Carla Frescura

Anomalous origin of coronary arteries and risk of sudden death : A study based on an autopsy population of congenital heart disease

Coronary arteries anomalies may be part of complex congenital malformations of the heart or be an isolated defect. In our anatomic collection of congenital heart disease, an isolated anomalous origin of coronary arteries was observed in 27 of 1,200 specimens (2.2%): left coronary artery from pulmonary trunk in five, origin from the wrong aortic sinus in 12 (both right and left coronary artery from the right sinus in four and from the left sinus in seven, left coronary artery from the posterior sinus in one), left circumflex branch from right aortic sinus or from very proximal right coronary artery in three, high takeoff of right coronary artery in three, stenosis of the coronary ostia attributable to valvelike ridge in four. In 16 (59%) patients (12 males and 4 females, age ranging from 2 months to 53 years; median, 14), the final outcome was sudden death; it occurred in all cases of left coronary artery origin from right aortic sinus, in 43% of right coronary artery origin from left aortic sinus, and in 40% of the left coronary artery from the pulmonary trunk. Sudden death was precipitated by effort in eight (50%) and was the first manifestation of the disease in eight (50%); previous symptoms consisted of recurrent syncope in four, palpitations in three, and chest pain in one. Five patients who died suddenly during effort were athletes. In conclusion, (1) more than half of our postmortem cases with anomalous origin of coronary arteries died suddenly, (2) all but two patients with sudden death had anomalous coronary artery origin from the aorta itself, (3) the fatal event was frequently precipitated by effort, (4) palpitations, syncope, and ventricular arrhythmias were the only prodromic symptoms and signs. Recognition during life of these coronary anomalies, by the use of noninvasive procedures, is mandatory to prevent the risk of sudden death and to plan surgical correction if clinically indicated.

Non-atherosclerotic coronary artery disease and sudden death in the young

Objective—To assess prevalence and type of non-atherosclerotic coronary artery disease in young people (≤35 years) who died suddenly. Design—A necropsy study of 150 consecutive cases of sudden death (that is, within 6 h of the onset of symptoms). Results—Death was attributed to coronary artery disease in 48 cases: in 16 (33%) of them the disease was non-atherosclerotic. Twelve subjects (eight males and four females, age range 2–35 years, mean 24·2) had congenital anomalies: a deep intramyocardial course in six, origin from the wrong sinus in three, and ostial obstructions in three. Sudden death was the first manifestation of disease in six cases. The other six had a history of palpitation or syncope or both. An electrocardiogram was available in five cases and showed ventricular arrhythmias in four; none had angina pectoris. Stress testing was available in two cases: neither showed any effort-dependent ST-T abnormalities. In six cases sudden death was related to physical exercise. Acquired non-atherosclerotic coronary artery disease was found in four cases: spontaneous coronary dissection in three previously symptom free patients and Kawasaki coronary arteritis in one child who had had acute myocardial infarction. Conclusion—One third of the cases of fatal coronary artery disease were non-atherosclerotic with coronary artery anomalies being the most frequent form. Coronary artery anomalies should be suspected in young patients who have symptoms of ventricular arrhythmias without any overt signs and symptoms of ischaemia.

Congenital heart disease and sudden death in the young

Sudden death is a frequent mode of fatal outcome in cardiac disease and does not exclude young people. The aim of this investigation was to establish whether and to what extent sudden death in the young may be ascribable to the substrate of underlying congenital heart disease. Among 182 young people (< or = 35 years) who died of cardiac sudden death and underwent postmortem examination, 58 (32%) had congenital heart disease. Seven showed an intrapericardial rupture of aortic dissection, in the setting of Marfan syndrome in two, isolated bicuspid aortic valve in two, and bicuspid aortic valve and isthmic coarctation in three; all exhibited equally severe degeneration of the aortic wall. Sixteen cases had conduction system anomalies, mostly bypass tracts; 15 coronary artery anomalies (three ostial valve-like stenosis, five origin from the wrong aortic sinus, and seven deep intramyocardial course); 12 hypertrophic cardiomyopathy; five postoperative congenital heart disease including scar following ventriculotomy, conduction system injury, and defects left unrepaired; and three congenital aortic valve stenosis. One third of sudden deaths in the young was ascribable to structural defects present since birth. A large spectrum of congenital heart disease involves the risk of sudden death, but most structural defects are usually not considered to be life threatening. Some of these concealed defects are potentially detectable in life by clinical imaging techniques.

Pulmonary vascular disease in infants with complete atrioventricular septal defect.

