A brief introduction on demographics is followed by a section on the aims of investigation of sudden cardiac death. Specific cardiac causes are dealt with in turn: congenital heart disease, coronary artery anomalies, cardiomyopathy, myocarditis and metabolic disease. A section is then devoted to cases where there is no morphological abnormality and death is due to ion channelopathy. There is a separate discussion of sudden infant death syndrome as a possible sudden cardiac death. The chapter closes with a brief discussion of commotio cordis.
The most widely accepted definition of sudden death is “sudden and unexpected death within an hour of onset of symptoms” . From the point of view of the pathologist the death under investigation may not have been witnessed or may have occurred during sleep, and it may be more accurate to view the death as sudden if the deceased was regarded as being in good health 24 hours before the death occurred . For practical purposes death may also be viewed as sudden if the patient is resuscitated after a cardiac arrest and survives for some time post–arrest under intensive care and dies of irreversible brain injury sustained as a consequence of the arrest [3, 4].
The figure for the incidence of sudden cardiac death in many studies has been complicated by referral bias, but in a population-based study in Denmark in 2014 the incidence of sudden death in children between the ages of 1 and 18 years was 1.5 per 100 000, while the incidence of sudden death due to cardiac causes in the same age range was 1.1 per 100 000 . In New Zealand the incidence of sudden cardiac death is given as 1.3 per 100 000 between the ages of 1 and 35 . In Northern England the incidence of sudden death from birth to 20 years has been reported as 3.3 per 100 000, with cardiac disease occurring in 0.76 per 100 000 . The apparent differences in the incidences may in part be explained by the different age ranges included in the studies and in particular in the English study by the inclusion of infants where the occurrence of sudden infant deaths complicates the picture.
In the United States the incidence of sudden cardiac death (excluding sudden infant death) is between 0.6 and 6.2 per 100 000 . The incidence in children with known congenital heart disease is much higher and of the order of 100 per 100 000 .
if death is due to cardiac causes
the nature of the cardiac disease and whether mechanical or arrhythmic
whether the cardiac disease is related to systemic disease
whether the cardiac disease is heritable
whether there is associated toxic or illicit drug use
Non-cardiac causes of death are excluded by the post-mortem examination. This may include histology of the major organs and microbiological culture of lung, blood or CSF. The heart is examined as detailed in Chapter 2. If the heart is structurally normal and no other cause of death is established, the possibility of an arrhythmic cause has seriously to be entertained. In all cases a small sample of tissue, usually spleen, should be frozen so that genetic testing may be carried out following genetic counselling of the family. The commoner causes of sudden cardiac death in the young are listed in Table 15.1 below. The list should not be taken as exhaustive.
|Hypoplastic left heart (Figure 15.1)|
|Transposition of the great arteries (Figure 15.2)|
|Pulmonary atresia with intact septum (Figure 15.3)|
|Critical aortic stenosis (Figure 15.4)|
|Common arterial trunk (Figure 15.5)|
|Interrupted aortic arch (Figure 15.6)|
|Total anomalous pulmonary venous connection (Figure 15.7)|
|Tetralogy of Fallot (Figure 15.8)|
|Hypertrophic (Figure 15.9), dilated (Figure 15.10), restrictive (Figure 15.11)|
|Non-compaction of the left ventricular myocardium (Figure 15.12)|
|Histiocytoid cardiomyopathy (Figure 15.13)|
|Coronary artery abnormalities:|
|Anomalous origin of left coronary artery from the pulmonary trunk (Figure 15.14)|
|Anomalous origin of left coronary artery from right sinus (Figure 15.15)|
|Kawasaki disease (Figure 15.16)|
|Fibromuscular dysplasia (Figure 15.17)|
|Idiopathic arterial calcification|
|Coronary artery dissection (Figure 15.18)|
|Aortic dissection (Figure 15.19)|
|Viral myocarditis (Figure 15.20)|
|Congenital disorders of glycosylation|
|Carnitine and related deficiencies|
|Homocystinuria (Figure 15.21)|
|Conduction system disturbance:|
|Long QT syndrome|
|Congenital heart block|
|Catecholaminergic polymorphic ventricular tachycardia (Figure 15.22)|
|Myxoma (Figure 15.23)|
|Fibroma (Figure 15.24)|
|Cystic atrioventricular nodal tumour (Figure 15.25)|
|Inflammatory myofibroblastic tumour (Figure 15.26)|
|Ruptured congenital diverticulum (Figure 15.27)|
|Papillary muscle rupture (Figure 15.28)|
|Infarction in the presence of normal coronary arteries (Figure 15.29)|
Figure 15.1 Hypoplastic left heart. A baby girl born at home by normal vaginal delivery at 39 weeks’ gestation. The baby was well at birth and there were no concerns. On day four of life she became unwell with cyanosis and poor respiration. She was dead on arrival at hospital. The short-axis view of the heart shows a small left ventricle with marked fibroelastosis of its lining. There was stenosis of aortic and mitral valves.
