Ventricular Septal Defect (VSD) is the presence of an opening in the ventricular septum, which can be located anywhere in the septum and is classified by its different anatomical types; VSDs vary in size and can be solitary (simple VSD) or combined with other intra- and extracardiac malformations (complex VSD). Its formation can be due to congenital causes or acquired, such as VSD after trauma or myocardial infarction.
Simple VSD is the most common cardiac malformation, with an incidence of about 2 per 1,000, accounting for 20% of all congenital heart diseases; if VSD is included in combination with other malformations, it will exceed 50% of all congenital heart diseases.
The clinical course of patients with VSD varies, depending on the location, size, left-to-right shunt flow and pulmonary vascular resistance of the VSD. Restrictive VSDs (5 mm) are more likely to become spontaneously smaller or heal up to 1 year of age, with spontaneous closure decreasing with increasing age and becoming less likely after 5 years of age. Major complications include recurrent respiratory infections, congestive heart failure, growth retardation, and infective endocarditis.
Pulmonary vascular resistance increases with age, with the possibility of eventual progression to Eisenmenger’s syndrome. (It usually appears at the age of 20-30 years and dies around 40 years).
Based on the principles of VSD embryologic and anatomic nomenclature and in combination with surgical incisions, VSDs are often classified into the following four types: Type I VSDs, also known as conical septal, supraventricular crestal, funnel septal, and infra-arterial, etc., originate from dysplasia of the bulbous trunk system, are often round and located in the funnel portion of the right ventricular outflow tract, directly below the pulmonary valve, with the superior border directly connected to the right coronary valve of the aorta. There is often no myocardial tissue above the defect, which is a fibrous strip between the pulmonary and aortic valve annuli, and the inferior border of the defect is myocardial, with the conduction bundle distant from the edge of the defect.
Type II VSD, or perimembranous VSD, is the most common and is located posteriorly and inferiorly to the supraventricular ridge, with the superior border adjacent to the right coronary and aortic valves and extending downward to the myocardial ridge and conical papillary muscle, with the conduction bundle traveling on its posterior border and adjacent to the tricuspid septal valve on the right; type III VSD, or atrioventricular access type or inflow tract type. The defect is located in the inflow tract of the ventricular septum and posteriorly below the tricuspid septal valve, with the superior edge of the defect extending to the septal annulus or separated by a thin muscle bundle. The conduction bundle is located at the inferior edge of the defect and is susceptible to intraoperative injury.
Type IV VSDs, the myocardial type, are located in the septal trabeculae and may be single or multiple. Because the edges of VSDs are in different planes and have different shapes, they are more difficult to expose during surgery and are suitable for interventional treatment.
Cardiac surgery has been using open-heart surgical patching to treat VSD for more than 50 years, and it has been considered the first and even the only method to treat all types of VSDs. However, surgical procedures are more invasive and require extracorporeal circulation support, increasing the occurrence of comorbidities and complications, and in complex precordial diseases requiring secondary surgery, the disruption of normal anatomy and physiology also makes the procedure more difficult.
In the past decade, transcatheter interventions for all types of VSD have developed rapidly. In this article, we review the indications for interventional treatment of VSD, interventional treatment of specific types of VSD, complications and their outlook in recent years, taking into account our own treatment experience.
In 1988, Lock et al. first published an article in Circulation detailing transcatheter intervention for VSD, which ushered in the era of VSD intervention. Over the years, various devices have been used in clinical practice, such as Lock Clamshell occluder, Cardio SEAL occluder, Sideris button patch, Coil spring ring, etc. These devices require large delivery sheaths, complex operation techniques, and difficulties in intraoperative retrieval of the devices, which greatly limit the promotion of these occluders in clinical practice.
Until 2002, Amplatzer, an American scientist, invented the Amplatzer VSD blocker named after him, which was successfully applied in clinical practice and was widely promoted. In the same year, with the localization of the blocker, the number of cases of interventional treatment of VSD in China increased rapidly.
