Autopsy in adults with congenital heart disease (ACHD)

Description: ASD is a direct communication between the atria allowing shunting of blood.

There are four types of ASD, depending on the location of the defect (Fig. 1a):

Most ASD cases are sporadic and very few run in families in an autosomal dominant pattern [11]. Ostium primum defects are common in individuals with Down syndrome or Ellis-Van Creveld syndrome. One third of ASD occur in association with other cardiac malformations [12].

Symptoms related to ASDs depend on the size of the defect and associated lesions/comorbidity. Many patients remain asymptomatic for many years and may remain undiagnosed throughout their lives, while others present in childhood. Many ASDs are nowadays diagnosed after the age of 40 years. Symptoms include arrhythmia, paradoxical embolism, right ventricular failure, and, more rarely, cerebral abscess and pulmonary hypertension.

ASD causing significant left-to-right shunting or other complications should be repaired, unless pulmonary vascular disease has developed. Most cases of secundum ASD are nowadays closed percutaneously, using an occluder device.

Failure to align the device can result in device embolization and is likely to occur in very large defects (>/ = 35 mm), with absent or deficient posterior or inferior rim. Moreover, percutaneous closure may be challenging in cases with a multi- fenestrated and/or aneurysmal atrial septum or proximity of the FO to the venous orifices [13, 14] (Table S2 supplement). When a transcatheter approach is not feasible or a primum or sinus venosus ASD is present, open-heart surgery is required to close the defect with a graft or prosthetic patch [15, 16] (Table 1).

Description: A group of common congenital heart defects characterized by holes in the ventricular septum.

There are several types of VSD (Fig. 1c): A perimembranous has the membranous septum incorporated into its postero-inferior border. Muscular VSDs are completely surrounded by muscle and can be located anywhere in the muscular ventricular septum. Subarterial VSDs (synonyms: supracristal, doubly committed or juxta arterial defects) are immediately adjacent to both the aortic and pulmonary valves and may have perimembranous or muscular border.

Patients with certain genetic abnormalities, e.g., Down syndrome, have a high incidence of associated VSDs: VSD is an integral part of tetralogy of Fallot, and VSDs are present in most patients with univentricular circulation or transposition of the great arteries.

VSDs with a maximal size of 2 mm or less are likely to close prenatally, while others may close within the first 10 years of life [21]. Residual scarring in the septum or scarring with aneurysmal dilatation of the membranous septum with redundant tricuspid valve tissue may be seen at autopsy at the site of spontaneously closed defect.

Persistent VSDs are often restrictive but may be larger. Large or multiple VSDs can lead to pulmonary hypertension and right ventricular hypertrophy, eventually with the development of Eisenmenger syndrome characterized by shunt reversal and cyanosis. Patients with a VSD and significant, irreversible pulmonary vascular disease are deemed inoperable.

For this reason, timely surgical closure is recommended for all large perimembranous VSDs, supracristal VSDs, and VSDs with aortic valve prolapse [22]. Muscular VSDs may be closed by percutaneous techniques. A large number of devices have been used for VSD occlusion, the Amplatzer VSD occlude device being the most popular (Table 1).

Description: The common arterial trunk (CAT), also known as truncus arteriosus, is a rare type of CHD (1–3% of cases) and therefore mentioned only briefly here.

The anomaly is characterized by a single (common) arterial trunk overriding a large VSD, supplying the coronary, systemic, and pulmonary arterial system. The latter arises from the common trunk either as separate right and left pulmonary arteries or as a single pulmonary trunk that subsequently bifurcates. This common trunk is guarded by a truncal valve, which is always in continuity with the mitral valve. In most cases, there is usual atrial arrangement (situs solitus) and concordant atrioventricular connections. In majority of cases, the truncal valve has three leaflets and is grossly dysplastic and incompetent, but it may also be stenotic. Approximately 30% of truncus arteriosus cases are associated with a genetic syndrome, frequently DiGeorge syndrome with 22q11deletion. The most significant variation in the aortic pathways associated with CAT is severe coarctation or complete interruption of the aortic arch, with the proximal aorta arising directly from the common trunk and the distal aorta fed through a patent arterial duct.

Without surgical repair, most truncus arteriosus patients die in early life, most frequently due to severe pulmonary arterial hypertension (PAH) or from heart failure and associated low flow conditions such as myocardial ischemia and necrotizing enterocolitis.

