- Open Access
Ventricular septal defect
© Spicer et al.; licensee BioMed Central. 2014
- Received: 24 April 2014
- Accepted: 28 August 2014
- Published: 19 December 2014
Ventricular septal defects are the commonest congenital cardiac malformations. They can exist in isolation, but are also found as integral components of other cardiac anomalies, such as tetralogy of Fallot, double outlet right ventricle, or common arterial trunk. As yet, there is no agreement on how best to classify such defects, nor even on the curved surface that is taken to represent the defect.
Based on our previous pathological and clinical experiences, we have reviewed the history of classification of holes between the ventricles. We proposed that the defects are best defined as representing the area of deficient ventricular septation. This then permits the recognition of clinically significant variants according to the anatomic borders, and the way the curved surface representing the area of deficient septation opens into the morphologically right ventricle.
Clinical manifestation depends on the size of the defect, and on the relationship between systemic and pulmonary vascular resistances. Symptoms include failure to thrive, along with the manifestations of the increase in flow of blood to the lungs. Diagnosis can be made by physical examination, but is confirmed by echocardiographic interrogation, which delineates the precise anatomy, and also provides the physiologic information required for optimal clinical decision-making. Cardiac catheterization offers additional information regarding hemodynamics, particularly if there is a concern regarding an increase in pulmonary vascular resistance. Hemodynamic assessment is rarely necessary to make decisions regarding management, although it can be helpful if assessing symptomatic adults with hemodynamically restrictive defects. In infants with defects producing large shunts, surgical closure is now recommended in most instances as soon as symptoms manifest. Only in rare cases is palliative banding of the pulmonary trunk now recommended. Closure with devices inserted on catheters is now the preferred approach for many patients with muscular defects, often using a hybrid procedure. Therapeutic closure should now be anticipated with virtually zero mortality, and with excellent anticipated long-term survival.
Ventricular septal defects are best defined as representing the borders of the area of deficient ventricular septation. An approach on this basis permits recognition of the clinically significant phenotypic variants.
- Conduction tissues
Accurate estimates of the prevalence of holes between the ventricles are difficult to achieve. When patients with bicuspid aortic valves and mitral valvar prolapse are excluded,  ventricular septal defects are recognized as being the commonest congenital cardiac malformations . The defects can exist in isolation, can be complicated by additional intracardiac lesions, or can be part of more complex combinations, such as tetralogy of Fallot, double outlet right ventricle, transposition, or functionally univentricular hearts. In this review, we focus on the isolated defect, although the system we describe for classification is valid for all situations in which there is defective ventricular septation . Although it would seem intuitive to define ventricular septal defects as no more than holes within the ventricular septum, the situation is not as clear-cut as might be imagined. Some defects exist in a location where, in the normal heart, there are no ventricular septal structures. Problems also exist in providing a uniform definition for the curved surface taken to represent the defect, which in most instances is non-planar. It is this problem that has underscored some of the differences existing in classification of the phenotypic variants . Other problems in classification reflect the different names given to holes that have the same phenotypic features . We begin our description of our results, therefore, with a discussion of the background underscoring description of the phenotypic variants. Accurate distinction of these variants is essential for correct diagnosis and, when appropriate, therapeutic closure.
Definition of the defect
Ventricular septal defect versus interventricular communication
Phenotypically different defects
Muscular and perimembranous defects can co-exist within the same heart, while muscular defects themselves can be multiple. Indeed, the hardest forms of multiple muscular defects to diagnose and treat are those represented by the so-called “swiss-cheese” septum. These defects almost certainly reflect failure of the septum itself to compact during its prenatal development .