1. Indications and contraindications for interventional treatment of VSD
At present, the VSD blocker approved by the U.S. Food and Drug Administration (FDA) is only a myocardial VSD device, and the perimembranous VSD blocker has not been approved by the FDA for clinical use so far, and because the proportion of myocardial VSD in all VSDs is small, only about 20%, the relevant foreign data are limited to the stage of small clinical trials, and there is no unified standard for VSD intervention.
Due to the localization of VSD blockers in 2002, the number of medical institutions and cases of VSD interventions in China has increased greatly. In order to standardize the treatment of this type of patients, the Pediatrics Branch of the Chinese Medical Association formulated guidelines for transcatheter interventions for congenital heart disease in China in 2004 [3], which is still mostly used as the standard.
Indications
① Perimembranous VSD: age usually ≥3 years; simple VSD with hemodynamic impact on the heart; VSD with the superior edge of the VSD ≥2 mm from the right coronary valve of the aorta, without aortic right coronary valve prolapse into the VSD and aortic regurgitation.
(ii) Myocardial VSD, usually ≥5 mm;
③residual shunt after surgical procedure;
④Other: Although the VSD is not congenital after myocardial infarction or trauma, the defect can still be closed using the technique of sealing the VSD with precordial disease.
Contraindications
①Active endocarditis, intracardiac hyperplasia, or other infections causing bacteraemia;
②The presence of thrombus at the blocker placement and venous thrombosis at the catheter insertion site;
③The anatomical location of the defect is poor, and the function of the aortic valve or atrioventricular valve is affected by the placement of the blocker.
④Severe pulmonary hypertension with bidirectional shunt.
2.Interventional treatment methods for VSD
Most of the VSD interventions adopt the traditional pathway introduced in the guidelines, establishing a trans-femoral vein-right ventricle-VSD-left ventricle-descending aorta-femoral artery track, delivering the blocker from the femoral vein side through the long sheath of delivery and inserting it in the ascending aorta or left ventricle. The anterior umbrella of the blocker is opened in the ascending aorta or left ventricle and withdrawn at the VSD, and the posterior umbrella is opened on the right ventricular surface side to block the VSD.
In some cases, such as when the initial blocker is not of the right size and needs to be replaced, the blocker can be pulled into the right ventricle by mistake, and the arteriovenous track needs to be re-established, prolonging the operation time and increasing the X-ray exposure time. Recently, Gu et al. adopted the guidewire retention technique, which does not remove the established track until the blocker is delivered, avoiding the repetition of the track establishment operation. 52 patients with the modified operation technique showed a significant reduction in operation time and exposure time compared to the conventional method, and there was no significant difference in complications compared to the conventional method.
When the A-V track was established by the conventional method, in some cases, when the long sheath was delivered to pass through the defect from the right ventricle, it could fail to pass through the defect opening because the defect opening was small and the track traveled over the right ventricular tendon, etc., and the long sheath could not pass through the defect opening and cause the blocking failure. Some scholars at home and abroad have tried to use a modified left ventricular approach for blocking successfully. Combined with imaging and cardiac ultrasound, careful observation of VSD morphology, size, course and its distance from the aortic valve, etc., and selection of suitable cases are the keys to successful surgery.
The left-sided approach simplifies the operation, eliminating the need to establish an orbit and reducing the operative time. However, due to the special design of the eccentric umbrella, it is not suitable for VSDs with defect edges <2 mm from the aortic valve, and because the larger delivery of the long sheath through the femoral artery will cause greater damage to it, the number of surgical cases is still limited.
3. Interventional occlusion of special defect locations
3.1 Occlusion of intracrural VSD
The intramural VSD is a type of type I VSD, which is located within the supraventricular crest structure and is surrounded by mainly myocardial tissue, and is actually a myocardial defect opening in the right ventricular outflow tract. The superior border of the defect consists of a muscular bridge consisting of a myocardial outflow tract septum and a separate inferior pulmonary artery funnel section that together separate the pulmonary valve annulus from the right coronary leaflet of the aortic valve.