Surgical repair is indicated in the neonatal period, or by 2–3 months of age due to the rapid progression of pulmonary vascular disease. Repaired cases achieve an 80% long-term survival [23]. The aim of surgical repair is to restore a normal physiologic circulation. The pulmonary arterial trunk (or branches) is detached from the truncus and attached to the right ventricle (RV) via a homograft (a valve conduit). The VSD is closed with a patch. The truncal valve becomes the neo-aortic valve, and, if necessary, it is repaired or replaced by an aortic homograft with coronary artery re-implantation (Table 1).

Description: Pulmonary stenosis is a common type of CHD and is frequently isolated but can also be associated with simple or complex congenital cardiac defects.

The stenosis can be valvular, localized at the site of pulmonary valve or its annulus, or, more rarely, in the subvalvular (muscular) infundibulum of the RV, or supravalvular in the pulmonary trunk or its branches. In pulmonary valvular stenosis, the valve is typically a dome-shaped diaphragm with a central perforation without recognizable leaflets. Isolated infundibular stenosis is frequently associated with a VSD. Restrictive VSDs can be associated with hypertrophic muscular bundles within the RV causing mid-ventricular obstruction (double-chambered RV).

The stenosis can be relieved by percutaneous dilatation with balloon (angioplasty) or by surgical maneuvers such as pulmonary commissurotomy, complete or partial removal of the malformed leaflets with or without enlargement of the annulus with a transannular patch. The presence of infundibular obstruction can be addressed through the pulmonary valve annulus if not too hypoplastic, or through the tricuspid valve ventriculotomy, which is rarely required nowadays for the resection of the hypertrophic muscle bands, as it is associated with long-term complication (RV dysfunction, ventricular tachycardia). In supravalvular stenosis, it is necessary to enlarge the pulmonary trunk with autologous or heterologous pericardium or with Gore-Tex (Table 1).

Description: The defining anatomical abnormalities of the tetralogy, as described by Étienne Fallot in 1888, are VSD with overriding aorta, pulmonary stenosis, and right ventricular hypertrophy (RVH).

TOF is the most common cyanotic CHD accounting for up to 9% of CHD [24]. It can be associated with trisomy 21, trisomy 18, trisomy 13, and DiGeorge syndrome, but in most patients, no genetic association can be found. Congenital abnormalities associated with ToF include bicuspid pulmonary valve, left pulmonary artery stenosis, coronary artery anomalies, right-sided aortic arch, anomalous pulmonary venous return, and skeletal abnormalities of the vertebrae and ribs [25‐27].

The severity of right ventricular outflow tract obstruction is variable, but when severe, there is right-to-left shunting through the VSD and systemic cyanosis. Most adult cases encountered nowadays in developed countries will have had reparative surgery early in life, with takedown of any previous palliative shunt (Table 1).

Definitive repair consists of patch closure of the VSD, with the overriding aorta supplied only by the LV and relief of pulmonary and subpulmonary stenosis by infundibular remodeling and/or a transannular patch. Surgical closure of the VSD may be done through a right ventriculotomy (more traditional approach) or with a transatrial approach through the tricuspid valve (more recent technique) (Fig. 2). Recently, a surgical technique with pulmonary valve reconstruction has been proposed by several authors to avoid or minimize the long-term pulmonary valve regurgitation that is inevitable with the traditional techniques [28‐30] (Table 1).

Nowadays, the life expectancy of patients with repaired ToF is felt to be similar to the general population [31], even though there persists a small risk of sudden cardiac death at all ages [32], and pulmonary regurgitation is common which frequently requires further intervention.

Early complications after repair include residual VSD, right ventricular outflow tract obstruction or pulmonary stenosis, and ventricular tachyarrhythmias (Table 1). Later complications include pulmonary regurgitation, progressive dilatation of the aorta with secondary aortic valve incompetence, progressive right ventricular dilatation, or aneurysm, following extensive ventriculotomy, infundibular remodeling, or transannular patching, and tricuspid valve incompetence. Patients with pulmonary atresia, at the extreme end of the spectrum of ToF, require an RV to PA conduits at repair, which typically becomes stenotic or regurgitant over time; a synthetic conduits may develop neointimal hyperplasia, while homograft conduits and valves tend to calcify.

Previous palliative shunts, right ventricular hypertrophy with fibrosis (Fig. 3), a prolonged QRS duration, ventricular dysfunction, and atrial arrhythmias have been shown to be predictors of death and sustained VT [33]. Patients felt to be at significant risk of sudden death may be offered an ICD as a primary prevention [34].

