Open access peer-reviewed chapter - ONLINE FIRST

Ventricular Septal Defects: A Review

Written By

Unnati Doshi and Elizabeth Wang-Giuffre

Submitted: March 31st, 2022 Reviewed: April 5th, 2022 Published: May 5th, 2022

DOI: 10.5772/intechopen.104809

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Congenital Heart Defects - Recent Advances Edited by P. Syamasundar Rao

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Congenital Heart Defects - Recent Advances [Working Title]

Dr. P. Syamasundar Rao

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Abstract

Ventricular septal defects (VSDs) account for up to 30% of all congenital cardiac anomalies and are one of the most common lesions encountered in day-to-day practice. The etiology is thought to be multifactorial inheritance but it is sometimes associated with chromosomal abnormalities such as aneuploidies and microdeletions. Most of these defects, close spontaneously and do not require treatment. Symptoms are primarily dependent upon the degree of shunt across the ventricles. Echocardiography remains the main modality of definitive diagnosis for isolated defects. Surgical repair is recommended in hemodynamically significant shunts or if there is aortic prolapse and regurgitation. Prognosis after surgical repair remains excellent especially with isolated defects but complete atrioventricular block or worsening valve regurgitation may occur in some patients. Newer techniques involving catheter based or hybrid device closures are being used in select cases such as muscular defects. Large unrepaired shunts, although uncommon in the developed world, may cause irreversible changes in pulmonary vasculature leading to Eisenmenger’s syndrome.

Keywords

  • ventricular septal defect
  • congenital heart defects
  • heart disease
  • pediatrics
  • Acyanotic heart defects

1. Introduction

The incidence of congenital heart disease varies from 6/1000 live births for moderate to severe forms and increases to ~75/1000 if trivial forms are included [1]. Ventricular septal defect (VSD) is a defect in the interventricular septum and one of the most common congenital cardiac anomalies accounting for up to 30% of all congenital heart defects [2]. Many trivial defects are unaccounted for as they close before one year of age or in fetal life and therefore, a precise prevalence is difficult to obtain. Prevalence is reported up to 5% in newborn babies [3]. They can occur in isolation or as a part of several other complex cardiac anomalies including tetralogy of Fallot, truncus arteriosus and atrioventricular septal defect. In this paper, we will primarily discuss isolated VSDs.

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2. Embryology/genetics

The interventricular septum (IVS) is composed of the mesenchymal and muscular portions. The ventricular septal growth starts around the fifth week of embryonic development and involves fusion of different septal components. The atrioventricular endocardial cushions form part of the interventricular septum [4]. The muscular interventricular septum arises from the primary fold or ring and grows upward from the floor of the ventricles towards the already fused endocardial cushions [5]. The outflow tract cushions composed of mesenchymal cells as well as neural crest cells contribute to the septation of the common outflow tract, the semilunar valves and also move downward into the ventricles forming the aortopulmonary septum. By the eighth week of gestation, when the endocardial cushions, muscular septum and aortopulmonary septum fuse, the membranous septum is formed and the ventricular septation is complete [6].

Several theories are currently postulated to determine factors affecting normal cardiac septation. The etiology of ventricular septal defect is heterogenous and may involve environmental and genetic factors, commonly referred to as multifactorial inheritance. Known chromosomal abnormalities such as aneuploidies (e.g. trisomy 21 or trisomy 18) and microdeletions such as DiGeorge syndrome are known to be associated with ventricular septal defects [7]. Single gene defects involving TBX-5 causes Holt Oram syndrome and is characterized by a constellation of birth defects, including ventricular septal defects. Transcription factor encoding genes such as TBX, NKX2–5,GATA4 play an important role in the ventricular septum positioning during cardiogenesis. Other genes that may play a possible role in cardiac septation include GATA6, HOMEX and PLG1 [8].

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3. Anatomy

Even though VSDs are encountered on a day to day basis by cardiologists and cardiovascular surgeons alike, its classification and nomenclature continues to remain variable among different groups. Two famous schools of thought come from descriptions by Soto et al. [9] and Van Praagh et al. [10].