Another popular system accounts for the presence of conoventricular and conal hypoplasia defects . As we understand this approach, conoventricular defects are produced by separation between the muscular outlet, or conal, septum and the remainder of the muscular septum. These lesions can be found with either alignment or malalignment between the conal septum and the apical muscular septum. They can also be found, when viewed from the right ventricle, with partly fibrous or exclusively muscular borders. The defects correlate with those we would describe as being either perimembranous or muscular, and opening either centrally or to the outlet of the right ventricle. The conal hypoplasia defects can have phenotypic features either of muscular defects opening to the right ventricular outlet, or else, with extreme hypoplasia of the subpulmonary conus, they represent the defects which we designate as being doubly committed and juxta-arterial.
We have discussed already the reason for underestimating the prevalence of ventricular septal defects. In many patients, the defects are small and the patients asymptomatic. The potential presence of these defects is based on auscultation of a heart murmur. The development, and common use, of cross-sectional echocardiography, and color-flow Doppler interrogation, now permits ready diagnosis of such small defects, which are usually found within the muscular ventricular septum. Those providing the initial estimates of prevalence, however, did not have access to such technology. Another difficulty in providing a precise number for prevalence is that many holes close spontaneously, and thus never come to the attention of physicians. Estimates based on clinical evaluation,  therefore, including those based on postmortem examination of specimens,  grossly underestimate the true prevalence within the overall population of holes between the ventricles. Evidence of this phenomenon is seen when comparisons are made between the incidence of defects as calculated using postmortem data,  and those derived using echocardiographic data. The Baltimore-Washington Infant Study , for example, which included echocardiographic examination as a means of diagnosis, revealed a prevalence of muscular defects ten times greater than those noted in previous studies.
As emphasized in our introduction, all studies show that holes between the ventricles in general are found in between one-third and one-half of all patients with congenitally malformed hearts. And, as we have already stated, when considered in isolation, having excluded mitral valvar prolapse and the aortic valve with two leaflets, ventricular septal defects remain the most common congenital cardiac malformations. While the holes between the ventricles can be found in patients with other cardiac anomalies, less than one-twentieth of the patients have chromosomal anomalies, yet ventricular septal defects remain the commonest individual lesion in those patients with abnormal chromosomes. Holes between the ventricles are slightly more common in females than males, albeit the differences in gender proved to be marginal when the estimates were made prior to the availability of echocardiographic diagnosis .
The physiologic consequences of any hole between the ventricles are related to its size, and to the relative resistances produced in the pulmonary and systemic vascular beds. Flow to the lungs increases after birth, in keeping with the marked decrease in pulmonary vascular resistance associated with mechanical expansion of the lungs, and exposure of the alveoli to oxygen, which is a potent pulmonary vasodilator. If the defect is large, then the pulmonary flow continues to increase relative to systemic flow concomitant with the regression of the smooth muscle of the intrapulmonary arteries. These changes are associated with the appearance of symptoms after four to six weeks in infants born at term, or after the first two weeks of life, or earlier, in the premature infant. The size of the defect also determines the extent of pulmonary flow, and hence symptoms. If the hole is small, it will be hemodynamically restrictive, thus limiting the size of the left-to-right shunt. If the defect is not hemodynamically restrictive, it will be associated with significant flow to the lungs, and with pulmonary hypertension. Eventually, the increase in pulmonary blood flow, and raised pulmonary pressures, will produce endothelial damage, and permanent changes in pulmonary vascular resistance. When pulmonary vascular resistance exceeds systemic vascular resistance, flow will be from right to left. This is called the Eisenmenger reaction, and will make the patient inoperable. Experience has shown that, to make the distinction regarding restrictive defects, the size of the defect can be related to the dimensions of the aortic root. Our experience suggests that defects half the size of the aortic root, or greater, will produce significant hemodynamic effects, and thus court the risk of producing pulmonary vascular disease. Surgical closure of large and non-restrictive defects can be undertaken at any time after birth in the setting of failure to thrive and symptoms of excessive pulmonary blood flow. In such circumstances, in order to prevent pulmonary vascular disease, the recommendation is usually to close these defects before the infant reaches one year of age.
