Isolated Congenital Complete Atrioventricular Block in Adult Life

Several publications have described the natural history in infancy and childhood of congenital complete atrioventricular block (CCHB) with and without structural heart disease.^12345678910 The signs and symptoms indicating a need for pacemaker (PM) treatment are now more or less well established.¹¹ The outcome of CCHB in adults is less well known, as reflected in the different attitudes regarding PM treatment. This is evidently because studies covering adult life are few, with small numbers of patients, and rarely prospective. An optimistic report was published in 1966, based on 6 cases followed up for 34 to 40 years.¹² Another recent report stated that “the main indication for PM implantation was symptoms alone.”¹³ Other publications indicate a less favorable outcome.^23101415 Our own interest dates back to 1963, with the experience of repeated Stokes-Adams (SA) attacks in a previously asymptomatic 15-year-old girl.¹⁶

A joint study on the natural history of CCHB was started in 1964 by members of the Association of European Paediatric Cardiologists, and a similar study was begun in 1967 in North America.³⁵⁶ In the late 1970s a follow-up of Swedish cases in adult life was carried out.¹⁴ This material has been reexamined, updated, and extended and forms the basis of the present report.

The aim of the study was to answer the following questions: What is the long-term natural history of a patient with CCHB who is asymptomatic in infancy and childhood? Can SA attacks be predicted in the patient? Do other symptoms or signs appear later in life?

Methods

The diagnostic criteria of congenital heart block proposed by Yater¹⁷ were applied, namely: “Heart block established in a young patient by graphic records. There must be some evidence of the existence of the slow pulse at a fairly early age and absence of a history of any infection which might cause the condition after birth: notably diphtheria, rheumatic fever, chorea and congenital syphilis.” The ECG criteria used are: the atria and ventricles should be completely dissociated, the ventricular rate (VR) should be slower than the atrial rate, and no captured beats should be present.

A registry of patients known in 1964 was gradually supplemented with younger patients when they had passed the age of 15 years without symptoms. The hospital records, including ECG tracings and, in the event of death, the autopsy findings, were studied.

A number of cases not strictly following the above-mentioned criteria were excluded. Examples are: patients in whom an occasional ECG recording showed captured beats; suspicion of endomyocarditis early in life; and diagnosis delayed until late childhood. All patients with a suspicion of associated congenital heart disease such as atrioventricular inversion, atrial septal defect, or persistent ductus arteriosus were excluded. Patients with symptoms such as fainting spells in childhood were also omitted.

In this way, 30 heart block patients were excluded. Among these, 6 had died: 1 woman from breast cancer at the age of 68, another woman with malignant melanoma at the age of 38, and the other 4 (2 women and 2 men) suddenly and unexpectedly at the ages of 15, 31, 43, and 46 years. Thus, these 30 patients are not included elsewhere in this presentation.

Study Group

The final group consisted of 102 patients, 61 women and 41 men. All patients could be traced, and up-to-date information was collected from the hospitals and from the patients. A low heart rate had been found and CCHB had been diagnosed in utero or by ECG in the neonatal period in 51 cases: before the age of 1 year in 9, between the ages of 1 and 5 years in 20, between 6 and 10 years in 15, and between 11 and 15 years of age in 7 cases. For evident reasons, the older patients are overrepresented in the groups with delayed ECG verification of the block. Repeated ECG recordings during infancy and childhood confirmed that the block was permanent and complete. A QRS complex of 0.12 second or wider was named “widened QRS complex.” A QT_c time of more than 0.45 second was named prolonged QT_c.

Data and recordings from physical working capacity tests were available in 86 cases. The tests were performed on an electrically braked bicycle ergometer with an increasing load, either in 6-minute periods or with shorter intervals. The work was carried out either to submaximal or to maximal capacity. Oxygen uptake and lactate levels were determined in a few patients only. The results of the last exercise test are expressed as the VR during maximal work performed (W/kg body wt). Data on the occurrence of ventricular ectopy during effort were recorded and compared with the natural history. Chest radiographic and echocardiographic information was not systematically collected.