In order to assess incidence and time of occurrence of pulmonary vascular disease, the lungs of 49 patients were studied histologically. Thirty-four lung specimens were obtained at autopsy, and 15 were open lung biopsies. Patients consisted of 24 males and 25 females ranging in age from 10 days to 14 years (median 9 months); 37 had Downs syndrome. Overall incidence of irreversible pulmonary vascular disease (grade 3 or more) under 1 year of age was 34.6%; grade 4 of pulmonary vascular disease was observed only in Down patients. In correlating pulmonary vascular resistance, measured during heart catheterization, with pulmonary vascular disease severity at histology, 6 out of 7 patients with pulmonary vascular resistance over 7 units per metre squared showed grade 4 of pulmonary vascular disease, and of these 4 were under 1 year of age. These findings suggest that a significant rate of pulmonary vascular disease occurs under 1 year of age, with most severe degrees in the time interval 7-12 months. They show that good correlation exists between pulmonary vascular resistance over 7 units per metre squared and grade 4 of pulmonary vascular disease. They demonstrate that the most severe pulmonary vascular disease is seen in Downs syndrome. Finally, they indicate that early surgical correction is mandatory and should be accomplished within 6 months of age.

Coronary arterial wall and atherosclerosis in youth (1–20 years): a histologic study in a northern Italian population

Based on the working hypothesis that coronary atherosclerosis begins in childhood, a histologic study was carried out on the subepicardial coronary arterial tree of 100 young persons (1-20 years), who had died from causes unrelated to the cardiovascular system. These subjects were natives of a well-defined geographic area in northern Italy, namely the region of Veneto. Intimal proliferations (musculo-elastic and fibro-elastic layers) were observed in 95.3% of the coronary arterial segments in the age group between one and five years. The more distal the coronary segments examined, the lesser was the intimal thickening. Raised mature fibrous plaques were detected in 23 segments from 15 patients (2 from subjects aged between six and 10 years; 4 between 11 and 15 years, and 9 between 16 and 20 years). Single vessel disease was present in 9, double vessel disease in 4 and triple vessel disease in 2 cases. The site most involved by plaques was the proximal part of the left anterior descending coronary artery. Only one plaque was of sufficient dimensions to be considered stenotic (50% luminal reduction). Plaques were rarely sudanophilic, and all seemed to arise in relation to previous intimal thickening. No qualitative nor quantitative sexual differences were observed. These data give rise to much concern, and one consistent with a recently observed occurrence of sudden coronary death in young people from the same geographic area.

Atresia of left atrioventricular orifice. Anatomical investigation in 62 cases.

Sixty-two hearts without a patent exit from the left atrium to the ventricular mass have been studied. All had situs solitus and laevocardia. The material consisted of 32 cases with coexistent aortic atresia and 30 cases with patent aortic root. Five hearts with aortic atresia were biventricular with atrioventricular concordance and imperforate left atrioventricular valves, and 27 hearts were univentricular of right ventricular type, with absent left atrioventricular connection. The anatomy of this group was uniform, with extreme hypoplasia of all the left cardiac segments. Among the cases with patent aortic root, five were biventricular, with atrioventricular concordance and imperforate left atrioventricular valves, and 24 had absent left atrioventricular connection, 15 with univentricular heart of right ventricular type and nine with univentricular heart of left ventricular type. The final heart had double inlet univentricular of left ventricular type with an imperforate left atrioventricular valve. In this second group the aorta was larger in cases with discordant ventriculoarterial connection or in those with double outlet from the main ventricular chamber. A normal sized aorta without aortic arch obstruction was observed in nine instances. These are of great interest in terms of surgical anatomy since definitive palliation may be feasible.

Preserving the pulmonary valve during early repair of tetralogy of Fallot: Anatomic substrates and surgical strategies

OBJECTIVE To describe the anatomy of the PV in tetralogy of Fallot (TOF) and to define the influence of PV anatomy on the development of surgical techniques for PV preservation during early repair. METHODS The PV was evaluated in 79 anatomic specimens of patients with TOF who had not undergone surgery for repair, and in 82 patients who underwent early TOF repair at our institution. New surgical techniques for PV preservation during early repair are described. RESULTS The PV in TOF was predominantly bicuspid (n = 118 of 160; 73.7%), less frequently tricuspid (n = 28 of 160; 17.5%), and seldom unicuspid (n = 14 of 160; 8.8%). In 82 cases (51.3%), the PV cusps were normal; in 78 cases (48.7%), they were thickened and dysplastic. Preservation of the PV was possible in 46 of 82 (56%) consecutive patients during TOF repair in our more recent experience, either using balloon dilation alone (18 of 46; 39%) or in association with other PV plasty procedures (28 of 46; 61%). Most bicuspid and tricuspid valves were salvageable, but unicuspid valves were not suitable. After a median follow-up time of 2.8 years (range, 0.5-6.8 years), the degree of PV regurgitation continued to be zero or mild in 40 patients (86%), and moderate in 6 (14%). CONCLUSIONS The majority of patients with TOF (>90%) have a bicuspid or tricuspid PV, which is the most favorable surgical anatomy for preserving the PV, independent of the degree of leaflet dysplasia. The recent introduction of more-complex PV plasty techniques, such as delamination plasty, allowed us to further extend the applicability of PV-preservation techniques.

