The emerging spectrum of cardiopulmonary pathology of the Coronavirus disease 2019 (COVID-19): Report of three autopsies from Houston, Texas and review of autopsy findings from other United States cities

This paper collates the pathological findings from initial published autopsy reports on 23 patients with coronavirus disease 2019 (COVID-19) from 5 centers in the United States of America, including 3 cases from Houston, Texas. Findings confirm that COVID-19 is a systemic disease with major involvement of the lungs and heart. Acute COVID-19 pneumonia has features of a distinctive acute interstitial pneumonia with a diffuse alveolar damage component, coupled with microvascular involvement with intra- and extravascular fibrin deposition and intravascular trapping of neutrophils, and, frequently, with formation of microthombi in arterioles. Major pulmonary thromboemboli with pulmonary infarcts and/or hemorrhage occurred in 5 of the 23 patients. Two of the Houston cases had interstitial pneumonia with diffuse alveolar damage pattern. One of the Houston cases had multiple bilateral segmental pulmonary thromboemboli with infarcts and hemorrhages coupled with, in nonhemorrhagic areas, a distinctive interstitial lymphocytic pneumonitis with intra-alveolar fibrin deposits and no hyaline membranes, possibly representing a transition form to acute fibrinous and organizing pneumonia. Multifocal acute injury of cardiac myocytes was frequently observed. Lymphocytic myocarditis was reported in 1 case. In addition to major pulmonary pathology, the 3 Houston cases had evidence of lymphocytic pericarditis, multifocal acute injury of cardiomyocytes without inflammatory cellular infiltrates, depletion of splenic white pulp, focal hepatocellular degeneration and rare glomerular capillary thrombosis. Each had evidence of chronic cardiac disease: hypertensive left ventricular hypertrophy (420 g heart), dilated cardiomyopathy (1070 g heart), and hypertrophic cardiomyopathy (670 g heart). All 3 subjects were obese (BMIs of 33.8, 51.65, and 35.2 Kg/m2). Overall, the autopsy findings support the concept that the pathogenesis of severe COVID-19 disease involves direct viral-induced injury of multiple organs, including heart and lungs, coupled with the consequences of a procoagulant state with coagulopathy

Anatomopathological changes of the cardiac conduction system in sudden cardiac death, particularly in infants: advances over the last 25 years

Sudden cardiac death (SCD) is defined as the unexpected death without an obvious noncardiac cause that occurs within 1 h of witnessed symptom onset (established SCD) or within 24 h of unwitnessed symptom onset (probable SCD). In the United States, its incidence is 69/100,000 per year. Dysfunctions of the cardiac conduction and autonomic nervous systems are known to contribute to SCD pathogenesis, even if most clinicians and cardiovascular pathologists lack experience with detailed examination of the cardiac conduction system and fail to recognize lesions that are crucial to explain the SCD itself. In this review, we sought to describe the advances over the last 25 years in the study of the anatomopathological changes of the conducting tissue, in SCD, in mature hearts and particularly in sudden infant death syndrome (SIDS) and sudden intrauterine unexpected death syndrome (SIUDS), through the articles published in our journal Cardiovascular Pathology (CVP). We carried out an extensive Medline search to retrieve and review all articles published in CVP in which the sudden unexpected death of one or more subjects believed healthy was reported, especially if associated with lesions of the conducting tissue in settings that revealed no other explained causes of death, particularly in infants and fetuses. The cardiac conduction findings of resorptive degeneration, His bundle dispersion, Mahaim fibers, cartilaginous meta-hyperplasia, persistent fetal dispersion, left-sided His bundle, septation of the bifurcation, atrioventricular node dispersion, sinus node hypoplasia, Zahn node, His bundle hypoplasia, atrioventricular node, and His bundle dualism were similarly detected in SIDS and SIUDS victims

Pathology of unexpected sudden cardiac death : Obstructive sleep apnea is part of the challenge