Soto et al., broadly divided the ventricular septum into the membranous and muscular portions. The membranous septum is separated by the septal leaflet of tricuspid valve tissue into atrioventricular and interventricular components. The muscular septum in turn is described as having three different components, (Figure 1): The inlet muscular septum is small and divides the mitral and tricuspid valves. The trabecular septum is the largest portion of the ventricular septum extending to the ventricular apex. The infundibular septum is the portion above the crista supraventricularis that separates the aortic and pulmonary valves. The other part of the crista is between the tricuspid and pulmonary valves [11].

Figure 1.

Anatomy of the ventricular septum from the right ventricular aspect.

Van Praagh and associates have described these defects as atrioventricular canal, muscular, conoventricular, and conal septal type ventricular septal defects.

Accordingly, the ventricular septal defects may be classified as follows: (Figure 2).

Figure 2.

Types of ventricular septal defects by location.

  1. Perimembranous defects: These are defects in the membranous septum and may further extend into inlet, trabecular or outlet muscular septum. On the left ventricular side, these defects typically lie in the outflow tract below the aortic valve. On the right ventricular side, the defects appear beneath the crista supraventricularis and posterior to the medial papillary muscle. All defects have a rim which is formed by the tricuspid, mitral and aortic fibrous continuity. Approximately 80% of ventricular septal defects occur in this area [2].

  2. Muscular defects are further divided into the inlet, trabecular and outlet septal defects. These account for ~5–20% of all VSDs.

  3. Subarterial infundibular defects are located in the area of the septum, adjacent to the arterial valves which are contiguous. These are also called doubly committed juxtaarterial/subarterial defects. They account for ~5–7% of all VSDs. Of note, it is more common among Asians with reported incidence up to 30% in Japanese population.

  4. Atrioventricular septal defects are located in the inlet septum and will not be reviewed in this chapter.

VSDs are also classified based on their size: those less than one-third (~33%) the size of the aortic valve annulus are considered as small; more than half (50%) as large and moderate being in between.

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4. Pathophysiology

The degree of shunting across the VSD is primarily dependent on the size of the defect. In large non-restrictive defects, the difference in the pulmonary vascular resistance (PVR) and systemic vascular resistance (SVR) determines the magnitude of the shunt. The degree of shunt is frequently described as the ratio of pulmonary blood flow (Qp) to systemic blood flow (Qs) and shunts with Qp:Qs ≥1.5 are typically considered hemodynamically significant.

In neonates, right after birth, there is significant drop in PVR as the gas exchange changes from placental circulation to the lung. Thereafter there is progressive rise in SVR, and decline of PVR, with consequent increase in pulmonary blood flow which continues over a period of the first 6–8 weeks of life. It is this rate of decline in PVR that determines the amount of left to right shunting in patients with VSDs.

In patients with small VSDs, the decrease in PVR does not influence pulmonary over circulation as the size of the defect intrinsically restricts flow. In comparison, in patients with large VSDs, the drop in PVR primarily determines the amount of pulmonary blood flow and direction of flow across the two ventricles. Once the pulmonary resistance decreases, blood flow from the left to the right ventricle causes over circulation to the lungs and increases preload to the left atrium and ventricle. Pulmonary mechanics are altered due to increased pulmonary blood flow including decreased lung compliance and tidal volume [12]. Another mechanism contributing to clinical symptoms of congestive heart failure is neurohormonal activation with increased levels of norepinephrine and renin – angiotensin seen in these infants [13]. In some patients, the medial muscle layer in the small pulmonary vessels does not regress as rapidly, in turn leading to slower decline of the PVR [14]. In such patients, there may be subsequent delay in development of symptoms.

