The atrial septum is probe patent in some 30% of the population, and is prone to have overt defects. Atrial septation is the coming together of several myocardial structures and mesenchymal tissues ...of intracardiac and extracardiac origin that must change identity to myocardium. We propose that the propensity for malformation of the atrial septum reflects this complicated morphogenesis. The morphogenesis of the atrial septum initiates from a ridge of mesenchyme, only a few hundred micrometres long, in the roof of the undivided atrial cavity. By growth of the myocardial primary septum, the mesenchymal ridge will be approximated to, and ultimately fuse, with the mesenchyme of the atrioventricular cushions. This fusion also takes in the so-called vestibular spine, and serves to close the primary atrial foramen. Interatrial communication is maintained by the development of perforations in the myocardial septum that will coalesce to produce the secondary foramen. Late in gestation, an infolding of the right atrial roof, previously identified as the secondary septum, will come to form the roof of the secondary foramen. Muscularisation of the mesenchymal ridge and vestibular spine serves to reinforce the attachment of the primary muscular septum to the atrioventricular insulating plane, with the muscularised components, and the cranial infolding, then producing the rims of the oval fossa as seen in the postnatal heart. We show that other lesions that produce the potential for interatrial shunting are outside the confines of the atrial septum, and hence are best considered as interatrial communications, rather than 'atrial septal defects'.
Congenital heart defects (CHDs) have undergone a large change in epidemiology due to prenatal screening and improved outcomes with surgery and percutaneous procedures. In patients with complex CHD ...there is an increased risk of sudden cardiac death (SCD) and up to 11% of all SCDs in the young occur in people with CHD. It is essential for clinicians to be aware of the risk factors, and for all patients to be followed up in specialised centres. When an SCD occurs, it is important that an autopsy is done and for the pathologist to have an in-depth knowledge of the particular defect and the corrective surgical techniques employed, as well as any complications due to these procedures. Both pathologist and cardiologist should work closely together to explain the cause of death to the family. A terminal cardiac arrhythmia explains many of the SCD cases, often with underlying cardiac fibrosis due to previous procedures. SCD may also be the first presentation of CHD, so great care is required when examining such cases and referral for a detailed expert opinion is recommended in all CHD-SCD cases.
Although sudden cardiac death (SCD) is one of the most important modes of death in Western countries, pathologists and public health physicians have not given this problem the attention it deserves. ...New methods of preventing potentially fatal arrhythmias have been developed and the accurate diagnosis of the causes of SCD is now of particular importance. Pathologists are responsible for determining the precise cause and mechanism of sudden death but there is still considerable variation in the way in which they approach this increasingly complex task. The Association for European Cardiovascular Pathology has developed these guidelines, which represent the minimum standard that is required in the routine autopsy practice for the adequate investigation of SCD. The present version is an update of our original article, published 10 years ago. This is necessary because of our increased understanding of the genetics of cardiovascular diseases, the availability of new diagnostic methods, and the experience we have gained from the routine use of the original guidelines. The updated guidelines include a detailed protocol for the examination of the heart and recommendations for the selection of histological blocks and appropriate material for toxicology, microbiology, biochemistry, and molecular investigation. Our recommendations apply to university medical centers, regionals hospitals, and all healthcare professionals practicing pathology and forensic medicine. We believe that their adoption throughout Europe will improve the standards of autopsy practice, allow meaningful comparisons between different communities and regions, and permit the identification of emerging patterns of diseases causing SCD. Finally, we recommend the development of regional multidisciplinary networks of cardiologists, geneticists, and pathologists. Their role will be to facilitate the identification of index cases with a genetic basis, to screen appropriate family members, and ensure that appropriate preventive strategies are implemented.
Sudden arrhythmic death syndrome (SADS), defined as sudden cardiac death (SCD) with a morphologically normal heart, is an important cause of sudden death. Hypoperfusion due to cardiac arrest followed ...by successful cardiopulmonary resuscitation (CPR) may induce histologic changes that mimic pathologic conditions. Detailed characterisation of such features and whether they could confound SADS diagnosis are not described.
Retrospective observational study analysing all consecutive cases of sudden death prospectively referred to a UK national cardiac pathology centre between 2017 and 2021. Cases showing hypoperfusion features were identified after review of clinical information and examination by expert cardiac pathologists.
