Clinical and pathologic findings of aortic dissection at autopsy: Review of 336 cases over nearly 6 decades.

BACKGROUND: We aimed to characterize the clinical and pathologic findings of aortic dissection (AD) over a nearly 60-year period. METHODS: The Jesse E. Edwards Registry of Cardiovascular Disease database was queried for cardiac specimens from autopsies with AD as a diagnosis and compared 2 cohorts: early (1956-1992) and current (1993-2015). RESULTS: From 1956 to 2015, 338 cases (166 early, 170 current) with AD were included (mean age: 60; 62% male). The AD was 86% type A and 14% type B. Sixty-two percent of cases were under medical care at time of death (61% early, 62% current, P = not significant). Of those under medical care, 63% were not diagnosed prior to death (64% early, 62% current, P = not significant). Risks for dissection did not differ between time intervals and include left ventricular hypertrophy, suggestive of hypertension (84%), prior cardiovascular surgery (38%), bicuspid valve (14%), and connective tissue disease (9%). An intimal tear was identified in the ascending aorta in the majority (68%), followed by descending (14%), root (9.5%), and arch (7%). Aortic rupture occurred in 58%, most frequently in the ascending aorta (41%). CONCLUSIONS: In a large cardiovascular registry, >60% of cases of AD were not detected clinically and first identified at autopsy. Although diagnostic techniques have significantly improved over the time interval, the percentage of AD discovered at autopsy did not differ from the early to the current era. The most prevalent risk factors for dissection including hypertension and prior cardiovascular surgery remain similar in both time periods. AD death is related to rupture of the aorta in the majority of cases.

Autosomal-dominant biventricular arrhythmogenic cardiomyopathy in a large family with a novel in-frame DSP nonsense mutation.

A novel autosomal-dominant in-frame deletion resulting in a nonsense mutation in the desmoplakin (DSP) gene was identified in association with biventricular arrhythmogenic cardiomyopathy across three generations of a large Caucasian family. Mutations that disrupt the function and structure of desmosomal proteins, including desmoplakin, have been extensively linked to familial arrhythmogenic right ventricular cardiomyopathy (ARVC). Analysis of data from 51 individuals demonstrated the previously undescribed variant p.Cys81Stop (c.243_251delCTTGATGCG) in DSP segregates with a pathogenic phenotype exhibiting variable penetrance and expressivity. The mutation's pathogenicity was first established due to two sudden cardiac deaths (SCDs), each with a biventricular cardiomyopathy identified on autopsy. Of the individuals who underwent genetic screening, 27 of 51 were heterozygous for the DSP mutation (29 total with two obligate carriers). Six of these were subsequently diagnosed with arrhythmogenic cardiomyopathy. An additional nine family members have a conduction disorder and/or myocardial structural changes characteristic of an evolving condition. Previous reports from both human patients and mouse studies proposed DSP mutations with a premature stop codon impart mild to no clinical symptoms. Loss of expression from the abnormal allele via the nonsense-mediated mRNA decay pathway has been implicated to explain these findings. We identified an autosomal-dominant DSP nonsense mutation in a large family that led to SCD and phenotypic expression of arrhythmogenic cardiomyopathy involving both ventricles. This evidence demonstrates the pathogenic significance of this type of desmosomal mutation and provides insight into potential clinical manifestations.

Uhl's anomaly: perspective of fetal echocardiography and histopathological correlation.

We report a case of Uhl's anomaly imaged at 19 weeks of gestation by fetal echocardiography with pathological confirmation by anatomical gross heart specimen and tissue histology. Uhl's anomaly of the right ventricle is a rare cardiac disorder with isolated right ventricular enlargement with almost complete absence of the right ventricular myocardium.

Patho-Histological Findings of Annular Rupture Related to Left Ventricular Outflow Tract (LVOT) Calcification Following Transcatheter Aortic Valve Replacement (TAVR).

Peri-aortic hematoma has been recently described as a potentially life-threatening complication following transcatheter aortic valve replacement (TAVR). Patient- and procedure-related factors exist that predispose to peri-aortic hematoma formation, which can progress to myocardial rupture at the aortic root-myocardial junction. While conservative therapy with blood pressure control is the expectant management following peri-aortic hematoma formation, myocardial rupture can occur at the site of the aortic annulus. Hence, interventionists and echocardiologists must be prepared for emergent intervention to salvage the patient once the complication is recognized. The present report highlights the patho-histological findings related to left ventricular outflow tract calcification following TAVR.

Expression of cathepsin K and tartrate-resistant acid phosphatase is not confined to osteoclasts but is a general feature of multinucleated giant cells: systematic analysis.

