Left Ventricular Mechanics and Geometry in Patients With Congenital Complete Atrioventricular Block
Background Radiographic evidence of cardiomegaly is common in patients with congenital complete atrioventricular block (CCAVB). It has been speculated that left ventricular (LV) remodeling and increased stroke volume counteract the bradycardia, but the effects of slow heart rate and atrioventricular asynchrony on LV dimensions, geometry, wall stress, and function have not been examined in detail.
Methods and Results Thirty patients with CCAVB without associated congenital heart disease (mean age, 8.5±5.3 years; range, 0.2 to 20 years) were included in a cross-sectional two-institution study. Thirty-five echocardiograms were performed using standard techniques. ECG and 24-hour ECG recordings were reviewed. Seven patients did not receive a pacemaker, whereas 23 patients underwent pacemaker implantation after the echocardiogram. Compared with normal control subjects, LV volume (Z score=1.5±1.3) and LV mass (Z=1.2±1.5) were significantly increased, whereas LV mass-to-volume ratio (1.1±0.3) and geometry (short-axis diameter/length ratio=0.65±0.09) were normal. LV end-systolic stress (ESS) (a measure of afterload) was normal (Z score=0.2±2.3), whereas shortening fraction (Z=3±2.9) and velocity of circumferential fiber shortening (VCF) (Z=3±3.1) were increased. The relationship between VCF and ESS (a preload-insensitive and afterload-adjusted index of contractility) was increased (Z=2.2±2) with only small increase in preload (Z=1.02±1.1). Regression analyses showed no significant change over age in LV mass, volume, geometry, loading conditions, or systolic function. Patients who ultimately met criteria for pacemaker implantation did not differ from those who did not in terms of heart rate or LV function but did have increased LV volume (Z score=1.8±1.4 versus 0.4±0.9, P=.03) and LV mass (Z score=1.7±1.2 versus 0.2±1.7, P=.001) compared to the unpaced group.
Conclusions In most patients with CCAVB, the LV was enlarged with normal geometry and enhanced systolic function during the first two decades of life. The degree of LV dilation and enhanced function did not significantly change with age. In patients who ultimately underwent pacemaker implantation LV function did not differ from those who remained unpaced, but evidence of a slightly increased load manifested as increased end-diastolic volume and mass.
Congenital complete AV block is a rare condition with a reported incidence between 1 in 15 000 and 1 in 25 000 live births, with most estimates at 1 in 22 000. Approximately 25% to 33% of these children will have associated heart disease.1 Survival to adulthood without pacemaker implantation has been well documented in patients with CCAVB.2–6 Several investigators have reported radiographic evidence of cardiomegaly in these patients.4,5,7 Some have postulated that the cardiomegaly may be related to LV remodeling and reorganization of myofibers to increase stroke volume and compensate for slow heart rate.8,9 Only limited information exists regarding LV adaptation to CCAVB. One report found that global LV function is normal in this population6; however, the effects of long-standing slow heart rates and AV asynchrony on LV dimensions, geometry, and function in patients with CCAVB have not been examined in detail.
The present study was designed to evaluate LV structure and function in patients with CCAVB to determine whether bradycardia and AV asynchrony are associated with any potentially adverse effects on cardiac mechanics during the first two decades of life. The study also aimed to determine whether patients who met criteria for pacemaker implantation during the study period differed in terms of LV structure or function from those who did not.
A cross-sectional study was performed at Children’s Hospital in Boston and Texas Children’s Hospital in Houston. Thirty patients with CCAVB who underwent 35 echocardiograms and had no significant structural heart disease were included. Patients who had undergone pacemaker implantation before the echocardiogram were not included in this study. The following information was obtained in each patient at the time of the echocardiogram: age, sex, height, weight, and heart rate. A 15-lead ECG was evaluated for the presence of CCAVB, and the most recent 24-hour ECG was reviewed for the maximum, minimum, and average heart rates and for ectopy. Study patients were assigned into two groups based on whether they subsequently underwent pacemaker implantation. Group 1 consisted of 7 patients who did not receive a pacemaker by the time the study was concluded. Group 2 consisted of 23 patients who underwent pacemaker implantation subsequent to their echocardiographic examination. Study patients were compared with a control group of 256 children and adolescents without heart disease (age, 7 days to 19 years; 134 boys and 122 girls) who were studied at the echocardiography laboratory of Children’s Hospital (Boston).10
Echocardiograms were performed with several commercially available cardiac scanners with transducer frequency appropriate for the patient’s size and acoustic windows. Sedation with oral chloral hydrate (70 to 100 mg/kg; maximal dose, 1 g) was used in infants when necessary. Each study included an evaluation of cardiac anatomy, ventricular function, and valve competence by two-dimensional imaging, pulsed, and color Doppler mapping. Studies were recorded on a 0.5-in (1.27-cm) super-VHS videocassette tape for subsequent review and offline analysis.