Chronic exposure of volume and pressure overload due to large uncorrected VSDs leads to structural and functional changes of the pulmonary vascular bed. There is development of endothelial dysfunction, smooth muscle proliferation, vascular remodeling, and intravascular thrombosis. These changes lead to increase in pulmonary vascular resistance and pulmonary arterial hypertension (PAH) [15]. The definition of PAH includes a mean pulmonary arterial pressure ≥ 25 mmHg at rest, a left atrial pressure ≤ 15 mmHg, and normal resting cardiac output, suggesting a resting pulmonary vascular resistance of ≥3 Woods units (WU). Eisenmenger’s syndrome (ES) is the most advanced stage of pulmonary arterial hypertension in patients with unrepaired shunts of congenital heart disease and often irreversible.

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5. Natural history of ventricular septal defects

Conventional descriptions of natural history of VSDs include spontaneous closure, progression to pulmonary vascular obstructive disease (PVOD), development of infundibular stenosis, and progression to aortic insufficiency. Each of these will be reviewed briefly.

5.1 Spontaneous closure

Approximately 70% of ventricular septal defects do not require any intervention either due to spontaneous closure or due to hemodynamically insignificant shunts. Trabecular muscular VSDs tend to close more often than membranous defects. Most defects close by 2 years of age but in some cases, closure may take place through 8 years of age. However, the process of spontaneous closure continues through adolescence and adulthood. Membranous defects close due to apposition of tricuspid valve leaflets against the VSD; also described as “aneurysmal” formation [16].

5.2 Progression to pulmonary vascular obstructive disease

PVOD may develop in 10% of untreated VSDs. This is likely to be due to the exposure of the pulmonary vascular bed to high flow and high pressure. Speedy diagnosis and closure of the VSD at least prior to 18 months of age is expected to decrease the incidence of development of PVOD.

With the advent of better echocardiographic imaging as well as its availability, the incidence of Eisenmenger’s syndrome and irreversible PVOD has decreased but still exists in less than 10% of patients. Such patients are often are diagnosed in adulthood, particularly in developing countries. In many of these patients, prognosis maybe worse after surgical repair. In a subset of patients with VSD and PAH, newer treatment modalities such as pulmonary vasodilators have made some patients amenable to repair. However, immediate post-operative survival does not necessarily assure good long-term outcomes [17].

5.3 Development of infundibular stenosis

Development of infundibular stenosis, originally described by Gasul, occurs in 8% of VSDs. Some specific signs, namely, right aortic arch and increased angle of the right ventricular outflow tract that may influence the VSDs to undergo Gasul’s transformation. Although the onset of infundibular stenosis ultimately needs surgery, it truly protects the pulmonary circulation and prevents development of PVOD.

5.4 Progression to aortic insufficiency

While most spontaneous VSD closures are due apposition of tricuspid valve tissue against the VSD, sometimes aortic valve cusps prolapse down towards the VSD to produce partial or complete closure. This may either be due to prolapse of an aortic valve cusp into the VSD or lack of support to the aortic root. This complication appears to occur more commonly with doubly committed subarterial VSDs than with other types.

Combination of VSD and aortic regurgitation (AR) due to prolapse of right coronary or, less frequently, non-coronary cusp is known as Laubry-Pezzi syndrome. Aortic valve prolapse can be seen in some patients with perimembranous defects and more commonly those with the subarterial defects where the tissue supporting aortic cusp is lacking. It is commonly seen in those with smaller defects due to venturi effect on the leaflets. The lifetime risk of developing aortic valve prolapse in patients with VSD is ~6.3% [18]. Long term follow up is recommended in these patients and surgery is indicated in patients with more than trivial AR. Based on a recent study of 261 pediatric and adult patients with VSD and AR, it was found that AR tends to be detected between the ages of 3–8 years [19]. Only the patients with aortic valve abnormalities or delayed operation had AR progression or persistence of more than mild degree of AR. The study authors concluded that surgical closure of subarterial VSD is indicated in patients with significant leaflet deformity as well as those with subarterial VSDs with moderate to severe AR.