OBJECTIVE: Cathepsin K and tartrate-resistant acid phosphatase (TRAP) are two proteins expressed in osteoclastic giant cells. Recently we showed that lesional multinucleated giant cells (MNGs) in pulmonary granulomatosis with polyangiitis expressed these proteins. We aimed to clarify whether the expression of these two proteins has any specificity or is a general feature of MNGs associated with multiple types of granulomatous inflammation. METHODS: In total, 7 Crohn's disease (CD), 5 GCA, 5 giant cell myocarditis (GCM), 11 sarcoidosis and 6 tuberculosis cases were examined for expression of cathepsin K and TRAP using immunohistochemistry (IHC). Protein expression was semi-quantitatively classified as none, weak, moderate or strong. In addition, tissue TRAP activity was examined using an enzymatic reaction. RESULTS: The expression of cathepsin K was robust in >95% of MNGs of all examined disease groups, whereas TRAP expression varied; CD, GCA and tuberculosis showed strong TRAP expression. TRAP expression in sarcoidosis and GCM was weaker (CD vs GCM, P = 0.04; CD vs sarcoidosis, P = 0.06). Compared with IHC, TRAP detection using an enzymatic colour reaction had limited sensitivity. CONCLUSION: Expression of TRAP and cathepsin K is a general feature of MNGs and their expression might be related to histopathological pattern.

Sudden death due to spontaneous acute dissection of the left subclavian artery with rupture during postpartum period: a case report.

Subclavian artery dissection is usually associated with coexisting aortic disease. Isolated and spontaneous acute subclavian artery dissection is uncommon and rarely reported. In addition, no case of left subclavian artery dissection during pregnancy and early puerperium has been described. We report the autopsy case of a 24-year-old female who died suddenly 3 days after delivery due to a spontaneous left subclavian artery dissection with rupture.

Sudden cardiac death in the young: A consensus statement on recommended practices for cardiac examination by pathologists from the Society for Cardiovascular Pathology.

Sudden cardiac death is, by definition, an unexpected, untimely death caused by a cardiac condition in a person with known or unknown heart disease. This major international public health problem accounts for approximately 15-20% of all deaths. Typically more common in older adults with acquired heart disease, SCD also can occur in the young where the cause is more likely to be a genetically transmitted process. As these inherited disease processes can affect multiple family members, it is critical that these deaths are appropriately and thoroughly investigated. Across the United States, SCD cases in those less than 40 years of age will often fall under medical examiner/coroner jurisdiction resulting in scene investigation, review of available medical records and a complete autopsy including toxicological and histological studies. To date, there have not been consistent or uniform guidelines for cardiac examination in these cases. In addition, many medical examiner/coroner offices are understaffed and/or underfunded, both of which may hamper specialized examinations or studies (e.g., molecular testing). Use of such guidelines by pathologists in cases of SCD in decedents aged 1-39 years of age could result in life-saving medical intervention for other family members. These recommendations also may provide support for underfunded offices to argue for the significance of this specialized testing. As cardiac examinations in the setting of SCD in the young fall under ME/C jurisdiction, this consensus paper has been developed with members of the Society of Cardiovascular Pathology working with cardiovascular pathology-trained, practicing forensic pathologists.

Iatrogenic aortic dissection of the descending aorta after percutaneous coronary intervention.

Aortic dissection is a rare and potentially fatal complication of coronary angiography. We report a case of a woman in her late 80s who underwent a left femoral approach coronary angiogram for evaluation of a transcatheter aortic valve replacement (TAVR). Following the procedure, she had a cardiac arrest and was found to have a descending aortic dissection on transoesophageal echocardiogram. Autopsy showed an acute intimal tear of the descending aorta, most likely related to catheter manipulation. Patients undergoing evaluation for TAVR, who tend to be elderly with concomitant atherosclerosis, are at risk for complications following cardiac catheterisation including aortic dissection.

Pathology of the aortic arch in hypoplastic left heart syndrome: surgical implications.

Aortic arch reconstruction plays an important role in the success of the Norwood procedure (NP) for hypoplastic left heart syndrome (HLHS). This study investigated the cardiac specimens to determine the etiology of distal aortic arch obstruction after the NP for HLHS and to locate coarctation of the aorta in HLHS untreated by surgery. This study examined 17 cardiac specimens: 9 that had NP and 8 not treated by surgery. The findings after NP showed frequent failure to resect the coarctation segment completely and failure to extend the augmentation patch into the descending aorta. Five (62.5%) of the eight hearts not treated by surgery had significant periductal coarctation of the aorta. After NP for nine patients, three (33%) had residual coarctation of the aorta. To minimize the risk of recurrent or persistent aortic arch obstruction after NP and to improve the long- and short-term outcome, the ductal tissue and the coarctation segment encircling the aortic lumen should be resected. The distal wall incision should be extended at least 5 mm beyond the distal aspect of the ductal tissue. These steps could avoid major aortic arch obstruction, promote growth of the native aortic tissue, and avoid ventricular dysfunction.