LV length in systole (measured on the video frame showing minimal dimension) and diastole (measured on the video frame showing maximal dimension) were measured from the apical four-chamber view between the plane of the mitral valve annulus and the apical endocardium. For assessment of LV systolic function, the two-dimensionally directed M-mode tracing of the LV minor axis between the papillary muscles tips, the indirect carotid arterial pulse tracing, phonocardiogram, and ECG were simultaneously recorded on hard copy at high paper speed (100 mm/s) as described previously.11 Right arm systolic and diastolic blood pressures were recorded at the same time using a Dinamap Vital Signs Monitor 8100T (Critikon).
LV Dimensions and Stress
All computer measurements were performed at Children’s Hospital in Boston by the same individual (P.S.G.). The M-mode tracing of the endocardial borders of the interventricular septum and the endocardial and epicardial borders of the LV posterior wall, arterial pulse tracing, onset of Q wave on the ECG, and first high-frequency component of the second heart sound on the phonocardiogram were digitized using a computer-based digitizing station with customized software.12 From the digitized data, the following instantaneous measurements were obtained by averaging three to six cardiac cycles: (1) LV pressure during ejection as has been previously described and validated against pressure measurements obtained through catheterization,13 (2) LV posterior wall thickness, and (3) LV internal dimensions in the short-axis plane. End-diastolic measurements were taken at the time of maximal LV dimension and end-systolic measurements were taken at the time of aortic valve closure (first high-frequency component of the second heart sound on the phonocardiogram). Because of concerns that conventional stress calculations in the presence of hypertrophy may misrepresent forces at the myocardial fiber level, Mirsky14 and Regen15 advocated the use of fiber stress instead of mean transmural wall stress as an index of afterload. In addition to accounting for lateral stress in the meridional and circumferential planes, fiber stress accounts for stress in the radial direction.15 Another concern is that in the presence of hypertrophy and increased mass-to-volume ration, endocardial-based indices of fiber shortening overestimate the extent and velocity of fiber shortening in sections of the wall that are not adjacent to the endocardium.19 Because it is not universally agreed which of the above is the most accurate method with which to assess afterload and fiber shortening in patients with CCAVB, endocardial, midwall wall stress, and fiberstress indices were calculated. (4) LV meridional wall stress (in g/cm2) was calculated throughout ejection according to the formula of Brodie et al.16 ESSm was measured at the onset of the aortic component of the second heart sound on the phonocardiogram. (5) ESSc (in g/cm2) was calculated according to the formula of Mirsky.15 (6) Fsm was calculated according to the formula of Regen.17 (7) ETc was measured from the arterial pulse tracing from the onset of upstroke to the onset of the dicrotic notch and adjusted to a heart rate of 60 bpm by dividing the heart rate by the square root of the RR interval on the ECG. When heart rate was ≤60 bpm, no adjustments were made. (8) SF was calculated as (end-diastolic dimension−end-systolic dimension)/end-diastolic dimension. (9) VCFc was calculated as SF divided by rate-adjusted ejection time. (10) LV volume was calculated using the modified Simpson’s rule.17 Ejection fraction was calculated as 100×(end-diastolic volume−end-systolic volume)/end-diastolic volume. LV mass was calculated as 1.05×(LV epicardial volume−LV endocardial volume).18 (11) LVEDDmw (in cm) was calculated as LVEDDmw=Ded+hed, where Ded is the LV endocardial end-diastolic diameter and hed is the LV end-diastolic posterior wall thickness. LVESDmw (in cm) was calculated using the formula of Shimizu et al.19 LV midwall shortening fraction and midwall velocity of circumferential fiber shortening were calculated from these end-diastolic and end-systolic midwall dimensions. (12) Cardiac output was calculated as the product of stroke volume×heart rate.