Figure 15.2 Transposition. A male infant born at 39 weeks’ gestation following an uncomplicated antenatal course and with an apparently unremarkable scan in the second trimester. He was well until around 30 minutes of age when he became markedly cyanotic and died despite resuscitation attempts. At post-mortem there was transposition with intact ventricular closed oval foramen and arterial duct.
Figure 15.3 Pulmonary atresia intact septum. One of twins born at 38 weeks’ gestation and known to have pulmonary atresia with intact septum. Died suddenly during anaesthesia for MRI visualisation of cardiac anatomy. A close-up view of the right ventricle in a four-chamber cut of the heart shows the marked hypertrophy of the myocardium and slit-like cavity. Thickened epicardial coronary arteries secondary to RV-coronary fistulae are visible.
Figure 15.4 Critical aortic stenosis. The aortic valve is stenotic and dysplastic and the left ventricular cavity small with endocardial fibrosis. There is some overlap with hypoplastic left heart in such cases.
Figure 15.5 Common arterial trunk. Six-day-old female infant with known common arterial trunk who died suddenly and unexpectedly and in whom no other cause of death was identified at post-mortem. The opened left ventricular outflow shows a VSD beneath the truncal valve and the orifice of the pulmonary arteries above it.
Figure 15.6 Interrupted aortic arch. Eleven-day-old girl who died suddenly after a two-day history of poor feeding. At post-mortem there was complete interruption of the aortic arch between the left common carotid and left subclavian arteries. There was also a dysplastic aortic valve, with possible stenosis, and a VSD. It is likely that the cause of death was heart failure because of increased left ventricular volume and pressure load, a left-to-right shunt through the VSD with increased pulmonary blood flow, possibly further augmented following onset of closure of the arterial duct.
Figure 15.7 Total anomalous pulmonary venous connection (TAPVC). A posterior view of the post-mortem specimen shows infra-diaphragmatic TAPVC. Frequently the connection is stenotic and with closure of the venous duct the infant develops acute cyanosis because of lack of venous return.
Figure 15.8 Tetralogy of Fallot. Two-day-old infant born at 38 weeks with antenatal diagnosis of tetralogy of Fallot. Died during attempted catheter stenting of pulmonary outflow. The right ventricle is opened and the parietal wall retracted. The VSD is visible above the septal leaflet of the tricuspid valve. Above this can be seen the narrowed pulmonary outflow tract. The valve was stenotic and dysplastic and there were aortopulmonary collateral arteries with absence of the arterial duct.
Figure 15.9 Hypertrophic cardiomyopathy. Twelve-year-old boy with known hypertrophic cardiomyopathy who collapsed and died during exercise. A short-axis cut of the ventricular myocardium shows concentric left ventricular hypertrophy. Histologically there was widespread myocyte disarray.
Figure 15.10 Dilated cardiomyopathy. A three-year-old with dilated cardiomyopathy secondary to neonatal myocarditis. Ejection fraction of approximately 15% and two previous cardiac arrests. Died suddenly. The four-chamber view shows a dilated left ventricle and atrium with endocardial fibrosis. The myocardium is extensively fibrotic.