Sudden Unexpected Death Due to Myocarditis in Young People, Including Athletes.

Sudden deaths in young active people and athletes are distinctly uncommon and frequently related to highly visible cardiovascular conditions including hypertrophic cardiomyopathy and congenital coronary anomalies. Myocarditis is also a cause of sudden death in the young, but frequently under-recognized clinically, and therefore deserving of the present analysis. Two large registries were interrogated for cases of myocarditis, and clinical, demographic, and pathologic findings were assessed. Of 97 cases of myocarditis identified, ages were 19.3 ± 6.2 years, 76% male, and 58 were physically active at or near the time of death. Almost one-half of the 97 cases (47%) had a viral prodrome or symptoms (i.e., syncope, malaise, chest pain or palpitations). Nine were evaluated by cardiologists, but in none was a diagnosis of myocarditis established before death. The inflammatory cellular infiltrate was predominantly lymphocytic (67%), was most frequently multifocal (59%) and involved the conduction system (including atrioventricular node), 38%. In conclusion, myocarditis is an important but under-recognized cause of sudden death in young people including competitive athletes. Clinical diagnosis is difficult because symptoms are nonspecific and often ignored, requiring high index of suspicion for diagnosis. Our data support the ACC/AHA consensus guidelines recommending removal of individuals with myocarditis from competitive sports during recovery. Selective examination of conduction systems showed a number of cases with involvement of myocarditis, suggesting a novel mechanism for sudden death.

Acute Myocardial Infarction-Like Events in Related Patients With a Desmoplakin-Associated Arrhythmogenic Cardiomyopathy.

Patients with familial arrhythmogenic cardiomyopathy typically present with ventricular arrhythmias or progressive heart failure. This paper characterizes a rare presentation of an underlying genetic cardiomyopathy with clinical manifestations mimicking an acute myocardial infarction in 2 siblings, each with the same mutation in the desmoplakin (DSP) gene. (Level of Difficulty: Advanced.).

Myocardial bridging, a frequent component of the hypertrophic cardiomyopathy phenotype, lacks systematic association with sudden cardiac death.

AIMS: The clinical significance attributable to myocardial bridging of left anterior descending coronary artery in hypertrophic cardiomyopathy (HCM) remains controversial. METHODS AND RESULTS: Prevalence and depth of coronary artery bridges (CBs) were assessed in 255 hearts, including 115 with HCM (median age 29, range 5-90; 75% male), and 140 controls. Coronary artery bridges were more common in HCM (47/115; 41%) than in patients who died of a variety of non-HCM-related causes (21/100; 21%; P = 0.002), or in patients with congenital aortic stenosis and left ventricular (LV) hypertrophy (5/40; 12%; P = 0.001). Among the HCM hearts, CBs were present in 33 of 77 patients (43%) with sudden death, in 10 of 27 (37%) with heart failure death (or heart transplantation), and in 4 of 11 (36%) with other modes of death (P = 0.826). Deeply embedded CBs (> or =2 mm) occurred with similar frequency in HCM patients with sudden (21 of 77; 27%) or heart failure death (5 of 27; 13%; P = 0.191). In sudden death patients, the presence of CB was unrelated to gender (33% in women and 45% in men, P = 0.406) and age (41% <18 years vs. 44% > or =18 years; P = 0.827). CONCLUSION: In this morphological analysis of more than 250 hearts, CBs are a frequent component of phenotypically expressed HCM, and more common than in other disorders with or without LV hypertrophy. Although no systematic association with HCM-related sudden death is evident, our findings do not exclude the possibility that CB could contribute to increased risk in some individual patients, potentially impacting management decision-making on a case-by-case basis.

Hypertrophic Cardiomyopathy and Sudden Death Initially Identified at Autopsy.