Contractility and Preload Indexes
The relationship between VCFc and ESS has been previously shown to be an afterload adjusted index of contractility that is relatively insensitive to preload.20 The position of the relation of VCFc to ESS for each patient was determined relative to the previously reported distribution of this index in normal subjects and calculated as the SVI.20 The SVI is equal to the number of SDs from the population mean VCFc for ESS and is expressed as Z score. In contrast, the relationship between FS and ESS (known as SSI) is an afterload-adjusted index of contractility sensitive to changes in preload.11,12,20 The SSI is equal to the number of SDs from the population mean FS for the given ESS. The relative magnitude of VCFc compared with FS is a measure of preload status, reflecting the fact that FS is directly related to end-diastolic fiber length, whereas VCFc is relatively independent of preload.11,12,20,21 Differences between ESS/VCFc relation and ESS/FS relation, therefore, reflect the functional consequences of altered preload, which was quantified as the functional preload index: FPI=SSI−SVI.
The degree of mitral regurgitation was graded qualitatively as trivial or none, mild, moderate, or severe on color-Doppler flow mapping of the regurgitant jet as described previously.22
Data are reported as mean±SD value for each group of measurements. To adjust for age-, body size–, and growth-related changes in LV dimensions and mechanics,10,23 all measurements are reported as Z scores. Z scores were computed as follows: Z score=(measured value−mean value of normal controls)/SD of normal control subjects. The mean Z score of the normal control group is 0.10 To determine whether Z scores differed from the normal population, one-factor analysis was performed with a hypothesized difference of zero. Correlation analysis and linear regression analysis with the least-squares method were used to evaluate the relationship between continuous variables. In these analyses, age was considered an independent variable, and LV dimensions and indices of function were considered dependent variables. Unpaired Student’s t test was used to compare paced with nonpaced patients. The Spearman rank correlation analysis was used to correlate the degree of mitral regurgitation with LV dimensions and indexes of function. Data analysis was performed using a commercially available statistical package (StatView 4.1, Abacus Concepts, Berkeley, Calif). For all tests, a value of P<.05 was considered statistically significant.
Characteristics of Study Patients
The demographic and clinical characteristics of the study patients are summarized in Table 1⇓. Thirty patients (16 male and 14 female) met the inclusion criteria for this study and underwent 35 echocardiograms. Two patients had serial echocardiograms. Twenty-three patients have subsequently undergone pacemaker implantation. The indications for pacemaker implantation were complex ventricular ectopy at rest or with exercise (n=6), bradycardia as defined in the American Heart Association/American College of Cardiology guidelines24 (n=6), exercise intolerance (n=4), syncope (n=3), LV enlargement (n=2), and pauses of >4 seconds (n=1). One patient had three indications for pacing: complex ventricular ectopy, exercise intolerance, and bradycardia. Seven patients remain unpaced. The age range of the entire group was 0.2 to 20 years (median, 8 years). There was no significant difference between the ages of the paced and unpaced patients.
Heart Rate and Blood Pressure
The average heart rate at the time of study was 47±6 bpm, and there was no difference between those who were subsequently paced and those who were not. On 24-hour ECG monitoring, the average, minimum, and maximum heart rates were not significantly different between groups (Table 1⇑). When heart rate was plotted against age, there was a slight but statistically significant inverse linear correlation (r2=−.34, P=.04) (Fig 1A⇓). When heart rate was adjusted to age (expressed as Z score), it became apparent that the degree of bradycardia relative to age-adjusted normal population is substantially more pronounced in infancy and early childhood compared with adolescence (Fig 1B⇓). Pulse pressure was wide due to a relatively low diastolic blood pressure in both groups. Compared with unpaced patients, both peak and end-systolic pressures were slightly increased in patients who were subsequently paced, but both parameters were within the normal range in both groups.
LV Dimensions and Geometry
Overall, the LV was moderately dilated with preservation of normal geometry. Compared with normal subjects, LV end-diastolic volume (Z score=1.5±1.3), LV end-diastolic dimension (Z score=1.8±1.3), and LV mass (Z=1.2±1.5) were significantly increased (P<.0001) (Table 2⇓), yet LV mass-to-volume ratio (1.1±0.3) and LV geometry (LV short-axis diameter/length ratio=0.65±0.09) remained normal. To determine whether the Z values of LV dimensions changed with age, multiple linear regression analyses were performed. These analyses showed that the BSA–adjusted LV internal dimensions, volume, and mass did not significantly change during the first two decades of life (Fig 2⇓).
