Endocardial tears and rupture tracts of left ventricular ruptures during acute myocardial infarction: an autopsy study of 50 out-of-hospital sudden death cases

We pathologically evaluated endocardial tears and rupture tracts of left ventricular ruptures during acute myocardial infarctions (50 sudden out-of-hospital death cases; 28 men and 22 women; age range 42–88 years; mean age 68.4 years). Endocardial tears were frequently seen at or near the base of the papillary muscles (54%) or in the area where the septum meets the free wall (42%). The endocardial tear was longer in the adjacent septum (mean 2.1±1.0 cm) than at the papillary muscle base (mean 1.0±0.8 cm). Accessory tears were observed near the main endocardial tear in about half of the cases (44%). The rupture tract was located well within the infarcted area in 88% and at the border of the infarcted and normal myocardium in 12%. Mature fresh thrombus was found on most main endocardial tears. In most rupture tracts, the thrombus was more mature in the subendocardial than in the subepicardial zone. Morphologically, this study confirmed that most cardiac ruptures start with an endocardial tear at or near the base of the papillary muscles or in the area where the septum meets the free wall, and rapidly progress independent of the histopathologic age of the infarction.     

Case report: Left ventricular noncompaction cardiomyopathy and RASopathies

The following is a case report of 6 patients with Noonan syndrome (NS) and/or a related RASsopathy that also have evidence of left ventricular noncompaction cardiomyopathy (LVNC). Noonan syndrome,a type of RASopathy, is an autosomal dominant disorder that is typically associated with congenital heart defects and hypertrophic cardiomyopathy. There have been minimal reports of Noonan syndrome or other RASopathy and the association of LVNC. This report promulgates 6 nonrelated cases of Noonan syndrome or unspecified RASopathy and LVNC.     

A case of noncompaction of the ventricular myocardium combined with situs ambiguous with polysplenia

A 33-year-old man was admitted to our hospital with chest pain and exertional dyspnea. Two-dimensional echocardiography showed prominent trabeculations and deep intertrabecular recesses, findings consistent with noncompaction of the ventricular myocardium. Thoracoabdominal CT and cardiac magnetic resonance imaging (CMR) revealed situs ambiguous with polysplenia and noncompaction of the left ventricular myocardium. CMR also demonstrated delayed enhancement of the trabeculations located at the apical portion of the left ventricle. The coronary angiogram was normal. This is the first case of noncompaction of the ventricular myocardium associated with situs ambiguous with polysplenia.     

Sudden unexpected death in patients with malignancy: a clinicopathologic study of 28 autopsy cases

Sudden unexpected death (SUD) in patients with malignancy has not been comprehensively studied. We defined SUD as intrinsic natural death within 24h after initial clinical presentation of the disease responsible for the death. Intra- and postoperative death and cases associated with a myelosuppressive state were excluded. Of 2,216 autopsy cases with malignancy registered at Saitama Cancer Center, Japan, 28 SUD cases (1.3%) were studied clinicopathologically. Fifteen cases (53.6%) died of non-neoplastic cardiovascular events (CVEs), with acute myocardial infarction (AMI) being the most common death (n=13). Ten cases (35.7%) died of neoplasm-related complications (NRCs), and a miscellaneous pathophysiology was apparent, including cardiac involvement by tumor cells (n=3), fistula formation between great vessels and the alimentary canal (n=3), hepatic rupture (n=2), cardiac tamponade (n=1), and neoplastic pulmonary emboli (n=1). An anaphylaxis reaction (AR) was the cause of SUD in three cases (10.7%). Our results imply that the main route for prevention of SUD in patients with malignancy is incorporation of measure against ischemic heart disease. In addition, a variety of mechanisms causing SUD as a complication of malignant neoplasms should be recognized, including AR. Accumulation of SUD cases is necessary to better understand the causes of SUD in patients with malignancy.     