Unexpected sudden cardiac death (SCD), sudden infant death syndrome (SIDS) and sudden intrauterine unexplained death (SIUD) are major unsolved, devastating forms of death that occur frequently. Obstructive sleep apnea (OSA) has been associated with increased cardiovascular and cerebrovascular morbidity and mortality, including sudden cardiac death (SCD). This editorial will review the pathology of SCD, including sudden infant death syndrome (SIDS) and sudden intrauterine unexplained death (SIUD); OSA with its cardiovascular consequences; the possible link between SCD and OSA, discussing the potential mechanisms underlying these two frequent, but yet overlooked pathologies. Finally, the possible preventive benefits of treating OSA and identifying patients at common risk for OSA and SCD and SIDS-SIUD to prevent unexpected deaths will be discussed. Post-mortem examination is of great importance in every case of SCD sine materia, with examination of the brainstem and cardiac conduction system on serial sections, when general autopsy fails, but it should be stressed that also the investigations of patients suffering from OSA should focus on the possibility of pathological findings in common with cases of SCD

Update on congenital heart disease and sudden infant/perinatal death : from history to future trends

Nel corso del 20\ub0 secolo, anatomo-patologi esperti hanno contribuito ad una caratterizzazione approfondita dell\u2019anatomia patologica e fisiopatologia associate alle cardiopatie congenite (CHD). A partire dagli anni \u201870, la prevalenza riportata di CHD alla nascita \ue8 aumentata, in seguito ai progressi delle metodologie diagnostiche. Nel corso degli anni, i trattamenti chirurgici si sono associati ad una notevole riduzione della mortalit\ue0 da CHD. I progressi sono dovuti anche alle aumentate conoscenze sulla biologia evolutiva e sulla patogenesi molecolare delle CHD. Nei paesi sviluppati, la sindrome della morte improvvisa del lattante (SIDS) \ue8 la forma pi\uf9 frequente di morte nel primo anno di vita, con un tasso di mortalit\ue0 dello 0.42 ogni 1000 nascite. La morte inaspettata fetale ha una incidenza 6-8 volte maggiore rispetto a quella della SIDS e rimane inspiegabile nel 40-80% dei casi, anche dopo autopsia. Gli specifici fattori di rischio ambientali, come il fumo materno, l\u2019inquinamento dell'aria e dell'acqua, la contaminazione degli alimenti, i pesticidi, ecc., possono interagire con la costituzione genetica in modo complesso, e possono portare a polimorfismi e/o a mutazioni di geni specifici, come polimorfismi nel gene trasportatore della serotonina, 5-HTT, il regolatore della concentrazione di serotonina sinaptica. Vengono esaminati gli sviluppi attuali di ricerca in questo settore.During the 20th century, expert pathologists contributed an in-depth characterisation of the anatomical pathology and associated pathophysiology of congenital heart disease (CHD). Starting in the 1970s, the reported CHD birth prevalence has been increasing, owing to advances in diagnostic methods. Over the years, surgical treatments have been associated with an enormous reduction of CHD mortality. Advances also have been made in understanding the developmental biology and molecular pathogenesis of CHD. In developed countries, sudden infant death syndrome (SIDS) is the most frequent form of death during the first year of life, with a death rate of 0.42 every 1000 births. Unexpected stillbirth has a six- to eightfold greater incidence than that of SIDS and remains unexplained in 40-80% of cases even after autopsy. Specific environmental risk factors, such as maternal smoking, air and water pollution, food contamination, pesticides, etc, can interact with the genetic constitution in complex ways, which may lead to polymorphisms and/or mutations of specific genes, such as polymorphisms in the serotonin transporter gene 5-HTT, the regulator of the synaptic serotonin concentration. Current directions of research in this area are reviewed

Pathobiology of cardiovascular diseases : an update

This article introduces the Second Special Issue of Cardiovascular Pathology (CVP), the official journal of the Society for Cardiovascular Pathology (SCVP). This CVP Special Issue showcases a series of commemorative review articles in celebration of the 25th anniversary of CVP originally published in 2016 and now compiled into a virtual collection with online access for the cardiovascular pathology community. This overview also provides updates on the major categories of cardiovascular diseases from the perspective of cardiovascular pathologists, highlighting publications from CVP, as well as additional important review articles and clinicopathologic references

Clinico-pathological assessment of left ventricular non-compaction cardiomyopathy in end stage heart failure patients undergoing orthotopic heart transplantation