The following load-dependent indices of global LV function were significantly increased: SF (Z score=3.0±2.9, P<.0001) and velocity of circumferential shortening (Z score=3.0±3.1, P<.0001). End-systolic stress was normal (Z score 0.2±2.3, P=.56). The SVI, a preload-insensitive index of contractility (Z=2.2±2) and the SSI (Z=3.2±2.1) were significantly increased (P<.0001) (Table 2⇑). Preload index was only slightly increased (Z=1.02±1.1). There were no significant differences in LV wall stress, SVI, SSI, and preload index between measurements in the meridional plane and the circumferential plane or between endocardial and midwall measurements (Table 2⇑). Cardiac index was low normal (2.3±0.8 L · min−1 · m−2). To determine whether the LV function or contractility changed with age, linear regression analyses were performed (Fig 2⇑). The enhanced LV contractility index remained unchanged with age (r2=.029, P=.3), as did the SF (r2=.009, P=.6).
In 23 of 30 patients, the degree of mitral regurgitation was mild or less. Mild to moderate mitral regurgitation was seen in 7 patients whose age ranged from 3.7 to 19.8 years, with a median of 11.8 years. None of the patients had moderate or severe mitral regurgitation. No significant correlation was found between the degree of mitral regurgitation and LV end-diastolic volume (P=.46), LV end-diastolic dimension (P=.2), or age (P=.09).
Comparison Between Paced and Unpaced Patients
The following indices of global function were increased in both groups and did not significantly differ between groups: SF, ejection fraction, VCFc, and SVI (Table 2⇑). There were also no significant differences between the groups in age or heart rate at the time of echocardiogram. There were no differences in average heart rate, minimum heart rate, or maximum heart rate on 24 ECG monitoring (Table 1⇑). Patients who were ultimately paced had significantly increased LV mass (Z score=1.7±1.2 versus 0.2±1.7, P=.001) and LV volume (Z score=1.8±1.4 versus 0.4±0.9, P=.028) at the time of the echocardiogram.
The results of this study demonstrate that on average, in patients with CCAVB the LV is moderately enlarged with normal geometry, normal wall stress, and enhanced systolic function during the first two decades of life. In the patients included in this study, the degree of LV dilation and enhanced function did not significantly differ with age.
LV Mechanics and Geometry
Previous studies of patients with CCAVB have speculated that these patients maintain their cardiac output by increasing their stroke volume.1,9 The increased stroke volume was postulated to be secondary to the increased time for diastolic filling, which resulted in increased end-diastolic volume with stretching of myocardial fibers and facilitation of myocardial contractility.9 In the present study, the increased LV end-diastolic volume was accompanied by a parallel increase in LV mass, thereby preserving normal LV wall stress. Normal LV geometry, expressed as the ratio between short-axis diameter and LV length, was also preserved. This observation contrasts with findings in patients in whom a volume load is acquired as a result of valve regurgitation or a shunt lesion. In patients with severe mitral or aortic valve regurgitation, the change in shape of the LV from an ellipsoid bullet-shaped to a globular geometry is associated with deterioration of systolic performance and contractility.25–27
In the patients with CCAVB evaluated in this study, enhanced systolic function appears primarily related to increased contractility without evidence of significantly altered loading conditions. There was evidence of marginally but not significantly elevated preload (afterload-adjusted fractional shortening was only slightly more elevated than afterload-adjusted velocity of circumferential fiber shortening) and normal afterload. The failure of a prolonged diastolic filling period in these subjects to result in a substantial increase in preload, considered as end-diastolic fiber stretch, is not surprising given the normal myocardial response to chronic volume load. Elevated diastolic stress normally elicits myocardial hypertrophy and remodeling with addition of fibers in series until stress is normalized.26,27 Because of this, persistent elevation of diastolic stress is an indication of inadequate hypertrophy and would not be expected in well-compensated hypertrophy with an appropriate mass-to-volume ratio as was found in these patients. These findings are in contrast to those in physiological hypertrophy in athletes,12 where reduced afterload is the primary factor responsible for elevated systolic function, without evidence of enhanced contractility. The etiology of the enhanced contractility in these patients is not known. Evidence of persistent elevation in contractility has been described in young patients with congenital chronic pressure overload hypertrophy secondary to coarctation of the aorta28 but has not been described in volume overload lesions. The enhanced contractility found in patients with CCAVB cannot be explained by an artifact caused by the use of endocardial indices because the results of midwall indices were essentially the same as the endocardial indices. The agreement between these indices is expected in light of the normal LV mass-to-volume ratio found in these patients.