5.5 Other natural history events

5.5.1 Double chambered right ventricle

First described in 1858 by TB Peacock, double chambered right ventricle may evolve as a complication in some patients with VSD. It is characterized by a mid-cavitary obstruction either due to hypertrophy of the crista supraventricularis or of septoparietal trabeculations causing the right ventricle to divide into a high-pressure proximal portion and a low-pressure distal portion. It can occur in up to 8–10% of patients with VSDs [20].

5.5.2 Development of infective endocarditis

VSDs even when not hemodynamically significant carry a lifetime risk of developing infective endocarditis (IE). The incidence of IE in unrepaired VSDs is 1.5 to 2.4 per 1000 patient-years, especially if associated with aortic insufficiency or with left ventricle-to-right atrial shunt [21]. Based on a Swedish registry study, risk of IE in adult VSD patients without previous intervention is 20–30 times higher than the general population [22]. The second natural history study reported risk of IE is twice as likely in unrepaired defects as compared to after surgical repair. However, the incidence of IE after closure of VSD was still higher than normal risk curve [23, 24]. Based on the 2007, AHA guidelines, prophylaxis for IE is not recommended on patients with isolated VSDs. The exceptions are VSDs within 6 months of surgical or intervention closure, with ES, with residual defects after surgery or patients with previous history of IE [25].

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6. Clinical presentation

Small VSDs: Patients with small VSDs are usually asymptomatic and are detected incidentally on routine physical examination. A holosystolic murmur with or without a thrill is best heard at the left lower sternal border in muscular and membranous defects while the holosystolic murmur is heard at the left upper sternal border in subarterial defects due to direction of VSD jet towards the pulmonary outflow tract. In very small defects, the murmur is shorter and does not last through the entire systole.

Moderate to large VSDs: Subjects with hemodynamically significant, moderate to large VSDs usually present with signs of congestive heart failure due to pulmonary over-circulation and left ventricular volume overload. Due to equalization of pressures in both right and left ventricles, the right ventricular impulse in the lower left sternal border or subxiphoid region is prominent. In patients with chronic left ventricular overload, the left ventricular impulse is hyperdynamic and shifts laterally. A mid diastolic flow rumble may be heard at the apex due to relative mitral stenosis from increased left to right shunt. This usually indicates a Qp:Qs >2:1.

Eisenmenger syndrome: Patients with ES may present with central cyanosis, clubbing, peripheral edema, abdominal tenderness, right ventricular heave, a loud pulmonary ejection click and an accentuated pulmonary component of the second heart sound.

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7. Diagnostic testing

7.1 Non-invasive imaging

In current times, transthoracic echocardiogram (TTE) is the main modality for definitive diagnosis of VSDs. It allows to delineate size and location of the defect as well as other details such as outflow tracts, associated lesions, evidence of chamber dilation and pressures (Figures 3-6). Transesophageal echocardiographic (TEE) imaging is routinely used for evaluation of anatomy intraoperatively. It also helps to better delineate associated pathologies especially those involving valve abnormalities such as valve prolapse and regurgitation. Postoperatively, it is used to detect presence of residual defects as well as ventricular function assessment.

Figure 3.

Echocardiographic parasternal long axis view showing perimembranous ventricular septal defect (VSD). RV = right ventricle; LV = left ventricle.

Figure 4.

Echocardiographic parasternal short axis color compare view showing perimembranous ventricular septal defect (VSD) at ~11o’ clock position. The red flow represents indicates left to right shunt during systole across it.

Figure 5.

Echocardigraphic image (parasternal short axis color compare view) showing subarterial ventricular septal defect (VSD) at ~12–1 o’clock position. The red flow represents indicates left to right shunt during systole across it.

Figure 6.

Echocardiographic parasternal long axis view showing trivial aortic regurgitation (AR) is seen by color flow in the presence of aortic cusp prolapse into the subarterial ventricular septal defect (VSD).