Hypertrophic cardiomyopathy (HC) is associated with a well-recognized risk for unexpected sudden death (SD). Most such reported patients have been referred to dedicated centers and/or expert cardiologists for risk stratification, with the number of SDs decreasing sharply due to penetration of the implantable cardioverter-defibrillator (ICDs) into HC practice. However, the clinical circumstances, and morphologic features of HC patients who incur SD without the opportunity to be considered for preventive intervention with ICDs are largely undefined. Using the long-standing unique Jesse Edwards Registry (St. Paul, Minnesota), we studied 86 selected heart specimens from young HC patients who died suddenly and unexpectedly without prior clinical evaluation, ages 31 ± 16 years. The patients were predominantly male (87%) with only modest phenotypic expression and maximum LV wall thickening of only 18 ± 4 mm. SD events occurred predominantly with sedentary/mild activities (66%) often in bed or asleep (32%), but also during physical activity (22%) including with organized competitive sports. This largely unappreciated sub-population of patients with HC (and SD) is characterized by mild-to-moderate degree of LV hypertrophy, representing a clinical challenge which is particularly relevant in the current ICD era for HC, with the potential for SD prevention.

Sudden death with circumferential subepicardial fibrofatty replacement: left-sided arrhythmogenic ventricular cardiomyopathy.

We report 5 cases of sudden cardiac death, with similar cardiac findings. All 5 cases had circumferential left ventricular subepicardial fibrofatty replacement of the myocardium, similar to the histologic features of arrhythmogenic right ventricular cardiomyopathy (ARVC). In these cases, the findings were predominantly in the left ventricle with minimal or no involvement of the right ventricle. Four of the 5 cases had siblings with either sudden death or cardiac symptoms. This report highlights 5 cases of sudden death in the young with histologic findings similar to ARVC, with predominant left ventricular involvement and questions whether the cases represent a larger spectrum of the cardiomyopathy known as ARVC, which perhaps should be more correctly termed as "arrhythmogenic cardiomyopathy" or represent a separate, potentially inheritable cardiomyopathic entity. We report these cases to familiarize forensic pathologists with this uncommon and potentially inheritable condition.

Histologic Examination of the Heart in the Forensic Autopsy.

Histologic examination of the myocardium, valves, and cardiac blood vessels is often as important as the gross examination. The diagnostic features and categories of heart disease are many and varied, possibly more than any other organ. We present a review of the histologic features of forensically important heart disease.

Prevalence, clinical profile, and significance of left ventricular remodeling in the end-stage phase of hypertrophic cardiomyopathy.

BACKGROUND: End stage (ES) is a recognized part of the hypertrophic cardiomyopathy (HCM) disease spectrum. Frequency, clinical profile and course, and treatment strategies in these patients remain incompletely defined. METHODS AND RESULTS: Three HCM cohorts comprised 1259 patients, including 44 (3.5%) characterized as ES with systolic dysfunction (ejection fraction <50% at rest; range 15% to 49%). ES developed at a wide age range (14 to 74 years), with 45% of patients < or = 40 years old. Although 29 patients (66%) died of progressive heart failure, had sudden death events, or underwent heart transplantation, 15 (34%) survived with medical management over 3+/-3 years. Duration from onset of HCM symptoms to ES identification was considerable (14+/-10 years), but ES onset to death/transplantation was brief (2.7+/-2 years). ES occurred with similar frequency in patients with or without prior myectomy (P=0.84). Appropriate defibrillator interventions were 10% per year in patients awaiting donor hearts. Most ES patients (n=23; 52%) showed substantial left ventricular (LV) remodeling with cavity dilatation. Less complete remodeling occurred in 21 patients (48%), including 5 with persistence of a nondilated and markedly hypertrophied LV. Pathology and magnetic resonance imaging showed extensive (transmural) fibrosis in 9 of 11 ES patients. At initial evaluation, patients who developed ES were younger with more severe symptoms, had a larger LV cavity, and more frequently had a family history of ES than other HCM patients. CONCLUSIONS: ES of nonobstructive HCM has an expanded and more diverse clinical expression than previously appreciated, including occurrence in young patients, heterogeneous patterns of remodeling, frequent association with atrial fibrillation, and impaired LV contractility that precedes cavity dilatation, wall thinning, and heart failure symptoms. ES is an unfavorable complication (mortality rate 11% per year) and a sudden death risk factor; it requires vigilance to permit timely recognition and the necessity for defibrillator implantation and heart transplantation.

Review of pathologic findings in remnant hearts following valve donation.