The clinical manifestation of an isolated defect is dependent on its pathophysiology. This, again, is related to its size, and the relationship between systemic and pulmonary vascular resistances. As discussed above, it is unusual to find symptoms at birth in infants born with holes between the ventricles. Instead, the symptoms typically become manifest between the ages of 4 and 8 weeks, concomitant with the decrease in pulmonary vascular resistance produced by remodeling of the pulmonary arterioles. Symptoms, however, will occur much earlier in infants born prematurely. Retardation of growth is a major manifestation of the increased flow of blood to the lungs. The increase in the work of breathing, related to the decrease in lung compliance, results in the need for increased caloric intake, which cannot be met during infancy. The increase in flow of blood to the lungs also results in decreased systemic flow, which further compromises the growth failure.
The increase in pulmonary flow, and hence in pulmonary arterial size, causes obstruction in both the large and small airways. It is the anatomic relationship between the pulmonary arteries and left atrium to the tracheobronchial tree that produces the obstruction of the large airways. It is intrapulmonary relationships that create obstruction of the small airways, with resulting pulmonary hyperinflation. The engorgement of the pulmonary arterial circulation may cause pulmonary oedema, and combined with compression of the airways, results in lower airway disease, and produces the symptoms of wheezing, tachypnea, and respiratory distress. If there is associated pulmonary stenosis, however, then flow to the lungs will be decreased. Depending on the extent of the obstruction, this can result in cyanosis.
An additional feature complicating some perimembranous defects, but particularly the doubly committed defects, is prolapse of the leaflets of the aortic valve, with ensuing aortic valvar incompetence . Further complications can be produced by development of muscular obstruction in either the right or left ventricular outflow tracts, or development of a fibrous ridge or shelf in the left ventricular outlet. Additional complications relate to the Eisenmenger reaction, and the development in some patients of bacterial endocarditis.
The findings at physical examination depend on the size of the defect, along with the changes in pulmonary vascular resistance. In patients with large defects, and low pulmonary vascular resistance, the precordium is hyperactive due to volume and pressure overload of the right ventricle. In such patients, there is a loud second heart sound, with components of both aortic and pulmonary valvar closure. A murmur is also present due to increased pulmonary flow. In patients with large defects, but low pulmonary resistances, the murmur is harsh and holosystolic. A diastolic rumble heard in the mitral area in such patients, due to functional mitral stenosis, will confirm the presence of a large defect. When the pulmonary vascular resistance is increased, however, the second heart sound can be loud and single, and it may not be possible to hear a murmur. It is when the defect is hemodynamically restrictive, and left ventricular pressure greater than the pressure in the right ventricle, that the murmur becomes dependent on the size of the defect. The murmur is typically loud, and often associated with a thrill. If the defect begins to close spontaneously, the murmur will become attenuated.
The chest x-ray is helpful in estimating the flow of blood to the lungs, and hence the significance of the defect. Pulmonary parenchymal findings consistent with increased pulmonary vascular markings are indicative of significant left-to-right shunting, and hence pulmonary over-circulation (Figure 11). Similarly, pulmonary hyperinflation, revealed by trapping of air in the lower airways, is another sign of a significant shunt that may require surgical intervention. Cardiomegaly is the rule in such instances. The electrocardiogram may show features of either left or right ventricular hypertrophy, but often shows features of biventricular hypertrophy (Figure 12).
Spectral Doppler interrogation in the parasternal long axis view is helpful for evaluating the velocity and direction of the blood shunting across the defect. Using this approach, it is possible to calculate the pressure gradient through the defect, this in turn revealing the extent to which the defect is restrictive. Taken overall, the sum of the images determines the location of the defect, and shows its precise relationship to neighbouring cardiac structures. The images also reveal, if present, stenosis or regurgitation of the arterial valves, in particular aortic valvar prolapse. In all instances, it is important to evaluate how the altered hemodynamics caused by the defect affect the size of the left-sided chambers, with dilation of the left atrium and ventricle implying the presence of a large shunt.