Although the majority of patients in this cohort had enhanced LV function, there were 2 patients whose function was depressed (fractional shortening, 26% and 28%). Others have reported patients with depressed LV function and cardiomyopathy despite the implantation of dual-chambered pacemakers in the neonatal period.29 It appears from the data presented by Moak et al29 that whatever causes these patients to have depressed function is not reversible with the institution of pacing. One could speculate that either there is more immunopathological damage to the heart, as Michaelsson et al30 suggested to be the cause for those with mitral regurgitation, or that the etiology of CCAVB in the subgroup of patients with depressed LV function is different from that of patients with normal function. In one reported case of a neonate with CCAVB, severe LV dysfunction was attributed to associated myocarditis.31 The etiology of depressed LV function in one of the 2 patients in our study is attributed to mitochondrial disease and is unknown in the other patient.
Concerns that the development of mitral regurgitation would be a complication of long-term CCAVB without pacing were addressed by Michaelsson et al,30 who reported a 16% incidence in adults with CCAVB; these patients had slower ventricular rates and the mitral regurgitation was postulated to result from overdistention of the heart. In the present study, mitral regurgitation was seen by color-coded Doppler in 77% of patients, with greater than mild regurgitation in 23%, and was first noted in patients as young as 4 years. However, the degree of mitral regurgitation did not correlate with heart rate, LV function, LV end-diastolic volume, or short-axis LV end-diastolic dimension. Because of the cross-sectional nature of this study, it is not possible to determine whether the degree of mitral regurgitation is progressive or is alleviated by pacemaker placement. In the study by Michaelsson et al,30 only 1 patient had resolution of his mitral regurgitation with pacemaker placement; however, this intervention occurred relatively late in the natural history of the disease.
Influence of Pacemaker Requirement
Patients who ultimately underwent pacemaker implantation did not differ from those who did not with respect to age or sex. Although the average and minimum heart rates measured from 24-hour ECG were slightly lower in patients who were eventually paced, these differences did not reach statistical significance. Most measurements of LV mechanics were similar in the two groups. The groups did not significantly differ from each other in terms of LV geometry, SF, and SVI. Those who underwent pacemaker placement had significantly increased LV mass and volume, which is consistent with the findings of Sholler and Walsh,32 whose symptomatic patients had cardiac enlargement on chest radiograms and ECG. This finding, however, may represent a selection bias because LV enlargement was considered an indication for pacemaker in 2 patients. There was no apparent relationship between changes in LV mechanics and indication for pacemaker placement based on the data in the present study. Of note, this patient population had a marginal cardiac index at rest (Table 2⇑), which may have contributed to the exercise intolerance reported by some patients and was the indication for pacemaker placement in 5 patients. In addition, LV dysfunction was not the reason for pacemaker implantation in the majority of patients who ultimately had a device implanted. In this study, we could not determine the optimal time for pacemaker placement or address the potential long-term benefits of pacing. The dilemma regarding optimal timing and patient selection for pacemaker implantation in children and adolescents with CCAVB was discussed elsewhere.33
Because of the rarity of CCAVB, the study design was cross sectional. This limitation precludes inference regarding the natural history of patients with CCAVB. In the 2 patients who were followed longitudinally over 15 years by echocardiograms, the longitudinal data followed the trend of the cross-sectional cohort.
In most patients with congenital AV block, the LV is moderately enlarged with normal geometry and enhanced systolic function during the first two decades of life. The degree of LV dilation and enhanced function did not significantly change with age. In patients who ultimately underwent pacemaker implantation, LV function did not differ from those who remained unpaced but had evidence of a slightly increased load manifested as increased end-diastolic volume and mass.
Selected Abbreviations and Acronyms
|CCAVB||=||congenital complete atrioventricular block|
|ESSc||=||end-systolic circumferential wall stress|
|ESSm||=||end-systolic meridional wall stress|
|ETc||=||heart rate–adjusted ejection time|
|Fsm||=||meridional fiber stress|
|LV||=||left ventricular, ventricle|
|LVEDDmw||=||left ventricular end-diastolic midwall dimension|
|LVESDmw||=||left ventricular end-systolic midwall dimension|
|VCFc||=||rate-adjusted mean velocity of circumferential fiber shortening|
We thank Emily Flynn-McIntosh for artwork.