Figure 15.11 Restrictive cardiomyopathy. One-year-old with restrictive cardiomyopathy. In this case the cause of death was embolism to the cerebral arteries from thrombus deriving from the heart. Note the dilated ventricles without significant endocardial fibrosis and the marked dilatation of the atria. The left atrial endocardium is especially thick.
Figure 15.12 Left ventricular non-compaction. Four-year-old with non-compaction cardiomyopathy. The cut surface of the ventricular myocardium shows hypertrophy of the muscular trabeculations with multiple cleft-like spaces lined by thickened endocardium extending almost to the epicardial surface.
(A) The heart is enlarged but shows no focal abnormality macroscopically.
(B) Histologically there are multiple foci of histiocytoid cells. These cells are rounded and finely vacuolated, lacking cross striations
Figure 15.14 Anomalous origin of the left coronary artery from the pulmonary artery. Four-month-old girl admitted in cardiac failure who arrested and could not be resuscitated. At post-mortem the heart was enlarged; the left ventricle was dilated and showed endocardial fibrosis. The left coronary artery arose from the pulmonary trunk. The picture shows a probe in the orifice of the left coronary artery in the pulmonary trunk. There was no communication with the aorta. The right coronary artery can be seen arising normally from the aorta. Histologically there was fibrosis in the left ventricular wall affecting the anterior septum and anterolateral wall including the anterior papillary muscle of the mitral valve and with dystrophic calcification of the anterior papillary muscle.
Figure 15.15 Origin of the left coronary artery form the right sinus of Valsalva. Sudden death aged eight years. The opened aorta shows the right sinus of Valsalva with the origin of the right coronary artery as normal. In addition, the left coronary artery arises obliquely and travels through the aortic wall to emerge at the expected site, this course passing between the aorta and pulmonary trunk. The left sinus does not contain a coronary artery orifice.
Figure 15.16 Kawasaki disease. Seven-month-old male infant with a febrile illness who died suddenly. At post-mortem the right coronary artery was aneurysmally dilated and showed complete thrombotic occlusion over a length of 2.5 cm. The left coronary artery appeared externally normal. The specimen shows the right coronary artery that has been opened longitudinally to display the thrombus. Histologically there was florid vasculitis.
Figure 15.17 Fibromuscular dysplasia Atrioventricular nodal artery. The artery to the AV node shows irregular muscular thickening and fibrosis with luminal narrowing in keeping with fibromuscular dysplasia. On its own this finding should not be taken as pathological and requires the presence of changes in other arteries before the diagnosis is entertained.
Figure 15.18 Coronary artery dissection. Epicardial coronary artery showing extensive tracking of blood between the outer media and the adventitia with luminal compression. Note the intense engorgement of the surrounding small vessels (Masson’s trichrome).
(A) The aortic root is dilated and there is an intimal tear in the ascending aorta with dissection of blood in the tunica media. Proximally the blood has tracked to the level of the aortic valve. Blood is evident on the adventitial surface particularly in the connective tissue between the aorta and the left atrium.
(B) Same case – the aortic root is viewed from the right side. There is haemorrhagic discolouration of the pericardial surface of the aorta and a horizontal tear is visible just above the right atrial appendage where the aneurysm has rupture into the pericardial space causing fatal haemopericardium.
(A) The heart shows a blotchy and haemorrhagic myocardium. While this appearance is characteristic of viral myocarditis, in many cases the heart may be macroscopically normal with only pericardial effusion to give a clue to the pathology.
(B) Histologically there is extensive lymphocytic permeation of the myocardium with myocyte destruction.
Figure 15.21 Homocystinuria. A fourteen-year-old boy with homocystinuria who collapsed suddenly and died. At post-mortem there was severe coronary artery vasculopathy. This epicardial artery and its main branch show florid intimal cellular proliferation typical of the effects of homocystinuria.
