Cthrc1 deficiency aggravates wound healing and promotes cardiac rupture after myocardial infarction via non-canonical WNT5A signaling pathway.

Cardiac fibroblasts are crucial for scar formation and cardiac repair after myocardial infarction (MI). Collagen triple helix repeat containing 1 (CTHRC1), an extracellular matrix protein, is involved in the pathogenesis of vascular remodeling, bone formation, and tumor progression. However, the role and underlying mechanism of CTHRC1 in post-MI wound repair are not fully clear. Bioinformatics analysis demonstrated CTHRC1 up-regulation in cardiac fibroblasts after ischemic cardiac injury. Serum levels of CTHRC1 were increased in MI mice and CTHRC1 expression was up-regulated in cardiac fibroblasts after MI. In vitro results showed that the induction of CTHRC1 expression in cardiac fibroblasts was mediated by canonical TGFß1-Smad2/3 signaling axis. Moreover, CTHRC1 improved wound healing and boosted cardiac fibroblast activation in vitro. Cthrc1 deficiency aggravated cardiac function and reduced collagen deposition as well as increased mortality attributable to cardiac rupture after MI. Consistent with above phenotypes, reduced the levels of myocardial CD31, α-smooth muscle actin, collagen I, and collagen III was observed, whereas myocardial expression of matrix metalloproteinase 2 and matrix metalloproteinase 9 were increased in Cthrc1 knockout mice post-MI. Above effects could be partly reversed by rCTHRC1 protein or rWNT5A protein. Our study indicates that cardiac fibroblast-derived, canonical TGFß1-Smad2/3-dependent CTHRC1 could improve wound repair and prevent cardiac rupture after MI via selectively activating non-canonical WNT5A-PCP signaling pathway.

Cardiac Overexpression of Chil1 Improves Wound Healing to Prevent Cardiac Rupture After Myocardial Infarction.

Timely formation of collagen-rich-scar is of importance to prevent ventricular rupture after myocardial infarction (MI). Chil1 (Chitinase 3-like 1) is a secreted protein associated with tissue remodeling response. However, its function in MI progression remains elusive. Chil1 was downregulated in the injured area overall post-MI. Overexpression of Chil1 markedly reduced cardiac rupture, increased wall thickness, and improved cardiac function post-MI due to collagen-rich-scar formation and extracellular matrix remodeling. In vitro, Chil1 induced the transformation of fibroblasts to myofibroblasts. Mechanistically, a phosphoproteomics study revealed that Chil1 binded to the EGFR enhancing RAF/MEK1/ERK signaling pathway to exert cardiac protection function. The effects of Chil1 on fibroblasts transformation and cardiac protections after MI were partially abolished by co-treated with RAF inhibitor. Together, our findings identify Chil1 as a protection factor in MI progression through binding to EGFR which further activates RAF/MEK1/ERK signaling pathway.

Aortic Chordae Tendineae Strands with Significant Aortic Regurgitation.

The aortic chordae tendineae strands are suggested to be embryonic remnants of the cusp formation process. We herein describe a 70-year-old male who was admitted to our hospital for shortness of breath and chest tightness. During echocardiographic examination, severe aortic regurgitation with a ruptured fibrous strand was detected. Moreover, another fibrous strand was found by three-dimensional transesophageal echocardiography (TEE). To our knowledge, this is the first literature review of aortic chordae tendineae strands, including diagnosis, management, and mechanisms of aortic regurgitation due to such informal strands.

Nuclear Receptor Nur77 Controls Cardiac Fibrosis through Distinct Actions on Fibroblasts and Cardiomyocytes.