Statistical Analysis

Data were analyzed using categorical data analysis models. The Catmod procedure of the SAS (1990) package was used.¹⁸ Presence or absence of a symptom was coded as 1 or 0, respectively. Continuous variables such as age and heart rate were included as such in the models by using the DIRECT statement.

Results

The age at the last follow-up or the age at death of the entire cohort of patients is presented in Fig 1, where the age at PM implantation is also indicated. The mean age at follow-up or at death was 38 years, median age 37 years, and range 16 to 66 years. The youngest living patient is 22 years old, so the shortest observation time after the age of 15 is 7 years. Of 32 living patients over the age of 45 years, 28 have a PM.

The age at death, syncope, or presyncope in 37 patients is presented in Fig 2. The attacks could apparently occur at any age with no preferential period.

There were 11 deaths. One man committed suicide at the age of 19 years. A few months earlier he had refused PM treatment recommended because of a low VR and an increasing size of the left ventricle. Four patients, men aged 24, 31, and 45 years and a 43-year-old woman, died after PM implantation. The indication for PM was syncope in 3 patients and heart failure in 1 patient; the cause of death in 2 was PM failure (generator depletion and lead fracture, respectively), and the other 2, who both died during sleep, were in heart failure and were waiting for surgery for mitral insufficiency. The other 6 patients died suddenly without any preceding symptoms. Autopsy was performed on 5 of these 6 patients, and no other cause of death was disclosed. Nineteen other patients had syncope attacks and survived, 6 of them after cardiac resuscitation. They all had a PM implanted afterward. Another 8 patients had repeated fainting spells and are on PM treatment.

In a number of cases the circumstance preceding syncope or death were known. Five patients died during sleep. Two had their attacks after micturition, 5 when resting after physical effort, and 4 in orthostatic situations (standing up after a medical examination, hanging up washing, waiting at a bus stop, and during an orthostatic test). Three patients had their SA attacks during pregnancy, 1 of them during anesthesia for planned cesarean section. No patient had syncope episodes during physical effort. Chest pain sensations were noted before the attacks in no fewer than 11 patients. Easy fatigability, nightmares, and psychical alterations were common findings preceding the attacks. Eight patients were treated with sedatives for anxiety and nervousness, probably caused by syncope sensations related to a slow VR. Mitral insufficiency was noted before the attacks in 4 patients.

The initial phase of the SA attack was documented on ECG in 5 patients. A 15-year-old girl had repeated episodes of ventricular arrest, starting every time with one ventricular ectopic beat. On two occasions the period of ventricular arrest turned into ventricular tachycardia. The same series of events occurred in a 37-year-old woman. Three other women of ages 21, 22, and 34, respectively, had periods of ventricular arrest without preceding ventricular ectopy. The 34-year-old woman had the arrest during anesthesia and the arrest was followed by ventricular fibrillation. In 4 of these patients, QT_c was prolonged at the time of the attacks.

Other Symptoms

Easy fatigability and effort dyspnea, increasing with age, were the dominant symptoms in 16 cases. Three patients developed cardiac failure, the two men with mitral insufficiency mentioned above and a 56-year-old woman who had been treated with a PM for 13 years. She had a low cardiac output and effort dyspnea before PM implantation and has developed heart failure during the last few years.

Other Diseases

Three patients had kyphoscoliosis, 2 had diabetes mellitus, and 12 had moderate systemic hypertension; 9 of these hypertensive patients were more than 50 years old. Two women, 26 and 34 years old, had collagen disease. Hypothyroidism after pregnancy was present in 2 women. One man was operated on for goiter, and the histological picture showed no signs of thyrotoxicosis.