Cardiac magnetic resonance imaging and computed tomography will reveal the morphology present, but these techniques are rarely needed once the diagnosis has been made echocardiographically. Cardiac catheterization can also be used to diagnose and delineate the anatomical and hemodynamic characteristics of the holes between the ventricles, including the degree and direction of the net shunting across the defect. Catheterization is particularly useful in those patients with high pulmonary pressures in order to measure the pulmonary vascular resistances. Angiography can also be useful in evaluating the presence of multiple defects. These invasive methods, nonetheless, are usually unnecessary for patients with isolated defects.
Patients are followed on an outpatient basis following the initial physical and echocardiographic evaluation. They can typically be referred, when necessary, for therapeutic closure based exclusively on these techniques.
Patients with double outlet right ventricle can present with a large left-to-right shunt and pulmonary over circulation when the interventricular communication is subaortic or doubly committed, and there is no subpulmonary obstruction. If there is overriding of one or other arterial valve in these circumstances, it can be moot as to whether the patient is considered to have double outlet as opposed to a ventricular septal defect, tetralogy of Fallot, or transposition with sub-pulmonary defect. Arbitration should be made on the basis of the proportions of the overriding arterial root supported by the right as opposed to the left ventricles. These features can now be shown with precision using computed tomographic angiography . As we have discussed, a pragmatic distinction can also be made according to whether the surgeon considered it necessary to tunnel one or other arterial valve to the left ventricle, as opposed to simply closing the hole between the ventricles.
Patients with the rare shunt that extends directly from the left ventricular outflow tract to the right atrium can also manifest with a murmur similar that produced by a hole between the ventricles. Indeed, such shunting can be part and parcel of a perimembranous ventricular septal defect, as pointed out by Gerbode and colleagues in their initial description of this lesion . Less frequently, the lesion is due to congenital absence of the atrioventricular component of the membranous septum . When there is shunting to the right atrium, ausculation is more likely to reveal a diastolic component to the murmur, which will radiate to the left mid-sternal border. On chest X-ray or electrocardiogram, the patient will have an enlarged right atrium due to the increased volume coming from the left ventricle. Once again, echocardiographic interrogation should reveal the true anatomic situation.
In most patients with holes between the ventricles, the defect is sufficiently small to restrict shunting to the extent that there are no symptoms. In such circumstances, additional palliative measures are unnecessary. When interventricular shunting is sufficient to prevent normal growth, producing difficulty in feeding, diaphoresis, or tachypnea, diuretics are the first line of medical palliation. When using diuretics at high doses, note should be taken of the side effects, especially hypokalemia, and a potassium-sparing diuretic used when appropriate. Afterload reduction may also be needed to encourage direct systemic flow from the left ventricle, thereby decreasing the amount of left-to-right shunting through the defect. Afterload reduction is achieved using inhibitors of angiotensin converting enzyme. Inotropy through digoxin is of benefit in those patients with large left-to-right shunts and volume overload of the left ventricle, although its use is increasingly coming under scrutiny. Inotropy and afterload reduction can also be achieved by giving milrinone intravenously, but such therapy is usually reserved for patients awaiting imminent surgery. In general, if a patient is symptomatic and needs palliation, it is preferable to refer for urgent surgical correction.
In patients referred for surgical correction, the defects are almost always closed nowadays by directly placing a patch from the right ventricular side, usually with the surgeon working through the tricuspid valve. It is only patients with large muscular apical defects that are either difficult to see, or to access, from the right ventricular side, or those with the so-called swiss-cheese septum presenting as neonates or infants, who require palliation by banding the pulmonary trunk. The effect of placing the band is to balance the relative pulmonary and systemic resistances, thus minimizing shunting through the defect, and thus protecting the pulmonary vascular bed from over-circulation. When referring patients for surgical correction, care must be taken to ensure that the shunting across the defect is from left-to-right, rather than right-to-left. The latter finding is indicative of so-called Eisenmenger physiology, showing that the pulmonary vascular resistance is so great as to allow decompression of the right ventricle through the defect. Closing such a defect would be detrimental, causing suprasystemic right ventricular systolic pressure, and potentiating the worsening of the pulmonary hypertension responsible for the Eisenmenger condition. It is in these circumstances that cardiac catheterization may be needed to measure with precision the pulmonary arterial pressures.