The failure of medical examiners/coroners (ME/C) to allow heart valve donation is a major problem encountered by tissue agencies. Even though many ME/C favor tissue donation they remain responsible for determination of cause and manner of death. In 2001, the Jesse E. Edwards Registry of Cardiovascular Disease was approached by one of the nation's largest tissue procurement agencies (The American Red Cross--ARC) for the purpose of performing cardiovascular pathologic examinations following valve donation. The affiliation existed from October 2001 to January 2005. This study was undertaken to review all 593 postvalve recovery heart remnants received during that time period to tabulate the abnormalities identified and to determine whether donation interfered with the determination of cause of death. For each case, a preliminary cause of death was provided by the ARC. The decedent's body height and weight were also provided. Using the preliminary cause of death, the 593 cases were divided into natural and nonnatural manner of death groups. This division of the cases resulted in 106 cases placed in the natural manner of death group and 487 cases in the nonnatural manner of death group. For each case, all cardiac findings including significant conditions, additional findings, incidental findings, and congenital abnormalities were tabulated. Within the natural manner of death group, 15 cases had a noncardiac cause of death and 91 cases had a cause of death suspected to be cardiac related. In the 91 cases, a total of 132 significant cardiac findings were identified and there were six structurally normal hearts including two infants. In the nonnatural manner of death group, 214 significant cardiac findings were identified and 222 cases had a structurally normal heart. In both natural and nonnatural groups, the most common cardiac abnormality was atherosclerotic coronary artery disease. Other frequently encountered conditions were also identified including 11 cases with acute angle of origin of a coronary artery (five cases natural group; six cases nonnatural group). An important feature of this review was the recognition of potentially inheritable conditions that were diagnosed in both natural and nonnatural manner of death groups. There were three cases of hypertrophic cardiomyopathy (one natural; two nonnatural), three cases of arrhythmogenic right ventricular cardiomyopathy (one natural; two nonnatural), and one case of mitral valve prolapse (natural). In reviewing these cases, we did not feel that valve donation severely impaired cardiac pathologic examination. The benefits of cardiovascular pathologic examination by a cardiac pathologist include the identification of significant and incidental findings and recognition of potentially inheritable conditions.

Pottery heart: a case of porcelain heart.

This is a rare image of a porcelain heart resulting from rheumatic pancarditis. We present a case of postmortem porcelain heart scanned by multislice computed tomography, and we show three-dimensional data reconstruction analyzed with a commercial workstation (Vitrea2; Vital Images, Inc., Minnetonka, MN). Three-dimensional volume-rendering technique imaging reveals massive calcification of the entire heart, creating a pottery appearance.

Comparison of the Frequency of Sudden Cardiovascular Deaths in Young Competitive Athletes Versus Nonathletes: Should We Really Screen Only Athletes?

The issue of sudden death in young athletes and consideration for the most practical and optimal strategy to identify those genetic and/or congenital heart diseases responsible for these tragic events continues to be debated. However, proponents of broad-based and mandatory national preparticipation screening, including with 12-lead electrocardiograms have confined the focus to a relatively small segment of the youthful population who choose to engage in competitive athletic programs at the high school, college, and elite-professional level. Therefore, lost in this discussion of preparticipation screening of athletes is that the larger population of young people not involved in competitive sports (and, therefore, a priori are excluded from systematic screening) who nevertheless may die suddenly of the same cardiovascular diseases as athletes. To substantiate this hypothesis, we accessed the forensic Hennepin County, Minnesota registry in which cardiovascular sudden deaths were 8-fold more common in nonathletes (n = 24) than athletes (n = 3) and threefold more frequent in terms of incidence. The most common diseases responsible for sudden death were hypertrophic cardiomyopathy (n = 6) and arrhythmogenic right ventricular cardiomyopathy (n = 4). These data raise ethical considerations inherent in limiting systematic screening for unsuspected genetic and/or congenital heart disease to competitive athletes.

Giant aneurysms of coronary arteries and saphenous vein grafts: angiographic findings and histopathological correlates.

INTRODUCTION: Giant aneurysms that develop in native coronary arteries or saphenous vein grafts are morphologically defined as abnormally expanded outpouching vascular structures >4 cm in diameter. The location, morphology, and content of giant aneurysms account for adverse cardiovascular effects. METHODS: Two cases of giant aneurysms were studied comprehensively by noninvasive and invasive cardiac methods and subsequent histopathology. The first patient had a giant aneurysm that developed over a course of several years in a saphenous vein graft whereas the second patient had a giant aneurysm occurring within a native coronary artery. Accompanying clinical and angiographic findings are described. RESULTS: Atherosclerosis and thrombosis were among the prominent histopathological findings. CONCLUSIONS: Atherosclerosis and associated thrombosis within giant aneurysms result in obstruction of flow, distal embolization, and development of acute coronary syndromes including recurrent ischemic chest pain, unstable angina, and acute myocardial infarction. The options for clinical management of giant coronary or vein graft aneurysms include surgical excision, percutaneous coil occlusion and stent deployment, or medical approach.