewed and examined by a doctor, who also evaluated the results of all investigations. All ECGs were classified according to the Minnesota code and reviewed by two of the authors (EMK and NS). One coder (NS) has participated in and been approved by an ECG coding standardization programme of the World Health Organization. The 1968 version of the Minnesota code which was used throughout this study defines third-degree A-V block thus: complete (third degree) A-V block (permanent or intermittent) in any lead [12]. The case records of individuals with third-degree A-V block were reviewed with regard to the following variables: (i) smoking at the time of the examination; (ii) symptoms of dysrhythmias (dizziness, syncope, palpitations); (iii) signs of atherosclerosis (myocardial infarction, angina pectoris or intermittent claudication); (iv) the use of drugs at the time of examination, particularly beta blockers, calcium blockers and digitalis; (v) hypertension (systolic blood pressure $ 160 mmhg and/or diastolic blood pressure $ 95 mmhg, or the participant being on

3 THE REYKJAVIK STUDY 83 antihypertensive drug therapy); (vi) heart rate; (vii) radiological evidence of cardiac enlargement (. 550 mm m 22 in men and. 500 mm m 22 in women); (viii) other ECG signs; (ix) the implantation of a pacemaker. The individuals having third-degree A-V block were contacted by telephone and specifically asked about signs and symptoms of cardiovascular diseases, hospital admissions and general health. All hospital and general practitioner records were obtained; any ECGs recorded before and after the index examination, if available, were reviewed with regard to third-degree A-V block and other ECG diagnoses. The implantation of a pacemaker was noted. Results Eleven individuals were found on at least one occasion to have third-degree A-V block: seven men and four women. The age range was 45± 64 years (mean 55.2 years). No one was diagnosed in stage 1, two individuals were diagnosed in stage 2, seven diagnosed in stage 3, two diagnosed in stage 4 and none diagnosed in stage 5. These individuals visited the centre 15 times. The prevalence was calculated at 0.04% with a 95% confidence interval of 0.02±0.07. On the visit when the block was diagnosed, five participants described symptoms suggesting dysrhythmias: all of them reported palpitations, and one also reported dizziness (Table 1). All of them also had a history of angina pectoris. Six individuals denied symptoms at the time of diagnosis. Only two participants had a pacemaker at the initial diagnosis. One of them had a history of Adams±Stokes attacks. He had been diagnosed as having third-degree A-V block and received a pacemaker 8 years before the visit. The underlying cause was believed to be familial. The other individual who had a pacemaker reported symptoms of dizziness 4 years before. The diagnosis of thirddegree A-V block was made 3 years before the screening visit, and he then received a pacemaker. The cause was believed to be coronary artery disease. Of the nine individuals who did not have a pacemaker at the study visit, four received a Table 1 Symptoms and medications used at diagnosis of total A-V block Patient No. Age Medication Symptoms at diagnosis Previous or subsequent symptoms, age at onset Blood pressure Pacemaker, years after exam 1 61 dig None Syncope, age /80 ±8 Chest pain, age Paroxysmal Paroxysmal palpitations, age /82 No palpitations Chest pain, age dig None Heart failure, age /72 No 4 53 dig Dizziness Paroxysmal palpitations Paroxysmal palpitations and dizziness Chest pain, age / Paroxysmal palpitations Paroxysmal palpitations, age 23 Chest pain, age 55 Heart failure, age / None 104/70 No 7 55 None Heart failure, age /90 13 Syncope, age None Dizziness, age /94 ± dig, bb None Chest pain, age /104 8 Heart failure, age dig, bb Irregular heart beat Palpitations and tiredness Heart failure, age 43 Chest pain, age /74 No dig, bb Paroxysmal palpitations dig: digitalis; bb: beta blocker. Chest pain, age 54 Paroxysmal palpitations, age /90 No

4 84 E. M. KOJIC et al. pacemaker 3, 7, 8 and 13 years later. Two of them had on subsequent visits total A-V block, one had a slow heart rate and second-degree A-V block, and one had atrial flutter with a slow ventricular response. Of the total group, six participants, or 55%, therefore eventually received a pacemaker. The ECGs of the individuals not receiving a pacemaker later showed atrial fibrillation in three individuals and a first-degree A-V block in two. Table 2 shows the ECG changes at the diagnosis of the A-V block, as well as a comparison with previous and subsequent ECGs. Eight participants had signs or symptoms of underlying heart diseases. Six had coronary artery disease, previous myocardial infarction or angina pectoris, one had cardiomyopathy and two had valvular heart disease. Four participants had arterial hypertension (Table 3). Six individuals took digitalis and/or beta blockers (Table 1). All of them had other possible causes of A- V block. Signs or symptoms of heart failure were searched for in hospital case