Out of 2,568 SCD cases, 126 (4.9%) were identified with hypoperfusion changes. Macroscopically, the commonest finding was left ventricular focal or diffuse subendocardial haemorrhage (13.5%). Microscopically, haemorrhage and contraction band necrosis (n = 50, 37.7%), subendocardial acute infarction (n = 44, 34.1%), interstitial mixed inflammatory cell infiltrates (n = 31, 24.9%), healing granulation tissue (n = 9, 7.1%) and subendocardial fibrosis (n = 1, 0.7%) were observed. These changes correlated to duration of survival following resuscitation. In a subcohort of 41 cases, autopsy pathologists misinterpreted such changes as ischaemic myocardial infarction (n = 7; 17%), myocarditis (n = 5; 12.1%), or other pathologies (n = 2; 4.8%) in 14 SADS cases.
We provide a comprehensive characterisation of hypoperfusion-related changes in the heart following successful CPR with survival, which are time related. These features can lead to diagnostic confusion among pathologists but knowledge of history of resuscitation with survival should help with general and expert pathology assessment and improve SADS diagnostic yield, prompting genetic screening of decedents’ relatives.
•The morphologic substrates of the human cardiac conduction system (CCS) were studied.•The vasculature, innervation, and collagen differed between the CCS and surrounding tissue.•The morphologic ...differences may play a role in the propagation of electrical signals.•This study sets a morphological benchmark for further investigation of arrhythmias.
The cardiac conduction system (CCS) creates and propagates electrical signals generating the heartbeat. This study aimed to assess the collagen content, vasculature, and innervation in the human sinoatrial and atrioventricular CCS, and surrounding tissue.
Ten sinoatrial and 17 atrioventricular CCS samples were collected from 17 adult human autopsied hearts. Masson trichrome stain was used to examine collagen, cardiomyocytes, and fat proportions. Immunohistochemically, vessels and lymphatics were studied by CD31 (pan-endothelial marker) and D2-40 (lymphatic endothelium marker) antibodies. General nerve densities were assessed by S100, while sympathetic nerves were studied using tyrosine hydroxylase, parasympathetic nerves with choline acetyltransferase, and GAP43 (neural growth marker) antibodies looked at these components. All components were quantified with QuPath software (Queens University, Belfast, Northern Ireland).
Interstitial collagen was more than two times higher in the sinoatrial vs. atrioventricular CCS (55% vs. 22%). The fat content was 6.3% in the sinoatrial CCS and 6.5% in the atrioventricular CCS. The lymphatic vessel density was increased in the sinoatrial and atrioventricular CCS compared to the surrounding tissue and was lower in the sinoatrial vs. atrioventricular CCS (P=.043). The overall vasculature density did not differ between the SA and AV CCS. The overall innervation and neural growth densities were significantly increased in the CCS compared to the surrounding tissue. The overall innervation was higher in the atrial vs. ventricular CCS (P=.018). The neural growth was higher in the atrial vs. ventricular CCS (P=.018). The sympathetic neural supply was dominant in all the studied regions with the highest density in the sinoatrial CCS.
Our results provide new insights into the unique morphology of the human CCS collagen, fat, vasculature, and innervation. A deeper understanding of the CCS anatomical components and morphologic substrates’ role will help in elucidating the causes of cardiac arrhythmias and provide a basis for further therapeutic interventions.
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Spontaneous coronary artery dissection (SCAD) and myocardial infarction with nonobstructed coronary arteries (MINOCA) are increasingly recognized causes of acute coronary syndrome and potentially of ...sudden cardiac death (SCD). SCAD has been correlated to coronary fibromuscular dysplasia (FMD), but the prevalence of SCAD and FMD among SCD victims is unclear. Therefore, we sought to assess characteristics of decedents with SCAD found at autopsy and to compare their clinical and pathological profile with MINOCA victims.
We reviewed a database of 5325 consecutive cases of SCDs referred to our cardiac pathology center between 1994 and 2017.
We identified 18 (0.3%) cases with SCAD and 37 (0.7%) with MINOCA. No signs of coronary FMD were found among SCAD and MINOCA victims. Compared to MINOCA, SCAD decedents were mostly females (78% versus 38%,
=0.006) and SCD occurred during peripartum more frequently in SCAD rather than MINOCA female victims (28% versus 3%,
=0.012) Infarcted myocardium was identified in all cases of MINOCA but only in 5 (28%) of SCAD decedents (
<0.001). Premortem cardiac symptoms were present in 100% of SCAD and 49% of MINOCA victims (
<0.001); substances use or abuse was reported in none of SCAD versus 43% of MINOCA decedents (
=0.001).
SCAD and MINOCA are rare causes of SCD. At autopsy, coronary FMD is not present among SCAD victims. Compared to MINOCA, SCAD victims are more frequently females, are linked to pregnancy, and always experienced premortem cardiac symptoms. Among MINOCA victims' substance use or abuse is common.