心肌致密化不全的超声心动图及临床特点分析

目的探讨心肌致密化不全的超声心动图及临床特点。方法选取20例心肌致密化不全患者,其中男性14例,女性6例;年龄3.5~81.0岁,平均年龄48.6岁。对其临床特点、心电图及超声心动图检查进行分析。结果临床症状以心慌、胸闷、气短等多见,占80%;1例出现偏瘫,2例合并先天性心脏病。90%伴有不同程度的心力衰竭。所有患者心电图出现异常,以心律失常多见(60%)。超声心动图检查所有患者均可探及纵横交错排列的肌小梁和大小不等深陷的小梁隐窝;非致密化心肌的厚度与致密化心肌的厚度比值(N/C)>2;彩色血流可见隐窝内血流与左心室相通。结论心肌致密化不全患者无特异临床表现及心电图改变,主要表现为反复发作的、进行性加重的心力衰竭和心律失常,栓塞事件少见。超声心动图可以显示该病的心肌结构,是该病的首选检查。     

Fever-induced QTc prolongation and ventricular fibrillation in a healthy young man

Long QT syndrome is associated with lethal tachyarrhythmia that can lead to syncope, seizure, and sudden death. Congenital long QT syndrome is a genetic disorder, characterized by delayed cardiac repolarization and prolongation of the QT interval on the electrocardiogram (ECG). Type 2 congenital long QT is linked to mutations in the human ether a go-go-related gene (HERG). There are environmental triggers of adverse cardiac events such as emotional and acoustic stimuli, but fever can also be a potential trigger of life-threatening arrhythmias in long QT syndrome type 2 patients. Herein, we report a healthy young man who experienced fever-induced polymorphic ventricular tachycardia and QT interval prolongation.     

Left ventricular mechanoreceptors: a haemodynamic study

1. To study the function of the left ventricular mechanoreceptors, a working left ventricle preparation was devised in dogs which permitted control of pressure and flow of the isolated perfused coronary circulation and of the flow of the isolated, separately perfused systemic circulation. The systemic circulation was perfused at a constant rate so that changes in systemic pressure reflected changes in systemic resistance.2. Increases in myocardial contractility produced by injection of catecholamines into the isolated, perfused coronary circulation produced a fall in the pressure (resistance) of the isolated, separately perfused (at a constant rate) systemic circulation.3. Completeness of isolation of the coronary and systemic circulations was shown by the marked difference in appearance times between the reflex hypotensive responses from catecholamine injections into the isolated coronary circulation and the direct hypertensive response from a similar injection when the circulations were connected as well as by the marked difference between the pressure pulses recorded simultaneously on both sides of the aortic balloon separating the two circulations.4. Myocardial beta receptor blockade produced by injection of propranolol into the isolated coronary circulation abolished or attenuated the changes in left ventricular myocardial contractility as well as the subsequent hypotensive responses following the similar injection of catecholamines.5. Electrical stimulation of a sympathetic nerve innervating the heart resulted in increases in left ventricular myocardial contractility and subsequent systemic hypotensive responses indistinguishable from those following injection of catecholamines.6. That distortion of the mechano- or stretch receptors in the left ventricular myocardium was the cause of the hypotensive responses was demonstrated by increasing left ventricular myocardial contractility by mechanically obstructing the left ventricular outflow which produced hypotensive responses similar to those following the injection of catecholamines or nerve stimulation.7. Bilateral high cervical vagotomy abolished the hypotensive responses following injection of catecholamines into the isolated coronary circulation or following left ventricular outflow obstruction in all but one instance, indicating the importance of vagal fibres to the afferent arm of the reflex.8. It is suggested that the left ventricular mechanoreceptors function normally to reduce the peripheral resistance in order to prepare the systemic circulation to receive the left ventricular output and, especially during exercise, to prepare the systemic circulation to receive the augmented cardiac output with a minimum alteration in the systemic blood pressure and to distribute this augmented output preferentially to the skeletal muscles.     

Sleep apnea in mice: a useful animal model for study of SIDS?