Mitral Insufficiency

Mitral insufficiency developed in 16 patients, 8 women and 8 men. In 6 of these patients the CCHB was diagnosed before or at birth. In 6 patients the diagnosis of regurgitation was established by means of physical examination only and in the other 10 patients by ultrasound and/or angiocardiography in addition. No patient had a history of rheumatic fever. The insufficiency was mild in 9 patients and moderate or severe in 7 patients. Two patients underwent surgery, one at the age of 22 years (annuloplasty) and the other at the age of 21 years (valve replacement). The age at the first appearance of insufficiency varied between 13 and 56 years (median age at onset, 33 years). One man had effort dyspnea during his last year of life and died suddenly at the age of 57 years, having not been treated with a PM. The other 15 patients received a PM. In 8 patients the main indication for PM was SA attacks (6) or presyncope (2). After the PM implantation, no significant signs of further deterioration of the valve disease were noted in 11 of the patients. The regurgitation disappeared after PM implantation in one case. Three men died 8 months, 6 months, and 1 week after implantation of PM at the ages of 24, 31, and 45 years, respectively. Two of these patients were in severe heart failure, and the 24-year-old man died after repeated SA attacks. The autopsy of this patient showed lead fracture. Autopsy of the 31-year-old man showed dilated mitral annulus and fibrosis of the left ventricle. The autopsy findings of the 45-year-old man showed dilated annulus, fibrosis, and signs of a fresh myocardial infarction of the left ventricle. This man had a history of mitral regurgitation for 3 months and died 1 week after PM implantation. There was a positive correlation (P<.001) between SA attacks and mitral regurgitation.

ECG Findings

VR and Atrial Rate at Rest

The mean VR in women was 42 beats per minute (bpm) and in men, 41 bpm. Fig 3 shows the VR and atrial rate (AR) in the material as related to age. Patients with a change of rhythm are not included. Repeated ECG recordings allowing a comparison of the individual VR with increasing age were available in 94 patients. A decrease in VR was noted in 76 patients. The VR was unchanged in 11 patients and in 7 patients it increased. In the group of 29 patients with syncope and presyncope, 17 patients had a VR <40 bpm at the recording immediately before the attack, but statistically low VR was not significantly correlated with future SA attacks or death. The decrease in VR with age was statistically significant (P<.0025).

Atrial Flutter-Fibrillation

Atrial tachydysrhythmias were noted in 4 patients with mitral insufficiency at the ages of 53, 46, 45, and 40 years, respectively. Two patients died. Atrial flutter was observed at the age of 8 years in another patient. She received a PM for SA attacks at the age of 30 years.

Change of Rhythm

The puzzling event of an apparently permanent complete atrioventricular (AV) block changing into a lower degree of block occurred in 6 patients (Table 1). Otherwise, these patients did not differ from the other patients reported. In 5 of the cases the block had changed to first-degree AV block and in 1 case to second-degree block. This latter patient was 26 years old, and the block was diagnosed in utero. Her mother had lupus erythematosus, and she herself had rheumatoid arthritis. None of these 6 patients had bundle-branch block pattern.

Wide QRS Escape Rhythm

Eight of 102 patients had widened QRS complexes: 4 had right bundle-branch block (RBBB) pattern, 1 with left anterior hemiblock in addition and another 4 patients had left bundle-branch block (LBBB) pattern. Two patients with RBBB and 1 with LBBB pattern had SA attacks, at the ages of 57, 22, and 16 years. The youngest patient showed a poor VR response to exercise when 10 years old, with an increase in VR from 40 to 55 bpm at a workload of 2.5 W/kg. The other 5 BBB cases have no symptoms and no PM so far and are 46, 41, 37, 27, and 26 years old. The maximal VR during exercise tests in these patients were 109, 102, 92, 93, and 74 bpm. In this group of patients only sporadic ectopic beats appeared during exercise. The presence of widened QRS complexes was statistically no predictor of SA attacks and/or death.