Electrocardiographic changes such as left atrial enlargement as well as left ventricular hypertrophy is seen in hemodynamically significant defects. Right ventricular hypertrophy maybe seen in patients with significant pulmonary arterial hypertension. Chest X-rays serve as adjuncts to clinical assessment. Cardiomegaly, and increased pulmonary vascular markings are seen in patients with moderate to large VSDs. Left atrial dilation may cause superior deviation of the left main bronchus. In patients with Eisenmenger’s, there is evidence of right heart enlargement with main pulmonary artery dilation without increased pulmonary vascular markings.

Advanced imaging such as cardiac magnetic resonance (CMR) imaging is not necessary in the routine evaluation of isolated VSDs. However, it is a helpful adjunct in the diagnosis of complex anatomical variants and in the evaluation of associated defects or complications such as double chambered right ventricle and pulmonary arterial hypertension (PAH). 3D phase contrast-CMR may help obtain additional information with regards to quantification of pulmonary blood flow.

7.2 Cardiac catheterization

Although a mainstay in diagnosis of all congenital heart defects in the past, cardiac catheterization is now reserved for cases requiring measurements of PVR. In the patients with PAH, cardiac catheterization may be undertaken to determine operability. Catheterization data indicating operability suggests the likelihood of a favorable versus an unfavorable outcome [17]. But, there is no validated consensus data accurate enough to define which patients will be free of major postoperative complications related to pulmonary vascular disease. However, a baseline ratio between indexed pulmonary vascular resistance (PVRi) and indexed systemic vascular resistance (SVRi) of <0.3 and PVRi of <6 indexed Woods units/m2 (iWU.m2) is indicative of favorable outcome. Pulmonary vasoreactivity study with O2 and iNO has been used to determine operability in subjects with PVRi of 6–9 iWU m2 or resistance ratio (PVRi/SVRi) of 0.3–0.5. A positive test is defined as decrease of both PVRi and resistance ratio by 1/5th of initial value as well as final PVRi of 6 iWUm2 and resistance ratio of <0.3. All patients should meet all of these criteria before being considered operable with decreased risk of serious postoperative complications [26, 27]. In patients with PVRi >10 iWUm2 and resistance ratio of >0.7, surgical repair is not beneficial [28].

Other protocols have been proposed for the vasoreactivity studies to assess operability as well as to assess prognosis and indication for specific anti PAH therapies. Measurements of resistance and flow in systemic and pulmonary vascular beds are carried out in several conditions such as room air, nitric oxide, IV epoprostenol or inhaled iloprost and in some cases oral phosphodiesterase 5 inhibitors. Some recommend to avoid use of high oxygen concentrations in these patients if other agents are available due to high amounts of dissolved oxygen as a potential source of error causing overestimation of Qp [29].

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8. Treatment

8.1 Medical management

Most small VSDs do not require intervention unless complications occur. In moderate to large defects, medical therapy is initiated if signs of pulmonary over-circulation and congestive heart failure develop. Standard medical therapy consists of diuretics, commonly furosemide. This helps to decrease preload and relieves symptoms such as tachypnea and tachycardia. Spironolactone is usually added to counter the hypokalemia related to the loop diuretic use. One other approach is afterload reduction, mostly with the use angiotensin converting enzyme (ACE) inhibitors such as captopril or enalapril to reduce the SVR which in turn decreases pulmonary blood flow and increases systemic flow. Digoxin, still preferred by some cardiologists, is not very commonly used anymore since the theoretical effect in the presence of normal systolic function is not well known. Medical therapy for congestive heart failure should be continued either until the defect size decreases, closes spontaneously, or until surgery as the case may be.