Risk stratification of patients with nonischemic dilated cardiomyopathy is primarily based on left ventricular ejection fraction (LVEF). Superior prognostic factors may improve patient selection for ...implantable cardioverter-defibrillators (ICDs) and other management decisions.
To determine whether myocardial fibrosis (detected by late gadolinium enhancement cardiovascular magnetic resonance LGE-CMR imaging) is an independent and incremental predictor of mortality and sudden cardiac death (SCD) in dilated cardiomyopathy.
Prospective, longitudinal study of 472 patients with dilated cardiomyopathy referred to a UK center for CMR imaging between November 2000 and December 2008 after presence and extent of midwall replacement fibrosis were determined. Patients were followed up through December 2011.
Primary end point was all-cause mortality. Secondary end points included cardiovascular mortality or cardiac transplantation; an arrhythmic composite of SCD or aborted SCD (appropriate ICD shock, nonfatal ventricular fibrillation, or sustained ventricular tachycardia); and a composite of HF death, HF hospitalization, or cardiac transplantation.
Among the 142 patients with midwall fibrosis, there were 38 deaths (26.8%) vs 35 deaths (10.6%) among the 330 patients without fibrosis (hazard ratio HR, 2.96 95% CI, 1.87-4.69; absolute risk difference, 16.2% 95% CI, 8.2%-24.2%; P < .001) during a median follow-up of 5.3 years (2557 patient-years of follow-up). The arrhythmic composite was reached by 42 patients with fibrosis (29.6%) and 23 patients without fibrosis (7.0%) (HR, 5.24 95% CI, 3.15-8.72; absolute risk difference, 22.6% 95% CI, 14.6%-30.6%; P < .001). After adjustment for LVEF and other conventional prognostic factors, both the presence of fibrosis (HR, 2.43 95% CI, 1.50-3.92; P < .001) and the extent (HR, 1.11 95% CI, 1.06-1.16; P < .001) were independently and incrementally associated with all-cause mortality. Fibrosis was also independently associated with cardiovascular mortality or cardiac transplantation (by fibrosis presence: HR, 3.22 95% CI, 1.95-5.31, P < .001; and by fibrosis extent: HR, 1.15 95% CI, 1.10-1.20, P < .001), SCD or aborted SCD (by fibrosis presence: HR, 4.61 95% CI, 2.75-7.74, P < .001; and by fibrosis extent: HR, 1.10 95% CI, 1.05-1.16, P < .001), and the HF composite (by fibrosis presence: HR, 1.62 95% CI, 1.00-2.61, P = .049; and by fibrosis extent: HR, 1.08 95% CI, 1.04-1.13, P < .001). Addition of fibrosis to LVEF significantly improved risk reclassification for all-cause mortality and the SCD composite (net reclassification improvement: 0.26 95% CI, 0.11-0.41; P = .001 and 0.29 95% CI, 0.11-0.48; P = .002, respectively).
Assessment of midwall fibrosis with LGE-CMR imaging provided independent prognostic information beyond LVEF in patients with nonischemic dilated cardiomyopathy. The role of LGE-CMR in the risk stratification of dilated cardiomyopathy requires further investigation.
The concept of non-atherosclerotic coronary artery pathology in sudden cardiac death (SCD) has not been given the attention it deserves.
To determine the incidence of non-atherosclerotic coronary ...artery pathology in SCD and raise awareness among cardiologists and pathologists alike.
Retrospective non-case-controlled analysis. Setting Cardiac pathology centre at the National Heart and Lung Institute and Royal Brompton Hospital.
Between 1994 and 2008, the hearts of 1647 people undergoing SCD were referred for pathological assessment to ascertain the precise aetiology of SCD.
Fifty (3.0%) of the 1647 cases of SCD were associated with non-atherosclerotic coronary pathology (31 male subjects (62%) and 19 female subjects (38%, age range (8 weeks-71 years)). Twenty four of the 50 cases had anomalous coronary arteries (48%); eight cases had coronary artery dissection (16%); six cases had coronary artery vasculitis (12%); six cases had coronary artery spasm (12%); three cases had idiopathic arterial calcification of infancy (6%); two cases had fibromuscular dysplasia (4%) and one case had a benign tumour occluding the left coronary ostium (2%). Only 20 of the 50 patients (40%) were documented to have experienced cardiac symptoms such as syncope, chest pain on exertion or breathlessness before their SCD. Twelve of the patients (24%) died during or immediately after physical exertion.
Non-atherosclerotic coronary disease is associated with sudden death in all age groups, particularly younger, male patients. Cardiologists need to be aware of these entities and investigate any patient who has cardiac symptoms especially with exertion.
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