Although the incidence of sudden infant death syndrome (SIDS) has been decreased by education programs to avoid sleeping in prone position, the pathological mechanisms of SIDS have not fully been understood. Basic research on sleep apnea using experimental animals may help further understanding and prevention of SIDS because the syndrome is thought as inability to wake up from respiratory arrest (apnea) during sleep. Although several animal models of sleep apnea have been described previously, mice would be useful experimental animals in that these animals are frequently used in genetic engineering. Those considerations prompted us to establish a method for measuring ventilation of mice concomitantly with electroencephalography and electromyography for assessing sleep–wake states. Normal wild-type mice developed two types of central sleep apneas (CSA), that is, post-sigh and spontaneous apneas, as normal humans do. Moreover, post-sigh apneas in mice were observed exclusively during slow-wave sleep (SWS) while spontaneous apneas were seen in both SWS and rapid eye movement (REM) sleep. These characteristics are very similar to those of sleep apneas in healthy human infants and children. Therefore, mice seem to be a promising experimental animal model for studying the genetic and molecular basis of respiratory regulation and dysregulation during sleep in humans, especially infants and children. However, we should keep in mind limitations in studying mice as an animal model of SIDS, since they are nocturnal rodents and they sleep in the prone position.     

A de novo BRPF1 variant in a case of Sudden Unexplained Death in Childhood

Sudden Unexplained Death in Childhood (SUDC), the death of a child that remains unexplained after a complete autopsy and investigation, is a rare and poorly understood entity. This case report describes a 3-year-old boy with history of language delay and ptosis, who died suddenly in his sleep without known cause. A pathogenic de novo frameshift mutation in BRPF1, a gene which has been associated with the syndrome of Intellectual Developmental Disorder with Dysmorphic Facies and Ptosis (IDDDFP), was identified during a post-mortem evaluation. The finding of a pathogenic variant in BRPF1, which has not previously been associated with sudden death, in an SUDC case has implications for this child's family and contributes to the broader field of SUDC research. This case demonstrates the utility of post-mortem genetic testing in SUDC.     

胎儿心室肌致密化不全一例

患者女,25岁。因停经20周,B超发现胎儿心律异常1d于2006年6月20日入院。临床诊断为胎儿心动过速性心律失常;患者既往体健,无遗传性疾病家族史。体检：患者生命体征止常,心、肺检查未见异常。胎儿心率240～250次/min（正常胎心率为120～160次／min）,心律尚齐;胎儿心脏B超：四腔切面可显示左、右心房、心窒比例基本对称,二尖瓣及三尖瓣可辨。[第一段]     

Xq28-linked noncompaction of the left ventricular myocardium: Prenatal diagnosis and pathologic analysis of affected individuals

Isolated noncompaction of the left ventricular myocardium (INVM) is characterized by the presence of numerous prominent trabeculations and deep intertrabecular recesses within the left ventricle, sometimes also affecting the right ventricle and interventricular septum. Familial occurrence of this disorder was described previously. We present a family in which 6 affected individuals demonstrated X-linked recessive inheritance of this trait. Affected relatives presented postnatally with left ventricular failure and arrhythmias, associated with the pathognomonic echocardiographic findings of INVM. The usual findings of Barth syndrome (neutropenia, growth retardation, elevated urinary organic acids, low carnitine levels, and mitochondrial abnormalities) were either absent or found inconsistently. Fetal echocardiograms obtained between 24–30 weeks of gestation in 3 of the affected males showed a dilated left ventricle in one heart, but were not otherwise diagnostic of INVM in any of the cases. Four of the affected individuals died during infancy, one is in cardiac failure at age 8 months, and one is alive following cardiac transplant at age 9 months. The hearts from infants who died or underwent transplantation appeared, on gross examination, to be enlarged, with coarse, deep ventricular trabeculations and prominent endocardial fibroelastosis. Histologically, there were loosely organized fascicles of myocytes in subepicardial and midmyocardial zones of both ventricles, and the myocytes showed thin, often angulated fibers with prominent central clearing and reduced numbers of filaments. Markedly elongated mitochondria were present in some ventricular myocytes from one specimen, but this finding was not reproducible. Genetic linkage analysis has localized INVM to the Xq28 region, where other myopathies with cardiac involvement have been located. Am. J. Med. Genet. 72:257–265, 1997. © 1997 Wiley-Liss, Inc.     