Medical management of patients with ES with anti – PAH drug therapy remains the main stay for treatment of Eisenmenger’s syndrome. Three groups of pulmonary vasodilators have emerged since 1995. These include, prostacyclins such as epoprostenol, treprostinil, iloprost; endothelin receptor antagonists (bosentan, ambrisentan, macitentan); and phosphodiesterase-5 inhibitors, namely tadalafil and sildenafil [30]. One of the newer FDA approved therapy is a soluble guanylate cyclase stimulator, Riociguat. They are often used as mono, dual or triple therapy, as per the clinical scenario. Detailed discussion of the pulmonary vasodilators is beyond the scope of this chapter. Optimizing hemoglobin and iron levels is important, usually with oral and occasionally intravenous iron supplementation may become necessary. Phlebotomies and routine anticoagulation are not recommended. When polycythemia is found to be problematic (hematocrit >70%), erythropheresis instead phlebotomy is recommended. Oxygen supplementation is not shown to provide symptomatic relief or survival benefits in patients with ES. Definitive treatment is lung transplantation with VSD closure or heart–lung transplantation.

8.2 Surgical intervention

Hemodynamically significant VSDs are those with congestive heart failure and pulmonary artery hypertension, and those causing failure to thrive or repeated respiratory infections [24]. VSDs producing cardiomegaly beyond a year of age are also considered hemodynamically significant [24].

Surgical closure of VSD remains the mainstay of treatment for most VSDs. Indications for surgical closure include hemodynamically significant shunts causing left ventricular volume overload and failure of medical therapy. A Qp:Qs >2:1 although difficult to calculate by non-invasive imaging modalities, is an indication for surgery in older and adult patients if there is normal or reversible pulmonary vascular resistance. Other indications include aortic valve prolapse with regurgitation, double chambered right ventricle with significant obstruction, left ventricular systolic dysfunction, or patients with previous history of bacterial endocarditis.

Majority of perimembranous VSDs are closed using a Dacron patch via right atriotomy with or without detachment of the tricuspid valve leaflets. Tricuspid valve detachment adds to the cardiopulmonary bypass and cross clamp time but there is no significant difference in postoperative residual shunts or degree of tricuspid regurgitation [31]. A transpulmonary approach is used in sub arterial, doubly committed VSDs. Although not widespread, some surgeons have reported use of the right axillary approach for closure of selected VSDs. Use of such methods are limited to certain centers and in mostly older adolescents and adults. Most muscular defects are difficult to close by surgical approach.

Surgery is relatively safe and the surgical mortality is low. Long term prognosis after surgical closure is excellent. After closure, catch up growth may take ~6–12 months and the left ventricular volume and mass eventually return to normal. Complications, although rare, include residual lesions, sinus node dysfunction, pulmonary hypertension, and modest progression of aortic insufficiency [32]. The incidence of complete heart block after closure of perimembranous defects is between 0.7 and 1% [33].

Although commonly used few decades ago, main pulmonary artery banding is rarely used in the management of most isolated VSDs. In rare situations such as in a child with other comorbidities where a complete repair is not feasible or where the VSD is difficult to close by standard techniques such as muscular “swiss-cheese” type defects, a main pulmonary artery banding procedure may be considered. Later, the band is removed with repair of main pulmonary artery and patch closure of VSD. In some cases, the muscular defects close spontaneously or at least become hemodynamically insignificant to require closure [32].

8.3 Percutaneous device closure

Device closure of VSDs is an alternative for some residual defects, centrally located muscular defects and those not amenable to surgery such as apical muscular defects [34]. Various devices have been used to close VSDs, since its initial description by Rashkind in the 1970s [35]. Since then, several devices including the Amplatzer muscular and membranous VSD occluders, Nit-occlud, and duct occluders I and II are being used for different types of VSD [36]. At this time, only the Amplatzer muscular VSD occluder has received approval for clinical use by the Food and Drug Administration (FDA) and others devices are used on “off-label” basis. Within a year of device placement, up to 92% of patients achieve complete closure of the muscular VSDs. Complications, although rare, include device embolization or malposition, valve regurgitation, residual shunt, hemolysis, arrhythmias, tamponade, cardiac perforation, and death [32]. Nit-occlud devices are associated with residual shunt when compared to other devices. Transient and permanent atrioventricular block is the most serious complication reported with device closure, especially with closure of perimembranous defects [37]. However, more recent studies have reported success of device closure of VSD may depend on patient selection as well as the distance of VSD to aorta and tricuspid valve [36]. The newer ADO II devices are being used in younger patients with perimembranous or muscular VSDs. In a single center trial, lesser complication rates with good success were reported [38]. However, longer, multicenter, prospective data is needed to establish the safety and efficacy.