Background: Previous studies reported that left ventricular non-compaction (LVNC) is a cardiomyopathy (CMP), familial or sporadic, arising from arrest of the normal process of trabecular remodeling during embryonic life. The diagnosis is usually made by echocardiography, but to date, there has been little research on the occurrence and clinico-pathological features of LVNC in the explanted hearts of orthotopic heart transplant (OHT) recipients. Design: The clinical, echocardiographic and pathologic findings were reviewed for evidence of LVNC in 57 patients with end stage heart failure (HF) undergoing OHT. Histologic studies graded semi-quantitatively remodeling parameters of fibrosis (F) (reactive and replacement), myocyte hypertrophy (H) and myocytolysis (M) in left ventricle (LV), right ventricle (RV), interventricular septum (S) and atria (A), Grades 0, negative; 1, mild/occasional foci; 2, moderate/multiple foci; 3, severe/extensive, and total sum (Segura AM et al. Cardiovasc Pathol 2011; 20:139-45). Absolute measurements of non-compacted (NC) and compacted (C) portions of the LV wall and NC/C ratios were calculated. Results: LVNC was observed in 0 of 29 ischemic CMP (ICMP) and in 3 of 28 (10.7%) non ischemic CMP (NICMP) patients- 2 men, 1 woman, mean age \ub1SEM, 38\ub18.1 years. The echocardiogram disclosed marked LV dilatation, prominent trabeculations without hypertrophy, positive for LVNC by St\uf6llberger criteria (Stollberger C et al. J Am Soc Echocardiogr 2004; 17:91\u2013100) and LV ejection fraction (EF) <20%. Mural thrombus was seen in 2/3 patients (66.7%). The heart weight mean \ub1 SEM was 510.7\ub149.8 (range, 428-600 gm), NC was 25.7\ub16.4 mm, C was 16+3 mm, NC/C ratio was 1.6/1.0\ub10.4. The H, M, F total scores were LV 7.5\ub10.2, S 6.5\ub10.5, RV 6\ub10.6, A 6.5\ub10.4. Conclusions. LVNC is an unusual form of NICMP in patients suffering from end stage HF undergoing OHT. Quantification of the extent and severity of fibrosis, hypertrophy, and myocytolysis, using a semi quantitative grading scale helps determine histopathologic features in these patients. Further studies in larger series, correlating the anatomo-clinical variables would improve our understanding of LVNC as a cause of advanced HF leading to OHT

Pathological assessment of end-stage heart failure in explanted hearts in correlation with hemodynamics in patients undergoing orthotopic heart transplantation

Background: To date, there has been little research, if any, on the pathological correlates of end-stage heart failure in the explanted hearts of orthotopic heart transplant (OHT) recipients in correlation with the patients' hemodynamics. We sought to compare the gross and histopathological parameters in hearts explanted-native or previously transplanted-from patients with end-stage heart failure with the clinical hemodynamics parameters at the time of OHT. Methods: Forty patients undergoing OHT were enrolled in this study and divided into two groups according to whether they suffered from ischemic (ICMP) or nonischemic cardiomyopathy (NICMP). All study patients were treated with OHT for end-stage heart failure at The University of Texas Health Science Center at Houston. The pathological investigations of the hearts were focused on the study of the underlying cause of heart failure leading the patient to OHT; on the quantification of the extent and severity of fibrosis, hypertrophy, and myocytolysis; and on validating a semiquantitative grading scale. Analyses of multiple sections of the explanted hearts were carried out. The heart weights were recorded and compared with the grades of fibrosis, hypertrophy of cardiomyocytes, and myocytolysis. The grades of fibrosis, hypertrophy, and myocytolysis were evaluated in right and left ventricles and atria (with areas of confluent infarction excluded). The pathological parameters were correlated with the patients' clinical parameters. Results: Twenty-two patients (20 men, 2 women, mean age\ub1S.E.M., 62.3\ub12.2 years) suffered from ICMP and 18 patients (9 men, 9 women, mean age\ub1S.E.M., 56.3\ub12.8 years) from NICMP. All the clinical and pathological measured variables were comparable between the two groups, except for pulmonary vascular resistance, which was higher in the NICMP group of patients, and the grade of myocytolysis, which was significantly higher in the ICMP vs. NICMP group. Most of the clinical and pathological variables were overall linearly correlated. Conclusions: Both ICMP and NICMP groups of end-stage heart failure requiring OHT presented high grades of fibrosis, hypertrophy, and myocytolysis. Heart failure is the final common pathway of a variety of primary cardiovascular diseases regardless of the ischemic or nonischemic nature of the cardiomyopathy