When the muscle at the superior border of the defect is poorly developed, the aortic valve leaflet is prone to prolapse into the defect. Because of the high position of the crista intracoronary VSD and the proximity to both the pulmonary valve and the aortic valve, it is easy to make the operation fail.
In recent years, scholars in China have made many attempts to perform interventional treatment for this type of VSD and have gained more clinical experience.
① The eccentric or even zero eccentric blocker is used for blocking;
② Application of modified pigtail catheter, so that the catheter opening is at an angle of about 90° to the catheter, which can meet the need of guiding the wire through the defect orifice and is conducive to the rapid establishment of the arterial-venous track;
③ The size of the defect orifice is easily underestimated and should be determined together with cardiac ultrasound and left ventriculography. Li Shijie et al. considered intracrural VSD with a diameter <7 mm, preferably 3-5 mm, and a red fire or columnar shunt on color Doppler as a better case suitable for interventional treatment.
3.2 Occlusion of subcritical VSD
The subdry VSD is another special type of type I VSD.
Intracrural ventricular defects are easily confused with subdry ventricular defects and need to be carefully differentiated from.
① The location of the defect: in the short-axis view of the great vessels, the intracrural ventricular defect is usually located between the 11:00 and 1:00 clock positions, while the subdry ventricular defect is mostly located after the 1:00 clock position;
(ii) Relationship between the defect and the pulmonary valve: the substem ventricular defect is located under the pulmonary valve and does not have any ventricular septal stump between it and the pulmonary valve annulus, whereas there is still a certain distance between the intracrural ventricular defect and the pulmonary valve annulus;
(3) Color flow characteristics: In the short-axis view of the great vessels, the shunt of the intracrural ventricular defect is basically perpendicular to the ventricular septum, while the shunt of the subdry ventricular defect is almost parallel to the ventricular septum.
Because of the lack of muscle tissue on the upper edge of the defect, the inferior dry ventricular defect is only composed of pulmonary valve annulus, and it is generally believed that the stability of blocking treatment is poor and will affect the function of aortic valve, so it has been listed as a contraindication to blocking treatment. No similar cases have been reported abroad. In China, although Ji Jufang et al. reported 7 cases of successful blocking treatment of sub-stem VSD.
However, the case data stated that the distance between the upper edge of the defect and the aortic valve was 1-2 mm, and the distance between the pulmonary valve was 4-6 mm, and the short-axis view of the aorta showed that the VSD was in the 12:00-1:00 clock direction, suggesting that the defect was still an intracrural VSD rather than a true subdegenerative VSD, so it was not recognized by the domestic counterparts. Therefore, subdermal VSD is still an absolute contraindication to interventional treatment.
3.3 Interventional treatment of membranous tumor type VSD
Membranous ventricular septal tumor is a tumor-like bulge formed by the tissue located in the perimembranous part of the septum protruding into the right ventricle. VSDs with membranous tumors have complex morphology, multiple exits, scattered locations, different relationships between the rupture and adjacent tissues and the degree of adhesion of membranous tumor tissues, which make them special in the selection of interventional occluders. The thickness of traditional VSD blocker is only 3 mm, especially for VSD with “large entrance and small exit”, there is no better way to intervene and the operation fails.
In recent years, many scholars have tried to use various methods to block this type of VSD. For example, Liu Han F and Hua Yimin of the Second Hospital of West China used bilateral symmetric umbrella treatment to measure seven diameters of membranous tumors by imaging, including the diameters of the left and right ventricular surfaces of the defect, the thickness of the septum, the longest diameter of the membranous tumor, the maximum diameter of the tumor, the maximum distance between the two ruptures and the maximum diameter of the rupture. Depending on the morphology of the tumor, we decided to block the exit or entrance of the membranous tumor.