When closing the defects, the surgeon needs to be aware of the precise location of the atrioventricular conduction axis, which may vary in its relationship to the borders of the defect . In the setting of straddling tricuspid valve, the axis will arise from an anomalous postero-inferior atrioventricular node ,. All the necessary information should now be provided for the surgeon subsequent to echocardiographic interrogation. It should now be exceedingly rare, therefore, for the patient to suffer iatrogenic atrioventricular dissociation, requiring postoperative insertion of a pacemaker . Indeed, the surgical closure of holes between the ventricles should now be accomplished with zero mortality, and minimal morbidity, with the expectation of excellent short and long term outcomes.
It is now also well established that, in the setting of concordant atrioventricular and ventriculo-arterial connections, and in the absence of overriding of the atrioventricular or arterial valves, both muscular and perimembranous defects can be closed percutaneously by insertion of devices using cardiac catheterisation ,. The outcomes subsequent to closure of such “isolated” perimembranous defects have been associated with co-morbidities, including atrioventricular dissociations, as well as interference with neighboring valvar structures. Experience in some centers has revealed iatrogenic heart block after device closure of perimembranous defects to be as high as 22% . Greater success has been achieved subsequent to closure of muscular defects, although muscular defects which are hemodynamically significant are usually found in infants. The smaller size of these patients may make transcatheter closure more technically challenging. Because of this, many centers now advocate using a hybrid approach, inserting devices in the operating room after surgical exposure of the defects.
The prognosis for the patient with an isolated defect is now excellent. As we have emphasized throughout our review, most patients having muscular ventricular septal defects can anticipate spontaneous closure of the hole. Perimembranous defects can close spontaneously due to apposition of adjacent tissue from the leaflets of the tricuspid valve. It is only doubly committed defects that usually always require closure, since failure to close such defects courts the risk of development of aortic valvar prolapse. Perimembranous or muscular defects co-existing with malalignment of the septal components, nonetheless, will also require surgical attention. Should surgery be indicated, the prognosis for surgical repair is excellent, and most congenital heart surgeons would now expect zero mortality in patients referred after timely diagnosis. The problem still remains, however, for those with significant pulmonary hypertension or Eisenmenger physiology. Prognosis is markedly worse in these instances, and is marked by progressive exercise intolerance, hypoxia, and right ventricular dysfunction. Even with the diagnostic tools that are available today, there will be an occasional patient that presents with an unrepaired or late repaired ventricular septal defect associated with pulmonary hypertension and pulmonary vascular disease. These patients can be referred for evaluation and treatment of evolving pulmonary vasodilator therapy that is now effective in providing stabilization and ameliorating symptoms. Endocarditis is a rare associated problem. When found, the defect is usually hemodynamically restrictive. The substrate is the high velocity jet across the defect creating a Venturi effect, with the subsequent potential for adhesion of platelets, and subsequently vegetations, on the endocardial surface of the defect or the septal leaflet of the tricuspid valve.
Holes between the ventricles are the commonest lesions found in patients with congenitally malformed hearts. As yet, however, there is no agreement as how best to classify such lesions, nor even on the location of the curved surface that is considered to represent the defect. Based on the review of our own clinical and pathological experiences, we propose that it is the borders of the area taken to represent deficient ventricular septation, as seen from the right ventricle, which should be identified as the defect. When assessed in this fashion, it is then possible to distinguish the phenotypic variants within the group of patients having such lesions on the basis of the anatomic borders of this curved surface, and the fashion in which it opens within the right ventricle. Recognising the variants in this fashion then permits rational analysis of all the clinical features of patients with such deficient ventricular septation in the setting of concordant atrioventricular and ventriculo-arterial connections.