Fibrosis is a hallmark of adverse cardiac remodeling, which promotes heart failure, but it is also an essential repair mechanism to prevent cardiac rupture, signifying the importance of appropriate regulation of this process. In the remodeling heart, cardiac fibroblasts (CFs) differentiate into myofibroblasts (MyoFB), which are the key mediators of the fibrotic response. Additionally, cardiomyocytes are involved by providing pro-fibrotic cues. Nuclear receptor Nur77 is known to reduce cardiac hypertrophy and associated fibrosis; however, the exact function of Nur77 in the fibrotic response is yet unknown. Here, we show that Nur77-deficient mice exhibit severe myocardial wall thinning, rupture and reduced collagen fiber density after myocardial infarction and chronic isoproterenol (ISO) infusion. Upon Nur77 knockdown in cultured rat CFs, expression of MyoFB markers and extracellular matrix proteins is reduced after stimulation with ISO or transforming growth factor-ß (TGF-ß). Accordingly, Nur77-depleted CFs produce less collagen and exhibit diminished proliferation and wound closure capacity. Interestingly, Nur77 knockdown in neonatal rat cardiomyocytes results in increased paracrine induction of MyoFB differentiation, which was blocked by TGF-ß receptor antagonism. Taken together, Nur77-mediated regulation involves CF-intrinsic promotion of CF-to-MyoFB transition and inhibition of cardiomyocyte-driven paracrine TGF-ß-mediated MyoFB differentiation. As such, Nur77 provides distinct, cell-specific regulation of cardiac fibrosis.

Validation of diagnostic criteria and histopathological characterization of cardiac rupture in the mouse model of nonreperfused myocardial infarction.

In patients with myocardial infarction (MI), cardiac rupture is an uncommon but catastrophic complication. In the mouse model of nonreperfused MI, reported rupture rates are highly variable and depend not only on the genetic background and sex of animals but also on the method used for documentation of rupture. In most studies, diagnosis of cardiac rupture is based on visual inspection during autopsy; however, criteria are poorly defined. We performed systematic histopathological analysis of whole hearts from C57BL/6J mice dying after nonreperfused MI and evaluated the reliability of autopsy-based criteria in identification of rupture. Moreover, we compared the cell biological environment of the infarct between rupture-related and rupture-independent deaths. Histopathological analysis documented rupture in 50% of mice dying during the first week post-MI. Identification of a gross rupture site was highly specific but had low sensitivity; in contrast, hemothorax had high sensitivity but low specificity. Mice with rupture had lower myofibroblast infiltration, accentuated macrophage influx, and a trend toward reduced collagen content in the infarct. Male mice had increased mortality and higher incidence of rupture. However, infarct myeloid cells harvested from male and female mice at the peak of the incidence of rupture had comparable inflammatory gene expression. In conclusion, the reliability of autopsy in documentation of rupture in infarcted mice is dependent on the specific criteria used. Macrophage-driven inflammation and reduced activation of collagen-secreting reparative myofibroblasts may be involved in the pathogenesis of post-MI cardiac rupture.NEW & NOTEWORTHY We show that cardiac rupture accounts for 50% of deaths in C57BL/6J mice undergoing nonreperfused myocardial infarction protocols. Overestimation of rupture events in published studies likely reflects the low specificity of hemothorax as a criterion for documentation of rupture. In contrast, identification of a gross rupture site has high specificity and low sensitivity. We also show that mice dying of rupture have increased macrophage influx and attenuated myofibroblast infiltration in the infarct. These findings are consistent with a role for perturbations in the balance between inflammatory and reparative responses in the pathogenesis of postinfarction cardiac rupture. We also report that the male predilection for rupture in infarcted mice is not associated with increased inflammatory activation of myeloid cells.

Primary cardiac angiosarcoma with right atrial wall rupture: A case report.