In 2007, Wang Zhen et al. used the domestic “small waist and large side” blocker for the treatment of membranous tumor type VSD. In 2007, Wang Zhen et al. successfully treated 49 patients with 5 cases of transient bundle branch block after surgery, and achieved good therapeutic results. However, it is difficult to confirm the degree of adhesion of the aneurysm tissue in the selection of the blocking exit or entrance, and the difference between the left and right disc diameters is not easy to grasp.
We successfully treated 19 cases of children with membranous aneurysm type VSD by using a domestic arterial catheter occluder, which was classified into four types according to the morphology of the membranous aneurysm. Based on the size of the outlet, the depth of the sac, the maximum distance between the two outlets and other factors, we selected different sizes of occluders to determine the blockage of the inlet or outlet, and achieved good results recently.
In conclusion, the interventional treatment of membranous tumor type VSD is still under continuous exploration, and we are looking forward to the emergence of newer blocking devices and the establishment of more simple operation specifications.
3.4 Interventional treatment of inflow tract type VSD
The inflow tract type VSD, i.e. type III VSD, is located under the posterior tricuspid septum, which is easily adherent to the tricuspid valve, and the inferior edge is adjacent to the AV node or the Hirschsprung bundle, so the operation is likely to damage the conduction bundle or tricuspid valve and cause serious complications. There are few cases of VSD intervention in this area, and it is considered a contraindication to intervention, as is the case of sub-stem VSD.
Xie Qilian et al. selected 46 cases of inflow tract type VSD for blocking treatment. 2 cases had recurrent intraoperative third degree AV block and abandoned the procedure, 4 cases had third degree AV block 3-6 days after the procedure, 11 cases had complete left or complete right bundle branch block after the procedure, 1 case abandoned the procedure because the blocker placement obviously affected tricuspid valve function, 3 cases had increased tricuspid regurgitation after the procedure, and 4 cases A small amount of residual shunt existed after blocker release.
Therefore, the limited data suggest that due to the specificity and morphological complexity of the inflow tract type VSD site, there is still a lack of sufficient experience in its interventional treatment, and it should still be carried out with clinical caution.
4. Complications and their prevention
4.1 Arrhythmia: It is the most common complication and can occur intraoperatively or postoperatively, such as premature ventricular beats, ventricular tachycardia, junctional tachycardia, bundle branch block and atrioventricular block. Most intraoperative complications are due to temporary compression of the conduction bundle by the catheter or guidewire or by the blocker, and most of them return to normal within a short period of time. Among all types of arrhythmias, the more serious ones are third-degree AV block, especially the delayed third-degree AV block that occurs after several days or even months in some cases, which endangers patients’ lives.
Therefore, the development of third-degree AV block after VSD interventional blockade is an important issue that needs to be faced by medical centers. Shen Junjun et al [16] from Guangdong Provincial People’s Hospital reported that after catheter intervention in 137 patients with perimembranous VSD, five cases developed high and third-degree AV block, all of which appeared within one week after the procedure, which is the higher reported serious arrhythmia at present. In 483 cases of perimembranous VSD treated by Song Zhiyuan et al [17], 43 cases (8.9%) developed various degrees of conduction block, including complete (incomplete) left and right bundle branch block and atrioventricular block.
Of these, 26 cases appeared intraoperatively and 17 cases appeared 2-6 days postoperatively. In total, 11 cases had third-degree AV block. The related reports are often reported in foreign data, and because of the small number of cases treated abroad, the proportion of arrhythmias is much higher than that reported in the domestic literature, and third-degree AV block even reaches 1-5%. The occurrence of postoperative heart block is considered to be related to the oversized blocker, patient’s age <5 years, body mass <10 kg, prolonged operation time, and intraoperative conduction block.
Therefore, to avoid serious complications, appropriate cases should be carefully selected and operated with caution, and the use of interventional block should be terminated promptly if high or complete atrioventricular block occurs intraoperatively. The postoperative observation period should be at least 1 week, and glucocorticoids should be applied for a short period of time to prevent the occurrence of conduction block. Once severe conduction block occurs, a temporary pacemaker or even permanent pacing therapy should be placed in a timely manner.