QT Time

A prolonged QT time (QT_c >0.45 second) was recorded on one or more occasions in 7 out of 102 patients (Table 2). In all cases, a normal QT_c time had previously been observed. SA attacks occurred in all 7 patients. The prolonged QT_c times were noted after the attack in 3 patients—12 hours, 14 days, and 3 weeks after, respectively. In 4 patients the SA attacks occurred after the recording of prolonged QT_c. The time interval varied between 6 months and 5 years. Three patients died, 1 from the attack and 1 from brain damage caused by the circulatory arrest. The third patient with repeated SA attacks had mitral insufficiency in addition and died 8 months after PM implantation. The other 4 patients have survived without symptoms and with PM treatment for 23, 21, 18, and 17 years, respectively. The ECG with prolonged QT_c showed a lower VR than earlier recordings, and 6 patients had rates of ≤40 bpm.

Exercise Tests

Data from exercise tests are presented in Fig 4. The 6 patients in whom the CCHB changed from complete to grade I or II have been excluded. The remaining 81 patients have been divided into 34 with a workload of less than 2 W/kg and 47 with a workload of 2 W/kg or more. In the group with a lower workload there are 7 patients with a VR increase of ≤25 bpm, compared with 2 patients in the group with a higher workload. The mean VR increase was 90 bpm in the lower workload group, with a range of 55 to 136 bpm, and in the group with the higher workload it was 115 bpm, with a range of 55 to 155 bpm. Resting VRs of <40 bpm were noted in 15 patients, and 7 of these had SA attacks later. There were 17 patients with a VR during exercise of <80 bpm, and in 8 of them SA attacks occurred. Ventricular ectopies were found to disappear during heavier workload in 8 patients, and only 1 had future SA attacks. In 22 patients ectopies were frequent and increased with a heavy workload. In this group 13 subsequently had syncope or presyncope. As many as 11 patients with future syncope attacks had an exercise test with a resting VR >40 bpm, a VR increase >80 bpm, and no ectopy. No significant statistical correlation was found between VR at rest or during effort, low working capacity or ectopies, and future SA attacks and/or death.

Pacemaker Treatment

A total of 54 patients were treated with PMs (Fig 1). The indications were syncope or presyncope in 27 patients. The indications for the remaining patients were general fatigue, effort dyspnea, dizziness, and, in 16 cases, also low VRs. Four of these had mitral insufficiency. Three patients, aged 21, 21, and 17 years, respectively, received their PMs mainly because of a low VR and frequent ectopies during effort. One patient, aged 22 years, was given a PM during pregnancy because of toxemia of pregnancy. The median age of the other 23 patients at time of implantation was 34 years and the range, 16 to 49 years.

Two patients with a failing PM died suddenly in 1967 (lead fracture) and 1978 (generator depletion), 8 months and 13 years, respectively, after PM implantation. Other serious PM complications were thrombosis of the superior vena cava in one case and endocarditis involving the tricuspid valve in another case. Two other patients with mitral regurgitation and severe heart failure died suddenly, 6 months and 1 week, respectively, after PM implantation, but no evidence of PM failure was disclosed. Age-related statistical analysis showed that the mortality was significantly lower in patients with a PM implanted (P<.03). The pacing therapies changed over the years in the same patient and from case to case. It is therefore not possible to evaluate the different techniques in this material.

Pregnancy

Twenty-four women without a PM gave birth, to 45 children in total. Three of these 24 had syncope attacks during pregnancy, and a PM was implanted in 2 women. Three other patients had fainting spells during pregnancy, and another 3 noted dizziness after delivery. One woman with toxemia of pregnancy had prophylactic PM implantation. Eight other women with a PM had uneventful pregnancies and deliveries of a total of 14 children.