Bone-marrow–derived CXCR4-positive tissue-committed stem cell recruitment in human right ventricular remodeling

The epicardium contributes to cardiac formation, particularly during embryogenesis. It remains to be seen if it is also involved in postnatal myocardial homeostasis. This study evaluates the topographic distribution of stem cells (c-Kit) and extracardiac progenitor cells (CXCR4+) and their contribution to ventricular remodeling in a model of pressure volume overload leading to right ventricle hypertrophy. Eleven specimens with hypoplastic left heart syndrome were evaluated and compared with 6 normal hearts from subjects matched for age and weight. All underwent Norwood procedure with the right ventricle becoming a systemic one, with pressure and volume overload leading to right ventricle remodeling. Transmural cardiac tissue samples from the right ventricle were analyzed by immunohistochemistry and morphometry. This is the first study to demonstrate that c-Kit-positive progenitor cells and tissue-committed stem cells (CXCR4+/CD45-) are higher in children with systemic right ventricle remodeling. We also show that the localization of cardiac progenitor and recruited CXCR4+ stem cells in the myocardium is site specific in hearts with right ventricle hypertrophy. These cells are mainly scattered in the interstitium of the epicardial layer. In contrast, myocyte proliferation is not a key process in right ventricular hypertrophy. Induced by the overexpression of SDF-1α by the myocardium, CXCR4 cell mobilization resembles SDF-1 homing factor distribution, showing transmural enhanced expression from the endocardium toward the epicardium. The study provides evidences of the site-specific epicardial localization of stem cells in a model of pressure/volume overload and suggests that the epicardium acts as a permissive niche in normal and pathologic conditions.

Intracardiac echocardiography: gross anatomy and magnetic resonance correlations and validations.

Purpose: The feasibility and safety of intracardiac echocardiography (ICE) in humans, using low frequency transducers, and its excellent tissue contrast capabilities that enhances the differentiation of intracardiac structures have been previously demonstrated. However, correlations among ICE imaging and anatomic sections or magnetic resonance (MR) scan planes have never been described before. This study was designed to correlate a simplified ICE approach with the anatomy of the right atrium and great vessels obtained by serial post-mortem sections and cardiac MR images. Methods: A stepwise approach to ICE, which is based on our experience on over 300 consecutive patients with interatrial communications, has been correlated with anatomic sections from pressure-perfused-fixed hearts and spin echo cardiac MR imaging. A 9F-9 MHz mechanical device was used to record four transverse and one longitudinal sections for an extensive evaluation of the intracardiac architecture. Results: ICE transverse and longitudinal views allowed the detection of all the required information. Moreover, the anatomic sections and cardiac MR scan planes allowed validation of all the structures imaged by ICE. The potential clinical applications of the ICE technique are further discussed. Conclusion: This paper demonstrates the basic accuracy of this new imaging modality. Therefore, mechanical ICE might be considered an active investment in cardiac catheterization laboratories, specifically in the percutaneous interventional procedure setting, discovering a new route (let’s see and treat) to sophisticated interventions. In this respect, there can be little doubt that the knowledge of cross-sectional mechanical ICE imaging provides the basis for understanding the heart anatomy.

Fatal outcome in Eisenmenger syndrome

AIM To assess correlations between fatal outcome and histologic findings of pulmonary vascular disease in different situations of Eisenmenger syndrome, either during the natural course or early-late after surgery. MATERIAL AND METHODS The clinical follow-up and fatal outcome of 20 patients affected by Eisenmenger syndrome were investigated. In addition to the pathologic report and gross reexamination of the heart, the lung tissue was studied by histology. Patients were divided into three groups: 6 non-operated patients who died during the natural course (Group 1), 11 patients who underwent correction of the congenital defect and died in the perioperative period (Group 2), and 3 patients who died late after surgery (Group 3). RESULTS In Group 1, five patients (83%) died of cardiac arrest a few days after the onset of hypoxic attacks; in four patients histology showed Grade IV pulmonary vascular disease with diffuse fibrinoid necrosis in the distal pulmonary arterial vasculature. In Group 2, nine patients (82%) died on the first or second postoperative day after a refractory pulmonary hypertensive crisis, with histologic evidence in three patients of fibrinoid necrosis of the distal pulmonary small arteries and arterioles. In Group 3, two patients (67%) died suddenly, 6 and 18 years after cardiac surgery, following onset of dyspnea and cardiogenic shock; autopsy showed aneurysmal dilatation of the pulmonary artery with massive thrombosis in the setting of Grades III-IV pulmonary vascular disease without fibrinoid necrosis. CONCLUSION Fatal outcome in Eisenmenger syndrome, either in the natural course or after refractory hypertensive attacks post surgery, is frequently associated with fibrinoid necrosis of the small pulmonary arteries and arterioles.