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Sudden cardiac death in the young is mostly a problem of cardiomyopathies, with either mechanical or electrical dysfunction (hypertrophic and arrhythmogenic, ion channel diseases), whereas in the adult–elderly population it is usually associated with coronary atherosclerosis and inherent ischaemic heart disease (coronary thrombosis, obstructive mutivessel disease, myocardial scars with decreased ejection fraction).1 In this issue of Heart, Hill and Sheppard,2 with a retrospective study on an impressive number (1800 cases) of sudden cardiac deaths, report 50 cases (2.7%) in which a coronary artery pathology other than atherosclerosis was the only plausible cause of death (see page 1119). In nearly 50% of non-atherosclerotic coronary sudden deaths, the morbid entity was congenital (anomalous origin and course of the coronary arteries), whereas the remaining were acquired. The age span was from infancy to old age. The authors should be congratulated for this commendable study, which draws attention to a neglected cause of sudden death. The results point to the need for in-vivo investigation to recognise and treat patients at risk. A similar paper was published years ago by our group, limited to a young population (≤35 years).3
The main issue that deserves comment is how can we be sure that these non-atherosclerotic coronary diseases were ‘responsible’ for sudden death, as resulting from the title of the paper. In the guidelines for autopsy diagnosis of sudden death, recently published by the Association for European Cardiovascular Pathology, with Dr Sheppard member and co-author,4 only a postmortem diagnosis of coronary artery occlusion may be associated with ‘certainty’ to sudden cardiac arrest.
Accordingly, among the reported non-atherosclerotic acquired coronary artery diseases, only coronary dissection or vasculites complicated by occlusive thrombosis should be considered to be definitely ‘responsible’ for sudden death. The same lipoma of the right coronary ostium reported by the authors (see their figure 2) does not appear to be occlusive, as it has been reported in cases of papillary fibroelastoma of aortic cusps impinging and occluding a coronary ostium.5
The uncertainty of non-atherosclerotic coronary artery disease as the real cause of sudden death is even more evident in the setting of congenital coronary artery anomalies. There can be no doubt when there is an anomalous origin of the coronary artery from the pulmonary trunk or when the tributary myocardium exhibits an acute infarct or post-infarction scar, as it was in the beautifully illustrated case of figure 4 with an atretic coronary artery. The simple observation of myocardial contraction bands under the microscope is not reliable, because it may be the consequence of reperfusion injury during a rescue manoeuvre. Although the origin of the left coronary artery from the right sinus of Valsalva has been labelled as ‘highly probable’,4 6 the high take-off or the origin of the right coronary artery from the left sinus are certainly ‘abnormal’, but they should be treated with caution as the cause of death, without ruling out other possible causes of ventricular fibrillation, such as ion channel diseases with electrical dysfunction and a structurally normal heart. This is particularly true for so-called myocardial bridging (intramyocardial course or intramural coronary artery) of the left anterior descending coronary artery,7 which should be considered as a variant of normal, like the patent foramen ovale, with a frequency of 20–30% in hearts of people dying from extracardiac causes. Even in hypertrophic cardiomyopathy, myocardial bridging, which is a common phenotypic expression of the disease, was proved not to be related to the risk of sudden death.8
Finally, we must disagree with the autopsy identification of coronary artery spasm as a cause of sudden death in six patients, because this is clearly a functional and dynamic substrate that the pathologist cannot diagnose at postmortem. The occurrence of coronary spasm should have been proved in vivo with angina at rest and ECG recording of transient ST-segment elevation (Prinzmetal variant or vasospastic angina).9 By the way, to be occlusive and to account for ischaemia, the vasospasm should happen in correspondence with an atherosclerotic plaque, a feature not reported by the authors in the alleged cases. Certainly, cocaine is well known to precipitate coronary vasospasm and sudden death; however, it may become occlusive if occurring in correspondence with an atherosclerotic plaque that has been demonstrated to be accelerated by drug abuse.10
Moreover, the important study of Hill and Sheppard2 presents some further limitations.
First, it is a retrospective study of an enormous number of sudden deaths, mostly carried out for consultancy on referred cases with a review of only coronary and myocardial histological sections, without the availability of the whole heart for re-examination. The published guidelines of the Association for European Cardiovascular Pathology recommend the preservation of the whole heart, to be sent to tertiary referral centres to allow an accurate re-examination and diagnosis.4
Second, the scarcity of clinical information and lack of availability of ECG made clinicopathological correlates and epicrisis difficult, or even impossible, for a definitive interpretation. In eight out of 50 reported cases, sudden death occurred during or immediately after physical exertion related to sport activity. Non-invasive coronary angiography, like multislice CT, is a powerful tool to be employed in selected cases with cardiac symptoms, as it would have been in 16 out of the 50 cases reported with a past medical history.
Third, it is amazing that no case of coronary artery embolism was reported, probably missed by the coroner or local pathologist. The source of embolism is usually the left cardiac chambers, particularly the left auricle in the setting of atrial fibrillation, but also friable endocavitary cardiac tumours, such as left atrial myxoma, may complicate with systemic embolism, including the coronary arterial tree, and may be suddenly fatal. In cases of coronary thromboembolism, in the absence of other sources, the patency of the foramen ovale should be checked, especially if a previous pulmonary embolism has occurred, for a possible paradoxical thromboembolism arising from the deep veins of the legs.
Identification of the true cause of sudden death entails profound implications for family members. Up to 30–40% of cases of sudden death in the young are related to heredo-familial, genetically determined heart diseases, either with mechanical or electrical dysfunction. Among these, several disease-causing genes and mutations have been discovered and genetic screening of family members, to detect carriers and to ensure non-carriers, is now feasible.
The diagnosis with certainty of a sudden coronary death, either acquired or congenital (which is exceptionally hereditary), allows us to rule out genetically transmissible diseases and to spare useless, costly and stressful investigations in family members. The responsibility of the pathologist is enormous, because a wrong or misleading postmortem diagnosis may even entail catastrophic consequences. The mission of the Association for European Cardiovascular Pathology (http://anpat.unipd.it/aecvp/) is to spread the expertise of cardiac pathology throughout Europe, to cope with this demand, by training young people with both a cardiological and pathological background, adopting the classic clinicopathological method.
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