Guest editor for this article was David J. Sahn, MD, Portland, Ore.
- Received June 5, 1997.
- Revision received July 25, 1997.
- Accepted August 1, 1997.
- Copyright © 1997 by American Heart Association
Ross BA. Atrioventricular block. In Garson A Jr, Bricker JT, McNamara DG, eds. The Science and Practice of Pediatric Cardiology. Philadelphia, Pa: Lea & Febiger; 1990:1803.
Michaelsson M, Engle MA. Congenital complete heart block: an international study of the natural history. Cardiovasc Clin. 1972;4:86–101.
Campbell M, Emanuel R. Six cases of congenital complete heart block followed for 34–40 years. Br Heart J. 1967;29:577–587.
Nakamura FF, Nadas AS. Complete heart block in infants and children. N Engl J Med. 1964;270:1261–1268.
Esscher EB. Congenital complete heart block in adolescence and adult life: a follow-up study. Eur Heart J. 1981;2:281–288.
Molthan ME, Miller RA, Hastreiter AR, Paul MH. Congenital heart block with fatal Adams-Stokes attacks in childhood. Pediatrics. 1962;30:32–41.
Scarpelli EM, Rudolph AM. The hemodynamics of congenital heart block. Prog Cardiovasc Dis. 1964;6:327–342.
Borow KM, Newburger JW. Noninvasive estimation of central aortic pressure using the oscillometric method for analyzing systemic artery pulsatile blood flow: comparative study of indirect systolic, diastolic, and mean brachial artery pressure with simultaneous direct ascending aortic pressure measurements. Am Heart J. 1982;103:879–886.
Mirsky I. Review of various theories for evaluation of left ventricular wall stress. In Mirsky I, Chiston DN, Sander J, eds. Cardiac Mechanics: Physiological, Chemical and Mathematical Considerations. New York, NY: Wiley; 1974:381–409.
Regen DM. Calculation of left ventricular wall stress. Circ Res. 1990;67:245–252.
Silverman NH, Ports TA, Snider AR, Schiller NB, Carlsson E, Heilborn DC. Determination of left ventricular volume in children: echocardiographic and angiographic comparisons. Circulation. 1980;62:548–557.
Reichek N, Helak J, Plappert T, St John Sutton M, Weber KT. Anatomic validation of left ventricular mass estimates from clinical two-dimensional echocardiography: initial results. Circulation. 1983;67:348–352.
Shimizu G, Zile MR, Blaustein AS, Gaasch WH. Left ventricular chamber filling and midwall fiber lengthening in patients with left ventricular hypertrophy: overestimation of fiber velocities by conventional midwall measurements. Circulation. 1985;71:266–272.
Nixon JV, Murray RG, Leonard PD, Mitchell JH, Blomqvist CG. Effect of large variations in preload on left ventricular performance characteristics in normal subjects. Circulation. 1982;65:698–703.
Sanders SP. Echocardiography. In Long WA, ed. Fetal and Neonatal Cardiology. Philadelphia, Pa: WB Saunders; 1990:301–326:
Dreifus LS, Fisch C, Griffin JC, Gillette PC, Mason JW, Parsonnet. Guidelines for implantation of cardiac pacemakers and antiarrhythmia devices: a report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Committee on Pacemaker Implantation). Circulation. 1991;84:455–467.
Sluysmans T, Sanders SP, van der Velde M, Matitiau A, Parness IA, Spevak PJ, Mayer JE, Colan SD. Natural history and patterns of recovery of contractile function in single left ventricle after Fontan operation. Circulation. 1992;86:1753–1761.
Ross J Jr. Adaptation of the left ventricle to chronic volume overload. Circ Res. 1974;34(suppl II):II-64-II-70.
Moak J, Barron K, Hougen T, Cohen M, Friedman R, Perez M, Buyon J. Congenital heart block: new observations. Pacing Clin Electrophysiol. 1996;19:613.
Michaelsson M, Jonzon A, Reisenfeld T. Isolated congenital complete atrioventricular block in adult life: a prospective study. Circulation. 1995;92:442–449.
Friedman RA. Congenital AV block: pace me now or pace me later. Circulation. 1995;92:283–285.