During adult life, reoperation for pulmonary valve regurgitation is often required in the presence of severe RV dilatation, RV dysfunction, and associated symptoms or progressive tricuspid regurgitation, with very low surgical risk [35]. Several types of bioprosthetic valves, homografts, and, more recently, percutaneous pulmonary valves are used in these patients, depending on availability and anatomical features [36] (Fig. 4) (Table 1, Tables S2 and S3 supplement).

Description: LVOTO in adults includes a series of stenotic lesions which can be single or at multiple sites along the tract. Obstruction can be subvalvular, valvular, and/or supravalvular.

Valvular AS is the most frequent form, accounting for 75% of LVOTO cases, while subvalvular and supravalvular account for 20–25% and 5–7%, respectively. AS can occur in isolation or in association with other forms of CHD such as VSD, mitral valve disease, or aortic coarctation (Shone complex).

Valvular stenosis is the most common cause of bicuspid aortic valve (BAV), with an estimated prevalence of 1–2% in the general population [37]. BAV represents the most common cause of aortic valve replacement or implantation in adult population < 70 years, due to leaflet calcification (Fig. 5). There is complete absence of one of the commissures or presence of a, often heavily calcified, ridge (“raphe”) between two cusps, resulting in a functionally bi-leaflet valve. It is recommended to describe the orientation of commissural anomaly of these valves: absent commissure (or raphe) between the left and the non-coronary (LC-NC) or between the right and the non-coronary leaflets (RC-NC, more frequently associated with aortic coarctation) or between the left and right cusps (LC-RC, more frequently associated with dysfunction and aortic root dilatation). Dilatation of the ascending aorta bears a related risk, albeit still rare, of aortic dissection and rupture with hemopericardium due to medial degeneration. One half of aortic dissections in the youth are associated with BAV.

BAV may be hereditary, and cardiological screening of the family, including echo, is advisable. Much rarer valve abnormalities are the tricuspid aortic valve due to dysplastic leaflets, with thickening or partial commissural fusions or annular hypoplasia; the quadricuspid valve (four normal-looking leaflets or with a double “raphe”); and the unicuspid aortic valve (single cusp with an eccentric “keyhole” or a dome-like appearance) and can be associated with a hypoplastic aortic annulus and ascending aorta. Subvalvular stenosis includes a wide range of anomalies from a discrete fibroelastic membrane/ring to a tunnel-like fibromuscular band. It can be complicated by valvular stenosis or with other abnormalities of the subaortic region, such as anomalous accessory mitral leaflet or accessory muscular band. Supravalvular stenosis is characterized either by a discrete focal stenosis at the sinotubular junction due to thickening of the aortic wall (seen in Williams Syndrome) [38], or an isolated fibrous membrane, or diffuse tubular hypoplasia of the ascending aorta and brachiocephalic vessels.

Patients may present very early in life or remain asymptomatic for many years. Progression of AS depends on the anatomical features of the valve and the degree of superimposed degenerative calcification or atherosclerosis. Symptomatic lesions in adults are surgically treated, with valves sent to the pathologist as a surgical specimen, but sometimes be found at autopsy, the cause of a severely hypertrophied left ventricle (or dilatation when the valve is severely regurgitant) (Table 1, Tables S2 and S3 supplement).

Description: CoA is a focal or segmental congenital narrowing of the aorta [22].

It usually occurs near the ductus/ligamentum arteriosum, in a para-, pre- or postductal location, causing a discrete aortic lumen narrowing or a hypoplastic segment of the aorta [22, 39, 40] (Fig. 6a). Often, discrete CoA and tubular hypoplasia can co-exist. CoA can occur as an isolated form or be associated with other vascular malformations or syndromes [41]. About 15–20% of affected individuals are asymptomatic until adulthood (Fig. 6b). Without repair, adult CoA has a high mortality rate (75% by the fifth decade of life). Therapeutic approach includes balloon dilatation, stent implantation, or surgery (end-to-end anastomosis, prosthetic patch or subclavian flap aortoplasty, or interposition of graft). All the methods may fail leading to re-coarctation and/or have complications [42‐45] (Table 1, Tables S2 and S3 supplement).

Description: Anatomically, the combination of concordant AV connections (the atria are connected to the correct/respective ventricles) and discordant VA connections (the ventricles are connected to the incorrect great arteries) results in systemic venous return being sent to the systemic circulation and pulmonary venous return sent back to the lungs (Fig. 7A).