Thirty-Year Follow-up

Forty of the 102 patients were already registered 30 years ago. The mean age at that time was 22 years, with a range of 15 to 44 years. During these 30 years, 8 patients died. The mean age at death was 42 years, with a range of 24 to 58 years. Fifteen patients survived SA attacks (12) or fainting spells (3) and received a PM. Another 13 patients received a PM for other reasons (dyspnea, low working capacity, mitral regurgitation). Twelve patients developed mitral regurgitation. Only 4 patients (52, 50, 49, and 47 years old) are free from symptoms and do not have a PM. In 2 of these patients the block has changed to a first-degree AV block. The natural history of these patients is further illustrated in Fig 5.

Discussion

Cases of associated structural heart disease have been omitted in this study and no patients with symptoms in infancy or childhood are included. The prognosis should therefore be better than in any other patients with CCHB. The finding of high mortality and morbidity rates in both young and older adults supports a much less optimistic view than has previously been held. Many of the patients were told when they were young that no further examinations were necessary “unless you became symptomatic.” This attitude is unwise, since deterioration both without symptoms and with symptoms not readily referable to the dysrhythmia, such as anxiety and mental confusion, was noted. Among the 48 patients who were not treated with a PM, the first SA attack was fatal in no fewer than 6 cases. Among the 54 patients who had a PM implanted, there were 4 deaths, 2 due to PM failure and 2 due to myocardial infarction and heart failure. We conclude that a reduction of mortality could have been achieved if PMs had been implanted earlier in life.

Risk Criteria

It could be argued that cases not diagnosed before or at birth should not be classified as “congenital.” In half of the present patients, CCHB was diagnosed in utero or at birth. With 12 cases having SA attacks in this “truly congenital” group, as compared with 15 among the patients diagnosed later, the age at diagnosis does not seem to be of prognostic importance.

It would be desirable to be able to point out signs predicting an increased risk in the individual patient. Low VRs—<40 bpm in the young, ≤35 bpm in the elderly—prolongation of the QT time and the appearance of frequent ectopies, as well as a low VR response during heavy work, have been reported as such indicators.^1119202122 There are several examples among these patients of syncope attacks occurring without any preceding signs. The only convincing risk factor in this study was a prolonged QT_c. All 7 patients with a prolonged QT_c suffered SA attacks.

Stokes-Adams Attacks

The term SA attack is not always clearly defined. According to Stokes’ own description, fainting spells can be looked upon as less-severe SA attacks. He wrote: “In some there is a momentary unsteadiness in walking and in others a tendency to faint; while in the more decided cases the patient becomes suddenly comatose.” In this study, the patients with fainting spells are described as a group separated from “the more decided cases.”

It is of interest to note that SA attacks never occurred during effort. Many patients stated that they felt better during physical activity than at rest, probably because of the higher VR during effort. Retardation of VR, exit block, during sleep as described by Levy et al¹⁹ might be the reason why 5 patients died during sleep. Very low VRs could explain why nightmares are so common in CCHB patients.

Ventricular Rate

It is well known that in CCHB the VR decreases with age during infancy and childhood. The decrease in VR in adults is to our knowledge a new observation. The AR did not decrease with age. We have no explanation for the decrease in VR, but it must reduce the ability to maintain an adequate cardiac output. It might be of interest to note that no age-related heart rate changes can be demonstrated in adults with sinus rhythm.²³

Mitral Regurgitation

Only 2 cases of CCHB with mitral valve involvement have been described previously. One was a 16-year-old boy reported in a follow-up study,¹⁴ and the other was a 41-year-old woman in whom the mitral insufficiency was ascribed to a prolapsing mitral valve.²⁴ In the present study, none of the 16 patients showed evidence of valvular lesions early in life. A lower VR was a frequent finding in this group of patients. It is possible that a very low VR with overdistension of the left ventricle and the papillary muscles caused the valve regurgitation. Another conceivable hypothesis is that mitral insufficiency is the long-term result of more extensive immunopathological damage to the fetal heart. The regurgitation is more common in the elderly patients. The risk of acquiring mitral insufficiency, with its deleterious consequences, in CCHB is a strong argument for PM treatment early in life.