Figure 15.22 Catecholaminergic polymorphic ventricular tachycardia. Twelve-year-old girl with a history of fainting episodes. Out of hospital cardiac arrest with resuscitation but suffered irreversible brain damage and died three weeks later. The heart is macroscopically normal other than for subendocardial necrosis secondary to the cardia arrest. Molecular investigation demonstrated homozygous deletion of Exon 1 of the CASQ2 gene indicating a diagnosis of catecholaminergic ventricular tachycardia.
Figure 15.23 Cardiac myxoma. Sudden death in a four-year-old. The heart shows a large myxoma arising from the right ventricular wall and occluding the right ventricular outflow tract.
Figure 15.24 Cardiac fibroma. Sudden death aged four months. At post-mortem there was a large reasonably well circumscribed mass in the left ventricular apex affecting almost the entire free wall of the ventricle and obstructing the left outflow tract. Histologically it was a fibroma.
Figure 15.25 Cystic atrioventricular nodal tumour. An eight-year-old boy with cardiac arrest. At post-mortem there was a cystic tumour of the AV node. The bundle of His is visible in the central fibrous body of the heart. Within this fibrous tissue are multiple epithelial structures, which on the extreme left are cystic. The appearances are characteristic.
Figure 15.26 Inflammatory myofibroblastic tumour. A section through a large coronary artery to show near occlusion by embolised inflammatory myofibroblastic tumour. The primary was a fungating mass in the left ventricular outflow tract.
(A) with a ruptured congenital diverticulum of the left atrioventricular junction.
(B) The diverticulum runs from the bottom left of the picture in a sinuous fashion through the atrioventricular junction to the epicardial surface where the attenuated wall underwent rupture. There is no inflammation. The included circumflex coronary artery is normal.
Figure 15.28 Ruptured papillary muscle. Infant with patent arterial duct who collapsed and died suddenly at seven weeks of age. At post-mortem the left ventricle was dilated. There was rupture of the insertion of the chordae of the mitral valve into the anterior papillary muscle, with a flail segment of mitral valve that prolapsed into the left atrium. The valve was structurally normal otherwise. There were no vegetations. The coronary arteries were normal. The two ends of the site of rupture are visible at the top centre of the picture and in the centre.
(A) An area of haemorrhagic infarction of the left ventricular myocardium is visible at the left atrioventricular junction with aneurysm formation. The coronary arteries were normal.
15.3 Congenital Heart Disease
The incidence of sudden cardiac death in children with congenital heart disease is of the order of 1 per 1000 . The risk is not uniform across the spectrum of defects. For some defects after operative correction the risk of sudden cardiac death is no higher than in the general population. The risk of sudden death is highest in cyanotic and left heart obstructive lesions and may be arrhythmic, embolic or circulatory. The risk of sudden death appears to increase with age and time after surgery and increases after the second post-operative decade. There is a high risk of acquired arrhythmia following repair in tetralogy of Fallot – ventricular tachycardia and re-entry tachycardia – and 0.5–0.6% risk of sudden cardiac death. There is also a high rate of arrhythmia in single-ventricle physiology post-Fontan repair .
Among unoperated disease, aortic stenosis is generally asymptomatic and sudden death is uncommon in the absence of significant myocardial hypertrophy. An additional factor such as stress, drugs, etc. is necessary to provoke fatal arrhythmia. Those with congenital aortic stenosis and endocardial fibroelastosis may have persistent pulmonary hypertension that may lead to sudden death .
The risk of coronary events after arterial switch appears to be bimodal, with a large peak perioperatively followed by a period of low risk, followed by a rising risk after about 15 years [12,13]. Long-term and arrhythmia-free survival is excellent after arterial switch operation. Although sequelae include chronotropic incompetence and neoaortic, pulmonary and coronary artery complications, most patients maintain normal systolic function and exercise capacity . Sudden cardiac death in asymptomatic patients as a result of coronary artery stenosis or occlusion is extremely rare .