RATIONALE: Cardiac angiosarcoma is the most common malignant tumor of the heart and a rare disease with rapid disease progression and poor prognosis. Cardiac wall rupture is an extremely rare complication. PATIENT CONCERNS: A 32-year-old woman presented with an acute onset of epigastric pain and chest discomfort at first time when she visited an emergency room. DIAGNOSES: A cardiac mass was identified on echocardiography and subsequently performed chest computed tomography and cardiac magnetic resonance imaging revealed the cardiac tumor at right atrium with right atrial wall rupture and hematogenous lung metastasis. Histopathologic diagnosis of metastatic angiosarcoma was done by open lung biopsy. INTERVENTIONS: The patient was treated with palliative chemotherapy for the primary cardiac tumor and hematogenous lung metastasis. OUTCOMES: The follow-up imaging studies revealed treatment response of the primary cardiac tumor and hematogenous lung metastasis. LESSONS: Clinical and radiologic evaluation of the cardiac angiosarcoma was well performed in our case with various diagnostic imaging modalities including echocardiography, chest computed tomography, cardiac magnetic resonance imaging, and fluorodeoxyglucose-positron emission tomography/computed tomography. This case report well demonstrates typical imaging findings of a rare cardiac tumor and emphasizes importance of early investigation for accurate diagnosis and proper management of the cardiac tumor.

Cardiac laceration following non-penetrating chest trauma in dog and cat.

Cardiac laceration with non-penetrating chest trauma is reported as a common cause of death in human following rapid deceleration in high-speed vehicular accident. In contrast, in veterinary medicine, traumatic rupture of heart and great-vessel structures appears to be an uncommon cause of death. Here we report three cases of cardiac laceration following non-penetrating chest trauma in a one cat and two dogs. In two of these cases, necropsy revealed a rupture of the heart associated with fractures of the ribs and lung contusion; only one case did not exhibit any external chest injury but revealed pericardial tear associated with hemothorax following rupture of the right auricle of the heart. However, in all three presented cases, the thoracic location of the injuries allowed to conclude that the cause of the cardiac rupture was due to a direct impact of the chest wall with a high speed object and consequent transmission of the kinetic force and compression of the heart between left and right thorax. These case reports underline the importance of a systematic and complete macroscopic evaluation of the heart in all cases of death following non-penetrating chest trauma in dog and cat such as in human. They also highlight how, in clinical and forensic practice, the cardiac injury following blunt chest trauma should be ruled out even in the cases of absence of external chest injury.

Cardiac rupture caused by traffic accident: Case reports and a literature review.

The commonest cause of blunt cardiac injuries is from traffic accidents followed by violent falls, sport activities, accidents or a fight but rupture of the heart is rare and lethal. The precise incidence of cardiac injury after a blunt chest trauma is unknown as rates vary greatly in the literature from between 7% and 76% of cases. Autopsy studies have shown that the right ventricle is the most frequently ruptured, followed by the left ventricle, right atrium, intraventricular septum, left atrium and interatrial septum with decreasing frequency. Post-mortem imaging is a rapidly advancing field of post-mortem investigations of trauma victims. The available literature dealing with the comparison of post-mortem computed tomography results with forensic autopsy indicates that conventional autopsy remains superior for the detection of organ and soft tissue injuries in all body regions.

[Morphological analysis of cardiac rupture due to blunt injury, cardiopulmonary resuscitation and myocardial infarction in forensic pathology].