records: three had a previous history of heart failure and four developed signs or symptoms of heart failure later. One patient was lost to follow-up. Four patients died of causes unrelated to the A-V block, although heart failure had been a contributing factor in the deaths of two of them. Four still have a pacemaker and are symptom-free, but two patients have had recurrent atrial fibrillation and have required repeated electroconversion. Discussion The prevalence of third-degree A-V block has mostly been studied amongst hospital patient populations. However, Johnson et al. investigated over symptom-free airmen. One was found to have thirddegree A-V block. Graybiel et al. and Manning, in their group of airmen, found none with third-degree A-V block; neither did Rose and co-workers in their study of over civil servants [2±5]. Johansson reviewed all ECGs filed in the Heart Laboratory, MalmoÈ General Hospital, during 1951±64, and found 201 cases of complete heart block (CHB). Assuming that most patients with CHB in MalmoÈ Table 2 The electrocardiogram: other ECG changes at diagnosis of total A-V block; comparison with previous and later ECGs Patient No. Previous ECGs Other changes at diagnosis of block Later ECGs variable block 1971 left bundle branch block; 1972 pacemaker rhythm 1962 total A-V block pacemaker since None found 1970 bradycardia 1980 atrial fibrillation sinus tachycardia 1970 ST-segment depression 1973 first-degree A-V block 1968 prolonged QT duration between 0,5 and 1,0 mm; T-wave abnormalities first degree 1970 ST depression > 1 mm; 1973 third-degree A-V block A-V block T-wave abnormalities 5 None found 1976 ST depression > 1 mm; 1983 third-degree A-V block T-wave abnormalities; extrasystolic beats 6 None found 1976 none 1976 first- and second-degree block 7 None found 1980 QRS complex transition zone to the right of lead V atrial fibrillation Sick sinus third-degree 1979 T-wave abnormalities; 1982 pacemaker rhythm A-V block pacemaker since None found 1979 none 1984 nodal arrythmia 1985 ischaemia 1987 bradycardia second-degree A-V block 10 Varying atrial fibrillation and flutter 1977 frequent premature atrial, nodal or ventricular beats 1982 normal 1987 normal 1990 nodal arrythmia 1990 atrial fibrillation 11 None found 1982 none 1986 atrial flutter 1993 atrial fibrillation

5 THE REYKJAVIK STUDY 85 Table 3 Possible aetiology of A-V block, other relevant diagnoses and outcome Patient No. Possible aetiology Other diagnoses Outcome 1 Idiopathic, fibrosis Old myocardial infarction 2 Coronary heart disease Coronary heart disease Diastolic hypertension 3 Alcoholic cardiomyopathy Cardiomyopathy 4 Valvular disease Coronary heart disease Aortic valve insufficiency Systolic hypertension Suspected glaucoma Proteinuria 5 Idiopathic, fibrosis Coronary heart disease Angina pectoris Diastolic hypertension Deceased, age 65: heart failure Deceased, age 74: gastrointestinal carcinoma Deceased, age 67: digitalis overdose possibly contributing Deceased, age 70: pneumonia 1994: symptom-free 6 Idiopathic, fibrosis None Lives abroad 7 Idiopathic, fibrosis Sideropenic anaemia 1994: symptom-free 8 Coronary heart disease Coronary heart disease 1994: symptom-free 9 Coronary heart disease Diastolic hypertension Angina pectoris Sideropenic anaemia Varicose veins, lower extremity 10 Rheumatic heart disease Aortic valve insufficiency 11 Digoxin Varicose veins, lower extremity 1994: symptom free Chronic atrial fibrillation Chronic atrial fibrillation would have their ECGs in the laboratory files, he estimated the prevalence of CHB to be 0.22% [13]. In Tecumseh, MI, USA, a population sample of 8641 men revealed two with third-degree A-V block [6], yielding a prevalence of 0.02%. This is the only study directly comparable to the Reykjavik Study. Our study has furthermore revealed that the block is frequently transient. This is in accord with findings in several other studies. In the study of Johansson, 70 of the 204 cases were transient [13]. In the study by Jensen et al. of patients with pacemakers because of Adams±Stokes attacks, 64 had chronic third-degree A-V block but in 67 it was intermittent [14]. Likewise, in the study by Shaw et al. of 214 patients with second-degree A-V block, 83 deteriorated to third-degree block, whilst 35 improved to normal or first-degree block [15]. Third-degree A-V block is sometimes connected with hypertension, but more frequently with coronary artery disease [16, 17]. However, chronic total A-V block is associated with fibrous degeneration of the conducting system in 40% of cases [18± 24]. This particularly applies in the elderly population [19]. Other possible causes are surgical operations, electrolyte disturbances, infections, tumours, Chagas' disease, rheumatic disease, calcification of the aortic valve, amyloidosis, sarcoidosis, scleroderma, drug intoxications, etc. In children, by far the commonest cause is congential [1, 23]. In our study, four individuals (36%) had third-degree A-V block of unknown origin or because of degeneration of the conductive system. The latter may also have been conducive to the block in the other individuals, although they also had manifest cardiovascular