We are indebted to Dr Lodewik H. S. Van Meirop, who established the cardiac archive used to prepare the majority of the photographic images, along with our colleagues at Lurie Children’s Hospital, Chicago, who permitted us access to their archive so as to provide the remaining images of cardiac specimens.
Disease name and synonyms.
Ventricular septal defect, Interventricular communication.
All aspects of production of the review had been approved by the University of Florida.
- Roberts WC: The 2 most common congenital heart diseases [Editorial]. Am J Cardiol. 1984, 53: 1198-10.1016/0002-9149(84)90662-3.View ArticlePubMedGoogle Scholar
- Mitchell SC, Korones SB, Berendes HW: Congenital heart disease in 56,109 births. Incidence and natural history. Circulation. 1971, 43: 323-332. 10.1161/01.CIR.43.3.323.View ArticlePubMedGoogle Scholar
- Soto B, Becker AE, Moulaert AJ, Lie JT, Anderson RH: Classification of ventricular septal defects. Br Heart J. 1980, 43: 332-343. 10.1136/hrt.43.3.332.View ArticlePubMedPubMed CentralGoogle Scholar
- Capelli H, Andrade JL, Somerville J: Classification of the site of ventricular septal defect by 2-dimensional echocardiography. Am J Cardiol. 1983, 51: 1474-1480. 10.1016/0002-9149(83)90660-4.View ArticlePubMedGoogle Scholar
- Jacobs JP, Burke RP, Quintessenza JA, Mavroudis C: Congenital Heart Surgery Nomenclature and Database Project: ventricular septal defect. Ann Thor Surg. 2000, 69 (Suppl 4): S25-S35. 10.1016/S0003-4975(99)01270-9.View ArticleGoogle Scholar
- Anderson RH, Spicer DE, Giroud JM, Mohun TJ: Tetralogy of fallot: nosological, morphological, and morphogenetic considerations. Cardiol Young. 2013, 23: 858-866. 10.1017/S1047951113001686.View ArticlePubMedGoogle Scholar
- Bailliard F, Spicer DE, Mohun TJ, Henry GW, Anderson RH: The problems that exist when considering the anatomic variability between the channels that permit interventricular shunting. Cardiol Young 2014, doi:10.1017/S1047951114000869,Google Scholar
- Anderson RH, Becker AE, Tynan M: Description of ventricular septal defects - or how long is a piece of string?. Int J Cardiol. 1986, 13: 267-278. 10.1016/0167-5273(86)90114-2.View ArticlePubMedGoogle Scholar
- Anderson RH, Spicer DE, Brown NA, Mohun TJ: The development of septation in the four-chambered heart. Anat Rec. 2014, 297: 1414-1429. 10.1002/ar.22949.View ArticleGoogle Scholar
- Milo S, Ho SY, Wilkinson JL, Anderson RH: Surgical anatomy and atrioventricular conduction tissues of hearts with isolated ventricular septal defects. J Thorac Cardiovasc Surg. 1980, 79: 244-255.PubMedGoogle Scholar
- Milo S, Ho SY, Macartney FJ, Wilkinson JL, Becker AE, Wenink ACG, Gittenberger-de Groot AC, Anderson RH: Straddling and overriding atrioventricular valves morphology and classification. Am J Cardiol. 1979, 44: 1122-1134. 10.1016/0002-9149(79)90178-4.View ArticlePubMedGoogle Scholar
- Spicer DE, Anderson RH, Backer CL: Clarifying the surgical morphology of inlet ventricular septal defects. Ann Thor Surg. 2013, 95: 236-241. 10.1016/j.athoracsur.2012.08.040.View ArticleGoogle Scholar
- Goor DA, Lillehei CW, Rees R, Edwards JE: Isolated ventricular septal defect. Development basis for various types and presentation of classification. Chest. 1970, 58: 468-482. 10.1378/chest.58.5.468.View ArticlePubMedGoogle Scholar