OBJECTIVE: To analyze the morphological features and forensic pathological characteristics of cardiac ruptures of different causes for their differential diagnosis. METHODS: We analyzed the data of 44 autopsy cases of cardiac rupture from 2014 to 2017 in our institute, including 11 cases caused by blunt violence with intact pericardium, 4 caused by cardiopulmonary resuscitation (CPR), 9 by myocardial infarction, and 20 by aorta dissection rupture.The gross features and histopathological characteristics of cardiac rupture and pericardial effusion were analyzed and compared. RESULTS: Cardiac ruptures caused by blunt violence varied in both morphology and locations, and multiple ruptures could be found, often accompanied with rib or sternum fractures; the volume of pericardial effusion was variable in a wide range; microscopically, hemorrhage and contraction band necrosis could be observed in the cardiac tissue surrounding the rupture.Cardiac ruptures caused by CPR occurred typically near the apex of the right ventricular anterior wall, and the laceration was often parallel to the interventricular septum with frequent rib and sternum fractures; the volume of pericardial blood was small without blood clots; microscopic examination only revealed a few hemorrhages around the ruptured cardiac muscular fibers.Cardiac ruptures due to myocardial infarction caused massive pericardial blood with blood clots, and the blood volume was significantly greater than that found in cases of CPR-induced cardiac rupture (P < 0.05);lacerations were confined in the left ventricular anterior wall, and the microscopic findings included myocardial necrosis, inflammatory cell infiltration, and mural thrombus.Cardiac tamponade resulting from aorta dissection rupture was featured by massive pericardial blood with blood clots, and the blood volume was much greater than that in cases of cardiac ruptures caused by blunt violence, myocardial infarction and CPR (P < 0.05). CONCLUSIONS: Hemorrhage, inflammatory cell infiltration, and lateral thrombi around the cardiac rupture, along with pericardial blood clots, are all evidences of antemortem injuries.

Fatality During Servicing of Fire Extinguisher.

Fire extinguisher is an integral part of emergency responses to small fires. Different types of fire extinguisher exists; cartridge-based fire extinguisher is commonly used. Despite their intended use for safety, such devices can become dangerous if not properly handled or maintained. This case report describes the death of a soldier from the explosion of a cartridge-based fire extinguisher during routine servicing. The case is the first reported in the medical literature. A safety device like fire extinguisher can become dangerous if not handled with care and due steps should be taken for the maintenance of such devices before being operated in the public domain.

A Case of Primary Bacterial Pericarditis with Recurrent Cardiac Tamponade.

Cardiac tamponade is an important and potentially lethal complication of acute pericarditis. However, recurrence of cardiac tamponade is rare when it is treated appropriately. We present a 49-year-old man with bacterial pericarditis and recurrent cardiac tamponade, which was caused by the rupture of an upper part of the left atrium (LA). According to the autopsy findings, bacteremia from Staphylococcus aureus developed on a substrate of poorly controlled diabetes mellitus and spread to the pericardium via the blood. Subsequently, tissue necrosis developed from the pulmonary trunk and aorta to the LA, leading to recurrence of cardiac rupture and cardiac tamponade.

Left sinus of valsalva aneurysm ruptured into left ventricle: A case report of 320-multidetector CT findings.

RATIONALE: Ruptured aneurysm originating from the left coronary sinus of Valsalva into the left ventricle (LV) is extremely rare. Imaging features of sinus aneurysm has been commonly reported using echocardiography or angiography. Here, we report multidetector computed tomography (MDCT) findings of left sinus of Valsalva aneurysm extending into the LV and caused severe aortic regurgitation (AR) in a 44-year-old male with latent infective endocarditis. The role of MDCT in preoperative surgical planning was also emphasized. PATIENT CONCERNS: The patient visited our hospital due to worsening exertional dyspnea for 3 months. DIAGNOSES: On cardiac computed tomography (CT) using 320-MDCT, a saccular aneurysm arising from the left coronary sinus of Valsalva extending into the LV was diagnosed as the cause of severe AR. INTERVENTIONS: The patient underwent resection of the aneurysm, aortic root reconstruction, and aortic valve replacement. OUTCOMES: The patient made an uneventful recovery. Follow-up echocardiography showed no paravalvular leakage with improved LV function. LESSONS: MDCT with wide coverage and high temporal resolution can provide exact and comprehensive information about complicated conditions, leading to confident surgical planning and successful management.

Sudden death after major head and neck cancer surgery due to undetected arrhythmogenic right ventricle cardiomyopathy (ARVC).