8.4 Hybrid approach

In rare cases, such as small infants with hemodynamically significant muscular VSDs a hybrid “perventricular” approach has been utilized without placing patient on cardiopulmonary bypass; this procedure is performed under TEE guidance. In these cases, access is obtained through a median sternotomy or subxiphoid incision. The device delivery sheath is inserted under TEE guidance from right to left ventricle. The success rate of closure with these devices is reported from 82 to 100% in different studies. Complications include arrythmias, device malposition or missing additional defects. Unsuccessful implantations are converted to conventional open-heart surgical repair [32]. These percutaneous perventricular approach has also been described for successful closure of subarterial VSDs in a small number of patients [39].

Detailed description of percutaneous and perventricular device closures of VSDs is beyond scope of this chapter; the interested is referred elsewhere [32].

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9. Eisenmengers syndrome

An unrepaired large VSD with unrestricted left to right shunt over a period of time, if not corrected, will lead to increased PVR and irreversible PVOD due to vascular remodeling. There is a bidirectional shunt initially and eventually, right to left shunt develops, as pulmonary artery pressures and PVR exceed systemic pressures and SVR, causing central cyanosis. There is a secondary erythrocytosis, polycythemia and coagulation abnormalities develop. Maladaptation of the right ventricle (RV) as a result of pressure and volume overload with time causes progressive right heart failure. Other factors that may influence risk of developing ES is presence of complex anatomy and underlying genetic and environmental factors. Diagnosis of ES is made by clinical features and echocardiography is a common monitoring tool. The patients may develop dyspnea, decreased exercise tolerance and syncope. Parameters such as O2 saturation, WHO functional class, level of exercise intolerance, reflected by six min walk distance, and NT proBNP are used for serial assessments as well as predictors of survival. Other models of risk stratification in these patients describe various clinical, laboratory and diagnostic markers to determine predictors of mortality [40]. Various other biomarkers reflecting RV dysfunction, endothelial dysfunction and some that may predict potential reversibility of pulmonary vascular lesions are being studied [17]. In a large adult study, older age, pre-tricuspid shunt (such as atrial septal defects and partial anomalous pulmonary venous return), O2 saturations at rest, absence of sinus rhythm, and presence of pericardial effusion were determined as predictors of mortality [41]. Right heart catheterization remains gold standard to confirm diagnosis of ES. In ES patients with established reversed shunt and significant vascular remodeling and PVOD repair is not indicated [17]. Pregnancy is associated maternal and fetal mortality and is contraindicated. Management of patients with ES with drug therapy was reviewed in the section on 8.1. Medical Management and will not be repeated. Many other novel treatment trials and targeted PAH therapies have promising results with improvement in functional capacity and hemodynamic parameters; however, prospective randomized studies are needed to assess their effect on mortality.

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10. Conclusions

Smaller VSDs may self-resolve and the majority of the patients do well without intervention. On the other hand, recognition of unrestrictive defects, and prompt medical and surgical intervention may prevent development of irreversible pulmonary vaso-occlusive disease. Newer therapeutic options such as a minimally invasive approach as well as catheter based closures are appealing and can dramatically improve cosmetic outcomes in many of these patients. Development of newer devices and ongoing trials provide promise in non-surgical approach for VSD closure. Adult patients with Eisenmenger’s syndrome continue to present a challenge due to increased morbidity and mortality. Specialized targeted anti pulmonary arterial hypertension therapies with endothelin receptor antagonists, phosphodiesterase 5 inhibitors and prostacyclins show improved exercise capacity and hemodynamics in this patient population.

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Written By

Unnati Doshi and Elizabeth Wang-Giuffre

Submitted: March 31st, 2022 Reviewed: April 5th, 2022 Published: May 5th, 2022