6 86 E. M. KOJIC et al. disease. Only one individual had symptoms attributable to the A-V block; five participants, however, complained of palpitations. In chronic third-degree A-V block the implantation of a pacemaker is associated with improved prognosis [15, 21]. However, patients under 60 with third-degree A-V block have a poorer prognosis than control patients without a block, although this does not apply to older patients. This is probably explained by higher incidence of underlying heart disease in the younger population [21]. In our study the four deaths cannot be attributed to the A-V block. The prognosis of our subjects was therefore more clearly related to the underlying heart disease than to the A-V block. In summary, we have found that, in a sample of the general population, few individuals are identified with total A-V block. Such a block is frequently associated with underlying cardiac disease, and does not as such strongly influence mortality and morbidity. Only about half those who are found to have third-degree A-V block under these circumstances need a permanent pacemaker, and the prognosis of these patients depends primarily on the underlying heart disease. References 1 Chung E. Atrioventricular conduction disturbances. In: Editor X, ed. Principles of Cardiac Arrythmias, 4th edn. New York: Williams and Wilkins, 1989; 273± Johnson RL, Averill KH, Lamb LE. Electrocardiographic findings in 67,375 asymptomatic subjects. VII. Atrioventricular block. Am J Cardiol 1960; 23: 153±77. 3 Graybiel A, McFarland RA, Gates DC, Webster FA. Analysis of the electrocardiograms obtained from 1000 young healthy aviators. Am Heart J 1944; 27: Manning GW. Electrocardiography in the selection of Royal Canadian Air Force aircrew. Circulation 1954; 10: 384. Quoted in Johnson RL [2]. 5 Rose G, Baxter PJ, Reid DD, McCartney P. Prevalence and prognosis of electrocardiographic findings in middle-aged men. Br Heart J 1978; 40: 636±43. 6 Ostrander LD, Brandt RL, Kjelsberg MO, Epstein FH. Electrocardiographic findings among the adult population of a total natural community, Tecumseh, Michigan. Circulation 1965; 31: 888±98. 7 OÈ nundarson PT, Thorgeirsson G, Jonmundsson E, Sigfusson N, Hardarson T. Chronic atrial fibrillation ± epidemiologic features and 14 years follow-up: a case control study. Eur Heart J 1987; 8: 521±7. 8 Hardarson T, Arnason A, Eliasson GJ, Palsson K, Eyjolfsson K, Sigfusson N. Left bundle branch block: prevalence, incidence, follow-up and outcome. Eur Heart J 1987; 8: 1075±9. 9 Thrainsdottir IS, Hardarson T, Thorgeirsson G, Sigvaldason H, Sigfusson N. The epidemiology of right bundle branch block and its association with cardiovascular morbidity ± The Reykjavik Study. Eur Heart J 1993; 14: 1590±6. 10 BjoÈrnsson OJ, Dvidsson D, Olafsson H, Olafsson O, Sigfusson N, Thorsteinsson TH. Report ABC, XVIII. Health survey in the Reykjavik area. Males. Stages I±III, 1967±68, 1970±71 and 1974±76. Participants, invitation, response etc. Reykjavik: Hjartavernd, BjoÈrnsson G, BjoÈrnsson OJ, Davidsson D et al. Report abc XXIV. Health survey in the Reykjavik area. Women. Stages I±III, 1968±69, 1971±72 and 1976±78. Participants, invitation, response etc. Reykjavk: Hjartavernd, Rose GA, Blackburn H. Cardiovascular survey methods. Monograph series No. 56. Geneva: World Health Organization, Johansson BW. Complete heart block. A clinical, hemodynamic and pharmacological study in patients with and without an artificial pacemaker. Acta Med Scand 1966; 180(Suppl.), Jensen G, Sigurd B, Meibom J, Sandùe E. Adam±Stokes syndrome caused by paroxysmal third-degree atrioventricular block. Br Heart J 1973; 35: 516± Shaw DB, Kekwick CA, Veale D, Gowers J, Whistance T. Survival in second degree atrioventricular block. Br Heart J 1985; 53: 587± Zoob M, Smith SK. The aetiology of complete heart-block. Br Med J 1963; 2: 1149± Ginks W, Sutton R, Siddons H, Leatham A. Unsuspected coronary artery disease as cause of chronic atrioventricular block in middle age. Br Heart J 1980; 44: 699± Harris A, Davies M, Redwood D, Leatham A, Siddons H. Aetiology of chronic heart block. A clinico-pathological correlation of 65 cases. Br Heart J 1969; 31: 206± Davies MJ. Pathology of the conducting tissue of the heart. London: Butterworths, Quoted in Ginks W. et al. [17]. 20 Siddons H. Deaths in long-term paced patients. Br Heart J 1974; 36: 1201±9. 21 Ginks W, Leatham A, Siddons H. Prognosis of patients paced for chronic atrioventricular block. Br Heart J 1979; 41: 633± Davies MJ, Harris A. Pathological basis of primary heart block. Br Heart J 1969; 31: 219± Lev M. Anatomic basis for atrioventricular block. Am J Med 1964; 37: 742±8. 24 Kennel AJ, Titus JL, McCallister BD, Pruitt RD. The vasculature of the atrioventricular conduction system in heart block. Am Heart J 1973; 85: 593±600. Received 6 July 1998; accepted 14 January Correspondence: Thordur Hardarson MD PhD, Department of Medicine, Landsptalinn, National University Hospital, IS 101, Reykjavk, Iceland (fax: ).