4.2 Residual shunt: In the interventional treatment of VSD, incomplete blockage is often encountered, i.e. residual shunt. The incidence is about 10%. The factors of occurrence are related to the small selection or displacement of the blocker, and are mostly seen in patients with VSD with membranous tumors. A small residual shunt (<2 mm) can be further reduced or even closed within 3 months due to cardiac endothelial cell proliferation. In the immediate postoperative period, if the residual shunt is still >2 mm, it is recommended to replace the larger blocker. Reinsertion of another blocker to close the valve has been attempted, but it is not recommended because of the high cost and complications.
4.3 Valvular insufficiency: including mild aortic insufficiency, mitral valve insufficiency, and tricuspid valve insufficiency. The incidence is 2-10%. It is often caused by damage to the valve structures or tendons during interventional procedures. Inadequate closure has also been reported as a result of valve damage due to repeated contact with the metallic blocker after placement of the blocker.
Aortic valve insufficiency is easily detected by postoperative ascending aortogram, and mitral or tricuspid regurgitation is clearly identified by cardiac ultrasound. Therefore, intraoperative ultrasound monitoring is more important. Operate gently and pay attention to the trajectory of the guiding wire and the delivery of the long sheath in the heart to avoid valve injury.
4.4 Mechanical hemolysis:Postoperative mechanical hemolysis can occur with a small incidence due to residual shunts and high velocity blood flow impacting metallic blockers. Hu, H. et al. summarized 445 patients with VSD treated with interventional blocking, and only one case showed carnitic hematuria within 24 hours after surgery, which was relieved after 72 hours after treatment with dexamethasone, sodium bicarbonate, and large amounts of rehydration. In case of persistent botrythematuria, it is generally recommended to remove the blocker and treat it with surgery or re-blocking as appropriate.
4.5 Other rare complications: including acute left heart failure, iliac vein thrombosis, inguinal hematoma, cardiac tamponade, lower extremity artery thrombosis, postoperative sudden death, infective endocarditis, etc. Careful operation and proper application of antiplatelet agents and antibiotics after surgery can reduce such complications.
5.Hybrid treatment of ventricular septal defect
Transcatheter peripheral vascular intervention for VSD has been widely proven to be effective and safe. However, for some patients with low weight and young age, they are prone to more serious vascular complications or even track cannot be established, especially for patients with complex precordial heart, which relies more on surgical procedures. In recent years there has been a quiet rise in combined medical-surgical Hybrid surgery, mostly translated as combined, hybrid or mosaic treatment, which refers to the delivery of a long sheath and blocker via right ventricular puncture under transesophageal ultrasound monitoring in the surgical suite, through a small extra-thoracic incision, to expose the right ventricular free wall for the purpose of radical VSD treatment.
Hybrid treatment requires a multidisciplinary collaboration platform composed of cardiac surgery, internal medicine, ultrasound, anesthesia, radiology, intensive care unit and other health care professionals. In some countries, “one-stop” Hybrid operating rooms have been established, and many difficult surgeries have been completed. In China, Fulbright Hospital also set up a Hybrid operating room in 2009 and carried out Hybrid treatment. However, due to the huge investment, it is not yet popular.
6.Conclusion
With the improvement of blocking devices and blocking technology, more and more indications of VSD will be expanded. Meanwhile, with the localization of blocking devices, the number of interventional techniques and treatment cases of VSD in China has greatly exceeded the number of foreign treatment cases. 2010 data showed [29] that foreign VSD interventional treatment was only clinically applied in some large centers, and the cumulative number of treatment cases was less than 2000, while the number of cases of perimembranous VSD treated by domestic blocking devices reached 20000 in China.
How to establish a standardized operation procedure, interventional physician qualification access, strict case boarding system and long-term postoperative follow-up of patients should be gradually recognized and paid attention to make the interventional treatment of VSD more effective and safe.