- Wells WJ, Lindesmith GG: Ventricular Septal Defect. Pediatric Cardiac Surgery. Edited by: Arciniegas E. 1985, Year Book Medical Publishers, Chicago, IllGoogle Scholar
- Van Praagh R, Geva T, Kreutzer J: Ventricular septal defects: how shall we describe, name and classify them?. J Am Coll Cardiol. 1989, 14: 1298-1299. 10.1016/0735-1097(89)90431-2.View ArticlePubMedGoogle Scholar
- Anderson RH, Ho SY, Falcao S, Daliento L, Rigby ML: The diagnostic features of atrioventricular septal defect with common atrioventricular junction. Cardiol Young. 1998, 8: 33-49. 10.1017/S1047951100004583.View ArticlePubMedGoogle Scholar
- Samanek M, Voriskova M: Congenital heart disease among 815,569 children born between 1980 and 1990 and their 15-year survival: a prospective Bohemia survival study. Pediatr Cardiol. 1999, 20: 411-417. 10.1007/s002469900502.View ArticlePubMedGoogle Scholar
- Lewis DA, Loffredo CA, Correa-Villasenor A, Wilson D, Martin GR: Descriptive epidemiology of membranous and muscular ventricular septal defects in the Baltimore-Washington Infant Study. Cardiol Young. 1996, 6: 281-290. 10.1017/S1047951100003905.View ArticleGoogle Scholar
- Hoffman JLE, Rudolph AM: The natural history of ventricular septal defects in infancy. Am J Cardiol. 1965, 16: 634-653. 10.1016/0002-9149(65)90047-0.View ArticlePubMedGoogle Scholar
- Van Praagh R, McNamara JJ: Anatomic types of ventricular septal defect with aortic insufficiency. Diagnostic and surgical considerations. Am Heart J. 1968, 75: 604-619. 10.1016/0002-8703(68)90321-9.View ArticlePubMedGoogle Scholar
- Anderson RH, Spicer DE, Henry GW, Rigsby CL, Hlavacek AM, Mohun TJ: What is aortic overriding. Cardiol Young 2014, doi:10.1017/S1047951114001139,Google Scholar
- Gerbode F, Hultgren H, Melrose D, Osborn J: Syndrome of left ventricular-right atrial shunt. Successful surgical repair of defect in five cases, with observation of bradycardia on closure. Ann Surg. 1958, 148: 433-446. 10.1097/00000658-195809000-00012.View ArticlePubMedPubMed CentralGoogle Scholar
- Andersen HO, de Leval MR, Tsang VT, Elliott MJ, Anderson RH, Cook AC: Is complete heart block after surgical closure of ventricular septum defects still an issue?. Ann Thorac Surg. 2006, 82: 948-957. 10.1016/j.athoracsur.2006.04.030.View ArticlePubMedGoogle Scholar
- Holzer R, Balzer D, Cao QL, Lock K, Hijazi ZM: Device closure of muscular ventricular septal defects using the Amplatzer muscular ventricular septal defect occluder: immediate and mid-term results of a U.S. registry. JACC. 2004, 43: 1257-1263. 10.1016/j.jacc.2003.10.047.View ArticlePubMedGoogle Scholar
- Butera G, Carminati M, Chessa M, Piazza L, Micheletti A, Negura DG, Abella R, Giamberti A, Frigiola A: Transcatheter closure of perimembranous ventricular septal defects: early and long-term results. JACC. 2007, 50: 1189-1195. 10.1016/j.jacc.2007.03.068.View ArticlePubMedGoogle Scholar
- Predescu D, Chaturvedi RR, Friedberg MK, Benson LN, Ozawa A, Lee KJ: Complete heart block associated with device closure of perimembranous ventricular septal defects. J Thorac Cardiovasc Surg. 2008, 136: 1223-1228. 10.1016/j.jtcvs.2008.02.037.View ArticlePubMedGoogle Scholar
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.