Wide QRS Escape Rhythm

A BBB pattern, in contrast to narrow QRS complexes, is believed to imply a poor long-term prognosis. The findings in this study offer limited support to this hypothesis, 3 out of 8 BBB cases having SA attacks. On the other hand, 2 of the patients with a BBB pattern died in their first attack.

Exercise Tests

A recent publication on the cardiorespiratory response to exercise in CCHB includes a literature review.²⁵ The authors state that neither the individual exercise response nor the exercise tolerance could be predicted from the resting VR and also that the VR response was below the 95% confidence limit throughout different exercise levels. The occurrence of a low VR at rest, a poor VR response, and the occurrence of ectopies during heavy work have been reported as poor prognostic signs.²³ Our study could not confirm these findings. In fact, 7 patients with future SA attacks had a VR at rest of >40 bpm, a satisfactory VR response, and no ectopy. When the VR response is compared with the exercise performance, a tendency toward a better response with heavier exercise is noted. Our research does not allow more detailed analysis in this respect. Determination of the ventilatory threshold would probably have been helpful in the assessment of the functional capacity.²⁵

QT_c Prolongation

The present study confirms that prolongation of the QT_c time is an unfavorable prognostic sign.²¹²² A prolonged QT_c time associated with CCHB has been described as a separate disease entity, and β-receptor blocking has been recommended together with PM treatment.²⁵ Another speculation is that a prolonged QT_c time is a sign of myocardial damage rather than a separate syndrome. In their study concerning prolongation of the QT_c time as a predictor of sudden death in myocardial infarction, Schwartz and Wolf²⁶ assume that local myocardial damage might be responsible for the QT prolongation. Similarly, episodes of excessively low VR and/or some other unknown factor might cause myocardial damage manifested by a longer QT_c. Six of the 7 patients with prolonged QT_c had VRs of ≤40 bpm at the time of ECG recording.

Change of Rhythm

It is difficult to imagine how a CCHB could change into a lower-degree block or even into sinus rhythm. Doubt could be raised if the block cases published^{1214272829303132} and the ones here reported—14 cases in all—are truly congenital: At least 4 of the cases were diagnosed in utero or at birth. In that sense they are congenital, and there is no indication that the other 10 cases were different. The degree and extension of the morphological findings in CCHB—fibrosis of the conductive system and other parts of the heart—are very different from case to case. It is quite possible that the morphological abnormalities in cases of CCHB changing in rhythm are discrete and that the block could be explained in electrophysiological terms such as decremental conduction.³³ In one of the patients, CCHB changed to AV block I after many years of PM treatment for SA attacks.

Conclusions

Patients changing into a lower degree of block are rare exceptions. In a life-long perspective, CCHB is a potentially life-threatening disease with significant morbidity in the group as a whole. There is a risk of SA attacks and sudden death at any age even in the absence of poor prognostic signs. It is possible that early PM implantation reduces or eliminates morbidity such as mitral valve insufficiency. We therefore recommend a PM to any adolescent patient with CCHB.

If a PM should be refused, an annual examination is recommended, with Holter monitoring, exercise testing, and echocardiography. The occurrence of decreasing VR, a low rate response, or frequent ectopies during effort, exit block periods or ectopies during monitoring, mitral insufficiency, a long QT_c time, and widened QRS complexes are all good reasons for discussing PM treatment again.

In summary: (1) 40 patients were followed for 30 years and only 4 remained free from symptoms and without a PM; (2) 11 of 102 patients died at a relatively young age; (3) SA attacks or fainting spells occurred in 35 patients, none during exertion; (4) mitral regurgitation developed in 16 patients; (5) the CCHB changed to a lower degree of block in 6 of the 102 patients; (6) VR decreased with age; (7) mitral regurgitation was a predictor of future SA attacks; (8) long QT_c was strongly linked to SA attacks; (9) low VRs, widened QRS complexes, low exercise response, and ectopies were not predictive of future SA attacks or death; and (10) a PM reduces mortality.

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Footnotes