For survival, a large ventricular or atrial communication is, thus, necessary to allow mixing of blood [46]. Over 60% of cases occur in isolation and require early atrial septostomy; the remaining are associated with other congenital defects, mainly VSD or obstruction of the (subpulmonic) left ventricular outflow tract (LVOT) or both (30%). Most commonly, the aorta is located in right anterior position relative to the pulmonary trunk.

In the absence of a large interatrial (ASD) or interventricular communication (VSD), the newborn with complete transposition usually succumbs rapidly upon closure of the oval fossa and the arterial duct due to severe desaturation of the arterial blood. This requires immediate surgical palliation by means of balloon atrial septostomy (Rashkind procedure [47, 48]) to improve hypoxemia. Permanent surgical correction can be achieved at a second stage by means of either atrial switch procedure (so-called physiological correction, Mustard [49] or Senning procedure [50], currently abandoned) (Fig. 7B) or, nowadays, arterial switch procedure (anatomical correction, Jatene procedure, (Fig. 7C) with excellent early and late-term survival and outcomes) [51] (Fig. 8) (Tables 1 and 2).

Description: Discordant atrioventricular and ventriculo-arterial connections (double discordance) result in a “physiologically correct” circulation through the heart in the absence of associated defects.

However, long-term outcome depends on adaptation of the RV and tricuspid valve to support the systemic circulation, similar to what was described for TGA patients after atrial switch repair [52]. Commonly associated defects include a VSD, pulmonary stenosis, and “Ebstein-like” malformation or other tricuspid valve pathology (15–80%) causing regurgitation [53]. In the absence of associated defects and a well-adapted systemic RV, ccTGA can remain asymptomatic for decades and may be diagnosed very late in life or at autopsy. However, the intrinsic abnormality of the AV conduction system, with the AV node aberrantly located anteriorly and the His bundle on the pulmonary outflow, puts ccTGA patients at risk of wear and tear injury, which explains onset of AV block and cardiac arrest. Reportedly, one half of this patient population requires a pacemaker [54] (Table 1).

Ebstein anomaly (EA) is rare (< 1% of all CHD cases). It usually occurs sporadically, but familial cases have been reported.

Description: The anatomical hallmark is displacement of the tricuspid hinge line (annulus) toward the RV apex affecting the septal and posterior leaflets.

This apical displacement of the valve results in the pretricuspid part of the RV becoming “atrialized” and thin-walled [55]. Ebstein anomaly is often associated with an atrial septal defect or patent foramen ovale, which may allow left to right shunting and cause systemic desaturation. Wolff-Parkinson-White syndrome (WPW) is present in up to 30% of patients. RV outflow tract obstruction is more often observed in young patients.

Symptoms depend on the severity of tricuspid regurgitation and size of the “functional” RV. This size is variable but can be limited to the outflow tract only, which then becomes dilated and hyperdynamic. Accordingly, the clinical presentation may vary from asymptomatic in very mild cases to deep cyanosis and heart failure (mostly in neonatal cases). Arrhythmias are common in adult life, and there is an increased risk of sudden death [56]. Wolff-Parkinson-White syndrome (WPW) is associated in up to 30% of patients.

Surgical repair with implication of the atrialized portion of the RV and closure of associated septal defects is the preferred option. Currently, the most commonly used technique is the “cone” reconstruction technique described by Da Silva, [57] (Table 2), which creates a cone-looking tricuspid valve from the available leaflet materials [58]. Rarely, when reconstruction is impossible, the valve is replaced with a bioprosthetic valve. Some patients may also undergo bidirectional Glenn anastomosis (anastomosis of the superior vena cava to the right pulmonary artery) to reduce RV preload and the risk of heart failure (Table 1).

It can be total (diagnosed and repaired early in life) or partial, when a solitary vein or all the venous connections from one lung drain into the right-sided atrium or the superior vena cava. Most frequently in adults, the right pulmonary veins drain into the superior vena cava, often associated with the sinus venosus ASD, or the right pulmonary veins drain into the right-sided atrium. In the “scimitar syndrome,” one or two right-sided pulmonary veins “pierce” the diaphragm and drain into the inferior vena cava, and there is dextroposition of the heart because of hypoplasia of the right lung; part of the lung can be sequestrated in terms of its bronchial supply; anomalous pulmonary arterial supply through systemic collateral arteries derived from the descending aorta. In other cases of partial anomalous pulmonary venous connection, the left pulmonary veins drain into the common venous truncus so that the blood enters the right atrium. The presence of an ASD allows the survival of patients with total anomalous pulmonary venous connection, with blood shunting the systemic circulation.