Distribution of biventricular disease in arrhythmogenic cardiomyopathy: an autopsy study

Arrhythmogenic cardiomyopathy is a rare cardiomyopathy characterized by fibrofatty replacement primarily of the right ventricular myocardium. It is a major cause of sudden death in the young and in athletes. There are few autopsy studies of the ventricular distribution of the disease. Fifty cases of sudden cardiac death with fibrofatty replacement in either ventricle from a single medical examiner's office were studied. Distribution of disease as determined grossly and microscopically was correlated with activity at time of death, race, and presence of inflammation. Extent of disease was right ventricular in 6 cases (12%; age, 25 ± 5 years), biventricular in 25 (50%; age, 36 ± 3 years), and left ventricular in 19 (38%; age, 37 ± 3 years) (P = .13). Inflammation was present in 44% of biventricular arrhythmogenic cardiomyopathy versus 74% of left ventricular arrhythmogenic cardiomyopathy and 83% of right ventricular arrhythmogenic cardiomyopathy (P = .06). Arrhythmogenic cardiomyopathy, when presenting with sudden death, is usually biventricular. There is a trend that univentricular involvement occurs at an earlier age and that right ventricular involvement shows more inflammation, suggesting different stages of disease.     

Wolffian附件肿瘤的临床病理观察

目的 观察Wolffian附件肿瘤的临床病理特点,探讨其病理诊断与鉴别诊断。方法 对3例Wolffian附件肿瘤进行HE及免疫组化染色（EnVision法）,并进行病理观察。结果 3例Wolffian附件肿瘤均为单侧,位于阔韧带或输卵管系膜。镜下肿瘤细胞呈弥漫实体状分布,可见成片的梭形或多边形细胞及排列紧密的管状结构。管腔内衬立方或柱状上皮,细胞无明显异型,核分裂象少见。管周有PAS阳性的基膜物质。免疫组化示肿瘤细胞vimentin、AE1／AE3、α-inhibin、calretinin和WT1均呈阳性,CD99呈灶性阳性,EMA和CK7呈阴性。结论 Wolffian附件肿瘤是具有独特发病部位和组织病理学特点的妇科肿瘤,需要和一系列其他妇科肿瘤鉴别。     

Next-generation sequencing (NGS) as a fast molecular diagnosis tool for left ventricular noncompaction in an infant with compound mutations in the MYBPC3 gene

Left ventricular noncompaction (LVNC) is a clinically heterogeneous disorder characterized by a trabecular meshwork and deep intertrabecular myocardial recesses that communicate with the left ventricular cavity. LVNC is classified as a rare genetic cardiomyopathy. Molecular diagnosis is a challenge for the medical community as the condition shares morphologic features of hypertrophic and dilated cardiomyopathies. Several genetic causes of LVNC have been reported, with variable modes of inheritance, including autosomal dominant and X-linked inheritance, but relatively few responsible genes have been identified.In this report, we describe a case of a severe form of LVNC leading to death at 6 months of life. NGS sequencing using a custom design for hypertrophic cardiomyopathy panel allowed us to identify compound heterozygosity in the MYBPC3 gene (p.Lys505del, p.Pro955fs) in 3 days, confirming NGS sequencing as a fast molecular diagnosis tool. Other studies have reported neonatal presentation of cardiomyopathies associated with compound heterozygous or homozygous MYBPC3 mutations. In this family and in families in which parental truncating MYBPC3 mutations are identified, preimplantation or prenatal genetic screening should be considered as these genotypes leads to neonatal mortality and morbidity.