BACKGROUND: Oral squamous cell carcinoma is the sixth most frequent malignancy in Austria. The incidence of arrhythmogenic right ventricle dysplasia (ARVC), an important cause of sudden cardiac death, is estimated at 1:5000 to 1:1000. CASE REPORT: We present a case of a 75-year-old woman who underwent major oncologic surgery for T4aN0M0 maxillary squamous cell carcinoma and reconstruction with a scapular-latissimus dorsi microvascular flap. The patient died suddenly during her postoperative care. Autopsy revealed pericardiac tamponade due to rupture of the right ventricular wall. Histologic examination showed ARVC in a sample taken directly from the ruptured area. Cause of death was secondary arrhythmia originating from the ARVC. The arrhythmia had led to rupture of the right ventricular wall and sudden cardiac death. DISCUSSION: As per our current knowledge, no cases of maxillary cancer and ARVC as co-morbidities have been reported in the literature. The patient had been given anti-arrhythmia treatment for previously detected atrial fibrillation, which could have been why the arrhythmia was not apparent on the electrocardiogram. Thus, although the appropriate preoperative diagnostics were performed according to current oncologic and anesthesiology guidelines, the potentially lethal cardiac condition of the patient could not be detected.

Left ventricular pseudoaneurysm versus aneurysm a diagnosis dilemma.

Free wall rupture of the left ventricle (LV) is a rare but life-threatening complication of acute myocardial infaction. Very rarely such rupture may be contained by the adhering pericardium creating a pseudoaneurysm. This condition warrants for an emergency surgery. Left ventricular aneurysm is the discrete thinning of the ventricular wall (<5 mm) with akinetic or dyskinetic wall motion causing an out-pouching of the ventricle. Given the propensity for pseudoaneurysms to rupture leading to cardiac tamponade, shock, and death, compared with a more benign natural history for true aneurysms, accurate diagnosis of these conditions is important. True aneurysm, usually, calls for an elective surgery. Clinically differentiating the two conditions remains a challenge. We report the case of a patient with LV pseudoaneurysm, initially diagnosed as true aneurysm at our institution. We have attempted to review the existing literature and discussed the characteristic findings of each entity.

Bone marrow transplantation modulates tissue macrophage phenotype and enhances cardiac recovery after subsequent acute myocardial infarction.

BACKGROUND: Bone marrow transplantation (BMT) is commonly used in experimental studies to investigate the contribution of BM-derived circulating cells to different disease processes. During studies investigating the cardiac response to acute myocardial infarction (MI) induced by permanent coronary ligation in mice that had previously undergone BMT, we found that BMT itself affects the remodelling response. METHODS AND RESULTS: Compared to matched naive mice, animals that had previously undergone BMT developed significantly less post-MI adverse remodelling, infarct thinning and contractile dysfunction as assessed by serial magnetic resonance imaging. Cardiac rupture in male mice was prevented. Histological analysis showed that the infarcts of mice that had undergone BMT had a significantly higher number of inflammatory cells, surviving cardiomyocytes and neovessels than control mice, as well as evidence of significant haemosiderin deposition. Flow cytometric and histological analyses demonstrated a higher number of alternatively activated (M2) macrophages in myocardium of the BMT group compared to control animals even before MI, and this increased further in the infarcts of the BMT mice after MI. CONCLUSIONS: The process of BMT itself substantially alters tissue macrophage phenotype and the subsequent response to acute MI. An increase in alternatively activated macrophages in this setting appears to enhance cardiac recovery after MI.

Cardiac rupture delayed for a week in an asymptomatic child following blunt trauma.

A two-year-old child was hit by a car outside his home and was immediately taken to hospital. There were no external injuries present over the body except two small abrasions on the occipital region of head. A computed tomography scan of the head was performed which revealed no cranio-cerebral injury. He was discharged from the hospital within few hours apparently well. The child was absolutely asymptomatic for a week, after which he suddenly died while playing at home. Autopsy revealed left ventricular free wall rupture and pericardial haematoma. This case report discusses the rare incidence of delayed cardiac rupture due to blunt trauma resulting in haemorrhagic tamponade in an asymptomatic child.