The timing of surgery depends on the severity of obstruction to venous return and oxygen saturations. Partial anomalous connections of the pulmonary veins may be of little functional significance and can be an incidental finding or can become symptomatic later in adulthood. Surgical repair “re-routes” pulmonary venous return to the left atrium using an autologous pericardial patch to create a tunnel in the right atrium through the ASD (Table 1).

Named after Francis Fontan, a brilliant French surgeon who invented the procedure in 1968, the Fontan procedure and the many modifications over the years are palliative surgical interventions designed for patients who cannot undergo biventricular repair [59] (Table 2). There are many types of congenital anomalies that can be palliated by the Fontan and modified Fontan procedures all of which have in common the feature of a univentricular physiology, whereby only one ventricle can be used to support the systemic circulation (Fig. 9). For example, in hypoplastic left heart syndrome, the LV is too small or inadequate to support the systemic circulation so the RV is, therefore, recruited to support the systemic circulation instead. Other such heart malformations are tricuspid atresia, pulmonary atresia with intact ventricular septum, hypoplastic left heart syndrome, double-inlet left or right ventricles, atrioventricular septal defect with unbalanced ventricles, and single ventricle with undefined morphology. The outcomes after these palliative procedures are nowadays optimal when performed at a young age, with an operative mortality of 5% and a midterm mortality at 10 years of approximately 10% depending on the type of defect. However, long-term complications are common and relate to the lack of a subpulmonary ventricle, which produces chronic systemic venous hypertension and a preload deprived systemic ventricle. The modes of death vary: perioperative (68%), sudden cardiac death (9%), thromboembolism (8%), heart failure (7%), and sepsis (3%) [60]. Heart failure is becoming the most common cause of death in adult patients and those with a systemic RV (Table 3). Liver complications are common late after Fontan operation, including cirrhosis and hepatocellular carcinoma. Protein-losing enteropathy and plastic bronchitis are also complications of the Fontan circulation.

The aim of a Fontan-type operation is to route the systemic venous blood flow directly into the pulmonary artery without the interposition of a ventricle. This can be achieved in different ways. The oldest procedure implies a direct atriopulmonary connection (right atrial appendage to pulmonary trunk which has been detached from the pulmonary valve). More recently, the Fontan procedure is performed by means of a total cavopulmonary connection, with an intracardiac tunnel or an extracardiac conduit, draining the blood flow from the inferior vena cava to the pulmonary artery, and with a bidirectional cavopulmonary shunt (termed bidirectional Glenn shunt), draining the blood flow from the superior vena cava directly to the confluent pulmonary arteries. The Fontan pathway may be fenestrated, allowing communication with the left-sided atrial chamber, as an escape (relief valve) mechanism in case of increasing pressures following intervention (Fig. 9).

Description: Congenital malformations of the coronary arteries are characterized by aberrant origin, course, or size of epicardial arteries.

They occur either as isolated anomalies or in combination with more complex congenital heart disease. Some of these are relatively benign lesions, but others have an increased risk of sudden death already early in life. For a detailed description of the anomalies in this chapter, see the manuscript published by the Development, Anatomy, and Pathology of the European Society of Cardiology (ESC) working group [61]. An anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) is a rare high-risk condition that presents early in life and causes early death in infancy unless repaired. However, rare cases of SCD have been reported even in adulthood [62].

Origin of the left or right coronary artery from the opposite (wrong) sinus is considered a low risk condition (Fig. 11a), except when there is anomalous (interarterial) course between aorta and pulmonary artery, in which case it is regarded as a “high-risk” anomaly associated with SCD (Fig. 11b). The so-called minor anomalies in coronary development have incidentally also been reported to precipitate arrhythmic cardiac arrest due to myocardial ischemia, mostly during efforts or sports activity.

“High takeoff” of a coronary artery is considered as a low-risk lesion (Fig. 11c), unless the artery exhibits also an intramural (aortic) course, which may cause ischemia during exercise. Coronary ostia originating up to 1.2 cm above the sinotubular junction are considered variants without clinical significance [63].

Congenital AV block and WPW syndrome may be associated with SCD. Usually, diagnosis is accomplished at ECG following syncope, epileptic seizures, or palpitations.

Congenital heart block in adolescents and adults is either related to the underlying condition or the result of surgery or intervention. It may also be precipitated by medication or endocarditis. Indeed, permanent pacing is commonly required in conditions such as those with congenitally corrected TGA or atrioventricular septal defects.

Wolff-Parkinson-White syndrome consists of ventricular preexcitation due to an anomalous AV connection of working myocardium leading to re-entry supraventricular tachycardia. Complicating factors such as atrial myocarditis and very short refractory period of the accessory pathway may lead to ventricular fibrillation and cardiac arrest [64].

Previous interventions can result in dense mediastinal adhesions, pericardial adhesions, lung scarring or atelectasis, and chest deformities. Chronic cyanosis can affect hemostasis and promotes perioperative bleeding, but paradoxically also thrombosis, and may also cause renal failure. Causes or contributors to death around redo procedures include ventricular or organ dysfunction,, infections, embolic events (e.g., thrombotic or air emboli), refractory congestive heart failure (e.g., persistent pleural effusion or ascites), migration of devices, laceration or perforation of vital cardiac structures, and injury to adjacent organs (e.g., the lung).

Heart failure (HF) is very often the clinical evolution in ACHD patients, even those operated early in life in the best clinical setting. HF can be part of the natural history of a defect, and/or a sequela of previous palliation or repair [65]. Heart transplantation is the ultimate option for patients with advanced heart failure refractory to treatment, with particular cases receiving mechanical circulatory support as destination therapy or as a bridge to transplantation [66, 67]. Over 30% of ACHD patients are likely to die of heart failure [68, 69]. All CHD can evolve to HF, but at “high risk” are the patients unrepaired cyanotic lesions and with univentricular hearts (failing Fontan circulation). The most common mechanism for the development of HF is ventricular dysfunction due to severe pressure or volume overload, myocardial ischemia, and prior surgery [70]. Ventricular dysfunction can also be worsened by arrhythmias, which are the result of abnormalities in the conduction system or parietal wall scarring due to surgery [71]. With the increase in survival of ACHD patients, comorbidity also contributes to the development of heart failure, which can be systemic hypertension, coronary atherosclerosis, myocarditis, diabetes mellitus, smoking, or drug abuse. The occurrence of acute heart failure must be also considered. This can be the consequence of rapid progression of preexistent chronic heart failure but can also be due to ischemia, acute coronary syndromes, tachy- or bradyarrhythmias, valvular insufficiency, cardiac tamponade, or pulmonary embolism [7].

Patients with congenital heart disease (CHD) are frequently affected by pulmonary arterial hypertension (PAH), especially when large systemic-to-pulmonary shunts are left untreated or are repaired late, before the onset of irreversible lung lesions [72, 73]. When pulmonary vascular disease becomes severe [74], the shunt reverses (from left to right to bidirectional) and cyanosis appears in the landmarks of Eisenmenger syndrome (ES) [75]. The exact prevalence of PAH in ACHD is unknown, but a European registry reported an estimated prevalence between 5 to 10%, and about 25–50% of these patients had ES [76]. International pulmonary hypertension guidelines classify PAH related to CHD (PAH-CHD) into four categories: ES; PAH associated with prevalent systemic-to-pulmonary shunts; PAH with small/coincidental defects; and PAH persisting, recurring, or developing after defect correction [77].

In general, the parameters associated with the onset and also severity of PAH-CHD are the type and dimension of the congenital defect, direction of the shunt, associated extracardiac anomalies, and the type and timing of surgery (palliative or definitive).

Morbidity and mortality rates are significant in PAH-CHD and are often the result of chronic hypoxia, cardiac dysfunction, and refractory congestive HF or sepsis/infections. In many patients, death may be sudden, due to hemoptysis, pulmonary hypertensive crisis, or arrhythmias of which the latter relate to long-standing cardiac overload or myocardial scars [78]. Acute deterioration of HF can also occur soon after inappropriate late closure of a septal defect or other communication, in ES patients, in whom such defects act as “relief valves” for the RV. Pulmonary causes of sudden onset death in PAH patients are thromboembolic events or hemoptysis due to rupture of small or large pulmonary vessels or bronchial arteries.

Sudden cardiac death (SCD) is not uncommon in both repaired and unrepaired/palliated ACHD patients (see also AECVP guidelines on SCD) [80].

The mechanism of cardiac arrest is in most cases arrhythmic, in the setting of severe electrical instability of the heart with a complete heart block or life-threatening ventricular arrhythmias arising in the “working” myocardium. Cases of “mechanical SCD” are rare and include hemorrhages due to aortic or pulmonary artery ruptures or dissections and (thrombo) embolization or sudden death in patients with severe obstructive lesions [81].

For practical purposes, there are three categories of patients in whom SCD may occur: